Clinical and metabolic evaluation of patients with history of renal calculi in Qazvin, Iran.

PubMed

Charkhchian, Maliheh; Samani, Simin; Merat, Ehsan

2015-12-01

Nephrolithiasis is a common clinical disorder with significant health and economic burden. We conducted this study to evaluate clinical and metabolic parameters in adult patients with history of renal calculi. A total of 213 patients with history of nephrolithiasis participated in this study. Evaluation included the measurement of serum calcium, uric acid, parathormone, renal function tests, urinalysis, and urinary tests for cystinuria. Also, parameters such as volume, creatinine, calcium, uric acid, citrate, and oxalate levels were measured on 24-h urine. All patients underwent urinary tract system sonography. Of total patients, 52% were males and 48% females. The mean age was 45.16 ± 13.16 years. Also, 51.2% of subjects had positive family history of nephrolithiasis. The mean body mass index was (26.8 ± 4.2) kg/m(2). The mean 24-h urine biochemical profiles were volume (1,748 ± 860 ml), Ca (183 ± 115), uric acid (544 ± 220), citrate (490 ± 351), and oxalate (17.1 ± 15.3) mg/day; urine calcium to creatinine ratio (0.15 ± 0.10) mg/mg, and urine calcium to weight ratio (2.4 ± 1.7) mg/kg. While there were weak positive correlations between the body mass index and urinary calcium (r = 0.101, P < 0.001) and uric acid (r = 0.200, P < 0.001), a weak negative correlation with urine pH (r = -0.104, P < 0.001) was found. Urine calcium, uric acid, and oxalate excretion were low in our patients while urine citrate was relatively high. Higher BMI maybe a risk factor for nephrolithiasis.

In Idiopathic Calcium Oxalate Stone Formers, Unattached Stones Show Evidence of Having Originated as Attached Stones on Randall’s Plaque

PubMed Central

Miller, Nicole L.; Williams, James C.; Evan, Andrew P.; Bledsoe, Sharon B.; Coe, Fredric L.; Worcester, Elaine M.; Munch, Larry C.; Handa, Shelly E.; Lingeman, James E.

2009-01-01

Objective To analyze the structure and composition of unattached stones in idiopathic calcium oxalate stone formers (ICSF) and compare them to attached stones from the same cohort in order to investigate whether more than one pathogenic mechanism exists for stone formation in ICSF. Patients and methods ICSF undergoing percutaneous nephrolithotomy or ureteroscopy for treatment of nephrolithiasis were consented for this study. All accessible renal papillae were endoscopically imaged using a digital endoscope. All stones were removed and determined by the operating surgeon to be attached or unattached to the underlying papilla. Micro-computed tomography (micro-CT), which provides three-dimensional analysis of entire stones, was used to compare the structure and composition of attached versus unattached stones. Results Of 115 stones collected from 9 patients (12 renal units), only 25 stones were found not to be attached to renal papillae. Of these 25 stones, 4 were lost and 12 showed definite morphological evidence of having been attached to tissue, probably having been knocked off of papillae during access. For the remaining 9 stones, micro-CT analysis revealed at least one internal region of calcium phosphate within each of these unattached calcium oxalate (CaOx) stones. That is, the internal structure of the unattached stones is consistent with their having originated attached to RP, and then having become detached but retained in the kidney, with new layers of CaOx eventually covering the original attachment site. Conclusions Micro CT analysis supports the hypothesis that in ICSF, both attached and unattached stones occur as a result of a common pathogenic mechanism. That is, in this type of stone former, CaOx stones—even those not showing morphology that betrays attachment—all originate attached to interstitial plaque on the renal papilla. PMID:19549258

Hereditary hypophosphatemic rickets with hypercalciuria and nephrolithiasis-identification of a novel SLC34A3/NaPi-IIc mutation.

PubMed

Phulwani, Priya; Bergwitz, Clemens; Jaureguiberry, Graciana; Rasoulpour, Majjid; Estrada, Elizabeth

2011-03-01

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is characterized by rickets, hyperphosphaturia, hypophosphatemia, elevated 1,25-dihydroxyvitamin-D, increased gastrointestinal calcium absorption and hypercalciuria. Serum calcium, 25-hydroxyvitamin-D and PTH levels are normal. Here we describe a boy with HHRH, nephrolithiasis, and compound heterozygosity for one previously described mutation (g.4225_50del) and a novel splice mutation (g.1226G>A) in SLC34A3, the gene encoding the renal sodium-phosphate co-transporter NaPi-IIc. The patient's mother and grandmother are carriers of g.4225_50del, and both have a history of nephrolithiasis associated with hypercalciuria and elevated 1,25-dihydroxyvitamin-D. His three siblings (2-6 years old), who are also carriers of g.4225_50del, have hypercalciuria but so far their renal ultrasounds are normal. Thus, SLC34A3/NaPi-IIc mutations appear to be associated with variable phenotypic changes at presentation, which can include recurrent nephrolithiasis. Copyright © 2011 Wiley-Liss, Inc.

Citrate and renal calculi: an update

NASA Technical Reports Server (NTRS)

Pak, C. Y.

1994-01-01

Citrate is an inhibitor of the crystallization of stone-forming calcium salts. Hypocitraturia, frequently encountered in patients with nephrolithiasis, is therefore an important risk factor for stone formation. Potassium citrate provides physiological and physicochemical correction and inhibits new stone formation, not only in hypocitraturic calcium nephrolithiasis but also in uric acid nephrolithiasis. Inhibition of stone recurrence has now been validated by a randomized trial. Ongoing research has disclosed additional causes of hypocitraturia (sodium excess, low intestinal alkali absorption, but not primary citrate malabsorption). Moreover, new insights on potassium citrate action have been shown, notably that some of absorbed citrate escapes oxidation and contributes to the citraturic response, that ingestion with a meal does not sacrifice physiological or physicochemical action, that orange juice mimics but does not completely duplicate its actions, that potassium citrate may have a beneficial bone-sparing effect, that it may reduce stone fragments following ESWL, and that danger of aluminum toxicity is not great in subjects with functioning kidneys. Finally, the research on potassium citrate has led to two promising products, calcium citrate as an optimum calcium supplement and potassium-magnesium citrate which may be superior to potassium citrate in the management of stone disease.

Incidence of nephrolithiasis in relation to environmental exposure to lead and cadmium in a population study.

PubMed

Hara, Azusa; Yang, Wen-Yi; Petit, Thibault; Zhang, Zhen-Yu; Gu, Yu-Mei; Wei, Fang-Fei; Jacobs, Lotte; Odili, Augustine N; Thijs, Lutgarde; Nawrot, Tim S; Staessen, Jan A

2016-02-01

Whether environmental exposure to nephrotoxic agents that potentially interfere with calcium homeostasis, such as lead and cadmium, contribute to the incidence of nephrolithiasis needs further clarification. We investigated the relation between nephrolithiasis incidence and environmental lead and cadmium exposure in a general population. In 1302 participants randomly recruited from a Flemish population (50.9% women; mean age, 47.9 years), we obtained baseline measurements (1985-2005) of blood lead (BPb), blood cadmium (BCd), 24-h urinary cadmium (UCd) and covariables. We monitored the incidence of kidney stones until October 6, 2014. We used Cox regression to calculate multivariable-adjusted hazard ratios for nephrolithiasis. At baseline, geometric mean BPb, BCd and UCd was 0.29µmol/L, 9.0nmol/L, and 8.5nmol per 24h, respectively. Over 11.5 years (median), nephrolithiasis occurred in 40 people. Contrasting the low and top tertiles of the distributions, the sex- and age-standardized rates of nephrolithiasis expressed as events per 1000 person-years were 0.68 vs. 3.36 (p=0.0016) for BPb, 1.80 vs. 3.28 (p=0.11) for BCd, and 1.65 vs. 2.95 (p=0.28) for UCd. In continuous analysis, with adjustments applied for sex, age, serum magnesium, and 24-h urinary volume and calcium, the hazard ratios expressing the risk associated with a doubling of the exposure biomarkers were 1.35 (p=0.015) for BPb, 1.13 (p=0.22) for BCd, and 1.23 (p=0.070) for UCd. In conclusion, our results suggest that environmental lead exposure is a risk factor for nephrolithiasis in the general population. Copyright © 2015 Elsevier Inc. All rights reserved.

What is the incidence of kidney stones after chemotherapy in patients with lymphoproliferative or myeloproliferative disorders?

PubMed

Mirheydar, Hossein S; Banapour, Pooya; Massoudi, Rustin; Palazzi, Kerrin L; Jabaji, Ramzi; Reid, Erin G; Millard, Frederick E; Kane, Christopher J; Sur, Roger L

2014-01-01

This study describes the incidence and risk factors of de novo nephrolithiasis among patients with lymphoproliferative or myeloproliferative diseases who have undergone chemotherapy. From 2001 to 2011, patients with lymphoproliferative or myeloproliferative disorders treated with chemotherapy were retrospectively identified. The incidence of image proven nephrolithiasis after chemotherapy was determined. Demographic and clinical variables were recorded. Patients with a history of nephrolithiasis prior to chemotherapy were excluded. The primary outcome was incidence of nephrolithiasis, and secondary outcomes were risk factors predictive of de novo stone. Comparative statistics were used to compare demographic and disease specific variables for patients who developed de novo stones versus those who did not. A total of 1,316 patients were identified and the incidence of de novo nephrolithiasis was 5.5% (72/1316; symptomatic stones 1.8% 24/1316). Among patients with nephrolithiasis, 72.2% had lymphoproliferative disorders, 27.8% had myeloproliferative disorders, and 25% utilized allopurinol. The median urinary pH was 5.5, and the mean serum uric acid, calcium, potassium and phosphorus levels were 7.5, 9.6, 4.3, and 3.8 mg/dL, respectively. In univariate analysis, mean uric acid (p=0.013), calcium (p<0.001)), and potassium (p=0.039) levels were higher in stone formers. Diabetes mellitus (p<0.001), hypertension (p=0.003), and hyperlipidemia (p<0.001) were more common in stone formers. In multivariate analysis, diabetes mellitus, hyperuricemia, and hypercalcemia predicted stone. We report the incidence of de novo nephrolithiasis in patients who have undergone chemotherapy. Diabetes mellitus, hyperuricemia, and hypercalcemia are patient-specific risk factors that increase the odds of developing an upper tract stone following chemotherapy.

Citrate, malate and alkali content in commonly consumed diet sodas: implications for nephrolithiasis treatment.

PubMed

Eisner, Brian H; Asplin, John R; Goldfarb, David S; Ahmad, Ardalanejaz; Stoller, Marshall L

2010-06-01

Citrate is a known inhibitor of calcium stone formation. Dietary citrate and alkali intake may have an effect on citraturia. Increasing alkali intake also increases urine pH, which can help prevent uric acid stones. We determined citrate, malate and total alkali concentrations in commonly consumed diet sodas to help direct dietary recommendations in patients with hypocitraturic calcium or uric acid nephrolithiasis. Citrate and malate were measured in a lemonade beverage commonly used to treat hypocitraturic calcium nephrolithiasis and in 15 diet sodas. Anions were measured by ion chromatography. The pH of each beverage was measured to allow calculation of the unprotonated anion concentration using the known pK of citric and malic acid. Total alkali equivalents were calculated for each beverage. Statistical analysis was done using Pearson's correlation coefficient. Several sodas contained an amount of citrate equal to or greater than that of alkali and total alkali as a lemonade beverage commonly used to treat hypocitraturic calcium nephrolithiasis (6.30 mEq/l citrate as alkali and 6.30 as total alkali). These sodas were Diet Sunkist Orange, Diet 7Up, Sprite Zero, Diet Canada Dry Ginger Ale, Sierra Mist Free, Diet Orange Crush, Fresca and Diet Mountain Dew. Colas, including Caffeine Free Diet Coke, Coke Zero, Caffeine Free Diet Pepsi and Diet Coke with Lime, had the lowest total alkali (less than 1.0 mEq/l). There was no significant correlation between beverage pH and total alkali content. Several commonly consumed diet sodas contain moderate amounts of citrate as alkali and total alkali. This information is helpful for dietary recommendations in patients with calcium nephrolithiasis, specifically those with hypocitraturia. It may also be useful in patients with low urine pH and uric acid stones. Beverage malate content is also important since malate ingestion increases the total alkali delivered, which in turn augments citraturia and increases urine pH. Copyright 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Kidney stones: Composition, frequency and relation to metabolic diagnosis.

PubMed

Spivacow, Francisco R; Del Valle, Elisa E; Lores, Ernesto; Rey, Paula G

Nephrolithiasis is one of the most frequent urologic diseases. The aim of this paper is to study the composition and frequency of 8854 patient kidney stones and in a subset of them their metabolic risk factors to be related to their type of calculi. Physicochemical and crystallographic methods were used to assess kidney stone composition. In a subset of 715 patients, we performed an ambulatory metabolic protocol with diagnostic purposes. From the total sample 79% of stones were made of calcium salts (oxalate and phosphate), followed by uric acid stones in 16.5%, calcium salts and uric acid in 2%, other salts in 1.9% and cystine in 0.6%. Male to female ratio was almost three times higher in calcium salts and other types of stones, reaching a marked male predominance in uric acid stones, M/F 18.8 /1.0. The major risk factors for calcium stones are idiopathic hypercalciuria, followed by unduly acidic urine pH and hyperuricosuria. In uric acid stones unduly acidic urine pH and less commonly hyperuricosuria are the most frequent biochemical diagnosis. Our results show that analysis of kidney stones composition and the corresponding metabolic diagnosis may provide a scientific basis for the best management and prevention of kidney stone formation, as well as it may help us to study the mechanisms of urine stone formation.

Nephrolithiasis: Molecular Mechanism of Renal Stone Formation and the Critical Role Played by Modulators

PubMed Central

Aggarwal, Kanu Priya; Narula, Shifa; Kakkar, Monica

2013-01-01

Urinary stone disease is an ailment that has afflicted human kind for many centuries. Nephrolithiasis is a significant clinical problem in everyday practice with a subsequent burden for the health system. Nephrolithiasis remains a chronic disease and our fundamental understanding of the pathogenesis of stones as well as their prevention and cure still remains rudimentary. Regardless of the fact that supersaturation of stone-forming salts in urine is essential, abundance of these salts by itself will not always result in stone formation. The pathogenesis of calcium oxalate stone formation is a multistep process and essentially includes nucleation, crystal growth, crystal aggregation, and crystal retention. Various substances in the body have an effect on one or more of the above stone-forming processes, thereby influencing a person's ability to promote or prevent stone formation. Promoters facilitate the stone formation while inhibitors prevent it. Besides low urine volume and low urine pH, high calcium, sodium, oxalate and urate are also known to promote calcium oxalate stone formation. Many inorganic (citrate, magnesium) and organic substances (nephrocalcin, urinary prothrombin fragment-1, osteopontin) are known to inhibit stone formation. This review presents a comprehensive account of the mechanism of renal stone formation and the role of inhibitors/promoters in calcium oxalate crystallisation. PMID:24151593

Nephrolithiasis and pyelonephritis in two West Indian manatees (Trichechus manatus spp.).

PubMed

Keller, Martha; Moliner, José L; Vásquez, Grettys; Cruz, Danilo; Bello, Orestes; Costidis, Alex M; Rommel, Sentiel A; Mays, Maron B Calderwood; Gearhart, Scott

2008-07-01

Two West Indian manatees (Trichechus manatus spp.) were reported with severe emaciation. One animal was a Florida manatee from the Everglades; the other was an Antillean manatee from Cuba. On necropsy, both animals had nephrolithiasis, pyelonephritis, and moderate to severe renomegaly. Histopathology revealed multifocal to diffuse pyelonephritis, interstitial nephritis, and nephrocalcinosis. The stones were analyzed and consisted primarily of calcium carbonate. Serum chemistry values for the Florida animal revealed no renal abnormalities. The mechanism of calculus formation remains unclear in manatees. In horses, another hindgut fermenter, the most common urolith is also calcium carbonate. Urinalyses performed on manatees are very similar to those of horses (i.e., alkaline urine, low specific gravity, and calcium carbonate crystals). Formation of uroliths in manatees may have a pathogenesis similar to equine urolithiasis.

Hereditary Hypophosphatemic Rickets With Hypercalciuria and Nephrolithiasis—Identification of a Novel SLC34A3/NaPi-IIc Mutation

PubMed Central

Phulwani, Priya; Bergwitz, Clemens; Jaureguiberry, Graciana; Rasoulpour, Majjid; Estrada, Elizabeth

2015-01-01

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is characterized by rickets, hyperphosphaturia, hypophosphatemia, elevated 1,25-dihydroxyvitamin-D, increased gastrointestinal calcium absorption and hypercalciuria. Serum calcium, 25-hydroxyvitamin-D and PTH levels are normal. Here we describe a boy with HHRH, nephrolithiasis, and compound heterozygosity for one previously described mutation (g.4225_50del) and a novel splice mutation (g.1226G>A) in SLC34A3, the gene encoding the renal sodium-phosphate co-transporter NaPi-IIc. The patient’s mother and grandmother are carriers of g.4225_50del, and both have a history of nephrolithiasis associated with hypercalciuria and elevated 1,25-dihydroxyvitamin-D. His three siblings (2–6 years old), who are also carriers of g.4225_50del, have hypercalciuria but so far their renal ultrasounds are normal. Thus, SLC34A3/NaPi-IIc mutations appear to be associated with variable phenotypic changes at presentation, which can include recurrent nephrolithiasis. PMID:21344632

Drosophila Melanogaster as an Emerging Translational Model of Human Nephrolithiasis

PubMed Central

Miller, Joe; Chi, Thomas; Kapahi, Pankaj; Kahn, Arnold J.; Kim, Man Su; Hirata, Taku; Romero, Michael F.; Dow, Julian A.T.; Stoller, Marshall L.

2013-01-01

Purpose The limitations imposed by human clinical studies and mammalian models of nephrolithiasis have hampered the development of effective medical treatments and preventative measures for decades. The simple but elegant Drosophila melanogaster is emerging as a powerful translational model of human disease, including nephrolithiasis and may provide important information essential to our understanding of stone formation. We present the current state of research using D. melanogaster as a model of human nephrolithiasis. Materials and Methods A comprehensive review of the English language literature was performed using PUBMED. When necessary, authoritative texts on relevant subtopics were consulted. Results The genetic composition, anatomic structure and physiologic function of Drosophila Malpighian tubules are remarkably similar to those of the human nephron. The direct effects of dietary manipulation, environmental alteration, and genetic variation on stone formation can be observed and quantified in a matter of days. Several Drosophila models of human nephrolithiasis, including genetically linked and environmentally induced stones, have been developed. A model of calcium oxalate stone formation is among the most recent fly models of human nephrolithiasis. Conclusions The ability to readily manipulate and quantify stone formation in D. melanogaster models of human nephrolithiasis presents the urologic community with a unique opportunity to increase our understanding of this enigmatic disease. PMID:23500641

Urinary pH as a Risk Factor for Stone Type

NASA Astrophysics Data System (ADS)

Sakhaee, Khashayar

2007-04-01

A high urinary pH is main risk factor for the calcium phosphate stone formation; however, its pathophysiologic mechanism has not been fully understood. The introduction of Topiramate in the treatment of various neurological disorders has been complicated by metabolic acidosis, significant hypocitraturia, elevated urinary pH, and calcium phosphate stone formation. This model provides a probe to investigate the pathophysiologic mechanism of calcium phosphate stone formation and perhaps to develop appropriate countermeasures in the future. On the other hand an unduly acidic urine predisposes one to uric acid nephrolithiasis. Our recent investigation linking low urinary pH, and defective renal ammoniagenesis to insulin resistance provides new knowledge to unfold the pathophysiology of uric acid nephrolithiasis. The metabolic profile leading to uric acid stone may emerge as one of the components of metabolic syndrome.

Urine risk factors in children with calcium kidney stones and their siblings

PubMed Central

Bergsland, Kristin J.; Coe, Fredric L.; White, Mark D.; Erhard, Michael J.; DeFoor, William R.; Mahan, John D.; Schwaderer, Andrew L.; Asplin, John R.

2012-01-01

Calcium nephrolithiasis in children is increasing in prevalence and tends to be recurrent. Although children have a lower incidence of nephrolithiasis than adults, its etiology in children is less well understood; hence treatments targeted for adults may not be optimal in children. To better understand metabolic abnormalities in stone forming children, we compared chemical measurements and the crystallization properties of 24-hour urine collections from 129 stone formers matched to 105 non-stone forming siblings and 183 normal, healthy children with no family history of stones; all aged 6 to 17 years. The principal risk factor for calcium stone formation was hypercalciuria. Stone formers have strikingly higher calcium excretion along with high supersaturation for calcium oxalate and calcium phosphate, and a reduced distance between the upper limit of metastability and supersaturation for calcium phosphate, indicating increased risk of calcium phosphate crystallization. Other differences in urine chemistry that exist between adult stone formers and normal individuals such as hyperoxaluria, hypocitraturia, abnormal urine pH and low urine volume were not found in these children. Hence, hypercalciuria and a reduction in the gap between calcium phosphate upper limit of metastability and supersaturation are crucial determinants of stone risk. This highlights the importance of managing hypercalciuria in children with calcium stones. PMID:22358148

Urine risk factors in children with calcium kidney stones and their siblings.

PubMed

Bergsland, Kristin J; Coe, Fredric L; White, Mark D; Erhard, Michael J; DeFoor, William R; Mahan, John D; Schwaderer, Andrew L; Asplin, John R

2012-06-01

Calcium nephrolithiasis in children is increasing in prevalence and tends to be recurrent. Although children have a lower incidence of nephrolithiasis than adults, its etiology in children is less well understood; hence, treatments targeted for adults may not be optimal in children. To better understand metabolic abnormalities in stone-forming children, we compared chemical measurements and the crystallization properties of 24-h urine collections from 129 stone formers matched to 105 non-stone-forming siblings and 183 normal, healthy children with no family history of stones, all aged 6 to 17 years. The principal risk factor for calcium stone formation was hypercalciuria. Stone formers have strikingly higher calcium excretion along with high supersaturation for calcium oxalate and calcium phosphate, and a reduced distance between the upper limit of metastability and supersaturation for calcium phosphate, indicating increased risk of calcium phosphate crystallization. Other differences in urine chemistry that exist between adult stone formers and normal individuals such as hyperoxaluria, hypocitraturia, abnormal urine pH, and low urine volume were not found in these children. Hence, hypercalciuria and a reduction in the gap between calcium phosphate upper limit of metastability and supersaturation are crucial determinants of stone risk. This highlights the importance of managing hypercalciuria in children with calcium stones.

Evaluation and medical management of kidney stones in children.

PubMed

Tasian, Gregory E; Copelovitch, Lawrence

2014-11-01

We review the current literature on the diagnostic evaluation and dietary and pharmacological management of children with nephrolithiasis. We searched MEDLINE(®), Embase(®) and the Cochrane Library from their inceptions to March 2014 for published articles in English on kidney stones and therapy in children 0 to 18 years old. Based on review of the titles and abstracts, 110 of the 1,014 articles (11%) were potentially relevant to the diagnostic evaluation and medical management of nephrolithiasis in children. We summarized this literature and drew on studies performed in adult populations to augment areas in which no studies of sufficient quality have been performed in children, and to highlight areas in need of research. During the last 25 years the incidence of nephrolithiasis in children has increased by approximately 6% to 10% annually and is now 50 per 100,000 adolescents. Kidney stones that form during childhood have a similar composition to those that form in adulthood. Approximately 75% to 80% of stones are composed of predominantly calcium oxalate, 5% to 10% are predominantly calcium phosphate, 10% to 20% are struvite and 5% are pure uric acid. The recurrence rate of nephrolithiasis in patients with stones that form during childhood is poorly defined. Ultrasound should be used as the initial imaging study to evaluate children with suspected nephrolithiasis, with noncontrast computerized tomography reserved for those in whom ultrasound is nondiagnostic and the suspicion of nephrolithiasis remains high. Current treatment strategies for children with kidney stone disease are based largely on extrapolation of studies performed in adult stone formers and single institution cohort or case series studies of children. Tamsulosin likely increases the spontaneous passage of ureteral stones in children. Increased water intake and reduction of salt consumption should be recommended for all children with a history of kidney stones. Potassium citrate is a potentially effective medication for children with calcium oxalate stones and concomitant hypocitraturia, as well as children with uric acid stones. However, long-term compliance with therapy and the effect on decreasing stone recurrence in children are unknown. Based largely on efficacy in adult populations, thiazide diuretics should be considered in the treatment of children with calcium based stones and persistent hypercalciuria refractory to reductions in salt intake. The incidence of kidney stone disease in children is increasing, yet few randomized clinical trials or high quality observational studies have assessed whether dietary or pharmacological interventions decrease the recurrence of kidney stones in children. Collaborative efforts and randomized clinical trials are needed to determine the efficacy and effectiveness of alternative treatments for children with nephrolithiasis, particularly those with calcium oxalate stones and concomitant hypercalciuria and hypocitraturia. Additional areas in need of study are the optimal length of time for a trial of stone passage in children, the cost-effectiveness of medical expulsive therapy vs analgesics alone, and the size and location of stones for which medical expulsive therapy is most effective. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Effectiveness of Treatment Modalities on Kidney Stone Recurrence.

PubMed

Zisman, Anna L

2017-10-06

Nephrolithiasis is highly prevalent across all demographic groups in the Western world and beyond, and its incidence rates are rising. In addition to the morbidity of the acute event, stone disease often becomes a lifelong problem that requires preventative therapy to diminish ongoing morbidity. Across the majority of stone types, increased fluid intake and targeted dietary modifications are mainstays of therapy. Specific dietary interventions associated with reduced calcium stone risk include adequate dietary calcium intake and restriction of sodium, protein, and oxalate intake, among others. Pharmaceutical therapy may be required if lifestyle changes are insufficient to minimize risk of stone recurrence, and must be targeted to the specific metabolic abnormalities portending risk for a given patient. Therapeutic options for idiopathic calcium stone disease include thiazides, citrate salts, and uric acid-lowering agents. Alkali salts are also the treatment of choice for uric acid stone disease. Management of struvite stone disease is largely surgical, but acetohydroxamic acid is a proven second line therapy. Cystinuria requires lifestyle modifications and may call for thiol-binding agents. Significant heterogeneity of the clinical population with stone disease has previously limited opportunities for large randomized controlled trials. However, as clinical phenotypes and genotypes are increasingly clarified, there are mounting opportunities for targeted randomized controlled trials in stone prevention. In the meantime, the currently available evidence for both lifestyle and pharmacologic interventions is reviewed herein. Copyright © 2017 by the American Society of Nephrology.

Nephrolithiasis and Osteomalacia associated with adefovir-induced Fanconi syndrome in a patient with hepatitis B.

PubMed

Lin, Jueying; Zhuo, Yufeng; Zhang, Dongdong

2017-08-29

An increasing number of case reports suggest that acquired renal Fanconi syndrome may be associated with prolonged use of adefovir against hepatitis B virus. Renal Fanconi syndrome is an uncommon disease, and its complication with nephrolithiasis is quite rare. Herein, we report a rare coexistence of nephrolithiasis and acquired renal Fanconi syndrome in a chronic hepatitis B-positive patient with prolonged adefovir therapy. The patient presented with osteomalacia and nephrolithiasis. Consequently, extracorporeal shock-wave lithotripsy and left double-J ureteral stent insertion were considered for obstructive nephropathy, which was caused by nephrolithiasis. However, osteomalacia had been misdiagnosed as osteoporosis before admission to our hospital. On admission, a complexity of multiple fractures, hypophosphataemia, glycosuria without hyperglycaemia and non-anion-gap metabolic acidosis indicated a diagnosis of acquired renal Fanconi syndrome induced by adefovir. After switching from adefovir to entecavir, the patient's symptoms and laboratory findings improved significantly. The mechanism responsible for nephrolithiasis in renal Fanconi syndrome is still unclear. We recommend regularly monitoring renal function and serum calcium and serum phosphate to prevent renal Fanconi syndrome during the prolonged use of adefovir for hepatitis B virus.

Novel porcine model for calcium oxalate stone formation.

PubMed

Trojan, Brandon P; Trojan, Sara J; Navetta, Andrew; Staches, Bryce; Sutton, Bryan; Filleur, Stephanie; Nelius, Thomas

2017-10-01

Mechanisms for calcium-based stone formation are not clearly delineated. Porcine are the most anatomically and physiologically congruent mammal to humans. Our objectives were to develop a cost-effective and easily reproducible porcine model for the study of calcium-based nephrolithiasis. Crossbred male pigs (n = 16) were assigned randomly to one of the following treatments: (1) control; (2) ethylene glycol (EG) + vitamin D (VD); (3) EG + ammonium chloride (AC); (4) EG + gentamicin (G); (5) EG + Lasix; (6) EG + VD + AC; (7) EG + VD + G. Treatments were administered for 28 days; blood and urine were collected on day 0, 14, and 28. At the endpoint of the study, renal tissue was collected for gross and microscopic analysis of crystal stone formation and inflammation. Stone-forming parameters were observed in serum and urine. For control versus all other treatments, by day 28, serum BUN and creatinine were less (P < 0.01), urinary creatinine, citrate and pH were greater (P < 0.01), and urinary oxalate was less (P < 0.01). Histopathological analysis of H&E staining and stone analysis revealed formation of calcium oxalate stones and crystal formation within the renal cortex and medulla for all animals except control. Nephrotoxicity was observed in one animal from treatment EG + G. The treatments explored in this experiment provided novel examples of cost-effective porcine models for the study of nephrolithiasis. EG + VD had the strongest indicators of nephrolithiasis without nephrotoxicity.

Nephrolithiasis as a common urinary system manifestation of inflammatory bowel diseases; a clinical review and meta-analysis.

PubMed

Ganji-Arjenaki, Mahboube; Nasri, Hamid; Rafieian-Kopaei, Mahmoud

2017-07-01

The extra-intestinal manifestations of inflammatory bowel disease (IBD) are common and involve other organs or systems for example; urinary system. For this review, we used a variety of sources by searching through Web of Science, PubMed, EMBASE, Scopus and directory of open access journals (DOAJ). Urinary complications may occur in up to 22% of patients and nephrolithiasis or renal/kidney stones have been suggested to be a common manifestation of disease in forms of uric acid, calcium phosphate or calcium oxalate. We performed a meta-analysis on five clinical trials and reported that correlation between IBD and formation of stone in renal system is positive and significant (Fix-effect model; CI: 95%, P <0.001, and randomeffect model; CI: 95%, P = 0.03). Based on the reports of the clinical trials, calcium oxalate is more prevalent in Crohn's disease (CD) than in ulcerative colitis (UC).

Signification of distal urinary acidification defects in hypocitraturic patients

PubMed Central

Forni Ogna, Valentina; Blanchard, Anne; Vargas-Poussou, Rosa; Ogna, Adam; Baron, Stéphanie; Bertocchio, Jean-Philippe; Prot-Bertoye, Caroline; Nevoux, Jérôme; Dubourg, Julie; Maruani, Gérard; Mendes, Margarida; Garcia-Castaño, Alejandro; Treard, Cyrielle; Lepottier, Nelly; Houillier, Pascal; Courbebaisse, Marie

2017-01-01

Background and objectives Hypocitraturia has been associated with metabolic acidosis and mineral disorders. The aim of this study was to investigate the occurrence of urinary acidification defects underlying hypocitraturia. Materials and methods This retrospective observational study included 67 patients (32 men), aged 40.7±15.1 years with hypocitraturia (<1.67 mmol/24-h) and nephrolithiasis, nephrocalcinosis, and/or bone demineralization, referred to our center from 2000 to 2015. We aimed to assess renal distal acidification capacity, prevalence and mechanisms of urinary acidification defects. Patients with low baseline plasma HCO3- (<22 mmol/L) were studied by bicarbonate loading or furosemide/fludrocortisone tests. Patients with normal baseline plasma HCO3- had an ammonium-chloride challenge test. A normal response was a decrease in urinary pH <5.3 and an increase in urinary NH4+ ≥33 μmol/min and defined idiopathic hypocitraturia. Results Eleven patients (16.4%) had low HCO3- and overt distal acidification defect. Three had a mutation in the gene encoding AE1, 4 had Gougerot-Sjögren syndrome and no cause was found in the remaining 4 cases. Fifty-six patients (83.6%) had normal HCO3-; of those, 33 (58.9%) had idiopathic hypocitraturia. Among the 23 (41%) remaining patients, 12 were unable to increase urinary NH4+ excretion (among them, 8 were able to decrease urinary pH and 4 were not) whereas 11 were able to increase urinary NH4+ excretion but unable to decrease urinary pH. These 11 patients had higher fasting urinary calcium, reflecting bone resorption, than the other 12 patients: median 0.41 [0.24–0.47] vs. 0.22 [0.08–0.37] mmol/mmol creatinine (P = 0.04). Conclusions Patients with hypocitraturia and normal plasma HCO3- frequently show a latent acidification defect that can be further dissected into one of several subtypes based on urinary pH and NH4+ response to the acid load. Those patients with impaired urine acidification capacity but preserved NH4+ excretion exhibit particularly high calciuria and should be identified to optimize nephrolithiasis prevention. PMID:28542241

Demographic, dietary, and urinary factors and 24-h urinary calcium excretion.

PubMed

Taylor, Eric N; Curhan, Gary C

2009-12-01

Higher urinary calcium is a risk factor for nephrolithiasis. This study delineated associations between demographic, dietary, and urinary factors and 24-h urinary calcium. Cross-sectional studies were conducted of 2201 stone formers (SF) and 1167 nonstone formers (NSF) in the Health Professionals Follow-up Study (men) and Nurses' Health Studies I and II (older and younger women). Median urinary calcium was 182 mg/d in men, 182 mg/d in older women, and 192 mg/d in younger women. Compared with NSF, urinary calcium as a fraction of calcium intake was 33 to 38% higher in SF (P values < or =0.01). In regression analyses, participants were combined because associations with urinary calcium were similar in each cohort and in SF and NSF. After multivariate adjustment, participants in the highest quartile of calcium intake excreted 18 mg/d more urinary calcium than those in the lowest (P trend =0.01). Caffeine and family history of nephrolithiasis were positively associated, whereas urinary potassium, thiazides, gout, and age were inversely associated, with urinary calcium. After multivariate adjustment, participants in the highest quartiles of urinary magnesium, sodium, sulfate, citrate, phosphorus, and volume excreted 71 mg/d, 37 mg/d, 44 mg/d, 61 mg/d, 37 mg/d, and 24 mg/d more urinary calcium, respectively, than participants in the lowest (P values trend < or =0.01). Intestinal calcium absorption and/or negative calcium balance is greater in SF than NSF. Higher calcium intakes at levels typically observed in free-living individuals are associated with only small increases in urinary calcium.

Kidney stones - self-care

MedlinePlus

... self-care; Nephrolithiasis and self-care; Stones and kidney - self-care; Calcium stones and self-care; Oxalate ... provider or the hospital because you have a kidney stone. You will need to take self-care ...

Demographic, Dietary, and Urinary Factors and 24-h Urinary Calcium Excretion

PubMed Central

Curhan, Gary C.

2009-01-01

Background and objectives: Higher urinary calcium is a risk factor for nephrolithiasis. This study delineated associations between demographic, dietary, and urinary factors and 24-h urinary calcium. Design, setting, participants, & measurements: Cross-sectional studies were conducted of 2201 stone formers (SF) and 1167 nonstone formers (NSF) in the Health Professionals Follow-up Study (men) and Nurses' Health Studies I and II (older and younger women). Results: Median urinary calcium was 182 mg/d in men, 182 mg/d in older women, and 192 mg/d in younger women. Compared with NSF, urinary calcium as a fraction of calcium intake was 33 to 38% higher in SF (P values ≤0.01). In regression analyses, participants were combined because associations with urinary calcium were similar in each cohort and in SF and NSF. After multivariate adjustment, participants in the highest quartile of calcium intake excreted 18 mg/d more urinary calcium than those in the lowest (P trend =0.01). Caffeine and family history of nephrolithiasis were positively associated, whereas urinary potassium, thiazides, gout, and age were inversely associated, with urinary calcium. After multivariate adjustment, participants in the highest quartiles of urinary magnesium, sodium, sulfate, citrate, phosphorus, and volume excreted 71 mg/d, 37 mg/d, 44 mg/d, 61 mg/d, 37 mg/d, and 24 mg/d more urinary calcium, respectively, than participants in the lowest (P values trend ≤0.01). Conclusions: Intestinal calcium absorption and/or negative calcium balance is greater in SF than NSF. Higher calcium intakes at levels typically observed in free-living individuals are associated with only small increases in urinary calcium. PMID:19820135

Effect of Hygrophila spinosa in ethylene glycol induced nephrolithiasis in rats.

PubMed

Ingale, Kundan G; Thakurdesai, Prasad A; Vyawahare, Neeraj S

2012-01-01

Hygrophila spinosa (Acanthaceae) is traditionally used to treat urinary calculi. The present study aimed to evaluate the antiurolithiatic activity of methanolic extract of Hygrophila spinosa (Acanthaceae) in ethylene glycol induced nephrolithiasic rats. Methanolic extract of Hygrophila spinosa (HSME) (250 and 500 mg/ kg body weight) was administered orally to male Wistar albino rats. Ethylene glycol (EG) was used to induce nephrolithiasis. The parameters studied included water intake, urinary volume, urinary pH, urinary and kidney oxalate and calcium, urinary magnesium and serum uric acid. Ethylene glycol feeding resulted in hyperoxaluria as well as increased renal excretion of calcium and serum uric acid along with decreased excretion of urinary magnesium. Treatment with HSME significantly reduced the elevated urinary oxalate, urinary calcium and serum uric acid with increase in reduced urinary magnesium. Ethylene glycol feeding also resulted in increased levels of calcium and oxalate in kidney which was decreased after the treatment with HSME. The increased deposition of stone forming constituents in the kidneys of ethylene glycol treated rats was significantly lowered by treatment with HSME. The results indicate that the aerial parts of Hygrophila spinosa are endowed with antiurolithiatic activity, thereby justifying its traditional claim.

Epidemiology of Nephrolithiasis in Personnel Returning from Operation Iraqi Freedom

DTIC Science & Technology

2009-01-01

16 A study of twins determined that urine char- cteristics, such as urinary calcium , oxalate , citrate, and uric cid, were highly heritable.15 The...revalence or incidence. An increase in urine calcium as reported in a small group of British naval personnel eployed to the Gulf Region during the summer...Urol. 1993;150:1757-1760. 4. Robertson WG, Peacock M, Heyburn PJ, et al. Epidemiological risk factors in calcium stone disease. Scand J Urol Nephrol

Significant differences in struvite and cystine stone frequency seen among Chinese nephrolithiasis patients living in North America compared to those living in China

PubMed Central

Chi, Thomas; Usawachintachit, Manint; Filippou, Pauline; Bayne, David; Hu, Weiguo; Chang, Helena; Xia, Lei; Chen, Qi; Xue, Wei; He, Hui; Long, Qingzhi; Arsovska, Olga; Taylor, Eric; Paterson, Ryan; Sur, Roger L.; Chew, Ben; Stoller, Marshall L.

2016-01-01

Background Interracial disparities in nephrolithiasis prevalence have been reported, but the interplay between genetics and the environment for urinary stone disease risk factors is poorly understood. To examine how environment may alter genetic predisposition for stone formation, we established the International Chinese Consortium on Nephrolithiasis (ICCON) as a multi-institutional collaboration to examine patterns of nephrolithiasis presentation between Chinese patients living in different countries. Methods Chinese patients undergoing percutaneous nephrolithotomy (PCNL) at six participating institutions in China and North America over 4 years were reviewed retrospectively. Patient demographics and clinical data were compared between Chinese patients living in China and North America. Results A total of 806 patients were included, encompassing 721 Chinese patients living in China and 85 living in North America. Nephrolithiasis patients living in China were more likely to be male (67% vs. 56%, P=0.02), present at a younger age (48.6±15.0 vs. 55.0±13.0 years, P<0.01), and have a lower BMI (24.6±4.0 vs. 25.9±5.7, P=0.04) but were less likely to form struvite stones (5.5% vs. 14.1%, P<0.01). No cystine stone patients were seen in North American Chinese patients, whereas 1.8% of nephrolithiasis patients living in China presented with cystine stones. Similar rates of calcium-based and uric acid calculi as well as urinary pH were seen among both groups. Conclusions Significant differences exist between Chinese nephrolithiasis patients living in China compared to those living in North America, highlighting the importance of environmental factors in addition to genetics in modulating risk for urinary stone disease. PMID:27298786

Novel activating mutation of human calcium-sensing receptor in a family with autosomal dominant hypocalcaemia.

PubMed

Baran, Natalia; ter Braak, Michael; Saffrich, Rainer; Woelfle, Joachim; Schmitz, Udo

2015-05-15

Autosomal dominant hypocalcaemia (ADH) is caused by activating mutations in the calcium sensing receptor gene (CaR) and characterised by mostly asymptomatic mild to moderate hypocalcaemia with low, inappropriately serum concentration of PTH. The purpose of the present study was to biochemically and functionally characterise a novel mutation of CaR. A female proband presenting with hypocalcaemia was diagnosed to have "idiopathic hypoparathyroidism" at the age of 10 with a history of muscle pain and cramps. Further examinations demonstrated hypocalcaemia in nine additional family members, affecting three generations. P136L CaR mutation was predicted to cause gain of function of CaR. Affected family members showed relevant hypocalcaemia (mean ± SD; 1.9 ± 0.1 mmol/l). Patient history included mild seizures and recurrent nephrolithiasis. Genetic analysis confirmed that hypocalcaemia cosegregated with a heterozygous mutation at codon 136 (CCC → CTC/Pro → Leu) in exon 3 of CaR confirming the diagnosis of ADH. For in vitro studies P136L mutant CaR was generated by site-directed mutagenesis and examined in transiently transfected HEK293 cells. Extracellular calcium stimulation of transiently transfected HEK293 cells showed significantly increased intracellular Ca(2+) mobilisation and MAPK activity for mutant P136L CaR compared to wild type CaR. The present study gives insight about a novel activating mutation of CaR and confirms that the novel P136L-CaR mutation is responsible for ADH in this family. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Acidosis and Urinary Calcium Excretion: Insights from Genetic Disorders

PubMed Central

Cordat, Emmanuelle; Chambrey, Régine; Dimke, Henrik; Eladari, Dominique

2016-01-01

Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibition of calcium transport processes within the renal tubule. The mechanisms whereby acid alters the integrity and stability of bone have been examined extensively in the published literature. Here, after briefly reviewing this literature, we consider the effects of acid on calcium transport in the renal tubule and then discuss why not all gene defects that cause renal tubular acidosis are associated with hypercalciuria and nephrocalcinosis. PMID:27468975

Effects of dietary carbohydrates on metabolism of calcium and other minerals in normal subjects and patients with noninsulin-dependent diabetes mellitus.

PubMed

Garg, A; Bonanome, A; Grundy, S M; Unger, R H; Breslau, N A; Pak, C Y

1990-04-01

Transient hypercalciuria has been noted after high carbohydrate meals which is independent of dietary calcium and is probably due to impaired renal calcium reabsorption mediated by an increase in plasma insulin levels. Based on these observations, some investigators believe that long term intake of high carbohydrate diets may increase the risk of nephrolithiasis and possibly osteoporosis. Using a randomized cross-over design, we compared high carbohydrate diets (60% carbohydrate and 25% fat) with high fat diets (50% fat and 35% carbohydrate) for effects on metabolism of calcium and other minerals in eight normal subjects and eight euglycemic patients with noninsulin-dependent diabetes mellitus. All other dietary constituents, such as protein, fiber, fluid, minerals (including Ca, Mg, Na, K, and P), and caffeine intake, were kept constant. Despite higher daylong levels of plasma insulin on the high carbohydrate diets compared to the high fat diet in both normal and noninsulin-dependent diabetic subjects, no changes in daily urinary excretion of calcium or other constituents, associated with renal stone risk, were observed. Furthermore, there was no change in fractional intestinal 47Ca absorption. Although hypercalciuria may ensue transiently after high carbohydrate meals, we conclude that substitution of simple or complex carbohydrates for fats in an isocaloric manner for a longer duration does not result in significant urinary calcium loss, and therefore, high intakes of digestible carbohydrates may not increase the risk of nephrolithiasis or osteoporosis via this mechanism.

Analyte variations in consecutive 24-hour urine collections in children.

PubMed

Ellison, Jonathan S; Hollingsworth, John M; Langman, Craig B; Asplin, John R; Schwaderer, Andrew L; Yan, Phyllis; Bierlein, Maggie; Barraza, Mark A; Defoor, William R; Figueroa, T Ernesto; Jackson, Elizabeth C; Jayanthi, Venkata R; Johnson, Emilie K; Joseph, David B; Shnorhavorian, Margarett

2017-12-01

The metabolic evaluation of children with nephrolithiasis begins with a 24-h urine collection. For adults, the diagnostic yield increases with consecutive collections; however, little is known regarding the variability of multiple 24-h studies in the pediatric population. We sought to evaluate the variability of consecutive 24-h urine collection in children through a multi-institutional study hypothesizing that compared with a single collection, consecutive 24-h urine collections would reveal a greater degree of clinically useful information in the evaluation of children at risk for nephrolithiasis. Including data from six institutions, we identified children less than 18 years of age considered at risk for recurrent nephrolithiasis, undergoing metabolic evaluation. We evaluated a subset of patients performing two collections with urine creatinine varying by 10% or less during a 7-day period. Discordance between repeat collections based on normative urine chemistry values was evaluated. A total of 733 children met inclusion criteria, and in over a third both urine calcium and urine volume differed by 30% or more between samples. Urine oxalate demonstrated greater variation between collections in children <5 years than among older children (p = 0.030) while variation in other parameters did not differ by age. Discordance between repeat samples based on normative values was most common for urine oxalate (22.5%) and the derived relative supersaturation ratios for both calcium phosphate (25.1%) and calcium oxalate (20.5%). The proportion of discordant samples, based on normative thresholds, as well as variability greater ≥30% and 50%, respectively, are shown in the table. Our analysis indicates that stone risk in as many as one in four children may be misclassified if normative values of only a single 24-h urine are used. In light of these findings, repeat 24-h urine collections prior to targeted intervention to modify stone risk are advised to increase diagnostic yield in children at risk for nephrolithiasis. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Personalized Intervention in Monogenic Stone Formers.

PubMed

Policastro, Lucas J; Saggi, Subodh J; Goldfarb, David S; Weiss, Jeffrey P

2017-10-20

Treatment of a first-time renal stone consists of acute management followed by medical efforts to prevent stone recurrence. Although nephrolithiasis is roughly 50% heritable, the presence of a family history usually does not affect treatment since most stone disease is regarded as polygenic, ie not attributable to a single gene. Recent evidence has suggested that single mutations could be responsible for a larger proportion of renal stones than previously thought. This intriguing possibility holds the potential to change the management paradigm in stone prevention from metabolically directed therapy to more specific approaches informed by genetic screening and testing. This review synthesizes new findings concerning monogenic kidney stone disease, and provides a concise and clinically useful reference for monogenic causes. It is expected that increased awareness of these etiologies will lead to increased use of genetic testing in recurrent stone formers and further research into the prevalence of monogenic stone disease. We assembled a complete list of genes known to cause or influence nephrolithiasis based on recent reviews and commentaries. We then comprehensively searched PubMed® and Google Scholar™ for all research on each gene having a pertinent role in nephrolithiasis. We determined which genes could be considered monogenic causes of nephrolithiasis. One gene, ALPL, was excluded since nephrolithiasis is a relatively minor aspect of the disorder associated with the gene (hypophosphatasia). We summarized selected studies and assembled clinically relevant details. A total of 27 genes were reviewed in terms of recent findings, mode of inheritance of stone disease, known or supposed prevalence of mutations in the general population of stone patients and specific therapies or considerations. There is a distinct opportunity for increased use of genetic testing to improve the lives of pediatric and adult stone patients. Several genes first reported in association with rare disease may be loci for novel mutations, heterozygous disease and forme frustes as causes of stones in the broader population. Cases of idiopathic nephrolithiasis should be considered as potentially having a monogenic basis. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Alkali absorption and citrate excretion in calcium nephrolithiasis

NASA Technical Reports Server (NTRS)

Sakhaee, K.; Williams, R. H.; Oh, M. S.; Padalino, P.; Adams-Huet, B.; Whitson, P.; Pak, C. Y.

1993-01-01

The role of net gastrointestinal (GI) alkali absorption in the development of hypocitraturia was investigated. The net GI absorption of alkali was estimated from the difference between simple urinary cations (Ca, Mg, Na, and K) and anions (Cl and P). In 131 normal subjects, the 24 h urinary citrate was positively correlated with the net GI absorption of alkali (r = 0.49, p < 0.001). In 11 patients with distal renal tubular acidosis (RTA), urinary citrate excretion was subnormal relative to net GI alkali absorption, with data from most patients residing outside the 95% confidence ellipse described for normal subjects. However, the normal relationship between urinary citrate and net absorbed alkali was maintained in 11 patients with chronic diarrheal syndrome (CDS) and in 124 stone-forming patients devoid of RTA or CDS, half of whom had "idiopathic" hypocitraturia. The 18 stone-forming patients without RTA or CDS received potassium citrate (30-60 mEq/day). Both urinary citrate and net GI alkali absorption increased, yielding a significantly positive correlation (r = 0.62, p < 0.0001), with the slope indistinguishable from that of normal subjects. Thus, urinary citrate was normally dependent on the net GI absorption of alkali. This dependence was less marked in RTA, confirming the renal origin of hypocitraturia. However, the normal dependence was maintained in CDS and in idiopathic hypocitraturia, suggesting that reduced citrate excretion was largely dietary in origin as a result of low net alkali absorption (from a probable relative deficiency of vegetables and fruits or a relative excess of animal proteins).

The effects of ambient temperature, humidity and season of year on urine composition in patients with nephrolithiasis.

PubMed

Eisner, Brian H; Sheth, Sonali; Herrick, Benjamin; Pais, Vernon M; Sawyer, Mark; Miller, Nicole; Hurd, Kimberly J; Humphreys, Mitchell R

2012-12-01

Study Type--Prognosis (cohort series) Level of Evidence 2b. What's known on the subject? and What does the study add? Epidemiologic studies have shown that warmer climates are associated with increased incidence of nephrolithiasis. Many hypothesize that this is due to dehydration and lower urine volumes. The current study of stone formers reports that greater temperatures are associated with significant increases in urine calcium which may shed light on the mechanism underlying the increased stone incidence associated with increased ambient temperature. • To understand the effects of temperature, humidity and season of year on 24-h urine composition in patients with nephrolithiasis. • A retrospective review was performed of patients evaluated at four metabolic stone clinics. • Multivariate linear regression models examined the relationship between mean temperature, average humidity, season of year and 24-h urine composition. • Multivariate models adjusted for known risk factors for stone disease. • Mean temperature and average humidity data were obtained from http://www.weatherunderground.com based on patient-provided addresses. • A total of 599 patients were included in the study, comprising 239 women and 360 men with a mean age of 53.6 years (sd 15.0). • Mean temperature was 16.9 °C (sd 4.8, range -21.1 to 38.3 °C) and average humidity was 58.1% (sd 23.5, range 11-100%). • On multivariate linear regression, increasing temperature was associated with increasing urine calcium (β = 11.3, 95% CI 2.2-20.0), super-saturation of calcium oxalate (β = 0.6, 95% CI 0.2-0.9), super-saturation of calcium phosphate (β = 0.14, 95% CI 0.03-0.2), and decreasing urine sodium (β = -5.2, 95% CI -10.3 to -0.1). • As seasons become warmer (i.e. from winter to autumn to spring to summer), changes were increased urine volume (β = 0.09, 95% CI 0.01-0.2) and decreased super-saturation of calcium phosphate (β = -0.2, 95% CI -0.3 to -0.03). • There were no associations between quintile of humidity and any 24-h urine constituents. • Increasing temperature may increase stone risk by increasing urine excretion of calcium, and the super-saturation of calcium oxalate and calcium phosphate. • These findings were independent of humidity and of season of year. • This appears to be related to a physiological impact of temperature itself, rather than to geographic location. © 2012 BJU INTERNATIONAL.

Biomimetic Randall's plaque as an in vitro model system for studying the role of acidic biopolymers in idiopathic stone formation.

PubMed

Chidambaram, Archana; Rodriguez, Douglas; Khan, Saeed; Gower, Laurie

2015-01-01

Randall's plaque (RP) deposits seem to be consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers. This group forms calcium oxalate renal stones without any systemic symptoms, which contributes to the difficulty of understanding and treating this painful and recurring disease. Thus, the development of an in vitro model system to study idiopathic nephrolithiasis, beginning with RP pathogenesis, can help in identifying how plaques and subsequently stones form. One main theory of RP formation is that calcium phosphate deposits initially form in the basement membrane of the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone. Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. Given that there are many acidic proteins and polysaccharides present in the renal tissue and urine, we have put forth the hypothesis that the PILP system may be involved in urolithiasis. Therefore, our goal is to develop an in vitro model system of these two stages of composite stone formation to study the role that various acidic macromolecules may play. In our initial experiments presented here, the development of "biomimetic" RP was investigated, which will then serve as a nidus for calcium oxalate overgrowth studies. To mimic the tissue environment, MatriStem(®) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. We found that when using the PILP process to mineralize this tissue matrix, the two sides led to dramatically different mineral textures, and they bore a striking resemblance to native RP, which was not seen in the tissue mineralized via the classical crystal nucleation and growth process. The interstitium side predominantly consisted of collagen-associated mineral, while the luminal side had much less mineral, which appeared to be tiny spherules embedded within the basement membrane. Although these studies are only preliminary, they support our hypothesis that kidney stones may involve non-classical crystallization pathways induced by the large variety of macromolecular species in the urinary environment. We believe that mineralization of native tissue scaffolds is useful for developing a model system of stone formation, with the ultimate goal of developing strategies to avoid RP and its detrimental consequences in stone formation, or developing therapeutic treatments to prevent or cure the disease. Supported by NIDDK grant RO1DK092311.

Effect of animal and vegetable protein intake on oxalate excretion in idiopathic calcium stone disease.

PubMed

Marangella, M; Bianco, O; Martini, C; Petrarulo, M; Vitale, C; Linari, F

1989-04-01

Oxalate excretion was measured in healthy subjects and idiopathic calcium stone-formers on dietary regimens which differed in the type and amount of protein allowed; 24-h urine collections were obtained from 41 practising vegetarians and 40 normal persons on a free, mixed, "mediterranean" diet. Twenty idiopathic calcium stone-formers were also studied while on two low calcium, low oxalate diets which differed in that animal protein was high in one and restricted in the other. Vegetarians had higher urinary oxalate levels than controls and although the calcium levels were markedly lower, urinary saturation with calcium/oxalate was significantly higher. This mild hypercalciuria was interpreted as being secondary to both a higher intake and increased fractional intestinal absorption of oxalate. Changing calcium stone-formers from a high to a low animal protein intake produced a significant decrease in calcium excretion but there was no variation in urinary oxalate. As a result, the decrease in calcium oxalate saturation was only marginal and not significant. It was concluded that dietary animal protein has a minimal effect on oxalate excretion. Mild hyperoxaluria of idiopathic calcium stone disease is likely to be intestinal in origin. Calcium stone-formers should be advised to avoid an excess of animal protein but the risks of a vegetable-rich diet should also be borne in mind.

The influence of maternal and paternal history on stone composition and clinical course of calcium nephrolithiasis in subjects aged between 15 and 25.

PubMed

Guerra, Angela; Ticinesi, Andrea; Allegri, Franca; Nouvenne, Antonio; Pinelli, Silvana; Folesani, Giuseppina; Lauretani, Fulvio; Maggio, Marcello; Borghi, Loris; Meschi, Tiziana

2016-11-01

Our aim was to compare the influence of maternal history of stones (MHS) and paternal history of stones (PHS) on composition of calculi and disease course in a group of patients with calcium nephrolithiasis (CN) aged between 15 and 25, the age range with the maximal influence of family history on disease expression. One-hundred thirty-five patients (68 F) with CN and one stone-forming parent were retrospectively selected from the database of our outpatient stone clinic, and categorized according to MHS or PHS. Data about stone disease course and composition of passed calculi, determined by chemical analysis or Fourier-transformed infrared spectrophotometry, were collected together with information on blood chemistry and 24-h urinary profile of lithogenic risk. The characteristics of disease course and stone composition were compared using logistic regression tests adjusted for age, sex, and BMI or analysis of covariance where appropriate. Patients with MHS (n = 46) had significantly higher urinary calcium/creatinine ratio and ammonium, a higher prevalence of urological treatments (57 vs 27 %, p < 0.001) and mixed calcium oxalate/calcium phosphate stone composition (69 vs 35 %, p = 0.002) than those with PHS. At multivariate logistic regression models, MHS was independently associated with urological treatments (OR 4.5, 95 %CI 1.9-10.7, p < 0.001) and the formation of calculi with mixed calcium oxalate/calcium phosphate composition (OR 5.8, 95 %CI 1.9-17.9, p = 0.002). The method of stone analysis did not affect this result. In conclusion, in subjects aged 15-25, MHS is associated with mixed calcium stones and with a higher risk for urological procedures, and should be, therefore, considered in the management of urolithiasis.

Sulfate and thiosulfate inhibit oxalate transport via a dPrestin (Slc26a6)-dependent mechanism in an insect model of calcium oxalate nephrolithiasis.

PubMed

Landry, Greg M; Hirata, Taku; Anderson, Jacob B; Cabrero, Pablo; Gallo, Christopher J R; Dow, Julian A T; Romero, Michael F

2016-01-15

Nephrolithiasis is one of the most common urinary tract disorders, with the majority of kidney stones composed of calcium oxalate (CaOx). Given its prevalence (US occurrence 10%), it is still poorly understood, lacking progress in identifying new therapies because of its complex etiology. Drosophila melanogaster (fruitfly) is a recently developed model of CaOx nephrolithiasis. Effects of sulfate and thiosulfate on crystal formation were investigated using the Drosophila model, as well as electrophysiological effects on both Drosophila (Slc26a5/6; dPrestin) and mouse (mSlc26a6) oxalate transporters utilizing the Xenopus laevis oocyte heterologous expression system. Results indicate that both transport thiosulfate with a much higher affinity than sulfate Additionally, both compounds were effective at decreasing CaOx crystallization when added to the diet. However, these results were not observed when compounds were applied to Malpighian tubules ex vivo. Neither compound affected CaOx crystallization in dPrestin knockdown animals, indicating a role for principal cell-specific dPrestin in luminal oxalate transport. Furthermore, thiosulfate has a higher affinity for dPrestin and mSlc26a6 compared with oxalate These data indicate that thiosulfate's ability to act as a competitive inhibitor of oxalate via dPrestin, can explain the decrease in CaOx crystallization seen in the presence of thiosulfate, but not sulfate. Overall, our findings predict that thiosulfate or oxalate-mimics may be effective as therapeutic competitive inhibitors of CaOx crystallization. Copyright © 2016 the American Physiological Society.

Medical management to prevent recurrent nephrolithiasis in adults: a systematic review for an American College of Physicians Clinical Guideline.

PubMed

Fink, Howard A; Wilt, Timothy J; Eidman, Keith E; Garimella, Pranav S; MacDonald, Roderick; Rutks, Indulis R; Brasure, Michelle; Kane, Robert L; Ouellette, Jeannine; Monga, Manoj

2013-04-02

Optimum management to prevent recurrent kidney stones is uncertain. To evaluate the benefits and harms of interventions to prevent recurrent kidney stones. MEDLINE, Cochrane, and other databases through September 2012 and reference lists of systematic reviews and randomized, controlled trials (RCTs). 28 English-language RCTs that studied treatments to prevent recurrent kidney stones and reported stone outcomes. One reviewer extracted data, a second checked accuracy, and 2 independently rated quality and graded strength of evidence. In patients with 1 past calcium stone, low-strength evidence showed that increased fluid intake halved recurrent composite stone risk compared with no treatment (relative risk [RR], 0.45 [95% CI, 0.24 to 0.84]). Low-strength evidence showed that reducing soft-drink consumption decreased recurrent symptomatic stone risk (RR, 0.83 [CI, 0.71 to 0.98]). In patients with multiple past calcium stones, most of whom were receiving increased fluid intake, moderate-strength evidence showed that thiazides (RR, 0.52 [CI, 0.39 to 0.69]), citrates (RR, 0.25 [CI, 0.14 to 0.44]), and allopurinol (RR, 0.59 [CI, 0.42 to 0.84]) each further reduced composite stone recurrence risk compared with placebo or control, although the benefit from allopurinol seemed limited to patients with baseline hyperuricemia or hyperuricosuria. Other baseline biochemistry measures did not allow prediction of treatment efficacy. Low-strength evidence showed that neither citrate nor allopurinol combined with thiazide was superior to thiazide alone. There were few withdrawals among patients with increased fluid intake, many among those with other dietary interventions and more among those who received thiazide and citrate than among control patients. Reporting of adverse events was poor. Most trial participants had idiopathic calcium stones. Nearly all studies reported a composite (including asymptomatic) stone recurrence outcome. In patients with 1 past calcium stone, increased fluid intake reduced recurrence risk. In patients with multiple past calcium stones, addition of thiazide, citrate, or allopurinol further reduced risk. Agency for Healthcare Research and Quality.

Hypercalciuric Bone Disease

NASA Astrophysics Data System (ADS)

Favus, Murray J.

2008-09-01

Hypercalciuria plays an important causal role in many patients with calcium oxalate (CaOx) stones. The source of the hypercalciuria includes increased intestinal Ca absorption and decreased renal tubule Ca reabsorption. In CaOx stone formers with idiopathic hypercalciuria (IH), Ca metabolic balance studies have revealed negative Ca balance and persistent hypercalciuria in the fasting state and during low dietary Ca intake. Bone resorption may also contribute to the high urine Ca excretion and increase the risk of bone loss. Indeed, low bone mass by DEXA scanning has been discovered in many IH patients. Thiazide diuretic agents reduce urine Ca excretion and may increase bone mineral density (BMD), thereby reducing fracture risk. Dietary Ca restriction that has been used unsuccessfully in the treatment of CaOx nephrolithiasis in the past may enhance negative Ca balance and accelerate bone loss. DEXA scans may demonstrate low BMD at the spine, hip, or forearm, with no predictable pattern. The unique pattern of bone histologic changes in IH differs from other causes of low DEXA bone density including postmenopausal osteoporosis, male hypogonadal osteoporosis, and glucocorticoid-induced osteoporosis. Hypercalciuria appears to play an important pathologic role in the development of low bone mass, and therefore correction of urine Ca losses should be a primary target for treatment of the bone disease accompanying IH.

Nephrocalcinosis: re-defined in the era of endourology

PubMed Central

Miller, Nicole L.; Humphreys, Mitchell R.; Coe, Fredric L.; Evan, Andrew P.; Bledsoe, Sharon B.; Handa, Shelly E.; Lingeman, James E.

2013-01-01

Nephrocalcinosis generally refers to the presence of calcium salts within renal tissue, but this term is also used radiologically in diagnostic imaging in disease states that also produce renal stones, so that it is not always clear whether it is tissue calcifications or urinary calculi that give rise to the characteristic appearance of the kidney on x-ray or computed tomography (CT). Recent advances in endoscopic imaging now allow the visual distinction between stones and papillary nephrocalcinosis, and intrarenal endoscopy can also verify the complete removal of urinary stones, so that subsequent radiographic appearance can be confidently attributed to nephrocalcinosis. This report shows exemplary cases of primary hyperparathyroidism, type I distal renal tubular acidosis, medullary sponge kidney, and common calcium oxalate stone formation. In the first three cases—all being conditions commonly associated with nephrocalcinosis—it is shown that the majority of calcifications seen by radiograph may actually be stones. In common calcium oxalate stones formers, it is shown that Randall's plaque can appear as a small calculus on CT scan, even when calyces are known to be completely clear of stones. In the current era with the use of non-contrast CT for the diagnosis of nephrolithiasis, the finding of calcifications in close association with the renal papillae is common. Distinguishing nephrolithiasis from nephrocalcinosis requires direct visual inspection of the papillae and so the diagnosis of nephrocalcinosis is essentially an endoscopic, not radiologic, diagnosis. PMID:21057942

Predictors of renal function in primary hyperparathyroidism.

PubMed

Walker, Marcella D; Nickolas, Thomas; Kepley, Anna; Lee, James A; Zhang, Chiyuan; McMahon, Donald J; Silverberg, Shonni J

2014-05-01

Current guidelines for parathyroidectomy in primary hyperparathyroidism (PHPT) include an estimated glomerular filtration rate (eGFR) less than 60 mL/min per 1.73 m(2). Although the biochemical abnormalities associated with PHPT could impair renal function, there are currently no data examining whether more severe hypercalcemia, hypercalciuria, or nephrolithiasis are associated with chronic kidney disease (CKD) in mild PHPT. This cross-sectional study evaluated predictors of renal function in PHPT. This is a case series of PHPT patients with (eGFR < 60 mL/min per 1.73 m(2)) and without (eGFR ≥ 60 mL/min per 1.73 m(2)) CKD. We studied 114 PHPT patients in a university hospital setting. We identified predictors of renal function using multiple linear regression. eGFR was associated with age, hypertension, antihypertensive medication use, fasting glucose, and 25-hydroxyvitamin D. eGFR was positively rather than negatively associated with several PHPT disease severity indices including history of nephrolithiasis, 24-hour urinary calcium excretion, and 1,25-dihydroxyvitamin D but not serum calcium or PTH levels. An eGFR less than 60 mL/min per 1.73 m(2) was observed in 15% (n = 17), all of whom had stage 3 CKD (eGFR 30-59 mL/min per 1.73 m(2)). Those with CKD were older, had higher 25-hydroxyvitamin D levels and lower 1,25-dihydroxyvitamin D levels, and were more likely to be hypertensive than those without CKD. There were no between-group (<60 vs ≥60 mL/min per 1.73 m(2)) differences in serum calcium, PTH, nephrolithiasis, or meeting surgical criteria other than eGFR. Multiple linear regression indicated that age and diastolic blood pressure were negatively associated with eGFR, whereas serum calcium, kidney stones, and alcohol use were positive predictors. Calculation of eGFR using either the Modification of Diet in Renal Disease or Chronic Kidney Disease Epidemiology Collaboration equation yielded similar results. PHPT patients with stage 3 CKD do not have biochemical or clinical evidence of more severe hyperparathyroidism compared with those without CKD. Traditional risk factors, rather than clinical or biochemical indices of PHPT, are associated with lower eGFR in mild PHPT.

Predictors of Renal Function in Primary Hyperparathyroidism

PubMed Central

Nickolas, Thomas; Kepley, Anna; Lee, James A.; Zhang, Chiyuan; McMahon, Donald J.; Silverberg, Shonni J.

2014-01-01

Context: Current guidelines for parathyroidectomy in primary hyperparathyroidism (PHPT) include an estimated glomerular filtration rate (eGFR) less than 60 mL/min per 1.73 m2. Although the biochemical abnormalities associated with PHPT could impair renal function, there are currently no data examining whether more severe hypercalcemia, hypercalciuria, or nephrolithiasis are associated with chronic kidney disease (CKD) in mild PHPT. Objective: This cross-sectional study evaluated predictors of renal function in PHPT. Design: This is a case series of PHPT patients with (eGFR < 60 mL/min per 1.73 m2) and without (eGFR ≥ 60 mL/min per 1.73 m2) CKD. Settings and Participants: We studied 114 PHPT patients in a university hospital setting. Outcome Measures: We identified predictors of renal function using multiple linear regression. Results: eGFR was associated with age, hypertension, antihypertensive medication use, fasting glucose, and 25-hydroxyvitamin D. eGFR was positively rather than negatively associated with several PHPT disease severity indices including history of nephrolithiasis, 24-hour urinary calcium excretion, and 1,25-dihydroxyvitamin D but not serum calcium or PTH levels. An eGFR less than 60 mL/min per 1.73 m2 was observed in 15% (n = 17), all of whom had stage 3 CKD (eGFR 30–59 mL/min per 1.73 m2). Those with CKD were older, had higher 25-hydroxyvitamin D levels and lower 1,25-dihydroxyvitamin D levels, and were more likely to be hypertensive than those without CKD. There were no between-group (<60 vs ≥60 mL/min per 1.73 m2) differences in serum calcium, PTH, nephrolithiasis, or meeting surgical criteria other than eGFR. Multiple linear regression indicated that age and diastolic blood pressure were negatively associated with eGFR, whereas serum calcium, kidney stones, and alcohol use were positive predictors. Calculation of eGFR using either the Modification of Diet in Renal Disease or Chronic Kidney Disease Epidemiology Collaboration equation yielded similar results. Conclusions: PHPT patients with stage 3 CKD do not have biochemical or clinical evidence of more severe hyperparathyroidism compared with those without CKD. Traditional risk factors, rather than clinical or biochemical indices of PHPT, are associated with lower eGFR in mild PHPT. PMID:24527717

Bilateral renal milk of calcium masquerading as nephrolithiasis in patients with spinal cord injury.

PubMed

Vaidyanathan, Subramanian; Hughes, Peter L; Soni, Bakul M

2007-01-01

Milk of calcium is a viscous colloidal suspension of calcium carbonate, calcium phosphate, or calcium oxalate, or a mixture of these compounds. The calcific material gravitates to the dependent portion of a cystic cavity. Crescent- or hemisphere-shaped calcium density with a sharp horizontal upper border at the milk of calcium-clear fluid interface confirms the diagnosis. Bilateral milk of calcium in the renal pelvis or in dilated calyces is very rare and has not been reported in patients with spinal cord injury. A 63-year-old male patient with T-10 paraplegia presented with recurrent urinary tract infections. X-ray of the kidneys, taken with the vertical beam while the patient lay supine, revealed a poorly defined opacity overlying the lower pole of the right kidney. Findings on ultrasonography of the kidneys were interpreted as a large, staghorn-type calculus in the dilated lower pole calyx of the right kidney. Because x-ray of the kidneys showed a poorly defined opacity overlying the lower pole of the right kidney, milk of calcium was suspected, and computed tomography (CT) of the kidneys was performed. Calcific debris with horizontal layering in the lower pole calyces of both kidneys was seen; this confirmed the diagnosis of milk of calcium. A 62-year-old female patient with C-7 tetraplegia underwent ileal conduit urinary diversion. Subsequently, she developed calculi in the right kidney, which were treated with shock wave lithotripsy. Follow-up x-ray revealed faintly opaque shadows with indistinct margins in the region of both kidneys. Intravenous urography showed cortical thinning at the upper poles and blunting of the calyces, suggestive of chronic pyelonephritis. The right renal pelvis was bulky, and bilateral renal calculi were diagnosed during ultrasonography; however, the presence of faintly radio-opaque shadows with indistinct margins raised suspicions of renal milk of calcium. A CT scan of the kidneys, which was performed in the supine and subsequently in the prone position, revealed gravity-dependent layering of calcific material in the pelves of both kidneys and in the midpole calyces of the right kidney, thus confirming the diagnosis of milk of calcium. In conclusion, CT scan of the kidneys confirmed the diagnosis of bilateral renal milk of calcium, a very rare entity in patients with spinal cord injury. Awareness of typical and unique features of milk of calcium during imaging enables physicians to recognize renal milk of calcium and to differentiate it from nephrolithiasis, thereby avoiding unwarranted interventions such as shock wave lithotripsy or endoscopic procedures.

Ossification of the cervical ligamentum flavum and osseous brown tumor: late manifestations of primary hyperparathyroidism misdiagnosed in a case of parathyroid carcinoma

PubMed Central

Sampanis, Nikolaos; Gavriilaki, Eleni; Paschou, Eleni; Kalaitzoglou, Asterios; Vasileiou, Sotirios

2016-01-01

Summary Parathyroid carcinoma represents an extremely rare neoplasm with diverse clinical manifestations. Herein we aimed at presenting an unique case of a young patient with late manifestations of parathyroid cancer and reviewing the relevant literature. A 45-year-old male patient presented in the Outpatient Clinic with an episode of nephrolithiasis. His personal medical history includes: recurrent episodes of nephrolithiasis, laminectomy in the cervical spine due to ossification of the cervical ligamentum flavum and surgical resection of a giant cell tumor of the brain. Laboratory testing revealed findings of primary hyperparathyroidism (serum calcium 16,0 mmol/l phosphorus 1,46 mg/dl and parathyroid hormone/PTH 8560 pg/ml). Neck ultrasound and technetium-99 m sestamibi scan were performed showing a parathyroid tumor. Due to the persistently high serum calcium and PTH levels, the high alkaline phosphatase levels (440 IU/L) and the late manifestations of HPT, surgical excision of the tumor was performed. The tumor was identified as parathyroid carcinoma. Immediately after surgery serum calcium and phosphorus levels were normalized. The patient is on a regular follow-up program with no signs of recurrence or metastasis one year after the excision. We describe the coexistence of rare late manifestations of HPT, which had not been adequately investigated at their onset in this young patient. Therefore, increased awareness is needed in order to recognize and further investigate signs or symptoms of HPT. PMID:27252748

Ossification of the cervical ligamentum flavum and osseous brown tumor: late manifestations of primary hyperparathyroidism misdiagnosed in a case of parathyroid carcinoma.

PubMed

Sampanis, Nikolaos; Gavriilaki, Eleni; Paschou, Eleni; Kalaitzoglou, Asterios; Vasileiou, Sotirios

2016-01-01

Parathyroid carcinoma represents an extremely rare neoplasm with diverse clinical manifestations. Herein we aimed at presenting an unique case of a young patient with late manifestations of parathyroid cancer and reviewing the relevant literature. A 45-year-old male patient presented in the Outpatient Clinic with an episode of nephrolithiasis. His personal medical history includes: recurrent episodes of nephrolithiasis, laminectomy in the cervical spine due to ossification of the cervical ligamentum flavum and surgical resection of a giant cell tumor of the brain. Laboratory testing revealed findings of primary hyperparathyroidism (serum calcium 16,0 mmol/l phosphorus 1,46 mg/dl and parathyroid hormone/PTH 8560 pg/ml). Neck ultrasound and technetium-99 m sestamibi scan were performed showing a parathyroid tumor. Due to the persistently high serum calcium and PTH levels, the high alkaline phosphatase levels (440 IU/L) and the late manifestations of HPT, surgical excision of the tumor was performed. The tumor was identified as parathyroid carcinoma. Immediately after surgery serum calcium and phosphorus levels were normalized. The patient is on a regular follow-up program with no signs of recurrence or metastasis one year after the excision. We describe the coexistence of rare late manifestations of HPT, which had not been adequately investigated at their onset in this young patient. Therefore, increased awareness is needed in order to recognize and further investigate signs or symptoms of HPT.

Kidney Calculi: Pathophysiology and as a Systemic Disorder.

PubMed

Shadman, Arash; Bastani, Bahar

2017-05-01

The pathophysiology of urinary stone formation is complex, involving a combination of metabolic, genetic, and environmental factors. Over the past decades, remarkable advances have been emerged in the understanding of the pathogenesis, diagnosis, and treatment of calcium kidney calculi. For this review, both original and review articles were found via PubMed search on pathophysiology, diagnosis, and management of urinary calculi. These resources were integrated with the authors' knowledge of the field. Nephrolithiasis is suggested to be associated with systemic disorders, including chronic kidney insufficiency, hematologic malignancies, endocrine disorders, autoimmune diseases, inflammatory bowel diseases, bone loss and fractures, hypertension, type 2 diabetes mellitus, metabolic syndrome, and vascular diseases like coronary heart diseases and most recently ischemic strokes. This is changing the perspective of nephrolithiasis from an isolated disorder to a systemic disease that justifies further research in understanding the underlying mechanisms and elaborating diagnostic-therapeutic options.

Renal Stone Risk During Spaceflight: Assessment and Countermeasure Validation

NASA Technical Reports Server (NTRS)

Pietrzyk, Robert A.; Whitson, Peggy A.; Sams, Clarence F.; Jones, Jeffery A.; Smith, Scott M.

2009-01-01

This viewgraph presentation describes the risks of renal stone formation in manned space flight. The contents include: 1) Risk; 2) Evidence; 3) Nephrolithiasis -A Multifactorial Disease; 4) Symptoms/signs; 5) Urolithiasis and Stone Passage; 6) Study Objectives; 7) Subjects; 8) Methods; 9) Investigation Results; 10) Potassium Citrate; 11) Calcium Balance; 12) Case Study; 13) Significant Findings; 14) Risk Mitigation Strategies and Recommended Actions; and 15) Future Potential.

Distal Renal Tubular Acidosis and Calcium Nephrolithiasis

NASA Astrophysics Data System (ADS)

Moe, Orson W.; Fuster, Daniel G.; Xie, Xiao-Song

2008-09-01

Calcium stones are commonly encountered in patients with congenital distal renal tubular acidosis, a disease of renal acidification caused by mutations in either the vacuolar H+-ATPase (B1 or a4 subunit), anion exchanger-1, or carbonic anhydrase II. Based on the existing database, we present two hypotheses. First, heterozygotes with mutations in B1 subunit of H+-ATPase are not normal but may harbor biochemical abnormalities such as renal acidification defects, hypercalciuria, and hypocitraturia which can predispose them to kidney stone formation. Second, we propose at least two mechanisms by which mutant B1 subunit can impair H+-ATPase: defective pump assembly and defective pump activity.

[Role of bones in the physiopathology of idiopathic hypercalciuria: effect of amino-bisphosphonate alendronate].

PubMed

Weisinger, J R; Alonzo, E; Machado, C; Carlini, R; Martinis, R; Paz-Martínez, V; Bellorín-Font, E

1997-01-01

Previous studies from our laboratory demonstrated that bone mineral content is affected in patients with idiopathic hypercalciuria and that there is a correlation between bone mineral loss and in-vitro cytokine production. At the same time we found that short term treatment with alendronate decreased urinary calcium in these subjects. In the present study we have examined the long-term effects of alendronate treatment (10 mg/day for one year) on urinary calcium, urinary hydroxyproline and bone mineral content in 18 idiopathic hypercalciuric and 8 normocalciuric stone formers. Clinical characteristics, as well as gender and age distribution were similar in both groups. Urinary calcium and hydroxyproline, were measured monthly. Calcium excretion decreased significantly at the end of the first month, and remained lower thereafter (277 +/- 28, before vs. 202 +/- 26 mg/g creatinine, after 12 months on alendronate, p < 0.01). Urinary hydroxyproline decreased significantly during the study (125.5 +/- 32.1 vs. 39.66 +/- 17.5 mg/g creatinine, p < 0.05). Serum calcium, glomerular filtration rate, and urinary sodium, did not change during the study. Lumbar spine bone density (trabecular bone) obtained with X ray absorptiometry revealed a significant increase from 1.162 +/- 0.231 to 1.197 +/- 0.248 g/cm2 (p < 0.01). These changes were associated with a significant decrease in IL-1 alpha mRNA transcription by unstimulated and lipopolysaccharide stimulated blood mononuclear cells, as tested by the reverse transcriptase polymerase chain reaction. No changes were observed in bone cortical sites (femoral neck). Normocalciuric subjects showed no significant changes in urinary calcium. In summary, the changes observed in urinary calcium excretion and different bone metabolic parameters, suggest a role of bone in the pathophysiology of idiopathic hypercalciuria.

Risk of calcium oxalate nephrolithiasis in postmenopausal women supplemented with calcium or combined calcium and estrogen.

PubMed

Domrongkitchaiporn, Somnuek; Ongphiphadhanakul, Boonsong; Stitchantrakul, Wasana; Chansirikarn, Sirinthorn; Puavilai, Gobchai; Rajatanavin, Rajata

2002-02-26

Recent studies showed that postmenopausal women lost less bone mass when supplemented with calcium or estrogen therapy. However, the safety of the treatments in terms of the risk of calcium oxalate stone formation is unknown. We therefore conducted this study to determine the alteration in calcium oxalate supersaturation after calcium supplement or after combined calcium and estrogen therapy in postmenopausal osteoporotic women. Fifty-six postmenopausal women were enrolled in this study. All subjects were more than 10 years postmenopausal with vertebral or femoral osteoporosis by bone mineral density criteria. They were randomly allocated to receive either 625 mg of calcium carbonate (250 mg of elemental calcium) at the end of a meal three times a day (group A, n=26) or calcium carbonate in the same manner plus 0.625 mg/day of conjugated equine estrogen and 5 mg medrogestone acetate from day 1-12 each month (group B, n=30). The age (mean +/- S.E.M.) was 66.3 +/- 1.2 and 65.1 +/- 1.1 years, weight 54.1 +/- 1.2 and 55.3 +/- 2.1 kg, in group A and group B, respectively. Urine specimens (24-h) were collected at baseline and 3 months after treatment for the determination of calcium oxalate saturation by using Tiselius's index (AP(CaOx)) and calcium/citrate ratio. After 3 months of treatment, there was no significant alteration from baseline for urinary excretion of calcium, citrate and oxalate. Urinary phosphate excretion was significantly reduced (6.3 +/- 0.7 vs. 5.1 +/- 0.7 mmol/day for group A and 8.2 +/- 0.9 vs. 5.8 +/- 0.7 mmol/day for group B, P<0.05), whereas net alkaline absorption was significantly elevated (10.1 +/- 3.6 vs. 20.1 +/- 4.4 meq/day for group A and 4.8 +/- 3.2 vs. 19.9 +/- 3.6 meq/day for group B, P<0.05). Calcium/citrate ratio and AP(CaOx) determined at baseline were not different from the corresponding values after treatment in both groups; calcium/citrate: 10.1 +/- 3.1 vs. 10.1 +/- 2.5 for group A and 9.3 +/- 1.8 vs. 11.9 +/- 2.5 for group B and AP(CaOx): 1.1 +/- 0.1 vs. 1.3 +/- 0.2 for group A and 1.2 +/- 0.2 vs. 1.1 +/- 0.1 for group B. There were eight and nine patients with high AP(CaOx), or >2, at baseline and after treatment, respectively. Calcium supplement with a meal or combined calcium supplement and estrogen therapy is not associated with a significant increased risk of calcium oxalate stone formation in the majority of postmenopausal osteoporotic patients. Determination of urinary saturation for calcium oxalate after calcium and estrogen supplements, especially at the initial phase of treatment, may be helpful in the avoidance of nephrolithiasis.

Familial microscopic hematuria caused by hypercalciuria and hyperuricosuria.

PubMed

Praga, M; Alegre, R; Hernández, E; Morales, E; Domínguez-Gil, B; Carreño, A; Andrés, A

2000-01-01

We report 12 patients belonging to five different families in whom persistent isolated microhematuria was associated with hypercalciuria and/or hyperuricosuria. Four patients had episodes of gross hematuria, three patients had passed renal stones, and a history of nephrolithiasis was obtained in four of the families (80%). Calcium oxalate and uric acid crystals were commonly observed in the urine sediments. Urinary erythrocytes had a normal appearance on phase-microscopic examination. Reduction of calciuria and uricosuria by thiazide diuretics, allopurinol, forced fluid intake, and dietetic measures led to a persistent normalization of urine sediment with complete disappearance of hematuria. Determination of calcium and uric acid urinary excretions should be included in the study of familial hematuria.

Influence of BMI in nephrolithiasis in an Appalachian pediatric population: A single-center experience.

PubMed

Murphy, Margaret O; Erpelding, Scott G; Chishti, Aftab S; Dugan, Adam; Ziada, Ali; Kiessling, Stefan G

2018-06-07

The prevalence of pediatric nephrolithiasis has increased significantly in the past 20 years. Metabolic abnormalities predisposing adults to nephrolithiasis in obese patients include increased urinary sodium and uric acid excretion as well as low urine pH; however, limited data are available in the pediatric population. The aim was to investigate whether obese pediatric patients presenting with nephrolithiasis have a unique metabolic profile similar to reported findings in obese adults with nephrolithiasis. A retrospective chart review was performed in children aged 1-18 years seen at Kentucky Children's Hospital between 2010 and 2016. Inclusion criteria included all patients with documented stones confirmed by ultrasonography or computed tomography. A total of 111 patient charts were reviewed in the study with a mean age of 11.8 ± 4.2 years. Seventy patients (63%) had a normal BMI and 41 patients (37%) were considered overweight/obese. There was no statistically significant relationship between BMI and stone recurrence. Obese patients had significantly decreased levels of urinary citrate, oxalate, magnesium, and potassium with significant elevations of urinary urea nitrogen, ammonia, and low urine pH compared with normal weight patients (Summary Figure). Several groups have reported on metabolic findings within obese and non-obese pediatric patients. A Turkish study reported increased oxalate excretion and hypocitraturia in obese patients while a Korean study also reported increased rates of hypocitraturia in recurrent stone formers. Similar to these studies, we did find significant differences in citrate within our study population; however, we found significantly lower levels of urinary oxalate in obese patients. The majority of these studies do not report an association with BMI and urine pH although this has been reported in the adult population and our findings support an inverse relationship between body mass index (BMI) and pH. Our group found a higher level of calcium phosphate stones, supporting of Eisner's findings that high BMI is associated with increased supersaturation of calcium phosphate. Limitations of our study include being a single center and retrospective in nature. Our study demonstrates differences in types of stones and urinary metabolites in an obese pediatric population suggestive of different metabolic profiles contributing to stone disease. We report similar association between BMI and urine pH, urinary potassium, and citrate. This study confirmed our primary hypothesis that obese pediatric patients would have a different urinary mineral profile as evidenced by lower levels of citrate and potassium and low urine pH; however, obese patients did not exhibit significantly elevated urinary sodium and uric acid when normalized to weight, as described in the adult population. Our study did not confirm our secondary hypothesis that stone composition would be associated with BMI status or stone recurrence. Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter.

PubMed

Prié, Dominique; Huart, Virginie; Bakouh, Naziha; Planelles, Gabrielle; Dellis, Olivier; Gérard, Bénédicte; Hulin, Philippe; Benqué-Blanchet, François; Silve, Caroline; Grandchamp, Bernard; Friedlander, Gérard

2002-09-26

Epidemiologic studies suggest that genetic factors confer a predisposition to the formation of renal calcium stones or bone demineralization. Low serum phosphate concentrations due to a decrease in renal phosphate reabsorption have been reported in some patients with these conditions, suggesting that genetic factors leading to a decrease in renal phosphate reabsorption may contribute to them. We hypothesized that mutations in the gene coding for the main renal sodium-phosphate cotransporter (NPT2a) may be present in patients with these disorders. We studied 20 patients with urolithiasis or bone demineralization and persistent idiopathic hypophosphatemia associated with a decrease in maximal renal phosphate reabsorption. The coding region of the gene for NPT2a was sequenced in all patients. The functional consequences of the mutations identified were analyzed by expressing the mutated RNA in Xenopus laevis oocytes. Two patients, one with recurrent urolithiasis and one with bone demineralization, were heterozygous for two distinct mutations. One mutation resulted in the substitution of phenylalanine for alanine at position 48, and the other in a substitution of methionine for valine at position 147. Phosphate-induced current and sodium-dependent phosphate uptake were impaired in oocytes expressing the mutant NPT2a. Coinjection of oocytes with wild-type and mutant RNA indicated that the mutant protein had altered function. Heterozygous mutations in the NPT2a gene may be responsible for hypophosphatemia and urinary phosphate loss in persons with urolithiasis or bone demineralization. Copyright 2002 Massachusetts Medical Society

Efficacy of Mixtures of Magnesium, Citrate and Phytate as Calcium Oxalate Crystallization Inhibitors in Urine.

PubMed

Grases, Felix; Rodriguez, Adrian; Costa-Bauza, Antonia

2015-09-01

The main aim of the current study was to evaluate the effectiveness of mixtures of magnesium, citrate and phytate as calcium oxalate crystallization inhibitors. A turbidimetric assay in synthetic urine was performed to obtain induction times for calcium oxalate crystallization in the absence and presence of different mixtures of inhibitors. The morphology of calcium oxalate crystals in the absence or presence of inhibitors and mixtures of the inhibitors was evaluated in 2 crystallization experiments at low and high calcium oxalate supersaturation. The crystals formed were examined using scanning electron microscopy. Examination of crystallization induction times revealed clear inhibitory effects of magnesium, citrate and phytate on calcium oxalate crystallization, supporting usefulness in the treatment and prevention of calcium oxalate nephrolithiasis. Significant synergistic effects between magnesium and phytate were observed. Scanning electron microscopy images revealed that phytate is a powerful crystal growth inhibitor of calcium oxalate, totally preventing the formation of trihydrate and monohydrate. In addition to crystallization inhibition capacity, citrate and magnesium avoided calcium oxalate crystallization by decreasing its supersaturation. The synergistic effect between magnesium and phytate on calcium oxalate crystallization suggests that a combination of these 2 compounds may be highly useful as antilithiasis therapy. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Management of male osteoporosis.

PubMed

Cortet, B; Vasseur, J; Grardel, B; Catanzariti, L; Marchandise, X; Delcambre, B

2001-05-01

The objective of this study was to evaluate the efficacy of treatments for male osteoporosis selected based on the cause of the disease. Sixty-three men with osteoporosis (T-score at the lumbar spine and/or femoral neck lower than -2.5) with a mean age of 53+/-11 years were studied. Forty-three (68.3%) had a history of fracturing without trauma (vertebral fractures, 37 patients, 57%). Treatments were as follows: idiopathic osteoporosis: calcium and vitamin D supplements (N = 10) or cyclical etidronate for 2 weeks followed by calcium and vitamin D supplements for 76 days (N = 29); moderate idiopathic phosphate diabetes: calcitriol and phosphate (N = 15); idiopathic hypercalciuria: hydrochlorothiazide (N = 6); and hypogonadism: testosterone (N = 3). Percentage change in bone mineral density (mean +/- standard error of the mean) after 18 months: calcium and vitamin D (lumbar spine: 0.6+/-2; femoral neck: 2.2+/-2.2); etidronate (lumbar spine: 3.6+/-1.4*; femoral neck: 0.5+/-1); calcitriol (lumbar spine: 7.0+/-3.5*; femoral neck: 0.0+/-1.4); thiazide diuretic (lumbar spine: 1+/-3.2; femoral neck: -2.3+/-3.7); and testosterone (lumbar spine: 6.8+/-6.4; femoral neck: 2.5+/-2.7), where *P < 0.05 versus baseline. Gastrointestinal side effects occurred in three patients (4.8%), including two on calcitriol-phosphate therapy and one on etidronate therapy. Of the six (9.5%) patients who experienced incident fractures, four were on etidronate, one on calcitriol-phosphate, and one on calcium-vitamin D. No patients discontinued their treatment because of side effects. Etidronate and the combination of calcitriol-phosphate produce a significant increase in lumbar spine bone mass in men with idiopathic osteoporosis or moderate idiopathic phosphate diabetes.

Calcium and phosphorus regulatory hormones and risk of incident symptomatic kidney stones.

PubMed

Taylor, Eric N; Hoofnagle, Andrew N; Curhan, Gary C

2015-04-07

Calcium and phosphorus regulatory hormones may contribute to the pathogenesis of calcium nephrolithiasis. However, there has been no prospective study to date of plasma hormone levels and risk of kidney stones. This study aimed to examine independent associations between plasma levels of 1,25-dihydroxyvitamin D (1,25[OH]2D), 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, fibroblast growth factor 23 (FGF23), parathyroid hormone, calcium, phosphate, and creatinine and the subsequent risk of incident kidney stones. This study was a prospective, nested case-control study of men in the Health Professionals Follow-Up Study who were free of diagnosed nephrolithiasis at blood draw. During 12 years of follow-up, 356 men developed an incident symptomatic kidney stone. Using risk set sampling, controls were selected in a 2:1 ratio (n=712 controls) and matched for age, race, and year, month, and time of day of blood collection. Baseline plasma levels of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, parathyroid hormone, calcium, phosphate, and creatinine were similar in cases and controls. Mean 1,25(OH)2D and median FGF23 levels were higher in cases than controls but differences were small and statistically nonsignificant (45.7 versus 44.2 pg/ml, P=0.07 for 1,25[OH]2D; 47.6 versus 45.1 pg/ml, P=0.08 for FGF23). However, after adjusting for body mass index, diet, plasma factors, and other covariates, the odds ratios of incident symptomatic kidney stones in the highest compared with lowest quartiles were 1.73 (95% confidence interval, 1.11 to 2.71; P for trend 0.01) for 1,25(OH)2D and 1.45 (95% confidence interval, 0.96 to 2.19; P for trend 0.03) for FGF23. There were no significant associations between other plasma factors and kidney stone risk. Higher plasma 1,25(OH)2D, even in ranges considered normal, is independently associated with higher risk of symptomatic kidney stones. Although of borderline statistical significance, these findings also suggest that higher FGF23 may be associated with risk. Copyright © 2015 by the American Society of Nephrology.

The effect of calcium plus vitamin D supplementation on the risk of venous thromboembolism. From the Women's Health Initiative Randomized Controlled Trial.

PubMed

Blondon, Marc; Rodabough, Rebecca J; Budrys, Nicole; Johnson, Karen C; Berger, Jeffrey S; Shikany, James M; Raiesdana, Azad; Heckbert, Susan R; Manson, JoAnn E; LaCroix, Andrea Z; Siscovick, David; Kestenbaum, Bryan; Smith, Nicholas L; de Boer, Ian H

2015-05-01

Experimental and epidemiological studies suggest that vitamin D may be implicated in haemostatic regulations and influence the risk of venous thromboembolism (VTE). The aim of this study was to investigate whether oral supplementation of vitamin D3 combined with calcium reduces the risk of VTE. In the randomised, double-blind, placebo-controlled Women's Health Initiative Calcium Plus Vitamin D trial, 36,282 postmenopausal women aged 50-79 years were randomised to receive 1,000 mg of calcium carbonate and 400 IU of vitamin D3 per day (n=18,176) or a matching placebo (n=18,106) during an average of seven years. This secondary analysis of the trial compared the incidence of VTE by treatment group using an intention-to-treat Cox regression analysis. The incidence of VTE did not differ between women randomised to calcium plus vitamin D and women randomised to placebo (320 vs 348 VTE events, respectively; hazard ratio (HR) 0.92, 95 % confidence interval (CI) 0.79-1.07). Results were not modified in an analysis using inverse-probability weights to take non-adherence into account (HR 0.94, 95 %CI 0.73-1.22) or in multiple subgroups. Whereas the risk of a non-idiopathic VTE was similar between groups, the risk of idiopathic VTE was lower in women randomised to calcium plus vitamin D (40 vs 65 events; HR 0.62, 95 %CI 0.42-0.92). In conclusion, daily supplementation with 1,000 mg of calcium and 400 IU of vitamin D did not reduce the overall incidence of VTE in generally healthy postmenopausal women. However, the observed reduced risk of idiopathic VTE in women randomised to calcium and vitamin D warrants further investigations.

Effect of Potassium Citrate on Calcium Phosphate Stones in a Model of Hypercalciuria

PubMed Central

Asplin, John R.; Frick, Kevin K.; Granja, Ignacio; Culbertson, Christopher D.; Ng, Adeline; Grynpas, Marc D.; Bushinsky, David A.

2015-01-01

Potassium citrate is prescribed to decrease stone recurrence in patients with calcium nephrolithiasis. Citrate binds intestinal and urine calcium and increases urine pH. Citrate, metabolized to bicarbonate, should decrease calcium excretion by reducing bone resorption and increasing renal calcium reabsorption. However, citrate binding to intestinal calcium may increase absorption and renal excretion of both phosphate and oxalate. Thus, the effect of potassium citrate on urine calcium oxalate and calcium phosphate supersaturation and stone formation is complex and difficult to predict. To study the effects of potassium citrate on urine supersaturation and stone formation, we utilized 95th-generation inbred genetic hypercalciuric stone-forming rats. Rats were fed a fixed amount of a normal calcium (1.2%) diet supplemented with potassium citrate or potassium chloride (each 4 mmol/d) for 18 weeks. Urine was collected at 6, 12, and 18 weeks. At 18 weeks, stone formation was visualized by radiography. Urine citrate, phosphate, oxalate, and pH levels were higher and urine calcium level was lower in rats fed potassium citrate. Furthermore, calcium oxalate and calcium phosphate supersaturation were higher with potassium citrate; however, uric acid supersaturation was lower. Both groups had similar numbers of exclusively calcium phosphate stones. Thus, potassium citrate effectively raises urine citrate levels and lowers urine calcium levels; however, the increases in urine pH, oxalate, and phosphate levels lead to increased calcium oxalate and calcium phosphate supersaturation. Potassium citrate induces complex changes in urine chemistries and resultant supersaturation, which may not be beneficial in preventing calcium phosphate stone formation. PMID:25855777

Vitamin D, Hypercalciuria and Kidney Stones

PubMed Central

Letavernier, Emmanuel; Daudon, Michel

2018-01-01

The estimated lifetime risk of nephrolithiasis is growing nowadays, and the formation of kidney stones is frequently promoted by hypercalciuria. Vitamin D, and especially its active metabolite calcitriol, increase digestive calcium absorption—as urinary calcium excretion is directly correlated with digestive calcium absorption, vitamin D metabolites could theoretically increase calciuria and promote urinary stone formation. Nevertheless, there was, until recently, low evidence that 25-hydroxyvitamin D serum levels would be correlated with kidney stone formation, even if high calcitriol concentrations are frequently observed in hypercalciuric stone formers. Low 25-hydroxyvitamin D serum levels have been associated with a broad spectrum of diseases, leading to a huge increase in vitamin D prescription in the general population. In parallel, an increased frequency of kidney stone episodes has been observed in prospective studies evaluating vitamin D alone or in association with calcium supplements, and epidemiological studies have identified an association between high 25-hydroxyvitamin D serum levels and kidney stone formation in some groups of patients. Moreover, urinary calcium excretion has been shown to increase in response to vitamin D supplements, at least in some groups of kidney stone formers. It seems likely that predisposed individuals may develop hypercalciuria and kidney stones in response to vitamin D supplements. PMID:29562593

Milia-like idiopathic calcinosis cutis in a child with Down syndrome.

PubMed

Kumar, Piyush; Savant, Sushil S; Nimisha, Esther; Das, Anupam; Debbarman, Panchami

2016-05-15

Idiopathic calcinosis cutis refers to progressive deposition of crystals of calcium phosphate in the skin and other areas of the body, in the absence of any inciting factor. Idiopathic calcinosis cutis may sometimes take the form of small, milia-like lesions. Most commonly, such milia like lesions are seen in the setting of Down syndrome. Herein, we report a 5-year-old girl with multiple asymptomatic discrete milia-like firm papules distributed over the face and extremities. A diagnosis of milia-like idiopathic calcinosis cutis associated with Down Syndrome was provisionally made and was confirmed by histopathology and karyotyping.

Prolonged exposure to 1,25(OH)2D3 and high ionized calcium induces FGF-23 production in intestinal epithelium-like Caco-2 monolayer: A local negative feedback for preventing excessive calcium transport.

PubMed

Rodrat, Mayuree; Wongdee, Kannikar; Panupinthu, Nattapon; Thongbunchoo, Jirawan; Teerapornpuntakit, Jarinthorn; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

2018-02-15

Overdose of oral calcium supplement and excessive intestinal calcium absorption can contribute pathophysiological conditions, e.g., nephrolithiasis, vascular calcification, dementia, and cardiovascular accident. Since our previous investigation has indicated that fibroblast growth factor (FGF)-23 could abolish the 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]-enhanced calcium absorption, we further hypothesized that FGF-23 produced locally in the enterocytes might be part of a local negative feedback loop to regulate calcium absorption. Herein, 1,25(OH) 2 D 3 was found to enhance the transcellular calcium transport across the epithelium-like Caco-2 monolayer, and this stimulatory effect was diminished by preceding prolonged exposure to high-dose 1,25(OH) 2 D 3 or high concentration of apical ionized calcium. Pretreatment with a neutralizing antibody for FGF-23 prevented this negative feedback regulation of calcium hyperabsorption induced by 1,25(OH) 2 D 3 . FGF-23 exposure completely abolished the 1,25(OH) 2 D 3 -enhanced calcium transport. Western blot analysis revealed that FGF-23 expression was upregulated in a dose-dependent manner by 1,25(OH) 2 D 3 or apical calcium exposure. Finally, calcium-sensing receptor (CaSR) inhibitors were found to prevent the apical calcium-induced suppression of calcium transport. In conclusion, prolonged exposure to high apical calcium and calcium hyperabsorption were sensed by CaSR, which, in turn, increased FGF-23 expression to suppress calcium transport. This local negative feedback loop can help prevent unnecessary calcium uptake and its detrimental consequences. Copyright © 2018 Elsevier Inc. All rights reserved.

A 10-Year Retrospective Review of Nephrolithiasis in the Navy and Navy Pilots.

PubMed

Masterson, James H; Phillips, Christopher J; Crum-Cianflone, Nancy F; Krause, Robert J; Sur, Roger L; L'Esperance, James O

2017-08-01

Little is known about the incidence of nephrolithiasis in the United States Navy. Navy pilots must be kidney stone-free and are often referred for treatment of small asymptomatic stones. The primary objectives of this study were to determine the incidence of nephrolithiasis and computerized tomography, proportion undergoing treatment and incidence of stone related mishaps in Navy pilots compared with other Navy personnel. We retrospectively studied the records of all Navy service members from 2002 to 2011 for nephrolithiasis based on ICD-9 stone codes to determine the mentioned rates. We also reviewed NSC (Naval Safety Center) data for a history of accidents associated with nephrolithiasis. Rates of disease were calculated using person-years of followup and inferential statistics were done using univariable and multivariable analyses. We evaluated 667,840 Navy personnel with a total of 3,238,331 person-years of followup. The annual incidence of nephrolithiasis was 240/100,000 person-years with a 5-year recurrence rate of 35.3%. On multivariable analysis pilots had nephrolithiasis incidence and treatment rates similar to those of the overall Navy population. Women had a higher incidence of nephrolithiasis compared with men (OR 1.17, p <0.0001). The rate of computerized tomography was lower in pilots than in the rest of the Navy (39 vs 66/10,000 person-years, p <0.0001). No recorded accidents were associated with kidney stones. Navy pilots had a similar incidence of nephrolithiasis and were no more likely to undergo a surgical procedure. Given that no accidents were associated with nephrolithiasis, this study suggests reconsidering current military policies necessitating pilots to be completely stone-free. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Astaxanthin modulates osteopontin and transforming growth factor β1 expression levels in a rat model of nephrolithiasis: a comparison with citrate administration.

PubMed

Alex, Manju; Sauganth Paul, M V; Abhilash, M; Mathews, Varghese V; Anilkumar, T V; Nair, R Harikumaran

2014-09-01

To evaluate the effect of astaxanthin on renal angiotensin-I converting enzyme (ACE) levels, osteopontin (OPN) and transforming growth factor β1 (TGF-β1) expressions and the extent of crystal deposition in experimentally induced calcium oxalate kidney stone disease in a male Wistar rat model. To compare the efficacy of astaxanthin treatment with a currently used treatment strategy (citrate administration) for kidney stones. The expression of OPN was assessed by immunohistochemistry. One step reverse transcriptase polymerase chain reaction followed by densitometry was used to assess renal OPN and TGF-β1 levels. Renal ACE levels were quantified by an enzyme-linked immunosorbent assay method. Crystal deposition in kidney was analysed by scanning electron microscopic (SEM)-energy-dispersive X-ray (EDX). The renal ACE levels and the expression of OPN and TGF-β1 were upregulated in the nephrolithiasis-induced rats. Astaxanthin treatment reduced renal ACE levels and the expression OPN and TGF-β1. SEM-EDX analysis showed that crystal deposition was reduced in the astaxanthin-treated nephrolithiatic group. Astaxanthin treatment was more effective than citrate administration in the regulation of renal ACE levels, OPN and TGF-β1 expressions. Astaxanthin administration reduced renal calcium oxalate crystal deposition possibly by modulating the renal renin-angiotensin system (RAS), which reduced the expression of OPN and TGF-β1 levels. Astaxanthin administration was more effective than citrate treatment in reducing crystal deposition and down-regulating the expression of OPN and TGF-β1. © 2013 The Authors. BJU International © 2013 BJU International.

Physicochemical action of potassium-magnesium citrate in nephrolithiasis

NASA Technical Reports Server (NTRS)

Pak, C. Y.; Koenig, K.; Khan, R.; Haynes, S.; Padalino, P.

1992-01-01

Effect of potassium-magnesium citrate on urinary biochemistry and crystallization of stone-forming salts was compared with that of potassium citrate at same dose of potassium in five normal subjects and five patients with calcium nephrolithiasis. Compared to the placebo phase, urinary pH rose significantly from 6.06 +/- 0.27 to 6.48 +/- 0.36 (mean +/- SD, p less than 0.0167) during treatment with potassium citrate (50 mEq/day for 7 days) and to 6.68 +/- 0.31 during therapy with potassium-magnesium citrate (containing 49 mEq K, 24.5 mEq Mg, and 73.5 mEq citrate per day). Urinary pH was significantly higher during potassium-magnesium citrate than during potassium citrate therapy. Thus, the amount of undissociated uric acid declined from 118 +/- 61 mg/day during the placebo phase to 68 +/- 54 mg/day during potassium citrate treatment and, more prominently, to 41 +/- 46 mg/day during potassium-magnesium citrate therapy. Urinary magnesium rose significantly from 102 +/- 25 to 146 +/- 37 mg/day during potassium-magnesium citrate therapy but not during potassium citrate therapy. Urinary citrate rose more prominently during potassium-magnesium citrate therapy (to 1027 +/- 478 mg/day from 638 +/- 252 mg/day) than during potassium citrate treatment (to 932 +/- 297 mg/day). Consequently, urinary saturation (activity product) of calcium oxalate declined significantly (from 1.49 x 10(-8) to 1.03 x 10(-8) M2) during potassium-magnesium citrate therapy and marginally (to 1.14 x 10(-8) M2) during potassium citrate therapy.(ABSTRACT TRUNCATED AT 250 WORDS).

Antinephrolithiatic and antioxidative efficacy of Dolichos biflorus seeds in a lithiasic rat model.

PubMed

Saha, Sarmistha; Verma, Ramtej J

2015-01-01

Dolichos biflorus sensu auct non L. (Fabaceae) is widely used for the treatment of kidney stones, leucorrhoea, urinary disorders, and menstrual troubles, and is known for its antioxidant activity. To evaluate the preventive effect of hydro-alcoholic extract of Dolichos biflorus seeds (DBE) in ethylene glycol induced nephrolithiasis. In vitro antioxidative capacity of DBE was estimated in terms of reducing power, superoxide radical, 2,2- diphenyl-1-picrylhydrazyl radical, and nitric oxide scavenging activity. A validated HPLC method was used for standardization using quercetin as a marker. Adult female Wistar rats were administered with DBE (150 and 300 mg/kg body weight/day) along with ethylene glycol (0.75%, v/v) for 28 d. The various biochemical parameters were measured in urine, serum, and kidney followed by histochemistry. Ethylene glycol caused a significant increase in calcium, oxalate, phosphate, and total protein in urine as well as in kidney whereas decrease in calcium, sodium, and magnesium in serum was observed (p < 0.001). Ethylene glycol also caused a significant increase in lipid peroxidation and concurrent decrease in activities of antioxidant enzymes in kidney (p < 0.001). However, the seed extract of D. biflorus caused significant restoration of all these parameters (p < 0.001). Histopathological and histochemical studies also showed the reduced calcifications in kidney of seed extract treated rats. These results indicated that seeds of D. biflorus have significant prophylactic effect in preventing the nephrolithiasis, which might be due to the antioxidant activity of the active compounds of the plant.

Cisapride stimulates contraction of idiopathic megacolonic smooth muscle in cats.

PubMed

Hasler, A H; Washabau, R J

1997-01-01

We have previously shown that cisapride, a substituted piperidinyl benzamide, stimulates contraction of healthy feline colonic smooth muscle. The purpose of the present investigation was to determine the effect of cisapride on feline idiopathic megacolonic smooth muscle function. Longitudinal smooth muscle strips from ascending and descending colon were obtained from cats with idiopathic megacolon, suspended in a 1.5 mM Ca(2+)-HEPES buffer solution (37 degrees C, 100% O2, pH 7.4), attached to isometric force transducers, and stretched to optimal muscle length (Lo). Control responses were obtained at each muscle site with acetylcholine (10(-8) to 10(-4) M), substance P (10(-11) to 10(-7) M), or potassium chloride (10 to 80 mM). Muscles were then stimulated with cumulative (10(-9) to 10(-6) M) doses of cisapride in the absence or presence of tetrodotoxin (10(-6) M) and atropine (10(-6) M), or in a 0 calcium HEPES buffer solution. In cats with idiopathic megacolon, cisapride stimulated contractions of longitudinal smooth muscle from both the ascending and the descending colon. Cisapride-induced contractions were similar in magnitude to those induced by substance P and acetylcholine in the ascending colon, but were less than those observed in the descending colon. Cisapride-induced contractions in megacolonic smooth muscle were only partially inhibited by tetrodotoxin and atropine, but were virtually abolished by removal of extracellular calcium. We concluded that cisapride-induced contractions of feline megacolonic smooth muscle are largely smooth muscle mediated and dependent on influx of extracellular calcium. Cisapride-induced contractions in megacolonic smooth muscle are only partially dependent on enteric cholinergic nerves. Thus, cisapride may be useful in the treatment of cats with idiopathic megacolon.

24-h urine metabolic profile: is it necessary in all kidney stone formers?

PubMed

Abu-Ghanem, Yasmin; Shvero, Asaf; Kleinmann, Nir; Winkler, Harry Z; Zilberman, Dorit E

2018-06-06

A 24-h urine metabolic profile (24-UMP) is an integral part of nephrolithiasis work-up. We aimed to explore whether it can be waived under certain circumstances. We reviewed our prospective registry database of patients seen at our outpatient clinic for nephrolithiasis between the years 2010 and 2017. Data included: gender, age at first stone, body mass index (BMI), self-reported comorbidities and family history of nephrolithiasis. A 24-UMP was obtained from each patient under random diet. The following were recorded: urine volume, urinary levels of sodium, calcium, uric acid, oxalate and citrate. Presence of at least one comorbidity (i.e., hypertension/diabetes/hyperlipidemia) was defined as "associated comorbidities" (AC). Their absence was defined as "no comorbidities" (NC). Subjects were divided into two subgroups: first-time and recurrent stone formers, which were further divided into two subgroups: 1st + AC; 1st + NC; recurrent + AC; recurrent + NC. 24-UMPs have been compared between the four groups. Four hundred and fifty-seven patients were included in the study. In the AC groups, patients demonstrated higher BMI levels (p = 0.001), and were statistically significantly obese (BMI > 30, p = 0.001) and older at first stone event (p = 0.001). First formers, either with AC or NC were more likely to have low urine volume (LUV) compared with recurrent formers (72.5 vs. 59.5%, p = 0.005). In the remaining metabolic abnormalities, no such differences were observed. First-time stone formers, either with or without AC are likely to demonstrate LUV as their primary metabolic abnormality in 24-UMP. Therefore, 24-UMP may be postponed until recurrent stone event.

Nephrolithiasis, stone composition, meteorology, and seasons in Malta: Is there any connection?

PubMed

Buttigieg, Jesmar; Attard, Stephanie; Carachi, Alexander; Galea, Ruth; Fava, Stephen

2016-01-01

The effect of seasons and meteorology on the incidence of nephrolithiasis has been studied in various regions around the globe, but seldom in the Mediterranean. This retrospective analysis aims at investigating these putative effects in the Maltese Islands, whose climate is typically Mediterranean, followed by a systematic review of the literature. Submission rate and chemical composition of all kidney stones after spontaneous passage or surgical removal between January 2009 and December 2011 were analyzed according to seasons and corresponding meteorology. A total of 389 stones were analyzed. A higher stone submission rate was observed in summer compared to winter (31.6% vs. 20.8%, P = 0.0008) and in the warm period compared to the cold period (57.1% vs. 42.9%, P = 0.0001). Significant correlation was established between the monthly number of stones and mean monthly maximum temperature (r = 0.50, P = 0.002), mean monthly temperature (r = 0.49, P = 0.003) and mean monthly Humidex (r = 0.49, P = 0.007). Humidex was found to be an independent predictor for stone submission (β = 0.49, P = 0.007). The majority of stones contained calcium (83.3%), combined with oxalate (77.6%), phosphate (14.7%), and carbonate (2.8%). Some stones (11.8%) contained a mixture of >1 negatively charged molecules. Urate (11.6%), cysteine (4.6%), and ammonium-magnesium-phosphate (0.5%) constituted the rest. There was no association between chemical composition and seasons. Literature review included 25 articles. Higher ambient temperature and warm seasons were the most commonly encountered risk factors for both presentation and etiology of nephrolithiasis. A significant positive correlation was noted between ambient temperature and stone submission rate, which was significantly higher during the warm months in Malta.

Postmenopausal Hormone Use and the Risk of Nephrolithiasis

PubMed Central

Maalouf, Naim M.; Sato, Alicia H.; Welch, Brian J.; Howard, Barbara V.; Cochrane, Barbara B.; Sakhaee, Khashayar; Robbins, John A.

2012-01-01

Background Observational studies examining the role of estrogen in the risk of kidney stone formation have shown conflicting results. However, randomized trial evidence on nephrolithiasis risk with estrogen therapy in postmenopausal women is lacking. Methods We reviewed the incidence of nephrolithiasis in the Women’s Health Initiative estrogen-alone and estrogen plus progestin trials conducted at 40 US clinical centers. A total of 10 739 postmenopausal women with hysterectomy were randomized to receive 0.625 mg/d of conjugated equine estrogens (CEE) or placebo, and 16 608 postmenopausal women without hysterectomy were randomized to receive placebo or estrogen plus progestin given as CEE plus medroxyprogesterone acetate (2.5 mg/d). The incidence of nephrolithiasis was determined for an average follow-up of 7.1 years for the CEE trial and 5.6 years for the estrogen plus progestin trial. Results Baseline demographic characteristics and risk factors for nephrolithiasis were similar in the placebo and treatment arms. Estrogen therapy was associated with a significant increase in nephrolithiasis risk from 34 to 39 cases per 10 000 person-years (hazard ratio, 1.21; 95% confidence interval, 1.03-1.44). Censoring data from women when they ceased to adhere to study medication increased the hazard ratio to 1.39 (95% confidence interval, 1.08-1.78). The increased nephrolithiasis risk was independent of progestin coadministration, and effects did not vary significantly according to prerandomization history of nephrolithiasis. Conclusions These data suggest that estrogen therapy increases the risk of nephrolithiasis in healthy postmenopausal women. These findings should be considered in decision making regarding postmenopausal estrogen use. The mechanisms underlying this higher susceptibility remain to be determined. PMID:20937929

Effects of polyphenols from grape seeds on renal lithiasis.

PubMed

Grases, Felix; Prieto, Rafel M; Fernandez-Cabot, Rafel A; Costa-Bauzá, Antonia; Tur, Fernando; Torres, Jose Juan

2015-01-01

Nephrolithiasis is a complex disease that results from a combination of factors related to both urine composition and kidney morphoanatomy. Development of calcium oxalate monohydrate papillary calculi is linked to initial subepithelial calcification of renal papilla. Progressive tissue calcification depends on preexisting injury and involves reactive oxygen species. Many plant extracts that protect against oxidative stress manifest antilithiasic activity. Our study focused on determining the effects of polyphenols on a lithiasis rat model. Rats were pretreated with polyphenols and grape seed extracts, followed by posterior induction of hyperoxalosis via treatment with ethylene glycol plus NH4Cl. The concentrations of calcium and other elements in kidney were determined, along with histological examination of kidney and 24 h urine analysis. Significant differences were observed in the renal calcium content between the control plus ethylene glycol-treated group and the epicatechin plus ethylene glycol-treated, red grape seed extract plus ethylene glycol-treated, and white grape seed extract plus ethylene glycol-treated groups, with reductions of about 50%. The antioxidant activity of polyphenols extracted from red and white grape seeds may be critical in the prevention of calcium oxalate monohydrate papillary calculus formation, particularly if calculi are induced by lesions caused by cytotoxic compounds with oxidative capacity.

Sensitivity of Noncontrast Computed Tomography for Small Renal Calculi With Endoscopy as the Gold Standard.

PubMed

Bhojani, Naeem; Paonessa, Jessica E; El Tayeb, Marawan M; Williams, James C; Hameed, Tariq A; Lingeman, James E

2018-04-03

To compare the sensitivity of noncontrast computed tomography (CT) with endoscopy for detection of renal calculi. Imaging modalities for detection of nephrolithiasis have centered on abdominal x-ray, ultrasound, and noncontrast CT. Sensitivities of 58%-62% (abdominal x-ray), 45% (ultrasound), and 95%-100% (CT) have been previously reported. However, these results have never been correlated with endoscopic findings. Idiopathic calcium oxalate stone formers with symptomatic calculi requiring ureteroscopy were studied. At the time of surgery, the number and the location of all calculi within the kidney were recorded followed by basket retrieval. Each calculus was measured and sent for micro-CT and infrared spectrophotometry. All CT scans were reviewed by the same genitourinary radiologist who was blinded to the endoscopic findings. The radiologist reported on the number, location, and size of each calculus. Eighteen renal units were studied in 11 patients. Average time from CT scan to ureteroscopy was 28.6 days. The mean number of calculi identified per kidney was 9.2 ± 6.1 for endoscopy and 5.9 ± 4.1 for CT (P <.004). The mean size of total renal calculi (sum of the longest stone diameters) per kidney was 22.4 ± 17.1 mm and 18.2 ± 13.2 mm for endoscopy and CT, respectively (P = .06). CT scan underreports the number of renal calculi, probably missing some small stones and being unable to distinguish those lying in close proximity to one another. However, the total stone burden seen by CT is, on average, accurate when compared with that found on endoscopic examination. Copyright © 2018 Elsevier Inc. All rights reserved.

Estimation of the oxalate content of foods and daily oxalate intake

NASA Technical Reports Server (NTRS)

Holmes, R. P.; Kennedy, M.

2000-01-01

BACKGROUND: The amount of oxalate ingested may be an important risk factor in the development of idiopathic calcium oxalate nephrolithiasis. Reliable food tables listing the oxalate content of foods are currently not available. The aim of this research was to develop an accurate and reliable method to measure the food content of oxalate. METHODS: Capillary electrophoresis (CE) and ion chromatography (IC) were compared as direct techniques for the estimation of the oxalate content of foods. Foods were thoroughly homogenized in acid, heat extracted, and clarified by centrifugation and filtration before dilution in water for analysis. Five individuals consuming self-selected diets maintained food records for three days to determine their mean daily oxalate intakes. RESULTS: Both techniques were capable of adequately measuring the oxalate in foods with a significant oxalate content. With foods of very low oxalate content (<1.8 mg/100 g), IC was more reliable than CE. The mean daily intake of oxalate by the five individuals tested was 152 +/- 83 mg, ranging from 44 to 352 mg/day. CONCLUSIONS: CE appears to be the method of choice over IC for estimating the oxalate content of foods with a medium (>10 mg/100 g) to high oxalate content due to a faster analysis time and lower running costs, whereas IC may be better suited for the analysis of foods with a low oxalate content. Accurate estimates of the oxalate content of foods should permit the role of dietary oxalate in urinary oxalate excretion and stone formation to be clarified. Other factors, apart from the amount of oxalate ingested, appear to exert a major influence over the amount of oxalate excreted in the urine.

Extracellular nucleotides inhibit oxalate transport by human intestinal Caco-2-BBe cells through PKC-δ activation

PubMed Central

Amin, Ruhul; Sharma, Sapna; Ratakonda, Sireesha

2013-01-01

Nephrolithiasis remains a major health problem in Western countries. Seventy to 80% of kidney stones are composed of calcium oxalate, and small changes in urinary oxalate affect risk of kidney stone formation. Intestinal oxalate secretion mediated by the anion exchanger SLC26A6 plays an essential role in preventing hyperoxaluria and calcium oxalate nephrolithiasis, indicating that understanding the mechanisms regulating intestinal oxalate transport is critical for management of hyperoxaluria. Purinergic signaling modulates several intestinal processes through pathways including PKC activation, which we previously found to inhibit Slc26a6 activity in mouse duodenal tissue. We therefore examined whether purinergic stimulation with ATP and UTP affects oxalate transport by human intestinal Caco-2-BBe (C2) cells. We measured [14C]oxalate uptake in the presence of an outward Cl− gradient as an assay of Cl−/oxalate exchange activity, ≥50% of which is mediated by SLC26A6. We found that ATP and UTP significantly inhibited oxalate transport by C2 cells, an effect blocked by the PKC inhibitor Gö-6983. Utilizing pharmacological agonists and antagonists, as well as PKC-δ knockdown studies, we observed that ATP inhibits oxalate transport through the P2Y2 receptor, PLC, and PKC-δ. Biotinylation studies showed that ATP inhibits oxalate transport by lowering SLC26A6 surface expression. These findings are of potential relevance to pathophysiology of inflammatory bowel disease-associated hyperoxaluria, where supraphysiological levels of ATP/UTP are expected and overexpression of the P2Y2 receptor has been reported. We conclude that ATP and UTP inhibit oxalate transport by lowering SLC26A6 surface expression in C2 cells through signaling pathways including the P2Y2 purinergic receptor, PLC, and PKC-δ. PMID:23596171

Calcium nephrolithiasis: effect of water hardness on urinary electrolytes.

PubMed

Schwartz, Bradley F; Schenkman, Noah S; Bruce, Jeremy E; Leslie, Stephen W; Stoller, Marshall L

2002-07-01

To analyze the impact of water hardness from public water supplies on calcium stone incidence and 24-hour urine chemistries in patients with known calcium urinary stone formation. Patients are frequently concerned that their public water supply may contribute to urinary stone disease. Investigators have documented an inverse relationship between water hardness and calcium lithogenesis. Others have found no such association. Patients who form calcium stones (n = 4833) were identified geographically by their zip code. Water hardness information from distinct geographic public water supplies was obtained, and patient 24-hour urine chemistries were evaluated. Drinking water hardness was divided into decile rankings on the basis of the public water supply information obtained from the Environmental Protection Agency. These data were compared with patient questionnaires and 24-hour urine chemistries. The calcium and magnesium levels in the drinking water were analyzed as independent variables. The number of total lifetime stone episodes was similar between patients residing in areas with soft public water and hard public water. Patients consuming the softest water decile formed 3.4 lifetime stones and those who consumed the hardest water developed 3.0 lifetime stones (P = 0.0017). The 24-hour urine calcium, magnesium, and citrate levels increased directly with drinking water hardness, and no significant change was found in urinary oxalate, uric acid, pH, or volume. The impact of water hardness on urinary stone formation remains unclear, despite a weak correlation between water hardness and urinary calcium, magnesium, and citrate excretion. Tap water, however, can change urinary electrolytes in patients who form calcium stones.

Seasonal variations in urinary risk factors among patients with nephrolithiasis

NASA Technical Reports Server (NTRS)

Hill, K.; Poindexter, J.; Pak, C. Y.

1991-01-01

Twenty-four hour urine specimens from 5,677 stone-forming patients throughout the United States were analyzed for seasonal variations in urinary risk factors for nephrolithiasis. Determinations were performed for urine volume, pH, calcium, oxalate, phosphorus, sodium, magnesium, citrate, sulfate, uric acid, and the relative supersaturation (RS) of calcium oxalate, brushite, monosodium urate, and uric acid. Criteria for significant seasonal variation included a significant difference in monthly means of risk factors, seasonal grouping of the data by the Student-Newman-Keuls multiple range test, consistent year-to-year trends and a physiologically significant range. Minimum urine volume of 1.54 +/- 0.70 SD L/day occurred in October while a maximum urine volume of 1.76 +/- 0.78 SD L/day was observed during February. Minimum urine pH of 5.94 +/- 0.64 SD was observed during July and August while a maximum pH of 6.18 +/- 0.61 SD was observed during February. Daily urinary excretion of sodium was lowest during August, 158 +/- 74 SD mEq/day and highest during February 177 +/- 70 SD mEq/day. The RS of brushite and uric acid were found to display significant pH-dependent seasonal variation with a maximum RS of uric acid 2.26 +/- 1.98 SD in June and a low of 1.48 +/- 1.30 SD in February. Maximum RS of brushite 2.75 +/- 2.58 was observed during February. Minimum RS of brushite 1.93 +/- 1.70 SD was observed in June. Phosphorus excretion displayed seasonal variation about a spring-fall axis with a maximum value 1042 +/- 373 SD mg/day in April and a minimum value of 895 +/- 289 SD mg/day. Urine volume, sodium, and pH were significantly lower during the summer (June, July, August) than in the winter (December, January, February). The RS of uric acid was higher, but that of brushite and monosodium urate was lower in the summer than in the winter. The seasonal changes observed in urine volume, pH, sodium, and the RS of brushite and uric acid are consistent with summertime sweating and increased physical activity. Seasonal variations in phosphorus excretion are probably dietary in origin. The summertime was characterized by an increased propensity for the crystallization of uric acid but not of calcium oxalate or calcium phosphate.

Annual Incidence of Nephrolithiasis among Children and Adults in South Carolina from 1997 to 2012

PubMed Central

Ross, Michelle E.; Song, Lihai; Sas, David J.; Keren, Ron; Denburg, Michelle R.; Chu, David I.; Copelovitch, Lawrence; Saigal, Christopher S.; Furth, Susan L.

2016-01-01

Background and objectives The prevalence of nephrolithiasis in the United States has increased substantially, but recent changes in incidence with respect to age, sex, and race are not well characterized. This study examined temporal trends in the annual incidence and cumulative risk of nephrolithiasis among children and adults living in South Carolina over a 16-year period. Design, setting, participants, & measurements We performed a population–based, repeated cross–sectional study using the US Census and South Carolina Medical Encounter data, which capture all emergency department visits, surgeries, and admissions in the state. The annual incidence of nephrolithiasis in South Carolina from 1997 to 2012 was estimated, and linear mixed models were used to estimate incidence rate ratios for age, sex, and racial groups. The cumulative risk of nephrolithiasis during childhood and over the lifetime was estimated for males and females in 1997 and 2012. Results Among an at-risk population of 4,625,364 people, 152,925 unique patients received emergency, inpatient, or surgical care for nephrolithiasis. Between 1997 and 2012, the mean annual incidence of nephrolithiasis increased 1% annually from 206 to 239 per 100,000 persons. Among age groups, the greatest increase was observed among 15–19 year olds, in whom incidence increased 26% per 5 years (incidence rate ratio, 1.26; 95% confidence interval, 1.22 to 1.29). Adjusting for age and race, incidence increased 15% per 5 years among females (incidence rate ratio, 1.15; 95% confidence interval, 1.14 to 1.16) but remained stable for males. The incidence among blacks increased 15% more per 5 years compared with whites (incidence rate ratio, 1.15; 95% confidence interval, 1.14 to 1.17). These changes in incidence resulted in doubling of the risk of nephrolithiasis during childhood and a 45% increase in the lifetime risk of nephrolithiasis for women over the study period. Conclusions The incidence of kidney stones has increased among young patients, particularly women, and blacks. PMID:26769765

Dietary treatment of urinary risk factors for renal stone formation. A review of CLU Working Group.

PubMed

Prezioso, Domenico; Strazzullo, Pasquale; Lotti, Tullio; Bianchi, Giampaolo; Borghi, Loris; Caione, Paolo; Carini, Marco; Caudarella, Renata; Ferraro, Manuel; Gambaro, Giovanni; Gelosa, Marco; Guttilla, Andrea; Illiano, Ester; Martino, Marangella; Meschi, Tiziana; Messa, Piergiorgio; Miano, Roberto; Napodano, Giorgio; Nouvenne, Antonio; Rendina, Domenico; Rocco, Francesco; Rosa, Marco; Sanseverino, Roberto; Salerno, Annamaria; Spatafora, Sebastiano; Tasca, Andrea; Ticinesi, Andrea; Travaglini, Fabrizio; Trinchieri, Alberto; Vespasiani, Giuseppe; Zattoni, Filiberto

2015-07-07

Diet interventions may reduce the risk of urinary stone formation and its recurrence, but there is no conclusive consensus in the literature regarding the effectiveness of dietary interventions and recommendations about specific diets for patients with urinary calculi. The aim of this study was to review the studies reporting the effects of different dietary interventions for the modification of urinary risk factors in patients with urinary stone disease. A systematic search of the Pubmed database literature up to July 1, 2014 for studies on dietary treatment of urinary risk factors for urinary stone formation was conducted according to a methodology developed a priori. Studies were screened by titles and abstracts for eligibility. Data were extracted using a standardized form and the quality of evidence was assessed. Evidence from the selected studies were used to form evidence-based guideline statements. In the absence of sufficient evidence, additional statements were developed as expert opinions. General measures: Each patient with nephrolithiasis should undertake appropriate evaluation according to the knowledge of the calculus composition. Regardless of the underlying cause of the stone disease, a mainstay of conservative management is the forced increase in fluid intake to achieve a daily urine output of 2 liters. HYPERCALCIURIA: Dietary calcium restriction is not recommended for stone formers with nephrolithiasis. Diets with a calcium content ≥ 1 g/day (and low protein-low sodium) could be protective against the risk of stone formation in hypercalciuric stone forming adults. Moderate dietary salt restriction is useful in limiting urinary calcium excretion and thus may be helpful for primary and secondary prevention of nephrolithiasis. A low-normal protein intake decrease calciuria and could be useful in stone prevention and preservation of bone mass. Omega-3 fatty acids and bran of different origin decreases calciuria, but their impact on the urinary stone risk profile is uncertain. Sports beverage do not affect the urinary stone risk profile. HYPEROXALURIA: A diet low in oxalate and/or a calcium intake normal to high (800-1200 mg/day for adults) reduce the urinary excretion of oxalate, conversely a diet rich in oxalates and/or a diet low in calcium increase urinary oxalate. A restriction in protein intake may reduce the urinary excretion of oxalate although a vegetarian diet may lead to an increase in urinary oxalate. Adding bran to a diet low in oxalate cancels its effect of reducing urinary oxalate. Conversely, the addition of supplements of fruit and vegetables to a mixed diet does not involve an increased excretion of oxalate in the urine. The intake of pyridoxine reduces the excretion of oxalate. HYPERURICOSURIA: In patients with renal calcium stones the decrease of the urinary excretion of uric acid after restriction of dietary protein and purine is suggested although not clearly demonstrated. HYPOCITRATURIA: The administration of alkaline-citrates salts is recommended for the medical treatment of renal stone-formers with hypocitraturia, although compliance to this treatment is limited by gastrointestinal side effects and costs. Increased intake of fruit and vegetables (excluding those with high oxalate content) increases citrate excretion and involves a significant protection against the risk of stone formation. Citrus (lemons, oranges, grapefruit, and lime) and non citrus fruits (melon) are natural sources of dietary citrate, and several studies have shown the potential of these fruits and/or their juices in raising urine citrate levels. There are enought basis to advice an adequate fluid intake also in children. Moderate dietary salt restriction and implementation of potassium intake are useful in limiting urinary calcium excretion whereas dietary calcium restriction is not recommended for children with nephrolithiasis. It seems reasonable to advice a balanced consumption of fruit and vegetables and a low consumption of chocolate and cola according to general nutritional guidelines, although no studies have assessed in pediatric stone formers the effect of fruit and vegetables supplementation on urinary citrate and the effects of chocolate and cola restriction on urinary oxalate in pediatric stone formers. Despite the low level of scientific evidence, a low-protein (< 20 g/day) low-salt (< 2 g/day) diet with high hydration (> 3 liters/day) is strongly advised in children with cystinuria. ELDERLY: In older patients dietary counseling for renal stone prevention has to consider some particular aspects of aging. A restriction of sodium intake in association with a higher intake of potassium, magnesium and citrate is advisable in order to reduce urinary risk factors for stone formation but also to prevent the loss of bone mass and the incidence of hypertension, although more hemodynamic sensitivity to sodium intake and decreased renal function of the elderly have to be considered. A diet rich in calcium (1200 mg/day) is useful to maintain skeletal wellness and to prevent kidney stones although an higher supplementation could involve an increase of risk for both the formation of kidney stones and cardiovascular diseases. A lower content of animal protein in association to an higher intake of plant products decrease the acid load and the excretion of uric acid has no particular contraindications in the elderly patients, although overall nutritional status has to be preserved.

Primary hyperparathyroidism with classic and severe skeletal involvement.

PubMed

Sandoval, Mark Anthony S; Paz-Pacheco, Elizabeth

2010-08-26

A 63-year-old woman has had multiple repeated fractures. A diagnosis of primary hyperparathyroidism (PHPT) was made after she was found to be hypercalcaemic with an elevated level of intact parathyroid hormone (iPTH). Radiographs revealed classic and severe bone findings in PHPT, features which were common in the past but are thought to be rare at this modern age. She also had nephrolithiasis and osteoporosis. An enlarged parathyroid gland was seen on ultrasound and CT scan, and hyperfunction was demonstrated by scintigraphy. Parathyroidectomy was performed. Histopathologic analysis revealed a parathyroid adenoma. She developed the hungry-bone syndrome 7 days postoperatively, which resolved with with administration of calcium and calcitriol.

The association of nephrolithiasis with metabolic syndrome and its components: a cross-sectional analysis.

PubMed

Liu, Yen-Tze; Yang, Pei-Yu; Yang, Yu-Wen; Sun, Hung-Yu; Lin, I-Ching

2017-01-01

Metabolic syndrome is a worldwide disorder and also the major risk factor of several systemic diseases. Evidence identifying the association between metabolic syndrome and nephrolithiasis is lacking, especially in Taiwan. The aim of this study was to investigate the association between nephrolithiasis and metabolic syndrome and its components. This was a cross-sectional study conducted in the Health Examination Department of a medical center in Changhua, Taiwan, from January 2010 to December 2010. We reviewed the medical records of patients who had visited the Health Examination Center of Changhua Christian Hospital in 2010. A total of 3,886 individuals were enrolled. According to the exclusion criteria, those with an age <20 years and an abnormal renal function were excluded. A total of 3,793 subjects were included. All P -values are two tailed, and P <0.05 was defined as statistically significant. The results showed a correlation between nephrolithiasis and metabolic syndrome and its components. The multivariate-adjusted odds ratio (OR) (95% confidence interval [CI]) of metabolic syndrome for nephrolithiasis was 1.318 (1.083-1.604), with a P -value of 0.006. Larger waist circumference (multivariable-adjusted OR 1.338; 95% CI 1.098-1.631; P =0.004), higher blood pressure (multivariable-adjusted OR 1.333; 95% CI 1.106-1.607; P =0.003), and increased fasting glucose (multivariable-adjusted OR 1.276; 95% CI 1.054-1.546; P =0.01) were associated with nephrolithiasis. This is the first study in Taiwan to investigate the relationship between metabolic syndrome and nephrolithiasis. The mechanism is controversial, and several hypotheses are offered. Adequate lifestyle modification and proper treatment in metabolic syndrome management may both contribute to nephrolithiasis prevention.

Pediatric Origins of Nephrolithiasis-Associated Atherosclerosis.

PubMed

Kusumi, Kirsten; Smith, Sally; Barr-Beare, Evan; Saxena, Vijay; Schober, Megan S; Moore-Clingenpeel, Melissa; Schwaderer, Andrew L

2015-11-01

To determine if nephrolithiasis-associated atherosclerosis has pediatric origins and to consider possible association between kidney stones and atherosclerosis-related proteins. We matched children aged 12-17 years with kidney stones and without kidney stones. Carotid artery intima-media thickness (cIMT) was measured by ultrasound. Participants' urine was investigated by enzyme-linked immunosorbent assay for the atherosclerosis-related proteins fibronectin 1, macrophage scavenger receptor 1, osteopontin, and vascular cell adhesion molecule 1 levels, and normalized to urine creatinine levels. Subjects with nephrolithiasis had higher cIMT in the right common carotid artery and overall mean measurement. Urine osteopontin and fibronectin 1 were significant predictors of cIMT. We have provided initial preliminary evidence that nephrolithiasis-associated atherosclerosis has pediatric origins and performed studies that begin to identify potential reasons for the association of nephrolithiasis and vascular disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Calcium sensitivity of dicarboxylate transport in cultured proximal tubule cells

PubMed Central

Schiro, Faith R.; Pajor, Ana M.; Hamm, L. Lee

2011-01-01

Urinary citrate is an important inhibitor of calcium nephrolithiasis and is primarily determined by proximal tubule reabsorption. The major transporter to reabsorb citrate is Na+-dicarboxylate cotransporter (NaDC1), which transports dicarboxylates, including the divalent form of citrate. We previously found that opossum kidney (OK) proximal tubule cells variably express either divalent or trivalent citrate transport, depending on extracellular calcium. The present studies were performed to delineate the mechanism of the effect of calcium on citrate and succinate transport in these cells. Transport was measured using isotope uptake assays. In some studies, NaDC1 transport was studied in Xenopus oocytes, expressing either the rabbit or opossum ortholog. In the OK cell culture model, lowering extracellular calcium increased both citrate and succinate transport by more than twofold; the effect was specific in that glucose transport was not altered. Citrate and succinate were found to reciprocally inhibit transport at low extracellular calcium (<60 μM), but not at normal calcium (1.2 mM); this mutual inhibition is consistent with dicarboxylate transport. The inhibition varied progressively at intermediate levels of extracellular calcium. In addition to changing the relative magnitude and interaction of citrate and succinate transport, decreasing calcium also increased the affinity of the transport process for various other dicarboxylates. Also, the affinity for succinate, at low concentrations of substrate, was increased by calcium removal. In contrast, in oocytes expressing NaDC1, calcium did not have a similar effect on transport, indicating that NaDC1 could not likely account for the findings in OK cells. In summary, extracellular calcium regulates constitutive citrate and succinate transport in OK proximal tubule cells, probably via a novel transport process that is not NaDC1. The calcium effect on citrate transport parallels in vivo studies that demonstrate the regulation of urinary citrate excretion with urinary calcium excretion, a process that may be important in decreasing urinary calcium stone formation. PMID:21123491

Calcium Tartrate Tetrahydrate, Case Report of a Novel Human Kidney Stone.

PubMed

Kleinguetl, Colin; Williams, James C; Ibrahim, Samar A; Daudon, Michel; Bird, Erin T; El Tayeb, Marawan M

2017-01-01

Background: Calcium tartrate tetrahydrate has been reported as the main mineral in urinary stones in rats that have significant tartrate in their diet, but in humans, there has been only one mention of calcium tartrate stones in the form of bladder stone, and that case was in Africa. Case Presentation: Patient is a 34-year-old Caucasian male who presented with typical symptoms of nephrolithiasis. CT abd/pelvis (renal stone protocol) revealed a 2 cm nonobstructing stone of the right renal pelvis. Patient underwent an uncomplicated right percutaneous nephrolithotomy and was noted to be stone free after surgery. Stone analysis was difficult with regard to determining composition, but was finally identified as calcium tartrate tetrahydrate. Conclusion: This was an unusual case, as this is the first recorded case of a calcium tartrate tetrahydrate outside of Africa. This type of stone had only been mainly described in rat models with dl- bitartrate in their diet. Our patient was an otherwise healthy, relatively muscular individual with no obvious source for this stone other than a vitamin and amino acid supplement that he takes regularly that contains l-carnitine (as tartrate) and choline (as bitartrate and citrate). The prevalence of this stone type is presently unknown, as stone analysis laboratories have not had the ability to recognize it. Although a connection between the supplement and stone formation is conjecture at this time, we believe this necessitates further investigation.

Nephrolithiasis in patients with inflammatory bowel disease in the community

PubMed Central

Cury, Dídia Bismara; Moss, Alan C; Schor, Nestor

2013-01-01

Background Inflammatory bowel disease (IBD) has been associated with renal stone formation. The objective of this study was to determine prospectively the prevalence of nephrolithiasis in a community-based population of patients with IBD and to analyze factors associated with renal calculus formation. Methods Screening renal ultrasound was performed in a well characterized cohort of patients seen between 2009 and 2012 at an IBD clinic. We enrolled 168 patients, including 93 with Crohn’s disease and 75 with ulcerative colitis. Clinical and phenotypic variables associated with asymptomatic nephrolithiasis were determined. Results Nephrolithiasis was detected in 36 patients with Crohn’s disease and in 28 patients with ulcerative colitis (38% for both). Although none of the patients had been previously hospitalized for symptomatic nephrolithiasis, nine with Crohn’s disease and five with ulcerative colitis had recurrent urinary tract infections or hydronephrosis. In patients with Crohn’s disease, ileocolonic (L3) disease was associated with a greater risk of nephrolithiasis than was ileal (L1) or colonic (L2) disease (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.8–7). Active ulcerative colitis (regardless of severity) represented a significant risk factor for formation of renal calculi (OR 4.2, 95% CI 1.1–15, P = 0.02). Conclusion In surgery-naïve patients with IBD in the community, asymptomatic nephrolithiasis is common and should be considered when renal dysfunction or infection is detected. PMID:23935383

Effects of Polyphenols from Grape Seeds on Renal Lithiasis

PubMed Central

Grases, Felix; Prieto, Rafel M.; Fernandez-Cabot, Rafel A.; Costa-Bauzá, Antonia; Tur, Fernando; Torres, Jose Juan

2015-01-01

Nephrolithiasis is a complex disease that results from a combination of factors related to both urine composition and kidney morphoanatomy. Development of calcium oxalate monohydrate papillary calculi is linked to initial subepithelial calcification of renal papilla. Progressive tissue calcification depends on preexisting injury and involves reactive oxygen species. Many plant extracts that protect against oxidative stress manifest antilithiasic activity. Our study focused on determining the effects of polyphenols on a lithiasis rat model. Rats were pretreated with polyphenols and grape seed extracts, followed by posterior induction of hyperoxalosis via treatment with ethylene glycol plus NH4Cl. The concentrations of calcium and other elements in kidney were determined, along with histological examination of kidney and 24 h urine analysis. Significant differences were observed in the renal calcium content between the control plus ethylene glycol-treated group and the epicatechin plus ethylene glycol-treated, red grape seed extract plus ethylene glycol-treated, and white grape seed extract plus ethylene glycol-treated groups, with reductions of about 50%. The antioxidant activity of polyphenols extracted from red and white grape seeds may be critical in the prevention of calcium oxalate monohydrate papillary calculus formation, particularly if calculi are induced by lesions caused by cytotoxic compounds with oxidative capacity. PMID:25883748

Evaluation of hemostasis parameters and the role of the oxidative damage to plasma proteins in the modulation of hemostasis in patients with nephrolithiasis before and after extracorporeal shock wave lithotripsy.

PubMed

Woźniak, Paweł; Kontek, Bogdan; Różański, Waldemar; Olas, Beata

2017-01-01

Extracorporeal shock wave lithotripsy (ESWL) is a commonly-used method in urology, which may modulate hemostasis and may induce lipid peroxidation in patients with nephrolithiasis. However, previous studies only examine changes occurring in patients 30-240 min after ESWL. The main aim of the present study was to determine whether oxidative stress may modulate the hemostatic activity of plasma in patients with nephrolithiasis before ESWL and the day after treatment ESWL. This will be performed by measuring selected parameters of hemostasis in these patients, both before ESWL and the following day, and assessing the level of oxidative damage to plasma proteins in these patients by measuring two biomarkers. Twelve patients with nephrolithiasis and 10 healthy participants were included. The following parameters of hemostasis were measured: the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) of plasma, the level of fibrinogen, the level of D-dimer and blood platelet count. In addition, two selected biomarkers of oxidative stress were measured: protein carbonylation level and the number of protein thiol groups. No difference was observed between patients with nephrolithiasis before and after ESWL and healthy controls with regard to PT, TT or APTT. Fibrinogen concentration and blood platelet count were lower in the nephrolithiasis patients in the period after ESWL than before ESWL. The nephrolithiasis patients demonstrated elevated D-dimer concentration after ESWL. However, although oxidative damage was observed in the plasma proteins in the nephrolithiasis patients, this was not influenced by ESWL. Oxidative stress may induce changes of hemostasis in patients with nephrolithiasis, both before and after ESWL. In addition, changes of hemostasis parameters such as fibrinogen, blood platelet count and D-dimer level can be observed in these patients, especially after ESWL, and this may suggest that ESWL modulates hemostasis. By having a better understanding of the influence of ESWL on hemostasis, this could lead to modifying patient care for those patients at increased risk of bleeding.

Comparative evaluation of ceftriaxone- and cefotaxime-induced biliary pseudolithiasis or nephrolithiasis: A prospective study in 154 children.

PubMed

Ustyol, L; Bulut, M D; Agengin, K; Bala, K A; Yavuz, A; Bora, A; Demiroren, K; Dogan, M

2017-06-01

Biliary lithiasis, or sludge, and nephrolithiasis have been reported as a possible complication of ceftriaxone therapy. However, no study related to cefotaxime-induced biliary pseudolithiasis or nephrolithiasis was observed in the literature. Therefore, we investigated the comparative formation of biliary pseudolithiasis and nephrolithiasis after cefotaxime and ceftriaxone therapies. The patients treated with ceftriaxone or cefotaxime were enrolled during the study period. Ultrasound imaging of the biliary and urinary tract was performed in all patients before and after the treatment. The patients with a positive sonographic finding at the end of treatment were followed up with monthly ultrasonography for 3 months. The present study showed that abnormal biliary sonographic findings were demonstrated in 18 children (20.9%) treated with ceftriaxone, 13 (15.1%) had biliary lithiasis, 5 (5.8%) had biliary sludge and 1 (1.2%) had nephrolithiasis. Abnormal biliary sonographic findings were demonstrated in only four (5.9%) children treated with cefotaxime who had biliary sludge and only one (1.5%) had nephrolithiasis. It was observed that older age was at significantly higher risk of developing biliary sludge or stone formation. Receiver operating characteristic analysis was performed to determine the residual risk and analysis found that 4.5 years was the cut-off value for age. The present study is unique in the literature for reporting for the first time gall bladder sludge and nephrolithiasis associated with cefotaxime use. Therefore, patients treated with cefotaxime should be monitored for serious complications like patients treated with ceftriaxone. Nevertheless, if third-generation cephalosporin is used, cefotaxime is recommended to be used rather than ceftriaxone.

Calcium, why and how much?

PubMed

Palmieri, G M

1995-01-01

Although calcium (Ca) is pivotal for the prevention of osteoporosis, its role in the prevention of other unrelated diseases such as arterial hypertension, cancer of the colon and nephrolithiasis is perplexing. No unitarian hypothesis explaining these unrelated effects of Ca has been postulated. Cytosolic Ca concentration is 10,000-fold lower than in the extracellular space, and this gradient is tightly maintained. Abnormal elevation of cytosolic Ca causes cell damage and death. Parathyroid hormone is a Ca agonist and the suppression of its secretion by Ca could explain the beneficial role of Ca intake in multiple diseases. Thus, parathyroid ablation improves hypertension in rats and cardiomyopathy in hamsters. Since anthropologic data suggests a higher Ca intake, of approximately 1,600 1,600 mg/day, in preneolithic than in modern diets, it is likely that our levels of PTH on genetically predisposed subjects with a loose cellular Ca control may aggravate frequent modern diseases and the process of aging. A higher Ca intake in both sexes should be one of the goals of preventive medicine of our time.

Whole exome sequencing frequently detects a monogenic cause in early onset nephrolithiasis and nephrocalcinosis.

PubMed

Daga, Ankana; Majmundar, Amar J; Braun, Daniela A; Gee, Heon Yung; Lawson, Jennifer A; Shril, Shirlee; Jobst-Schwan, Tilman; Vivante, Asaf; Schapiro, David; Tan, Weizhen; Warejko, Jillian K; Widmeier, Eugen; Nelson, Caleb P; Fathy, Hanan M; Gucev, Zoran; Soliman, Neveen A; Hashmi, Seema; Halbritter, Jan; Halty, Margarita; Kari, Jameela A; El-Desoky, Sherif; Ferguson, Michael A; Somers, Michael J G; Traum, Avram Z; Stein, Deborah R; Daouk, Ghaleb H; Rodig, Nancy M; Katz, Avi; Hanna, Christian; Schwaderer, Andrew L; Sayer, John A; Wassner, Ari J; Mane, Shrikant; Lifton, Richard P; Milosevic, Danko; Tasic, Velibor; Baum, Michelle A; Hildebrandt, Friedhelm

2018-01-01

The incidence of nephrolithiasis continues to rise. Previously, we showed that a monogenic cause could be detected in 11.4% of individuals with adult-onset nephrolithiasis or nephrocalcinosis and in 16.7-20.8% of individuals with onset before 18 years of age, using gene panel sequencing of 30 genes known to cause nephrolithiasis/nephrocalcinosis. To overcome the limitations of panel sequencing, we utilized whole exome sequencing in 51 families, who presented before age 25 years with at least one renal stone or with a renal ultrasound finding of nephrocalcinosis to identify the underlying molecular genetic cause of disease. In 15 of 51 families, we detected a monogenic causative mutation by whole exome sequencing. A mutation in seven recessive genes (AGXT, ATP6V1B1, CLDN16, CLDN19, GRHPR, SLC3A1, SLC12A1), in one dominant gene (SLC9A3R1), and in one gene (SLC34A1) with both recessive and dominant inheritance was detected. Seven of the 19 different mutations were not previously described as disease-causing. In one family, a causative mutation in one of 117 genes that may represent phenocopies of nephrolithiasis-causing genes was detected. In nine of 15 families, the genetic diagnosis may have specific implications for stone management and prevention. Several factors that correlated with the higher detection rate in our cohort were younger age at onset of nephrolithiasis/nephrocalcinosis, presence of multiple affected members in a family, and presence of consanguinity. Thus, we established whole exome sequencing as an efficient approach toward a molecular genetic diagnosis in individuals with nephrolithiasis/nephrocalcinosis who manifest before age 25 years. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Predictive value of preoperative inflammatory response biomarkers for metabolic syndrome and post-PCNL systemic inflammatory response syndrome in patients with nephrolithiasis.

PubMed

Tang, Kun; Liu, Haoran; Jiang, Kehua; Ye, Tao; Yan, Libin; Liu, Peijun; Xia, Ding; Chen, Zhiqiang; Xu, Hua; Ye, Zhangqun

2017-10-17

Neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) were promising biomarkers used to predict diagnosis and prognosis in various inflammatory responses diseases and cancers. However, there have been no reports regarding these biomarkers in kidney stone patients. This study aimed to evaluate the predictive value of inflammatory biomarkers for metabolic syndrome (MetS) and post-PCNL SIRS in nephrolithiasis patients. We retrospectively enrolled 513 patients with nephrolithiasis and 204 healthy controls. NLR, dNLR, LMR and PLR in nephrolithiasis patients were significantly higher than control group. Patients with renal stone have higher NLR, dNLR, LMR and PLR than those without. ROC curve analysis indicated NLR, dNLR, LMR and PLR for predicting patients with nephrolithiasis and MetS, displayed AUC of 0.730, 0.717, 0.627 and 0.606. Additionally, ROC curves, using post-PCNL SIRS as the end-point for NLR, dNLR, LMR and PLR with AUC of 0.831, 0.813, 0.723 and 0.685. Multivariate analysis revealed that NLR, dNLR represented independent factors for predicting post-PCNL SIRS. While LMR independently associated with MetS. These resluts demonstrate preoperative NLR, dNLR and LMR appears to be effective predictors of post-PCNL SIRS and LMR of MetS in nephrolithiasis patients.

Ephedrine- and guaifenesin-induced nephrolithiasis.

PubMed

Bennett, Stephen; Hoffman, Nathan; Monga, Manoj

2004-12-01

Ephedrine and guaifenesin are herbal supplements that have experienced increased use over the past decade. Ephedrine has been used as a stimulant and weight-loss product, guaifenesin as an expectorant and cough suppressant; both are found in combination in many antitussives and expectorants. This paper reviews the reported cases of ephedrine- and guaifenesin-induced nephrolithiasis, as well as the diagnostic techniques and treatments that have been successfully used for these stones. A systematic review of the literature pertaining to nephrolithiasis and the compounds ephedrine and guaifenesin was conducted. Ephedrine and guaifenesin use results in over 35% of urinary stones that are related to pharmaceutical metabolites, and collectively are present in 0.1% of all urinary stones. These calculi are radiolucent, requiring the use of computerized tomography (CT scan) for diagnosis. Alkalinization therapy offers an alternative to surgical intervention and may have a role in prevention of recurrence. Ephedrine and guaifenesin have been shown to cause nephrolithiasis in cases of abuse when taken individually or in combination. It is important for the clinician to be aware of the potential for these compounds to cause nephrolithiasis.

Total flavonoids of Desmodium styracifolium attenuates the formation of hydroxy-L-proline-induced calcium oxalate urolithiasis in rats.

PubMed

Zhou, Jianfu; Jin, Jing; Li, Xiong; Zhao, Zhongxiang; Zhang, Lei; Wang, Qian; Li, Jing; Zhang, Qiuhong; Xiang, Songtao

2018-06-01

Desmosium styracifolium (D. styracifolium), which is considered as a Chinese herbal medicine, has been reported to treat the kidney stone diseases. However, the potential phytochemically active components and the underlying mechanisms associated with its efficacy in targeting urolithiasis remain to be elucidated. This study aims to investigate the anti-urolithiatic effect of total flavonoids of D. styracifolium (TFDS) on calcium oxalate (CaOx) renal stones in Sprague-Dawley rats. Animal models of CaOx urolithiasis were established in male Sprague-Dawley rats by adding 5% w/w hydroxy-L-proline (HLP) in regular rat chow. The TFDS orally at 100, 400 mg/kg, respectively, were administered along with HLP for 28 days. At the end of 28 days of treatment, urine and serum samples were collected for crystalluria determination and various biochemical analysis. Kidney tissues were isolated and processed for antioxidant parameters measurement and histopathological examinations. HLP-induced hyperoxaluria alone reliably caused CaOx nephrolithiasis in rats. We showed that TFDS significantly reduced crystalluria and CaOx crystal deposits in the kidney sections as compared to untreated HLP group. Also, TFDS was observed to decrease urinary oxalate excretion, alleviate the pro-acidosis condition, improve the impaired renal functions and renal epithelial cell injury. Moreover, TFDS protected against the oxidative stress changes via reducing MDA content, increasing CAT and GSH-Px activities in renal homogenate, as well as attenuating the expression of MCP-1, OPN and TGF-β proteins. These results indicated that TFDS had beneficial effect on inhibition of CaOx formation in the rat kidney probably through a combination of antioxidant, anti-inflammatory, urine alkalinizing activities, and lowering the concentration of urinary stone-forming constituents. Thus, TFDS might have clinical implications in preventing oxidative renal cell injury and, ultimately, kidney stone formation. The data provide a rationale for the medicinal use of TFDS in nephrolithiasis and identify this agent as a potential source of new antiurolithic drugs.

Cynodon dactylon extract as a preventive and curative agent in experimentally induced nephrolithiasis.

PubMed

Atmani, F; Sadki, C; Aziz, M; Mimouni, M; Hacht, B

2009-04-01

Cynodon dactylon (Poaceae family) decoction was used in the treatment of kidney stones. However, no scientific study was undertaken so far to demonstrate the beneficial effect of the plant. Thus, the aim of the current study is to evaluate the effect of Cynodon aqueous extract as a preventive and curative agent in experimentally induced nephrolithiasis in a rat model. Ethylene glycol (EG) was used in the experiment to induce calcium oxalate (CaOx) deposition into kidneys. In preventive protocol, Cynodon decoction was administered in the same day with EG to evaluate the ability of the extract to prevent crystal deposition. However, in curative protocol, rats were first rendered nephrolithiasic and then the extract was administered to assess the ability of the plant to eliminate the pre-existing crystal deposition. In both protocols, urinary biochemical and other variables were measured during the course of the study. Crystalluria and renal histology were examined as well. The results showed that, in both protocols, all measured variables were similar for both the rat groups. Nevertheless, urinary biochemical analysis was apparently unaffected by the extract except oxalate in preventive protocol, and calcium, sodium, and potassium in curative protocol which were significantly highly excreted in treated rats compared to untreated animals. Crystalluria was characterized mostly by the presence of large quantities of CaOx monohydrate and CaOx dihydrate particles in untreated rats. However, crystalluria was mainly dominated by the presence of CaOx dihydrate particles with reduced size. The most apparent beneficial effect of Cynodon extract was seen in kidney tissues where reduced levels of CaOx deposition have been noticed especially in medullary and papillary sections from treated rats. We concluded that C. dactylon extract has beneficial effect in preventing and eliminating CaOx deposition into kidneys. Such findings provide a scientific explanation for its use in the treatment of kidneys stones.

Occult urolithiasis in asymptomatic primary hyperparathyroidism.

PubMed

Tay, Yu-Kwang Donovan; Liu, Minghao; Bandeira, Leonardo; Bucovsky, Mariana; Lee, James A; Silverberg, Shonni J; Walker, Marcella D

2018-05-01

Recent international guidelines suggest renal imaging to detect occult urolithiasis in all patients with asymptomatic primary hyperparathyroidism (PHPT), but data regarding their prevalence and associated risk factors are limited. We evaluated the prevalence and risk factors for occult urolithiasis. Cross-sectional analysis of 96 asymptomatic PHPT patients from a university hospital in the United States with and without occult nephrolithiasis. Occult urolithiasis was identified in 21% of patients. Stone formers had 47% higher 24-hour urinary calcium excretion (p = 0.002). Although available in only a subset of patients (n = 28), activated vitamin D [1,25(OH) 2 D] was 29% higher (p = 0.02) in stone formers. There was no difference in demographics, BMI, calcium or vitamin D intake, other biochemistries, renal function, BMD, or fractures. Receiver operating characteristic curves indicated that urinary calcium excretion and 1,25(OH) 2 D had an area under the curve of 0.724 (p = 0.003) and 0.750 (p = 0.04), respectively. A urinary calcium threshold of >211mg/day provided a sensitivity of 84.2% and a specificity of 55.3% while a 1,25(OH) 2 D threshold of >91pg/mL provided a sensitivity and specificity of 62.5% and 90.0% respectively for the presence of stones. Occult urolithiasis is present in about one-fifth of patients with asymptomatic PHPT and is associated with higher urinary calcium and 1,25(OH) 2 D. Given that most patients will not have occult urolithiasis, targeted imaging in those most likely to have occult stones rather than screening all asymptomatic PHPT patients may be useful. The higher sensitivity of urinary calcium versus 1,25(OH) 2 D suggests screening those with higher urinary calcium may be an appropriate approach.

Scrotal calcinosis: idiopathic or dystrophic?

PubMed

Dubey, Suparna; Sharma, Rajeev; Maheshwari, Veena

2010-02-15

Scrotal calcinosis is a rare benign local process characterized by multiple, painless, hard scrotal nodules in the absence of any systemic metabolic disorder. Histological examination reveals extensive deposition of calcium in the dermis, which may be surrounded by histiocytes and an inflammatory giant cell reaction. Numerous theories have been propounded to explain the pathogenesis of this condition, but the principal debate revolves around whether the calcium is deposited at the site of previous epithelial cysts or the calcified nodules are purely idiopathic. This is the largest study of scrotal calcinosis to date with 100 cases, on which clinical, biochemical, radiological, cytopathological, and histopathological examinations were conducted. The histological picture shows a continuous spectrum of changes ranging from intact epithelial cysts (41.0%) - both normal and inflamed; through inflamed cysts containing calcific material in the lumen but with intact cyst wall (53.0%); calcified inflamed cysts with partial epithelial lining (11.0%); to 'naked' calcium deposits lying in the dermis (100%), sometimes compressing surrounding collagen fibres to form a pseudocyst (56.0%). The presence of normal values of calcium and phosphorus along with this spectrum of changes in histology both support the theory that these form by dystrophic calcification of epithelial cysts in a progression that involves inflammation, rupture, calcification and obliteration of the cyst wall.

Nutrition and renal stone disease in space

NASA Technical Reports Server (NTRS)

Zerwekh, Joseph E.

2002-01-01

There is a growing body of evidence from the National Aeronautics and Space Administration and the Russian space program showing that humans exposed to the microgravity environment of space have a greater risk for developing renal stones. Increased bone resorption and the attendant hypercalciuria and hyperphosphaturia contribute significantly to raising the urinary state of saturation with respect to the calcium salts, namely calcium oxalate and calcium phosphate. In addition, other environmental and dietary factors may adversely affect urine composition and increase stone formation risk during space flight. For example, reductions in urinary volume, pH, and citrate contribute to raising stone formation risk. In addition to raising the risk for calcium stone formation, this metabolic profile is conducive to the formation of uric acid stones. Although observations to date have suggested that there may actually be a reduced food intake during the early phase of flight, crew members on longer-duration flights may increase food intake and be at increased risk for stone formation. Taken together, these findings support the use of nutritional recommendations for crew members that would serve to reduce the stone-forming propensity of the urinary environment. Pharmacologic intervention should be directed at raising urinary volumes, diminishing bone losses, and preventing reductions in urinary pH and citrate. Success in reducing the risk for stone formation in astronauts would also be of potential major benefit to the estimated 20 million Americans with nephrolithiasis.

Treatment and prevention of kidney stones: an update.

PubMed

Frassetto, Lynda; Kohlstadt, Ingrid

2011-12-01

The incidence of nephrolithiasis (kidney stones) is rising worldwide, especially in women and with increasing age. Kidney stones are associated with chronic kidney disease. Preventing recurrence is largely specific to the type of stone (e.g., calcium oxalate, calcium phosphate, cystine, struvite [magnesium ammonium phosphate]), and uric acid stones); however, even when the stone cannot be retrieved, urine pH and 24-hour urine assessment provide information about stone-forming factors that can guide prevention. Medications, such as protease inhibitors, antibiotics, and some diuretics, increase the risk of some types of kidney stones, and patients should be counseled about the risks of using these medications. Managing diet, medication use, and nutrient intake can help prevent the formation of kidney stones. Obesity increases the risk of kidney stones. However, weight loss could undermine prevention of kidney stones if associated with a high animal protein intake, laxative abuse, rapid loss of lean tissue, or poor hydration. For prevention of calcium oxalate, cystine, and uric acid stones, urine should be alkalinized by eating a diet high in fruits and vegetables, taking supplemental or prescription citrate, or drinking alkaline mineral waters. For prevention of calcium phosphate and struvite stones, urine should be acidified; cranberry juice or betaine can lower urine pH. Antispasmodic medications, ureteroscopy, and metabolic testing are increasingly being used to augment fluid and pain medications in the acute management of kidney stones.

Gastrointestinal citrate absorption in nephrolithiasis

NASA Technical Reports Server (NTRS)

Fegan, J.; Khan, R.; Poindexter, J.; Pak, C. Y.

1992-01-01

Gastrointestinal absorption of citrate was measured in stone patients with idiopathic hypocitraturia to determine if citrate malabsorption could account for low urinary citrate. Citrate absorption was measured directly from recovery of orally administered potassium citrate (40 mEq.) in the intestinal lavage fluid, using an intestinal washout technique. In 7 stone patients citrate absorption, serum citrate levels, peak citrate concentration in serum and area under the curve were not significantly different from those of 7 normal subjects. Citrate absorption was rapid and efficient in both groups, with 96 to 98% absorbed within 3 hours. The absorption of citrate was less efficient from a tablet preparation of potassium citrate than from a liquid preparation, probably due to a delayed release of citrate from wax matrix. However, citrate absorption from solid potassium citrate was still high at 91%, compared to 98% for a liquid preparation. Thus, hypocitraturia is unlikely to be due to an impaired gastrointestinal absorption of citrate in stone patients without overt bowel disease.

Probabilistic Modeling of the Renal Stone Formation Module

NASA Technical Reports Server (NTRS)

Best, Lauren M.; Myers, Jerry G.; Goodenow, Debra A.; McRae, Michael P.; Jackson, Travis C.

2013-01-01

The Integrated Medical Model (IMM) is a probabilistic tool, used in mission planning decision making and medical systems risk assessments. The IMM project maintains a database of over 80 medical conditions that could occur during a spaceflight, documenting an incidence rate and end case scenarios for each. In some cases, where observational data are insufficient to adequately define the inflight medical risk, the IMM utilizes external probabilistic modules to model and estimate the event likelihoods. One such medical event of interest is an unpassed renal stone. Due to a high salt diet and high concentrations of calcium in the blood (due to bone depletion caused by unloading in the microgravity environment) astronauts are at a considerable elevated risk for developing renal calculi (nephrolithiasis) while in space. Lack of observed incidences of nephrolithiasis has led HRP to initiate the development of the Renal Stone Formation Module (RSFM) to create a probabilistic simulator capable of estimating the likelihood of symptomatic renal stone presentation in astronauts on exploration missions. The model consists of two major parts. The first is the probabilistic component, which utilizes probability distributions to assess the range of urine electrolyte parameters and a multivariate regression to transform estimated crystal density and size distributions to the likelihood of the presentation of nephrolithiasis symptoms. The second is a deterministic physical and chemical model of renal stone growth in the kidney developed by Kassemi et al. The probabilistic component of the renal stone model couples the input probability distributions describing the urine chemistry, astronaut physiology, and system parameters with the physical and chemical outputs and inputs to the deterministic stone growth model. These two parts of the model are necessary to capture the uncertainty in the likelihood estimate. The model will be driven by Monte Carlo simulations, continuously randomly sampling the probability distributions of the electrolyte concentrations and system parameters that are inputs into the deterministic model. The total urine chemistry concentrations are used to determine the urine chemistry activity using the Joint Expert Speciation System (JESS), a biochemistry model. Information used from JESS is then fed into the deterministic growth model. Outputs from JESS and the deterministic model are passed back to the probabilistic model where a multivariate regression is used to assess the likelihood of a stone forming and the likelihood of a stone requiring clinical intervention. The parameters used to determine to quantify these risks include: relative supersaturation (RS) of calcium oxalate, citrate/calcium ratio, crystal number density, total urine volume, pH, magnesium excretion, maximum stone width, and ureteral location. Methods and Validation: The RSFM is designed to perform a Monte Carlo simulation to generate probability distributions of clinically significant renal stones, as well as provide an associated uncertainty in the estimate. Initially, early versions will be used to test integration of the components and assess component validation and verification (V&V), with later versions used to address questions regarding design reference mission scenarios. Once integrated with the deterministic component, the credibility assessment of the integrated model will follow NASA STD 7009 requirements.

Biochemical analysis of tunica vaginalis fluid in patients with or without idiopathic hydroceles.

PubMed

Madlala, T S; Rencken, R K; Bornman, M S; Reif, S; Joubert, H F; Van der Merwe, C A

1994-10-01

To establish the differences, if any, between the biochemical composition of idiopathic hydrocele fluid and the fluid normally present in the tunica vaginalis. Aspiration and sclerotherapy of 37 idiopathic hydroceles from patients who presented to this urology clinic were performed. The biochemical content of the fluid was compared with that of the tunica vaginalis fluid from a small group of controls (n = 8), taken from patients undergoing orchidectomy for carcinoma of the prostate. Differences in several measurements were recorded; in particular, there were significantly higher concentrations of calcium, albumin, total protein and creatine-kinase in the hydrocele group. The levels of potassium, aspartate transaminase, alanine transaminase and alkaline phosphatase were significantly lower in the hydrocele group. Whether these differences have a role in the causation of an idiopathic hydrocele is, at this stage, speculative. A similar study on a larger scale would probably be more conclusive.

Clinical effectiveness in the diagnosis and acute management of pediatric nephrolithiasis.

PubMed

Van Batavia, Jason P; Tasian, Gregory E

2016-12-01

The incidence of pediatric nephrolithiasis has risen over the past few decades leading to a growing public health burden. Children and adolescents represent a unique patient population secondary to their higher risks from radiation exposure as compared to adults, high risk of recurrence, and longer follow up time given their longer life expectancies. Ultrasound imaging is the first-line modality for diagnosing suspected nephrolithiasis in children. Although data is limited, the best evidence based medicine supports the use of alpha-blockers as first-line MET in children, especially when stones are small and in a more distal ureteral location. Surgical management of pediatric nephrolithiasis is similar to that in adults with ESWL and URS first-line for smaller stones and PCNL reserved for larger renal stone burden. Clinical effectiveness in minimizing risks in children and adolescents with nephrolithiasis centers around ED pathways that limit CT imaging, strict guidance to ALARA principles or use of US during surgical procedures, and education of both patients and families on the risks of repeat ionizing radiation exposures during follow up and acute colic events. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Inappropriate phosphate excretion in idiopathic hypercalciuria: the key to a common cause and future treatment?

PubMed Central

Williams, C P; Child, D F; Hudson, P R; Soysa, L D; Davies, G K; Davies, M G; De Bolla, A R

1996-01-01

AIMS: To present experimental evidence in support of a proposed common cause for absorptive hypercalciuria, renal hypercalciuria, renal phosphate leak and enhancement of 1,25-(OH)2-vitamin D concentrations in patients presenting with renal stone disease; and to suggest further investigation with a view to new management. METHODS: An oral calcium loading test was administered to 15 patients with renal stones and 10 normal controls in the fasting state: urine and blood were collected hourly. After the second urine sample, 400 mg calcium dissolved in water was administered orally. Serum calcium, albumin, parathyroid hormone (PTH), and phosphate were measured together with urine calcium clearance and urinary phosphate from which the TmPO4/glomerular filtration rate (GFR) ratio was calculated. Serum 1,25-(OH)2-vitamin D was measured in the first serum sample. In addition, 24 hour urine calcium results were collected retrospectively from the patients' case notes over the previous 18 months. RESULTS: In the basal state, renal stone patients had an overall greater phosphaturia (lower TmPO4/GFR: median 1.72 compared with 2.10 in controls) and increased calcium clearance. Serum corrected calcium and PTH concentrations did not differ between the groups. After calcium loading, serum calcium and urine calcium clearance rose in both groups, with patients with renal stones experiencing a greater percentage fall in phosphaturia. In both groups TmPO4/GFR fell (greater phosphaturia) with increased serum corrected calcium, with the patients showing notably greater phosphaturia for any given calcium concentration. Patients also had notably greater phosphaturia compared with the serum calcium concentration for any given PTH value. Serum 1,25-(OH)2-vitamin D was higher in patients than controls and for any 1,25-(OH)2-vitamin D concentration phosphaturia measured against serum calcium was greater in patients than controls. 1,25-(OH)2-vitamin D did not correlate with phosphaturia relative to serum calcium concentrations within the patient and control groups. CONCLUSIONS: It is proposed that patients with idiopathic hypercalciuria have an "inappropriately' high phosphate excretion for any given serum calcium concentration. Loss of phosphate may induce increased activation of 1,25-(OH)2-vitamin D. Some of the commonly described causes of stone formation may be manifestations of a single mechanism. PMID:8944605

Oxalate and Sucralose Absorption in Idiopathic Calcium Oxalate Stone Formers

PubMed Central

Knight, John; Jiang, Juquan; Wood, Kyle D.; Holmes, Ross P.; Assimos, Dean G.

2011-01-01

Objectives Oxalate has been hypothesized to undergo absorption in the large and small intestine by both paracellular and transepithelial transport. Sucralose is a chlorinated sugar that is absorbed by paracellular mechanisms. This study's objective was to better understand intestinal oxalate transport by correlating oxalate and sucralose absorption in idiopathic calcium oxalate stone formers. Methods Idiopathic calcium oxalate stone formers were recruited to provide urine specimens on both a self-selected diet and following a meal containing 90 mg of 13C2-oxalate and 5 grams of sucralose, and a stool sample for determination of Oxalobacter formigenes colonization. The 24 hour urine collections were fractionated into the first 6 hours and the subsequent 18 hours. Sucralose and oxalate excretion were measured during these periods and used to estimate absorption. Results A total of 38 subjects were evaluated. The majority of both the 13C2-oxalate and sucralose absorption occurred within the 0-6 hour collection. The 13C2-oxalate and sucralose absorptions were significantly correlated at the 0-6 hour, the 6-24 hour, and the total 24 hour time periods (p<0.04). All five oxalate hyperabsorbers(> 15% absorption) also absorbed significantly more sucralose during the 0-6 hour and whole 24 hour time points (p<0.04). Oxalobacter formigenes colonization did not significantly alter oxalate absorption. Conclusion The results suggest that the majority of oxalate is absorbed in the proximal portion of the gastrointestinal tract and that paracelluar transport is involved. Augmented paracellular transport, as evidenced by increased sucralose absorption, may also influence oxalate absorption. PMID:21676449

Severe hypocalcaemia as a cause of seemingly idiopathic bilateral lower limb oedema.

PubMed

Hung, Aaron Karnell Dachuan

2014-01-10

The existing scientific literature has not drawn a link between severe hypocalcaemia and its role in recalcitrant peripheral oedema. This phenomenon is particularly relevant in oncological and geriatric medicine as bone strengthening but serum calcium-lowering agents such as bisphosphonates and denosumab are used for osteoporosis and/or bone metastasis. This case report, through metastatic prostate cancer in a 66-year-old man with bone metastasis being treated with a monoclonal antibody denosumab, proposes the mechanism of hypocalcaemic oedema as being akin to calcium deprivation such as those induced by calcium channel antagonism. It demonstrates the importance of calcium supplementation as a concurrent treatment while patients are on these osteoclast inhibiting agents.

Spondyloarthritis, diffuse idiopathic skeletal hyperostosis (DISH) and chondrocalcinosis.

PubMed

Armas, Jácome Brugues; Couto, Ana Rita; Bettencourt, Bruno Filipe

2009-01-01

The authors describe the main clinical and radiological findings of common enthesopathic disorders-spondylarthritis (SpA), chondrocalcinosis/calcium pyrophosphate dehydrate crystal deposition disease (CPPD CDD) and diffuse idiopathic skeletal hyperostosis (DISH), stressing similarities and differences which may help in the differential diagnosis. They emphasize the clinical presentation of the "pseudoankylosing spondylitis" forms of CPPD CDD. They also review the most relevant genes and molecular mechanisms associated with these conditions and with another enthesopathic disorder with high prevalence in the Japanese population-ossification of the posterior longitudinal ligament (OPLL).

Urinary neutrophil gelatinase-associated lipocalin, a biomarker for systemic inflammatory response syndrome in patients with nephrolithiasis.

PubMed

Zhu, Wei; Liu, Min; Wang, Guang-Chun; Che, Jian-Ping; Xu, Yun-Fei; Peng, Bo; Zheng, Jun-Hua

2014-03-01

The objective of this study was to determine the diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL), C-reactive protein (CRP), and procalcitonin (PCT) in the prognosis of patients presenting with the systemic inflammatory response syndrome (SIRS) with nephrolithiasis. Urine NGAL protein levels were measured by enzyme-linked immunosorbent assay in 87 patients presenting with nephrolithiasis who were diagnosed as SIRS. Additionally, 52 patients presenting with nephrolithiasis but without urinary tract infection and 30 healthy controls were also included in the study. Levels of serum CRP and PCT were also taken into consideration. Median urinary NGAL levels were significantly increased in the SIRS cohorts compared with nephrolithiasis without urinary tract infection patients (4.28 ng/mL versus 2.69 ng/mL, P < 0.001), and NGAL was markedly elevated even in the early stage of SIRS (3.23 ng/mL versus 2.69 ng/mL, P < 0.001). According to the receiver-operating characteristic analysis, NGAL demonstrated a high diagnostic value compared with either PCT or CRP. In the later stage of SIRS, NGAL remained a highly sensitive (76.8%) and specific (86.5%) diagnostic marker compared with either PCT or CRP. Moreover, the area under the curves of NGAL (0.822) were also superior to those seen in either PCT (0.657) or CRP (0.761). Urinary NGAL is a highly sensitive and specific predictor of SIRS for patients presenting with nephrolithiasis. Further study of NGAL as a reliable biomarker of SIRS is required. Copyright © 2014 Elsevier Inc. All rights reserved.

Influence of nutritional status, laboratory parameters and dietary patterns upon urinary acid excretion in calcium stone formers.

PubMed

Tessaro, Carolini Zanette Warmling; Ramos, Christiane Ishikawa; Heilberg, Ita Pfeferman

2018-04-26

Obesity and Metabolic Syndrome (MS) are associated with low urinary pH and represent risk factors for nephrolithiasis, especially composed by uric acid. Acidogenic diets may also contribute to a reduction of urinary pH. Propensity for calcium oxalate precipitation has been shown to be higher with increasing features of the MS. A retrospective evaluation of anthropometric and body composition parameters, MS criteria and the dietary patterns of overweight and obese calcium stone formers and their impact upon urinary pH and other lithogenic parameters was performed. Data regarding anthropometry, body composition, serum and urinary parameters and 3-days dietary records were obtained from medical records of 102(34M/68F) calcium stone formers. A negative correlation was found between urinary pH, waist circumference and serum uric acid levels (males). The endogenous production of organic acids (OA) was positively correlated with triglycerides levels and number of features of MS (males), and with glucose, uric acid and triglycerides serum levels, and number of features of MS (females). No significant correlations were detected between Net Acid Excretion (NAE) or Potential Renal Acid Load of the diet with any of the assessed parameters. A multivariate analysis showed a negative association between OA and urinary pH. The endogenous production of OA and not an acidogenic diet were found to be independently predictive factors for lower urinary pH levels in calcium stone formers. Hypercalciuric and/or hyperuricosuric patients presented higher OA levels and lower levels of urinary pH.

Nephrolithiasis in identical twins: the impact of nature vs nurture.

PubMed

Haleblian, George E; Cantor, David A; Sur, Roger L; Assimos, Dean G; Preminger, Glenn M

2007-09-01

To assess possible underlying metabolic abnormalities in three sets of monozygotic twins, to evaluate the interplay among the factors of kidney stone formation, a complex multifactorial process influenced by environmental, genetic and anatomical factors. Three sets of identical twins with either cystine or calcium oxalate stones were identified. Demographic data, medical histories and the results of 24-h urine testing, with samples collected on self-selected diets, were reviewed and analysed. The cystinuric twins had very similar cystine excretion rates, while stone activity was significantly more pronounced in one. Metabolic abnormalities were concordant in one set of twins with calcium oxalate stones, both being hypercalciuric and hyperuricosuric. However, metabolic abnormalities were discordant in the other pair, one twin with hypercalciuria and the other with hypocitraturia. Two of the three pairs had low urinary volume. These results support previous observations that environmental, genetic and potentially, anatomical factors play roles in kidney-stone formation. Additional controlled studies of monozygotic stone-forming twins might help to define the interplay between environmental and genetic factors, and allow the identification of susceptibility genes involved in stone generation.

Dent Disease in Chinese Children and Findings from Heterozygous Mothers: Phenotypic Heterogeneity, Fetal Growth, and 10 Novel Mutations.

PubMed

Li, Fucheng; Yue, Zhihui; Xu, Tingting; Chen, Minghui; Zhong, Liangying; Liu, Ting; Jing, Xiangyi; Deng, Jia; Hu, Bin; Liu, Yuling; Wang, Haiyan; Lai, Kar N; Sun, Liangzhong; Liu, Jinsong; Maxwell, Patrick H; Wang, Yiming

2016-07-01

To characterize the phenotypes of Dent disease in Chinese children and their heterozygous mothers and to establish genetic diagnoses. Using a modified protocol, we screened 1288 individuals with proteinuria. A diagnosis of Dent disease was established in 19 boys from 16 families by the presence of loss of function/deleterious mutations in CLCN5 or OCRL1. We also analyzed 16 available patients' mothers and examined their pregnancy records. We detected 14 loss of function/deleterious mutations of CLCN5 in 15 boys and 2 mutations of OCRL1 in 4 boys. Of the patients, 16 of 19 had been wrongly diagnosed with other diseases and 11 of 19 had incorrect or unnecessary treatment. None of the patients, but 6 of 14 mothers, had nephrocalcinosis or nephrolithiasis at diagnosis. Of the patients, 8 of 14 with Dent disease 1 were large for gestational age (>90th percentile); 8 of 15 (53.3%) had rickets. We also present predicted structural changes for 4 mutant proteins. Pediatric Dent disease often is misdiagnosed; genetic testing achieves a correct diagnosis. Nephrocalcinosis or nephrolithiasis may not be sensitive diagnostic criteria. We identified 10 novel mutations in CLCN5 and OCRL1. The possibility that altered CLCN5 function could affect fetal growth and a possible link between a high rate of rickets and low calcium intake are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Distinguishing characteristics of idiopathic calcium oxalate kidney stone formers with low amounts of Randall's plaque.

PubMed

Wang, Xiangling; Krambeck, Amy E; Williams, James C; Tang, Xiaojing; Rule, Andrew D; Zhao, Fang; Bergstralh, Eric; Haskic, Zejfa; Edeh, Samuel; Holmes, David R; Herrera Hernandez, Loren P; Lieske, John C

2014-10-07

Overgrowth of calcium oxalate on Randall's plaque is a mechanism of stone formation among idiopathic calcium oxalate stone-formers (ICSFs). It is less clear how stones form when there is little or no plaque. Participants were a consecutive cohort of ICSFs who underwent percutaneous nephroscopic papillary mapping in the kidney or kidneys containing symptomatic stones and a papillary tip biopsy from a representative calyx during a stone removal procedure between 2009 and 2013. The distribution of Randall's plaque coverage was analyzed and used to divide ICSFs into those with a high (≥5%; mean, 10.5%; n=10) versus low (<5%; mean, 1.5%; n=32) amount of plaque coverage per papilla. Demographic and laboratory features were compared between these two groups. Low-plaque stone formers tended to be obese (50% versus 10%; P=0.03) and have a history of urinary tract infection (34% versus 0%; P=0.04). They were less likely to have multiple prior stone events (22% versus 80%; P=0.002) and had a lower mean 24-hour urine calcium excretion (187±86 mg versus 291±99 mg; P<0.01). Morphologically, stones from patients with low amounts of plaque lacked a calcium phosphate core by microcomputed tomography. Papillary biopsies from low plaque stone-formers revealed less interstitial and basement membrane punctate crystallization. These findings suggest that other pathways independent of Randall's plaque may contribute to stone pathogenesis among a subgroup of ICSFs who harbor low amounts of plaque. Copyright © 2014 by the American Society of Nephrology.

[Psychological aspects of treating staghorn nephrolithiasis using percutaneous and retrograde nephrolithotripsy].

PubMed

Podoinitsyn, A A; Dutov, V V

2016-11-01

To investigate the level of anxiety and the severity of asthenic state in patients with staghorn nephrolithiasis treated by of minimally invasive therapies - percutaneous nephrolithotripsy (PNLT) and retrograde nephrolithotripsy (RNLT). This study analyzed the psychological state of 150 patients with staghorn nephrolithiasis aged 25 to 75 years before and after PNLT and RNLT. Testing was performed at baseline, at 5-7 day of hospital stay (average time of preparing for surgery) and after treatment with the use of various questionnaires: Anxiety Scale, Asthenic conditions scale and Pain questionnaire. The follow-up findings shower positive changes, including reduction in the level of anxiety and severity of asthenia in patients of different age groups. The decrease in anxiety level and severity of fatigue was associated with decreased rates of neuropathic component of pain. The psychological state of patients with staghorn nephrolithiasis depends on the characteristics of minimally invasive methods of treatment and requires attending physicians and medical personnel to take into consideration the mental and emotional state of patients.

Fad diets and their effect on urinary stone formation.

PubMed

Nouvenne, Antonio; Ticinesi, Andrea; Morelli, Ilaria; Guida, Loredana; Borghi, Loris; Meschi, Tiziana

2014-09-01

The influence of unhealthy dietary habits on urinary stone formation has been widely recognized in literature. Dietary advice is indeed the cornerstone prescription for prevention of nephrolithiasis as well. However, only a small amount of medical literature has addressed the influence of popular or fad diets, often self-prescribed for the management of obesity and overweight or for cultural beliefs, on the risk of kidney stones. Thereby in this paper we analyze the current knowledge on the effects of some popular diets on overall lithogenic risk. High-protein diets, like Dukan diet, raise some concerns, since animal proteins are able to increase urinary calcium and to decrease urinary citrate excretion, thus leading to a high overall lithogenic risk. Low-carbohydrate diets, like Atkins diet or zone diet, may have a protective role against kidney stone formation, but there are also evidences stating that this dietary approach may rise calciuria and decrease citraturia, since it is generally associated to a relatively high intake of animal proteins. Vegan diet can be harmful for urinary stone disease, especially for the risk of hyperuricemia and micronutrient deficiencies, even if only few studies have addressed this specific matter. On the other side, the benefits of a lacto-ovo-vegetarian diet on kidney stone prevention have been largely emphasized, provided that the intake of calcium and oxalate is balanced. Traditional Mediterranean diet should exert a protective effect on nephrolithiasis as well, even if specific studies have not been carried out yet. High phytate and antioxidant content of this diet have however demonstrated to be beneficial in preventing the formation of new or recurrent calculi. Anyway, at the current state of knowledge, the most effective dietary approach to prevent kidney stone disease is a mild animal protein restriction, a balanced intake of carbohydrates and fats and a high intake of fruit and vegetables. Other fundamental aspects, which are often neglected in fad diets, are a normal intake of milk and dairy products and salt restriction. All these nutritional aspects should be greatly taken into account when patients who are willing to undergo fad or commercial diets ask for dietary advice.

Fad diets and their effect on urinary stone formation

PubMed Central

Nouvenne, Antonio; Ticinesi, Andrea; Morelli, Ilaria; Guida, Loredana; Meschi, Tiziana

2014-01-01

The influence of unhealthy dietary habits on urinary stone formation has been widely recognized in literature. Dietary advice is indeed the cornerstone prescription for prevention of nephrolithiasis as well. However, only a small amount of medical literature has addressed the influence of popular or fad diets, often self-prescribed for the management of obesity and overweight or for cultural beliefs, on the risk of kidney stones. Thereby in this paper we analyze the current knowledge on the effects of some popular diets on overall lithogenic risk. High-protein diets, like Dukan diet, raise some concerns, since animal proteins are able to increase urinary calcium and to decrease urinary citrate excretion, thus leading to a high overall lithogenic risk. Low-carbohydrate diets, like Atkins diet or zone diet, may have a protective role against kidney stone formation, but there are also evidences stating that this dietary approach may rise calciuria and decrease citraturia, since it is generally associated to a relatively high intake of animal proteins. Vegan diet can be harmful for urinary stone disease, especially for the risk of hyperuricemia and micronutrient deficiencies, even if only few studies have addressed this specific matter. On the other side, the benefits of a lacto-ovo-vegetarian diet on kidney stone prevention have been largely emphasized, provided that the intake of calcium and oxalate is balanced. Traditional Mediterranean diet should exert a protective effect on nephrolithiasis as well, even if specific studies have not been carried out yet. High phytate and antioxidant content of this diet have however demonstrated to be beneficial in preventing the formation of new or recurrent calculi. Anyway, at the current state of knowledge, the most effective dietary approach to prevent kidney stone disease is a mild animal protein restriction, a balanced intake of carbohydrates and fats and a high intake of fruit and vegetables. Other fundamental aspects, which are often neglected in fad diets, are a normal intake of milk and dairy products and salt restriction. All these nutritional aspects should be greatly taken into account when patients who are willing to undergo fad or commercial diets ask for dietary advice. PMID:26816783

Determinants of calcium and oxalate excretion in subjects with calcium nephrolithiasis: the role of metabolic syndrome traits.

PubMed

Ticinesi, Andrea; Guerra, Angela; Allegri, Franca; Nouvenne, Antonio; Cervellin, Gianfranco; Maggio, Marcello; Lauretani, Fulvio; Borghi, Loris; Meschi, Tiziana

2018-06-01

The association of metabolic syndrome (MetS) traits with urinary calcium (UCE) or oxalate excretion (UOE) is uncertain in calcium stone formers (CSFs). Our aim was to investigate this association in a large group of Caucasian CSFs. We retrospectively reviewed data of CSFs evaluated at our Kidney Stone Clinic from 1984 to 2015. Data on body mass index (BMI), MetS traits defined according to international consensus, family history of urolithiasis, anti-hypertensive treatments, calcemia, renal function, and 24-h urinary profile of lithogenic risk were collected. The association between MetS traits and UCE or UOE was tested with multivariate linear regression models accounting for a long list of potential confounders. We included 3003 CSFs, aged 44 ± 14 years. The prevalence of hypertension, diabetes, overweight (BMI ≥ 25 kg/m 2 ) and dyslipidemia was 17, 2, 42 and 38%, respectively. Median values of UCE and UOE were 211 mg/24 h (IQR 143-296) and 28 mg/24 h (IQR 22-34), respectively. At a multivariate model, including age, sex, date of examination, drug treatments, family history, renal function, blood calcium and urinary factors as covariates, hypertension was a significant positive determinant of UCE (β ± SE 0.23 ± 0.07, p = 0.003), but overweight, dyslipidemia and diabetes were not. No MetS trait was significantly associated with UOE in multivariate models. In a large group of Caucasian CSFs, hypertension was the only MetS trait significantly associated with UCE, while no MetS trait was associated with oxalate excretion.

Therapeutic effects of aqueous extracts of Petroselinum sativum on ethylene glycol-induced kidney calculi in rats.

PubMed

Saeidi, Jafar; Bozorgi, Hadi; Zendehdel, Ahmad; Mehrzad, Jamshid

2012-01-01

To investigate the therapeutic effects of the aqueous extract of Petroselinum Sativum aerial parts and roots on kidney calculi. Thirty-six male Wistar rats were randomly assigned into 6 groups and treated for 30 days. Group A served as normal control and group B received 1% ethylene glycol in drinking water. Groups C, D, E, and F received 1% ethylene glycol from day 0 and were used as the treatment subjects. Rats in groups C and D received 200 and 600 mg/kg body weight of aerial parts aqueous extract, respectively, and those in groups E and F received 200 and 600 mg/kg body weight of root aqueous extract in drinking water, respectively, from the 14th day of the experiment. On the 14th and 30th days of the experiment, serum level of magnesium (1.71 ± 0.12 and 3.81 ± 0.25, respectively) decreased significantly while serum level of calcium (10.45 ± 0.26 and 11.33 ± 0.18, respectively) increased significantly in group B compared with the control group (14th day: magnesium = 2.87 ± 0.17 and calcium = 8.80 ± 0.00 and 30th day: magnesium = 6.01 ± 0.00 and calcium = 8.30 ± 0.22; P < .001). In the treatment groups of C, D, E, and F, the number of deposits decreased significantly compared with group B on the 30th day (P < .001). The weight of the kidneys increased significantly in group B (2.01 ± 0.17) compared with the control group (1.52 ± 0.07) and decreased significantly in treatment groups (P < .05). Petroselinum Sativum has a therapeutic effect on calcium oxalate stones in rats with nephrolithiasis and reduces the number of calcium oxalate deposits.

Renal Calculi

PubMed Central

Yendt, E. R.

1970-01-01

The pathogenesis of renal calculi is reviewed in general terms followed by the results of investigation of 439 patients with renal calculi studied by the author at Toronto General Hospital over a 13-year period. Abnormalities of probable pathogenetic significance were encountered in 76% of patients. Idiopathic hypercalciuria was encountered in 42% of patients, primary hyperparathyroidism in 11%, urinary infection in 8% and miscellaneous disorders in 8%. The incidence of uric acid stones and cystinuria was 5% and 2% respectively. In the remaining 24% of patients in whom no definite abnormalities were encountered the mean urinary magnesium excretion was less than normal. Of 180 patients with idiopathic hypercalciuria, only 24 were females. In the diagnosis of hyperparathyroidism, the importance of detecting minimal degrees of hypercalcemia is stressed; attention is also drawn to the new observation that the upper limit of normal for serum calcium is slightly lower in females than in males. The efficacy of various measures advocated for the prevention of renal calculi is also reviewed. In the author's experience the administration of thiazides has been particularly effective in the prevention of calcium stones. Thiazides cause a sustained reduction in urinary calcium excretion and increase in urinary magnesium excretion. These agents also appear to affect the skeleton by diminishing bone resorption and slowing down bone turnover. PMID:5438766

Identification of mineral compositions in some renal calculi by FT Raman and IR spectral analysis

NASA Astrophysics Data System (ADS)

Tonannavar, J.; Deshpande, Gouri; Yenagi, Jayashree; Patil, Siddanagouda B.; Patil, Nikhil A.; Mulimani, B. G.

2016-02-01

We present in this paper accurate and reliable Raman and IR spectral identification of mineral constituents in nine samples of renal calculi (kidney stones) removed from patients suffering from nephrolithiasis. The identified mineral components include Calcium Oxalate Monohydrate (COM, whewellite), Calcium Oxalate Dihydrate (COD, weddellite), Magnesium Ammonium Phosphate Hexahydrate (MAPH, struvite), Calcium Hydrogen Phosphate Dihydrate (CHPD, brushite), Pentacalcium Hydroxy Triphosphate (PCHT, hydroxyapatite) and Uric Acid (UA). The identification is based on a satisfactory assignment of all the observed IR and Raman bands (3500-400 cm- 1) to chemical functional groups of mineral components in the samples, aided by spectral analysis of pure materials of COM, MAPH, CHPD and UA. It is found that the eight samples are composed of COM as the common component, the other mineral species as common components are: MAPH in five samples, PCHT in three samples, COD in three samples, UA in three samples and CHPD in two samples. One sample is wholly composed of UA as a single component; this inference is supported by the good agreement between ab initio density functional theoretical spectra and experimental spectral measurements of both sample and pure material. A combined application of Raman and IR techniques has shown that, where the IR is ambiguous, the Raman analysis can differentiate COD from COM and PCHT from MAPH.

Identification of mineral compositions in some renal calculi by FT Raman and IR spectral analysis.

PubMed

Tonannavar, J; Deshpande, Gouri; Yenagi, Jayashree; Patil, Siddanagouda B; Patil, Nikhil A; Mulimani, B G

2016-02-05

We present in this paper accurate and reliable Raman and IR spectral identification of mineral constituents in nine samples of renal calculi (kidney stones) removed from patients suffering from nephrolithiasis. The identified mineral components include Calcium Oxalate Monohydrate (COM, whewellite), Calcium Oxalate Dihydrate (COD, weddellite), Magnesium Ammonium Phosphate Hexahydrate (MAPH, struvite), Calcium Hydrogen Phosphate Dihydrate (CHPD, brushite), Pentacalcium Hydroxy Triphosphate (PCHT, hydroxyapatite) and Uric Acid (UA). The identification is based on a satisfactory assignment of all the observed IR and Raman bands (3500-400c m(-1)) to chemical functional groups of mineral components in the samples, aided by spectral analysis of pure materials of COM, MAPH, CHPD and UA. It is found that the eight samples are composed of COM as the common component, the other mineral species as common components are: MAPH in five samples, PCHT in three samples, COD in three samples, UA in three samples and CHPD in two samples. One sample is wholly composed of UA as a single component; this inference is supported by the good agreement between ab initio density functional theoretical spectra and experimental spectral measurements of both sample and pure material. A combined application of Raman and IR techniques has shown that, where the IR is ambiguous, the Raman analysis can differentiate COD from COM and PCHT from MAPH. Copyright © 2015 Elsevier B.V. All rights reserved.

The Hypercalciurias CAUSES, PARATHYROID FUNCTIONS, AND DIAGNOSTIC CRITERIA

PubMed Central

Pak, Charles Y. C.; Ohata, Masahiro; Lawrence, E. Clint; Snyder, W.

1974-01-01

The causes for the hypercalciuria and diagnostic criteria for the various forms of hypercalciuria were sought in 56 patients with hypercalcemia or nephrolithiasis (Ca stones), by a careful assessment of parathyroid function and calcium metabolism. A study protocol for the evaluation of hypercalciuria, based on a constant liquid synthetic diet, was developed. In 26 cases of primary hyperparathyroidism, characteristic features were: hypercalcemia, high urinary cyclic AMP (cAMP, 8.58±3.63 SD μmol/g creatinine; normal, 4.02±0.70 μmol/g creatinine), high immunoreactive serum parathyroid hormone (PTH), hypercalciuria, the urinary Ca exceeding absorbed Ca from intestinal tract (CaA), high fasting urinary Ca (0.2 mg/mg creatinine or greater), and low bone density by 125I photon absorption. The results suggest that hypercalciuria is partly secondary to an excessive skeletal resorption (resorptive hypercalciuria). The 22 cases with renal stones had normocalcemia, hypercalciuria, intestinal hyperabsorption of calcium, normal or low serum PTH and urinary cAMP, normal fasting urinary Ca, and normal bone density. Since their CaA exceeded urinary Ca, the hypercalciuria probably resulted from an intestinal hyperabsorption of Ca (absorptive hypercalciuria). The primacy of intestinal Ca hyperabsorption was confirmed by responses to Ca load and deprivation under a metabolic dietary regimen. During a Ca load of 1,700 mg/day, there was an exaggerated increase in the renal excretion of Ca and a suppression of cAMP excretion. The urinary Ca of 453±154 SD mg/day was significantly higher than the control group's 211±42 mg/day. The urinary cAMP of 2.26±0.56 μmol/g creatinine was significantly lower than in the control group. In contrast, when the intestinal absorption of calcium was limited by cellulose phosphate, the hypercalciuria was corrected and the suppressed renal excretion of cAMP returned towards normal. Two cases with renal stones had normocalcemia, hypercalciuria, and high urinary cAMP or serum PTH. Since CaA was less than urinary Ca, the hypercalciuria may have been secondary to an impaired renal tubular reabsorption of Ca (renal hypercalciuria). Six cases with renal stones had normal values of serum Ca, urinary Ca, urinary cAMP, and serum PTH (normocalciuric nephrolithiasis). Their CaA exceeded urinary Ca, and fasting urinary Ca and bone density were normal. The results support the proposed mechanisms for the hypercalciuria and provide reliable diagnostic criteria for the various forms of hypercalciuria. PMID:4367891

Identification, Characterisation and Clinical Development of the New Generation of Breast Cancer Susceptibility Alleles

DTIC Science & Technology

2010-03-01

amino acid substitution in this gene has been associated with uric acid nephrolithiasis (32). Recent GWAS have identified another variant within this...Identification of a novel gene and a common variant associated with uric acid nephrolithiasis in a Sardinian genetic isolate. Am J Hum Genet 72

A case report of nephrogenic diabetes insipidus with idiopathic Fanconi syndrome in a child who presented with vitamin D resistant rickets.

PubMed

Patra, Soumya; Nadri, Gulnaz; Chowdhary, Harish; Pemde, Harish K; Singh, Varinder; Chandra, Jagdish

2014-05-01

Fanconi syndrome is a complex of multiple tubular dysfunctions of proximal tubular cells, occurring alone or in association with a variety of inherited (primary) or acquired (secondary) disorders. It is characterized by aminoaciduria, normoglycemic glycosuria, tubular proteinuria without hematuria, metabolic acidosis without anion gap and excessive urinary excretion of phosphorous, calcium, uric acid, bicarbonate, sodium, potassium and magnesium. Diabetes insipidus is a disease of collecting tubules and children mainly present with dehydration and hypernatremia. We are reporting the first case of idiopathic Fanconi's syndrome along with nephrogenic diabetes insipidus in a child who presented to us with vitamin D resistant rickets. Medline search did not reveal any case of nephrogenic diabetes insipidus (NDI) associated with idiopathic Fanconi syndrome. We hypothesized that the NDI may be due to to severe hypokalemia induced tubular dysfunction.

Nephrogenic diabetes insipidus with idiopathic Fanconi's syndrome in a child who presented as vitamin D resistant rickets.

PubMed

Patra, Soumya; Nadri, Gulnaz; Chowdhary, Harish; Pemde, Harish K; Singh, Varinder; Chandra, Jagdish

2011-10-01

Fanconi's syndrome is a complex of multiple tubular dysfunctions of proximal tubular cells occurring alone or in association with a variety of inherited (primary) or acquired (secondary) disorders. It is characterized by aminoaciduria, normoglycaemic glycosuria, tubular proteinuria without hematuria, metabolic acidosis without anion gap and excessive urinary excretion of phosphorous, calcium, uric acid, bicarbonate, sodium, potassium, and magnesium. Whereas diabetes insipidus is a disease of collecting tubules and child mainly presents with dehydration and hypernatremia. Though all the cases published till date were secondary to drugs, myeloma, hematological disorders, etc., we are reporting the first case of idiopathic Fanconi's syndrome along with nephrogenic diabetes insipidus in a child who presented to us as resistant rickets. Medline search did not reveal any case of nephrogenic diabetes insipidus associated with idiopathic Fanconi syndrome. We hypothesized that the NDI may be due to of severe hypokalemia induced tubular dysfunction.

Nephrolithiasis.

PubMed

Stewart, C

1988-08-01

The management of the patient presenting to the Emergency Department with nephrolithiasis or renal colic should include evaluation of the patient for concurrent diseases, risk factors for stone formation, and possible etiologies for stones. Suspicion of ureterolithiasis is based on a cogent history and physical examination and reinforced by a finding of hematuria. Diagnosis should be based upon a promptly performed intravenous pyelogram, unless the patient is truly allergic to contrast media or has substantial risk of a contrast-induced renal failure. A solitary flat plate of the abdomen adds no useful information and is an unnecessary expense to the patient. Essential laboratory data include a urinalysis, CBC, and electrolyte, BUN, creatinine, and serum calcium levels. A urine culture should be obtained in all patients because urinalysis alone may not be sufficient to exlude a urinary tract infection. Initial treatment of the patient with an uncomplicated renal colic should include hydration, relief of pain, and reassurance. Evaluation by a consultant may be done as an outpatient on a nonemergent basis. If the colic has not resolved after 72 hours, hospitalization generally is recommended. If the patient has vomiting, dehydration, a complete obstruction, or a solitary kidney, hospitalization in indicated and urgent consultation recommended. If the patient has fever or other signs of infection, emergent consultation and immediate hospitalization are essential. Retained obstructing stones are generally managed by urologic consultants. It is in the care of the patient with the retained stone that greatest advances have been made in the past 10 years. Patients should be counseled that the retained stone no longer calls for extended hospitalization and convalescence.

Effect of fruit extract on renal stone formation and kidney injury in rats.

PubMed

Partovi, Nasrin; Ebadzadeh, Mohammad Reza; Fatemi, S Jamilaldin; Khaksari, Mohammad

2018-05-01

This study investigated the effect of oral administration of Cactus fruit extracts on calcium oxalate deposition, malondialdehyde (MDA) and superoxide dismutase (SOD) activity in rat model. About 42 rats were used for the study. The animals were divided into seven groups. Control group maintained on regular rat food and drinking water throughout the study period, whereas in other groups nephrolithiasis was induced by ethylene glycol. Rats in kidney stone group were sacrificed after 28 days and all remaining groups after 58 days. Treatment groups were treated with 1 and 100 mg/kg of aqueous and ethanolic extracts of Cactus fruit for 30 days. After treatment, SOD activity was increased and MDA was decreased significantly. CaOx depositions were decreased significantly, especially in ethanolic extract of Cactus fruit in high dose (100 mg/kg).

Nephrocalcinosis (Enamel Renal Syndrome) Caused by Autosomal Recessive FAM20A Mutations

PubMed Central

Jaureguiberry, Graciana; De la Dure-Molla, Muriel; Parry, David; Quentric, Mickael; Himmerkus, Nina; Koike, Toshiyasu; Poulter, James; Klootwijk, Enriko; Robinette, Steven L.; Howie, Alexander J.; Patel, Vaksha; Figueres, Marie-Lucile; Stanescu, Horia C.; Issler, Naomi; Nicholson, Jeremy K.; Bockenhauer, Detlef; Laing, Christopher; Walsh, Stephen B.; McCredie, David A.; Povey, Sue; Asselin, Audrey; Picard, Arnaud; Coulomb, Aurore; Medlar, Alan J.; Bailleul-Forestier, Isabelle; Verloes, Alain; Le Caignec, Cedric; Roussey, Gwenaelle; Guiol, Julien; Isidor, Bertrand; Logan, Clare; Shore, Roger; Johnson, Colin; Inglehearn, Christopher; Al-Bahlani, Suhaila; Schmittbuhl, Matthieu; Clauss, François; Huckert, Mathilde; Laugel, Virginie; Ginglinger, Emmanuelle; Pajarola, Sandra; Spartà, Giuseppina; Bartholdi, Deborah; Rauch, Anita; Addor, Marie-Claude; Yamaguti, Paulo M.; Safatle, Heloisa P.; Acevedo, Ana Carolina; Martelli-Júnior, Hercílio; dos Santos Netos, Pedro E.; Coletta, Ricardo D.; Gruessel, Sandra; Sandmann, Carolin; Ruehmann, Denise; Langman, Craig B.; Scheinman, Steven J.; Ozdemir-Ozenen, Didem; Hart, Thomas C.; Hart, P. Suzanne; Neugebauer, Ute; Schlatter, Eberhard; Houillier, Pascal; Gahl, William A.; Vikkula, Miikka; Bloch-Zupan, Agnès; Bleich, Markus; Kitagawa, Hiroshi; Unwin, Robert J.; Mighell, Alan; Berdal, Ariane; Kleta, Robert

2013-01-01

Background/Aims Calcium homeostasis requires regulated cellular and interstitial systems interacting to modulate the activity and movement of this ion. Disruption of these systems in the kidney results in nephrocalcinosis and nephrolithiasis, important medical problems whose pathogenesis is incompletely understood. Methods We investigated 25 patients from 16 families with unexplained nephrocalcinosis and characteristic dental defects (amelogenesis imperfecta, gingival hyperplasia, impaired tooth eruption). To identify the causative gene, we performed genome-wide linkage analysis, exome capture, next-generation sequencing, and Sanger sequencing. Results All patients had bi-allelic FAM20A mutations segregating with the disease; 20 different mutations were identified. Conclusions This au-tosomal recessive disorder, also known as enamel renal syndrome, of FAM20A causes nephrocalcinosis and amelogenesis imperfecta. We speculate that all individuals with biallelic FAM20A mutations will eventually show nephrocalcinosis. PMID:23434854

Antiurolithiatic and antioxidant efficacy of Musa paradisiaca pseudostem on ethylene glycol-induced nephrolithiasis in rat

PubMed Central

Panigrahi, Padma Nibash; Dey, Sahadeb; Sahoo, Monalisa; Dan, Ananya

2017-01-01

Objective: Musa paradisiaca has been used in the treatment of urolithiasis by the rural people in South India. Therefore, we plan to evaluate its efficacy and possible mechanism of antiurolithiatic effect to rationalize its medicinal use. Materials and Methods: Urolithiasis was induced in hyperoxaluric rat model by giving 0.75% ethylene glycol (EG) for 28 days along with 1% ammonium chloride (AC) for the first 14 days. Antiurolithiatic effect of aqueous-ethanol extract of M. paradisiaca pseudostem (MUSA) was evaluated based on urine and serum biochemistry, microscopy of urine, oxidative/nitrosative indices, kidney calcium content, and histopathology. Results: Administration of EG and AC resulted in increased crystalluria and oxaluria, hypercalciuria, polyuria, crystal deposition in urine, raised serum urea, and creatinine as well as nitric oxide concentration and erythrocytic lipid peroxidation in lithiatic group. However, MUSA treatment significantly restored the impairment in above kidney function test as that of standard treatment, cystone in a dose-dependent manner. Conclusions: The present findings demonstrate the efficacy of MUSA in EG-induced urolithiasis, which might be mediated through inhibiting various pathways involved in renal calcium oxalate formation, antioxidant effect, and potential to inhibit biochemical markers of renal impairment. PMID:28458427

Antiurolithiatic and antioxidant efficacy of Musa paradisiaca pseudostem on ethylene glycol-induced nephrolithiasis in rat.

PubMed

Panigrahi, Padma Nibash; Dey, Sahadeb; Sahoo, Monalisa; Dan, Ananya

2017-01-01

Musa paradisiaca has been used in the treatment of urolithiasis by the rural people in South India. Therefore, we plan to evaluate its efficacy and possible mechanism of antiurolithiatic effect to rationalize its medicinal use. Urolithiasis was induced in hyperoxaluric rat model by giving 0.75% ethylene glycol (EG) for 28 days along with 1% ammonium chloride (AC) for the first 14 days. Antiurolithiatic effect of aqueous-ethanol extract of M. paradisiaca pseudostem (MUSA) was evaluated based on urine and serum biochemistry, microscopy of urine, oxidative/nitrosative indices, kidney calcium content, and histopathology. Administration of EG and AC resulted in increased crystalluria and oxaluria, hypercalciuria, polyuria, crystal deposition in urine, raised serum urea, and creatinine as well as nitric oxide concentration and erythrocytic lipid peroxidation in lithiatic group. However, MUSA treatment significantly restored the impairment in above kidney function test as that of standard treatment, cystone in a dose-dependent manner. The present findings demonstrate the efficacy of MUSA in EG-induced urolithiasis, which might be mediated through inhibiting various pathways involved in renal calcium oxalate formation, antioxidant effect, and potential to inhibit biochemical markers of renal impairment.

Late diagnosis of primary hyperoxaluria after failed kidney transplantation.

PubMed

Spasovski, Goce; Beck, Bodo B; Blau, Nenad; Hoppe, Bernd; Tasic, Velibor

2010-09-01

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive inborn error of the glyoxylate metabolism that is based on absence, deficiency or mislocalization of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase. Hyperoxaluria leads to recurrent formation of calculi and/or nephrocalcinosis and often early end-stage renal disease (ESRD) accompanied by systemic calcium oxalate crystal deposition. In this report, we describe an adult female patient with only one stone passage before development of ESRD. With unknown diagnosis of PH, the patient received an isolated kidney graft and developed an early onset of graft failure. Although initially presumed as an acute rejection, the biopsy revealed calcium oxalate crystals, which then raised a suspicion of primary hyperoxaluria. The diagnosis was later confirmed by hyperoxaluria, elevated plasma oxalate levels and mutation of the AGXT gene, showing the patient to be compound heterozygous for the c.33_34InsC and c.508G > A mutations. Plasma oxalate levels did not decrease after high-dose pyridoxine treatment. Based on this case report, we would recommend in all patients even with a minor history of nephrolithiasis but progression to chronic renal failure to exclude primary hyperoxaluria before isolated kidney transplantation is considered.

Type 2 Diabetes and Uric Acid Nephrolithiasis

NASA Astrophysics Data System (ADS)

Maalouf, Naim M.

2008-09-01

Type 2 diabetes is associated with an increased propensity for uric acid nephrolithiasis. In individuals with diabetes, this increased risk is due to a lower urine pH that results from obesity, dietary factors, and impaired renal ammoniagenesis. The epidemiology and pathogenesis of uric acid stone disease in patients with diabetes are hereby reviewed, and potential molecular mechanisms are proposed.

Use of Potassium Citrate to Reduce the Risk of Renal Stone Formation During Spaceflight

NASA Technical Reports Server (NTRS)

Whitson, P. A.; Pietrzyk, R. A.; Sams, C. F.; Jones, J. A.; Nelman-Gonzalez, M.; Hudson, E. K.

2008-01-01

Introduction: NASA s Vision for Space Exploration centers on exploration class missions including the goals of returning to the moon and landing on Mars. One of NASA s objectives is to focus research on astronaut health and the development of countermeasures that will protect crewmembers during long duration voyages. Exposure to microgravity affects human physiology and results in changes in the urinary chemical composition favoring urinary supersaturation and an increased risk of stone formation. Nephrolithiasis is a multifactorial disease and development of a renal stone is significantly influenced by both dietary and environmental factors. Previous results from long duration Mir and short duration Shuttle missions have shown decreased urine volume, pH, and citrate levels and increased calcium. Citrate, an important inhibitor of calcium-containing stones, binds with urinary calcium reducing the amount of calcium available to form stones. Citrate inhibits renal stone recurrence by preventing crystal growth, aggregation, and nucleation and is one of the most common therapeutic agents used to prevent stone formation. Methods: Thirty long duration crewmembers (29 male, 1 female) participated in this study. 24-hour urines were collected and dietary monitoring was performed pre, in, and postflight. Crewmembers in the treatment group received two potassium citrate (KCIT) pills, 10 mEq/pill, ingested daily beginning 3 days before launch, all inflight days and through 14 days postflight. Urinary biochemical and dietary analyses were completed. Results: KCIT treated subjects exhibited decreased urinary calcium excretion and maintained the levels of calcium oxalate supersaturation risk at their preflight levels. The increased urinary pH levels in these subjects reduced the risk of uric acid stones. Discussion: The current study investigated the use of potassium citrate as a countermeasure to minimize the risk of stone formation during ISS missions. Results suggest that supplementation with potassium citrate decreases the risk of stone formation during and immediately after spaceflight.

Renal Stone Risk during Spaceflight: Assessment and Countermeasure Validation

NASA Technical Reports Server (NTRS)

Whitson, Peggy A.; Pietrzyk, Robert A.; Jones, Jeffery A.; Sams, Clarence F.; Hudson, Ed K.; Nelman-Gonzalez, Mayra

2009-01-01

NASA's Vision for Space Exploration centers on exploration class missions including the goals of returning to the moon and landing on Mars. One of NASA's objectives is to focus research on astronaut health and the development of countermeasures that will protect crewmembers during long duration voyages. Exposure to microgravity affects human physiology and results in changes in the urinary chemical composition favoring urinary supersaturation and an increased risk of stone formation. Nephrolithiasis is a multifactorial disease and development of a renal stone is significantly influenced by both dietary and environmental factors. Previous results from long duration Mir and short duration Shuttle missions have shown decreased urine volume, pH, and citrate levels and increased calcium. Citrate, an important inhibitor of calcium-containing stones, binds with urinary calcium reducing the amount of calcium available to form stones. Citrate inhibits renal stone recurrence by preventing crystal growth, aggregation, and nucleation and is one of the most common therapeutic agents used to prevent stone formation. Methods: Thirty long duration crewmembers (29 male, 1 female) participated in this study. 24-hour urines were collected and dietary monitoring was performed pre-, in-, and postflight. Crewmembers in the treatment group received two potassium citrate (KCIT) pills, 10 mEq/pill, ingested daily beginning 3 days before launch, all in-flight days and through 14 days postflight. Urinary biochemical and dietary analyses were completed. Results: KCIT treated subjects exhibited decreased urinary calcium excretion and maintained the levels of calcium oxalate supersaturation risk at their preflight levels. The increased urinary pH levels in these subjects reduced the risk of uric acid stones. Discussion: The current study investigated the use of potassium citrate as a countermeasure to minimize the risk of stone formation during ISS missions. Results suggest that supplementation with potassium citrate decreases the risk of stone formation during and immediately after spaceflight.

A novel method for predicting kidney stone type using ensemble learning.

PubMed

Kazemi, Yassaman; Mirroshandel, Seyed Abolghasem

2018-01-01

The high morbidity rate associated with kidney stone disease, which is a silent killer, is one of the main concerns in healthcare systems all over the world. Advanced data mining techniques such as classification can help in the early prediction of this disease and reduce its incidence and associated costs. The objective of the present study is to derive a model for the early detection of the type of kidney stone and the most influential parameters with the aim of providing a decision-support system. Information was collected from 936 patients with nephrolithiasis at the kidney center of the Razi Hospital in Rasht from 2012 through 2016. The prepared dataset included 42 features. Data pre-processing was the first step toward extracting the relevant features. The collected data was analyzed with Weka software, and various data mining models were used to prepare a predictive model. Various data mining algorithms such as the Bayesian model, different types of Decision Trees, Artificial Neural Networks, and Rule-based classifiers were used in these models. We also proposed four models based on ensemble learning to improve the accuracy of each learning algorithm. In addition, a novel technique for combining individual classifiers in ensemble learning was proposed. In this technique, for each individual classifier, a weight is assigned based on our proposed genetic algorithm based method. The generated knowledge was evaluated using a 10-fold cross-validation technique based on standard measures. However, the assessment of each feature for building a predictive model was another significant challenge. The predictive strength of each feature for creating a reproducible outcome was also investigated. Regarding the applied models, parameters such as sex, acid uric condition, calcium level, hypertension, diabetes, nausea and vomiting, flank pain, and urinary tract infection (UTI) were the most vital parameters for predicting the chance of nephrolithiasis. The final ensemble-based model (with an accuracy of 97.1%) was a robust one and could be safely applied to future studies to predict the chances of developing nephrolithiasis. This model provides a novel way to study stone disease by deciphering the complex interaction among different biological variables, thus helping in an early identification and reduction in diagnosis time. Copyright © 2017 Elsevier B.V. All rights reserved.

Antioxidant and Renoprotective Effects of Mushroom Extract: Implication in Prevention of Nephrolithiasis

PubMed Central

Schulman, Ariel; Chaimowitz, Matthew; Choudhury, Muhammad; Eshghi, Majid; Konno, Sensuke

2016-01-01

Background The pathogenesis of nephrolithiasis (kidney stone) remains elusive, while several therapeutic options are available but not effective as we expected. Accumulating data yet suggest that oxidative stress (generation of oxygen free radicals) may play a primary role in its occurrence. Particularly, calcium oxalate (CaOx) is a key element in the most common form (> 75%) of kidney stones, and its crystal form known as CaOx monohydrate (COM) has been shown to exert oxidative stress, facilitating CaOx stone formation. Hence, diminishing oxidative stress with certain antioxidants could be a potential strategic approach. We are interested in a bioactive extract of Poria mushroom, PE, which has been shown to have antioxidant and renoprotective activities. Accordingly, we investigated if PE might have antioxidant activity that would have implication in prevention of kidney stone formation. Methods Renal epithelial LLC-PK1 cells were employed and exposed to COM or hydrogen peroxide (H2O2) as a positive control capable of exerting oxidative stress. Possible antioxidant and protective effects of PE against oxidative stress (exerted by COM or H2O2) were assessed by cell viability test and lipid peroxidation (LPO) assay. To explore its protective mechanism, two glycolytic parameters, hexokinase (HK) activity and ATP synthesis, were examined and cell cycle analysis was also performed. Results Both H2O2 and COM led to a significant (P < 0.05) reduction in cell viability, accompanied by severe oxidative stress assessed by LPO assay. Such oxidative stress also caused the significant decline in HK activity and cellular ATP level, indicating the inhibition of glycolysis. Cell cycle analysis further indicated that oxidative stress interfered with cell cycle, inducing a G1 cell cycle arrest that presumably results in the cessation of cell proliferation. However, PE was capable of significantly preventing or diminishing all these cellular effects mediated through oxidative stress (exerted by H2O2 and COM). Conclusions The present study shows that the mushroom extract PE appears to have antioxidant and renoprotective effects against oxidative stress exerted by COM in renal cells. Therefore, PE with antioxidant activity is considered a promising natural agent that may have clinical implications in prevention of nephrolithiasis primarily induced by oxidative stress. PMID:27829958

Development of a two-stage in vitro model system to investigate the mineralization mechanisms involved in idiopathic stone formation: stage 1-biomimetic Randall's plaque using decellularized porcine kidneys.

PubMed

Lovett, Archana C; Khan, Saeed R; Gower, Laurie B

2018-05-18

Idiopathic calcium oxalate (CaOx) stone formers form stones that are commonly attached to calcium phosphate (CaP) deposits in the renal tissue, known as Randall's plaques (RP). Plaques are suggested to originate in the renal tubular basement membrane, where they exhibit a morphology of concentrically laminated apatitic spherules, while in the interstitial regions, the collagen fibrils and vesicles become mineralized. We hypothesize that these minerals might form by non-classical crystallization mechanisms, such as via amorphous precursors, some of which might originate from a polymer-induced liquid-precursor (PILP) process. Thus, our goal is to identify mineralogical 'signatures' of various stone formation mechanisms. To do this for idiopathic CaOx stones, we are developing a two-stage model system of CaP-CaOx composite stones, consisting of stage (1) CaP mineralized plaque, followed by stage (2) CaOx overgrowth into a stone. For the studies presented here, decellularized porcine kidneys were mineralized with CaP using polyaspartic acid or the protein osteopontin (OPN) to induce the PILP process and create biomimetic RP. Analysis of the PILP-mineralized tissues shows features that resemble the native plaques, including mineral spherules and collagen with intrafibrillar mineral. In contrast, the classical crystallization produced large apatitic spherulites, which is a very different morphology, but one which is also found in some stones. An alternative hypothesis regarding Randall's plaque, and if or when it becomes pathological, is discussed.

Impaired calcium sensing distinguishes primary hyperparathyroidism (PHPT) patients with low bone mineral density.

PubMed

Weber, Thomas J; Koh, James; Thomas, Samantha M; Hogue, Joyce A; Scheri, Randall P; Roman, Sanziana A; Sosa, Julie A

2017-09-01

A subset of PHPT patients exhibit a more severe disease phenotype characterized by bone loss, fractures, recurrent nephrolithiasis, and other dysfunctions, but the underlying reasons for this disparity in clinical presentation remain unknown. We sought to identify new mechanistic indices that could inform more personalized management of PHPT. Pre-, peri-, and postoperative data and demographic, clinical, and pathological information from patients undergoing parathyroidectomy for PHPT were collected. Univariate and partial Spearman correlation was used to estimate the association of parathyroid tumor calcium sensing capacity with select variables. An unselected series of 237 patients aged >18years and undergoing parathyroidectomy for PHPT were enrolled. Calcium sensing capacity, expressed as the concentration required for half-maximal biochemical response (EC50), was evaluated in parathyroid tumors from an unselected series of 74 patients and assessed for association with clinical parameters. The hypothesis was that greater disease severity would be associated with attenuated calcium sensitivity and biochemically autonomous parathyroid tumor behavior. Parathyroid tumors segregated into two distinct groups of calcium responsiveness (EC50<3.0 and ≥3.0mM). The low EC50 group (n=27) demonstrated a mean calcium EC50 value of 2.49mM [95% confidence interval (CI): 2.43-2.54mM], consistent with reference normal activity. In contrast, the high EC50 group (n=47) displayed attenuated calcium sensitivity with a mean EC50 value of 3.48mM [95% CI: 3.41-3.55mM]. Retrospective analysis of the clinical registry data suggested that high calcium EC50 patients presented with a more significant preoperative bone mineral density (BMD) deficit with a t-score of -2.7, (95% CI: -3.4 to -1.9) versus 0.9, (95% CI: -2.1 to -0.4) in low EC50 patients (p<0.001). After adjusting for gender, age, BMI, 25 OH vitamin D level and preoperative iPTH, lowest t-score and calcium EC50 were inversely correlated, with a partial Spearman correlation coefficient of -0.35 (p=0.02). Impaired calcium sensing in parathyroid tumors is selectively observed in a subset of patients with more severe bone mineral density deficit. Assessment of parathyroid tumor biochemical behavior may be a useful predictor of disease severity as measured by bone mineral density in patients with PHPT. Copyright © 2017 Elsevier Inc. All rights reserved.

Diet and renal stone formation.

PubMed

Trinchieri, A

2013-02-01

The relationship between diet and the formation of renal stones is demonstrated, but restrictive diets do not take into account the complexity of metabolism and the complex mechanisms that regulate the saturation and crystallization processes in the urine. The restriction of dietary calcium can reduce the urinary excretion of calcium but severe dietary restriction of calcium causes hyperoxaluria and a progressive loss of bone mineral component. Furthermore urinary calcium excretion is influenced by other nutrients than calcium as sodium, potassium, protein and refined carbohydrates. Up to 40% of the daily excretion of oxalate in the urine is from dietary source, but oxalate absorption in the intestine depends linearly on the concomitant dietary intake of calcium and is influenced by the bacterial degradation by several bacterial species of intestinal flora. A more rational approach should be based on the cumulative effects of foods and different dietary patterns on urinary saturation rather than on the effect of single nutrients. A diet based on a adequate intake of calcium (1000-1200 mg per day) and containment of animal protein and salt can decrease significantly urinary supersaturation for calcium oxalate and reduce the relative risk of stone recurrence in hypercalciuric renal stone formers. The DASH-style diet that is high in fruits and vegetables, moderate in low-fat dairy products and low in animal proteins and salt is associated with a lower relative supersaturation for calcium oxalate and a marked decrease in risk of incident stone formation. All the diets above mentioned have as a common characteristic the reduction of the potential acid load of the diet that can be correlated with a higher risk of recurrent nephrolithiasis, because the acid load of diet is inversely related to urinary citrate excretion. The restriction of protein and salt with an adequate calcium intake seem to be advisable but should be implemented with the advice to increase the intake of vegetables that can carry a plentiful supply of alkali that counteract the acid load coming from animal protein. New prospective studies to evaluate the effectiveness of the diet for the prevention of renal stones should be oriented to simple dietary advices that should be focused on a few specific goals easily controlled by means of self-evaluation tools, such as the LAKE food screener.

Pathological Calcification and Ossification in Relation to Leriche and Policard's Theory.

PubMed

Jones, W; Roberts, R E

1933-05-01

(1) Pathology of calcification and ossification.-The Leriche-Policard theories. Hyperaemia of bone causes decalcification. Reduced blood supply causes sclerosis. Diminution of vascularity of fibrous tissue causes calcification. Excess of calcium, adequate blood supply and fibroblasts give rise to bone anywhere. Subperiosteal ossification. "Myositis ossificans."(2) Radiological significance of density of bone shadows.-Decalcification of disuse, of infections, of neoplasms. Traumatic and infective scquestra. Evidence that a fragment of bone is avascular.(3) Hyperaemic decalcification of bone.-Delayed and non-union of fractures. Kummel's disease. Spontaneous hyperaemic dislocation of the atlas. Hyperaemic decalcification and nephrolithiasis.(4) Anaemic sclerosis of bone.-Syphilitic bone disease. Malignant bone disease. Fragility of sclerosed bone-Paget's, Kienboch's, Kohler's and Panner's, Albers-Schönberg's diseases.(5) Pathological calcification.-Calcification of supraspinatus tendon. Calcification of tumours-angioma, haematoma, and thrombosed vessels, lipoma, cysts, etc. Calcification of semilunar cartilages and intervertebral discs.(6) Pathological ossification.-Ossification of tendons. Ossification of semilunar cartilages.

The Roles and Mechanisms of Intestinal Oxalate Transport in Oxalate Homeostasis

PubMed Central

Hatch, Marguerite; Freel, Robert W.

2008-01-01

The mammalian intestine has an important role in the dynamics of oxalate exchange and thereby is significant in the etiology of calcium oxalate nephrolithiasis. Here we review some of the phenomenological observations that have led to the conclusion that anion exchangers (antiporters) are important mediators of secondarily active, net oxalate transport along the intestine (both absorptive and secretory). Understanding the mechanisms of transepithelial oxalate transport has been radically advanced in recent years by the identification of the SLC26 family of anion transporters which has facilitated the identification of specific proteins mediating individual apical or basolateral oxalate transport pathways. Moreover, identification of specific exchangers has underscored their relative importance to oxalate homeostasis as revealed by using knockout mouse models and facilitated studies of oxalate transport regulation in heterologous expression systems. Finally, the significance of oxalate degrading bacteria to oxalate homeostasis is considered from basic and applied perspectives. PMID:18359395

Degradation of oxalate in rats implanted with immobilized oxalate oxidase.

PubMed

Raghavan, K G; Tarachand, U

1986-01-20

Accumulation of oxalate leads to hyperoxaluria and calcium oxalate nephrolithiasis in man. Since oxalate is a metabolic end product in mammals, the feasibility of its enzymic degradation has been tested in vivo in rats by administering exogenous oxalate oxidase. Oxalate oxidase, isolated from banana fruit peels, in its native form was found to be non-active at the physiological pH of the recipient animal. However, its functional viability in the recipient animal was ensured by its prior binding with ethylenemaleic anhydride, thus shifting its pH activity curve towards the alkaline range. Rats implanted with dialysis membrane capsules containing such immobilized oxalate oxidase in their peritoneal cavities effectively metabolized intraperitoneally injected [14C]oxalate as well as its precursor [14C]glyoxalate. The implantation of capsules containing coentrapped multienzyme preparations of oxalate oxidase, catalase and peroxidase led to a further degradation of administered [14C]oxalate in rats.

Narcotic Use and Postoperative Doctor Shopping by Patients with Nephrolithiasis Requiring Operative Intervention: Implications for Patient Safety.

PubMed

Kappa, Stephen F; Green, Elizabeth A; Miller, Nicole L; Herrell, Stanley D; Mitchell, Christopher R; Mir, Hassan R; Resnick, Matthew J

2016-09-01

We sought to determine perioperative patterns of narcotic use and the prevalence of postoperative doctor shopping among patients with nephrolithiasis requiring operative management. We retrospectively reviewed the records of consecutive patients residing in Tennessee who required ureteroscopy with laser lithotripsy for nephrolithiasis at a single institution from January to December 2013. Using the Tennessee CSMD (Controlled Substances Medication Database) patients were categorized by the number of postoperative narcotic providers. Doctor shopping behavior was identified as any patient seeking more than 1 narcotic provider within 3 months of surgery. Demographic and clinical characteristics associated with doctor shopping behavior were identified. During the study period 200 eligible patients underwent ureteroscopy with laser lithotripsy for nephrolithiasis, of whom 48 (24%) were prescribed narcotics by more than 1 provider after surgery. Compared to those receiving narcotics from a single provider, patients with multiple narcotic providers were younger (48.1 vs 54.2 years, p <0.001), less educated (high school education or less in 83.3% vs 58.7%, p = 0.014), more likely to have a history of mental illness (37.5% vs 16%, p <0.01) and more likely to have undergone prior stone procedures (66% vs 42%, p <0.01). Additionally, these patients demonstrated more frequent preoperative narcotic use (87.5% vs 63.2%), longer postoperative narcotic use (39.1 vs 6.0 days) and a higher morphine equivalent dose per prescription (44.7 vs 35.2 dose per day, each p <0.001). Postoperative doctor shopping is common among patients with nephrolithiasis who require operative management. Urologists should be aware of available registry data to decrease the likelihood of redundant narcotic prescribing. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Lateral approach to nephrotomy in the management of unilateral renal calculi in a rabbit (Oryctolagus cuniculus).

PubMed

Martorell, Jaime; Bailon, Diego; Majó, Natalia; Andaluz, Anna

2012-04-01

A 5-year-old 2.23-kg (4.91-lb) spayed female Lop rabbit (Oryctolagus cuniculus) was evaluated because of a history of lethargy, polyuria, and polydipsia of 1 month's duration. The referring veterinarian made a presumptive diagnosis of hypercalcemia of unknown etiology on the basis of a plasma total calcium concentration of 14.0 mg/dL. Physical examination findings were unremarkable. Hematologic and plasma biochemical analysis revealed nonregenerative, normocytic, normochromic anemia (PCV, 28%) with heteropenia (23%; 1,334 heterophils/mL) and a total plasma calcium concentration of 16 mg/dL. Radiographic and ultrasonographic examination revealed radiodense and hyperechoic structures in both renal pelves and right unilateral nephrolithiasis. Nephrotomy was performed via laparotomy with a right lateral approach. A nephrolith composed of calcium carbonate and carbonate apatite was removed from the right renal pelvis. The rabbit's plasma tested positive for antibodies against Encephalitozoon cuniculi by means of an indirect immunofluorescence assay, and fenbendazole (20 mg/kg [9.1 mg/lb], p.o., q 24 h) was administered for 28 days. Although plasma calcium concentration was not substantially decreased after treatment (values were 14.1 and 15.1 mg/dL 1 week and 3 months after surgery, respectively), the patient did not have clinical signs of hypercalcemia and died of unrelated causes approximately 1 year after surgery. To the authors' knowledge, this is the first report of a nephrotomy performed in a rabbit via a lateral abdominal approach. This approach allowed easy location of the kidney and also reduced manipulation, thus decreasing the risk of damaging the abdominal viscera and potentially decreasing postoperative pain.

Effect of grapefruit juice on urinary lithogenicity.

PubMed

Goldfarb, D S; Asplin, J R

2001-07-01

An increased risk of nephrolithiasis has been associated with the ingestion of grapefruit juice in epidemiological studies. To our knowledge the basis of this effect of grapefruit juice has not been studied previously. We studied the effect of grapefruit juice consumption on urinary chemistry and measures of lithogenicity. Ten healthy men and women between ages of 25 and 40 years participated. Each subject drank 240 ml. of tap water at least 3 times daily for 7 days during the control period. This period was followed by a second 7 days experimental period during which they drank 240 ml. of grapefruit juice 3 times daily. In each 7-day period urine was collected for 24 hours during the last 3 days. Urine chemical analysis was performed, supersaturations of calcium oxalate, calcium phosphate and uric acid were calculated and urinary lithogenicity was measured. Urine volume and creatinine excretion were the same during the control and experimental periods. Grapefruit juice ingestion was associated with an increase in mean oxalate excretion plus or minus standard deviation of 41.1 +/- 9.2 to 51.9 +/- 12.0 mg. per 24 hours (p = 0.001) and in mean citrate excretion of 504.8 +/- 226.5 to 591.4 +/- 220.0 mg. per 24 hours (p = 0.01). There was no net change in the supersaturation or upper limit of metastability of calcium oxalate, calcium phosphate or uric acid. Crystal aggregation and growth inhibition by urinary macromolecules was not affected by grapefruit juice ingestion. Offsetting changes in urine chemistry caused by the ingestion of grapefruit juice led to no net change in calculated supersaturation. No changes in lithogenicity were demonstrated. The results do not demonstrate an effect of grapefruit juice for increasing lithogenicity. The basis of the observations of epidemiological studies remain unexplained.

Acute intraoperative reactions during the injection of calcium sulfate bone cement for the treatment of unicameral bone cysts: a review of four cases.

PubMed

Nystrom, Lukas; Raw, Robert; Buckwalter, Joseph; Morcuende, Jose A

2008-01-01

Unicameral bone cysts can predispose patients to pathologic fracture and deformities of growth. Treatment options vary from continuous decompression with transcortical placement of a cannulated screw to percutaneous aspiration and injection of medical-grade calcium sulfate. From 2005 to 2007, we treated 22 patients with unicameral bone cysts using aspiration and injection of calcium sulfate. Three patients experienced acute laryngospasm and one patient developed tachyarrhythmia, temporarily, associated with injection of calcium sulfate. All reactions occurred in patients under age 18 without predisposing risk factors and resolved spontaneously with supportive care. Although the mechanism is unclear, we hypothesize that these reactions are either due to the nociceptive stimulus of the calcium sulfate injection or a systemic calcium bolus. Clinicians using this product for this indication should be aware that such reactions may occur. We suggest endotracheal intubation and communication to the anesthesiologist about the time of the injection in preparation for these idiopathic responses. Further research is necessary to determine exactly how this reaction occurs and how it can be avoided.

Acute Intraoperative Reactions During the Injection of Calcium Sulfate Bone Cement for the Treatment of Unicameral Bone Cysts: A Review of Four Cases

PubMed Central

Nystrom, Lukas; Raw, Robert; Buckwalter, Joseph; Morcuende, Jose A.

2008-01-01

Unicameral bone cysts can predispose patients to pathologic fracture and deformities of growth. Treatment options vary from continuous decompression with transcortical placement of a cannulated screw to percutaneous aspiration and injection of medical-grade calcium sulfate. From 2005 to 2007, we treated 22 patients with unicameral bone cysts using aspiration and injection of calcium sulfate. Three patients experienced acute laryngospasm and one patient developed tachyarrhythmia, temporarily, associated with injection of calcium sulfate. All reactions occurred in patients under age 18 without predisposing risk factors and resolved spontaneously with supportive care. Although the mechanism is unclear, we hypothesize that these reactions are either due to the nociceptive stimulus of the calcium sulfate injection or a systemic calcium bolus. Clinicians using this product for this indication should be aware that such reactions may occur. We suggest endotracheal intubation and communication to the anesthesiologist about the time of the injection in preparation for these idiopathic responses. Further research is necessary to determine exactly how this reaction occurs and how it can be avoided. PMID:19223954

Enamel renal syndrome with associated amelogenesis imperfecta, nephrolithiasis, and hypocitraturia: A case report.

PubMed

Bhesania, Dhvani; Arora, Ankit; Kapoor, Sonali

2015-09-01

Numerous cases of enamel renal syndrome have been previously reported. Various terms, such as enamel renal syndrome, amelogenesis imperfecta and gingival fibromatosis syndrome, and enamel-renal-gingival syndrome, have been used for patients presenting with the dental phenotype characteristic of this condition, nephrocalcinosis or nephrolithiasis, and gingival findings. This report describes a case of amelogenesis imperfecta of the enamel agenesis variety with nephrolithiasis in a 21-year-old male patient who complained of small teeth. The imaging modalities employed were conventional radiography, cone-beam computed tomography, and renal sonography. Such cases are first encountered by dentists, as other organ or metabolic diseases are generally hidden. Hence, cases of amelogenesis imperfecta should be subjected to advanced diagnostic modalities, incorporating both dental and medical criteria, in order to facilitate comprehensive long-term management.

N-acetylcysteine with apocynin prevents hyperoxaluria-induced mitochondrial protein perturbations in nephrolithiasis.

PubMed

Sharma, Minu; Sud, Amit; Kaur, Tanzeer; Tandon, Chanderdeep; Singla, S K

2016-09-01

Diminished mitochondrial activities were deemed to play an imperative role in surged oxidative damage perceived in hyperoxaluric renal tissue. Proteomics is particularly valuable to delineate the damaging effects of oxidative stress on mitochondrial proteins. The present study was designed to apply large-scale proteomics to describe systematically how mitochondrial proteins/pathways govern the renal damage and calcium oxalate crystal adhesion in hyperoxaluria. Furthermore, the potential beneficial effects of combinatorial therapy with N-acetylcysteine (NAC) and apocynin were studied to establish its credibility in the modulation of hyperoxaluria-induced alterations in mitochondrial proteins. In an experimental setup with male Wistar rats, five groups were designed for 9 d. At the end of the experiment, 24-h urine was collected and rats were euthanized. Urinary samples were analyzed for kidney injury marker and creatinine clearance. Transmission electron microscopy revealed distorted renal mitochondria in hyperoxaluria but combinatorial therapy restored the normal mitochondrial architecture. Mitochondria were isolated from renal tissue of experimental rats, and mitochondrial membrane potential was analyzed. The two-dimensional electrophoresis (2-DE) based comparative proteomic analysis was performed on proteins isolated from renal mitochondria. The results revealed eight differentially expressed mitochondrial proteins in hyperoxaluric rats, which were identified by Matrix-assisted laser desorption/ionization time of flight/time of flight (MALDI-TOF/TOF) analysis. Identified proteins including those involved in important mitochondrial processes, e.g. antioxidant defense, energy metabolism, and electron transport chain. Therapeutic administration of NAC with apocynin significantly expunged hyperoxaluria-induced discrepancy in the renal mitochondrial proteins, bringing them closer to the controls. The results provide insights to further understand the underlying mechanisms in the development of hyperoxaluria-induced nephrolithiasis and the therapeutic relevance of the combinatorial therapy.

Whey versus soy protein diets and renal status in rats.

PubMed

Aparicio, Virginia A; Nebot, Elena; Tassi, Mohamed; Camiletti-Moirón, Daniel; Sanchez-Gonzalez, Cristina; Porres, Jesús M; Aranda, Pilar

2014-09-01

Different dietary protein sources can promote different renal statuses. We examined the effects of whey protein (WP) and soy protein (SP) intake on plasma, urinary, and morphological renal parameters in rats. One hundred and twenty Wistar rats were randomly distributed into 2 experimental groups fed with either WP or SP diets over 12 weeks. These diets were based on commercial WP or SP isolates. The urinary calcium content was higher in the WP diet compared to the SP diet group (P<.001) whereas the urinary citrate level was lower (P<.001). The urinary pH was more acidic in the WP diet group compared to the SP diet group (P<.001); however, no differences were observed between the groups for any of the renal morphological parameters analyzed (all, P>.05) or other plasma renal markers such as albumin or urea concentrations. The increase of acid and urinary calcium and the lower urinary citrate level observed in the WP diet group could increase the incidence of nephrolithiasis compared to the SP diet group. Despite the WP showed poorer acid-base profile, no significant morphological renal changes were observed. These results suggest that the use of SP instead of WP appears to promote a more alkaline plasma and urinary profile, with their consequent renal advantages.

Cholelithiasis and Nephrolithiasis in HIV-Positive Patients in the Era of Combination Antiretroviral Therapy

PubMed Central

Lin, Kuan-Yin; Liao, Sih-Han; Liu, Wen-Chun; Cheng, Aristine; Lin, Shu-Wen; Chang, Sui-Yuan; Tsai, Mao-Song; Kuo, Ching-Hua; Wu, Mon-Ro; Wang, Hsiu-Po; Hung, Chien-Ching; Chang, Shan-Chwen

2015-01-01

Objectives This study aimed to describe the epidemiology and risk factors of cholelithiasis and nephrolithiasis among HIV-positive patients in the era of combination antiretroviral therapy. Methods We retrospectively reviewed the medical records of HIV-positive patients who underwent routine abdominal sonography for chronic viral hepatitis, fatty liver, or elevated aminotransferases between January 2004 and January 2015. Therapeutic drug monitoring of plasma concentrations of atazanavir was performed and genetic polymorphisms, including UDP-glucuronosyltransferase (UGT) 1A1*28 and multidrug resistance gene 1 (MDR1) G2677T/A, were determined in a subgroup of patients who received ritonavir-boosted or unboosted atazanavir-containing combination antiretroviral therapy. Information on demographics, clinical characteristics, and laboratory testing were collected and analyzed. Results During the 11-year study period, 910 patients who underwent routine abdominal sonography were included for analysis. The patients were mostly male (96.9%) with a mean age of 42.2 years and mean body-mass index of 22.9 kg/m2 and 85.8% being on antiretroviral therapy. The anchor antiretroviral agents included non-nucleoside reverse-transcriptase inhibitors (49.3%), unboosted atazanavir (34.4%), ritonavir-boosted lopinavir (20.4%), and ritonavir-boosted atazanavir (5.5%). The overall prevalence of cholelithiasis and nephrolithiasis was 12.5% and 8.2%, respectively. Among 680 antiretroviral-experienced patients with both baseline and follow-up sonography, the crude incidence of cholelithiasis and nephrolithiasis was 4.3% and 3.7%, respectively. In multivariate analysis, the independent factors associated with incident cholelithiasis were exposure to ritonavir-boosted atazanavir for >2 years (adjusted odds ratio [AOR], 6.29; 95% confidence interval [CI], 1.12–35.16) and older age (AOR, 1.04; 95% CI, 1.00–1.09). The positive association between duration of exposure to ritonavir-boosted atazanavir and incident cholelithiasis was also found (AOR, per 1-year exposure, 1.49; 95% CI, 1.05–2.10). The associated factors with incident nephrolithiasis were hyperlipidemia (AOR, 3.97; 95% CI, 1.32–11.93), hepatitis B or C coinfection (AOR, 3.41; 95% CI, 1.09–10.62), and exposure to abacavir (AOR, 12.01; 95% CI, 1.54–93.54). Of 180 patients who underwent therapeutic drug monitoring of plasma atazanavir concentrations and pharmacogenetic investigations, we found that the atazanavir concentrations and UGT 1A1*28 and MDR1 G2677T/A polymorphisms were not statistically significantly associated with incident cholelithiasis and nephrolithiasis. Conclusions In HIV-positive patients in the era of combination antiretroviral therapy, a high prevalence of cholelithiasis and nephrolithiasis was observed, and exposure to ritonavir-boosted atazanavir for >2 years was associated with incident cholelithiasis. PMID:26360703

Amyotrophic lateral sclerosis immunoglobulins increase Ca2+ currents in a motoneuron cell line.

PubMed

Mosier, D R; Baldelli, P; Delbono, O; Smith, R G; Alexianu, M E; Appel, S H; Stefani, E

1995-01-01

The sporadic form of amyotrophic lateral sclerosis (ALS) is an idiopathic and eventually lethal disorder causing progressive degeneration of cortical and spinal motoneurons. Recent studies have shown that the majority of patients with sporadic ALS have serum antibodies that bind to purified L-type voltage-gated calcium channels and that antibody titer correlates with the rate of disease progression. Furthermore, antibodies purified from ALS patient sera have been found to alter the physiologic function of voltage-gated calcium channels in nonmotoneuron cell types. Using whole-cell patch-clamp techniques, immunoglobulins purified from sera of 5 of 6 patients with sporadic ALS are now shown to increase calcium currents in a hybrid motoneuron cell line, VSC4.1. These calcium currents are blocked by the polyamine funnel-web spider toxin FTX, which has previously been shown to block Ca2+ currents and evoked transmitter release at mammalian motoneuron terminals. These data provide additional evidence linking ALS to an autoimmune process and suggest that antibody-induced increases in calcium entry through voltage-gated calcium channels may occur in motoneurons in this disease, with possible deleterious effects in susceptible neurons.

Comparison of ultrasound versus computed tomography for the detection of kidney stones in the pediatric population: a clinical effectiveness study.

PubMed

Roberson, Nathaniel P; Dillman, Jonathan R; O'Hara, Sara M; DeFoor, William R; Reddy, Pramod P; Giordano, Richard M; Trout, Andrew T

2018-07-01

The incidence of pediatric nephrolithiasis in the United States is increasing. There is a paucity of literature comparing the diagnostic performance of computed ultrasound (US) to tomography (CT) in the pediatric population. To determine the diagnostic performance of renal US for nephrolithiasis in children using a clinical effectiveness approach. Institutional review board approval with a waiver of informed consent was obtained for this retrospective, HIPAA-complaint investigation. Billing records and imaging reports were used to identify children (≤18 years old) evaluated for nephrolithiasis by both US and unenhanced CT within 24 h between March 2012 and March 2017. Imaging reports were reviewed for presence, number, size and location of kidney stones. Diagnostic performance of US (reference standard=CT) was calculated per renal unit (left/right kidney) and per renal sector (four sectors per kidney). For sector analysis, US was considered truly positive if a stone was identified at CT in the same or an adjacent sector. There were 68 renal stones identified by CT in 30/69 patients (43%). Mean patient age was 14.7±3.6 years, and 35 were boys. For detecting nephrolithiasis in any kidney, US was 66.7% (48.8-80.8%) sensitive and 97.4% (86.8-99.9%) specific (positive predictive value=95.2% [77.3-99.8%], negative predictive value=79.2% [65.7-88.3%], positive likelihood ratio=26.0). Per renal sector, US was 59.7% (46.7-71.4%) sensitive and 97.4% (95.5-98.5%) specific (positive predictive value=72.3% [58.2-83.1%], negative predictive value=95.4% [93.2-96.9%], positive likelihood ratio=22.5). Of the 30 stones not detected by US, only 3 were >3 mm at CT. In clinical practice, US has high specificity for detecting nephrolithiasis in children but only moderate sensitivity and false negatives are common.

Antioxidants inhibition of high plasma androgenic markers in the pathogenesis of ethylene glycol (EG)-induced nephrolithiasis in Wistar rats.

PubMed

Naghii, Mohammad Reza; Mofid, Mahmood; Hedayati, Mehdi; Khalagi, Kazem

2014-04-01

The association between serum gonadal steroids and urolithiasis in males received only limited attention. Calcium oxalate urolithiasis is induced by administration of ethylene glycol in drinking water. It appears that the administration of natural antioxidants has been used to protect against nephrolithiasis in human and experimental animals. The purpose is to study the potential role of antioxidants as inhibitors of high plasma androgenic markers or hyperandrogenicity in the pathogenesis of ethylene glycol-induced nephrolithiasis in Wistar rats. Male Wistar rats were studied in 4-week period. Group 1 (control) was fed a standard commercial diet. Group 2 received the same diet with 0.5 % of ethylene glycol. Group 3 received EG plus the diet and water added with antioxidant nutrients and lime juice as the dietary source of citrate. Group 4 and Group 5 were treated similar to Group 2 and Group 3 with 0.75 % of ethylene glycol. For antioxidant supplementation, the standard diet enriched with 4,000.0 μg vitamin E and 1,500.0 IU vitamin A for each rat per day added to the diet once a week, and provided daily with 5.0 mg vitamin C, 400.0 μg vitamin B6, 20.0 μg selenium, 12.0 mg zinc, and 2.0 mg boron for each rat per day in their drinking water. After treatment period, collection of blood was performed and kidneys were removed and used for histopathological examination. The results based on various assays, measuring size of crystal deposition, and histological examinations showed that high concentration of androgens acts as promoter for the formation of renal calculi due to ethylene glycol consumption and the inhibitory role of antioxidant complex in the formation of renal calculi disease. Data revealed that the size and the mean number of crystal deposits determined in EG 0.75 % treated groups (G4) were significantly higher than the EG-treated groups, added with antioxidant nutrients and lime juice (G5). The mean concentration of androgens in Group 4 increased after EG 0.75 % administration, and decreased after antioxidants supplementation in Group 5. Elevated concentration of androgens (as promoters of the formation of renal calculi) as a result of EG consumption and their decreasing following antioxidant supplementations along with the slight decrease in malondialdehyde level provides a scientific rational for preventive and treatment roles of antioxidant nutrient complex in kidney stone disease.

Unique Cardiac Purkinje Fiber Transient Outward Current β-Subunit Composition

PubMed Central

Xiao, Ling; Koopmann, Tamara T.; Ördög, Balázs; Postema, Pieter G.; Verkerk, Arie O.; Iyer, Vivek; Sampson, Kevin J.; Boink, Gerard J.J.; Mamarbachi, Maya A.; Varro, Andras; Jordaens, Luc; Res, Jan; Kass, Robert S.; Wilde, Arthur A.; Bezzina, C.R.; Nattel, Stanley

2015-01-01

Rationale A chromosomal haplotype producing cardiac overexpression of dipeptidyl peptidase-like protein-6 (DPP6) causes familial idiopathic ventricular fibrillation. The molecular basis of transient outward current (Ito) in Purkinje fibers (PFs) is poorly understood. We hypothesized that DPP6 contributes to PF Ito and that its overexpression might specifically alter PF Ito properties and repolarization. Objective To assess the potential role of DPP6 in PF Ito. Methods and Results Clinical data in 5 idiopathic ventricular fibrillation patients suggested arrhythmia origin in the PF-conducting system. PF and ventricular muscle Ito had similar density, but PF Ito differed from ventricular muscle in having tetraethylammonium sensitivity and slower recovery. DPP6 overexpression significantly increased, whereas DPP6 knockdown reduced, Ito density and tetraethylammonium sensitivity in canine PF but not in ventricular muscle cells. The K+-channel interacting β-subunit K+-channel interacting protein type-2, essential for normal expression of Ito in ventricular muscle, was weakly expressed in human PFs, whereas DPP6 and frequenin (neuronal calcium sensor-1) were enriched. Heterologous expression of Kv4.3 in Chinese hamster ovary cells produced small Ito; Ito amplitude was greatly enhanced by coexpression with K+-channel interacting protein type-2 or DPP6. Coexpression of DPP6 with Kv4.3 and K+-channel interacting protein type-2 failed to alter Ito compared with Kv4.3/K+-channel interacting protein type-2 alone, but DPP6 expression with Kv4.3 and neuronal calcium sensor-1 (to mimic PF Ito composition) greatly enhanced Ito compared with Kv4.3/neuronal calcium sensor-1 and recapitulated characteristic PF kinetic/pharmacological properties. A mathematical model of cardiac PF action potentials showed that Ito enhancement can greatly accelerate PF repolarization. Conclusions These results point to a previously unknown central role of DPP6 in PF Ito, with DPP6 gain of function selectively enhancing PF current, and suggest that a DPP6-mediated PF early-repolarization syndrome might be a novel molecular paradigm for some forms of idiopathic ventricular fibrillation. PMID:23532596

Idiopathic Fanconi's syndrome with nephrogenic diabetes insipidus in a child who presented as vitamin D resistant rickets--a case report and review of literature.

PubMed

Patra, Soumya; Nadri, Gulnaz; Chowdhary, Harish; Pemde, Harish K; Singh, Varinder; Chandra, Jagdish

2011-01-01

Fanconi's syndrome is a complex of multiple tubular dysfunctions of proximal tubular cells occurring alone or in association with a variety of inherited (primary) or acquired (secondary) disorders. It is characterized by aminoaciduria, normoglycemic glycosuria, tubular proteinuria without hematuria, metabolic acidosis without anion gap and excessive urinary excretion of phosphorous, calcium, uric acid, bicarbonate, sodium, potassium and magnesium. Diabetes insipidus is a disease of collecting tubules and a child mainly presents with dehydration and hypernatremia. We report the first case of idiopathic Fanconi's syndrome along with nephrogenic diabetes insipidus (NDI) in a child who presented to us as resistant rickets. Medline search did not reveal any case of nephrogenic diabetes insipidus associated with idiopathic Fanconi's syndrome. We hypothesized that the NDI may be due to severe hypokalemia induced tubular dysfunction. The child was treated for hypophosphatemic rickets with severe metabolic acidosis and the treatment for NDI was also given. Now he has healed rickets and normal blood pH, sodium and osmolarity.

Clinical evaluation of cats with nonobstructive urinary tract diseases.

PubMed

Buffington, C A; Chew, D J; Kendall, M S; Scrivani, P V; Thompson, S B; Blaisdell, J L; Woodworth, B E

1997-01-01

To identify the underlying cause of clinical signs in cats with nonobstructive diseases of the bladder and urethra. Prospective case series. 109 cats examined by the urology service of The Ohio State University's veterinary teaching hospital because of stranguria, hematuria, pollakiuria, or urination in inappropriate locations. History was obtained and a CBC, serum biochemical analyses, serologic tests for FeLV and feline immunodeficiency virus, urinalysis, bacterial culture of urine, and contrast radiography or urethrocystoscopy (females only) were performed. 16 cats had cystic calculi: 8 had struvite uroliths, 7 had calcium oxalate uroliths, and 1 had a urolith of unknown composition in conjunction with an anatomic defect. Anatomic defects, including diverticulae, urethral strictures, and a malpositioned urethra, were identified in 12 cats. A urinary tract infection was identified in 1 cat, and neoplasia was diagnosed in 2. One of the cats with neoplasia also had a struvite urolith. The remaining 80 cats did not have an anatomic defect, urolith, or tumor. Ten of these cats also did not have radiographic or cystoscopic abnormalities and were presumed to have a behavioral disorder. The remaining 70 cats had radiographic or cystoscopic abnormalities, and idiopathic cystitis was diagnosed. In 14 of the cats with idiopathic cystitis, results of a urinalysis were normal. Cats with idiopathic cystitis were significantly more likely to eat dry food exclusively (59%) than were cats in the general population (19%). Results suggest that idiopathic cystitis occurs commonly in cats with stranguria, hematuria, pollakiuria, or inappropriate elimination and is associated with consumption of dry foods. Contrast radiography or cystoscopy is necessary for differentiating idiopathic cystitis from behavioral disorders in some cats.

HOW DO STONES FORM? IS UNIFICATION OF THEORIES ON STONE FORMATION POSSIBLE?

PubMed Central

Bird, Victoria Y.; Khan, Saeed R.

2017-01-01

Summary There are two basic pathways for formation of calcium based kidney stones. Most idiopathic calcium oxalate (CaOx) stones are formed in association with sub-epithelial plaques of calcium phosphate (CaP), known as Randall’s plaques, on renal papillary surfaces. Crystal formation and retention within the terminal collecting ducts, the ducts of Bellini, leading to the formation of Randall’s plugs, is the other pathway. Both pathways require supersaturation leading to crystallization, regulated by various crystallization modulators produced in response to changing urinary conditions. High supersaturation, as a result of a variety of genetic and environmental factors, leads to crystallization in the terminal collecting ducts, eventually plugging their openings into the renal pelvis. Stasis behind the plugs may lead to the formation of attached or unattached stones in the tubular lumen. Deposition of crystals on the plug surface facing the pelvic or tubular urine may result in stone formation on the Randall’s plugs. Kidneys of idiopathic stone formers may be subjected to oxidative stress as a result of increased urinary excretion of calcium/oxalate/phosphate and/or decrease in the production of functional crystallization inhibitors or in relation to co-morbidities such as hypertension, atherosclerosis, or acute kidney injury. We have proposed that production of reactive oxygen species (ROS) causes dedifferentiation of epithelial/endothelial cells into osteoblast type cells and deposition of CaP in the basement membrane of renal tubules or vessels. Growth, aggregation and melding of CaP crystals leads to the formation of plaque which grows by further calcification of interstitial collagen and membranous vesicles. Plaque becomes exposed to pelvic urine once the covering papillary epithelium is breached. Surface layers of CaP are replaced by CaOx through direct transformation or demineralization of CaP and mineralization of CaOx. Alternatively, or in addition, CaOx crystals nucleate directly on the plaque surface. Stone growth may also depend upon supersaturation in the pelvic urine, triggering further nucleation, growth and aggregation. PMID:28221139

MRP-1 and BCRP Promote the Externalization of Phosphatidylserine in Oxalate-treated Renal Epithelial Cells: Implications for Calcium Oxalate Urolithiasis.

PubMed

Li, YiFu; Yu, ShiLiang; Gan, XiuGuo; Zhang, Ze; Wang, Yan; Wang, YingWei; An, RuiHua

2017-09-01

To investigate the possible involvement of multidrug resistance-associated protein 1 (MRP-1) and breast cancer resistance protein (BCRP) in the oxalate-induced redistribution of phosphatidylserine (PS) in renal epithelial cell membranes. A western blot analysis was used to examine the MRP-1 and BCRP expression levels. Surface-expressed PS was detected by the annexin V-binding assay. The cell-permeable fluorogenic probe 2,7-dichlorofluorescein diacetate was used to measure the intracellular reactive oxygen species (ROS) level. A rat model of hyperoxaluria was obtained using 0.5% ethylene glycol and 1.0% ammonium chloride. In addition, certain animals received verapamil (50 mg/kg body weight), which is a common inhibitor of MRP-1 and BCRP. The degree of nephrolithiasis was assessed histomorphometrically using sections stained by Pizzolato method and by measuring the calcium oxalate crystal content in the renal tissue. Oxalate produced a concentration-dependent increase in the synthesis of MRP-1 and BCRP. Treatment with MK571 and Ko143 (MRP-1- and BCRP-specific inhibitors, respectively) significantly attenuated the oxalate-induced PS externalization. Adding the antioxidant N-acetyl-l-cysteine significantly reduced MRP-1 and BCRP expression. In vivo, markedly decreased nephrocalcinosis was observed compared with that in the rat model of hyperoxaluria without verapamil treatment. Oxalate induces the upregulation of MRP-1 and BCRP, which act as phospholipid floppases causing PS externalization in the renal epithelial cell membrane. The process is mediated by intracellular ROS production. The ROS-mediated increase in the synthesis of MRP-1 and BCRP can play an important role in hyperoxaluria-promoted calcium oxalate urolithiasis by facilitating phosphatidylserine redistribution in renal epithelial cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Thiazides diuretics in the treatment of nephrolithiasis: are we using them in an evidence-based fashion?

PubMed

Vigen, Rebecca; Weideman, Rick A; Reilly, Robert F

2011-09-01

In the 1980s a change occurred in hydrochlorothiazide prescribing practices for hypertension from high-dose (50 mg/day) to low-dose (12.5-25 mg/day) therapy. However, randomized controlled trials (RCT) for prevention of calcium-containing kidney stones (CCKS) employed only high doses (≥ 50 mg/day). We hypothesized that these practices have resulted in underdosing of hydrochlorothiazide for prevention of CCKS. Patients with a filled prescription for thiazide diuretics that underwent a 24-h urine stone risk factor analysis were eligible. Those with evidence that thiazide was prescribed for CCKS were further analyzed. Of 107 patients, 102 were treated with hydrochlorothiazide, 4 with indapamide, and one with chlorthalidone. Only 35% of hydrochlorothiazide-treated patients received 50 mg/day; a dose previously shown to reduce stone recurrence. Fifty-two percent were prescribed 25 mg and 13% 12.5 mg daily, doses that were not studied in RCT. Evidence-based hydrochlorothiazide use was suboptimal regardless of where the patient received care (Nephrology or Endocrinology clinic). In a small subset of patients (n = 6) with 24-h urinary calcium excretion measured at baseline and after 2 hydrochlorothiazide doses (25 and ≥ 50 mg), there was a trend toward decreased urinary calcium excretion as the dose was increased from 25 to ≥ 50 mg/day (p = 0.051). Low-dose hydrochlorothiazide was often used for prevention of CCKS despite the fact that there is no evidence that it is effective in this setting. This may have resulted from a practice pattern of using lower doses for hypertension therapy or a lack of knowledge of RCT results in treatment of CCKS.

INDUCIBLE TRANSIENT CENTRAL RETINAL ARTERY VASOSPASM: A CASE REPORT.

PubMed

Mishulin, Aleksey; Ghandi, Sachin; Apple, Daniel; Lin, Xihui; Hu, Jonathan; Abrams, Gary W

2017-09-27

To report a case of inducible transient central retinal artery vasospasm with associated imaging. Observational case report. A 51-year-old man presented for outpatient follow-up for recurrent inducible transient vision loss in his right eye. He experienced an episode during examination and was found to have central retinal artery vasospasm. Fundus photography and fluorescein angiography obtained during his vasospastic attack confirmed retinal arterial vasospasm. Treatment with a calcium-channel blocker (nifedipine) has been effective in preventing recurrent attacks. Idiopathic primary vasospasm is a rare cause of transient vision loss that is difficult to confirm because of the transient nature. We obtained imaging showing the initiation and resolution of the vasospastic event. The patient was then successfully treated with a calcium-channel blocker.

Theobromine Inhibits Uric Acid Crystallization. A Potential Application in the Treatment of Uric Acid Nephrolithiasis

PubMed Central

Grases, Felix; Rodriguez, Adrian; Costa-Bauza, Antonia

2014-01-01

Purpose To assess the capacity of methylxanthines (caffeine, theophylline, theobromine and paraxanthine) to inhibit uric acid crystallization, and to evaluate their potential application in the treatment of uric acid nephrolithiasis. Materials and Methods The ability of methylxathines to inhibit uric acid nucleation was assayed turbidimetrically. Crystal morphology and its modification due to the effect of theobromine were evaluated by scanning electron microscopy (SEM). The ability of theobromine to inhibit uric acid crystal growth on calculi fragments resulting from extracorporeal shock wave lithotripsy (ESWL) was evaluated using a flow system. Results The turbidimetric assay showed that among the studied methylxanthines, theobromine could markedly inhibit uric acid nucleation. SEM images showed that the presence of theobromine resulted in thinner uric acid crystals. Furthermore, in a flow system theobromine blocked the regrowth of post-ESWL uric acid calculi fragments. Conclusions Theobromine, a natural dimethylxanthine present in high amounts in cocoa, acts as an inhibitor of nucleation and crystal growth of uric acid. Therefore, theobromine may be clinically useful in the treatment of uric acid nephrolithiasis. PMID:25333633

Bilateral uric acid nephrolithiasis and ureteral hypertrophy in a free-ranging river otter (Lontra canadensis)

USGS Publications Warehouse

Grove, Robert A.; Bildfell, Rob; Henny, Charles J.; Buhler, D.R.

2003-01-01

We report the first case of uric acid nephrolithiasis in a free-ranging river otter (Lontra canadensis). A 7 yr old male river otter collected from the Skagit River of western Washington (USA) had bilateral nephrolithiasis and severely enlarged ureters (one of 305 examined [0.33%]). The uroliths were 97% uric acid and 3% protein. Microscopic changes in the kidney were confined to expansion of renal calyces, minor loss of medullary tissue, and multifocal atrophy of the cortical tubules. No inflammation was observed in either kidney or the ureters. The ureters were enlarged due to marked hypertrophy of smooth muscle plus dilation of the lumen. Fusion of the major calyces into a single ureteral lumen was several cm distal to that of two adult male otters used as histopathologic control specimens. This case report is part of a large contaminant study of river otters collected from Oregon and Washington. It is important to understand diseases and lesions of the otter as part of our overall evaluation of this population.

Obesity and kidney stone disease: a systematic review.

PubMed

Carbone, Antonio; Al Salhi, Yazan; Tasca, Andrea; Palleschi, Giovanni; Fuschi, Andrea; De Nunzio, Cosimo; Bozzini, Giorgio; Mazzaferro, Sandro; Pastore, Antonio L

2018-05-31

Currently, abdominal obesity has reached an epidemic stage and obesity represents an important challenge for worldwide health authorities. Epidemiologic studies have demonstrated that the stone risk incidence increases with body mass index (BMI), through multiple pathways. Metabolic syndrome and diabetes are associated with an increased renal stones disease incidence. The aim of this systematic review was to investigate the prevalence, morbidity, risk factors involved in the association between obesity and urolithiasis. The search involved finding relevant studies from MEDLINE, EMBASE, Ovid, the Cochrane Central Register of Controlled Trials, CINAHL, Google Scholar, and individual urological journals between January 2001 and May 2017. The inclusion criteria were for studies written in the English language, reporting on the association between obesity and urinary stones. The underlying pathophysiology of stone formation in obese patients is thought to be related to insulin resistance, dietary factors, and a lithogenic urinary profile. Uric acid stones and calcium oxalate stones are observed frequently in these patients. Insulin resistance is thought to alter the renal acid-base metabolism, resulting in a lower urine pH, and increasing the risk of uric acid stone disease. Obesity is also associated with excess nutritional intake of lithogenic substances and with an increase in urinary tract infection incidence. Recent studies highlighted that renal stone disease increases the risk of myocardial infarction, progression of chronic kidney disease, and diabetes. Contemporary, bariatric surgery has been shown to be associated with hyperoxaluria and oxalate nephropathy. Certainly, the many health risks of obesity, including nephrolithiasis, will add more burden on urologists and nephrologists. Obesity related nephrolithiasis seems to necessitate weight loss as primary treatment, but the recognition of the associated complications is necessary to prevent induction of new and equally severe medical problems. The optimal approach to obesity control that minimizes stone risk needs to be determined in order to manage obesity-induced renal stones disease.

Extensive characterizations of bacteria isolated from catheterized urine and stone matrices in patients with nephrolithiasis.

PubMed

Tavichakorntrakool, Ratree; Prasongwattana, Vitoon; Sungkeeree, Seksit; Saisud, Phitsamai; Sribenjalux, Pipat; Pimratana, Chaowat; Bovornpadungkitti, Sombat; Sriboonlue, Pote; Thongboonkerd, Visith

2012-11-01

Urinary tract infections are generally known to be associated with nephrolithiasis, particularly struvite stone, in which the most common microbe found is urea-splitting bacterium, i.e. Proteus mirabilis. However, our observation indicated that it might not be the case of stone formers in Thailand. We therefore extensively characterized microorganisms associated with all types of kidney stones. A total of 100 kidney stone formers (59 males and 41 females) admitted for elective percutaneous nephrolithotomy were recruited and microorganisms isolated from catheterized urine and cortex and nidus of their stones were analyzed. From 100 stone formers recruited, 36 cases had a total of 45 bacterial isolates cultivated from their catheterized urine and/or stone matrices. Among these 36 cases, chemical analysis by Fourier-transformed infrared spectroscopy revealed that 8 had the previously classified 'infection-induced stones', whereas the other 28 cases had the previously classified 'metabolic stones'. Calcium oxalate (in either pure or mixed form) was the most common and found in 64 and 75% of the stone formers with and without bacterial isolates, respectively. Escherichia coli was the most common bacterium (approximately one-third of all bacterial isolates) found in urine and stone matrices (both nidus and periphery). Linear regression analysis showed significant correlation (r = 0.860, P < 0.001) between bacterial types in urine and stone matrices. Multidrug resistance was frequently found in these isolated bacteria. Moreover, urea test revealed that only 31% were urea-splitting bacteria, whereas the majority (69%) had negative urea test. Our data indicate that microorganisms are associated with almost all chemical types of kidney stones and urea-splitting bacteria are not the major causative microorganisms found in urine and stone matrices of the stone formers in Thailand. These data may lead to rethinking and a new roadmap for future research regarding the role of microorganisms in kidney stone formation.

Epidemiology and Health-Related Quality of Life in Hypoparathyroidism in Norway

PubMed Central

Løvås, Kristian; Debowska, Aleksandra; Eriksen, Erik F.; Evang, Johan A.; Fossum, Christian; Fougner, Kristian J.; Holte, Synnøve E.; Lima, Kari; Moe, Ragnar B.; Myhre, Anne Grethe; Kemp, E. Helen; Nedrebø, Bjørn G.; Svartberg, Johan; Husebye, Eystein S.

2016-01-01

Objective: The epidemiology of hypoparathyroidism (HP) is largely unknown. We aimed to determine prevalence, etiologies, health related quality of life (HRQOL) and treatment pattern of HP. Methods: Patients with HP and 22q11 deletion syndrome (DiGeorge syndrome) were identified in electronic hospital registries. All identified patients were invited to participate in a survey. Among patients who responded, HRQOL was determined by Short Form 36 and Hospital Anxiety and Depression scale. Autoantibodies were measured and candidate genes (CaSR, AIRE, GATA3, and 22q11-deletion) were sequenced for classification of etiology. Results: We identified 522 patients (511 alive) and estimated overall prevalence at 102 per million divided among postsurgical HP (64 per million), nonsurgical HP (30 per million), and pseudo-HP (8 per million). Nonsurgical HP comprised autosomal dominant hypocalcemia (21%), autoimmune polyendocrine syndrome type 1 (17%), DiGeorge/22q11 deletion syndrome (15%), idiopathic HP (44%), and others (4%). Among the 283 respondents (median age, 53 years [range, 9–89], 75% females), seven formerly classified as idiopathic were reclassified after genetic and immunological analyses, whereas 26 (37% of nonsurgical HP) remained idiopathic. Most were treated with vitamin D (94%) and calcium (70%), and 10 received PTH. HP patients scored significantly worse than the normative population on Short Form 36 and Hospital Anxiety and Depression scale; patients with postsurgical scored worse than those with nonsurgical HP and pseudo-HP, especially on physical health. Conclusions: We found higher prevalence of nonsurgical HP in Norway than reported elsewhere. Genetic testing and autoimmunity screening of idiopathic HP identified a specific cause in 21%. Further research is necessary to unravel the causes of idiopathic HP and to improve the reduced HRQOL reported by HP patients. PMID:27186861

Epidemiology and Health-Related Quality of Life in Hypoparathyroidism in Norway.

PubMed

Astor, Marianne C; Løvås, Kristian; Debowska, Aleksandra; Eriksen, Erik F; Evang, Johan A; Fossum, Christian; Fougner, Kristian J; Holte, Synnøve E; Lima, Kari; Moe, Ragnar B; Myhre, Anne Grethe; Kemp, E Helen; Nedrebø, Bjørn G; Svartberg, Johan; Husebye, Eystein S

2016-08-01

The epidemiology of hypoparathyroidism (HP) is largely unknown. We aimed to determine prevalence, etiologies, health related quality of life (HRQOL) and treatment pattern of HP. Patients with HP and 22q11 deletion syndrome (DiGeorge syndrome) were identified in electronic hospital registries. All identified patients were invited to participate in a survey. Among patients who responded, HRQOL was determined by Short Form 36 and Hospital Anxiety and Depression scale. Autoantibodies were measured and candidate genes (CaSR, AIRE, GATA3, and 22q11-deletion) were sequenced for classification of etiology. We identified 522 patients (511 alive) and estimated overall prevalence at 102 per million divided among postsurgical HP (64 per million), nonsurgical HP (30 per million), and pseudo-HP (8 per million). Nonsurgical HP comprised autosomal dominant hypocalcemia (21%), autoimmune polyendocrine syndrome type 1 (17%), DiGeorge/22q11 deletion syndrome (15%), idiopathic HP (44%), and others (4%). Among the 283 respondents (median age, 53 years [range, 9-89], 75% females), seven formerly classified as idiopathic were reclassified after genetic and immunological analyses, whereas 26 (37% of nonsurgical HP) remained idiopathic. Most were treated with vitamin D (94%) and calcium (70%), and 10 received PTH. HP patients scored significantly worse than the normative population on Short Form 36 and Hospital Anxiety and Depression scale; patients with postsurgical scored worse than those with nonsurgical HP and pseudo-HP, especially on physical health. We found higher prevalence of nonsurgical HP in Norway than reported elsewhere. Genetic testing and autoimmunity screening of idiopathic HP identified a specific cause in 21%. Further research is necessary to unravel the causes of idiopathic HP and to improve the reduced HRQOL reported by HP patients.

Is the renal kallikrein-kinin system a factor that modulates calciuria?

PubMed

Negri, Armando Luis

Renal tubular calcium reabsorption is one of the principal factors that determine serum calcium concentration and calcium excretion. Calcium excretion is regulated by the distal convoluted tubule and connecting tubule, where the epithelial calcium channel TRPV5 can be found, which limits the rate of transcellular calcium transport. The dynamic presence of the TRPV5 channel on the surface of the tubular cell is mediated by an endosomal recycling process. Different intrarenal factors are involved in calcium channel fixation in the apical membrane, including the anti-ageing hormone klotho and tissue kallikrein (TK). Both proteins are synthesised in the distal tubule and secreted in the tubular fluid. TK stimulates active calcium reabsorption through the bradykinin receptor B2 that compromises TRPV5 activation through the protein kinase C pathway. TK-deficient mice show hypercalciuria of renal origin comparable to that seen in TRPV5 knockout mice. There is a polymorphism with loss of function of the human TK gene R53H (allele H) that causes a marked decrease in enzymatic activity. The presence of the allele H seems to be common at least in the Japanese population (24%). These individuals have a tendency to greater calcium and sodium excretion in urine that is more evident during furosemide infusion. Future studies should analyse if manipulating the renal kallikrein-kinin system can correct idiopathic hypercalciuria with drugs other than thiazide diuretics. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Autosomal Dominant Hypercalciuria in a Mouse Model Due to a Mutation of the Epithelial Calcium Channel, TRPV5

PubMed Central

Loh, Nellie Y.; Verkaart, Sjoerd; Tammaro, Paolo; Gorvin, Caroline M.; Stechman, Michael J.; Ahmad, Bushra N.; Hannan, Fadil M.; Piret, Sian E.; Evans, Holly; Bellantuono, Ilaria; Hough, Tertius A.; Fraser, William D.; Hoenderop, Joost G. J.; Ashcroft, Frances M.; Brown, Steve D. M.; Bindels, René J. M.; Cox, Roger D.; Thakker, Rajesh V.

2013-01-01

Hypercalciuria is a major cause of nephrolithiasis, and is a common and complex disorder involving genetic and environmental factors. Identification of genetic factors for monogenic forms of hypercalciuria is hampered by the limited availability of large families, and to facilitate such studies, we screened for hypercalciuria in mice from an N-ethyl-N-nitrosourea mutagenesis programme. We identified a mouse with autosomal dominant hypercalciuria (HCALC1). Linkage studies mapped the Hcalc1 locus to a 11.94 Mb region on chromosome 6 containing the transient receptor potential cation channel, subfamily V, members 5 (Trpv5) and 6 (Trpv6) genes. DNA sequence analysis of coding regions, intron-exon boundaries and promoters of Trpv5 and Trpv6 identified a novel T to C transition in codon 682 of TRPV5, mutating a conserved serine to a proline (S682P). Compared to wild-type littermates, heterozygous (Trpv5 682P/+) and homozygous (Trpv5 682P/682P) mutant mice had hypercalciuria, polyuria, hyperphosphaturia and a more acidic urine, and ∼10% of males developed tubulointerstitial nephritis. Trpv5 682P/682P mice also had normal plasma parathyroid hormone but increased 1,25-dihydroxyvitamin D3 concentrations without increased bone resorption, consistent with a renal defect for the hypercalciuria. Expression of the S682P mutation in human embryonic kidney cells revealed that TRPV5-S682P-expressing cells had a lower baseline intracellular calcium concentration than wild-type TRPV5-expressing cells, suggesting an altered calcium permeability. Immunohistological studies revealed a selective decrease in TRPV5-expression from the renal distal convoluted tubules of Trpv5 682P/+ and Trpv5 682P/682P mice consistent with a trafficking defect. In addition, Trpv5682P/682P mice had a reduction in renal expression of the intracellular calcium-binding protein, calbindin-D28K, consistent with a specific defect in TRPV5-mediated renal calcium reabsorption. Thus, our findings indicate that the TRPV5 S682P mutant is functionally significant and study of HCALC1, a novel model for autosomal dominant hypercalciuria, may help further our understanding of renal calcium reabsorption and hypercalciuria. PMID:23383183

Autosomal dominant hypercalciuria in a mouse model due to a mutation of the epithelial calcium channel, TRPV5.

PubMed

Loh, Nellie Y; Bentley, Liz; Dimke, Henrik; Verkaart, Sjoerd; Tammaro, Paolo; Gorvin, Caroline M; Stechman, Michael J; Ahmad, Bushra N; Hannan, Fadil M; Piret, Sian E; Evans, Holly; Bellantuono, Ilaria; Hough, Tertius A; Fraser, William D; Hoenderop, Joost G J; Ashcroft, Frances M; Brown, Steve D M; Bindels, René J M; Cox, Roger D; Thakker, Rajesh V

2013-01-01

Hypercalciuria is a major cause of nephrolithiasis, and is a common and complex disorder involving genetic and environmental factors. Identification of genetic factors for monogenic forms of hypercalciuria is hampered by the limited availability of large families, and to facilitate such studies, we screened for hypercalciuria in mice from an N-ethyl-N-nitrosourea mutagenesis programme. We identified a mouse with autosomal dominant hypercalciuria (HCALC1). Linkage studies mapped the Hcalc1 locus to a 11.94 Mb region on chromosome 6 containing the transient receptor potential cation channel, subfamily V, members 5 (Trpv5) and 6 (Trpv6) genes. DNA sequence analysis of coding regions, intron-exon boundaries and promoters of Trpv5 and Trpv6 identified a novel T to C transition in codon 682 of TRPV5, mutating a conserved serine to a proline (S682P). Compared to wild-type littermates, heterozygous (Trpv5(682P/+)) and homozygous (Trpv5(682P/682P)) mutant mice had hypercalciuria, polyuria, hyperphosphaturia and a more acidic urine, and ∼10% of males developed tubulointerstitial nephritis. Trpv5(682P/682P) mice also had normal plasma parathyroid hormone but increased 1,25-dihydroxyvitamin D(3) concentrations without increased bone resorption, consistent with a renal defect for the hypercalciuria. Expression of the S682P mutation in human embryonic kidney cells revealed that TRPV5-S682P-expressing cells had a lower baseline intracellular calcium concentration than wild-type TRPV5-expressing cells, suggesting an altered calcium permeability. Immunohistological studies revealed a selective decrease in TRPV5-expression from the renal distal convoluted tubules of Trpv5(682P/+) and Trpv5(682P/682P) mice consistent with a trafficking defect. In addition, Trpv5(682P/682P) mice had a reduction in renal expression of the intracellular calcium-binding protein, calbindin-D(28K), consistent with a specific defect in TRPV5-mediated renal calcium reabsorption. Thus, our findings indicate that the TRPV5 S682P mutant is functionally significant and study of HCALC1, a novel model for autosomal dominant hypercalciuria, may help further our understanding of renal calcium reabsorption and hypercalciuria.

Hydronephrosis of one kidney

MedlinePlus

... Acute hydronephrosis; Urinary obstruction; Unilateral hydronephrosis; Nephrolithiasis - hydronephrosis; Kidney stone - hydronephrosis; Renal calculi - hydronephrosis; Ureteral calculi - hydronephrosis; ...

Idiopathic infantile arterial calcification: a rare cause of sudden unexpected death in childhood.

PubMed

Guimarães, Susana; Lopes, José Manuel; Oliveira, José Bessa; Santos, Agostinho

2010-07-27

Unexpected child death investigation is a difficult area of forensic practice in view of the wide range of possible genetic, congenital, and acquired natural and nonnatural causes. Idiopathic infantile arterial calcification (IIAC) is a rare autosomic recessive disease usually diagnosed postmortem. Inactivating mutations of the ENPP1 gene were described in 80% of the cases with IIAC. We report a case of a 5-year-old girl submitted to a forensic autopsy due to sudden death and possible medical negligence/parents child abuse. Major alterations found (intimal proliferation and deposition of calcium hydroxyapatite around the internal elastic lamina and media of arteries; acute myocardial infarct, stenotic and calcified coronary artery; perivascular and interstitial myocardial fibrosis; and subendocardial fibroelastosis) were diagnostic of IIAC. We reviewed IIAC cases published in the English literature and highlight the importance of adequate autopsy evaluation in cases of sudden child death.

Idiopathic Infantile Arterial Calcification: A Rare Cause of Sudden Unexpected Death in Childhood

PubMed Central

Guimarães, Susana; Lopes, José Manuel; Oliveira, José Bessa; Santos, Agostinho

2010-01-01

Unexpected child death investigation is a difficult area of forensic practice in view of the wide range of possible genetic, congenital, and acquired natural and nonnatural causes. Idiopathic infantile arterial calcification (IIAC) is a rare autosomic recessive disease usually diagnosed postmortem. Inactivating mutations of the ENPP1 gene were described in 80% of the cases with IIAC. We report a case of a 5-year-old girl submitted to a forensic autopsy due to sudden death and possible medical negligence/parents child abuse. Major alterations found (intimal proliferation and deposition of calcium hydroxyapatite around the internal elastic lamina and media of arteries; acute myocardial infarct, stenotic and calcified coronary artery; perivascular and interstitial myocardial fibrosis; and subendocardial fibroelastosis) were diagnostic of IIAC. We reviewed IIAC cases published in the English literature and highlight the importance of adequate autopsy evaluation in cases of sudden child death. PMID:21151691

BIOPSY PROVEN MEDULLARY SPONGE KIDNEY: Clinical findings, histopathology, and role of osteogenesis in stone and plaque formation

PubMed Central

Evan, Andrew P.; Worcester, Elaine M.; Williams, James C.; Sommer, Andre J.; Lingeman, James E.; Phillips, Carrie L.; Coe, Fredric L.

2015-01-01

Medullary sponge kidney (MSK) is associated with recurrent stone formation, but the clinical phenotype is unclear because patients with other disorders may be incorrectly labeled MSK. We studied 12 patients with histologic findings pathognomonic of MSK. All patients had an endoscopically recognizable pattern of papillary malformation, which may be segmental or diffuse. Affected papillae are enlarged and billowy, due to markedly enlarged inner medullary collecting ducts (IMCD), which contain small, mobile ductal stones. Patients had frequent dilation of Bellini ducts, with occasional mineral plugs. Stones may form over white (Randall’s) plaque, but most renal pelvic stones are not attached, and have a similar morphology as ductal stones, which are a mixture of calcium oxalate and apatite. Patients had no abnormalities of urinary acidification or acid excretion; the most frequent metabolic abnormality was idiopathic hypercalciuria. Although both Runx2 and Osterix are expressed in papillae of MSK patients, no mineral deposition was seen at the sites of gene expression, arguing against a role of these genes in this process. Similar studies in idiopathic calcium stone formers showed no expression of these genes at sites of Randall’s plaque. The most likely mechanism for stone formation in MSK appears to be crystallization due to urinary stasis in dilated IMCD with subsequent passage of ductal stones into the renal pelvis where they may serve as nuclei for stone formation. PMID:25615853

The general practitioner and nephrolithiasis

PubMed Central

Croppi, Emanuele; Cioppi, Federica; Vitale, Corrado

2008-01-01

Nephrolithiasis is a multifactorial disease the genesis of which is influenced by genetic, metabolic and environmental factors which determine a series of alterations in the urinary excretion of a number of substances, the cause of the disease itself. The general practitioner is often the first professional to be consulted as regards clinical and therapeutic treatment at the moment of the onset of nephrolithiasis, renal colic, inasmuch as contacted directly by the patient. His role however should not be limited to this initial phase but becomes of strategic importance throughout the subsequent diagnostic procedure; this is especially true with regard to relapses, in correctly placing the patient and, if necessary, referring him/her to the most appropriate specialist area. Running through the entire process which the lithiasic patient encounters from the onset of the disease until therapeutic treatment begins, it is clear how an appropriate initial approach can, in many cases, simplify and optimise such process. On the basis therefore of a complete medical record, and a few simple, biochemical and instrumental tests, the general practitioner is in a position to decide whether to treat the patient directly or to refer him/her to the most appropriate specialist field for investigation at a higher level. Over the last decades nephrolithiasis has progressively changed from being a disease of mainly surgical pertinence to being one of multidisciplinary medical interest in which the figure of the General Practitioner has a primary role, both during the initial diagnostic phase, by means of the correct physio-pathological identification of the problem, and in the subsequent phases as regards the choice and co-ordination of the various specialists involved. PMID:22460998

Nephrolithiasis as a presenting feature of chronic sarcoidosis.

PubMed Central

Rizzato, G.; Fraioli, P.; Montemurro, L.

1995-01-01

BACKGROUND--Renal calculi have been reported to occur in about 10% of patients with chronic sarcoidosis, but nephrolithiasis as a presentation of this disease has not been studied. METHODS--The charts of 618 patients with histologically proven sarcoidosis, seen in the period October 1978-1992, were reviewed in order to identify nephrolithiasis at presentation. RESULTS--Seventeen patients had renal calculi which preceded other manifestations of sarcoidosis. In six the occurrence of calculi suggested the diagnosis. Another eight patients had a previous history of recurrent colic with calculi. The time intervals between the first calculus and the appearance of other manifestations of sarcoidosis ranged from one to 25 years, but it was over four years in only two cases and all had at least one calculus in the year before the diagnosis was made. In the other three patients appearance of the calculus was distant in time and was probably unrelated to their sarcoidosis. In most cases the sarcoidosis was chronic and needed long term treatment with corticosteroids. Four patients had further calculi during follow up (one month to 16 years) due to an improper withdrawal of treatment decided by the patient in two cases, and to the reduction in the corticosteroid dose in the other two. CONCLUSIONS--Calculi were the presenting feature of sarcoidosis in six (1%) patients, and were the first manifestation of the disease in a total of 14 (2.2%). This frequency is over 20 times the likely incidence of calculi in the general population. Renal calculi may therefore be a rare primary manifestation of sarcoidosis. In such cases the disease is likely to be chronic and to require long term corticosteroid therapy. Sarcoidosis should always be suspected in cases of nephrolithiasis of unknown origin. PMID:7597671

Calcium Sensing Receptor Mutations Implicated in Pancreatitis and Idiopathic Epilepsy Syndrome Disrupt an Arginine-rich Retention Motif

PubMed Central

Stepanchick, Ann; McKenna, Jennifer; McGovern, Olivia; Huang, Ying; Breitwieser, Gerda E.

2010-01-01

Calcium sensing receptor (CaSR) mutations implicated in familial hypocalciuric hypercalcemia, pancreatitis and idiopathic epilepsy syndrome map to an extended arginine-rich region in the proximal carboxyl terminus. Arginine-rich motifs mediate endoplasmic reticulum retention and/or retrieval of multisubunit proteins so we asked whether these mutations, R886P, R896H or R898Q, altered CaSR targeting to the plasma membrane. Targeting was enhanced by all three mutations, and Ca2+-stimulated ERK1/2 phosphorylation was increased for R896H and R898Q. To define the role of the extended arginine-rich region in CaSR trafficking, we independently determined the contributions of R890/R891 and/or R896/K897/R898 motifs by mutation to alanine. Disruption of the motif(s) significantly increased surface expression and function relative to wt CaSR. The arginine-rich region is flanked by phosphorylation sites at S892 (protein kinase C) and S899 (protein kinase A). The phosphorylation state of S899 regulated recognition of the arginine-rich region; S899D showed increased surface localization. CaSR assembles in the endoplasmic reticulum as a covalent disulfide-linked dimer and we determined whether retention requires the presence of arginine-rich regions in both subunits. A single arginine-rich region within the dimer was sufficient to confer intracellular retention comparable to wt CaSR. We have identified an extended arginine-rich region in the proximal carboxyl terminus of CaSR (residues R890 - R898) which fosters intracellular retention of CaSR and is regulated by phosphorylation. Mutation(s) identified in chronic pancreatitis and idiopathic epilepsy syndrome therefore increase plasma membrane targeting of CaSR, likely contributing to the altered Ca2+ signaling characteristic of these diseases. PMID:20798521

In vitro anti-inflammatory activity of selected oxalate-degrading probiotic bacteria: potential applications in the prevention and treatment of hyperoxaluria.

PubMed

Giardina, Silvana; Scilironi, Cristina; Michelotti, Angela; Samuele, Alberta; Borella, Fabio; Daglia, Maria; Marzatico, Fulvio

2014-03-01

Oxalate (Ox) is a very common component of the human diet, capable to collect in the renal tissue and bind calcium to form calcium oxalate (CaOx) crystals. A supersaturation of CaOx crystal may cause nephrocalcinosis and nephrolithiasis. The inflammation derived from the CaOx crystal accumulation, together with innate or secondary renal alterations, could strongly affect the renal function. In this case a consumption of probiotics with either oxalate-degrading activity at intestinal level and systemic anti-inflammatory activity could be an alternative approach to treat the subjects with excess of urinary oxalate excretion. 11 strains of lactic acid bacteria (Lactobacilli and Bifidobacteria), already included in the list of bacteria safe for the human use, were investigated for their capability to degrade oxalate by mean of RP-HPLC-UV method and modulate inflammation in an in vitro model system based on peripheral blood mononuclear cells. Four promising bacterial strains (Lactobacillus plantarum PBS067, Lactobacillus acidophilus LA-14, Bifidobacterium breve PBS077, Bifidobacterium longum PBS078) were identified as innovative biological tools for the prevention and the therapeutic treatment of hyperoxaluria and the inflammatory events associated to the Ox accumulation. The oxalate-degrading activity of some probiotics and their capability to modulate the release of inflammation mediators could be exploited as a new nutraceutical and therapeutic approach for the treatment of oxalate accumulation and the related inflammatory state. © 2014 Institute of Food Technologists®

Improving nutritional quality and fungal tolerance in soya bean and grass pea by expressing an oxalate decarboxylase.

PubMed

Kumar, Vinay; Chattopadhyay, Arnab; Ghosh, Sumit; Irfan, Mohammad; Chakraborty, Niranjan; Chakraborty, Subhra; Datta, Asis

2016-06-01

Soya bean (Glycine max) and grass pea (Lathyrus sativus) seeds are important sources of dietary proteins; however, they also contain antinutritional metabolite oxalic acid (OA). Excess dietary intake of OA leads to nephrolithiasis due to the formation of calcium oxalate crystals in kidneys. Besides, OA is also a known precursor of β-N-oxalyl-L-α,β-diaminopropionic acid (β-ODAP), a neurotoxin found in grass pea. Here, we report the reduction in OA level in soya bean (up to 73%) and grass pea (up to 75%) seeds by constitutive and/or seed-specific expression of an oxalate-degrading enzyme, oxalate decarboxylase (FvOXDC) of Flammulina velutipes. In addition, β-ODAP level of grass pea seeds was also reduced up to 73%. Reduced OA content was interrelated with the associated increase in seeds micronutrients such as calcium, iron and zinc. Moreover, constitutive expression of FvOXDC led to improved tolerance to the fungal pathogen Sclerotinia sclerotiorum that requires OA during host colonization. Importantly, FvOXDC-expressing soya bean and grass pea plants were similar to the wild type with respect to the morphology and photosynthetic rates, and seed protein pool remained unaltered as revealed by the comparative proteomic analysis. Taken together, these results demonstrated improved seed quality and tolerance to the fungal pathogen in two important legume crops, by the expression of an oxalate-degrading enzyme. © 2016 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

KIDNEY STONES: AN UPDATE ON CURRENT PHARMACOLOGICAL MANAGEMENT AND FUTURE DIRECTIONS

PubMed Central

Xu, Hongshi; Zisman, Anna L.; Coe, Fredric L.; Worcester, Elaine M.

2013-01-01

Introduction Kidney stones are a common problem worldwide with substantial morbidities and economic costs. Medical therapy reduces stone recurrence significantly. Much progress has been made in the last several decades in improving therapy of stone disease. Areas covered 1) effect of medical expulsive therapy on spontaneous stone passage, 2) pharmacotherapy in the prevention of stone recurrence, 3) future directions in the treatment of kidney stone disease. Expert Opinion fluid intake to promote urine volume of at least 2.5L each day is essential to prevent stone formation. Dietary recommendations should be adjusted based on individual metabolic abnormalities. Properly dosed thiazide treatment is the standard therapy for calcium stone formers with idiopathic hypercalciuria. Potassium alkali therapy is considered for hypocitraturia, but caution should be taken to prevent potential risk of calcium phosphate stone formation. For absorptive hyperoxaluria, low oxalate diet and increased dietary calcium intake are recommended. Pyridoxine has been shown effective in some cases of primary hyperoxaluria type I. Allopurinol is used in calcium oxalate stone formers with hyperuricosuria. Treatment of cystine stones remains challenging. Tiopronin can be used if urinary alkalinization and adequate fluid intake are insufficient. For struvite stones, complete surgical removal coupled with appropriate antibiotic therapy is necessary. PMID:23438422

Pathological Calcification and Ossification in Relation to Leriche and Policard's Theory

PubMed Central

Jones, Watson; Roberts, R. E.

1933-01-01

(1) Pathology of calcification and ossification.—The Leriche-Policard theories. Hyperæmia of bone causes decalcification. Reduced blood supply causes sclerosis. Diminution of vascularity of fibrous tissue causes calcification. Excess of calcium, adequate blood supply and fibroblasts give rise to bone anywhere. Subperiosteal ossification. “Myositis ossificans.” (2) Radiological significance of density of bone shadows.—Decalcification of disuse, of infections, of neoplasms. Traumatic and infective scquestra. Evidence that a fragment of bone is avascular. (3) Hyperæmic decalcification of bone.—Delayed and non-union of fractures. Kummel's disease. Spontaneous hyperæmic dislocation of the atlas. Hyperæmic decalcification and nephrolithiasis. (4) Anæmic sclerosis of bone.—Syphilitic bone disease. Malignant bone disease. Fragility of sclerosed bone—Paget's, Kienboch's, Kohler's and Panner's, Albers-Schönberg's diseases. (5) Pathological calcification.—Calcification of supraspinatus tendon. Calcification of tumours—angioma, hæmatoma, and thrombosed vessels, lipoma, cysts, etc. Calcification of semilunar cartilages and intervertebral discs. (6) Pathological ossification.—Ossification of tendons. Ossification of semilunar cartilages. PMID:19989304

Kidney Stones as an Underrecognized Clinical Sign in Pediatric Cushing Disease.

PubMed

Rahman, Sara H; Papadakis, Georgios Z; Keil, Margaret F; Faucz, Fabio R; Lodish, Maya B; Stratakis, Constantine A

2016-03-01

To investigate the prevalence of kidney stones in a population of children with Cushing disease (CD) and to compare it with the prevalence of kidney stones in healthy children. Clinical and biochemical data from 139 pediatric patients with CD (68 females, 71 males) were analyzed retrospectively. Computed tomography scans were reviewed for kidney stones. Among 139 patients, 27 with CD (19.4%) had either radiographic evidence and/or a history of kidney stones. Those with kidney stones had higher urine free cortisol (P = .008) and transsphenoidal surgery at an older age (P = .007). The average urinary calcium/creatinine ratio was elevated in patients with CD (0.22 ± 0.11). The prevalence of kidney stones was higher in children with CD than in normal children (19.42% vs 1.0%; P < .001). Our results illustrate that kidney stones are an underestimated complication of pediatric CD, especially when compared with the prevalence of nephrolithiasis in the general pediatric population. Long-term consequences for kidney function are not known and need to be studied. Published by Elsevier Inc.

Normocalcemic primary hyperparathyroidism in clinical practice: an indolent condition or a silent threat?

PubMed Central

Marques, Thyciara Fontenele; Vasconcelos, Renata; Diniz, Erik; Rêgo, Daniela; Griz, Luiz; Bandeira, Francisco

2015-01-01

Objective To describe the characteristics of normocalcemic primary hyperparathyroidism (NPHPT) in patients seen for osteoporosis evaluation. Patients and methods We examined the records of 156 women who came to the hospital to be screened for osteoporosis. Measurements of total calcium, PTH, 25-hydroxy vitamin D, and β-C-telopeptide were recorded. Bone mineral density and T-scores were evaluated by densitometry of the lumbar spine, femoral neck and distal one-third of the radius. The latter was only measured in patients with primary hyperparathyroidism. Nephrolithiasis and bone fractures were documented by a review of the medical records. Results We identified 14 patients with NPHPT, accounting for 8.9% of the population studied. In the medical records, the occurrence of kidney stones was reported in 28.6% of the patients with NPHPT, in contrast with only 0.7% of the noncarriers. Regarding the presence of general fractures, 21.4% of the patients with NPHPT were affected versus 16.2% of noncarriers. Conclusion Data from our study suggest that NPHPT has a diverse phenotypic presentation, implying that this may not be an “indolent” disease. PMID:21881813

Effect of indapamide on urinary calcium excretion in patients with and without urinary stone disease.

PubMed

Ceylan, Kadir; Topal, Cevat; Erkoc, Reha; Sayarlioglu, Hayriye; Can, Saban; Yilmaz, Yuksel; Dogan, Ekrem; Algun, Ekrem; Gonulalan, Hasan

2005-06-01

Indapamide is an antihypertensive agent similar to thiazides, but with some different effects. Thiazide and thiazide-like diuretics are useful in preventing recurrent urinary stone formation due to their hypocalciuric effects. To determine the hypocalciuric and other effects on certain laboratory parameters of indapamide 1.5 mg in different patient groups. Four groups of patients recruited from urology and nephrology outpatient departments were experiencing non-hypercalciuric urinary stone disease (group 1), idiopathic hypercalciuria (group 2), urinary stone disease with hypercalciuria (group 3), and essential hypertension (group 4). In all patients, fasting serum uric acid, calcium, sodium, potassium, cholesterol, triglyceride, parathyroid hormone (PTH) values, and morning second-spot urine calcium and creatinine levels were assessed before and 8 weeks after treatment with indapamide. Urinary calcium excretion was reduced significantly in all groups: group 1 from 0.10 +/- 0.02 to 0.07 +/- 0.03 (mean +/-SD; 30% reduction; p < 0.001), group 2 from 0.30 +/- 0.15 to 0.15 +/- 0.10 (50% reduction; p < 0.001), group 3 from 0.35 +/- 0.15 to 0.20 +/- 0.10 (43% reduction; p < 0.001), and group 4 from 0.10 +/- 0.03 to 0.08 +/- 0.02 (20% reduction; p < 0.0010). These results should be interpreted with caution since no control group was included in this study. Mean serum uric acid and triglyceride levels were significantly increased, and mean PTH and potassium levels and diastolic and systolic blood pressure were significantly decreased in all groups. Few temporary adverse effects, such as dizziness and fatigue, were noticed and none of them caused discontinuation of treatment. Indapamide 1.5 mg/day is effective in decreasing calciuria in patients with non-hypercalciuric urinary stone disease, idiopathic hypercalciuria, urinary stone disease with hypercalciuria, and essential hypertension. This could be achieved with few adverse effects similar to those of thiazides and indapamide 2.5 mg. Indapamide decreased the PTH levels in all groups. Long-term clinical benefits of these effects should be evaluated prospectively with further randomized studies.

Prevalence of coeliac disease in idiopathic hypoparathyroidism and effect of gluten-free diet on calcaemic control.

PubMed

Saha, Soma; Saini, Savita; Makharia, Govind K; Datta Gupta, Siddhartha; Goswami, Ravinder

2016-04-01

Patients with idiopathic hypoparathyroidism (IH) require variable doses of calcium and 1-α-(OH)D. The reasons for such variability are not clear. As autoimmune mechanisms may play a role in IH, there is a possibility of coexistent coeliac disease with calcium/vitamin D malabsorption. We assessed the prevalence of coeliac disease and antitissue transglutaminase autoantibodies (anti-tTGAbs) in IH and analysed the effect of a gluten-free diet on calcaemic control. A total of 171 patients with IH and 126 healthy controls were screened for anti-tTGAb. IH patients with anti-tTGAb >20 RU/ml underwent duodenoscopy and intestinal biopsy; those with biopsy-proven coeliac disease were followed up on a gluten-free diet. Eleven of 171 (6·4%) patients with IH and seven of 126 (5·6%) controls had anti-tTGAb (P = 0·81). There was no difference in the clinical and biochemical parameters at diagnosis and during long-term follow-up of 7·2 ± 4·8 year (mean serum total calcium = 1·88 ± 0·16 vs 1·82 ± 0·36 mmol/l, P = 0·52; phosphorus = 1·81 ± 0·17 vs 1·87 ± 0·36 mmol/l, P = 0·53) in IH patients with and without anti-tTGAb. Although CaSRAb positivity was comparable in the two groups, IH patients with anti-tTGAb had higher TPOAb positivity (45·5% vs 12·8%, P = 0·02). Coeliac disease was diagnosed in only 2/9 patients with IH on biopsy, both of whom showed improved calcaemic control with a gluten-free diet. The prevalence of coeliac autoimmunity (6·4%) and coeliac disease (1·2%) in patients with IH seems to be similar to that in the general population. Notwithstanding this modest prevalence, it is important to be aware of the potential occurrence of coeliac disease with IH and the beneficial effect of a gluten-free diet on calcium control. © 2015 John Wiley & Sons Ltd.

The growing prevalence of kidney stones and opportunities for prevention.

PubMed

Richman, Katherine; O'Bell, John; Pareek, Gyan

2014-12-02

The prevalence of kidney stones is climbing in the United States. Several investigators have demonstrated an association between metabolic syndrome and kidney stones and some have proposed a causal link. Risk factors for nephrolithiasis can be identified with a 24-hour urine collection and preventive measures can be customized to meet the needs of individual patients. Dietary and pharmacologic interventions are available to address urinary risk factors such as inadequate urine volume, hypercalcuria, hyperoxaluria, hyperuricosuria and hypocitraturia. Given that morbidity and healthcare costs associated with nephrolithiasis are on the rise, deterring stone formation is increasingly important. Multidisciplinary clinics that foster collaboration between urologists, nephrologists and dieticians offer patients effective prevention and treatment strategies.

Vitamin D supplementation for prevention of mortality in adults.

PubMed

Bjelakovic, Goran; Gluud, Lise Lotte; Nikolova, Dimitrinka; Whitfield, Kate; Wetterslev, Jørn; Simonetti, Rosa G; Bjelakovic, Marija; Gluud, Christian

2011-07-06

The available evidence on vitamin D and mortality is inconclusive. To assess the beneficial and harmful effects of vitamin D for prevention of mortality in adults. We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index Expanded, and Conference Proceedings Citation Index-Science (to January 2011). We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials. We included randomised trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention. Vitamin D could have been administered as supplemental vitamin D (vitamin D(3) (cholecalciferol) or vitamin D(2) (ergocalciferol)) or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol) or 1,25-dihydroxyvitamin D (calcitriol)). Six authors extracted data independently. Random-effects and fixed-effect model meta-analyses were conducted. For dichotomous outcomes, we calculated the risk ratios (RR). To account for trials with zero events, meta-analyses of dichotomous data were repeated using risk differences (RD) and empirical continuity corrections. Risk of bias was considered in order to minimise risk of systematic errors. Trial sequential analyses were conducted to minimise the risk of random errors. Fifty randomised trials with 94,148 participants provided data for the mortality analyses. Most trials included elderly women (older than 70 years). Vitamin D was administered for a median of two years. More than one half of the trials had a low risk of bias. Overall, vitamin D decreased mortality (RR 0.97, 95% confidence interval (CI) 0.94 to 1.00, I(2) = 0%). When the different forms of vitamin D were assessed separately, only vitamin D(3) decreased mortality significantly (RR 0.94, 95% CI 0.91 to 0.98, I(2) = 0%; 74,789 participants, 32 trials) whereas vitamin D(2), alfacalcidol, or calcitriol did not. Trial sequential analysis supported our finding regarding vitamin D(3), corresponding to 161 individuals treated to prevent one additional death. Vitamin D(3) combined with calcium increased the risk of nephrolithiasis (RR 1.17, 95% CI 1.02 to 1.34, I(2) = 0%). Alfacalcidol and calcitriol increased the risk of hypercalcaemia (RR 3.18, 95% CI 1.17 to 8.68, I(2) = 17%). Data on health-related quality of life and health economics were inconclusive. Vitamin D in the form of vitamin D(3) seems to decrease mortality in predominantly elderly women who are mainly in institutions and dependent care. Vitamin D(2), alfacalcidol, and calcitriol had no statistically significant effect on mortality. Vitamin D(3) combined with calcium significantly increased nephrolithiasis. Both alfacalcidol and calcitriol significantly increased hypercalcaemia.

[TITANIUM NICKELIDE TECHNOLOGIES IN MINIMALLY INVASIVE SURGERY OF KIDNEY AND UPPER URINARY TRACT].

PubMed

Feofilov, L V

2015-01-01

The most common pathology of the kidney and upper urinary tract includes nephrolithiasis, ureteral strictures and renal cysts. In the treatment of patients with these diseases, the majority of surgeons prefer minimally invasive techniques, including endoscopic surgery. The complication rate of percutaneous surgery is a major factor in encouraging the search for new treatments. We have analyzed the results of 402 x-ray-endoscopic operations performed with the use of technologies based on titanium nickelide materials in patients with nephrolithiasis, ureteral strictures and kidney cysts. The high effectiveness and reliability of porous titanium nickelide cryoapplicator was noted in control of percutaneous channel bleeding and prevention. The proposed suspension nephropexy with fine titanium granules in coexisting nephrolithiasis and nephroptosis demonstrated 1.5 times greater effectiveness compared to the traditional nephropexy, reducing duration of nephrostomy and rehabilitation by almost 3 times. The proposed methods of intubation by permanent and temporary stents with shape memory after percutaneous ureteropelvic junction stricture correction are promising in the treatment of patients with this pathology of the upper urinary tract. Application of titanium nickelide implants in simple renal cyst surgery has led to a significant increase in the effectiveness of these operations, improvement in long-term results and patients' quality of life.

Renal papillary necrosis

MedlinePlus

... asking your provider. Alternative Names Necrosis - renal papillae; Renal medullary necrosis Images Kidney anatomy Kidney - blood and urine flow References Bushinsky DA, Monk RD. Nephrolithiasis and nephrocalcinosis. ...

Vitamin D-Mediated Hypercalcemia: Mechanisms, Diagnosis, and Treatment

PubMed Central

Tebben, Peter J.; Singh, Ravinder J.

2016-01-01

Hypercalcemia occurs in up to 4% of the population in association with malignancy, primary hyperparathyroidism, ingestion of excessive calcium and/or vitamin D, ectopic production of 1,25-dihydroxyvitamin D [1,25(OH)2D], and impaired degradation of 1,25(OH)2D. The ingestion of excessive amounts of vitamin D3 (or vitamin D2) results in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] that bind to the vitamin D receptor, albeit with lower affinity than the active form of the vitamin, 1,25(OH)2D, and the formation of 5,6-trans 25(OH)D, which binds to the vitamin D receptor more tightly than 25(OH)D. In patients with granulomatous disease such as sarcoidosis or tuberculosis and tumors such as lymphomas, hypercalcemia occurs as a result of the activity of ectopic 25(OH)D-1-hydroxylase (CYP27B1) expressed in macrophages or tumor cells and the formation of excessive amounts of 1,25(OH)2D. Recent work has identified a novel cause of non-PTH-mediated hypercalcemia that occurs when the degradation of 1,25(OH)2D is impaired as a result of mutations of the 1,25(OH)2D-24-hydroxylase cytochrome P450 (CYP24A1). Patients with biallelic and, in some instances, monoallelic mutations of the CYP24A1 gene have elevated serum calcium concentrations associated with elevated serum 1,25(OH)2D, suppressed PTH concentrations, hypercalciuria, nephrocalcinosis, nephrolithiasis, and on occasion, reduced bone density. Of interest, first-time calcium renal stone formers have elevated 1,25(OH)2D and evidence of impaired 24-hydroxylase-mediated 1,25(OH)2D degradation. We will describe the biochemical processes associated with the synthesis and degradation of various vitamin D metabolites, the clinical features of the vitamin D-mediated hypercalcemia, their biochemical diagnosis, and treatment. PMID:27588937

Status of therapeutic gene transfer to treat canine dilated cardiomyopathy in dogs.

PubMed

Sleeper, Meg M; Bish, Lawrence T; Sweeney, H Lee

2010-07-01

Therapeutic gene transfer holds promise as a way to treat dilated cardiomyopathy from any underlying cause because the approach attempts to address metabolic disturbances that occur at the molecular level of the failing heart. Calcium-handling abnormalities and increased rates of apoptosis are abnormalities that occur in many types of heart disease, and gene therapies that target these metabolic defects have proven to be beneficial in numerous rodent models of heart disease. The authors are currently evaluating this approach to treat canine idiopathic dilated cardiomyopathy.

Kidney stones

MedlinePlus

... Eidman KE, et al. Recurrent nephrolithiasis in adults: comparative effectiveness of preventive medical strategies [Internet]. Rockville, MD. Agency for Healthcare Research and Quality (US) 2012; Report No.: 12-EHC049- ...

Loss of Cystic Fibrosis Transmembrane Regulator Impairs Intestinal Oxalate Secretion.

PubMed

Knauf, Felix; Thomson, Robert B; Heneghan, John F; Jiang, Zhirong; Adebamiro, Adedotun; Thomson, Claire L; Barone, Christina; Asplin, John R; Egan, Marie E; Alper, Seth L; Aronson, Peter S

2017-01-01

Patients with cystic fibrosis have an increased incidence of hyperoxaluria and calcium oxalate nephrolithiasis. Net intestinal absorption of dietary oxalate results from passive paracellular oxalate absorption as modified by oxalate back secretion mediated by the SLC26A6 oxalate transporter. We used mice deficient in the cystic fibrosis transmembrane conductance regulator gene (Cftr) to test the hypothesis that SLC26A6-mediated oxalate secretion is defective in cystic fibrosis. We mounted isolated intestinal tissue from C57BL/6 (wild-type) and Cftr -/- mice in Ussing chambers and measured transcellular secretion of [ 14 C]oxalate. Intestinal tissue isolated from Cftr -/- mice exhibited significantly less transcellular oxalate secretion than intestinal tissue of wild-type mice. However, glucose absorption, another representative intestinal transport process, did not differ in Cftr -/- tissue. Compared with wild-type mice, Cftr -/- mice showed reduced expression of SLC26A6 in duodenum by immunofluorescence and Western blot analysis. Furthermore, coexpression of CFTR stimulated SLC26A6-mediated Cl - -oxalate exchange in Xenopus oocytes. In association with the profound defect in intestinal oxalate secretion, Cftr -/- mice had serum and urine oxalate levels 2.5-fold greater than those of wild-type mice. We conclude that defective intestinal oxalate secretion mediated by SLC26A6 may contribute to the hyperoxaluria observed in this mouse model of cystic fibrosis. Future studies are needed to address whether similar mechanisms contribute to the increased risk for calcium oxalate stone formation observed in patients with cystic fibrosis. Copyright © 2016 by the American Society of Nephrology.

Kidney stone composition in the Kingdom of Saudi Arabia
.

PubMed

Amir, Abdulrazack; Matlaga, Brian R; Ziemba, Justin B; Sheikh, Salwa

2018-05-01

Urolithiasis is a globally-distributed disease; however, its prevalence varies across countries and regions. Countries in the Middle East have been reported to have particularly high nephrolithiasis prevalence rates. To date, however, we have an incomplete understanding of the composition of stones seen in this region. Therefore, we performed a study to characterize stone composition over a 14-year period in the Eastern Province of the Kingdom of Saudi Arabia (KSA). A retrospective review of all adult patients who had the composition of their upper urinary tract calculi analyzed at Johns Hopkins Aramco Healthcare (JHAH) between 1999 and 2013 was performed. Patient demographics and pathology results were obtained from the electronic medical record. A total of 1,747 stones were analyzed in the study period. The results are presented in the Table. Male patients predominated (79%). For both men and women, the majority of stones were calcium oxalate: 85.2% male, 85.9% female. Uric acid stones were the next most common: 10.1% male; 9.0% female. Overall, there were no significant differences between gender with regards to the distribution of stone types. This study represents one of the largest characterizations of stone composition in the Middle East. There remains a significant gender disparity in stone prevalence in the Eastern Province of KSA, with males affected to a significantly greater extent. Calcium oxalate is the most common type of stone, and this is true for both men and women. Future investigations of dietary and environmental factors can build on these initial epidemiologic findings.
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Intronic deletions in the SLC34A3 gene: A cautionary tale for mutation analysis of hereditary hypophosphatemic rickets with hypercalciuria

PubMed Central

Ichikawa, Shoji; Tuchman, Shamir; Padgett, Leah R.; Gray, Amie K.; Baluarte, H. Jorge; Econs, Michael J.

2013-01-01

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare metabolic disorder, characterized by hypophosphatemia, variable degrees of rickets/osteomalacia, and hypercalciuria secondary to increased serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels. HHRH is caused by mutations in the SLC34A3 gene, which encodes sodium-phosphate co-transporter type IIc. A 6 ½-year-old female presented with a history of nephrolithiasis. Her metabolic evaluation revealed increased 24- hour urine calcium excretion with high serum calcium, low intact parathyroid hormone (PTH) levels, and elevated 1,25(OH)2D level. In addition, the patient had low to low-normal serum phosphorus with high urine phosphorus. The patient had normal stature; without rachitic or boney deformities or a history of fractures. Genetic analysis of SLC34A3 revealed the patient to be a compound heterozygote for a novel single base pair deletion in exon 12 (c.1304delG) and 30-base pair deletion in intron 6 (g.1440–1469del). The single-base pair mutation causes a frameshift, which results in premature stop codon. The intronic deletion is likely caused by misalignment of the 4-basepair homologous repeats and results in the truncation of an already small intron to 63 bp, which would impair proper RNA splicing of the intron. This is the fourth unique intronic deletion identified in patients with HHRH, suggesting the frequent occurrence of sequence misalignments in SLC34A3 and the importance of screening introns in patients with HHRH. PMID:24176905

Intronic deletions in the SLC34A3 gene: a cautionary tale for mutation analysis of hereditary hypophosphatemic rickets with hypercalciuria.

PubMed

Ichikawa, Shoji; Tuchman, Shamir; Padgett, Leah R; Gray, Amie K; Baluarte, H Jorge; Econs, Michael J

2014-02-01

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare metabolic disorder, characterized by hypophosphatemia, variable degrees of rickets/osteomalacia, and hypercalciuria secondary to increased serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels. HHRH is caused by mutations in the SLC34A3 gene, which encodes sodium-phosphate co-transporter type IIc. A 6-1/2-year-old female presented with a history of nephrolithiasis. Her metabolic evaluation revealed increased 24-hour urine calcium excretion with high serum calcium, low intact parathyroid hormone (PTH), and elevated 1,25(OH)2D. In addition, the patient had low to low-normal serum phosphorus with high urine phosphorus. The patient had normal stature; without rachitic or boney deformities or a history of fractures. Genetic analysis of SLC34A3 revealed the patient to be a compound heterozygote for a novel single base pair deletion in exon 12 (c.1304delG) and 30-base pair deletion in intron 6 (g.1440-1469del). The single-base pair mutation causes a frameshift, which results in premature stop codon. The intronic deletion is likely caused by misalignment of the 4-basepair homologous repeats and results in the truncation of an already small intron to 63bp, which would impair proper RNA splicing of the intron. This is the fourth unique intronic deletion identified in patients with HHRH, suggesting the frequent occurrence of sequence misalignments in SLC34A3 and the importance of screening introns in patients with HHRH. © 2013.

Can a Simplified 12-Hour Nighttime Urine Collection Predict Urinary Stone Risk?

PubMed

Hinck, Bryan D; Ganesan, Vishnuvardhan; Tarplin, Sarah; Asplin, John; Granja, Ignacio; Calle, Juan; Sivalingam, Sri; Monga, Manoj

2017-10-01

To determine if there is correlation between nighttime 12-hour and traditional 24-hour urine collection in regard to chemistry values and the supersaturations of calcium oxalate, calcium phosphate, and uric acid for the metabolic evaluation of nephrolithiasis. Ninety-five patients were prospectively enrolled from 2013 to 2015. Patients >18 years of age who presented to a tertiary stone clinic and who would normally be counseled for 24-hour urine collection were eligible for the study. Participants completed 24-hour urine collections twice, with each divided into 2 separate 12-hour collections. Day-time collection began after the first morning void and continued for 12 hours. The night collection proceeded for the next 12 hours through the first morning void. Forty-nine 24-hour samples from 35 patients met inclusion criteria and were included in the analysis. Overall, there was strong correlation between the night 12-hour and the 24-hour urine collections with R 2 ranging from 0.76 for pH to 0.96 for Citrate. In our analysis of variability, the nighttime 12-hour collection differed from the 24-hour collection by 30% in 1-9 patients (2.0%-18.4%) based on individual chemistry value. Diagnosis of underlying metabolic abnormalities was concordant in 92% of patients. A 12-hour nighttime collection has strong correlation with 24-hour urine collection. As such, simplifying the metabolic evaluation to a 12-hour overnight collection may be feasible-improving compliance and decreasing patient burden. Copyright © 2017 Elsevier Inc. All rights reserved.

[Epidemiological study on urinary stones in the region of Fez and the risk of recurrence].

PubMed

El Habbani, R; Chaqroune, A; Sqalli Houssaini, T; Arrayhani, M; El Ammari, J; Dami, F; Chouhani, B A; Lahrichi, A

2016-04-01

In Morocco, few works on morpho-constitutional analysis of urinary calculi have been published, especially for patients in the region of Fez. This work aims to make a retrospective epidemiological study on the nature of urinary calculi with patients from the region of Fez and control the urine of the same patients after a period of three months to report on the risk of recurrence. Urinary stones were collected mostly in the nephrology service and urology service at the Hassan II Hospital in Fez. These calculations after being dried for 24 hours at room temperature underwent a morphological analysis, followed by infrared spectroscopic analysis Fourier transform. After a period of about three months, morning urine of the same patients was analyzed by crystalluria to control the presence of crystals that reflect a risk of recurrence. In our series of 123 samples, the age of patients ranges from 2-79 years. The prevalence was higher for men with a sex ratio of 1.3. The results of the analysis calculations showed that 61% were formed of calcium oxalate and 15% of uric acid and 25% of stones were carbapatite, struvite, cystine… The study by crystalluria urine revealed the presence of the crystals in 69% of patients' nephrolithiasis. The results of our study are conformed to the series of results in other regions of Morocco regarding the predominance of calcium oxalate stones. The presence of crystals in the urine of 69% of patients may indicate other recurrences. 4. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Extensive molecular analysis suggested the strong genetic heterogeneity of idiopathic chronic pancreatitis.

PubMed

Sofia, Valentina Maria; Da Sacco, Letizia; Surace, Cecilia; Tomaiuolo, Anna Cristina; Genovese, Silvia; Grotta, Simona; Gnazzo, Maria; Petrocchi, Stefano; Ciocca, Laura; Alghisi, Federico; Montemitro, Enza; Martemucci, Luigi; Elce, Ausilia; Lucidi, Vincenzina; Castaldo, Giuseppe; Angioni, Adriano

2016-05-26

Genetic features of Chronic Pancreatitis (CP) have been extensively investigated mainly testing genes associated to the trypsinogen activation pathway. However, different molecular pathways involving other genes may be implicated in CP pathogenesis. 80 patients with Idiopathic CP were investigated using Next Generation Sequencing approach with a panel of 70 genes related to six different pancreatic pathways: premature activation of trypsinogen; modifier genes of Cystic Fibrosis phenotype; pancreatic secretion and ion homeostasis; Calcium signalling and zymogen granules exocytosis; autophagy; autoimmune pancreatitis related genes. We detected mutations in 34 out of 70 genes examined; 64/80 patients (80.0%) were positive for mutations in one or more genes, 16/80 patients (20.0%) had no mutations. Mutations in CFTR were detected in 32/80 patients (40.0%) and 22 of them exhibited at least one mutation in genes of other pancreatic pathways. Of the remaining 48 patients, 13/80 (16.3%) had mutations in genes involved in premature activation of trypsinogen and 19/80 (23.8%) had mutations only in genes of the other pathways: 38/64 patients positive for mutations showed variants in two or more genes (59.3%). Our data, although to be extended with functional analysis of novel mutations, suggest a high rate of genetic heterogeneity in chronic pancreatitis and that trans-heterozygosity may predispose to the idiopathic CP phenotype.

New techniques on the horizon: interventional radiology and interventional endoscopy of the urinary tract ('endourology').

PubMed

Berent, Allyson

2014-01-01

Interventional radiology and interventional endoscopy (IR/IE) uses contemporary imaging modalities, such as fluoroscopy and endoscopy, to perform diagnostic and therapeutic procedures in various body parts. The majority of IR/IE procedures currently undertaken in veterinary medicine pertain to the urinary tract, and this subspecialty has been termed 'endourology'. This technology treats diseases of the renal pelvis, ureter(s), bladder and urethra. In human medicine, endourology has overtaken traditional open urologic surgery in the past 20-30 years, and in veterinary medicine similar progress is occurring. This article presents a brief overview of some of the more common IR/IE procedures currently being performed for the treatment of urinary tract disease in veterinary patients. These techniques include percutaneous nephrolithotomy for lithotripsy of problematic nephrolithiasis, mesenchymal stem cell therapy for chronic kidney disease, sclerotherapy for the treatment of idiopathic renal hematuria, various diversion techniques for ureteral obstructions, laser lithotripsy for lower urinary tract stone disease, percutaneous cystolithotomy for removal of bladder stones, hydraulic occluder placement for refractory urinary incontinence, percutaneous cystostomy tube placement for bladder diversion, urethral stenting for benign and malignant urethral obstructions, and antegrade urethral catheterization for treatment of urethral tears. The majority of the data presented in this article is solely the experience of the author, and some of this has only been published and/or presented in abstract form or small case series. For information on traditional surgical approaches to these ailments readers are encouraged to evaluate other sources.

Solubility of ammonium acid urate nephroliths from bottlenose dolphins (Tursiops truncatus).

PubMed

Argade, Sulabha; Smith, Cynthia R; Shaw, Timothy; Zupkas, Paul; Schmitt, Todd L; Venn-Watson, Stephanie; Sur, Roger L

2013-12-01

Nephrolithiasis has been identified in managed populations of bottlenose dolphins (Tursiops truncatus); most of these nephroliths are composed of 100% ammonium acid urate (AAU). Several therapies are being investigated to treat and prevent nephrolithiasis in dolphins including the alkalization of urine for dissolution of nephroliths. This study evaluates the solubility of AAU nephroliths in a phosphate buffer, pH range 6.0-8.0, and in a carbonate-bicarbonate buffer, pH range 9.0-10.8. AAU nephroliths were obtained from six dolphins and solubility studies were conducted using reverse-phase high performance liquid chromatography with ultraviolet detection at 290 nm. AAU nephroliths were much more soluble in a carbonate-bicarbonate buffer, pH range 9.0-10.8 compared to phosphate buffer pH range 6.0-8.0. In the pH range 6.0-8.0, the solubility was 45% lower in potassium phosphate buffer compared to sodium phosphate buffer. When citrate was used along with phosphate in the same pH range, the solubility was improved by 13%. At pH 7 and pH 8, 150 mM ionic strength buffer was optimum for dissolution. In summary, adjustment of urinary pH alone does not appear to be a useful way to treat AAU stones in bottlenose dolphins. Better understanding of the pathophysiology of AAU nephrolithiasis in dolphins is needed to optimize kidney stone prevention and treatment.

Kidney stones and subclinical atherosclerosis in young adults: the CARDIA study.

PubMed

Reiner, Alexander P; Kahn, Arnold; Eisner, Brian H; Pletcher, Mark J; Sadetsky, Natalia; Williams, O Dale; Polak, Joseph F; Jacobs, David R; Stoller, Marshall L

2011-03-01

Recent reports suggest that nephrolithiasis and atherosclerosis share a number of risk factors. To our knowledge there has been no previous examination of the relationship between kidney stones and subclinical atherosclerotic disease. We studied the relationship between nephrolithiasis, and carotid wall thickness and carotid stenosis assessed by B-mode ultrasound in the general community using data from the CARDIA study. The CARDIA study is a United States, population based, observational study of 5,115 white and African-American men and women between the ages of 18 and 30 years at recruitment in 1985 to 1986. By the year 20 examination 200 (3.9%) CARDIA participants had reported ever having kidney stones. Symptomatic kidney stones were associated with greater carotid wall thickness measured at the year 20 examination, particularly of the internal carotid/bulb region. Using a composite dichotomous end point of carotid stenosis and/or the upper quartile of internal carotid/bulb wall thickness, the association of kidney stones with carotid atherosclerosis was significant (OR 1.6, 95% CI 1.1-2.3, p=0.01), even after adjusting for major atherosclerotic risk factors. The association between a history of kidney stones and subclinical carotid atherosclerosis in young adults adds further support to the notion that nephrolithiasis and atherosclerosis share common systemic risk factors and/or pathophysiology. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Novel mutations of the AGXT gene causing primary hyperoxaluria type 1.

PubMed

Yuen, Yuet-Ping; Lai, Chi-Kong; Tong, Gensy Mei-Wah; Wong, Ping-Nam; Wong, Francis Kim-Ming; Mak, Siu-Ka; Lo, Kin-Yee; Wong, Andrew Kui-Man; Tong, Sui-Fan; Chan, Yan-Wo; Lam, Ching-Wan

2004-01-01

Primary hyperoxaluria type 1 (PH1), an inherited cause of nephrolithiasis, is due to a functional defect of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). A definitive PH1 diagnosis can be established by analyzing AGT activity in liver tissue or mutation analysis of the AGXT gene. The molecular basis of PH1 in three Chinese patients, two with adult-onset and one with childhood-onset recurrent nephrolithiasis, was established by analyzing the entire AGXT gene. Three novel mutations (c2T>C, c817insAG and c844C>T) and two previously reported mutations (c33insC and 679-IVS6+2delAAgt) were identified. c2T>C converts the initiation codon from ATG to ACG, which predicts significant reduction, if not complete abolition, of protein translation. c817insAG leads to a frameshift and changes the amino acid sequence after codon 274. c844C>T changes glutamine at codon 282 to a termination codon, resulting in protein truncation. This is the first report describing AGXT gene mutations in Chinese patients with PH1. AGXT genotypes cannot fully explain the clinical heterogeneity of PH1, and other factors involved in disease pathogenesis remain to be identified. Our experience emphasizes the importance of excluding PH1 in patients with recurrent nephrolithiasis to avoid delay or inappropriate management.

Homozygous SLC2A9 Mutations Cause Severe Renal Hypouricemia

PubMed Central

Gray, Nicola K.; Campbell, Susan; Shu, Xinhua; Sawyer, Lindsay; Richardson, William; Rechavi, Gideon; Amariglio, Ninette; Ganon, Liat; Sela, Ben-Ami; Bahat, Hilla; Goldman, Michael; Weissgarten, Joshua; Millar, Michael R.; Wright, Alan F.; Holtzman, Eliezer J.

2010-01-01

Hereditary hypouricemia may result from mutations in the renal tubular uric acid transporter URAT1. Whether mutation of other uric acid transporters produces a similar phenotype is unknown. We studied two families who had severe hereditary hypouricemia and did not have a URAT1 defect. We performed a genome-wide homozygosity screen and linkage analysis and identified the candidate gene SLC2A9, which encodes the glucose transporter 9 (GLUT9). Both families had homozygous SLC2A9 mutations: A missense mutation (L75R) in six affected members of one family and a 36-kb deletion, resulting in a truncated protein, in the other. In vitro, the L75R mutation dramatically impaired transport of uric acid. The mean concentration of serum uric acid of seven homozygous individuals was 0.17 ± 0.2 mg/dl, and all had a fractional excretion of uric acid >150%. Three individuals had nephrolithiasis, and three had a history of exercise-induced acute renal failure. In conclusion, homozygous loss-of-function mutations of GLUT9 cause a total defect of uric acid absorption, leading to severe renal hypouricemia complicated by nephrolithiasis and exercise-induced acute renal failure. In addition to clarifying renal handling of uric acid, our findings may provide a better understanding of the pathophysiology of acute renal failure, nephrolithiasis, hyperuricemia, and gout. PMID:19926891

Calcium-binding protein S100A4 confers mesenchymal progenitor cell fibrogenicity in idiopathic pulmonary fibrosis

PubMed Central

Xia, Hong; Gilbertsen, Adam; Herrera, Jeremy; Racila, Emilian; Peterson, Mark; Griffin, Timothy; Benyumov, Alexey; Yang, Libang; Bitterman, Peter B.; Henke, Craig A.

2017-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a prevalence of 1 million persons worldwide. The fibrosis spreads from affected alveoli into contiguous alveoli and leads to death by asphyxiation. We previously discovered that the IPF lung harbors fibrogenic mesenchymal progenitor cells (MPCs) that serve as a cell of origin for disease-mediating myofibroblasts. In a prior genomewide transcriptional analysis, we found that IPF MPCs displayed increased expression of S100 calcium-binding A4 (S100A4), a protein linked to cancer cell proliferation and invasiveness. Here, we have examined whether S100A4 mediates MPC fibrogenicity. Ex vivo analysis revealed that IPF MPCs had increased levels of nuclear S100A4, which interacts with L-isoaspartyl methyltransferase to promote p53 degradation and MPC self-renewal. In vivo, injection of human IPF MPCs converted a self-limited bleomycin-induced mouse model of lung fibrosis to a model of persistent fibrosis in an S100A4-dependent manner. S100A4 gain of function was sufficient to confer fibrotic properties to non-IPF MPCs. In IPF tissue, fibroblastic foci contained cells expressing Ki67 and the MPC markers SSEA4 and S100A4. The expression colocalized in an interface region between myofibroblasts in the focus core and normal alveolar structures, defining this region as an active fibrotic front. Our findings indicate that IPF MPCs are intrinsically fibrogenic and that S100A4 confers MPCs with fibrogenicity. PMID:28530639

Inorganic phosphorus (Pi) in CSF is a biomarker for SLC20A2-associated idiopathic basal ganglia calcification (IBGC1).

PubMed

Hozumi, Isao; Kurita, Hisaka; Ozawa, Kazuhiro; Furuta, Nobuyuki; Inden, Masatoshi; Sekine, Shin-Ichiro; Yamada, Megumi; Hayashi, Yuichi; Kimura, Akio; Inuzuka, Takashi; Seishima, Mitsuru

2018-05-15

Idiopathic basal ganglia calcification (IBGC), also called Fahr's disease or recently primary familial brain calcification (PFBC), is characterized by abnormal deposits of minerals including calcium mainly and phosphate in the brain. Mutations in SLC20A2 (IBGC1 (merged with former IBGC2 and IBGC3)), which encodes PiT-2, a phosphate transporter, is the major cause of IBGC. Recently, Slc20a2-KO mice have been showed to have elevated levels of inorganic phosphorus (Pi) in cerebrospinal fluid (CSF); however, CSF Pi levels in patients with IBGC have not been fully examined. We investigated the cases of 29 patients with IBGC including six patients with SLC20A2 mutation and three patients with PDGFB mutation, and 13 controls. The levels of sodium (Na), potassium (K), chloride (Cl), calcium (Ca), and Pi in sera and CSF were determined by potentiometry and colorimetry. Moreover, clinical manifestations were investigated in the IBGC patients with high Pi levels in CSF. The study revealed that the average level of Pi in the CSF of the total group of patients with IBGC is significantly higher than that of the control group, and the levels of Pi in CSF of the IBGC patients with SLC20A2 mutations are significantly higher than those of the IBGC patients with PDGFB mutations, the other IBGC patients and controls. Results of this study suggest that the levels of CSF Pi will be a good biomarker for IBGC1. Copyright © 2018 Elsevier B.V. All rights reserved.

Primary hyperparathyroidism: recent advances.

PubMed

Walker, Marcella D; Bilezikian, John P

2018-07-01

The purpose of this review is to describe recent advances and changes in the evaluation and management of primary hyperparathyroidism (PHPT). Although it has long been recognized that asymptomatic PHPT is associated with bone loss, particularly at cortical skeletal sites when evaluated with dual-energy X-ray absorptiometry, new imaging techniques suggest that trabecular skeletal deterioration as well as clinically silent vertebral fractures and nephrolithiasis are common. Nonclassical targets of asymptomatic PHPT as well as the effect of vitamin D deficiency and treatment upon PHPT presentation have been the subject of recent intense investigation. Randomized clinical trials are now available regarding the effect of parathyroidectomy (PTX) upon both classical and nonclassical target organs. They have confirmed results from observational studies with regard to the skeletal benefits of PTX but have not consistently shown improvements in nonclassical symptoms. These findings have led to recommendations for more extensive renal and skeletal evaluation and broader criteria for PTX in PHPT. In addition to dual-energy X-ray absorptiometry, vertebral and renal imaging is recommended. When available, trabecular imaging techniques may be helpful. PTX criteria now include subclinical kidney stones, vertebral fractures and hypercalciuria, in addition to those based on age, serum calcium, bone densitometry and renal function.

Nephropathy in dietary hyperoxaluria: A potentially preventable acute or chronic kidney disease

PubMed Central

Glew, Robert H; Sun, Yijuan; Horowitz, Bruce L; Konstantinov, Konstantin N; Barry, Marc; Fair, Joanna R; Massie, Larry; Tzamaloukas, Antonios H

2014-01-01

Hyperoxaluria can cause not only nephrolithiasis and nephrocalcinosis, but also renal parenchymal disease histologically characterized by deposition of calcium oxalate crystals throughout the renal parenchyma, profound tubular damage and interstitial inflammation and fibrosis. Hyperoxaluric nephropathy presents clinically as acute or chronic renal failure that may progress to end-stage renal disease (ESRD). This sequence of events, well recognized in the past in primary and enteric hyperoxalurias, has also been documented in a few cases of dietary hyperoxaluria. Estimates of oxalate intake in patients with chronic dietary hyperoxaluria who developed chronic kidney disease or ESRD were comparable to the reported average oxalate content of the diets of certain populations worldwide, thus raising the question whether dietary hyperoxaluria is a primary cause of ESRD in these regions. Studies addressing this question have the potential of improving population health and should be undertaken, alongside ongoing studies which are yielding fresh insights into the mechanisms of intestinal absorption and renal excretion of oxalate, and into the mechanisms of development of oxalate-induced renal parenchymal disease. Novel preventive and therapeutic strategies for treating all types of hyperoxaluria are expected to develop from these studies. PMID:25374807

Bone disease in primary hyperparathyroidism

PubMed Central

Bandeira, Francisco; Cusano, Natalie E.; Silva, Barbara C.; Cassibba, Sara; Almeida, Clarissa Beatriz; Machado, Vanessa Caroline Costa; Bilezikian, John P.

2015-01-01

Bone disease in severe primary hyperparathyroidism (PHPT) is described classically as osteitis fibrosa cystica (OFC). Bone pain, skeletal deformities and pathological fractures are features of OFC. Bone mineral density is usually extremely low in OFC, but it is reversible after surgical cure. The signs and symptoms of severe bone disease include bone pain, pathologic fractures, proximal muscle weakness with hyperreflexia. Bone involvement is typically characterized as salt-and-pepper appearance in the skull, bone erosions and bone resorption of the phalanges, brown tumors and cysts. In the radiography, diffuse demineralization is observed, along with pathological fractures, particularly in the long bones of the extremities. In severe, symptomatic PHPT, marked elevation of the serum calcium and PTH concentrations are seen and renal involvement is manifested by nephrolithiasis and nephrocalcinosis. A new technology, recently approved for clinical use in the United States and Europe, is likely to become more widely available because it is an adaptation of the lumbar spine DXA image. Trabecular bone score (TBS) is a gray-level textural analysis that provides an indirect index of trabecular microarchitecture. Newer technologies, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), have provided further understanding of the microstructural skeletal features in PHPT. PMID:25166047

[Analysis of the Cochrane Review: Vitamin D supplementation for prevention of cancer in adults. Cochrane Database Syst Rev. 2014, 6:CD007469].

PubMed

Cardoso, André Torres; Nanji, Liliana; Costa, João; Vaz-Carneiro, António

2014-01-01

Vitamin D has been mentioned in the literature has a potentially important agent for preventing the development of tumors, namely breast, colon, prostate and ovary tumors. However, the currently available evidence on the subject is contradictory and inconclusive. In this Cochrane systematic review, patients taking supplemental vitamin D on its various forms (cholecalciferol, ergocalciferol, alfacalcidol or calcitriol), regardless the dose, duration and route of administration, were compared with placebo, healthy adults without any intervention or adults with a disease in a stable phase, non-related with vitamin D metabolism. The results showed that currently, there is no firm evidence that vitamin D supplementation increases or decreases the risk of cancer occurrence, mainly in elderly community-dwelling women. Though at risk of type I errors due to small samples and substantial dropout of participants during the trials, the administration of supplemental cholecalciferol led to a 12% (CI 95%: 2 a 22%) decreased in cancer mortality, while the administration of supplemental vitamin D decreased all-cause mortality by 7% (CI 95%: 2 a 12%). The combined administration of supplements of cholecalciferol and calcium induced an increased incidence of nephrolithiasis.

Is It Safe to Reduce Water Intake in the Overactive Bladder Population? A Systematic Review.

PubMed

Wood, Lauren N; Markowitz, Melissa A; Parameshwar, Pooja S; Hannemann, Alex J; Ogawa, Shellee L; Anger, Jennifer T; Eilber, Karyn S

2018-03-01

Overactive bladder imposes a significant socioeconomic burden on the health care system. It is a commonly held belief that increased fluid intake (8 glasses of water per day) is beneficial for health. However, increased fluid intake exacerbates overactive bladder symptoms. Thus, it is imperative that clinicians appropriately educate patients for whom increased water intake may be detrimental (women with overactive bladder), in contrast to patients with comorbidities that necessitate increased water intake (nephrolithiasis). We systematically reviewed the literature to determine the potential health advantages of increased water intake and identify specific subpopulations that need increased hydration. We systematically reviewed published articles from 1972 through 2017 on PubMed® and the Cochrane Library. The data were reviewed independently by 2 individuals. Studies were included if they explored water intake in relation to the risk of a particular disease. Level 1 evidence supported increased fluid intake in patients with nephrolithiasis. There was no available evidence to support increased fluid intake in patients with cardiovascular disease, constipation, venous thromboembolism, headaches, cognitive function or bladder cancer. Dehydration may exacerbate some conditions, specifically chronic constipation and headache intensity. Increased fluid intake may have a role in preventing stroke recurrence but not in preventing primary stroke. The available reviewed literature suggests no benefit to drinking 8 glasses of water per day in patients without nephrolithiasis. Also, excess fluid intake can exacerbate symptoms of overactive bladder. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Clinical value of crystalluria and quantitative morphoconstitutional analysis of urinary calculi.

PubMed

Frochot, Vincent; Daudon, Michel

2016-12-01

Crystalluria is a marker of urine supersaturation with substances deriving from metabolic disorders, inherited diseases or drugs. The investigation of crystalluria must be done according to a protocol which includes the delivery to the laboratory of a proper urine sample, the use of a microscope equipped with polarized light, the accurate knowledge of urine pH, and a comprehensive examination of the crystals, which is based on their identification, quantification and size measurement. For unusual crystals, infrared spectroscopy may also be needed. If the formation of stones is always preceded by crystalluria, the reverse is not true. In addition to the crystalline composition, stone morphology provides valuable information on stone activity and, for some crystalline species, major information regarding the underlying pathology. Fourier transform infrared spectroscopy (FTIR) reliably identify specific forms of nephrolithiasis, as common-type stones made of calcium oxalate (CaOx) and/or calcium phosphate that is combined with morphology classification; using this method, stones may be classified into 6 types subdivided in 22 subtypes. The investigation of crystalluria is an inexpensive and valuable tool for the detection and the monitoring of inherited and acquired diseases associated with urinary stone formation or acute or chronic renal function impairment from intrarenal crystal precipitation. Selective FTIR identification of the composition of core (or the umbilication), middle part, and surface of every stone allows identification of the initiating lithogenic process (in the nucleus or in the Randall's plaque) and the factors which subsequently contributed to stone growth. In conclusion, the proposed morpho-constitutional method of urinary stone analysis, which moreover is rapid and low cost, provides clinically relevant orientations for targeted etiologic evaluation. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Hypophosphatemic Rickets with Hypercalciuria due to Mutation in SLC34A3/NaPi-IIc can be Masked by Vitamin D Deficiency and can be Associated with Renal Calcifications

PubMed Central

Kremke, B.; Bergwitz, C.; Ahrens, W.; Schütt, S.; Schumacher, M.; Wagner, V.; Holterhus, P.-M.; Jüppner, H.; Hiort, O.

2015-01-01

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is caused by mutations in SLC34A3, the gene encoding the renal sodium-phosphate co-transporter NaPi-IIc. Despite increased urinary calcium excretion, HHRH is typically not associated with kidney stones prior to treatment. However, here we describe two sisters, who displayed nephrolithiasis or nephrocalcinosis upon presentation. The index patient, II-4, presented with short stature, bone pain, and knee X-rays suggestive of mild rickets at age 8.5 years. Laboratory evaluation showed hypophosphatemia, elevated 1,25(OH) 2 vitamin D levels, and hypercalciuria, later also developing vitamin D deficiency. Her sister, II-6, had a low normal serum phosphorous level, biochemically vitamin D deficiency and no evidence for osteomalacia, but had undergone left nephro-ureterectomy at age 17 because of ureteral stricture secondary to renal calculi. Nucleotide sequence analysis of DNA from II-4 and II-6 revealed a homozygous missense mutation c.586G>A (p.G196R) in SLC34A3/NaPi-IIc. Ultrasonographic examinations prior to treatment showed grade I nephrocalcinosis for II-4, while II-6 had grade I-II nephrocalcinosis in her remaining kidney. Four siblings and the mother were heterozygous carriers of the mutation, but showed no biochemical abnormalities. With oral phosphate supplements, hypophosphatemia and hypercalciuria improved in both homozygous individuals. Renal calcifications that are presumably due to increased urinary calcium excretion can be the presenting finding in homozygous carriers of G196R in SLC34A3/NaPi-IIc, and some or all laboratory features of HHRH may be masked by vitamin D deficiency. PMID:18523928

Hypophosphatemic rickets with hypercalciuria due to mutation in SLC34A3/NaPi-IIc can be masked by vitamin D deficiency and can be associated with renal calcifications.

PubMed

Kremke, B; Bergwitz, C; Ahrens, W; Schütt, S; Schumacher, M; Wagner, V; Holterhus, P-M; Jüppner, H; Hiort, O

2009-02-01

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is caused by mutations in SLC34A3, the gene encoding the renal sodium-phosphate co-transporter NaPi-IIc. Despite increased urinary calcium excretion, HHRH is typically not associated with kidney stones prior to treatment. However, here we describe two sisters, who displayed nephrolithiasis or nephrocalcinosis upon presentation. The index patient, II-4, presented with short stature, bone pain, and knee X-rays suggestive of mild rickets at age 8.5 years. Laboratory evaluation showed hypophosphatemia, elevated 1,25(OH) (2) vitamin D levels, and hypercalciuria, later also developing vitamin D deficiency. Her sister, II-6, had a low normal serum phosphorous level, biochemically vitamin D deficiency and no evidence for osteomalacia, but had undergone left nephro-ureterectomy at age 17 because of ureteral stricture secondary to renal calculi. Nucleotide sequence analysis of DNA from II-4 and II-6 revealed a homozygous missense mutation c.586G>A (p.G196R) in SLC34A3/NaPi-IIc. Ultrasonographic examinations prior to treatment showed grade I nephrocalcinosis for II-4, while II-6 had grade I-II nephrocalcinosis in her remaining kidney. Four siblings and the mother were heterozygous carriers of the mutation, but showed no biochemical abnormalities. With oral phosphate supplements, hypophosphatemia and hypercalciuria improved in both homozygous individuals. Renal calcifications that are presumably due to increased urinary calcium excretion can be the presenting finding in homozygous carriers of G196R in SLC34A3/NaPi-IIc, and some or all laboratory features of HHRH may be masked by vitamin D deficiency.

Dietary intake of fiber, fruit and vegetables decreases the risk of incident kidney stones in women: a Women's Health Initiative report.

PubMed

Sorensen, Mathew D; Hsi, Ryan S; Chi, Thomas; Shara, Nawar; Wactawski-Wende, Jean; Kahn, Arnold J; Wang, Hong; Hou, Lifang; Stoller, Marshall L

2014-12-01

We evaluated the relationship between dietary fiber, fruit and vegetable intake, and the risk of kidney stone formation. Overall 83,922 postmenopausal women from the Women's Health Initiative observational study were included in the analysis and followed prospectively. Cox proportional hazards regression analyses were used to evaluate the associations between total dietary fiber, fruit and vegetable intake, and the risk of incident kidney stone formation, adjusting for nephrolithiasis risk factors (age, race/ethnicity, geographic region, diabetes mellitus, calcium supplementation, hormone therapy use, body mass index and calibrated caloric intake; and dietary water, sodium, animal protein and calcium intake). Women with a history of kidney stones (3,471) were analyzed separately. Mean age of the women was 64±7 years, 85% were white and 2,937 (3.5%) experienced a kidney stone in a median followup of 8 years. In women with no history of kidney stones higher total dietary fiber (6% to 26% decreased risk, p <0.001), greater fruit intake (12% to 25% decreased risk, p <0.001) and greater vegetable intake (9% to 22% decreased risk, p=0.002) were associated with a decreased risk of incident kidney stone formation in separate adjusted models. In women with a history of stones there were no significant protective effects of fiber, fruit or vegetable intake on the risk of kidney stone recurrence. Greater dietary intake of fiber, fruits and vegetables was associated with a reduced risk of incident kidney stones in postmenopausal women. The protective effects were independent of other known risk factors for kidney stones. In contrast, there was no reduction in risk in women with a history of stones. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Sex Difference in the Clinical Presentation of Primary Hyperparathyroidism: Influence of Menopausal Status.

PubMed

Castellano, Elena; Attanasio, Roberto; Boriano, Alberto; Pellegrino, Micaela; Garino, Francesca; Gianotti, Laura; Borretta, Giorgio

2017-11-01

Female-to-male ratio in primary hyperparathyroidism (PHPT) is 3:1, but data on sex impact on the clinical presentation are limited. We evaluated, retrospectively, sex difference in biochemistry and clinical presentation at diagnosis in a monocentric series of 417 patients with PHPT: 93 men (58.6 ± 14.5 years), and 324 women (61.7 ± 12.8 years), of whom 54 were premenopausal (pre-F) and 270 postmenopausal (post-F). Men were significantly younger (P = 0.046) and more frequently symptomatic than women (62.3% vs 47%, P = 0.016). No sex difference was found in serum parathyroid hormone, calcium, creatinine, 25-hydroxy-vitamin D, and urinary calcium levels, whereas serum phosphate was higher in women. Nephrolithiasis (detected by imaging or history of passing stones) was more frequent in men (50.5% vs 33% in women, P = 0.003) and osteoporosis (T-score <-2.5 at any site) was more frequent in women (52.2% vs 35.5% in men, P = 0.0066). Symptomatic patients were 43.3%, 64.8%, and 62.3% in post-F women, pre-F women, and men, respectively. Kidney stones were less frequent and osteoporosis more frequent in post-F women than in pre-F women (28.1% vs 59.2% and 58.9% vs 18.5%, respectively). After combining symptomatic and asymptomatic patients meeting surgical criteria recommended by current guidelines, no sex difference was observed in the proportion of patients to be referred for surgery (84.6% in men vs 84.9% in women). Biochemical activity of PHPT seems to be independent of sex, but clinical presentation is different, mostly due to menopausal state. However, surgical referral was indicated equally in men and women. Copyright © 2017 Endocrine Society

Novel calcium-sensing receptor cytoplasmic tail deletion mutation causing autosomal dominant hypocalcemia: molecular and clinical study.

PubMed

Obermannova, Barbora; Sumnik, Zdenek; Dusatkova, Petra; Cinek, Ondrej; Grant, Michael; Lebl, Jan; Hendy, Geoffrey N

2016-04-01

Autosomal dominant hypocalcemia (ADH) is a rare disorder caused by activating mutations of the calcium-sensing receptor (CASR). The treatment of ADH patients with 1α-hydroxylated vitamin D derivatives can cause hypercalciuria leading to nephrocalcinosis. We studied a girl who presented with hypoparathyroidism and asymptomatic hypocalcemia at age 2.5 years. Mutations of CASR were investigated by DNA sequencing. Functional analyses of mutant and WT CASRs were done in transiently transfected human embryonic kidney (HEK293) cells. The proband and her father are heterozygous for an eight-nucleotide deletion c.2703_2710delCCTTGGAG in the CASR encoding the intracellular domain of the protein. Transient expression of CASR constructs in kidney cells in vitro suggested greater cell surface expression of the mutant receptor with a left-shifted extracellular calcium dose-response curve relative to that of the WT receptor consistent with gain of function. Initial treatment of the patient with calcitriol led to increased urinary calcium excretion. Evaluation for mosaicism in the paternal grandparents of the proband was negative. We describe a novel naturally occurring deletion mutation within the CASR that apparently arose de novo in the father of the ADH proband. Functional analysis suggests that the cytoplasmic tail of the CASR contains determinants that regulate the attenuation of signal transduction. Early molecular analysis of the CASR gene in patients with isolated idiopathic hypoparathyroidism is recommended because of its relevance to clinical outcome and treatment choice. In ADH patients, calcium supplementation and low-dose cholecalciferol avoids hypocalcemic symptoms without compromising renal function. © 2016 European Society of Endocrinology.

Kidney stones - what to ask your doctor

MedlinePlus

Nephrolithiasis - what to ask your doctor; Renal calculi - what to ask your doctor; What to ask your doctor about kidney stones ... Strategies for nonmedical management of upper urinary tract calculi. In: Wein AJ, Kavoussi LR, Partin AW, Peters ...

Assessment of urinary inhibitor or promoter activity in uric acid nephrolithiasis

PubMed Central

Doizi, Steeve; Rodgers, Kathy; Poindexter, John; Sakhaee, Khashayar; Maalouf, Naim M.

2017-01-01

Purpose To assess the presence of a reduced inhibitor activity or an increased promoter activity in urine of idiopathic uric acid stone formers (IUASF) compared to non-stone formers (NSF) independent of urinary pH. Methods 30 IUASF, 9 obese NSF and 12 lean NSF collected 24-hour urine under metabolic diet. Three urine aliquots per subject were used to assess spontaneous nucleation (SN, de novo crystal formation), crystal growth (CG) using a 0.1 mg/mL seed of anhydrous uric acid (UA) and steady state (SS) of UA solubility using a 5 mg/mL seed of UA (assessing maximum amount of UA dissolvable in urine). All experiments were conducted for 6 hours at a constant pH of 5.0. UA concentration was measured in filtered aliquots at 0, 3 and 6 hours. Results At baseline, 24-hour urinary pH was significantly lower and UA saturation significantly higher in IUASF. No significant SN occurred and a similar SS UA concentration was reached in the three groups. IUASF and lean NSF displayed a similar decrease in UA concentration during CG, while obese NSF started with higher UA concentration and consequently displayed higher magnitude of decrease in UA concentration for CG. Conclusions This study suggests that there is no significant difference between IUASF and NSF in terms of promoter or inhibitor activity in whole urine against UA stone formation when urine pH is maintained constant. The findings suggest that UA stone formation is dictated by a high urinary saturation with respect to UA, driven primarily by a low urine pH. PMID:26723865

Impaired osteoblast function in osteoporosis: comparison between calcium balance and dynamic histomorphometry.

PubMed

Arlot, M; Edouard, C; Meunier, P J; Neer, R M; Reeve, J

1984-09-01

Osteoblast function was investigated in 27 patients with idiopathic osteoporosis. Transiliac bone biopsy specimens were taken after double labelling with tetracycline, and metabolic calcium balance was studied almost simultaneously. Many of the patients showed poor double labelling of their otherwise unremarkable trabecular osteoid, suggesting impaired formation of bone at many of these surfaces. This phenomenon was not accompanied by increased width of osteoid seams (as seen in osteomalacia), indicating that formation of the matrix and its mineralisation were in equilibrium. For the first time, highly significant positive correlations (p less than 0.01) were found between indices of bone formation, determined by labelling with tetracycline, and calcium balance. Thus some patients with osteoporosis who are rapidly losing bone have low rates of formation of trabecular bone both by individual osteoblasts and in relation to available bone surfaces. As histological indices of bone resorption also independently correlated strongly and inversely (p less than 0.01) with calcium balance the rate of initiation of new basic multicellular units by osteoclastic resorption of trabecular surfaces (or the depth of resorption at these surfaces) also appears to be an important determinant of mineral balance. The mechanisms that regulate the effective life span of mature osteoblasts require further investigation, particularly as some promising treatments that can increase trabecular bone volume in osteoporosis, such as parathyroid peptide hPTH (1-34) and sodium fluoride, must work through a reversal of osteoblastic depression.

Ten-year single-center experience of the ketogenic diet: factors influencing efficacy, tolerability, and compliance.

PubMed

Wibisono, Cinthya; Rowe, Natalie; Beavis, Erin; Kepreotes, Helen; Mackie, Fiona E; Lawson, John A; Cardamone, Michael

2015-04-01

To evaluate the efficacy, tolerability, and compliance of 3 ketogenic diets, the classical ketogenic diet, medium-chain triglyceride (MCT), and modified Atkins diet. A single-center, retrospective study of 48 children with intractable epilepsy receiving ketogenic diets from 2003 to 2012. Patient demographics, epilepsy history, nutritional management, and side effects were collated. Compliance and tolerability were assessed by recording reasons for diet modification and cessation. The value of potassium citrate supplementation for preventing nephrolithiasis was reviewed. Median age at ketogenic diet initiation was 3.8 years (IQR: 2.3-7 years). The majority had intractable epilepsy, and 33 of the 48 children (69%) had epileptic encephalopathies. Three (6%) patients became seizure free, 35 (73%) reported <50%-90% reduction, and 10 (21%) had 0%-50% reduction during a 2-year period. Diet duration or ketogenic diet type did not predict reduction in seizures (P = .381; P = .272). Constipation (n = 31, 65%) was very common. Food refusal (n = 3, 6%) and poor parental compliance (n = 5, 10%) were common reasons cited for cessation. There were lower rates of side effects for modified Atkins diet. Diet cessation was greatest for MCT; however, 3 patients on MCT ceased therapy because adequate seizure control was achieved. Nephrolithiasis was reported in 1 patient before potassium citrate was used and 2 patients noncompliant with potassium citrate supplementation developed hypercalciuria. The 3 ketogenic diets were comparably effective in seizure control and generally well-tolerated. Potassium citrate supplementation is an effective prophylactic supplement for the prevention of nephrolithiasis. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Study of Tomography Of Nephrolithiasis Evaluation (STONE): methodology, approach and rationale.

PubMed

Valencia, Victoria; Moghadassi, Michelle; Kriesel, Dana R; Cummings, Steve; Smith-Bindman, Rebecca

2014-05-01

Urolithiasis (kidney stones) is a common reason for Emergency Department (ED) visits, accounting for nearly 1% of all visits in the United States. Computed tomography (CT) has become the most common imaging test for these patients but there are few comparative effectiveness data to support its use in comparison to ultrasound. This paper describes the rationale and methods of STONE (Study of Tomography Of Nephrolithiasis Evaluation), a pragmatic randomized comparative effectiveness trial comparing different imaging strategies for patients with suspected urolithiasis. STONE is a multi-center, non-blinded pragmatic randomized comparative effectiveness trial of patients between ages 18 and 75 with suspected nephrolithiasis seen in an ED setting. Patients were randomized to one of three initial imaging examinations: point-of-care ultrasound, ultrasound performed by a radiologist or CT. Participants then received diagnosis and treatment per usual care. The primary aim is to compare the rate of severe SAEs (Serious Adverse Events) between the three arms. In addition, a broad range of secondary outcomes was assessed at baseline and regularly for six months post-baseline using phone, email and mail questionnaires. Excluding 17 patients who withdrew after randomization, a total of 2759 patients were randomized and completed a baseline questionnaire (n=908, 893 and 958 in the point-of-care ultrasound, radiology ultrasound and radiology CT arms, respectively). Follow-up is complete, and full or partial outcomes were assessed on over 90% of participants. The detailed methodology of STONE will provide a roadmap for comparative effectiveness studies of diagnostic imaging conducted in an ED setting. Published by Elsevier Inc.

Evidence for net renal tubule oxalate secretion in patients with calcium kidney stones

PubMed Central

Zisman, Anna L.; Asplin, John R.; Worcester, Elaine M.; Coe, Fredric L.

2011-01-01

Little is known about the renal handling of oxalate in patients with idiopathic hypercalciuria (IH). To explore the role of tubular oxalate handling in IH and to evaluate whether differences exist between IH and normal controls, we studied 19 IH subjects, 8 normal subjects, and 2 bariatric stone formers (BSF) during a 1-day General Clinical Research Center protocol utilizing a low-oxalate diet. Urine and blood samples were collected at 30- to 60-min intervals while subjects were fasting and after they ate three meals providing known amounts of calcium, phosphorus, sodium, protein, oxalate, and calories. Plasma oxalate concentrations and oxalate-filtered loads were similar between patients (includes IH and BSF) and controls in both the fasting and fed states. Urinary oxalate excretion was significantly higher in patients vs. controls regardless of feeding state. Fractional excretion of oxalate (FEOx) was >1, suggesting tubular secretion of oxalate, in 6 of 19 IH and both BSF, compared with none of the controls (P < 0.00001). Adjusted for water extraction along the nephron, urine oxalate rose more rapidly among patients than normal subjects with increases in plasma oxalate. Our findings identify tubular secretion of oxalate as a key mediator of hyperoxaluria in calcium stone formers, potentially as a means of maintaining plasma oxalate in a tight range. PMID:21123489

Metabolic factors associated with urinary calculi in children.

PubMed

Naseri, Mitra; Varasteh, Abdol Reza; Alamdaran, Seied Ali

2010-01-01

We aimed to identify metabolic and anatomical abnormalities present in children with urinary calculi. Metabolic evaluation was done in 142 pediatric calculus formers. Evaluation included serum biochemistry; measurement of daily excretion of urinary calcium, uric acid, oxalate, citrate, and magnesium (in older children); and measurement of calcium, uric acid, oxalate, and creatinine in random urine samples in nontoilet-trained patients. Urinary tests for cystinuria were also performed. All of the patients underwent renal ultrasonography. Sixty-one patients (42.7%) had metabolic abnormalities. Anatomical abnormalities were found in 12 patients (8.4%). Three children (2.1%) had infectious calculi, and 3(2.1%) had a combination of metabolic and anatomic abnormalities. In 66 children (46.2 %) we did not find any reasons for calculus formation (idiopathic). Urinalysis revealed hypercalciuria in 25 (17.6%), hyperuricosuria in 23 (16.1%), hyperoxaluria in 17 (11.9%), cystinuria in 9 (6.3%), hypocitraturia in 3 (2.1%), and low urinary magnesium level in 1 (0.7%) patients. Sixteen patients (11.2%) had mixed metabolic abnormalities. Metabolic abnormalities are common in pediatric patients with urinary calculi. In our study, calcium and uric acid abnormalities were the most common, and vesicoureteral reflux seemed to be the most common urological abnormality which led to urinary stasis and calculus formation.

High-protein weight-loss diets: are they safe and do they work? A review of the experimental and epidemiologic data.

PubMed

Eisenstein, Julie; Roberts, Susan B; Dallal, Gerard; Saltzman, Edward

2002-07-01

Recommendations for increased consumption of protein are among the most common approaches of popular or fad diets. This review summarizes the effects of dietary protein on satiety, energy intake, thermogenesis, and weight loss, as well as its effect on a variety of health outcomes in adults. In short-term studies, dietary protein modulates energy intake via the sensation of satiety and increases total energy expenditure by increasing the thermic effect of feeding. Whereas these effects did not contribute to weight and fat loss in those studies in which energy intake was fixed, one ad libitum study does suggest that a high-protein diet results in a greater decrease in energy intake, and therefore greater weight and fat loss. In terms of safety, there is little long-term information on the health effects of high-protein diets. From the available data, however, it is evident that the consumption of protein greater than two to three times the U.S. Recommended Daily Allowance contributes to urinary calcium loss and may, in the long term, predispose to bone loss. Caution with these diets is recommended in those individuals who may be predisposed to nephrolithiasis or kidney disease, and particularly in those with diabetes mellitus.

Optimum nutrition for kidney stone disease.

PubMed

Heilberg, Ita P; Goldfarb, David S

2013-03-01

We summarize the data regarding the associations of individual dietary components with kidney stones and the effects on 24-hour urinary profiles. The therapeutic recommendations for stone prevention that result from these studies are applied where possible to stones of specific composition. Idiopathic calcium oxalate stone-formers are advised to reduce ingestion of animal protein, oxalate, and sodium while maintaining intake of 800 to 1200 mg of calcium and increasing consumption of citrate and potassium. There are few data regarding dietary therapy of calcium phosphate stones. Whether the inhibitory effect of citrate sufficiently counteracts increasing urine pH to justify more intake of potassium and citrate is not clear. Reduction of sodium intake to decrease urinary calcium excretion would also be expected to decrease calcium phosphate stone recurrence. Conversely, the most important urine variable in the causation of uric acid stones is low urine pH, linked to insulin resistance as a component of obesity and the metabolic syndrome. The mainstay of therapy is weight loss and urinary alkalinization provided by a more vegetarian diet. Reduction in animal protein intake will reduce purine ingestion and uric acid excretion. For cystine stones, restriction of animal protein is associated with reduction in intake of the cystine precursor methionine as well as cystine. Reduction of urine sodium results in less urine cystine. Ingestion of vegetables high in organic anion content, such as citrate and malate, should be associated with higher urine pH and fewer stones because the amino acid cystine is soluble in more alkaline urine. Because of their infectious origin, diet has no definitive role for struvite stones except for avoiding urinary alkalinization, which may worsen their development. Published by Elsevier Inc.

Five Patients With Burning Mouth Syndrome in Whom an Antidepressant (Serotonin-Noradrenaline Reuptake Inhibitor) Was Not Effective, but Pregabalin Markedly Relieved Pain.

PubMed

Ito, Mikiko; Tokura, Tatsuya; Yoshida, Keizo; Nagashima, Wataru; Kimura, Hiroyuki; Umemura, Eri; Tachibana, Masako; Miyauchi, Tomoya; Kobayashi, Yuka; Arao, Munetaka; Ozaki, Norio; Kurita, Kenichi

2015-01-01

Burning mouth syndrome (BMS) causes idiopathic pain or a burning sensation in clinically normal oral mucosa. Burning mouth syndrome is a chronic disease with an unknown etiology. Burning mouth syndrome is also idiopathic, and a consensus regarding diagnosis/treatment has not been reached yet. Recent studies have supported the suggestion that BMS is a neuropathic pain disorder in which both the peripheral and central nervous systems are involved. Tricyclic antidepressants (nortriptyline and amitriptyline), serotonin-noradrenaline reuptake inhibitors (SNRIs) (duloxetine and milnacipran), and antiepileptic drugs, potential-dependent calcium channel α2δ subunit ligands (gabapentine and pregabalin), are currently recommended as the first-choice drugs for neuropathic pain. In this study, we report 5 patients with BMS in whom there was no response to SNRI (milnacipran or duloxetine), or administration was discontinued because of adverse reactions, but in whom pregabalin therapy markedly reduced or led to the disappearance of pain in a short period. Pregabalin, whose mechanism of action differs from that of SNRIs, may become a treatment option for BMS patients who are not responsive to or are resistant to SNRIs.

Spontaneous ureteral rupture in a patient with systemic lupus erythematosus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benson, C.H.; Pennebaker, J.B.; Harisdangkul, V.

1983-08-01

A patient with known systemic lupus erythematosus had fever and symptoms of a lower urinary tract infection. Bone scintigraphy showed left ureteral perforation and necrosis with no demonstrable nephrolithiasis. It is speculated that this episode was due to lupus vasculitis.

A patient with hypophosphatemia, a femoral fracture, and recurrent kidney stones: report of a novel mutation in SLC34A3.

PubMed

Page, Kathleen; Bergwitz, Clemens; Jaureguiberry, Graciana; Harinarayan, Chittari V; Insogna, Karl

2008-10-01

To determine if there was a genetic contribution to our patient's unusual clinical presentation of nephrolithiasis and nonhealing stress fracture. We describe a 31-year-old man who had rickets as a child and developed a femur insufficiency fracture and recurrent nephrolithiasis as an adult after moving to the United States from India. The patient's clinical course and results from radiographic and biochemical analyses are described. Analysis of the SLC34A3 gene was performed using genomic DNA samples from the patient and his family members. Before referral to the Yale Bone Center, the patient was treated with calcitriol, ergocalciferol, and phosphate. Changing therapy to phosphate alone led to clinical improvement. Genetic analysis revealed that the patient is a compound heterozygote for mutations in the SLC34A3 gene. On 1 allele, he has a previously described missense mutation in exon 7: c.575C>T (p.Ser192Leu). The other allele carries a novel nonsense mutation in exon 3: c.145C>T (p.Gln49X). One unaffected sibling is a carrier of the missense mutation and 1 sister with a history of flank pain is a carrier of the novel mutation. Hereditary hypophosphatemic rickets with hypercalciuria is a rare metabolic disorder associated with mutations in SLC34A3, the gene that encodes the renal sodium phosphate cotransporter NaPi-IIc. Although hypercalciuria is a distinguishing feature of the disease, nephrolithiasis is rarely described. The patient's atypical clinical presentation illustrates that both environmental and genetic factors potentially affect phenotypic expression of SLC34A3 mutations.

[Ultraminipercutaneous nephrolithotripsy in treating kidney stones].

PubMed

Martov, A G; Dutov, S V; Andronov, A S

2016-04-01

Percutaneous nephrolithotripsy (PNL) is the recommended method of surgical treatment of kidney stones of size greater than 2 cm. Trends in the development of modern urology have been steadily toward less traumatic method to treat nephrolithiasis - minimally invasive PNL. The present work aimed to explore of the possibilities of one of the modern variants of minimally invasive PNL - ultra-mini-PNL in treating nephrolithiasis. The study included 60 patients (mean age 45.6+/-7.2 years) with isolated kidney calculus, up to 2.0 cm or several stones with a total size of up to 2.5 cm. All patients were found to have 77 kidney stones, six of which had a size of 10 mm, 51 had a size of 11-15 mm and 20 had a size of 16-20 mm. 45% of patients had isolated renal pelvic stones and 28.3% had stones in the renal pelvis and lower calyx. All patients underwent ultra-mini-PNL using nephroscope size 7.5 Ch and tube size 12 Fr. The average duration of surgery from the moment of the puncture of the pyelocaliceal system to installing the nephrostomy tube was 65.4 minutes. Complete clearance of stones after single-stage ultra-mini-PNL was observed in 80% of cases. Nephrostomy tube was removed on days 2-3. The average postoperative hospital stay was 5.1 days. The most common complication was postoperative exacerbation of pyelonephritis (13.3% of patients), successfully treated with conservative measures. There were no cases of postoperative bleeding, accompanied by anemia and needed a blood transfusion. Considering high effectiveness and low rate of complications of ultra-mini-PNL, it can be successfully used in treating nephrolithiasis among a wide group of patients.

Identifying and managing the risks of medical ionizing radiation in endourology.

PubMed

Yecies, Todd; Averch, Timothy D; Semins, Michelle J

2018-02-01

The risks of exposure to medical ionizing radiation is of increasing concern both among medical professionals and the general public. Patients with nephrolithiasis are exposed to high levels of ionizing radiation through both diagnostic and therapeutic modalities. Endourologists who perform a high-volume of fluoroscopy guided procedures are also exposed to significant quantities of ionizing radiation. The combination of judicious use of radiation-based imaging modalities, application of new imaging techniques such as ultra-low dose computed tomography (CT) scan, and modifying use of current technology such as increasing ultrasound and pulsed fluoroscopy utilization offers the possibility of significantly reducing radiation exposure. We present a review of the literature regarding the risks of medical ionizing radiation to patients and surgeons as it pertains to the field of endourology and interventions that can be performed to limit this exposure. A review of the current state of the literature was performed using MEDLINE and PubMed. Interventions designed to limit patient and surgeon radiation exposure were identified and analyzed. Summaries of the data were compiled and synthesized in the body of the text. While no level 1 evidence exists demonstrating the risk of secondary malignancy with radiation exposure, the preponderance of evidence suggests a dose and age dependent increase in malignancy risk from ionizing radiation. Patients with nephrolithiasis were exposed to an average effective dose of 37mSv over a 2 year period. Multiple evidence-based interventions to limit patient and surgeon radiation exposure and associated risk were identified. Current evidence suggest an age and dose dependent risk of secondary malignancy from ionizing radiation. Urologists must act in accordance with ALARA principles to safely manage nephrolithiasis while minimizing radiation exposure.

Intestinal Calcium Absorption among Hypercalciuric Patients with or without Calcium Kidney Stones.

PubMed

Vezzoli, Giuseppe; Macrina, Lorenza; Rubinacci, Alessandro; Spotti, Donatella; Arcidiacono, Teresa

2016-08-08

Idiopathic hypercalciuria is a frequent defect in calcium kidney stone formers that is associated with high intestinal calcium absorption and osteopenia. Characteristics distinguishing hypercalciuric stone formers from hypercalciuric patients without kidney stone history (HNSFs) are unknown and were explored in our study. We compared 172 hypercalciuric stone formers with 36 HNSFs retrospectively selected from patients referred to outpatient clinics of the San Raffaele Hospital in Milan from 1998 to 2003. Calcium metabolism and lumbar bone mineral density were analyzed in these patients. A strontium oral load test was performed: strontium was measured in 240-minute urine and serum 30, 60, and 240 minutes after strontium ingestion; serum strontium concentration-time curve and renal strontium clearance were evaluated to estimate absorption and excretion of divalent cations. Serum strontium concentration-time curve (P<0.001) and strontium clearance (4.9±1.3 versus 3.5±2.7 ml/min; P<0.001) were higher in hypercalciuric stone formers than HNSFs, respectively. The serum strontium-time curve was also higher in hypercalciuric stone formers with low bone mineral density (n=42) than in hypercalciuric stone formers with normal bone mineral density (n=130; P=0.03) and HNSFs with low (n=22; P=0.01) or normal bone mineral density (n=14; P=0.02). Strontium clearance was greater in hypercalciuric stone formers with normal bone mineral density (5.3±3.4 ml/min) than in hypercalciuric stone formers and HNSFs with low bone mineral density (3.6±2.5 and 3.1±2.5 ml/min, respectively; P=0.03). Multivariate regression analyses displayed that strontium absorption at 30 minutes was positively associated calcium excretion (P=0.03) and negatively associated with lumbar bone mineral density z score (P=0.001) in hypercalciuric stone formers; furthermore, hypercalciuric patients in the highest quartile of strontium absorption had increased stone production risk (odds ratio, 5.06; 95% confidence interval, 1.2 to 20.9; P=0.03). High calcium absorption in duodenum and jejunum may expose hypercalciuric patients to the risk of stones because of increased postprandial calcium concentrations in urine and tubular fluid. High calcium absorption may identify patients at risk of bone loss among stone formers. Copyright © 2016 by the American Society of Nephrology.

Uric acid nephrolithiasis: An update.

PubMed

Cicerello, Elisa

2018-04-01

Uric acid nephrolithiasis appears to increase in prevalence. While a relationship between uric acid stones and low urinary pH has been for long known, additional association with various metabolic conditions and pathophysiological basis has recently been elucidated. Some conditions such as diabetes and metabolic syndrome disease, excessive dietary intake, and increased endogenous uric acid production and/or defect in ammoniagenesis are associated with low urinary pH. In addition, the phenomenon of global warming could result in an increase in areas with greater climate risk for uric acid stone formation. There are three therapeutic steps to be taken for management of uric acid stones: identification of urinary pH profiles, assessment of urinary volume status, and identification of disorders leading to excessive uric acid production. However, the most important factor for uric acid stone formation is acid urinary pH, which is a prerequisite for uric acid precipitation. This article reviews recent insights into the pathophysiology of uric acid stones and their management.

Prophylactic effect of coconut water (Cocos nucifera L.) on ethylene glycol induced nephrocalcinosis in male wistar rat.

PubMed

Gandhi, M; Aggarwal, M; Puri, S; Singla, S K

2013-01-01

Many medicinal plants have been employed during ages to treat urinary stones though the rationale behind their use is not well established. Thus, the present study was proposed to evaluate the effect of coconut water as a prophylactic agent in experimentally induced nephrolithiasis in a rat model. The male Wistar rats were divided randomly into three groups. Animals of group I (control) were fed standard rat diet. In group II, the animals were administrated 0.75% ethylene glycol in drinking water for the induction of nephrolithiasis. Group III animals were administrated coconut water in addition to ethylene glycol. All the treatments were continued for a total duration of seven weeks. Treatment with coconut water inhibited crystal deposition in renal tissue as well as reduced the number of crystals in urine. Furthermore, coconut water also protected against impaired renal function and development of oxidative stress in the kidneys. The results indicate that coconut water could be a potential candidate for phytotherapy against urolithiasis.

[Pharmacological characteristics of drugs targeted on calcium-sensing receptor.-properties of cinacalcet hydrochloride as allosteric modulator].

PubMed

Nagano, Nobuo; Tsutsui, Takaaki

2016-06-01

Calcimimetics act as positive allosteric modulators of the calcium-sensing receptor (CaSR), thereby decreasing parathyroid hormone (PTH) secretion from the parathyroid glands. On the other hand, negative allosteric modulators of the CaSR with stimulatory effect on PTH secretion are termed calcilytics. The calcimimetic cinacalcet hydrochloride (cinacalcet) is the world's first allosteric modulator of G protein-coupled receptor to enter the clinical market. Cinacalcet just tunes the physiological effects of Ca(2+), an endogenous ligand, therefore, shows high selectivity and low side effects. Calcimimetics also increase cell surface CaSR expression by acting as pharmacological chaperones (pharmacoperones). It is considered that the cinacalcet-induced upper gastrointestinal problems are resulted from enhanced physiological responses to Ca(2+) and amino acids via increased sensitivity of digestive tract CaSR by cinacalcet. While clinical developments of calcilytics for osteoporosis were unfortunately halted or terminated due to paucity of efficacy, it is expected that calcilytics may be useful for the treatment of patients with activating CaSR mutations, asthma, and idiopathic pulmonary artery hypertension.

Elevated Vitamin D Receptor Levels in Genetic Hypercalciuric Stone-Forming Rats Are Associated With Downregulation of Snail

PubMed Central

Bai, Shaochun; Wang, Hongwei; Shen, Jikun; Zhou, Randal; Bushinsky, David A; Favus, Murray J

2010-01-01

Patients with idiopathic hypercalciuria (IH) and genetic hypercalciuric stone-forming (GHS) rats, an animal model of IH, are both characterized by normal serum Ca, hypercalciuria, Ca nephrolithiasis, reduced renal Ca reabsorption, and increased bone resorption. Serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels are elevated or normal in IH and are normal in GHS rats. In GHS rats, vitamin D receptor (VDR) protein levels are elevated in intestinal, kidney, and bone cells, and in IH, peripheral blood monocyte VDR levels are high. The high VDR is thought to amplify the target-tissue actions of normal circulating 1,25(OH)2D levels to increase Ca transport. The aim of this study was to elucidate the molecular mechanisms whereby Snail may contribute to the high VDR levels in GHS rats. In the study, Snail gene expression and protein levels were lower in GHS rat tissues and inversely correlated with VDR gene expression and protein levels in intestine and kidney cells. In human kidney and colon cell lines, ChIP assays revealed endogenous Snail binding close to specific E-box sequences within the human VDR promoter region, whereas only one E-box specifically bound Snail in the rat promoter. Snail binding to rat VDR promoter E-box regions was reduced in GHS compared with normal control intestine and was accompanied by hyperacetylation of histone H3. These results provide evidence that elevated VDR in GHS rats likely occurs because of derepression resulting from reduced Snail binding to the VDR promoter and hyperacetylation of histone H3. © 2010 American Society for Bone and Mineral Research. PMID:19929616

[The role of urinary tract infection in the development of recurrent nephrolithiasis].

PubMed

Khamidullin, K R; Pushkarev, A M; Tarasenko, A I; Pavlov, V N

2017-10-01

This is a literature review on the role of microbial flora in the development of recurrent urolithiasis. The authors outline pathogenetic aspects of recurrent stone formation associated bacterial flora. A number of studies reported that standard urine culture has limited sensitivity in detecting urinary tract infection.

[Antiurolithiasic effect of a plant mixture of Herniaria glabra, Agropyron repens, Equisetum arvense and Sambucus nigra (Herbensurina®) in the prevention of experimentally induced nephrolithiasis in rats].

PubMed

Crescenti, Anna; Puiggròs, Francesc; Colomé, Arnau; Poch, Josep Antón; Caimari, Antoni; Bas, Josep Maria; Boqué, Noemí; Arola, Lluís

2015-12-01

To determine the effect of a botanical formulation of Herniaria glabra, Agropyron repens, Equisetum arvense, and Sambucus nigra as a preventive agent in an experimentally induced nefrolithiasis model in rats. Six groups of six Wistar male rats each were induced for nefrolithiasis by treatment with 0.75% ethylene glycol (EG) and 1% ammonium chloride for three days and then EG only for 15 days. One group was treated with placebo (control group) and the other groups (treated groups) were treated with 30 mg/Kg, 60 mg/Kg, 125 mg/Kg, 250 mg/Kg and 500 mg/Kg of the plant extract formulation (PEF). 24-h urine and water samples were collected one day before EG administration and at 7, 13 and 18 days to determine diuresis, crystalluria and urine biochemistry. The kidneys were removed for histological analysis. The phytochemical characterization of PEF and each of its component plant extracts was performed using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. Animals treated with 125 mg/Kg of the PEF had statistically significantly lower calcium oxalate crystals deposits content compared to the control group. All PEF doses statistically significantly decreased the number of microcalcifications compared to the control group. Furthermore, the number of kidneys affected by subcapsular fibrosis was statistically significantly higher in control group than in treated groups with the PEF. The diuresis of the 125 mg/Kg and 500 mg/Kg PEF-treated groups was statistically significantly higher than that of the control group. A phytochemical analysis demonstrated the presence of flavonoids, dicarboxylic acids and saponins. Treatment with PEF prevents deposits of calcium oxalate crystals formation and of microcalcifications in the kidney, and reduces the risk of fibrosis subcapsular. 125 mg/Kg of PEF is the dose that has a greater effect on the studied parameters.

Protective Effects of Pistacia lentiscus L. fruit extract against calcium oxalate monohydrate induced proximal tubular injury.

PubMed

Cheraft-Bahloul, Nassima; Husson, Cécile; Ourtioualous, Meriam; Sinaeve, Sébastien; Atmani, Djebbar; Stévigny, Caroline; Nortier, Joëlle L; Antoine, Marie-Hélène

2017-09-14

The world prevalence of kidney stones is increasing and plants are frequently used to treat urolithiasis. Pistacia lentiscus L, a plant which freely grows around the Mediterranean basin areas, is widely used for various pathologies. P. lentiscus has an important impact as it has economical value on top of its pharmacological interest. Decoctions of its aerial parts and/or resin are used to treat kidney stones. To in vitro assess the potential nephroprotective effect of Pistacia lentiscus ethanolic fruit extract (PLEF) on proximal tubular cells in response to the adhesion of calcium oxalate monohydrate (COM) crystals. Human Kidney [HK]-2 cells were incubated with and without COM in the presence or absence of PLEF. Cell viability was measured by the resazurin assay. The expression of E-cadherin was analyzed by PCR. The extracellular production of H 2 O 2 was measured by Amplex® Red H 2 O 2 Assay. The numbers of detached or non-adherent COM crystals in the presence of PLEF were microscopically captured and counted using ImageJ software. The interaction of PLEF with COM and the effect of PLEF on crystal size were analyzed by flow cytometry. The spectrophotometric measurement of turbidity was performed for assessing the COM concentration. PLEF incubated with COM was able to increase the cell viability. The decrease of E-cadherin expression after incubation with COM was counteracted by PLEF. Overproduction of H 2 O 2 induced by COM was also inhibited by PLEF. Observations using flow cytometry showed that interactions between PLEF and the COM crystals occurred. PLEF was also effective in reducing the particles size and in lowering COM concentration. Our data show that COM tubulotoxicity can be significantly reversed by PLEF -at least in part- via an inhibition of COM crystals adhesion onto the apical membrane. This early beneficial effect of PLEF needs to be further investigated as a useful strategy in nephrolithiasis prevention. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Hyperparathyroidism in pregnancy: options for localization and surgical therapy.

PubMed

McMullen, Todd P W; Learoyd, Diana L; Williams, David C; Sywak, Mark S; Sidhu, Stan B; Delbridge, Leigh W

2010-08-01

Hyperparathyroidism in pregnancy is a threat to the health of both mother and fetus. The mothers suffer commonly from nephrolithiasis, hyperemesis, or even hypercalcemic crisis. Untreated disease will commonly complicate fetal development and fetal death is a significant risk. Treatment options, including medical and surgical therapy, are debated in the literature. This is a case series comprising seven patients with primary hyperparathyroidism in pregnancy. Data collected included symptoms at diagnosis, biochemical abnormalities, pathologic findings, treatment regimes, and subsequent maternal and fetal outcomes. Seven women, aged 20 to 39 years, presented with hyperparathyroidism during pregnancy. The earliest presented at 8 weeks and the latest at 38 weeks. Four of seven patients experienced renal calculi. Calcium levels were 2.7-3.5 mmol/l. All were found to have solitary parathyroid adenomas, of which two were in ectopic locations. Fetal complications included three preterm deliveries and one fetal death with no cases of neonatal tetany. Maternal and fetal complications could not be predicted based on duration or severity of hypercalcemia. Three patients were treated during pregnancy with surgery, and two of these had ectopic glands that required reoperations with a novel approach using Tc-99m sestamibi scanning during pregnancy to assist in localizing the abnormal gland. Four cases were treated postpartum with a combination of open and minimally invasive approaches after localization. No operative complications or fetal loss related to surgery were observed in this cohort. Primary hyperparathyroidism in pregnancy represents a significant risk for maternal and fetal complications that cannot be predicted by duration of symptoms or serum calcium levels. Surgical treatment should be considered early, and a minimally invasive approach with ultrasound is best suited to mitigating risk to mother and fetus. Equally important, Tc-99m sestamibi imaging may be used safely for localization of the parathyroids after negative cervical explorations.

A de novo mutation in KCNN3 associated with autosomal dominant idiopathic non-cirrhotic portal hypertension.

PubMed

Koot, Bart G P; Alders, Marielle; Verheij, Joanne; Beuers, Ulrich; Cobben, Jan M

2016-04-01

Non-cirrhotic portal hypertension is characterized by histopathological abnormalities in the liver, mostly affecting small intrahepatic portal veins that cause portal hypertension in the absence of cirrhosis. It can be secondary to coagulation disorders or toxic agents. However, most cases are idiopathic non-cirrhotic portal hypertension (INCPH) and familial cases are rare. We report a family in which a father and three of his four children conceived with three different mothers are affected by INCPH. Whole exome and Sanger sequencing showed the father to have a de novo single nucleotide substitution c.1348G>C in the KCNN3 gene that was transmitted to all three of his affected offspring. The KCNN3 gene encodes small conductance calcium-activated potassium (SK) channel 3. SK channels are involved in the regulation of arterial and venous vascular tone by causing smooth muscle relaxation on activation. No data exist on the expression and function of SK channels in portal veins. The autosomal dominant inheritance in this unique pedigree and the single de novo mutation identified, strongly suggests that KCNN3 mutations have a pathogenetic role in INCPH. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Bone mineral density in children with idiopathic nephrotic syndrome.

PubMed

El-Mashad, Ghada Mohamed; El-Hawy, Mahmoud Ahmed; El-Hefnawy, Sally Mohamed; Mohamed, Sanaa Mansour

To assess bone mineral density (BMD) in children with idiopathic nephrotic syndrome (NS) and normal glomerular filtration rate (GFR). Cross-sectional case-control study carried out on 50 children: 25 cases of NS (16 steroid-sensitive [SSNS] and nine steroid-resistant [SRNS] under follow up in the pediatric nephrology unit of Menoufia University Hospital, which is tertiary care center, were compared to 25 healthy controls with matched age and sex. All of the participants were subjected to complete history taking, thorough clinical examination, laboratory investigations (serum creatinine, blood urea nitrogen [BUN], phosphorus [P], total and ionized calcium [Ca], parathyroid hormone [PTH], and alkaline phosphatase [ALP]). Bone mineral density was measured at the lumbar spinal region (L2-L4) in patients group using dual-energy X-ray absorptiometry (DXA). Total and ionized Ca were significantly lower while, serum P, ALP, and PTH were higher in SSNS and SRNS cases than the controls. Osteopenia was documented by DXA scan in 11 patients (44%) and osteoporosis in two patients (8%). Fracture risk was mild in six (24%), moderate in two (8%), and marked in three (12%) of patients. Bone mineralization was negatively affected by steroid treatment in children with NS. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Reduced vertebral bone density in hypercalciuric nephrolithiasis

NASA Technical Reports Server (NTRS)

Pietschmann, F.; Breslau, N. A.; Pak, C. Y.

1992-01-01

Dual-energy x-ray absorptiometry and single-photon absorptiometry were used to determine bone density at the lumbar spine and radial shaft in 62 patients with absorptive hypercalciuria, 27 patients with fasting hypercalciuria, and 31 nonhypercalciuric stone formers. Lumbar bone density was significantly lower in patients with absorptive (-10%) as well as in those with fasting hypercalciuria (-12%), with 74 and 92% of patients displaying values below the normal mean, whereas only 48% of the nonhypercalciuric stone formers had bone density values below the normal mean. In contrast, radial bone density was similar in all three groups of renal stone formers investigated. The comparison of urinary chemistry in patients with absorptive hypercalciuria and low normal bone density compared to those with high normal bone density showed a significantly increased 24 h urinary calcium excretion on random diet and a trend toward a higher 24 h urinary uric acid excretion and a higher body mass index in patients with low normal bone density. Moreover, among the patients with absorptive hypercalciuria we found a statistically significant correlation between the spinal bone density and the 24 h sodium and sulfate excretion and the urinary pH. These results gave evidence for an additional role of environmental factors (sodium and animal proteins) in the pathogenesis of bone loss in absorptive hypercalciuria. In conclusion, our data suggest an osteopenia of trabecular-rich bone tissues in patients with fasting and absorptive hypercalciurias.

Hyaluronan and Stone Disease

NASA Astrophysics Data System (ADS)

Asselman, Marino

2008-09-01

Kidney stones cannot be formed as long as crystals are passed in the urine. However, when crystals are retained it becomes possible for them to aggregate and form a stone. Crystals are expected to be formed not earlier than the distal tubules and collecting ducts. Studies both in vitro and in vivo demonstrate that calcium oxalate monohydrate crystals do not adhere to intact distal epithelium, but only when the epithelium is proliferating or regenerating, so that it possesses dedifferentiated cells expressing hyaluronan, osteopontin (OPN) and their mutual receptor CD44 at the apical cell membrane. The polysaccharide hyaluronan is an excellent crystal binding molecule because of its negative ionic charge. We hypothesized that the risk for crystal retention in the human kidney would be increased when tubular cells express hyaluronan at their apical cell membrane. Two different patient categories in which nephrocalcinosis frequently occurs were studied to test this hypothesis (preterm neonates and kidney transplant patients). Hyaluronan (and OPN) expression at the luminal membrane of tubular cells indeed was observed, which preceded subsequent retention of crystals in the distal tubules. Tubular nephrocalcinosis has been reported to be associated with decline of renal function and thus further studies to extend our knowledge of the mechanisms of retention and accumulation of crystals in the kidney are warranted. Ultimately, this may allow the design of new strategies for the prevention and treatment of both nephrocalcinosis and nephrolithiasis in patients.

Phenotypic and functional analysis of human SLC26A6 variants in patients with familial hyperoxaluria and calcium oxalate nephrolithiasis.

PubMed

Monico, Carla G; Weinstein, Adam; Jiang, Zhirong; Rohlinger, Audrey L; Cogal, Andrea G; Bjornson, Beth B; Olson, Julie B; Bergstralh, Eric J; Milliner, Dawn S; Aronson, Peter S

2008-12-01

Urinary oxalate is a major risk factor for calcium oxalate stones. Marked hyperoxaluria arises from mutations in 2 separate loci, AGXT and GRHPR, the causes of primary hyperoxaluria (PH) types 1 (PH1) and 2 (PH2), respectively. Studies of null Slc26a6(-/-) mice have shown a phenotype of hyperoxaluria, hyperoxalemia, and calcium oxalate urolithiasis, leading to the hypothesis that SLC26A6 mutations may cause or modify hyperoxaluria in humans. Cross-sectional case-control. Cases were recruited from the International Primary Hyperoxaluria Registry. Control DNA samples were from a pool of adult subjects who identified themselves as being in good health. PH1, PH2, and non-PH1/PH2 genotypes in cases. Homozygosity or compound heterozygosity for SLC26A6 variants. Functional expression of oxalate transport in Xenopus laevis oocytes. 80 PH1, 6 PH2, 8 non-PH1/PH2, and 96 control samples were available for SLC26A6 screening. A rare variant, c.487C-->T (p.Pro163Ser), was detected solely in 1 non-PH1/PH2 pedigree, but this variant failed to segregate with hyperoxaluria, and functional studies of oxalate transport in Xenopus oocytes showed no transport defect. No other rare variant was identified specifically in non-PH1/PH2. Six additional missense variants were detected in controls and cases. Of these, c.616G-->A (p.Val206Met) was most common (11%) and showed a 30% reduction in oxalate transport. To test p.Val206Met as a potential modifier of hyperoxaluria, we extended screening to PH1 and PH2. Heterozygosity for this variant did not affect plasma or urine oxalate levels in this population. We did not have a sufficient number of cases to determine whether homozygosity for p.Val206Met might significantly affect urine oxalate. SLC26A6 was effectively ruled out as the disease gene in this non-PH1/PH2 cohort. Taken together, our studies are the first to identify and characterize SLC26A6 variants in patients with hyperoxaluria. Phenotypic and functional analysis excluded a significant effect of identified variants on oxalate excretion.

Phenotypic and Functional Analysis of Human SLC26A6 Variants in Patients With Familial Hyperoxaluria and Calcium Oxalate Nephrolithiasis

PubMed Central

Monico, Carla G.; Weinstein, Adam; Jiang, Zhirong; Rohlinger, Audrey L.; Cogal, Andrea G.; Bjornson, Beth B.; Olson, Julie B.; Bergstralh, Eric J.; Milliner, Dawn S.; Aronson, Peter S.

2008-01-01

Background Urinary oxalate is a major risk factor for calcium oxalate stones. Marked hyperoxaluria arises from mutations in two separate loci, AGXT and GRHPR, the causes of primary hyperoxaluria (PH) types 1 and 2, respectively. Studies of null Slc26a6 (−/−) mice have revealed a phenotype of hyperoxaluria, hyperoxalemia and calcium oxalate urolithiasis, leading to the hypothesis that SLC26A6 mutations may cause or modify hyperoxaluria in humans. Study Design Cross-sectional, case-control. Setting & Participants Cases were recruited from the International Primary Hyperoxaluria Registry. Control DNA samples were from a pool of adult subjects who identified themselves as being in good health. Predictor PH1, PH2, non-PH1/PH2 genotypes in cases. Outcomes & Measures Homozygosity or compound heterozygosity for SLC26A6 variants. Functional expression of oxalate transport in Xenopus oocytes. Results A total of 80 PH1, 6 PH2, 8 non-PH1/PH2 and 96 control samples were available for SLC26A6 screening. A rare variant, c.487C>T (p.Pro163Ser) was detected solely in one non-PH1/PH2 pedigree but this variant failed to segregate with hyperoxaluria, and functional studies of oxalate transport in Xenopus oocytes revealed no transport defect. No other rare variant was identified specifically in non-PH1/PH2. Six additional missense variants were detected in controls and in cases. Of these, c.616G>A (p.Val206Met) was most common (11%), and showed a 30% reduction in oxalate transport. To test p.Val206Met as a potential modifier of hyperoxaluria, we extended screening to PH1 and PH2. Heterozygosity for this variant did not affect plasma or urine oxalate in this population. Limitations We did not have a sufficient number of cases to determine whether homozygosity for p.Val206Met might significantly affect urine oxalate. Conclusions SLC26A6 was effectively ruled out as the disease gene in this non-PH1/PH2 cohort. Taken together, our studies are the first to identify and characterize SLC26A6 variants in hyperoxaluria. Phenotypic and functional analysis excluded a significant effect of identified variants on oxalate excretion. PMID:18951670

Multiple Sub-Epidermal Calcified Nodule Mimicking Eruptive Xanthoma: A Case Report and Review of the Literature

PubMed Central

Ozuguz, Pinar; Balta, Ilknur; Bozkurt, Ozlem; Unverdi, Hatice; Dostbil, Ahmet

2013-01-01

Sub-epidermal calcified nodule (SCN) is an uncommon form of idiopathic calcinosis. It usually occurs in children, particularly in the head and neck region, presenting as a solitary, painless, yellow-white nodule with papillomatous features. These lesions occur twice as common in males compared with females. The pathogenesis is uncertain, but the clinical and histological features of this lesion are distinctive. We report a case of 22-year-old man with multiple nodules bilaterally located on the dorsum of hands simulating eruptive xanthoma. Histopathological examination of one of the excised lesion confirmed the diagnosis showing epidermal and sub-epidermal deposition of calcium. This paper presents a review of the literature and adds a new case of SCN. PMID:24082201

[Peculiarities of upper urinary tract drainage during surgical treatment of staghorn and multiple nephrolithiasis].

PubMed

Imamverdiev, S B; Talybov, T A; Mamedov, R N

2014-01-01

This work was designed to evaluate methods of kidney drainage used in the surgical treatment of 250 patients with staghorn and multiple nephrolithiasis (SMN). All of them underwent open surgery that was followed by drainage of the upper urinary tract in 192 patients. Internal stenting was used in 111 cases, pyelostomy in 28, nephrostomy in 47, and internal stenting with nephrostoma in 6 cases. 91 and 20 patients had a stent inserted into the upper urinary tract in a retrograde and antegrade manner respectively. Retrograde stenting was bilateral in 14 and unilateral in 66 cases. 85% of the cases with ureter stents were followed up as outpatients for 4-5 weeks and only 10% for 6-7 weeks. Forty and ten patients with stents presented with marked dysuria and hematuria respectively. On the whole, combined antibacterial treatment with drainage of the upper urinary tract significantly improved long-term results of SMN treatment. It is concluded that nephrostomy and pyelostomy should be performed on days 14-18 and 10-12 respectively whereas the stent needs to be removed between weeks 2 and 8 after surgery.

The Natural History of Idiopathic Scoliosis During Growth: A Meta-Analysis.

PubMed

Di Felice, Francesca; Zaina, Fabio; Donzelli, Sabrina; Negrini, Stefano

2018-05-01

The aim of the study was to provide a meta-analysis of current literature concerning the natural history of idiopathic scoliosis during growth. A comprehensive search of Medline, Embase, And Scopus databases was conducted up to November 2016. Eligible works were prospective or retrospective studies that enrolled patients with infantile idiopathic scoliosis, juvenile idiopathic scoliosis, or adolescent idiopathic scoliosis, followed up without any treatment from the time of detection. A meta-analysis for proportion was performed. The following studies were grouped per diagnosis: infantile idiopathic scoliosis, juvenile idiopathic scoliosis, and adolescent idiopathic scoliosis. Of the 1797 citations screened, we assessed 61 full-text articles and included 13 of these (2301 participants). Three studies included infantile idiopathic scoliosis patients (347 participants), five studies included a mixed population of juvenile idiopathic scoliosis and adolescent idiopathic scoliosis (1330 participants), and five studies included adolescent idiopathic scoliosis patients only (624 participants). The random pooled estimated progression rate was 49% (95% confidence interval = 1%-97%) for infantile idiopathic scoliosis, 49% in a mixed group of patients affected by juvenile idiopathic scoliosis or adolescent idiopathic scoliosis (95% confidence interval = 19%-79%), and 42% in adolescent idiopathic scoliosis (95% confidence interval = 11%-73%). During growth, idiopathic scoliosis tends to progress in a high percentage of cases. The progression rate varies according to the age at diagnosis, with infantile scoliosis being the most unpredictable. There are many confounders, such as age, Risser sign and baseline Cobb angles that were not consistent among studies, making the data very heterogeneous.

Novel Therapeutic Strategies for Reducing Right Heart Failure Associated Mortality in Fibrotic Lung Diseases

PubMed Central

Levy, Matthew; Oyenuga, Olusegun

2015-01-01

Fibrotic lung diseases carry a significant mortality burden worldwide. A large proportion of these deaths are due to right heart failure and pulmonary hypertension. Underlying contributory factors which appear to play a role in the mechanism of progression of right heart dysfunction include chronic hypoxia, defective calcium handling, hyperaldosteronism, pulmonary vascular alterations, cyclic strain of pressure and volume changes, elevation of circulating TGF-β, and elevated systemic NO levels. Specific therapies targeting pulmonary hypertension include calcium channel blockers, endothelin (ET-1) receptor antagonists, prostacyclin analogs, phosphodiesterase type 5 (PDE5) inhibitors, and rho-kinase (ROCK) inhibitors. Newer antifibrotic and anti-inflammatory agents may exert beneficial effects on heart failure in idiopathic pulmonary fibrosis. Furthermore, right ventricle-targeted therapies, aimed at mitigating the effects of functional right ventricular failure, include β-adrenoceptor (β-AR) blockers, angiotensin-converting enzyme (ACE) inhibitors, antioxidants, modulators of metabolism, and 5-hydroxytryptamine-2B (5-HT2B) receptor antagonists. Newer nonpharmacologic modalities for right ventricular support are increasingly being implemented. Early, effective, and individualized therapy may prevent overt right heart failure in fibrotic lung disease leading to improved outcomes and quality of life. PMID:26583148

A multiregional Italian cohort of 24-hour urine metabolic evaluation in renal stone formers.

PubMed

Esperto, Francesco; Marangella, Martino; Trinchieri, Alberto; Petrarulo, Michele; Miano, Roberto

2018-02-01

Nephrolithiasis is a common condition with several studies documenting an increased prevalence over the past four decades. EAU and AUA guidelines recommend 24-hour urine metabolic evaluation in high-risk stone formers. Aim of this study is to retrospectively evaluate the first three years of experience with LithoTest® (Biohealth Italia Srl, Turin, Italy) through the analysis of demographic, clinical and biochemical data collected from a large cohort of patients with kidney stones. We retrospectively analyzed data from the LithoCenter database, including data from outpatient consultations, between January 2007 and December 2009 from all over Italy. LithoTest® was performed through a 24-hour urine collection and included measurements of urine volume and pH, 24-hour excretion of creatinine as well as main cations and anions, including calcium, magnesium sodium potassium, ammonium, uric acid, oxalate, citrate, phosphate, inorganic sulphate and chloride. Urine state of saturation for calcium oxalate (βCaOx), calcium hydrogen phosphate or brushite (βbsh) and uric acid (βUA) were also calculated by means of the computer program LithoRisk. Brand's test for cystinuria was also carried out. Statistical analysis was performed using the S-PSS software v. 22.0. The number of patients with data available for analysis was 435, of whom 236 were male (54%) and 199 female (46%). Complete 24-hour urine measurements were available for all 435 patients. Compared to men, women had significantly lower values for creatinine, urate, oxalate, phosphate, sodium, potassium, magnesium and chloride excretion, whereas 24-hour pH and citrate excretion were higher. No significant differences were found for the other examined variables. βCaOx and βUA were significantly higher in men than women, whereas no significant difference was found for βbsh. There was a direct relationship between calcium and sodium urine excretion. Excessive sodium excretion was recorded in 191 patients (44%) and low urine volumes in 201 (46.2%). Hyperoxaluria was observed in 118 patients (27.3%), hypercalciuria in 115 (26.6%), hyperuricosuria in 153 (35.4%), hypomagnesuria in 96 (22.2%), and hypocitraturia in 134 patients (31%). Hyperexcretion of sodium, hypocitraturia and hyperoxaluria were most frequent in males. βCaOx was significantly higher in the setting of hypercalciuria, hypocitraturia, hyperoxaluria and urine pH below 5.5. Our findings in a large cohort of high-risk stone-forming patients show significant differences in urinary metabolic profiles between men and women. Carrying on the collection and analysis of data by LithoTest® from 2009 to 2015 and matching urinary and dietary data could eventually improve our understanding on the metabolic profile of stone-formers in Italy.

Multiple sclerosis and nephrolithiasis: a matched-case comparative study.

PubMed

Ganesan, Vishnu; Chen, Wen Min; Jain, Rajat; De, Shubha; Monga, Manoj

2017-06-01

To compare stone composition and serum/urine biochemistries in stone formers with multiple sclerosis (MS) against stone formers without MS and to examine the association between mobility, methods of bladder emptying, and stone formation. In this retrospective case-control study, we identified patients diagnosed with MS and kidney stone disease who were seen at our institution between 2001 and 2016. For the first part of the study, up to two controls (stone formers without a history of MS) were identified for each case and matched on age, body mass index, and sex. For the second part of this study, matched controls (MS patients without a history of stones) were identified in a 1:1 ratio in a similar fashion. Results of 24-h urine biochemistry studies, stone compositions, serum laboratory measures, medications, history of stone surgeries, mobility, and method of bladder emptying were collected. In all, 587 patients were identified who had both MS and a history of stone disease. Of these, 118 patients had a stone composition available. When compared to matched controls, patients with MS were significantly more likely to have calcium phosphate stones (42% vs 15%, P < 0.001) and struvite stones (8% vs 3%, P = 0.03) and less likely to have calcium oxalate monohydrate stones (39% vs 64%, P < 0.001). Among those patients with a composition available, those with MS were more likely to have undergone a percutaneous nephrolithotomy (PCNL; 25% vs 12%, P = 0.005) or a cystolithopaxy (16% vs 3%, P < 0.001) compared to their matched controls. In all, 61 patients had a complete 24-h urinary stone panel. There were no significant differences in urinary pH, volume, creatinine, calcium, citrate, oxalate, sodium, and uric acid as well as rates of hypocitraturia, hyperoxaluria, hypercalciuria, and hyperuricosuria among patients with MS. Use of intermittent straight catheterisation [ISC; odds ratio (OR) 3.50, 95% confidence interval (CI) 1.89-6.47]; P < 0.001] or an indwelling catheter (OR 9.78, 95% CI 4.81-19.88; P < 0.001) for bladder emptying was significantly associated with stone disease. There was no association between level of mobility and stone disease (P = 0.10). Similar to findings seen in patients with spinal cord injuries, patients with MS have a high incidence of calcium phosphate stones and struvite stones when compared with matched controls. Additionally, they were more likely to undergo PCNL. The method of bladder management appears to be a risk factor in the development of stone disease. These findings suggest the importance of prompt treatment of urinary tract infections in this population and delay the use of ISC, suprapubic tube, or an indwelling Foley, when possible. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Improvements in Intracorporeal Lithotripters for Percutaneous Nephrolithotomy

NASA Astrophysics Data System (ADS)

Kuo, Ramsay L.

2007-04-01

Percutaneous nephrolithotomy (PNL) is an effective minimally invasive surgical approach for the treatment of large renal stone burden. Intracorporeal lithotripters (ICL) are utilized during PNL to fragment calculi, with some devices capable of concurrently removing fragments as well. Much progress has been made in the design of ICL devices, resulting in potentially more efficient treatment of nephrolithiasis.

Changes in Renal Function and Blood Pressure in Patients with Stone Disease

NASA Astrophysics Data System (ADS)

Worcester, Elaine M.

2007-04-01

Stone disease is a rare cause of renal failure, but a history of kidney stones is associated with an increased risk for chronic kidney disease, particularly in overweight patients. Loss of renal function seems especially notable for patients with stones associated with cystinuria, hyperoxaluria, and renal tubular acidosis, in whom the renal pathology shows deposits of mineral obstructing inner medullary collecting ducts, often diffusely. However, even idiopathic calcium oxalate stone formers have a mild but significant decrease in renal function, compared to age, sex and weight-matched normals, and appear to lose renal function with age at a slightly faster rate than non-stone formers. There is also an increased incidence of hypertension among stone formers, although women are more likely to be affected than men.

[Diagnosis and treatment of pulmonary hypertension].

PubMed

Román, J Sánchez; Hernández, F J García; Palma, M J Castillo; Medina, C Ocaña

2008-03-01

Pulmonary arterial hypertension is an idiopathic process or can be associated with another circumstances (connective tissue diseases, congenital heart disease, portal hypertension, exposure to appetite suppressants or another drugs or infectious agents such as HIV). Most patients are diagnosed as the result of an evaluation of symptoms, whereas others are diagnosed incidentally or during screening of asymptomatic populations at risk. We reviews systematic screening for the approach to diagnosing pulmonary arterial hypertension. A diagnostic algorithm can guide the evaluation but it can be modified according to specific clinical circumstances. The number of therapeutic options has increased.in the last years. We reviews the use of calcium-channel blockers, prostacyclin (and analogues), endothelin-receptor antagonists, and phosphodiesterase-5 inhibitors, and the use of combination therapy, and provides specific recommendations about the actual treatment.

Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia.

PubMed Central

Laurence, J; Mitra, D; Steiner, M; Lynch, D H; Siegal, F P; Staiano-Coico, L

1996-01-01

Progressive loss of CD4+ T lymphocytes, accompanied by opportunistic infections characteristic of the acquired immune deficiency syndrome, ahs been reported in the absence of any known etiology. The pathogenesis of this syndrome, a subset of idiopathic CD4+ T lymphocytopenia (ICL), is uncertain. We report that CD4+ T cells from seven of eight ICL patients underwent accelerated programmed cell death, a process facilitated by T cell receptor cross-linking. Apoptosis was associated with enhanced expression of Fas and Fas ligand in unstimulated cell populations, and partially inhibited by soluble anti-Fas mAb. In addition, apoptosis was suppressed by aurintricarboxylic acid, an inhibitor of calcium-dependent endonucleases and proteases, in cells from four of seven patients, The in vivo significance of these findings was supported by three factors: the absence of accelerated apoptosis in persons with stable, physiologic CD4 lymphopenia without clinical immune deficiency; detection of serum antihistone H2B autoantibodies, one consequence of DNA fragmentation, in some patients; and its selectivity, with apoptosis limited to the CD4 population in some, and occurring among CD8+ T cells predominantly in those individuals with marked depletion of both CD4+ T lymphocytes linked to clinical immune suppression have evidence for accelerated T cell apoptosis in vitro that may be pathophysiologic and amenable to therapy with apoptosis inhibitors. PMID:8609222

Deficiency in GnRH receptor trafficking due to a novel homozygous mutation causes idiopathic hypogonadotropic hypogonadism in three prepubertal siblings.

PubMed

Zhang, Rui; Linpeng, Siyuan; Li, Zhuo; Cao, Yingxi; Tan, Hu; Liang, Desheng; Wu, Lingqian

2018-08-30

Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by low levels of gonadotropins and delayed or absent sexual development. Most of the patients are diagnosed in late adolescence or early adulthood. Determining the diagnosis of IHH in prepubertal patients can be challenging. Making a timely, correct diagnosis has important clinical implications. Here we aimed to identify the genetic cause of IHH in three prepubertal siblings from a Chinese Han family and give appropriate treatment advice. Using whole exome sequencing (WES), we identified a novel homozygous GNRHR mutation (NM_000406; c.364C>T, p.L122F) in two prepubertal boys with cryptorchidism and micropenis. Sanger sequencing showed that their younger asymptomatic sister also had the homozygous GNRHR mutation. This mutation was inherited from the father and the mother. Immunofluorescence analysis showed that in permeabilized cells, expression of the mutant receptor on the cell membrane was significantly lower than that of wild-type. Calcium mobilization assays demonstrated that c.364C>T in the GNRHR gene is a complete loss-of-function mutation that caused IHH. These results may contribute to the genetic diagnosis of the three prepubertal siblings with IHH. According to this diagnosis, timely hormonal treatment can be given for the three prepubertal patients to induce pubertal development, especially for the asymptomatic female. Copyright © 2018 Elsevier B.V. All rights reserved.

Physicochemical analysis of urinary stones from Dharmapuri district

NASA Astrophysics Data System (ADS)

Aslin Shamema, A.; Thanigai Arul, K.; Senthil Kumar, R.; Narayana Kalkura, S.

2015-01-01

Nephrolithiasis is a common disease caused by the multifactorial components such as geographical location, bacterial infection, low urine volume, and low intake of water. This disease induces severe metabolic abnormalities in the human body. As the prevalence of this disease was high in Dharmapuri district located in Tamil Nadu, urinary stones removed from the patients pertaining to this district were collected and to identify the toxic elements present in the stones. The presence of functional groups and phases of the stones were analyzed using X-ray diffraction (XRD), Fourier transform Raman spectroscopy and Fourier transform infrared spectroscopy (FT-IR). The majority of stones were found to be calcium oxalate monohydrate (COM) and mixed stones having minor existence of struvite and uric acid. Hexagonal shaped COM crystals, needle shaped uric acid crystals and layered arrangement of struvite crystals in the core region were revealed by Scanning Electron Microscopy (SEM). Thermo Gravimetric Analysis (TGA) was used to determine the thermal stability and the hardness of the stone which was measured using Vickers hardness (HV). The presence of toxic elements in stones such as zirconium and mercury was identified using Energy Dispersive X-ray Spectroscopy (EDS). The EDS analysis showed higher concentration of zirconium in the core region compared to the periphery. The percentage of zirconium was relatively high compared to other toxic elements in the stones. The Vickers hardness results indicated that high HV values in the core region than the periphery and this might be due to the presence of zirconium.

Pkd1 transgenic mice: adult model of polycystic kidney disease with extrarenal and renal phenotypes

PubMed Central

Kurbegovic, Almira; Côté, Olivier; Couillard, Martin; Ward, Christopher J.; Harris, Peter C.; Trudel, Marie

2010-01-01

While high levels of Pkd1 expression are detected in tissues of patients with autosomal dominant polycystic kidney disease (ADPKD), it is unclear whether enhanced expression could be a pathogenetic mechanism for this systemic disorder. Three transgenic mouse lines were generated from a Pkd1-BAC modified by introducing a silent tag via homologous recombination to target a sustained wild-type genomic Pkd1 expression within the native tissue and temporal regulation. These mice specifically overexpressed the Pkd1 transgene in extrarenal and renal tissues from ∼2- to 15-fold over Pkd1 endogenous levels in a copy-dependent manner. All transgenic mice reproducibly developed tubular and glomerular cysts leading to renal insufficiency. Interestingly, Pkd1TAG mice also exhibited renal fibrosis and calcium deposits in papilla reminiscent of nephrolithiasis as frequently observed in ADPKD. Similar to human ADPKD, these mice consistently displayed hepatic fibrosis and ∼15% intrahepatic cysts of the bile ducts affecting females preferentially. Moreover, a significant proportion of mice developed cardiac anomalies with severe left-ventricular hypertrophy, marked aortic arch distention and/or valvular stenosis and calcification that had profound functional impact. Of significance, Pkd1TAG mice displayed occasional cerebral lesions with evidence of ruptured and unruptured cerebral aneurysms. This Pkd1TAG mouse model demonstrates that overexpression of wild-type Pkd1 can trigger the typical adult renal and extrarenal phenotypes resembling human ADPKD. PMID:20053665

Percutaneous Nephrolithotomy in Autosomal Dominant Polycystic Kidney Disease: Is it Different from Percutaneous Nephrolithotomy in Normal Kidney?

PubMed

Singh, Vishwajeet; Sinha, Rahul Janak; Gupta, Dheeraj Kumar

2013-08-01

Nephrolithiasis has been reported in 20-28% of patients, of whom 50% are symptomatic for stone disease and 20% require definite urologic intervention. The management of nephrolithiasis includes oral alkali dissolution therapy, extracorporeal shock wave lithotripsy and surgical treatment. In such patients, percutaneous nephrolithotomy (PNL) as a method of stone treatment has been reported in few cases with limited experience. The aim of this study is to present our experience of PNL in autosomal dominant polycystic kidney disease (ADPKD) and assessing the outcome results. From 2002 to 2011, 22 patients (26 renal units) suffering from ADPKD with stone were managed by PNL. Demographic characteristics, operative parameters and postoperative complications were recorded and analysed. The overall success rate of PNL was 82.1% and PNL with extracorporeal shock wave lithotripsy for clinically significant residual fragments was 92.85% respectively. The hematuria required blood transfusion (n = 9), postoperative fever due to cyst infection (n = 4) and paralytic ileus (n = 3) were recorded. The PNL in ADPKD PNL is safe and effective but have more postoperative complications such as bleeding requiring transfusions, fever due to cyst infection and paralytic ileus.

Incidental kidney stones: a single center experience with kidney donor selection

PubMed Central

Kim, Irene K.; Tan, Jane C.; Lapasia, Jessica; Elihu, Arvand; Busque, Stephan; Melcher, Marc L.

2014-01-01

The presence of kidney stones has been a relative contraindication for living donation. With the widespread use of more sensitive imaging techniques as part of the routine living donor workup, kidney stones are more frequently detected, and their clinical significance in this setting is largely unknown. Records from 325 potential kidney donors who underwent MRA or CT-angiography were reviewed; 294 proceeded to donation. The prevalence of kidney stones found incidentally during donor evaluation was 7.4% (24 of 325). Sixteen donors with stones proceeded with kidney donation. All incidental calculi were nonobstructing and small (median 2 mm; range 1–9 mm). Eleven recipients were transplanted with allografts containing stones. One recipient developed symptomatic nephrolithasis after transplantation. This recipient was found to have newly formed stones secondary to hyperoxaluria, suggesting a recipient-driven propensity for stone formation. The remaining ten recipients have stable graft function, postoperative ultrasound negative for nephrolithiasis, and no sequelae from stones. No donor developed symptomatic nephrolithiasis following donation. Judicious use of allografts with small stones in donors with normal metabolic studies may be acceptable, and careful follow-up in recipients of such allografts is warranted. PMID:22168332

Uric Acid Nephrolithiasis: A Systemic Metabolic Disorder

PubMed Central

Moe, Orson W.

2014-01-01

Uric acid nephrolithiasis is characteristically a manifestation of a systemic metabolic disorder. It has a prevalence of about 10% among all stone formers, the third most common type of kidney stone in the industrialized world. Uric acid stones form primarily due to an unduly acid urine; less deciding factors are hyperuricosuria and a low urine volume. The vast majority of uric acid stone formers have the metabolic syndrome, and not infrequently, clinical gout is present as well. A universal finding is a low baseline urine pH plus insufficient production of urinary ammonium buffer. Persons with gastrointestinal disorders, in particular chronic diarrhea or ostomies, and patients with malignancies with a large tumor mass and high cell turnover comprise a less common but nevertheless important subset. Pure uric acid stones are radiolucent but well visualized on renal ultrasound. A 24 h urine collection for stone risk analysis provides essential insight into the pathophysiology of stone formation and may guide therapy. Management includes a liberal fluid intake and dietary modification. Potassium citrate to alkalinize the urine to a goal pH between 6 and 6.5 is essential, as undissociated uric acid deprotonates into its much more soluble urate form. PMID:25045326

Idiopathic ophthalmodynia and idiopathic rhinalgia: two topographic facial pain syndromes.

PubMed

Pareja, Juan A; Cuadrado, María L; Porta-Etessam, Jesús; Fernández-de-las-Peñas, César; Gili, Pablo; Caminero, Ana B; Cebrián, José L

2010-09-01

To describe 2 topographic facial pain conditions with the pain clearly localized in the eye (idiopathic ophthalmodynia) or in the nose (idiopathic rhinalgia), and to propose their distinction from persistent idiopathic facial pain. Persistent idiopathic facial pain, burning mouth syndrome, atypical odontalgia, and facial arthromyalgia are idiopathic facial pain syndromes that have been separated according to topographical criteria. Still, some other facial pain syndromes might have been veiled under the broad term of persistent idiopathic facial pain. Through a 10-year period we have studied all patients referred to our neurological clinic because of facial pain of unknown etiology that might deviate from all well-characterized facial pain syndromes. In a group of patients we have identified 2 consistent clinical pictures with pain precisely located either in the eye (n=11) or in the nose (n=7). Clinical features resembled those of other localized idiopathic facial syndromes, the key differences relying on the topographic distribution of the pain. Both idiopathic ophthalmodynia and idiopathic rhinalgia seem specific pain syndromes with a distinctive location, and may deserve a nosologic status just as other focal pain syndromes of the face. Whether all such focal syndromes are topographic variants of persistent idiopathic facial pain or independent disorders remains a controversial issue.

Effect of basal ganglia calcification on its glucose metabolism and dopaminergic function in idiopathic hypoparathyroidism.

PubMed

Modi, Sagar; Arora, Geetanjali; Bal, Chandra Shekhar; Sreenivas, Vishnubhatla; Kailash, Suparna; Sagar, Rajesh; Goswami, Ravinder

2015-10-01

The functional significance of basal ganglia calcification (BGC) in idiopathic hypoparathyroidism (IH) is not clear. To assess the effect of BGC on glucose metabolism and dopaminergic function in IH. (18) F-FDG and (99m) Tc-TRODAT-1 nuclear imaging were performed in 35 IH patients with (n = 26) and without (n = 9) BGC. Controls were subjects without hypoparathyroidism or BGC (nine for (18) F-FDG and 12 for (99m) Tc-TRODAT-1). Relationship of the glucose metabolism and dopaminergic function was assessed with the neuropsychological and biochemical abnormalities. (18) F-FDG uptake in IH patients with calcification at caudate and striatum was less than that of IH patients without calcification (1·06 ± 0·13 vs 1·24 ± 0·09, P = <0·0001 and 1·06 ± 0·09 vs 1·14 ± 0·08, P = 0·03, respectively). (18) F-FDG uptake did not correlate with neuropsychological dysfunctions. (18) F-FDG uptake in IH without BGC was significantly lower than that of controls. The mean (99m) Tc-TRODAT-1 uptake at basal ganglia was comparable between IH with and without BGC and between IH without BGC and controls. Serum calcium-phosphorus ratio maintained by the patients correlated with (18) F-FDG uptake at striatum (r = 0·57, P = 0·001). For every 0·1 unit reduction in calcium-phosphorus ratio, (18) F-FDG uptake decreased by 2·5 ± 0·68% (P = 0·001). BGC was associated with modest reduction (15%) in (18) F-FDG uptake at basal ganglia in IH but did not affect dopaminergic function. (18) F-FDG uptake did not correlate with neuropsychological dysfunctions. Interestingly, chronic hypocalcaemia-hyperphosphataemia also contributed to reduction in (18) F-FDG uptake which was independent of BGC. © 2014 John Wiley & Sons Ltd.

Mechanisms of oxygen sensing: a key to therapy of pulmonary hypertension and patent ductus arteriosus

PubMed Central

Weir, E K; Obreztchikova, M; Vargese, A; Cabrera, J A; Peterson, D A; Hong, Z

2008-01-01

Specialized tissues that sense acute changes in the local oxygen tension include type 1 cells of the carotid body, neuroepithelial bodies in the lungs, and smooth muscle cells of the resistance pulmonary arteries and the ductus arteriosus (DA). Hypoxia inhibits outward potassium current in carotid body type 1 cells, leading to depolarization and calcium entry through L-type calcium channels. Increased intracellular calcium concentration ([Ca++]i) leads to exocytosis of neurotransmitters, thus stimulating the carotid sinus nerve and respiration. The same K+ channel inhibition occurs with hypoxia in pulmonary artery smooth muscle cells (PASMCs), causing contraction and providing part of the mechanism of hypoxic pulmonary vasoconstriction (HPV). In the SMCs of the DA, the mechanism works in reverse. It is the shift from hypoxia to normoxia that inhibits K+ channels and causes normoxic ductal contraction. In both PA and DA, the contraction is augmented by release of Ca++ from the sarcoplasmic reticulum, entry of Ca++ through store-operated channels (SOC) and by Ca++ sensitization. The same three ‘executive' mechanisms are partly responsible for idiopathic pulmonary arterial hypertension (IPAH). While vasoconstrictor mediators constrict both PA and DA and vasodilators dilate both vessels, only redox changes mimic oxygen by having directly opposite effects on the K+ channels, membrane potential, [Ca++]i and tone in the PA and DA. There are several different hypotheses as to how redox might alter tone, which remain to be resolved. However, understanding the mechanism will facilitate drug development for pulmonary hypertension and patent DA. PMID:18641675

Idiopathic Intracranial Hypertension (Pseudotumor Cerebri)

MedlinePlus

... Asked Questions Español Condiciones Chinese Conditions Idiopathic Intracranial Hypertension (Pseudotumor Cerebri) En Español Read in Chinese What is idiopathic intracranial hypertension? Idiopathic intracranial hypertension (IIH) is a disorder that ...

MECHANISMS OF HUMAN KIDNEY STONE FORMATION

PubMed Central

Evan, Andrew P.; Worcester, Elaine M.; Coe, Fredric L.; Williams, James; Lingeman, James E.

2014-01-01

The precise mechanisms of kidney stone formation and growth are not completely known, even though human stone disease appears to be one of the oldest diseases known to medicine. With the advent of the new digital endoscope and detailed renal physiological studies performed on well phenotyped stone formers, substantial advances have been made in our knowledge of the pathogenesis of the most common type of stone former, the idiopathic calcium oxalate stone former (ICSF) as well as nine other stone forming groups. The observations from our group on human stone formers and those of others on model systems have suggested four entirely different pathways for kidney stone formation. Calcium oxalate stone growth over sites of Randall’s plaque appear to be the primary mode of stone formation for those patients with hypercalciuria. Overgrowths off the ends of Bellini duct plugs have been noted in most stone phenotypes, do they result in a clinical stone? Micro-lith formation does occur within the lumens of dilated inner medullary collecting ducts of cystinuric stone formers and appear to be confined to this space. Lastly, cystinuric stone formers also have numerous small, oval, smooth yellow appearing calyceal stones suggestive of formation in free solution. The scientific basis for each of these four modes of stone formation are reviewed and used to explore novel research opportunities. PMID:25108546

Protecting Bone Health in Pediatric Rheumatic Diseases: Pharmacological Considerations.

PubMed

Zhang, Yujuan; Milojevic, Diana

2017-06-01

Bone health in children with rheumatic conditions may be compromised due to several factors related to the inflammatory disease state, delayed puberty, altered life style, including decreased physical activities, sun avoidance, suboptimal calcium and vitamin D intake, and medical treatments, mainly glucocorticoids and possibly some disease-modifying anti-rheumatic drugs. Low bone density or even fragility fractures could be asymptomatic; therefore, children with diseases of high inflammatory load, such as systemic onset juvenile idiopathic arthritis, juvenile dermatomyositis, systemic lupus erythematosus, and those requiring chronic glucocorticoids may benefit from routine screening of bone health. Most commonly used assessment tools are laboratory testing including serum 25-OH-vitamin D measurement and bone mineral density measurement by a variety of methods, dual-energy X-ray absorptiometry as the most widely used. Early disease control, use of steroid-sparing medications such as disease-modifying anti-rheumatic drugs and biologics, supplemental vitamin D and calcium, and promotion of weight-bearing physical activities can help optimize bone health. Additional treatment options for osteoporosis such as bisphosphonates are still controversial in children with chronic rheumatic diseases, especially those with decreased bone density without fragility fractures. This article reviews common risk factors leading to compromised bone health in children with chronic rheumatic diseases and discusses the general approach to prevention and treatment of bone fragility.

Procoagulant expression in platelets and defects leading to clinical disorders.

PubMed

Solum, N O

1999-12-01

Hemostasis is a result of interactions between fibrillar structures in the damaged vessel wall, soluble components in plasma, and cellular elements in blood represented mainly by platelets and platelet-derived material. During formation of a platelet plug at the damaged vessel wall, factors IXa and VIIIa form the "tenase" complex, leading to activation of factor X on the surface of activated platelets. Subsequently, factors Xa and Va form the "prothrombinase" complex, which catalyzes the formation of thrombin from prothrombin, leading to fibrin formation. An enhanced expression of negatively charged phosphatidylserine in the outer membrane leaflet resulting from a breakdown of the phospholipid asymmetry is essential for the formation of the procoagulant surface. An ATP-driven and inward-acting aminophospholipid "translocase" and a "floppase" counterbalancing this have been postulated to maintain the dynamic state of phospholipid asymmetry. A phospholipid-nonspecific "scramblase," believed to be responsible for the fast breakdown of the asymmetry during cell activation, has recently been isolated from erythrocytes, cloned, and characterized. An intracellular calcium-binding segment and one or more thioesterified fatty acids are probably of importance for calcium-induced activation of this transporter protein. Cytosolic calcium ions also activate the calcium-dependent protease calpain associated with shedding of microvesicles from the transformed platelet membrane. These are shed with a procoagulant surface and with surface-exposed P-selectin from the alpha-granules. Theoretically, therefore, microvesicles can be involved in both coagulation and inflammation. Scott syndrome is probably caused by a defect in the activation of an otherwise normal scramblase, resulting in a relatively severe bleeding tendency. In Stormorken syndrome, the patients demonstrate a spontaneous surface expression of aminophospholipids. Activated platelets and the presence of procoagulant microvesicles have been demonstrated in several clinical conditions, such as thrombotic and idiopathic thrombocytopenia, disseminated intravascular coagulation, and HIV-1 infection, and have been found to be associated with fibrin in thrombosis. Procoagulant microvesicles may also be formed from other cells as a result of apoptosis.

HYPERCALCURIA AND METABOLIC BONE DISEASE

PubMed Central

Rosenberg, Milton L.

1954-01-01

Hypercalcuria leading to nephrocalcinosis and nephrolithiasis may be secondary to a number of causes. In most instances, the history, physical examination, a few simple laboratory tests and x-ray study of the bones will reveal the true primary diagnosis. Specific treatment, if instituted early, will result in a satisfactory response and prevent the progression of renal complications. ImagesFigure 1.Figure 2.Figure 3.Figure 4. PMID:13209371

Risk of chronic and end stage kidney disease in patients with nephrolithiasis.

PubMed

Shoag, Jonathan; Halpern, Joshua; Goldfarb, David S; Eisner, Brian H

2014-11-01

We examine kidney stone disease as a potential risk factor for chronic kidney disease, end stage kidney disease and treatment with dialysis. The NHANES (National Health and Nutrition Examination Survey) 2007-2010 database was interrogated for patients with a history of kidney stones. Demographics and comorbid conditions including age, gender, body mass index, diabetes, hemoglobin A1c, hypertension, gout and smoking were also assessed. Multivariate analysis adjusting for patient demographics and comorbidities was performed to assess differences in the prevalence of chronic kidney disease and treatment with dialysis between the 2 groups. History of nephrolithiasis was assessed with the question, "Have you ever had kidney stones?" Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 ml/minute/1.73 m(2) and/or a urinary albumin-to-creatinine ratio greater than 30 mg/gm. Statistical calculations were performed using Stata® software with determinations of p values and 95% CI where appropriate. The study included an analysis of 5,971 NHANES participants for whom data on chronic kidney disease and kidney stones were available, of whom 521 reported a history of kidney stones. On multivariate analysis a history of kidney stones was associated with chronic kidney disease and treatment with dialysis (OR 1.50, 1.10-2.04, p = 0.013 and OR 2.37, 1.13-4.96, p = 0.025, respectively). This difference appeared to be driven by women, where a history of kidney stones was associated with a higher prevalence of chronic kidney disease (OR 1.76, 1.13-2.763, p = 0.016) and treatment with dialysis (OR 3.26, 1.48-7.16, p = 0.004). There was not a significant association between kidney stone history and chronic kidney disease or treatment with dialysis in men. Kidney stone history is associated with an increased risk of chronic kidney disease and treatment with dialysis among women even after adjusting for comorbid conditions. Large scale prospective studies are needed to further characterize the relationship between nephrolithiasis and chronic kidney disease. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Ultrasonography versus computed tomography for suspected nephrolithiasis.

PubMed

Smith-Bindman, Rebecca; Aubin, Chandra; Bailitz, John; Bengiamin, Rimon N; Camargo, Carlos A; Corbo, Jill; Dean, Anthony J; Goldstein, Ruth B; Griffey, Richard T; Jay, Gregory D; Kang, Tarina L; Kriesel, Dana R; Ma, O John; Mallin, Michael; Manson, William; Melnikow, Joy; Miglioretti, Diana L; Miller, Sara K; Mills, Lisa D; Miner, James R; Moghadassi, Michelle; Noble, Vicki E; Press, Gregory M; Stoller, Marshall L; Valencia, Victoria E; Wang, Jessica; Wang, Ralph C; Cummings, Steven R

2014-09-18

There is a lack of consensus about whether the initial imaging method for patients with suspected nephrolithiasis should be computed tomography (CT) or ultrasonography. In this multicenter, pragmatic, comparative effectiveness trial, we randomly assigned patients 18 to 76 years of age who presented to the emergency department with suspected nephrolithiasis to undergo initial diagnostic ultrasonography performed by an emergency physician (point-of-care ultrasonography), ultrasonography performed by a radiologist (radiology ultrasonography), or abdominal CT. Subsequent management, including additional imaging, was at the discretion of the physician. We compared the three groups with respect to the 30-day incidence of high-risk diagnoses with complications that could be related to missed or delayed diagnosis and the 6-month cumulative radiation exposure. Secondary outcomes were serious adverse events, related serious adverse events (deemed attributable to study participation), pain (assessed on an 11-point visual-analogue scale, with higher scores indicating more severe pain), return emergency department visits, hospitalizations, and diagnostic accuracy. A total of 2759 patients underwent randomization: 908 to point-of-care ultrasonography, 893 to radiology ultrasonography, and 958 to CT. The incidence of high-risk diagnoses with complications in the first 30 days was low (0.4%) and did not vary according to imaging method. The mean 6-month cumulative radiation exposure was significantly lower in the ultrasonography groups than in the CT group (P<0.001). Serious adverse events occurred in 12.4% of the patients assigned to point-of-care ultrasonography, 10.8% of those assigned to radiology ultrasonography, and 11.2% of those assigned to CT (P=0.50). Related adverse events were infrequent (incidence, 0.4%) and similar across groups. By 7 days, the average pain score was 2.0 in each group (P=0.84). Return emergency department visits, hospitalizations, and diagnostic accuracy did not differ significantly among the groups. Initial ultrasonography was associated with lower cumulative radiation exposure than initial CT, without significant differences in high-risk diagnoses with complications, serious adverse events, pain scores, return emergency department visits, or hospitalizations. (Funded by the Agency for Healthcare Research and Quality.).

Can Stoss Therapy Be Used in Children with Vitamin D Deficiency or Insufficiency without Rickets?

PubMed

Koçyiğit, Cemil; Çatlı, Gönül; İnce, Gülberat; Özkan, Elif Büşra; Dündar, Bumin Nuri

2017-06-01

Stoss vitamin D treatment has been recommended for its non-skeletal benefits in adults, but there is a lack of data on the optimal dose of vitamin D stoss therapy in children with vitamin D deficiency/insufficiency without rickets. This study aimed to compare efficiency/side effects of two different stoss therapy regimens (10 000 IU/kg and 300 000 IU vitamin D3) administered in children with vitamin D deficiency/insufficiency without rickets. Sixty-four children who had vitamin D deficiency/insufficiency were studied. A serum 25-hydroxyvitamin-D (25-OH-D) level of 15-20 ng/mL was considered as vitamin D insufficient and <15 ng/mL was considered as vitamin D deficient. The patients were divided into two groups according to the stoss therapy doses they received. Serum calcium, phosphate, alkaline phosphatase, 25-OH-D, parathyroid hormone levels, and spot urine calcium/creatinine ratios before/after treatment were recorded. Wrist radiography and renal ultrasonography were performed. The mean age of the subjects was 10.6±4.4 years. Thirty-two children were treated with a single vitamin D3 dose of 10 000 IU/kg and 32 patients received 300 000 IU. No difference was found in 25-OH-D levels between the two groups at presentation. The mean level of 25-OH-D was higher in the 10 000 IU/kg group at the second week of therapy. There was no difference between the groups at post-treatment weeks 4 and 12. The 25-OH-D was found to be below optimal levels (≥30 ng/mL) in 66.5% and <20 ng/mL in 21.8% of patients at the third month in both groups. None developed hypercalcemia and/or hypercalciuria. Nephrolithiasis was not detected in any patient. This study showed that both doses of stoss therapy used in the treatment of vitamin D insufficiency/deficiency are effective and safe. However, an optimal level of 25-OH-D cannot be maintained for more than three months.

Effect of urine pH and magnesium on calcium oxalate saturation.

PubMed

Ferrè, Silvia; Grange, Jacob S; Adams-Huet Ms, Beverley; Moe, Orson W; Maalouf, Naim M

2017-11-01

Hypomagnesiuria is a common biochemical finding in patients with calcium oxalate (CaOx) nephrolithiasis. Clinical trials using Mg supplements as therapy against CaOx stones have shown mixed results. We tested the effect of Mg administration in healthy subjects under conditions of controlled urine pH (UpH) on urinary Ca excretion rate (UCaV) and CaOx saturation. This is a 4-phase, double blind, placebo-controlled, metabolic crossover study performed in healthy volunteers. Mg lactate (MgLact 2 ) was used as Mg supplement. High UpH and low UpH were achieved by administration of potassium citrate (K 3 Citrate) and ammonium chloride (NH 4 Cl), respectively, with potassium balance maintained by KCl. Eight participants completed 4 phases of study. The interventions successfully modulated 24-h UpH (7.0 ± 0.4 vs. 5.7 ± 0.6 in high vs low pH phases; P<0.001). Administration of MgLact 2 increased UMgV [175.8 ± 40.2 vs 93.4 ± 39.7 mg/day (7.2 ± 1.7 vs 3.8 ± 1.6 mmol/day), high vs low Mg phase; P<0.001], and increased pH both at low (5.6 ± 0.5 to 5.8 ± 0.7; P = 0.02) and high UpH (6.9 ± 0.4 to 7.0 ± 0.3; P = 0.01). At a given urine pH, Mg supplementation marginally increased UCaV, but did not alter UOxV or CaOx saturation. Provision of an alkali load significantly lowered UCaV and saturation of CaOx at any level of UMgV. Compared to changes in UMgV, changes in UpH play a more significant role in determining urine CaOx saturation in healthy subjects. Mg supplements are likely to reduce CaOx saturation if they also raise urine pH.

Idiopathic Ophthalmodynia and Idiopathic Rhinalgia: A Prospective Series of 16 New Cases.

PubMed

Pareja, Juan A; Montojo, Teresa; Guerrero, Ángel L; Álvarez, Mónica; Porta-Etessam, Jesús; Cuadrado, María L

2015-01-01

Idiopathic ophthalmodynia and idiopathic rhinalgia were described a few years ago. These conditions seem specific pain syndromes with a distinctive location in the eye or in the nose. We aimed to present a new prospective series in order to verify the consistency of these syndromes. We performed a descriptive study of all patients referred to our regional neurologic clinics from 2010 to 2014 because of facial pain exclusively felt in the eye or in the nose fulfilling the proposed diagnostic criteria for idiopathic ophthalmodynia and idiopathic rhinalgia. There were 9 patients with idiopathic ophthalmodynia and 7 patients with idiopathic rhinalgia, with a clear female preponderance, and a mean age at onset in the fifth decade. The pain was usually moderate and the temporal pattern was generally chronic. Only one patient reported accompaniments (hypersensitivity to the light and to the flow of air in the symptomatic eye). Preventive treatment with amitriptyline, pregabalin, or gabapentin was partially or totally effective. The clinical features of this new series parallels those of the original description, thus indicating that both idiopathic ophthalmodynia and idiopathic rhinalgia have clear-cut clinical pictures with excellent consistency both inter- and intra-individually. © 2015 American Headache Society.

[Determination of 25(OH)D serum levels in children with systemic lupus erythematosus and juvenile idiopathic arthritis].

PubMed

Rosiles, Vanessa Hernández; Salazar, Carolina Duarte; Velazquez, Rocío Maldonado; Ruiz, Rodolfo Rivas; Clark, Patricia

It is well recognized that vitamin D has a direct effect in bone and muscle and has been associated as well with some rheumatologic diseases. Reports in children are scarce. The aim of this study was to determine the concentration level of 25(OH)D in a group of patients with systemic lupus erythematosus (SLE) and juvenile idiopathic arthritis (JIA) and compare them with healthy controls. Vitamin D (25(OH)D) was measured with isotope-dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS), PTH with immunoradiometric assay (IRMA), calcium, phosphorus and alkaline phosphatase by colorimetric assay in 37 patients with SLE, 37 patients with JIA and 79 healthy controls. Mean 25(OH)D concentration levels were as follows: SLE 18.9±7.92ng/ml, JIA 21.97±5.55ng/ml and 23.6±3.07ng/ml in healthy controls. There was a significant difference between SLE patients vs. healthy controls (p <0.05); 29.7% of SLE patients, 35.1% of JIA patients and 31.6% of healthy controls had deficient levels of vitamin D. One third of the total sample of children in this study had deficient levels of vitamin D. Patients with SLE presented a significant difference compared with healthy controls. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Vertebral Fractures and Bone Mineral Density in Patients With Idiopathic Hypoparathyroidism on Long-Term Follow-Up.

PubMed

Chawla, Himika; Saha, Soma; Kandasamy, Devasenathipathy; Sharma, Raju; Sreenivas, Vishnubhatla; Goswami, Ravinder

2017-01-01

Bone mineral density (BMD) is increased in idiopathic hypoparathyroidism (IH). Parathyroid hormone (PTH) deficiency, hypocalcemic seizures, and anticonvulsants could compromise skeletal health in IH. We assessed vertebral fractures (VFs) and related factors in IH and change in BMD during follow-up. VFs were assessed by morphometry. BMD was assessed by dual-energy X-ray absorptiometery at the lumbar spine, hip, and forearm. Change in BMD was assessed in a subset after a 10-year follow-up. The endocrine clinic of All India Institute of Medical Sciences, New Delhi, India. Included were 104 patients with IH and 64 healthy controls. Hypocalcemia, hyperphosphatemia, normal kidney function, and low serum PTH levels were used to diagnose IH. VFs were seen in 18.3% of patients with IH and 4.7% of controls (odds ratio, 4.54; 95% confidence interval, 1.28 to 16.04). Use of anticonvulsants and menopause were significantly associated (P < 0.05) with VF. Mean BMD at lumbar spine and hip were higher by 21.4% and 8.6%, respectively, in IH than in controls (P < 0.001), respectively. BMD significantly increased during follow-up at all sites. Change in BMD correlated with maintenance of the serum calcium/phosphorus ratio during follow-up. Despite increased BMD, prevalence of vertebral-fractures is greater in patients with IH, especially in postmenopausal women and those on anticonvulsant therapy. Copyright © 2017 by the Endocrine Society

Current insights into the aetiology of adolescent idiopathic scoliosis.

PubMed

Latalski, Michal; Danielewicz-Bromberek, A; Fatyga, M; Latalska, M; Kröber, M; Zwolak, P

2017-10-01

Scoliosis occurs in about 0.2-0.6% of the general population. In the majority of cases the cause of this entity remains mostly unidentified. The search for the causes covers almost all aspects of its possible origin. We collected and systematised the contemporary theories and concepts concerning the aetiology of adolescent idiopathic scoliosis. Genetic and hereditary factors are commonly accepted as possible causes; however, the identification of the single gene responsible for the development of this condition seems impossible, which suggests multifactorial mechanism of its formation. Dysfunctions of the nervous system are recognised risks related to the development of scoliosis, but they are classified as belonging to a separate aetiological category. Scoliosis develops at the quickest rate during the child's growth spurt, which prompted the research on the role of the growth hormone in scoliosis aetiology. Melatonin is another hormone that is studied as a possible factor involved in development of this entity. In cases of progressive scoliosis, increased activity of calmodulin-a protein that regulates the levels of calcium ions-has been observed. The scientists have characterised numerous qualitative and quantitative changes in the composition of the tissue of intervertebral discs, spinal ligaments and paraspinal muscles. Some of the theories, explaining the nature of this entity, presented in this review seem to have only a purely theoretical value; their proliferation only confirms the fact that the actual nature of this condition has not been unveiled yet, and suggests its multifactorial aetiology.

Fluid Distribution Pattern in Adult-Onset Congenital, Idiopathic, and Secondary Normal-Pressure Hydrocephalus: Implications for Clinical Care.

PubMed

Yamada, Shigeki; Ishikawa, Masatsune; Yamamoto, Kazuo

2017-01-01

In spite of growing evidence of idiopathic normal-pressure hydrocephalus (NPH), a viewpoint about clinical care for idiopathic NPH is still controversial. A continuous divergence of viewpoints might be due to confusing classifications of idiopathic and adult-onset congenital NPH. To elucidate the classification of NPH, we propose that adult-onset congenital NPH should be explicitly distinguished from idiopathic and secondary NPH. On the basis of conventional CT scan or MRI, idiopathic NPH was defined as narrow sulci at the high convexity in concurrent with enlargement of the ventricles, basal cistern and Sylvian fissure, whereas adult-onset congenital NPH was defined as huge ventricles without high-convexity tightness. We compared clinical characteristics and cerebrospinal fluid distribution among 85 patients diagnosed with idiopathic NPH, 17 patients with secondary NPH, and 7 patients with adult-onset congenital NPH. All patients underwent 3-T MRI examinations and tap-tests. The volumes of ventricles and subarachnoid spaces were measured using a 3D workstation based on T2-weighted 3D sequences. The mean intracranial volume for the patients with adult-onset congenital NPH was almost 100 mL larger than the volumes for patients with idiopathic and secondary NPH. Compared with the patients with idiopathic or secondary NPH, patients with adult-onset congenital NPH exhibited larger ventricles but normal sized subarachnoid spaces. The mean volume ratio of the high-convexity subarachnoid space was significantly less in idiopathic NPH than in adult-onset congenital NPH, whereas the mean volume ratio of the basal cistern and Sylvian fissure in idiopathic NPH was >2 times larger than that in adult-onset congenital NPH. The symptoms of gait disturbance, cognitive impairment, and urinary incontinence in patients with adult-onset congenital NPH tended to progress more slowly compared to their progress in patients with idiopathic NPH. Cerebrospinal fluid distributions and disease progression were significantly different among the patients with adult-onset congenital NPH, idiopathic NPH and secondary NPH. This finding indicates that the pathogenesis of adult-onset congenital NPH may differ from those of idiopathic and secondary NPH. Therefore, adult-onset congenital NPH should be definitively distinguished from the categories of idiopathic and secondary NPH.

Effects of food and antacids on the pharmacokinetics of eltrombopag in healthy adult subjects: two single-dose, open-label, randomized-sequence, crossover studies.

PubMed

Williams, Daphne D; Peng, Bin; Bailey, Christine K; Wire, Mary B; Deng, Yanli; Park, Jung Wook; Collins, David A; Kapsi, Shiva G; Jenkins, Julian M

2009-04-01

Eltrombopag is the first orally self-administered, small-molecule, nonpeptide thrombopoietin receptor agonist for the treatment of chronic idiopathic thrombocytopenic purpura. The aim of these studies was to assess the effect of food and antacids on the pharmacokinetic and safety profiles of eltrombopag. Two independent, single-dose, open-label, randomized-sequence, crossover studies of oral eltrombopag were conducted in healthy adult volunteers. The first study (study A) compared eltrombopag 50 mg (tablets or capsules) administered in the fasted state or tablets with a high-fat, high-calcium breakfast. The second study (study B) investigated eltrombopag tablets (75 mg) administered in the fasted state; immediately after a low-fat, low-calcium meal or a high-fat, low-calcium meal; 1 hour before a high-fat, low-calcium meal; or with an antacid containing aluminum hydroxide and magnesium carbonate. Vital signs were recorded and electrocardiogram and clinical laboratory tests were performed at screening, within 24 hours before and within 48 hours after each dose of study medication. Symptom assessment was performed and adverse events (AEs) were assessed previous to study drug administration through follow-up in terms of severity and relationship to study medication. In study A, 18 male subjects (mean age, 23.0 years; weight, 70.3 kg; white race, 94.4%) who received a high-fat, high-calcium breakfast had reduced bioavailability of eltrombopag in terms of AUC(0-infinity)) by 59% (geometric mean ratio [GMR], 0.41; 90% CI, 0.36-0.46) and C(max) by 65% (GMR, 0.35; 90% CI, 0.30-0.41) compared with subjects in a fasted state. In study B, the bioavailability in 26 subjects (14 male, 12 female; mean age, 35.6 years; weight, 76.0 kg; white race, 65.4%) was not significantly changed when administered with food that was low in calcium, despite the fat content (GMRs ranged from 0.87-1.03 for AUC(0-infinity) and 0.85-1.01 for C(max) across the 3 studied meals). Mean plasma AUC(0-infinity)) and C(max) values decreased by approximately 70% (GMR, 0.30; 90% CI, 0.24-0.36 for AUC(0-infinity)) and 0.24-0.38 for C(max)) when administered with a metal cation-containing antacid. No serious AEs were reported and all AEs were rated as mild to moderate in intensity. The most frequently reported AE was headache (study A, 6.3%; study B, 12.0%-29.2%). Concomitant administration of eltrombopag with high-calcium food or an antacid containing aluminum and magnesium was associated with significantly reduced systemic exposure, whereas low-calcium meals were not. A single dose of eltrombopag was generally well tolerated in these healthy volunteers.

Expression of HSP47 in Usual Interstitial Pneumonia and Nonspecific Interstitial Pneumonia

PubMed Central

Kakugawa, Tomoyuki; Mukae, Hiroshi; Hayashi, Tomayoshi; Ishii, Hiroshi; Nakayama, Seiko; Sakamoto, Noriho; Yoshioka, Sumako; Sugiyama, Kanako; Mine, Mariko; Mizuta, Yohei; Kohno, Shigeru

2005-01-01

Background Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagens, and its expression is increased in various fibrotic diseases. The aim of this study was to determine whether quantitative immunohistochemical evaluation of the expression levels of HSP47, type I procollagen and α-smooth muscle actin (SMA) allows the differentiation of idiopathic usual interstitial pneumonia (UIP) from UIP associated with collagen vascular disease (CVD) and idiopathic nonspecific interstitial pneumonia (NSIP). Methods We reviewed surgical lung biopsy specimens of 19 patients with idiopathic UIP, 7 with CVD-associated UIP and 16 with idiopathic NSIP and assigned a score for the expression of HSP47, type I procollagen and α-SMA in type II pneumocytes and/or lung fibroblasts (score 0 = no; 1 = weak; 2 = moderate; 3 = strong staining). Results The expression level of HSP47 in type II pneumocytes of idiopathic UIP was significantly higher than in CVD-associated UIP and idiopathic NSIP. The expression of HSP47 in fibroblasts was significantly higher in idiopathic UIP and idiopathic NSIP than in CVD-associated UIP. The expression of type I procollagen in type II pneumocytes was significantly higher in idiopathic UIP than in idiopathic NSIP. The expression of type I procollagen in fibroblasts was not different in the three groups, while the expression of α-SMA in fibroblasts was significantly higher in idiopathic UIP than in idiopathic NSIP. Conclusion Our results suggest the existence of different fibrotic pathways among these groups involved in the expression of HSP47 and type I procollagen. PMID:15955241

Bardoxolone Methyl Evaluation in Patients With Pulmonary Hypertension (PH) - LARIAT

ClinicalTrials.gov

2018-06-08

Pulmonary Arterial Hypertension; Pulmonary Hypertension; Interstitial Lung Disease; Idiopathic Interstitial Pneumonia; Idiopathic Pulmonary Fibrosis; Sarcoidosis; Respiratory Bronchiolitis Associated Interstitial Lung Disease; Desquamative Interstitial Pneumonia; Cryptogenic Organizing Pneumonia; Acute Interstitial Pneumonitis; Idiopathic Lymphoid Interstitial Pneumonia; Idiopathic Pleuroparenchymal Fibroelastosis

Surgical Management of Nephrolithiasis in the Bottlenose Dolphin: Collaborations Between the Urologist and Veterinarian.

PubMed

Sur, Roger L; Meegan, Jenny M; Smith, Cynthia R; Schmitt, Todd; L'Esperance, James; Hendrikson, Dean; Woo, Jason R

2018-01-01

Background: Cohorts of bottlenose ( Tursiops truncatus ) dolphins are at significant risk for nephrolithiasis development. However, effective surgical treatment has been limited due to absence of literature and also familiarity by both veterinarians and urologists. Recently a joint veterinarian and urology team were called to treat local bottlenose dolphins in San Diego, CA, and they performed several cases. The fund of knowledge from these cases is presented for future providers who may be asked to surgically treat these animals. Case Presentation: Two surgical kidney stone cases were performed by a joint veterinarian and physician team. An effective ureteroscopic stone removal was performed on a 39-year-old female bottlenose dolphin with 9.7 mm distal ureteral calculus. The second case involved laparoscopic ureterolithotomy on a 31-year-old male bottlenose dolphin with a 6-mm right distal ureteral calculus that previously failed retrograde ureteroscopic removal. The stone was not effectively removed laparoscopically as well due to failure to progress associated with operative machinery malfunction. The dolphin was ultimately euthanized. Conclusion: Despite suboptimal outcome in one case, extremely valuable lessons were learned during both cases. We present our surgical experiences, as well as pertinent anatomical differences, in these animals with the hope that this discussion will facilitate future surgical kidney stone treatment of dolphins.

Surgical Management of Nephrolithiasis in the Bottlenose Dolphin: Collaborations Between the Urologist and Veterinarian

PubMed Central

Meegan, Jenny M.; Smith, Cynthia R.; Schmitt, Todd; L'Esperance, James; Hendrikson, Dean; Woo, Jason R.

2018-01-01

Abstract Background: Cohorts of bottlenose (Tursiops truncatus) dolphins are at significant risk for nephrolithiasis development. However, effective surgical treatment has been limited due to absence of literature and also familiarity by both veterinarians and urologists. Recently a joint veterinarian and urology team were called to treat local bottlenose dolphins in San Diego, CA, and they performed several cases. The fund of knowledge from these cases is presented for future providers who may be asked to surgically treat these animals. Case Presentation: Two surgical kidney stone cases were performed by a joint veterinarian and physician team. An effective ureteroscopic stone removal was performed on a 39-year-old female bottlenose dolphin with 9.7 mm distal ureteral calculus. The second case involved laparoscopic ureterolithotomy on a 31-year-old male bottlenose dolphin with a 6-mm right distal ureteral calculus that previously failed retrograde ureteroscopic removal. The stone was not effectively removed laparoscopically as well due to failure to progress associated with operative machinery malfunction. The dolphin was ultimately euthanized. Conclusion: Despite suboptimal outcome in one case, extremely valuable lessons were learned during both cases. We present our surgical experiences, as well as pertinent anatomical differences, in these animals with the hope that this discussion will facilitate future surgical kidney stone treatment of dolphins. PMID:29756043

Metabolic syndrome and uric acid nephrolithiasis: insulin resistance in focus.

PubMed

Spatola, Leonardo; Ferraro, Pietro Manuel; Gambaro, Giovanni; Badalamenti, Salvatore; Dauriz, Marco

2018-06-01

Uric acid nephrolithiasis (UAN) is an increasingly common disease in ethnically diverse populations and constitutes about 10% of all kidney stones. Metabolic syndrome and diabetes mellitus are accounted among the major risk factors for UAN, together with environmental exposure, individual lifestyle habits and genetic predisposition. The development and overt manifestation of UAN appears to stem on the background of insulin resistance, which acts at the kidney level by reducing urinary pH, thus hampering the ability of the kidney to generate renal ammonium in response to an acid load. Unduly acidic urinary pH and overt UAN are both considered renal manifestations of insulin resistance. The mechanisms underlying increased endogenous acid production and/or defective ammonium excretion are yet to be completely understood. Although the development of UAN and, more in general, of kidney stones largely recognizes modifiable individual determining factors, the rising prevalence of diabetes, obesity and accompanying metabolic disorders calls for the identification of novel therapeutic approaches and intervention targets. This review aims at providing an updated picture of existing evidence on the relationship between insulin resistance and UAN in the context of metabolic syndrome and in light of the most recent advancements in our understanding of its genetic signature. Copyright © 2018. Published by Elsevier Inc.

Sigmoid Sinus Diverticulum, Dehiscence, and Venous Sinus Stenosis: Potential Causes of Pulsatile Tinnitus in Patients with Idiopathic Intracranial Hypertension?

PubMed

Lansley, J A; Tucker, W; Eriksen, M R; Riordan-Eva, P; Connor, S E J

2017-09-01

Pulsatile tinnitus is experienced by most patients with idiopathic intracranial hypertension. The pathophysiology remains uncertain; however, transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence have been proposed as potential etiologies. We aimed to determine whether the prevalence of transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence was increased in patients with idiopathic intracranial hypertension and pulsatile tinnitus relative to those without pulsatile tinnitus and a control group. CT vascular studies of patients with idiopathic intracranial hypertension with pulsatile tinnitus ( n = 42), without pulsatile tinnitus ( n = 37), and controls ( n = 75) were independently reviewed for the presence of severe transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence according to published criteria. The prevalence of transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence in patients with idiopathic intracranial hypertension with pulsatile tinnitus was compared with that in the nonpulsatile tinnitus idiopathic intracranial hypertension group and the control group. Further comparisons included differing degrees of transverse sinus stenosis (50% and 75%), laterality of transverse sinus stenosis/sigmoid sinus diverticulum/dehiscence, and ipsilateral transverse sinus stenosis combined with sigmoid sinus diverticulum/dehiscence. Severe bilateral transverse sinus stenoses were more frequent in patients with idiopathic intracranial hypertension than in controls ( P < .001), but there was no significant association between transverse sinus stenosis and pulsatile tinnitus within the idiopathic intracranial hypertension group. Sigmoid sinus dehiscence (right- or left-sided) was also more common in patients with idiopathic intracranial hypertension compared with controls ( P = .01), but there was no significant association with pulsatile tinnitus within the idiopathic intracranial hypertension group. While our data corroborate previous studies demonstrating increased prevalence of sigmoid sinus diverticulum/dehiscence and transverse sinus stenosis in idiopathic intracranial hypertension, we did not establish an increased prevalence in patients with idiopathic intracranial hypertension with pulsatile tinnitus compared with those without. It is therefore unlikely that these entities represent a direct structural correlate of pulsatile tinnitus in patients with idiopathic intracranial hypertension. © 2017 by American Journal of Neuroradiology.

Comparison of CSF Distribution between Idiopathic Normal Pressure Hydrocephalus and Alzheimer Disease.

PubMed

Yamada, S; Ishikawa, M; Yamamoto, K

2016-07-01

CSF volumes in the basal cistern and Sylvian fissure are increased in both idiopathic normal pressure hydrocephalus and Alzheimer disease, though the differences in these volumes in idiopathic normal pressure hydrocephalus and Alzheimer disease have not been well-described. Using CSF segmentation and volume quantification, we compared the distribution of CSF in idiopathic normal pressure hydrocephalus and Alzheimer disease. CSF volumes were extracted from T2-weighted 3D spin-echo sequences on 3T MR imaging and quantified semi-automatically. We compared the volumes and ratios of the ventricles and subarachnoid spaces after classification in 30 patients diagnosed with idiopathic normal pressure hydrocephalus, 10 with concurrent idiopathic normal pressure hydrocephalus and Alzheimer disease, 18 with Alzheimer disease, and 26 control subjects 60 years of age or older. Brain to ventricle ratios at the anterior and posterior commissure levels and 3D volumetric convexity cistern to ventricle ratios were useful indices for the differential diagnosis of idiopathic normal pressure hydrocephalus or idiopathic normal pressure hydrocephalus with Alzheimer disease from Alzheimer disease, similar to the z-Evans index and callosal angle. The most distinctive characteristics of the CSF distribution in idiopathic normal pressure hydrocephalus were small convexity subarachnoid spaces and the large volume of the basal cistern and Sylvian fissure. The distribution of the subarachnoid spaces in the idiopathic normal pressure hydrocephalus with Alzheimer disease group was the most deformed among these 3 groups, though the mean ventricular volume of the idiopathic normal pressure hydrocephalus with Alzheimer disease group was intermediate between that of the idiopathic normal pressure hydrocephalus and Alzheimer disease groups. The z-axial expansion of the lateral ventricle and compression of the brain just above the ventricle were the common findings in the parameters for differentiating idiopathic normal pressure hydrocephalus from Alzheimer disease. © 2016 by American Journal of Neuroradiology.

Comparison of monocyte gene expression among patients with neurocysticercosis-associated epilepsy, Idiopathic Epilepsy and idiopathic headaches in India.

PubMed

Prabhakaran, Vasudevan; Drevets, Douglas A; Ramajayam, Govindan; Manoj, Josephine J; Anderson, Michael P; Hanas, Jay S; Rajshekhar, Vedantam; Oommen, Anna; Carabin, Hélène

2017-06-01

Neurocysticercosis (NCC), a neglected tropical disease, inflicts substantial health and economic costs on people living in endemic areas such as India. Nevertheless, accurate diagnosis using brain imaging remains poorly accessible and too costly in endemic countries. The goal of this study was to test if blood monocyte gene expression could distinguish patients with NCC-associated epilepsy, from NCC-negative imaging lesion-free patients presenting with idiopathic epilepsy or idiopathic headaches. Patients aged 18 to 51 were recruited from the Department of Neurological Sciences, Christian Medical College and Hospital, Vellore, India, between January 2013 and October 2014. mRNA from CD14+ blood monocytes was isolated from 76 patients with NCC, 10 Recovered NCC (RNCC), 29 idiopathic epilepsy and 17 idiopathic headaches patients. A preliminary microarray analysis was performed on six NCC, six idiopathic epilepsy and four idiopathic headaches patients to identify genes differentially expressed in NCC-associated epilepsy compared with other groups. This analysis identified 1411 upregulated and 733 downregulated genes in patients with NCC compared to Idiopathic Epilepsy. Fifteen genes up-regulated in NCC patients compared with other groups were selected based on possible relevance to NCC, and analyzed by qPCR in all patients' samples. Differential gene expression among patients was assessed using linear regression models. qPCR analysis of 15 selected genes showed generally higher gene expression among NCC patients, followed by RNCC, idiopathic headaches and Idiopathic Epilepsy. Gene expression was also generally higher among NCC patients with single cyst granulomas, followed by mixed lesions and single calcifications. Expression of certain genes in blood monocytes can distinguish patients with NCC-related epilepsy from patients with active Idiopathic Epilepsy and idiopathic headaches. These findings are significant because they may lead to the development of new tools to screen for and monitor NCC patients without brain imaging.

Relation between adolescent idiopathic scoliosis and morphologic somatotypes.

PubMed

LeBlanc, R; Labelle, H; Rivard, C H; Poitras, B

1997-11-01

A prospective and controlled comparative study. To verify the difference in morphologic appearance between a group of adolescents with progressive adolescent idiopathic scoliosis and a control group of normal adolescents. In a previous retrospective study, the possibility of a relation between progressive adolescent idiopathic scoliosis and specific morphotypes was demonstrated. Fifty-two adolescent girls with progressive adolescent idiopathic scoliosis were compared with an age-matched control group of 62 unaffected girls using a classification technique based on morphologic somatotypes. Morphotypes were evaluated with standardized pre-established criteria based on Sheldon's technique. Patients with progressive adolescent idiopathic scoliosis showed significantly less mesomorphism (mean value of 0.88 +/- 0.51) than control girls (mean value of 1.72 +/- 0.52). Adolescent girls with progressive adolescent idiopathic scoliosis have a morphologic somatotype that is different from the normal adolescent population. Subjects with progressive adolescent idiopathic scoliosis are significantly less mesomorphic than control girls. This observation may be of value as a predictive factor for early identification of subjects with adolescent idiopathic scoliosis at greater risk of progression.

Microorganisms and calcium oxalate stone disease.

PubMed

Goldfarb, David S

2004-01-01

Microorganisms may have a role in the pathogenesis and prevention of kidney stones. The subjects of this review include nanobacteria, Oxalobacter formigenes, and lactic acid bacteria. Not reviewed here is the well-described role of infections of the urinary tract with Proteus species and other urease-producing organisms associated with struvite stone formation. Nanobacteria have been proposed to be very small (0.08-0.5 nm), ubiquitous organisms that could play a role in stone formation. The theory is that nanobacteria can nucleate carbonate apatite on their surfaces and thereby provide the nidus for stone formation. However, their existence remains uncertain and many investigators are openly skeptical. Recent investigations suggest that they are artifacts, and not actually living organisms, but their proponents continue to study them. O. formigenes is an obligate anaerobe which may be important in the prevention of stone formation. Its sole substrate for generation of ATP is oxalate. It may thereby metabolize its human host's dietary oxalate and diminish intestinal absorption and subsequent urinary excretion of oxalate. There is evidence that the organism's absence, perhaps sometimes due to courses of antibiotics, may be a cause of hyperoxaluria and stone formation. In early investigations, patients not colonized with the organism can be recolonized. Urinary oxalate can be diminished by accompanying an oxalate-containing meal with the organism. One study demonstrated that a preparation of lactic acid bacteria successfully reduced urinary oxalate excretion in 6 patients with calcium oxalate stones and hyperoxaluria. The mechanism of this effect is uncertain since these bacteria lacked the gene possessed by O. formigenes which codes for that organism's oxalate uptake mechanism. The author is currently completing a small randomized controlled clinical trial with this preparation in calcium stone-forming patients with idiopathic hyperoxaluria. Copyright (c) 2004 S. Karger AG, Basel.

Mitochondrial Dysfunction in Parkinson's Disease: Pathogenesis and Neuroprotection

PubMed Central

Mounsey, Ross B.; Teismann, Peter

2011-01-01

Mitochondria are vitally important organelles involved in an array of functions. The most notable is their prominent role in energy metabolism, where they generate over 90% of our cellular energy in the form of ATP through oxidative phosphorylation. Mitochondria are involved in various other processes including the regulation of calcium homeostasis and stress response. Mitochondrial complex I impairment and subsequent oxidative stress have been identified as modulators of cell death in experimental models of Parkinson's disease (PD). Identification of specific genes which are involved in the rare familial forms of PD has further augmented the understanding and elevated the role mitochondrial dysfunction is thought to have in disease pathogenesis. This paper provides a review of the role mitochondria may play in idiopathic PD through the study of experimental models and how genetic mutations influence mitochondrial activity. Recent attempts at providing neuroprotection by targeting mitochondria are described and their progress assessed. PMID:21234411

Marked increase in urinary excretion of apolipoproteins in children with nephrolithiasis associated with hypercalciuria.

PubMed

Kovacevic, Larisa; Lu, Hong; Caruso, Joseph A; Govil-Dalela, Tuhina; Thomas, Ronald; Lakshmanan, Yegappan

2017-06-01

Using a proteomic approach, we aimed to identify and compare the urinary excretion of proteins involved in lipid transport and metabolism in children with kidney stones and hypercalciuria (CAL), hypocitraturia (CIT), and normal metabolic work-up (NM), and in healthy controls (HCs). Additionally, we aimed to confirm these results using ELISA, and to examine the relationship between the urinary excretion of selected proteins with demographic, dietary, blood, and urinary parameters. Prospective, controlled, pilot study of pooled urine from CAL, CIT, and NM versus age- and gender-matched HCs, using liquid chromatography-mass spectrometry. Relative protein abundance was estimated using spectral counting. Results were confirmed by ELISA performed on individual samples. Of the 1,813 proteins identified, 230 met the above criteria. Of those, 5 proteins (apolipoprotein A-II [APOA2]; apolipoprotein A-IV [APOA4]; apolipoprotein C-III [APOA3]; fatty acid-binding protein, liver [FABPL]; fatty acid-binding protein, adipocyte [FABP4]) involved in lipid metabolism and transport were found in the CAL group, with significant differences compared with HCs. ELISA analysis indicated statistically significant differences in the urinary excretion of APOC3, APOA4, and FABPL in the CAL group compared with HCs. Twenty-four-hour urinary calcium excretion correlated significantly with concentrations of ApoC3 (r = 0.77, p < 0.001), and FABPL (r = 0.80, p = 0.005). We provide proteomic data showing increased urinary excretion of lipid metabolism/transport-related proteins in children with kidney stones and hypercalciuria. These findings suggest that abnormalities in lipid metabolism might play a role in kidney stone formation.

Occurrence of idiopathic pulmonary fibrosis during immunosuppressive treatment: a case report.

PubMed

Cerri, Stefania; Sgalla, Giacomo; Richeldi, Luca; Luppi, Fabrizio

2016-05-25

Immunosuppressive therapy has been-until the recent release of new guidelines on diagnosis and management-the recommended treatment for idiopathic pulmonary fibrosis. However, its efficacy in patients with idiopathic pulmonary fibrosis has always been a matter of debate. We report the occurrence of idiopathic pulmonary fibrosis in a white man receiving chronic immunosuppressive treatment following a heart transplant. This case report suggests that the immune mechanisms targeted by azathioprine and cyclosporine do not play a role in the pathogenesis of idiopathic pulmonary fibrosis.

Vitamin D supplementation for prevention of cancer in adults.

PubMed

Bjelakovic, Goran; Gluud, Lise Lotte; Nikolova, Dimitrinka; Whitfield, Kate; Krstic, Goran; Wetterslev, Jørn; Gluud, Christian

2014-06-23

The evidence on whether vitamin D supplementation is effective in decreasing cancers is contradictory. To assess the beneficial and harmful effects of vitamin D supplementation for prevention of cancer in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, Science Citation Index Expanded, and the Conference Proceedings Citation Index-Science to February 2014. We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials. We included randomised trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention in adults who were healthy or were recruited among the general population, or diagnosed with a specific disease. Vitamin D could have been administered as supplemental vitamin D (vitamin D₃ (cholecalciferol) or vitamin D₂ (ergocalciferol)), or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol), or 1,25-dihydroxyvitamin D (calcitriol)). Two review authors extracted data independently. We conducted random-effects and fixed-effect model meta-analyses. For dichotomous outcomes, we calculated the risk ratios (RRs). We considered risk of bias in order to assess the risk of systematic errors. We conducted trial sequential analyses to assess the risk of random errors. Eighteen randomised trials with 50,623 participants provided data for the analyses. All trials came from high-income countries. Most of the trials had a high risk of bias, mainly for-profit bias. Most trials included elderly community-dwelling women (aged 47 to 97 years). Vitamin D was administered for a weighted mean of six years. Fourteen trials tested vitamin D₃, one trial tested vitamin D₂, and three trials tested calcitriol supplementation. Cancer occurrence was observed in 1927/25,275 (7.6%) recipients of vitamin D versus 1943/25,348 (7.7%) recipients of control interventions (RR 1.00 (95% confidence interval (CI) 0.94 to 1.06); P = 0.88; I² = 0%; 18 trials; 50,623 participants; moderate quality evidence according to the GRADE instrument). Trial sequential analysis (TSA) of the 18 vitamin D trials shows that the futility area is reached after the 10th trial, allowing us to conclude that a possible intervention effect, if any, is lower than a 5% relative risk reduction. We did not observe substantial differences in the effect of vitamin D on cancer in subgroup analyses of trials at low risk of bias compared to trials at high risk of bias; of trials with no risk of for-profit bias compared to trials with risk of for-profit bias; of trials assessing primary prevention compared to trials assessing secondary prevention; of trials including participants with vitamin D levels below 20 ng/mL at entry compared to trials including participants with vitamin D levels of 20 ng/mL or more at entry; or of trials using concomitant calcium supplementation compared to trials without calcium. Vitamin D decreased all-cause mortality (1854/24,846 (7.5%) versus 2007/25,020 (8.0%); RR 0.93 (95% CI 0.88 to 0.98); P = 0.009; I² = 0%; 15 trials; 49,866 participants; moderate quality evidence), but TSA indicates that this finding could be due to random errors. Cancer occurrence was observed in 1918/24,908 (7.7%) recipients of vitamin D₃ versus 1933/24,983 (7.7%) in recipients of control interventions (RR 1.00 (95% CI 0.94 to 1.06); P = 0.88; I² = 0%; 14 trials; 49,891 participants; moderate quality evidence). TSA of the vitamin D₃ trials shows that the futility area is reached after the 10th trial, allowing us to conclude that a possible intervention effect, if any, is lower than a 5% relative risk reduction. Vitamin D₃ decreased cancer mortality (558/22,286 (2.5%) versus 634/22,206 (2.8%); RR 0.88 (95% CI 0.78 to 0.98); P = 0.02; I² = 0%; 4 trials; 44,492 participants; low quality evidence), but TSA indicates that this finding could be due to random errors. Vitamin D₃ combined with calcium increased nephrolithiasis (RR 1.17 (95% CI 1.03 to 1.34); P = 0.02; I² = 0%; 3 trials; 42,753 participants; moderate quality evidence). TSA, however, indicates that this finding could be due to random errors. We did not find any data on health-related quality of life or health economics in the randomised trials included in this review. There is currently no firm evidence that vitamin D supplementation decreases or increases cancer occurrence in predominantly elderly community-dwelling women. Vitamin D₃ supplementation decreased cancer mortality and vitamin D supplementation decreased all-cause mortality, but these estimates are at risk of type I errors due to the fact that too few participants were examined, and to risks of attrition bias originating from substantial dropout of participants. Combined vitamin D₃ and calcium supplements increased nephrolithiasis, whereas it remains unclear from the included trials whether vitamin D₃, calcium, or both were responsible for this effect. We need more trials on vitamin D supplementation, assessing the benefits and harms among younger participants, men, and people with low vitamin D status, and assessing longer duration of treatments as well as higher dosages of vitamin D. Follow-up of all participants is necessary to reduce attrition bias.

47-year-old man with left leg numbness.

PubMed

Mahta, Ali; Kim, Ryan Y; Saad, Ali G; Kesari, Santosh

2013-03-01

A 47-year-old white male with a history of uveitis, hypercalcemia and nephrolithiasis presented with acute onset partial seizure. On exam he had decreased sensation to light touch on his left lower extremity. A Brain MRI revealed a right frontal mass, which was initially thought to be a metastatic lesion or a primary brain tumor. However, biopsy of the lesion revealed it to be a non-caseating granulomatous lesion consistent with neurosarcoidosis.

The CARRA Registry

ClinicalTrials.gov

2015-11-16

Juvenile Idiopathic Arthritis; Systemic Lupus Erythematosus; Mixed Connective Tissue Disease; Juvenile Ankylosing Spondylitis; Juvenile Dermatomyositis; Localized Scleroderma; Systemic Sclerosis; Vasculitis; Sarcoid; Fibromyalgia, Primary; Auto-inflammatory Disease; Idiopathic Uveitis Idiopathic

Idiopathic granulomatous mastitis masquerading as carcinoma of the breast: a case report and review of the literature

PubMed Central

Tuli, Richard; O'Hara, Brian J; Hines, Janet; Rosenberg, Anne L

2007-01-01

Background Idiopathic granulomatous mastitis is an uncommon, benign entity with a diagnosis of exclusion. The typical clinical presentation of idiopathic granulomatous mastitis often mimics infection or malignancy. As a result, histopathological confirmation of idiopathic granulomatous mastitis combined with exclusion of infection, malignancy and other causes of granulomatous disease is absolutely necessary. Case Presentation We present a case of a young woman with idiopathic granulomatous mastitis, initially mistaken for mastitis as well as breast carcinoma, and successfully treated with a course of corticosteroids. Conclusion There is no clear clinical consensus regarding the ideal therapeutic management of idiopathic granulomatous mastitis. Treatment options include expectant management with spontaneous remission, corticosteroid therapy, immunosuppressive agents and extensive surgery for refractory cases. PMID:17662130

Osteoporosis in premenopausal women.

PubMed

Langdahl, Bente L

2017-07-01

The scope of this review was to review the newest developments in the context of the existing knowledge on premenopausal bone fragility. Fragility fractures are common in postmenopausal women and men and diagnostic criteria for osteoporosis have been agreed and multiple pharmacological treatments have been developed over the last 25 years. In premenopausal women, fragility fractures and very low bone mass are uncommon and osteoporosis in premenopausal women has therefore attracted much less interest. Recent studies have highlighted that lifestyle and dietary habits affect premenopausal bone mass. Bone mass may be improved by sufficient intake of calcium and vitamin D together with increased physical activity in premenopausal women with idiopathic osteoporosis. If pharmacological treatment is needed, teriparatide has been demonstrated to efficiently increase bone mass; however, no fracture studies and no comparative studies against antiresorptive therapies have been conducted. Pregnancy affects bone turnover and mass significantly, but pregnancy-associated osteoporosis is a rare and heterogeneous condition. The diagnosis of osteoporosis should only be considered in premenopausal women with existing fragility fractures, diseases or treatments known to cause bone loss or fractures. Secondary causes of osteoporosis should be corrected or treated if possible. The women should be recommended sufficient intake of calcium and vitamin and physical activity. In women with recurrent fractures or secondary causes that cannot be eliminated, for example glucocorticoid or cancer treatment, pharmacological intervention with bisphosphonates or teriparatide (not in the case of cancer) may be considered.

Diagnosis of narcolepsy and idiopathic hypersomnia. An update based on the International classification of sleep disorders, 2nd edition.

PubMed

Billiard, Michel

2007-10-01

Defining the precise nosological limits of narcolepsy and idiopathic hypersomnia is an ongoing process dating back to the first description of the two conditions. The most recent step forward has been done within the preparation of the second edition of the "International classification of sleep disorders" published in June 2005. Appointed by Dr Emmanuel Mignot, the Task Force on "Hypersomnias of central origin, not due to a circadian rhythm sleep disorder, sleep related breathing disorder, or other causes of disturbed nocturnal sleep" thoroughly revisited the nosology of narcolepsy and of idiopathic hypersomnia. Narcolepsy is now distinguished into three different entities, narcolepsy with cataplexy, narcolepsy without cataplexy and narcolepsy due to medical condition, and idiopathic hypersomnia into two entities, idiopathic hypersomnia with long sleep time and idiopathic hypersomnia without long sleep time. Nevertheless there are still a number of pending issues. What are the limits of narcolepsy without cataplexy? Is there a continuum in the pathophysiology of narcolepsy with and without cataplexy? Should sporadic and familial forms of narcolepsy with cataplexy appear as subgroups in the classification? Are idiopathic hypersomnia with long sleep time and idiopathic hypersomnia without long sleep time, two forms of the same condition or two different conditions? Is there a pathophysiological relationship between narcolepsy without cataplexy and idiopathic hypersomnia without long sleep time?

Vitamin D deficiency in chronic idiopathic urticaria.

PubMed

Movahedi, Masoud; Tavakol, Marzieh; Hirbod-Mobarakeh, Armin; Gharagozlou, Mohammad; Aghamohammadi, Asghar; Tavakol, Zahra; Momenzadeh, Kaveh; Nabavi, Mohammad; Dabbaghzade, Abbas; Mosallanejad, Asieh; Rezaei, Nima

2015-04-01

Chronic urticaria is the most common skin diseases, characterized by chronic cutaneous lesions which severely debilitates patients in several aspects of their everyday life. Vitamin D is known to exert several actions in the immune system and to influence function and differentiation of mast cells, central role players in the pathogenesis of chronic idiopathic urticaria. This study was performed to evaluate the relationship between vitamin D levels and susceptibility to chronic idiopathic urticaria. One hundred and fourteen patients with chronic idiopathic urticaria were recruited in this study along with one hundred and eighty seven sex-matched and age-matched healthy volunteers as the control group. For each patient, urticaria activity score was calculated and autologous serum skin test was done. Vitamin D metabolic statue was measured in serum as 25 hydroxyvitamin D using enzyme immunoassay method. Patients with chronic idiopathic urticaria significantly showed lower levels of vitamin D. Vitamin D deficiency was significantly associated with increased susceptibility to chronic idiopathic urticaria. There was a significant positive correlation between vitamin D levels and urticaria activity score. This study showed that patients with chronic idiopathic urticaria had reduced levels of vitamin D, while vitamin D deficiency could increase susceptibility to chronic idiopathic urticaria.

Radiographic and MRI characteristics of lumbar disseminated idiopathic spinal hyperostosis and spondylosis deformans in dogs.

PubMed

Togni, A; Kranenburg, H J C; Morgan, J P; Steffen, F

2014-07-01

To evaluate clinical signs, describe lesions and differences in the magnetic resonance imaging appearance of spinal new bone formations classified as disseminated idiopathic spinal hyperostosis and/or spondylosis deformans on radiographs and compare degeneration status of the intervertebral discs using the Pfirrmann scale. Retrospective analysis of 18 dogs presented with spinal disorders using information from radiographic and magnetic resonance imaging examinations. All dogs were found to be affected with both disseminated idiopathic spinal hyperostosis and spondylosis deformans. Neurological signs due to foraminal stenosis associated with disseminated idiopathic spinal hyperostosis were found in two dogs. Spondylosis deformans was associated with foraminal stenosis and/or disc protrusion in 15 cases. The Pfirrmann score on magnetic resonance imaging was significantly higher in spondylosis deformans compared with disseminated idiopathic spinal hyperostosis and signal intensity of new bone due to disseminated idiopathic spinal hyperostosis was significantly higher compared to spondylosis deformans. Differences between disseminated idiopathic spinal hyperostosis and spondylosis deformans found on magnetic resonance imaging contribute to an increased differentiation between the two entities. Clinically relevant lesions in association with disseminated idiopathic spinal hyperostosis were rare compared to those seen with spondylosis deformans. © 2014 British Small Animal Veterinary Association.

Idiopathic anaphylaxis.

PubMed

Fenny, Nana; Grammer, Leslie C

2015-05-01

Idiopathic anaphylaxis is a diagnosis of exclusion after other causes have been thoroughly evaluated and excluded. The pathogenesis of idiopathic anaphylaxis remains uncertain, although increased numbers of activated lymphocytes and circulating histamine-releasing factors have been implicated. Signs and symptoms of patients diagnosed with idiopathic anaphylaxis are indistinguishable from the manifestations of other forms of anaphylaxis. Treatment regimens are implemented based on the frequency and severity of patient symptoms and generally include the use of epinephrine autoinjectors, antihistamines, and steroids. The prognosis of idiopathic anaphylaxis is generally favorable with well-established treatment regimens and effective patient education. Copyright © 2015 Elsevier Inc. All rights reserved.

Epidemiologic Insights into Stone Disease as a Systemic Disorder

NASA Astrophysics Data System (ADS)

Curhan, Gary C.

2007-04-01

Examining the epidemiology of stone disease can provide insight into etiology. There is a growing body of evidence that stone disease is not simply a disorder of the kidney. In fact, nephrolithiasis is clearly a systemic disorder. Conditions associated with stone disease include the classic ones such as inflammatory bowel disease and primary hyperparathyroidism. More recent studies have demonstrated strong associations with obesity, gout, diabetes and hypertension. Future studies will help uncover the underlying common pathophysiologic abnormalities.

Pediatric Ureteroscopy.

PubMed

Ost, Michael C; Fox, Patrick J

2018-05-01

In recent years, the incidence of nephrolithiasis in the pediatric population appears to be increasing. 1 This has placed a new emphasis on surgical management of stones in children. In the past, extracorporeal shockwave lithotripsy was the preferred management technique for stones in children. 2 More recently, though, advances in endoscopy have allowed ureteroscopy to be adapted to the pediatric population and this approach has become more frequently utilized not just for lower ureteral calculi but also for proximal ureteral and renal stones.

Triglycerides in the human kidney cortex: relationship with body size.

PubMed

Bobulescu, Ion Alexandru; Lotan, Yair; Zhang, Jianning; Rosenthal, Tara R; Rogers, John T; Adams-Huet, Beverley; Sakhaee, Khashayar; Moe, Orson W

2014-01-01

Obesity is associated with increased risk for kidney disease and uric acid nephrolithiasis, but the pathophysiological mechanisms underpinning these associations are incompletely understood. Animal experiments have suggested that renal lipid accumulation and lipotoxicity may play a role, but whether lipid accumulation occurs in humans with increasing body mass index (BMI) is unknown. The association between obesity and abnormal triglyceride accumulation in non-adipose tissues (steatosis) has been described in the liver, heart, skeletal muscle and pancreas, but not in the human kidney. We used a quantitative biochemical assay to quantify triglyceride in normal kidney cortex samples from 54 patients undergoing nephrectomy for localized renal cell carcinoma. In subsets of the study population we evaluated the localization of lipid droplets by Oil Red O staining and measured 16 common ceramide species by mass spectrometry. There was a positive correlation between kidney cortex trigyceride content and BMI (Spearman R = 0.27, P = 0.04). Lipid droplets detectable by optical microscopy had a sporadic distribution but were generally more prevalent in individuals with higher BMI, with predominant localization in proximal tubule cells and to a lesser extent in glomeruli. Total ceramide content was inversely correlated with triglycerides. We postulate that obesity is associated with abnormal triglyceride accumulation (steatosis) in the human kidney. In turn, steatosis and lipotoxicity may contribute to the pathogenesis of obesity-associated kidney disease and nephrolithiasis.

Ambient temperature as a contributor to kidney stone formation: implications of global warming.

PubMed

Fakheri, Robert J; Goldfarb, David S

2011-06-01

Nephrolithiasis is a common disease across the world that is becoming more prevalent. Although the underlying cause for most stones is not known, a body of literature suggests a role of heat and climate as significant risk factors for lithogenesis. Recently, estimates from computer models predicted up to a 10% increase in the prevalence rate in the next half century secondary to the effects of global warming, with a coinciding 25% increase in health-care expenditures. Our aim here is to critically review the medical literature relating stones to ambient temperature. We have categorized the body of evidence by methodology, consisting of comparisons between geographic regions, comparisons over time, and comparisons between people in specialized environments. Although most studies are confounded by other factors like sunlight exposure and regional variation in diet that share some contribution, it appears that heat does play a role in pathogenesis in certain populations. Notably, the role of heat is much greater in men than in women. We also hypothesize that the role of a significant human migration (from rural areas to warmer, urban locales beginning in the last century and projected to continue) may have a greater impact than global warming on the observed worldwide increasing prevalence rate of nephrolithiasis. At this time the limited data available cannot substantiate this proposed mechanism but further studies to investigate this effect are warranted.

Juvenile Idiopathic Arthritis

MedlinePlus

... Is Juvenile Idiopathic Arthritis the same as Juvenile Rheumatoid Arthritis? Yes, Juvenile Idiopathic Arthritis (JIA) is a new ... of chronic inflammatory diseases that affect children. Juvenile Rheumatoid Arthritis (JRA) is the older term that was used ...

Prevalence of functional disorders of androgen excess in unselected premenopausal women: a study in blood donors.

PubMed

Sanchón, Raúl; Gambineri, Alessandra; Alpañés, Macarena; Martínez-García, M Ángeles; Pasquali, Renato; Escobar-Morreale, Héctor F

2012-04-01

The polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. On the contrary, the prevalences of other disorders of androgen excess such as idiopathic hyperandrogenism and idiopathic hirsutism remain unknown. We aimed to obtain an unbiased estimate of the prevalence in premenopausal women of (i) signs of androgen excess and (ii) PCOS, idiopathic hyperandrogenism and idiopathic hirsutism. A multicenter prevalence survey included 592 consecutive premenopausal women (393 from Madrid, Spain and 199 from Bologna, Italy) reporting spontaneously for blood donation. Immediately before donation, we conducted clinical and biochemical phenotyping for androgen excess disorders. We determined the prevalence of (i) hirsutism, acne and alopecia as clinical signs of androgen excess and (ii) functional disorders of androgen excess, including PCOS, defined by the National Institute of Child Health and Human Development/National Institute of Health criteria, idiopathic hyperandrogenism and idiopathic hirsutism. Regarding clinical signs of hyperandrogenism, hirsutism and acne were equally frequent [12.2% prevalence; 95% confidence interval (CI): 9.5-14.8%], whereas alopecia was uncommon (1.7% prevalence, 95% CI: 0.7-2.7%). Regarding functional disorders of androgen excess, PCOS and idiopathic hirsutism were equally frequent (5.4% prevalence, 95% CI: 3.6-7.2) followed by idiopathic hyperandrogenism (3.9% prevalence, 95% CI: 2.3-5.4). Clinical signs of hyperandrogenism and functional disorders of androgen excess show a high prevalence in premenopausal women. The prevalences of idiopathic hyperandrogenism and idiopathic hirsutism are similar to that of PCOS, highlighting the need for further research on the pathophysiology, consequences for health and clinical implications of these functional forms of androgen excess.

Idiopathic paraproteinaemia. I. Studies in an animal model--the ageing C57BL/KaLwRij mouse.

PubMed Central

Radl, J; Hollander, C F; van den Berg, P; de Glopper, E

1978-01-01

A search for a suitable animal model for studies on idiopathic paraproteinaemia showed that an age-dependent increase in the appearance of homogeneous immunoglobulins in serum was common to all of the seven mouse strains investigated to date. The highest frequency was found in C57Bl/KaLwRij mice. Further investigations in this strain demonstrated that, except for some quantitative differences, most of the features of human and C57BL Mouse idiopathic paraproteinaemia were essentially the same. No clear-cut correlation was found between the idiopathic paraproteinaemia and, in the old C57B1 mice, a rather frequently occurring reticulum cell sarcoma B and amyloidosis. The mouse idiopathic paraproteinaemia can be regarded as an analogue of the human idiopathic paraproteinaemia and therefore as a suitable model for further experimental studies. PMID:367647

Idiopathic hypersomnia: a report of three adolescent-onset cases in a two-generation family.

PubMed

Janácková, Sona; Motte, Jacques; Bakchine, Serge; Sforza, Emilia

2011-04-01

Idiopathic hypersomnia is an uncommon sleep disorder characterized by prolonged sleep time and excessive daytime sleepiness without cataplexy. This study concerned a case of familial occurrence. The proband expressed an idiopathic hypersomnia with long sleep time at the age of 12 years. Clinical interview and ad libitum polysomnographic study did not reveal any symptoms of narcolepsy or other sleep disorders. Family history revealed that a 20-year-old sister had experienced symptoms of hypersomnia from the age of 16 and their mother had been diagnosed with idiopathic hypersomnia previously. The diagnosis of idiopathic hypersomnia with long sleep time was confirmed in the sister by clinical interview and ad libitum polysomnography. Human leukocyte antigen (HLA) did not reveal the DQB1-0602 phenotype in the proband and relatives. This report confirms the hypothesis of a genetic predisposition in idiopathic hypersomnia.

Idiopathic intracranial hypertension and sickle cell disease: two case reports.

PubMed

Segal, Laura; Discepola, Marino

2005-12-01

Two patients with sickle cell disease presented with headaches and visual disturbances, typical complaints of this disorder. However, prompt diagnosis of idiopathic intracranial hypertension and initiation of medical therapy lead to improved symptoms and restored vision. Ophthalmologists should consider sickle cell disease to be an independent risk factor for idiopathic intracranial hypertension when a patient is being assessed for visual disturbances. Although a rare condition, idiopathic intracranial hypertension has several key signs useful in establishing a diagnosis. It is critical to recognize the warning signs and symptoms to prevent devastating ophthalmologic complications. We report the first cases of idiopathic intracranial hypertension in patients with the novel Quebec-Chori beta-chain variant of sickle cell disease.

Acute exacerbation of idiopathic pulmonary fibrosis triggered by Aspergillus empyema.

PubMed

Suzuki, Atsushi; Kimura, Tomoki; Kataoka, Kensuke; Matsuda, Toshiaki; Yokoyama, Toshiki; Mori, Yuta; Kondoh, Yasuhiro

2018-01-01

Acute exacerbation (AE) is a severe and life-threatening complication of idiopathic pulmonary fibrosis (IPF). In 2016, the definition and diagnostic criteria for AE-IPF were updated by an international working group. The new definition includes any acute, clinically significant respiratory deterioration (both idiopathic and triggered events) characterized by evidence of new widespread alveolar abnormality in patients with IPF. There are no currently proven beneficial management strategies for idiopathic and triggered AE-IPF. This is the first report describing AE-IPF triggered by Aspergillus empyema, which was improved by a combination of corticosteroid, systemic antifungal therapy, local antifungal therapy, and additional pharmacological therapies. Future research may reveal optimal strategies for both idiopathic and triggered AE-IPF.

Vocal cord paralysis: What matters between idiopathic and non-idiopathic cases?

PubMed

Özbal Koç, Ayça Eltaf; Türkoğlu, Seda Babakurban; Erol, Ozan; Erbek, Selim

2016-01-01

This study aims to evaluate the demographic and clinical characteristics of patients with idiopathic and non-idiopathic vocal cord paralysis (VCP). This retrospective cohort was performed on data extracted from medical files of 92 consecutive patients (43 males, 49 females; median age 52.1±23.1 years; min. 1 - max. 87) with VCP diagnosed in the otorhinolaryngology department between April 2012 and December 2015. Diagnoses associated with VCP, side of involvement (right, left or bilateral) and previous medical histories were noted and compared between patients with idiopathic and non-idiopathic VCP. Vocal cord paralysis occurred on the left side (n=56, 60.9%), right side (n=28, 30.4%) or bilaterally (n=8, 8.7%). A clinical entity related with VCP was identified in 63 patients (68.5%), while 29 (31.5%) patients had idiopathic VCP. Most common etiologies for VCP were thyroid surgery (n=32, 34.8%), cardiovascular surgery (n=9, 9.8%), lung cancer (n=6, 6.5%) and cardiac anomalies (n=4, 4.3%), respectively. Patients with idiopathic VCP were significantly older (p<0.001), while gender distribution (p=0.121) and side of involvement (p=0.340) did not differ between two groups. Vocal cord paralysis is a relatively common clinical entity with substantial rate of morbidity. Identification of the underlying etiology and awareness on the clinical characteristics are keystones for foreseeing complications and determining the appropriate therapeutic modality.

MOnitored supplementation of VItamin D in preterm infants (MOSVID trial): study protocol for a randomised controlled trial.

PubMed

Kołodziejczyk, Alicja; Borszewska-Kornacka, Maria K; Seliga-Siwecka, Joanna

2017-09-11

The pivotal role of vitamin D (vit D) in skeletal health is well known. Neonatal vit D storage at birth is dependent on maternal levels, and newborns receive 50-70% of their mother's 25-hydroxyvitamin D [25(OH)D]. Deficiency of vit D can lead to prematurity bone disease, with an incidence of up to 55% in infants weighing < 1000 g. The aim of this study is to assess the effectiveness of monitored supplementation of vit D in a population of preterm infants. Preterm infants born at 24-32 weeks of gestation will be recruited within the first 7 days of life. Depending on the type of feeding, and after reaching partial enteral feeding or at 7 days of life, vit D supplementation will consist of 500 IU and an additional 150-300 IU/kg included in human milk fortifiers (if fed exclusively with breast milk) or 190 IU/kg in milk formulas. Subjects will be randomised to either monitored (with an option of dose modification based on 25(OH)D levels as per protocol) or standard therapy up to 52 weeks of post-conceptional age (PCA). The primary outcome measure will be the number of neonates with deficiency or excess levels of 25(OH)D at 40  ±2 weeks of PCA. Additional 25(OH)D levels will be measured at birth, at 4 and 8 weeks of age, and/or at 35 and 52  ±2 weeks of PCA. Secondary objectives will include the incidence of osteopenia, nephrocalcinosis and nephrolithiasis. Serum parameters of calcium phosphorus metabolism will also be measured. Despite multiple years of research and numerous publications, there is still a lack of consensus in regard to how much vit D infants should receive and how long they should receive it. Because 80% of calcium and phosphorus placental transfer occurs between 24 and 40 weeks of gestation, preterm infants are especially prone to adverse effects of vit D insufficiency. However, both inadequate and excessive amounts of vit D may be unsafe and lead to serious health issues. The results of our study may shed new light on these concerns and contribute to optimising vit D supplementation. ClinicalTrials.gov, NCT03087149 . Registered on 15 March 2017.

Urinary metabonomics elucidate the therapeutic mechanism of Orthosiphon stamineus in mouse crystal-induced kidney injury.

PubMed

Gao, Songyan; Chen, Wei; Peng, Zhongjiang; Li, Na; Su, Li; Lv, Diya; Li, Ling; Lin, Qishan; Dong, Xin; Guo, Zhiyong; Lou, Ziyang

2015-05-26

Orthosiphon stamineus (OS), a traditional Chinese herb, is often used for promoting urination and treating nephrolithiasis. Urolithiasis is a major worldwide public health burden due to its high incidence of recurrence and damage to renal function. However, the etiology for urolithiasis is not well understood. Metabonomics, the systematic study of small molecule metabolites present in biological samples, has become a valid and powerful tool for understanding disease phenotypes. In this study, a urinary metabolic profiling analysis was performed in a mouse model of renal calcium oxalate crystal deposition to identify potential biomarkers for crystal-induced renal damage and the anti-crystal mechanism of OS. Thirty six mice were randomly divided into six groups including Saline, Crystal, Cystone and OS at dosages of 0.5g/kg, 1g/kg, and 2g/kg. A metabonomics approach using ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) was developed to perform the urinary metabolic profiling analysis. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were utilized to identify differences between the metabolic profiles of mice in the saline control group and crystal group. Using partial least squares-discriminant analysis, 30 metabolites were identified as potential biomarkers of crystal-induced renal damage. Most of them were primarily involved in amino acid metabolism, taurine and hypotaurine metabolism, purine metabolism, and the citrate cycle (TCA). After the treatment with OS, the levels of 20 biomarkers had returned to the levels of the control samples. Our results suggest that OS has a protective effect for mice with crystal-induced kidney injury via the regulation of multiple metabolic pathways primarily involving amino acid, energy and choline metabolism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Comparison of miniaturized percutaneous nephrolithotomy and flexible ureterorenoscopy for moderate size renal stones in elderly patients.

PubMed

Ozgor, Faruk; Yanaral, Fatih; Savun, Metin; Ozdemir, Harun; Caglar, Ufuk; Sarilar, Omer

2018-06-01

Life expectancy has become longer, thus the number of elderly people who require treatment for nephrolithiasis has increased. We aimed to analyze the efficacy of flexible ureterorenoscopy (f-URS) and miniaturized percutaneous nephrolithotomy (mPNL) in the management of 10 and 30 mm renal stones in patients aged >60 years. In prospective non-randomized series, the data of patients who underwent f-URS or mPNL for kidney stones between July 2013 and July 2016 were analyzed. The procedure was accepted as successful if the patient was achieved complete stone clearance according to CT imaging between 1-3 months postoperatively. In total 60 patients and 58 patients were underwent f-URS and mPNL, respectively. The mean operation time, fluoroscopy time and hospitalization time were significantly shorter for the f-URS (p < 0.001, p < 0.001, p < 0.001, respectively). According to Clavien classification system, complication rates were not significantly different between the groups (p = 0.673). The stone-free rate was 81.7% for the f-URS group and 77.6% for the mPNL group after a single-session procedure (p = 0.747). Calcium oxalate monohydrate stones were the most common stone type in both groups. In multivariate analysis, multiple stones localization was only independent factor to predict complications. Our study had showed that both f-URS and mPNL are effective treatment modalities for 10-30-mm renal stones in elderly patients. Additionally, presence of stones in multiple location was the only predictive factor for complication development. Copyright © 2017 Kaohsiung Medical University. Published by Elsevier Taiwan. All rights reserved.

The influence of renal manifestations to the progression of autosomal dominant polycystic kidney disease

PubMed Central

Idrizi, A; Barbullushi, M; Petrela, E; Kodra, S; Koroshi, A; Thereska, N

2009-01-01

Background: Renal stones, urinary tract infections (UTI) and gross hematuria (GH) are the most important renal manifestations of autosomal dominant polycystic kidney disease (ADPKD). They are not only common, but are also frequent cause of morbidity, influencing renal dysfunction. The aim of this study was to evaluate the frequency of these manifestations in our patients with ADPKD and their impact on renal function. Methods: One hundred eighty ADPKD patients were included in the study. Subjects were studied for the presence of UTI, gross hematuria frequency and responsible factors of nephrolithiasis. Survival times were calculated as the time to renal replacement therapy or time of serum creatinine value up to 10 mg/dl. Kaplan-Meier product-limit survival curves were constructed, and log rank test was used to compare the survival curves. Results: Kidney stones were present in 76/180 (42% of pts). The stones were composed of urate (47%) calcium oxalate (39%), and other compounds 14%. UTI was observed in 60% (108 patients). Patients treated with urinary disinfectants had a significant lower frequency of urinary infection (p<0.001) and hematuria (p<0.001) after one year than untreated patients. Gross hematuria was present in 113 patients (63%). In 43 patients hematuria was diagnosed before age 30 (38%), while in 70 patients it was diagnosed after age 30 (62%). Conclusions: UTI is frequent in our ADPKD patients. The correct treatment of UTI decreases its frequency and has beneficial role in the rate of progression to renal failure in ADPKD patients. Patients with recurrent episodes of gross hematuria may be at risk for more severe renal disease. PMID:19918304

Identification of a novel AGXT gene mutation in primary hyperoxaluria after kidney transplantation failure.

PubMed

M'dimegh, Saoussen; Omezzine, Asma; Hamida-Rebai, Mériam Ben; Aquaviva-Bourdain, Cécile; M'barek, Ibtihel; Sahtout, Wissal; Zellama, Dorsaf; Souche, Geneviéve; Achour, Abdellatif; Abroug, Saoussen; Bouslama, Ali

2016-11-01

Primary hyperoxaluria is a genetic disorder in glyoxylate metabolism that leads to systemic overproduction of oxalate. Functional deficiency of alanine-glyoxylate aminotransferase in this disease leads to recurrent nephrolithiasis, nephrocalcinosis, systemic oxalosis, and kidney failure. The aim of this study was to determine the molecular etiology of kidney transplant loss in a young Tunisian individual. We present a young man with end-stage renal disease who received a kidney allograft and experienced early graft failure. There were no improvement in kidney function; he required hemodialysis and graft biopsy revealed calcium oxalate crystals, which raised suspicion of primary hyperoxaluria. Genetic study in the AGXT gene by PCR direct sequencing identified three missense changes in heterozygote state: the p. Gly190Arg mutation next to two other novels not previously described. The classification of the deleterious effect of the missense changes was developed using the summered results of four different mutation assessment algorithms, SIFT, PolyPhen, Mutation Taster, and Align-GVGD. This system classified the changes as polymorphism in one and as mutation in other. The patient was compound heterozygous mutations. Structural analysis showed that the novel mutation, p.Pro28Ser mutation, affects near the dimerization interface of AGT and positioned on binding site instead of the inhibitor, amino-oxyacetic acid (AOA). With the novel AGXT mutation, the mutational spectrum of this gene continues to broaden in our population. The diagnosis of PH1 was not recognized until after renal transplant with fatal consequences, which led us to confirm the importance of screening before planning for kidney transplantation in population with a relatively high frequency of AGXT mutation carriers. Copyright © 2016 Elsevier B.V. All rights reserved.

Substantia Nigra Free Water Increases Longitudinally in Parkinson Disease.

PubMed

Guttuso, T; Bergsland, N; Hagemeier, J; Lichter, D G; Pasternak, O; Zivadinov, R

2018-02-01

Free water in the posterior substantia nigra obtained from a bi-tensor diffusion MR imaging model has been shown to significantly increase over 1- and 4-year periods in patients with early-stage idiopathic Parkinson disease compared with healthy controls, which suggests that posterior substantia nigra free water may be an idiopathic Parkinson disease progression biomarker. Due to the known temporal posterior-to-anterior substantia nigra degeneration in idiopathic Parkinson disease, we assessed longitudinal changes in free water in both the posterior and anterior substantia nigra in patients with later-stage idiopathic Parkinson disease and age-matched healthy controls for comparison. Nineteen subjects with idiopathic Parkinson disease and 19 age-matched healthy control subjects were assessed on the same 3T MR imaging scanner at baseline and after approximately 3 years. Baseline mean idiopathic Parkinson disease duration was 7.1 years. Both anterior and posterior substantia nigra free water showed significant intergroup differences at baseline ( P < .001 and P = .014, respectively, idiopathic Parkinson disease versus healthy controls); however, only anterior substantia nigra free water showed significant longitudinal group × time interaction increases ( P = .021, idiopathic Parkinson disease versus healthy controls). There were no significant longitudinal group × time interaction differences found for conventional diffusion tensor imaging or free water-corrected DTI assessments in either the anterior or posterior substantia nigra. Results from this study provide further evidence supporting substantia nigra free water as a promising disease-progression biomarker in idiopathic Parkinson disease that may help to identify disease-modifying therapies if used in future clinical trials. Our novel finding of longitudinal increases in anterior but not posterior substantia nigra free water is potentially a result of the much longer disease duration of our cohort compared with previously studied cohorts and the known posterior-to-anterior substantia nigra degeneration that occurs over time in idiopathic Parkinson disease. © 2018 by American Journal of Neuroradiology.

Anterior hypopituitarism is rare and autoimmune disease is common in adults with idiopathic central diabetes insipidus.

PubMed

Hannon, M J; Orr, C; Moran, C; Behan, L A; Agha, A; Ball, S G; Thompson, C J

2012-05-01

Central diabetes insipidus is a rare clinical condition with a heterogenous aetiology. Up to 40% of cases are classified as idiopathic, although many of these are thought to have an autoimmune basis. Published data have suggested that anterior hypopituitarism is common in childhood-onset idiopathic diabetes insipidus. We aimed to assess the incidence of anterior hypopituitarism in a cohort of adult patients with idiopathic diabetes insipidus. We performed a retrospective review of the databases of two pituitary investigation units. This identified 39 patients with idiopathic diabetes insipidus. All had undergone magnetic resonance imaging scanning and dynamic pituitary testing (either insulin tolerance testing or GHRH/arginine and short synacthen testing) to assess anterior pituitary function. One patient had partial growth hormone deficiency; no other anterior pituitary hormonal deficits were found. Thirty-three percent had at least one autoimmune disease in addition to central diabetes insipidus. Our data suggest that anterior hypopituitarism is rare in adult idiopathic diabetes insipidus. Routine screening of these patients for anterior hypopituitarism may not, therefore, be indicated. The significant prevalence of autoimmune disease in this cohort supports the hypothesis that idiopathic diabetes insipidus may have an autoimmune aetiology. © 2012 Blackwell Publishing Ltd.

The Prevalence and Characteristics of Primary Headache and Dream-Enacting Behaviour in Japanese Patients with Narcolepsy or Idiopathic Hypersomnia: A Multi-Centre Cross-Sectional Study.

PubMed

Suzuki, Keisuke; Miyamoto, Masayuki; Miyamoto, Tomoyuki; Inoue, Yuichi; Matsui, Kentaro; Nishida, Shingo; Hayashida, Kenichi; Usui, Akira; Ueki, Yoichiro; Nakamura, Masaki; Murata, Momoyo; Numao, Ayaka; Watanabe, Yuji; Suzuki, Shiho; Hirata, Koichi

2015-01-01

Because the prevalence and characteristics of primary headache have yet to be thoroughly studied in patients with hypersomnia disorders, including narcolepsy and idiopathic hypersomnia, we examined these parameters in the Japanese population. In a multicentre cross-sectional survey, among 576 consecutive outpatients with sleep disorders, 68 narcolepsy patients and 35 idiopathic hypersomnia patients were included. Additionally, 61 healthy control subjects participated. Semi-structured headache questionnaires were administered to all participants. The patients with narcolepsy (52.9%) and idiopathic hypersomnia (77.1%) more frequently experienced headache than the healthy controls (24.6%; p<0.0001). The prevalence rates were 23.5%, 41.2% and 4.9% for migraine (p<0.0001) and 16.2%, 23.5% and 14.8% (p = 0.58) for tension-type headache among the narcolepsy patients, the idiopathic hypersomnia patients and the control subjects, respectively. Those who experienced migraine more frequently experienced excessive daytime sleepiness, defined as an Epworth Sleepiness Scale score of ≥10, than those who did not experience headache among the patients with narcolepsy (93.8% vs. 65.6%, p = 0.040) and idiopathic hypersomnia (86.7% vs. 37.5%, p = 0.026). Dream-enacting behaviour (DEB), as evaluated by the rapid eye movement sleep disorders questionnaire, was more frequently observed in the narcolepsy patients than in the idiopathic hypersomnia patients and the control subjects. An increased DEB frequency was observed in the narcolepsy patients with migraines compared to those without headache. Migraines were frequently observed in patients with narcolepsy and idiopathic hypersomnia. DEB is a characteristic of narcolepsy patients. Further studies are required to assess the factors that contribute to migraines in narcolepsy and idiopathic hypersomnia patients.

The Prevalence and Characteristics of Primary Headache and Dream-Enacting Behaviour in Japanese Patients with Narcolepsy or Idiopathic Hypersomnia: A Multi-Centre Cross-Sectional Study

PubMed Central

Suzuki, Keisuke; Miyamoto, Masayuki; Miyamoto, Tomoyuki; Inoue, Yuichi; Matsui, Kentaro; Nishida, Shingo; Hayashida, Kenichi; Usui, Akira; Ueki, Yoichiro; Nakamura, Masaki; Murata, Momoyo; Numao, Ayaka; Watanabe, Yuji; Suzuki, Shiho; Hirata, Koichi

2015-01-01

Background Because the prevalence and characteristics of primary headache have yet to be thoroughly studied in patients with hypersomnia disorders, including narcolepsy and idiopathic hypersomnia, we examined these parameters in the Japanese population. Methods In a multicentre cross-sectional survey, among 576 consecutive outpatients with sleep disorders, 68 narcolepsy patients and 35 idiopathic hypersomnia patients were included. Additionally, 61 healthy control subjects participated. Semi-structured headache questionnaires were administered to all participants. Results The patients with narcolepsy (52.9%) and idiopathic hypersomnia (77.1%) more frequently experienced headache than the healthy controls (24.6%; p<0.0001). The prevalence rates were 23.5%, 41.2% and 4.9% for migraine (p<0.0001) and 16.2%, 23.5% and 14.8% (p = 0.58) for tension-type headache among the narcolepsy patients, the idiopathic hypersomnia patients and the control subjects, respectively. Those who experienced migraine more frequently experienced excessive daytime sleepiness, defined as an Epworth Sleepiness Scale score of ≥10, than those who did not experience headache among the patients with narcolepsy (93.8% vs. 65.6%, p = 0.040) and idiopathic hypersomnia (86.7% vs. 37.5%, p = 0.026). Dream-enacting behaviour (DEB), as evaluated by the rapid eye movement sleep disorders questionnaire, was more frequently observed in the narcolepsy patients than in the idiopathic hypersomnia patients and the control subjects. An increased DEB frequency was observed in the narcolepsy patients with migraines compared to those without headache. Conclusions Migraines were frequently observed in patients with narcolepsy and idiopathic hypersomnia. DEB is a characteristic of narcolepsy patients. Further studies are required to assess the factors that contribute to migraines in narcolepsy and idiopathic hypersomnia patients. PMID:26418536

Epithelial to mesenchymal transition-related proteins ZEB1, β-catenin, and β-tubulin-III in idiopathic pulmonary fibrosis.

PubMed

Chilosi, Marco; Caliò, Anna; Rossi, Andrea; Gilioli, Eliana; Pedica, Federica; Montagna, Licia; Pedron, Serena; Confalonieri, Marco; Doglioni, Claudio; Ziesche, Rolf; Grubinger, Markus; Mikulits, Wolfgang; Poletti, Venerino

2017-01-01

Epithelial to mesenchymal transition has been suggested as a relevant contributor to pulmonary fibrosis, but how and where this complex process is triggered in idiopathic pulmonary fibrosis is not fully understood. Beta-tubulin-III (Tubβ3), ZEB1, and β-catenin are partially under the negative control of miR-200, a family of micro-RNAs playing a major role in epithelial to mesenchymal transition, that are reduced in experimental lung fibrosis and idiopathic pulmonary fibrosis. We wonder whether in situ expression of these proteins is increased in idiopathic pulmonary fibrosis, to better understand the significance of miR-200 feedback loop and epithelial to mesenchymal transition. We investigated the immunohistochemical and immunofluorescent expression and precise location of ZEB1, Tubβ3, and β-catenin in tissue samples from 34 idiopathic pulmonary fibrosis cases and 21 controls (5 normal lungs and 16 other interstitial lung diseases). In 100% idiopathic pulmonary fibrosis samples, the three proteins were concurrently expressed in fibroblastic foci, as well in damaged epithelial cells overlying these lesions and in pericytes within neo-angiogenesis areas. These results were also confirmed by immunofluorescence assay. In controls the abnormal expression of the three proteins was absent or limited. This is the first study that relates concurrent expression of Tubβ3, ZEB1, and β-catenin to abnormal epithelial and myofibroblast differentiation in idiopathic pulmonary fibrosis, providing indirect but robust evidence of miR-200 deregulation and epithelial to mesenchymal transition activation in idiopathic pulmonary fibrosis. The abnormal expression and localization of these proteins in bronchiolar fibro-proliferative lesions are unique for idiopathic pulmonary fibrosis, and might represent a disease-specific marker in challenging lung biopsies.

Idiopathic Hypersomnia: A Study of 77 Cases

PubMed Central

Anderson, Kirstie N.; Pilsworth, Samantha; Sharples, Linda D.; Smith, Ian E.; Shneerson, John M.

2007-01-01

Study Objectives: To review the clinical and polysomnographic characteristics of idiopathic hypersomnia as well as the long-term response to treatment. Setting: The Respiratory Support and Sleep Centre at Papworth Hospital, Cambridge, UK. Patients and Design: A large database of more than 6000 patients with sleep disorders was reviewed. A retrospective study of the clinical and polysomnographic characteristics of 77 patients with idiopathic hypersomnia was performed. Comparison with a similar group of patients with narcolepsy was performed. The response to drug treatment was assessed in 61 patients over a mean follow-up of 3.8 years. Measurements and Results: Idiopathic hypersomnia was 60% as prevalent as narcolepsy. Comparison with a similar group of patients with narcolepsy showed that those with idiopathic hypersomnia were more likely to have prolonged unrefreshing daytime naps, a positive family history, increased slow-wave sleep, and a longer sleep latency on the Multiple Sleep Latency Test. The results of the Multiple Sleep Latency Test were not helpful in predicting disease severity or treatment response. The clinical features were heterogeneous and of variable severity. The majority of patients with idiopathic hypersomnia had symptoms that remained stable over many years, but 11% had spontaneous remission, which was never seen in narcolepsy. Two thirds of patients with idiopathic hypersomnolence had a sustained improvement in daytime somnolence with medication, although a third needed high doses or combinations of drugs. Conclusions: Idiopathic hypersomnolence has characteristic clinical and polysomnographic features but the prolonged latency on the Multiple Sleep Latency Test raises doubt about the validity of this test within the current diagnostic criteria. The disease often responds well to treatment and a substantial minority of patients appear to spontaneously improve. Citation: Anderson KN; Pilsworth S; Sharples LD; Smith IE; Shneerson JM. Idiopathic hypersomnia: a study of 77 cases. SLEEP 2007;30(10):1274-1281. PMID:17969461

Comparison of plasma, liver, and skeletal muscle carnitine concentrations in cats with idiopathic hepatic lipidosis and in healthy cats.

PubMed

Jacobs, G; Cornelius, L; Keene, B; Rakich, P; Shug, A

1990-09-01

Concentrations of total, free, and esterified carnitine were determined in plasma, liver, and skeletal muscle from cats with idiopathic hepatic lipidosis and compared with values from healthy cats. The mean concentrations of plasma, liver, and skeletal muscle total carnitine; plasma and skeletal muscle free carnitine; and plasma and liver esterified carnitine were greater (P less than 0.05) in cats with idiopathic hepatic lipidosis than in control cats. The mean for the ratio of free/total carnitine in plasma and liver was lower (P less than 0.05) in cats with idiopathic hepatic lipidosis than in control cats. These data suggest that carnitine deficiency does not contribute to the pathogenesis of feline idiopathic hepatic lipidosis.

Histopathology Predicts the Mechanism of Stone Formation

NASA Astrophysics Data System (ADS)

Evan, Andrew P.

2007-04-01

About 5% of American women and 12% of men will develop a kidney stone at some time in their life and these numbers appear to be on the rise. Despite years of scientific research into the mechanisms of stone formation and growth, limited advances have been made until recently. Randall's original observations and thoughts on the mechanisms for kidney stone formation have been validated for idiopathic calcium oxalate stone formers (ICSF) but not for most other stone forming groups. Our current studies on selected groups of human stone formers using intraoperative papillary biopsies has shown overwhelming evidence for the presence of Randall's plaque in ICSF and that stone formation and growth are exclusively linked to its availability to urinary ions and proteins. Intense investigation of the plaque-stone junction is needed if we are to understand the factors leading to the overgrowth process on exposed regions of plaque. Such information should allow the development of treatment strategies to block stone formation in ICSF patients. Patients who form brushite stones, or who form apatite stones because of distal renal tubular acidosis (dRTA), or patients with calcium oxalate stones due to obesity bypass procedures, or patients with cystinuria, get plugged inner medullary collecting ducts (IMCD) which leads to total destruction of the lining cells and focal sites of interstitial fibrosis. These stone formers have plaque but at levels equal to or below non-stone formers, which would suggest that they form stones by a different mechanism than do ICSF patients.

Pseudohypoparathyroidism: defective excretion of 3′,5′-AMP in response to parathyroid hormone

PubMed Central

Chase, Lewis R.; Melson, G. Leland; Aurbach, G. D.

1969-01-01

Urinary excretion of cyclic adenosine 3′,5′-monophosphate (3′,5′-AMP) was tested in normal subjects and patients with pseudohypoparathyroidism, idiopathic hypoparathyroidism, surgical hypoparathyroidism, and pseudopseudohypoparathyroidism under basal conditions and after a 15 min infusion of purified parathyroid hormone. Basal excretion of the nucleotide was less than normal in the patients with hypocalcemic disorders and greater than normal in pseudopseudohypoparathyroidism. Parathyroid hormone caused a marked increase in excretion of 3′,5′-AMP in all subjects except those with pseudohypoparathyroidism; nine patients with this disorder did not respond to the hormone and four showed a markedly deficient response. Radioimmunoassay showed that parathyroid hormone circulated in increased amounts in plasma from patients with pseudohypoparathyroidism and became undetectable when serum calcium was increased above 12 mg/100 ml. Suppression of parathyroid hormone secretion by induction of hypercalcemia did not alter the deficient response to exogenous hormone. The results indicate that: (a) parathyroid hormone circulates in abnormally high concentrations in pseudohypoparathyroidism and secretion of the hormone responds normally to physiological control by calcium; (b) testing urinary excretion of 3′,5′-AMP in response to infusion of purified parathyroid hormone appears to be an accurate and sensitive index for establishing the diagnosis of pseudohypoparathyroidism; and (c) the metabolic defect of the disorder can be accounted for by a lack of or defective form of parathyroid hormone-sensitive adenyl cyclase in bone and kidney. PMID:4309802

A procedure to detect abnormal sensorimotor control in adolescents with idiopathic scoliosis.

PubMed

Pialasse, Jean-Philippe; Mercier, Pierre; Descarreaux, Martin; Simoneau, Martin

2017-09-01

This work identifies, among adolescents with idiopathic scoliosis, those demonstrating impaired sensorimotor control through a classification procedure comparing the amplitude of their vestibular-evoked postural responses. The sensorimotor control of healthy adolescents (n=17) and adolescents with idiopathic scoliosis (n=52) with either mild (Cobb angle≥15° and ≤30°) or severe (Cobb angle >30°) spine deformation was assessed through galvanic vestibular stimulation. A classification procedure sorted out adolescents with idiopathic scoliosis whether the amplitude of their vestibular-evoked postural response was dissimilar or similar to controls. Compared to controls, galvanic vestibular stimulation evoked larger postural response in adolescents with idiopathic scoliosis. Nonetheless, the classification procedure revealed that only 42.5% of all patients showed impaired sensorimotor control. Consequently, identifying patients with sensorimotor control impairment would allow to apply personalized treatments, help clinicians to establish prognosis and hopefully improve the condition of patients with adolescent idiopathic scoliosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Angiopoietin-2 polymorphism in women with idiopathic recurrent miscarriage.

PubMed

Pietrowski, Detlef; Tempfer, Clemens; Bettendorf, Hertha; Bürkle, Bernd; Nagele, Fritz; Unfried, Gertrud; Keck, Christoph

2003-10-01

To investigate the relationship between idiopathic recurrent miscarriage and a polymorphism of the gene encoding for angiopoietin-2 (ANGPT2), an autochthonous modulator of angiogenesis during pregnancy. Prospective case control study. Academic research institution. One hundred thirty-one women with a history of three or more consecutive pregnancy losses before 20 weeks' gestation, and 125 healthy, postmenopausal controls with at least two live births and no history of pregnancy loss. Peripheral venous puncture. Polymerase chain reaction and restriction fragment length polymorphism analysis were performed to identify the different ANGPT2 alleles. No association between mutant (mt) allele and the occurrence of idiopathic recurrent miscarriage was found. Between women with primary and secondary idiopathic recurrent miscarriage, no statistically significant differences with respect to allele frequencies were observed. This is the first report on the ANGPT2 gene polymorphism in women with idiopathic recurrent miscarriage, demonstrating that the investigated polymorphism is not associated with idiopathic recurrent miscarriage in a white population.

Voltage-gated potassium channel (K(v) 1) autoantibodies in patients with chagasic gut dysmotility and distribution of K(v) 1 channels in human enteric neuromusculature (autoantibodies in GI dysmotility).

PubMed

Hubball, A W; Lang, B; Souza, M A N; Curran, O D; Martin, J E; Knowles, C H

2012-08-01

Autoantibodies directed against specific neuronal antigens are found in a significant number of patients with gastrointestinal neuromuscular diseases (GINMDs) secondary to neoplasia. This study examined the presence of antineuronal antibodies in idiopathic GINMD and GINMD secondary to South American Trypanosomiasis. The GI distribution of voltage-gated potassium channels (VGKCs) was also investigated. Seventy-three patients were included in the study with diagnoses of primary achalasia, enteric dysmotility, chronic intestinal pseudo-obstruction, esophageal or colonic dysmotility secondary to Chagas' disease. Sera were screened for specific antibodies to glutamic acid decarboxylase, voltage-gated calcium channels (VGCCs; P/Q subtype), nicotinic acetylcholine receptors (nAChRs; α3 subtype), and voltage-gated potassium channels (VGKCs, K(V) 1 subtype) using validated immunoprecipitation assays. The distribution of six VGKC subunits (K(V) 1.1-1.6), including those known to be antigenic targets of anti-VGKC antibodies was immunohistochemically investigated in all main human GI tract regions. Three patients (14%) with chagasic GI dysmotility were found to have positive anti-VGKC antibody titers. No antibodies were detected in patients with idiopathic GINMD. The VGKCs were found in enteric neurons at every level of the gut in unique yet overlapping distributions. The VGKC expression in GI smooth muscle was found to be limited to the esophagus. A small proportion of patients with GI dysfunction secondary to Chagas' disease have antibodies against VGKCs. The presence of these channels in the human enteric nervous system may have pathological relevance to the growing number of GINMDs with which anti-VGKC antibodies have been associated. © 2012 Blackwell Publishing Ltd.

In-hospital costs associated with chronic constipation in Belgium: a retrospective database study

PubMed Central

Chevalier, P; Lamotte, M; Joseph, A; Dubois, D; Boeckxstaens, G

2014-01-01

Background Real-life data on the economic burden of chronic idiopathic constipation are scarce. The objectives of this study were to assess hospitalization resource use and costs associated with chronic constipation and its complications in Belgium. Methods This was a single country, retrospective study using the IMS Hospital Disease Database (2008), which comprises data on 34% of acute hospital beds in Belgium and contains information on patient demographics, length of stay (LOS), billed costs, drug use, diagnoses, and procedures. Stays with a primary diagnosis of constipation, or a secondary diagnosis of constipation and a concomitant diagnosis of a constipation-related complication, were selected. Patients with diagnoses of colorectal cancer, ulcerative colitis or Crohn's disease, or who had stays involving potentially constipation-inducing procedures, were excluded as having secondary constipation. Patients receiving opioids, calcium-antagonists, antipsychotics or antidepressants were excluded as having drug-induced constipation. Key Results In total, 1541 eligible patients were identified. The average unadjusted cost per day in hospital for idiopathic constipation was €441 (€311 ± 1.4 in day clinic visits without overnight stays; €711 ± 14.0 in full hospitalizations with complications). The average LOS in a full hospitalization setting was 7.0 and 4.0 days in stays with and without complications, respectively. The most frequent drug and procedural treatments were osmotically acting laxatives (with complications: 42.61%; without complications: 35.69%), and transanal enema (2.32% and 2.03%), respectively. Conclusions & Inferences The burden of constipation is often underestimated; it is a condition reflected by hospital-related costs comparable to such indications as migraine, which increase when associated with complications. PMID:24325294

In-hospital costs associated with chronic constipation in Belgium: a retrospective database study.

PubMed

Chevalier, P; Lamotte, M; Joseph, A; Dubois, D; Boeckxstaens, G

2014-03-01

Real-life data on the economic burden of chronic idiopathic constipation are scarce. The objectives of this study were to assess hospitalization resource use and costs associated with chronic constipation and its complications in Belgium. This was a single country, retrospective study using the IMS Hospital Disease Database (2008), which comprises data on 34% of acute hospital beds in Belgium and contains information on patient demographics, length of stay (LOS), billed costs, drug use, diagnoses, and procedures. Stays with a primary diagnosis of constipation, or a secondary diagnosis of constipation and a concomitant diagnosis of a constipation-related complication, were selected. Patients with diagnoses of colorectal cancer, ulcerative colitis or Crohn's disease, or who had stays involving potentially constipation-inducing procedures, were excluded as having secondary constipation. Patients receiving opioids, calcium-antagonists, antipsychotics or antidepressants were excluded as having drug-induced constipation. In total, 1541 eligible patients were identified. The average unadjusted cost per day in hospital for idiopathic constipation was €441 (€311 ± 1.4 in day clinic visits without overnight stays; €711 ± 14.0 in full hospitalizations with complications). The average LOS in a full hospitalization setting was 7.0 and 4.0 days in stays with and without complications, respectively. The most frequent drug and procedural treatments were osmotically acting laxatives (with complications: 42.61%; without complications: 35.69%), and transanal enema (2.32% and 2.03%), respectively. The burden of constipation is often underestimated; it is a condition reflected by hospital-related costs comparable to such indications as migraine, which increase when associated with complications. © 2013 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd.

Recurrent acute pancreatitis: an approach to diagnosis and management.

PubMed

Kedia, Saurabh; Dhingra, Rajan; Garg, Pramod Kumar

2013-01-01

Recurrent acute pancreatitis (RAP) is defined as more than two attacks of acute pancreatitis (AP) without any evidence of underlying chronic pancreatitis (CP). As the known causes of AP are generally taken care of, RAP usually occurs in the idiopathic group, which forms 20%-25% of cases of AP. The causes of idiopathic RAP (IRAP) can be mechanical, toxic-metabolic, anatomical, or miscellaneous. Microlithiasis commonly reported from the West is not a common cause of IRAP among Indian patients. Pancreas divisum (PD) is now believed as a cofactor, the main factor being associated genetic mutations. The role of Sphincter of Oddi dysfunction (SOD) as a cause of IRAP remains controversial. Malignancy should be ruled out in any patient with IRAP > 50 years of age. Early CP can present initially as RAP. The work-up of patients with IRAP includes a detailed history and investigations. Primary investigations include liver function tests (LFT), serum calcium and triglyceride, abdominal ultrasonography (USG) and contrast-ehhanced computed tomography (CECT) abdomen. Endoscopic ultrasound (EUS), magnetic resonance cholangiopancreatography (MRCP) and possibly endoscopic retrograde cholangiopancreatography (ERCP) are indicated in the secondary phase if the work-up is negative after the primary investigations. EUS is advised usually 6-8 weeks after an acute episode. Treatment of patients with IRAP is aimed at the specific aetiology. In general, empirical cholecystectomy should be discouraged with the availability and widespread use of EUS. Endoscopic sphincterotomy is advised if there is strong suspicion of SOD. Minor papilla sphincterotomy should be carried out in those with PD but with limited expectations. Regular follow-up of patients with IRAP is necessary because most patients are likely to develop CP in due course.

[Hearing and balance in metabolic bone diseases].

PubMed

Zatoński, Tomasz; Temporale, Hanna; Krecicki, Tomasz

2012-03-01

There are reports that hearing loss is one of the clinical manifestations of metabolic bone diseases. Demineralization can lead to a reduction in ossicular mass. Paget's disease can reveal loss of mineral density of the cochlear bone. Ear bone remodeling in osteoporosis is similar to the changes in otosclerosis. Moreover, osteoporosis, osteogenesis imperfecta and otosclerosis have a similar genetic mechanism. According to some researchers osteopenia and osteoporosis may well be associated with idiopathic benign positional vertigo (BPV). Dysfunction of the organ of hearing and balance in patients with renal insufficiency may be due to disturbances in calcium phosphate balance and renal osteodystrophy in the course of the disease. Proving the presence of hearing loss in patients with metabolic bone diseases may lead to determining the new indications for bone densitometry in some patients with hearing impairment. Furthermore, audiological examination in patients with osteoporosis may be important because of the impact of hearing loss on prognosis for patients with metabolic bone diseases.

Bone Genes in the Kidney of Stone Formers

NASA Astrophysics Data System (ADS)

Evan, Andrew P.; Bledsoe, Sharon B.

2008-09-01

Intraoperative papillary biopsies from kidneys of idiopathic-calcium oxalate stone formers (ICSF) have revealed a distinct pattern of mineral deposition in the interstitium of the renal papilla. The earliest sites of these deposits, termed Randall's plaque, are found in the basement membrane of thin loops of Henle and appear to spread into the surrounding interstitium down to the papillary epithelium. Recent studies show kidney stones of ICSF patients grow attached to the renal papilla and at sites of Randall's plaque. Together these observations suggest that plaque formation may be the critical step in stone formation. In order to control plaque formation and thereby reduce future kidney stone development, the mechanism of plaque deposition must be understood. Because the renal papilla has unique anatomical features similar to bone and the fact that the interstitial deposits of ICSF patients are formed of biological apatite, this paper tests the hypothesis that sites of interstitial plaque form as a result of cell-mediated osteoblast-like activity.

Molecular analysis of the AGXT gene in patients suspected with hyperoxaluria type 1 and three novel mutations from Turkey.

PubMed

Isiyel, Emel; Ezgu, Sevcan A Bakkaloglu; Caliskan, Salim; Akman, Sema; Akil, Ipek; Tabel, Yilmaz; Akinci, Nurver; Ozdogan, Elif Bahat; Ozel, Ahmet; Eroglu, Fehime Kara; Ezgu, Fatih S

2016-12-01

Primary hyperoxaluria type 1 (PH1) is a rare, autosomal recessive disease, caused by the defect of AGXT gene encoding hepatic peroxisomal alanine glyoxylateaminotransferase (AGT). This enzyme is responsible for the conversion of glyoxylate to glycine. The diagnosis of PH1 should be suspected in infants and children with nephrocalcinosis or nephrolithiasis. Early diagnosis and treatment is crucial in preventing disease progression to end stage kidney disease (ESKD). In this study, AGXT gene sequence analyses were performed in 82 patients who were clinically suspected (hyperoxaluria and nephrolithiasis or nephrocalcinosis with or without renal impairment) to have PH1. Disease causing mutations have been found in fifteen patients from thirteen families (18%). Novel mutations have been found (c.458T>A (p.L153X), c.733_734delAA (p.Lys245Valfs*11), c.52 C>T (p.L18F)) in three of 13 families. There were 3-year lag time between initial symptoms and the time of PH1 is suspected; additionally, 5.5-year lag time between initial symptoms and definitive diagnosis. Consanguinity was detected in 77% of the patients with mutation. After genetic diagnosis, one patient received combined kidney and liver transplantation. AGXT gene sequencing is now the choice of diagnosis of PH1 due to its non-invasive nature compared to liver enzyme assay. Early diagnosis and accurate treatment in PH1 is important for better patient outcomes. Copyright © 2016. Published by Elsevier Inc.

Idiopathic granulomatous mastitis: a diagnostic dilemma for the breast radiologist.

PubMed

Sripathi, Smiti; Ayachit, Anurag; Bala, Archana; Kadavigere, Rajagopal; Kumar, Sandeep

2016-08-01

Idiopathic granulomatous mastitis is a chronic inflammatory disease of the breast, which is often difficult to differentiate both clinically and radiologically from infectious aetiologies such as tuberculosis, fungal infections, and also from malignancy, thus posing a diagnostic dilemma. We present a pictorial review of the commonly encountered imaging findings in idiopathic granulomatous mastitis on mammography and ultrasound. Mammographic and ultrasound findings of histopathologically proven cases of granulomatous mastitis are discussed. Idiopathic granulomatous mastitis has varied and non-specific appearances on ultrasound and mammography. Histopathology is essential to establish diagnosis. • Idiopathic granulomatous mastitis often poses a diagnostic dilemma for the radiologist by mimicking malignancy. • It has varied and non-specific appearances on mammography and ultrasound. • Histopathology is mandatory to establish the diagnosis and decide management.

Allelic variation of the FRMD7 gene in congenital idiopathic nystagmus.

PubMed

Self, James E; Shawkat, Fatima; Malpas, Crispin T; Thomas, N Simon; Harris, Christopher M; Hodgkins, Peter R; Chen, Xiaoli; Trump, Dorothy; Lotery, Andrew J

2007-09-01

To perform a genotype-phenotype correlation study in an X-linked congenital idiopathic nystagmus pedigree (pedigree 1) and to assess the allelic variance of the FRMD7 gene in congenital idiopathic nystagmus. Subjects from pedigree 1 underwent detailed clinical examination including nystagmology. Screening of FRMD7 was undertaken in pedigree 1 and in 37 other congenital idiopathic nystagmus probands and controls. Direct sequencing confirmed sequence changes. X-inactivation studies were performed in pedigree 1. The nystagmus phenotype was extremely variable in pedigree 1. We identified 2 FRMD7 mutations. However, 80% of X-linked families and 96% of simplex cases showed no mutations. X-inactivation studies demonstrated no clear causal link between skewing and variable penetrance. We confirm profound phenotypic variation in X-linked congenital idiopathic nystagmus pedigrees. We demonstrate that other congenital nystagmus genes exist besides FRMD7. We show that the role of X inactivation in variable penetrance is unclear in congenital idiopathic nystagmus. Clinical Relevance We demonstrate that phenotypic variation of nystagmus occurs in families with FRMD7 mutations. While FRMD7 mutations may be found in some cases of X-linked congenital idiopathic nystagmus, the diagnostic yield is low. X-inactivation assays are unhelpful as a test for carrier status for this disease.

Evidence for human leukocyte antigen-related susceptibility in idiopathic childhood ischemic stroke.

PubMed

Zou, Li-Ping; Guo, Yu-Hong; Fang, Fang; Jin, Hong; Wu, Hu-Sheng; Mix, Eilhard

2002-01-01

Stroke in children is a relatively uncommon condition and frequently associated with other diseases like cardiopathies, sickle cell disease and chronic smoking. In contrast to stroke in adults, it is rarely caused by atherosclerosis, hypertension or diabetes mellitus. Childhood stroke of unknown causes is called idiopathic stroke. The etiology of idiopathic stroke is unknown. However, several so-called idiopathic diseases develop on the basis of a genetic predisposition. As an approach to investigate this possibility in idiopathic childhood ischemic stroke, we studied the relationship between clinical and immunogenetic features in this disease. We demonstrate that the gene frequencies and relative risk of HLA-B51 were markedly increased in our patients compared with controls (p < 0.001). Thirteen of seventeen HLA-B51-positive patients had had a preceding respiratory infection, which was a higher proportion than in the control group (p < 0.05). In the patient group, the alleles HLA-DRB1*0802, -DRAI*0401 and -DQBI*0402 were also significantly increased, defining the haplotype DRB1*0802-DRA1*0401-DQB1*0402 as a high-risk haplotype for idiopathic childhood ischemic stroke. Transient viral or bacterial infections, which involve vasculitis and vascular occlusion in the brain, can trigger idiopathic childhood ischemic stroke on the basis of an genetic predisposition. Copyright 2002 S. Karger AG, Basel

The consequences of idiopathic partial epilepsies in relation to neuropsychological functioning: a closer look at the associated mathematical disability.

PubMed

Sart, Z Hande; Demirbilek, Veysi; Korkmaz, Bariş; Slade, Peter D; Dervent, Ayşin; Townes, Brenda D

2006-03-01

Although the seizure prognosis is mostly favorable in idiopathic partial epilepsies, there is some empirical evidence showing that subtle neuropsychological impairments, with a consequent risk of academic underachievement, are not rare. We investigated neuropsychological functioning including attention, memory, visuomotor ability, and executive functioning with a closer look at the associated mathematical ability in patients with idiopathic partial epilepsies. A battery of age-appropriate, neuropsychological and mathematics achievement tests was administered to 30 participants with idiopathic partial epilepsy [13 children with benign epilepsy with centrotemporal spikes (BECTS), 17 children with idiopathic childhood occipital epilepsies (ICOE)], and to 30 healthy participants matched for age, sex, handedness, and socioeconomic status. Results did not support any impairment in overall neuropsychological functioning in participants with idiopathic partial epilepsies, whereas, isolated deficits did exist. The mean performance of the IPE group was significantly lower than the control group in six out of 12, neuropsychological measures: drawing (p < 0.01), digit span (p < 0.05), verbal learning (p < 0.01), object assembly (p < 0.01), similarities (p < 0.05), and vocabulary (p < 0.001). Results suggested that one should be cautious regarding neuropsychological and academic prognosis in the so-called benign idiopathic partial epilepsies of childhood.

Natural history of idiopathic diabetes insipidus.

PubMed

Richards, Gail E; Thomsett, Michael J; Boston, Bruce A; DiMeglio, Linda A; Shulman, Dorothy I; Draznin, Martin

2011-10-01

To determine what percentage of diabetes insipidus (DI) in childhood is idiopathic and to assess the natural history of idiopathic DI. We conducted a retrospective chart review of 105 patients with DI who were born or had DI diagnosed between 1980-1989 at 3 medical centers. A second cohort of 30 patients from 6 medical centers in whom idiopathic DI was diagnosed after 1990 was evaluated retrospectively for subsequent etiologic diagnoses and additional hypothalamic/pituitary deficiencies and prospectively for quality of life. In the first cohort, 11% of patients had idiopathic DI. In the second cohort, additional hypothalamic/pituitary hormone deficiencies developed in 33%, and 37% received an etiologic diagnosis for DI. Health-related quality of life for all the patients with idiopathic DI was comparable with the healthy reference population. Only a small percentage of patients with DI will remain idiopathic after first examination. Other hormone deficiencies will develop later in one-third of those patients, and slightly more than one-third of those patients will have an etiology for the DI diagnosed. Long-term surveillance is important because tumors have been diagnosed as long as 21 years after the onset of DI. Quality of life for these patients is as good as the reference population. Copyright © 2011 Mosby, Inc. All rights reserved.

Prospective study of bacteraemia in acute haemorrhagic diarrhoea syndrome in dogs.

PubMed

Unterer, S; Lechner, E; Mueller, R S; Wolf, G; Straubinger, R K; Schulz, B S; Hartmann, K

2015-03-21

In dogs with idiopathic acute haemorrhagic diarrhoea syndrome (AHDS), a serious loss of intestinal mucosal barrier integrity occurs. However, the incidence of bacterial translocation in dogs with idiopathic AHDS is not known. Thus, the objectives of this prospective study were to identify the incidence of bacteraemia, to evaluate the frequency of septic events and the influence of bacteraemia on various clinical and laboratory parameters, duration of hospitalisation and survival of dogs with idiopathic AHDS. The study included 87 dogs with idiopathic AHDS. Twenty-one healthy dogs served as control group. To evaluate clinical significance of bacterial translocation, blood culture results were compared between patients and controls. Clinical and laboratory parameters were compared between patients with positive and negative blood cultures. There was no significant difference in either incidence of bacteraemia between patients with idiopathic AHDS (11 per cent) and controls (14 per cent) or in severity of clinical signs, laboratory parameters, duration of hospitalisation or mortality between blood culture-positive and culture-negative dogs with idiopathic AHDS. The results of this study suggest that the incidence of bacteraemia in dogs with idiopathic AHDS is low and not different from that of healthy control dogs. Bacteraemia does not influence the clinical course or survival and thus antibiotic treatment is not indicated to prevent sepsis. British Veterinary Association.

Genetic (idiopathic) epilepsy with photosensitive seizures includes features of both focal and generalized seizures.

PubMed

Xue, Jiao; Gong, Pan; Yang, Haipo; Liu, Xiaoyan; Jiang, Yuwu; Zhang, Yuehua; Yang, Zhixian

2018-04-19

Clinically, some patients having genetic (idiopathic) epilepsy with photosensitive seizures were difficult to be diagnosed. We aimed to discuss whether the genetic (idiopathic) epilepsy with photosensitive seizures is a focal entity, a generalized entity or a continuum. Twenty-two patients with idiopathic epilepsies and photoconvulsive response (PCR) were retrospectively recruited. In the medical records, the seizure types included "generalized tonic-clonic seizures (GTCS)" in 15, "partial secondarily GTCS (PGTCS)" in 3, partial seizures (PS) in 3, myoclonic seizures in 2, eyelid myoclonus in one, and only febrile seizures in one. Seizure types of PCR included GTCS (1/22), PGTCS (6/22), PS (9/22), electrical seizures (ES) (3/22) and GTCS/PGTCS (3/22). Combined the medical history with PCR results, they were diagnosed as: idiopathic (photosensitive) occipital lobe epilepsy (I(P)OE) in 12, genetic (idiopathic) generalized epilepsy (GGE) in one, GGE/I(P)OE in 5, pure photosensitive seizure in one, and epilepsy with undetermined generalized or focal seizure in 3. So, the dichotomy between generalized and focal seizures might have been out of date regarding to pathophysiological advances in epileptology. To some extent, it would be better to recognize the idiopathic epilepsy with photosensitive seizures as a continuum between focal and generalized seizures.

Acute Idiopathic Scrotal Edema: Systematic Literature Review.

PubMed

Santi, Maristella; Lava, Sebastiano A G; Simonetti, Giacomo D; Bianchetti, Mario G; Milani, Gregorio P

2018-06-01

 Existing information on acute idiopathic scrotal edema relies on small case series and textbooks.  We searched reports with no date limits on acute idiopathic scrotal edema.  Thirty-seven studies were included. Sixteen case series addressed the prevalence of acute idiopathic scrotal edema among males with acute scrotum: among 3,403 cases, the diagnosis of acute idiopathic scrotal edema was made in 413 cases (12%). Twenty-four reports addressed history, findings, management, and course of acute idiopathic scrotal edema in 311 patients. The patients mostly ranged in age from 5 to 8 years, presented with acute scrotal redness and swelling, associated or not with mild pain. Ninety percent or more of the cases developed in patients without atopic diathesis and were not preceded by inguinoscrotal surgery, acute febrile illnesses, or trauma. They were afebrile; in good general condition; and presented without pruritus, nausea or vomiting, or abdominal pain. The lesions were bilateral in two-thirds and unilateral in one-third of the cases. The condition resolved spontaneously within 2 to 3 days without sequelae. Approximately 10% of the cases experienced a recurrence.  Acute idiopathic scrotal edema is a self-limiting condition that accounts for ≥ 10% of cases of acute scrotum in children and adolescents. Georg Thieme Verlag KG Stuttgart · New York.

Effect of acid suppression therapy on gastroesophageal reflux and cough in idiopathic pulmonary fibrosis: an intervention study.

PubMed

Kilduff, Claire E; Counter, Melanie J; Thomas, Gareth A; Harrison, Nicholas K; Hope-Gill, Benjamin D

2014-01-01

Chronic cough affects more than 70 percent of patients with Idiopathic Pulmonary Fibrosis and causes significant morbidity. Gastroesophageal reflux is the cause of some cases of chronic cough; and also has a postulated role in the aetiology of Idiopathic Pulmonary Fibrosis. A high prevalence of acid; and more recently non-acid, reflux has been observed in Idiopathic Pulmonary Fibrosis cohorts. Therefore, gastroesophageal reflux may be implicated in the pathogenesis of cough in Idiopathic Pulmonary Fibrosis. Eighteen subjects with Idiopathic Pulmonary Fibrosis underwent 24-hour oesophageal impedance and cough count monitoring after the careful exclusion of causes of chronic cough other than gastroesophageal reflux. All 18 were then treated with high dose acid suppression therapies. Fourteen subjects underwent repeat 24-hour oesophageal impedance and cough count monitoring after eight weeks. Total reflux and acid reflux frequencies were within the normal range in the majority of this cohort. The frequencies of non-acid and proximal reflux events were above the normal range. Following high dose acid suppression therapy there was a significant decrease in the number of acid reflux events (p = 0.02), but an increase in the number of non-acid reflux events (p = 0.01). There was no change in cough frequency (p = 0.70). This study confirms that non-acid reflux is prevalent; and that proximal oesophageal reflux occurs in the majority, of subjects with Idiopathic Pulmonary Fibrosis. It is the first study to investigate the effect of acid suppression therapy on gastroesophageal reflux and cough in patients with Idiopathic Pulmonary Fibrosis. The observation that cough frequency does not improve despite verifiable reductions in oesophageal acid exposure challenges the role of acid reflux in Idiopathic Pulmonary Fibrosis associated cough. The finding that non-acid reflux is increased following the use of acid suppression therapies cautions against the widespread use of acid suppression in patients with Idiopathic Pulmonary Fibrosis given the potential role for non-acid reflux in the pathogenesis of cough and Idiopathic Pulmonary Fibrosis itself. The study was registered with the Cardiff and Vale University Local Health Board Research and Development Committee (09/CMC/4619) and the South East Wales Ethics Committee (09/WSE04/57).

Effect of acid suppression therapy on gastroesophageal reflux and cough in idiopathic pulmonary fibrosis: an intervention study

PubMed Central

2014-01-01

Background Chronic cough affects more than 70 percent of patients with Idiopathic Pulmonary Fibrosis and causes significant morbidity. Gastroesophageal reflux is the cause of some cases of chronic cough; and also has a postulated role in the aetiology of Idiopathic Pulmonary Fibrosis. A high prevalence of acid; and more recently non-acid, reflux has been observed in Idiopathic Pulmonary Fibrosis cohorts. Therefore, gastroesophageal reflux may be implicated in the pathogenesis of cough in Idiopathic Pulmonary Fibrosis. Methods Eighteen subjects with Idiopathic Pulmonary Fibrosis underwent 24-hour oesophageal impedance and cough count monitoring after the careful exclusion of causes of chronic cough other than gastroesophageal reflux. All 18 were then treated with high dose acid suppression therapies. Fourteen subjects underwent repeat 24-hour oesophageal impedance and cough count monitoring after eight weeks. Results Total reflux and acid reflux frequencies were within the normal range in the majority of this cohort. The frequencies of non-acid and proximal reflux events were above the normal range. Following high dose acid suppression therapy there was a significant decrease in the number of acid reflux events (p = 0.02), but an increase in the number of non-acid reflux events (p = 0.01). There was no change in cough frequency (p = 0.70). Conclusions This study confirms that non-acid reflux is prevalent; and that proximal oesophageal reflux occurs in the majority, of subjects with Idiopathic Pulmonary Fibrosis. It is the first study to investigate the effect of acid suppression therapy on gastroesophageal reflux and cough in patients with Idiopathic Pulmonary Fibrosis. The observation that cough frequency does not improve despite verifiable reductions in oesophageal acid exposure challenges the role of acid reflux in Idiopathic Pulmonary Fibrosis associated cough. The finding that non-acid reflux is increased following the use of acid suppression therapies cautions against the widespread use of acid suppression in patients with Idiopathic Pulmonary Fibrosis given the potential role for non-acid reflux in the pathogenesis of cough and Idiopathic Pulmonary Fibrosis itself. Study registration The study was registered with the Cardiff and Vale University Local Health Board Research and Development Committee (09/CMC/4619) and the South East Wales Ethics Committee (09/WSE04/57). PMID:24876887

Familial or Sporadic Idiopathic Scoliosis – classification based on artificial neural network and GAPDH and ACTB transcription profile

PubMed Central

2013-01-01

Background Importance of hereditary factors in the etiology of Idiopathic Scoliosis is widely accepted. In clinical practice some of the IS patients present with positive familial history of the deformity and some do not. Traditionally about 90% of patients have been considered as sporadic cases without familial recurrence. However the exact proportion of Familial and Sporadic Idiopathic Scoliosis is still unknown. Housekeeping genes encode proteins that are usually essential for the maintenance of basic cellular functions. ACTB and GAPDH are two housekeeping genes encoding respectively a cytoskeletal protein β-actin, and glyceraldehyde-3-phosphate dehydrogenase, an enzyme of glycolysis. Although their expression levels can fluctuate between different tissues and persons, human housekeeping genes seem to exhibit a preserved tissue-wide expression ranking order. It was hypothesized that expression ranking order of two representative housekeeping genes ACTB and GAPDH might be disturbed in the tissues of patients with Familial Idiopathic Scoliosis (with positive family history of idiopathic scoliosis) opposed to the patients with no family members affected (Sporadic Idiopathic Scoliosis). An artificial neural network (ANN) was developed that could serve to differentiate between familial and sporadic cases of idiopathic scoliosis based on the expression levels of ACTB and GAPDH in different tissues of scoliotic patients. The aim of the study was to investigate whether the expression levels of ACTB and GAPDH in different tissues of idiopathic scoliosis patients could be used as a source of data for specially developed artificial neural network in order to predict the positive family history of index patient. Results The comparison of developed models showed, that the most satisfactory classification accuracy was achieved for ANN model with 18 nodes in the first hidden layer and 16 nodes in the second hidden layer. The classification accuracy for positive Idiopathic Scoliosis anamnesis only with the expression measurements of ACTB and GAPDH with the use of ANN based on 6-18-16-1 architecture was 8 of 9 (88%). Only in one case the prediction was ambiguous. Conclusions Specially designed artificial neural network model proved possible association between expression level of ACTB, GAPDH and positive familial history of Idiopathic Scoliosis. PMID:23289769

Periprosthetic Tissue Loss in Patients With Idiopathic Vitreous Inflammation After the Boston Keratoprosthesis.

PubMed

Grassi, Christina M; Cruzat, Andrea; Taniguchi, Elise V; Crnej, Alja; Colby, Kathryn A; Dohlman, Claes H; Chodosh, James

2015-11-01

Idiopathic vitritis is a poorly understood complication after Boston keratoprosthesis surgery with unclear etiology. We sought to determine whether an association exists between periprosthetic corneal tissue loss and the development of idiopathic vitritis in keratoprosthesis recipients. Thirteen Boston type I keratoprosthesis recipient eyes with a history of idiopathic vitritis and 34 type I keratoprosthesis recipient eyes with no history of idiopathic vitritis underwent anterior segment optical coherence tomography (AS-OCT) at a median time postoperatively of 2.4 years versus 1.9 years (range, 0.5-14.2 vs. 0.1-13.6 years), respectively. Areas of corneal graft tissue loss ("gaps") around the keratoprosthesis stem were identified and analyzed by 2 masked observers. The difference in the presence, number, and size of gaps was compared between cases and controls. A periprosthetic gap was identified more commonly in idiopathic vitritis cases than in controls on AS-OCT (11/13, 86% vs. 11/34, 33.3%, P < 0.001). The number of gaps between cases and controls was also significantly different (2.6 ± 1.6 vs. 0.5 ± 0.8, P < 0.001), but not the estimated gap area (0.056 ± 0.049 mm² vs. 0.039 ± 0.025 mm², P = 0.22). A significantly higher proportion of keratoprosthesis recipient eyes with idiopathic vitritis had corneal tissue loss around the keratoprosthesis stem than did controls. Tissue loss could serve as an entry point for debris or bacterial components, triggering idiopathic vitritis. Our study underscores the utility of AS-OCT imaging in the postoperative management of keratoprosthesis patients.

Perspective: Update on Idiopathic Intracranial Hypertension

PubMed Central

Bruce, Beau B.; Biousse, Valérie; Newman, Nancy J.

2011-01-01

Purpose Provide an update on various features of idiopathic intracranial hypertension. Design Perspective. Methods Selected articles on the epidemiology, clinical and imaging features, natural history, pathophysiology, and treatment of idiopathic intracranial hypertension were reviewed and interpreted in the context of the authors’ clinical and research experience. Results Idiopathic intracranial hypertension is primarily a disease of obese women of childbearing age, but it can affect patients of any weight, sex, and age. Although a relatively rare disorder, idiopathic intracranial hypertension’s associated costs in the U.S. entail hundreds of millions of dollars. Even following treatment, headaches are frequently persistent and may require the continued involvement of a neurologist. Quality of life reductions and depression are common among idiopathic intracranial hypertension patients. However, visual dysfunction, especially visual field abnormalities, represents the major morbidity of this disorder, and serial automated perimetry remains the primary mode of patient monitoring. Patients who are men, black, very obese, or anemic are at higher risk of visual loss. Vitamin A metabolism, adipose tissue as an actively secreting endocrine tissue, and cerebral venous abnormalities are areas of active study regarding idiopathic intracranial hypertension’s pathophysiology. Treatment studies show that lumbar puncture is a valuable treatment (in addition to its crucial diagnostic role) and that weight management is critical. However, open questions remain regarding the efficacy of acetazolamide, CSF diversion procedures, and cerebral venous stenting. Conclusions Many questions remain unanswered about idiopathic intracranial hypertension. Ongoing studies, especially an ongoing NIH-funded clinical trial of acetazolamide, should provide more insight into this important, yet poorly understood syndrome of isolated intracranial hypertension. PMID:21696699

Treatment of idiopathic pulmonary fibrosis with losartan: a pilot project.

PubMed

Couluris, Marisa; Kinder, Brent W; Xu, Ping; Gross-King, Margaret; Krischer, Jeffrey; Panos, Ralph J

2012-10-01

Idiopathic pulmonary fibrosis is a progressive interstitial lung disease with no current effective therapies. Treatment has focused on antifibrotic agents to stop proliferation of fibroblasts and collagen deposition in the lung. We present the first clinical trial data on the use of losartan, an antifibrotic agent, to treat idiopathic pulmonary fibrosis. The primary objective was to evaluate the effect of losartan on progression of idiopathic pulmonary fibrosis measured by the change in percentage of predicted forced vital capacity (%FVC) after 12 months. Secondary outcomes included the change in forced expiratory volume at 1 second, diffusing capacity of carbon monoxide, 6-minute walk test distance, and baseline/transition dyspnea index. Patients with idiopathic pulmonary fibrosis and a baseline %FVC of ≥50 % were treated with losartan 50 mg by mouth daily for 12 months. Pulmonary function testing, 6-minute walk, and breathlessness indices were measured every 3 months. Twenty participants with idiopathic pulmonary fibrosis were enrolled and 17 patients were evaluable for response. Twelve patients had a stable or improved %FVC at study month 12. Similar findings were observed in secondary end-point measures, including 58, 71, and 65 % of patients with stable or improved forced expiratory volume at 1 second, diffusing capacity for carbon monoxide, and 6-minute walk test distance, respectively. No treatment-related adverse events that resulted in early study discontinuation were reported. Losartan stabilized lung function in patients with idiopathic pulmonary fibrosis over 12 months. Losartan is a promising agent for the treatment of idiopathic pulmonary fibrosis and has a low toxicity profile.

Idiopathic hypersomnia: a study of 77 cases.

PubMed

Anderson, Kirstie N; Pilsworth, Samantha; Sharples, Linda D; Smith, Ian E; Shneerson, John M

2007-10-01

To review the clinical and polysomnographic characteristics of idiopathic hypersomnia as well as the long-term response to treatment. The Respiratory Support and Sleep Centre at Papworth Hospital, Cambridge, UK. A large database of more than 6000 patients with sleep disorders was reviewed. A retrospective study of the clinical and polysomnographic characteristics of 77 patients with idiopathic hypersomnia was performed. Comparison with a similar group of patients with narcolepsy was performed. The response to drug treatment was assessed in 61 patients over a mean follow-up of 3.8 years. Idiopathic hypersomnia was 60% as prevalent as narcolepsy. Comparison with a similar group of patients with narcolepsy showed that those with idiopathic hypersomnia were more likely to have prolonged unrefreshing daytime naps, a positive family history, increased slow-wave sleep, and a longer sleep latency on the Multiple Sleep Latency Test. The results of the Multiple Sleep Latency Test were not helpful in predicting disease severity or treatment response. The clinical features were heterogeneous and of variable severity. The majority of patients with idiopathic hypersomnia had symptoms that remained stable over many years, but 11% had spontaneous remission, which was never seen in narcolepsy. Two thirds of patients with idiopathic hypersomnolence had a sustained improvement in daytime somnolence with medication, although a third needed high doses or combinations of drugs. Idiopathic hypersomnolence has characteristic clinical and polysomnographic features but the prolonged latency on the Multiple Sleep Latency Test raises doubt about the validity of this test within the current diagnostic criteria. The disease often responds well to treatment and a substantial minority of patients appear to spontaneously improve.

Multiple idiopathic external apical root resorption: report of four cases.

PubMed

Cholia, S S; Wilson, P H R; Makdissi, J

2005-07-01

Multiple idiopathic external root resorption is an unusual condition that may present in a cervical or an apical form. In this article, we review the published literature relating to multiple idiopathic external apical root resorption and present four clinical cases. We consider the aetiology of this condition and discuss the various treatment options.

Electronic protocol of respiratory physical therapy in patients with idiopathic adolescent scoliosis.

PubMed

Cano, Danila Vieira Baldini; Malafaia, Osvaldo; Alves, Vera Lúcia dos Santos; Avanzi, Osmar; Pinto, José Simão de Paula

2011-01-01

To create a clinical database of respiratory function in patients with adolescent idiopathic scoliosis; computerize and store this clinical data through the use of a software; incorporate this electronic protocol to the SINPE© (Integrated Electronic Protocols System) and analyze a pilot project with interpretation of results. From the literature review a computerized data bank of clinical data of postural deviations was set up (master protocol). Upon completion of the master protocol a specific protocol of respiratory function in patients with adolescent idiopathic scoliosis was designed and a pilot project was conducted to collect and analyze data from ten patients. It was possible to create the master protocol of postural deviations and the specific protocol of respiratory function in patients with adolescent idiopathic scoliosis. The data collected in the pilot project was processed by the SINPE ANALYZER©, generating charts and statistics. The establishment of the clinical database of adolescent idiopathic scoliosis was possible. Computerization and storage of clinical data using the software were viable. The electronic protocol of adolescent idiopathic scoliosis could be incorporated into the SINPE© and its use in the pilot project was successful.

Juvenile idiopathic arthritis.

PubMed

Boros, Christina; Whitehead, Ben

2010-09-01

Juvenile idiopathic arthritis is the most common rheumatic disease in childhood, occurring in approximately 1:500 children. Despite a recent expansion in treatment options and improvement of outcomes, significant morbidity still occurs. This article outlines the clinical manifestations, assessment, detection of complications, treatment options and monitoring requirements, with the aid of guidelines recently published by The Royal Australian College of General Practitioners, which provide practical support for general practitioners to ensure best practice care and to prevent lifelong disability in patients with juvenile idiopathic arthritis. General practice plays an important role in the early detection, initial management and ongoing monitoring of children with juvenile idiopathic arthritis. Early detection involves understanding the classification framework for subtypes of juvenile idiopathic arthritis, and being aware of the clinical manifestations and how to look for them, through history, examination and appropriate investigation. The major extra-articular manifestations of juvenile idiopathic arthritis are uveitis and growth disturbance. Treatment options include nonsteroidal anti-inflammatory drugs, methotrexate, biologic agents, and corticosteroids. Management using a multidisciplinary approach can prevent long term sequelae. Unfortunately, approximately 50% of children will have active disease as adults.

The contribution of the SPINK1 c.194+2T>C mutation to the clinical course of idiopathic chronic pancreatitis in Chinese patients.

PubMed

Sun, Chang; Liao, Zhuan; Jiang, Lili; Yang, Fu; Xue, Geng; Zhou, Qi; Chen, Ruiwen; Sun, Shuhan; Li, Zhaoshen

2013-01-01

Recent data suggest that the serine protease inhibitor Kazal type 1 (SPINK1) gene mutation is associated with idiopathic chronic pancreatitis. However, few studies have focused on the serine protease inhibitor Kazal type 1 c.194+2T>C mutation. Therefore, our goal was to study the prevalence and impact of serine protease inhibitor Kazal type 1 mutations on the clinical profile of idiopathic chronic pancreatitis patients in China. A retrospective-cohort study of 118 Chinese patients with idiopathic chronic pancreatitis was performed, and genetic tests were carried out to detect SPINK1 mutations. Subjects without pancreatitis were used as controls. In total, 118 idiopathic chronic pancreatitis patients and 100 control subjects were evaluated. The serine protease inhibitor Kazal type 1 c.194+2T>C variant was present in 44.9% of patients with idiopathic chronic pancreatitis. The frequency of diabetes in idiopathic chronic pancreatitis patients with the serine protease inhibitor Kazal type 1 c.194+2T>C mutation (39.6%) was higher than that of patients without the mutation (9.2%). The time to occurrence of diabetes mellitus after idiopathic chronic pancreatitis symptom onset is significantly influenced by the c.194+2T>C mutation (p<0.001). In addition, the mean age of diabetes onset in patients with the serine protease inhibitor Kazal type 1 c.194+2T>C mutation (38.33 ± 9.50) was significantly younger than that of patients without this mutation (49.67 ± 6.74). The presence of the serine protease inhibitor Kazal type 1 c.194+2T>C mutation seems to be associated with idiopathic chronic pancreatitis and could predispose individuals to pancreatic diabetes onset at an earlier age. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The influence of thermoplastic thoraco lumbo sacral orthoses on standing balance in subjects with idiopathic scoliosis.

PubMed

Khanal, Minoo; Arazpour, Mokhtar; Bahramizadeh, Mahmood; Samadian, Mohammad; Hutchins, Stephen W; Kashani, Reza Vahab; Mardani, Mohammad A; Tari, Hossein Vahid; Aboutorabi, Atefeh; Curran, Sarah; Sadeghi, Heidar

2016-08-01

Idiopathic scoliosis patients have postural equilibrium problems. The objective of this study was to assess postural control in subjects with idiopathic scoliosis following a 4-month intervention in an unbraced position. Quasi-experimental. Eight healthy girls and eight girls with idiopathic scoliosis took part. A Kistler force platform was used with a frequency of 100 Hz for recording data. The center of pressure was recorded in different positions out of brace for scoliosis and healthy subjects. Test conditions were single limb and double limb stance, with eyes open and closed, and foam and rigid surfaces. The data reflected a weak balance of idiopathic scoliosis subjects compared to healthy subjects. After 1 and 4 months of wearing the brace, center of pressure and center of gravity sway increased in the majority of the tests, although there were no significant differences in any of the test conditions (p > 0.05). While the center of pressure sway in medio-lateral direction decreased after 4 months of wearing a brace, in other variables center of pressure and center of gravity sway increased. Idiopathic scoliosis patients have weak balance in comparison to healthy subjects. In addition, following a period of 4 months of wearing a brace, balance parameters in the scoliosis subjects did not improve. The results show that we need more follow-up of orthoses wearing in idiopathic scoliosis subjects and suggest more studies at least 1-year follow-up to identify the efficiency of brace wear on balance. Scoliosis can alter postural stability and balance performance during quiet standing. Spinal deformity can alter a subject's ability to compensate for postural changes and cause gait deviations. This study investigated balance differences between the healthy and idiopathic scoliosis patients and the results of thoraco lumbo sacral orthosis brace wear. It might provide some new insight into the conservative treatment of idiopathic scoliosis patients for clinicians and researchers. © The International Society for Prosthetics and Orthotics 2015.

Flow void of cerebrospinal fluid in idiopathic normal pressure hydrocephalus of the elderly: can it predict outcome after shunting?

PubMed

Krauss, J K; Regel, J P; Vach, W; Jüngling, F D; Droste, D W; Wakhloo, A K

1997-01-01

We investigate the predictive value of cerebrospinal fluid (CSF) flow void on outcome after shunting in a prospective series of patients with idiopathic normal pressure hydrocephalus (NPH). The degree and extension of CSF flow void were examined on T2-weighted magnetic resonance imaging scans of 37 elderly patients with idiopathic NPH who underwent subsequent shunting. The degree of flow void was assessed in comparison with the signal of large cerebral arteries. The extension was evaluated via the calculation of sum scores for the occurrence of flow void in different locations of the ventricular system. Those parameters were not considered in the decision to perform shunting. CSF flow void in the aqueduct and the adjacent third and fourth ventricles of the 37 patients with idiopathic NPH was compared with that of 37 age-matched control patients. CSF flow void scores in patients with idiopathic NPH were investigated for correlations between postoperative outcome scores and ventricular width indices. No difference was found between the occurrence of aqueductal CSF flow void in patients with idiopathic NPH and the control group. A significant difference, however, was noted for the extension of the CSF flow void, which was greater in the NPH group. Postoperative improvement was found in 33 of 37 patients with idiopathic NPH at a mean follow-up of 15.6 months. Only small, statistically not significant correlations were found between CSF flow void and postoperative outcome. Flow void sum scores, however, correlated significantly with ventricular width indices. The degree and extension of CSF flow void on T2-weighted magnetic resonance imaging scans have little predictive value for outcome after shunting in patients with idiopathic NPH. The greater extension of the CSF flow void in patients with NPH is most likely related to increased ventricular width. It is not useful to consider CSF flow void findings on conventional magnetic resonance imaging scans in making the decision to offer shunting in patients with idiopathic NPH.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keane, T.J.; Van Dyk, J.; Rider, W.D.

Interstitial pneumonia is a frequent and often fatal complication of allogenic bone marrow transplantation. Thirty to 40 percent of such cases are of unknown etiology and have been labelled as cases of idiopathic interstitial pneumonia. Idiopathic cases are more commonly associated with the use of total body irradiation; their occurrence appears to be independent of immunosupression or graft versus host disease. Evidence is presented from the literature suggesting that the development of idiopathic interstitial pneumonia is related to the absolute absorbed dose of radiation to lung. The similarity of idiopathic pneumonia to radiation pneumonitis seen in a different clinical settingmore » is described.« less

Idiopathic burning mouth syndrome: a common treatment-refractory somatoform condition responsive to ECT.

PubMed

McGirr, Alexander; Davis, Lindsay; Vila-Rodriguez, Fidel

2014-04-30

Somatic symptom disorders are common causes of disability and suffering, and can pose significant management challenges. Idiopathic burning mouth syndrome is a challenging somatic symptom disorder with relatively high prevalence, particularly among post-menopausal women. Here, we present the case of a woman with severe treatment refractory idiopathic burning mouth syndrome and comorbid major depressive disorder, who was successfully treated with bitemporal electroconvulsive therapy. This case highlights the potential effectiveness of electroconvulsive therapy in idiopathic burning mouth syndrome when other treatment options have been exhausted. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Prevalence of the HLA-DQB1*0602 allele in narcolepsy and idiopathic hypersomnia patients seen at a sleep disorders outpatient unit in São Paulo.

PubMed

Coelho, Fernando Morgadinho Santos; Pradella-Hallinan, Márcia; Predazzoli Neto, Mario; Bittencourt, Lia Rita Azeredo; Tufik, Sérgio

2009-03-01

Narcolepsy (with and without cataplexy) and idiopathic hypersomnia, are disorders with common features but with different HLA-DQB1*0602 allele prevalence. The present study describes the prevalence of HLA-DQB1*0602 allele in narcoleptics with and without cataplexy and in patients with idiopathic hypersomnia. Subjects comprised 68 patients who were diagnosed for narcolepsy or idiopathic hypersomnia and 23 healthy controls according to the International Classification of Sleep Disorders-2. Subjects comprised 43 patients with narcolepsy and cataplexy, 11 patients with narcolepsy but without cataplexy, 14 patients with idiopathic hypersomnia and 23 healthy controls. Genotyping of HLA-DQB1*0602 allele was performed for all subjects. The prevalence of the HLA-DQB1*0602 allele was increased in idiopathic hypersomnia and in narcoleptic patients with and without cataplexy when compared to healthy subjects (p = 0.04; p = 0.03 and p < 0.0001, respectively). This finding is in accordance with those of previous studies. The gold standard exam of narcolepsy with cataplexy is Hypocretin-1 dosage, but in patients without cataplexy and idiopathic hypersomnia, there are no specific diagnostic lab findings. The presence of the HLA-DQB1* 0602 allele may be important for the differential diagnosis of situations that resemble those sleep disorders such as secondary changes in sleep structure due to drugs' consumption.

Obesity is a significant susceptibility factor for idiopathic AA amyloidosis.

PubMed

Blank, Norbert; Hegenbart, Ute; Dietrich, Sascha; Brune, Maik; Beimler, Jörg; Röcken, Christoph; Müller-Tidow, Carsten; Lorenz, Hanns-Martin; Schönland, Stefan O

2018-03-01

To investigate obesity as susceptibility factor in patients with idiopathic AA amyloidosis. Clinical, biochemical and genetic data were obtained from 146 patients with AA amyloidosis. Control groups comprised 40 patients with long-standing inflammatory diseases without AA amyloidosis and 56 controls without any inflammatory disease. Patients with AA amyloidosis had either familial Mediterranean fever (FMF) or long-standing rheumatic diseases as underlying inflammatory disease (n = 111, median age 46 years). However, in a significant proportion of patients with AA amyloidosis no primary disease was identified (idiopathic AA; n = 37, median age 60 years). Patients with idiopathic AA amyloidosis were more obese and older than patients with AA amyloidosis secondary to FMF or rheumatic diseases. Serum leptin levels correlated with the body mass index (BMI) in all types of AA amyloidosis. Elevated leptin levels of more than 30 µg/l were detected in 18% of FMF/rheumatic + AA amyloidosis and in 40% of patients with idiopathic AA amyloidosis (p = .018). Finally, the SAA1 polymorphism was confirmed as a susceptibility factor for AA amyloidosis irrespective of the type of the disease. Obesity, age and the SAA1 polymorphism are susceptibility factors for idiopathic AA amyloidosis. Recent advances in treatment of FMF and rheumatic disorders will decrease the incidence of AA amyloidosis due to these diseases. Idiopathic AA, however, might be an emerging problem in the ageing and increasingly obese population.

Castleman Disease Presenting as an Abdominal Mass.

PubMed

Shariati, Farnaz; Verter, Elizabeth; Chang, Wendy; Huang, Li; Joshi, Virendra

2017-01-01

Unicentric Castleman disease is a rare condition of lymphoid hyperplasia, of which only 15% of cases occur in the abdomen. We report a 66-year-old man who presented with complaints of abdominal pain. Computed tomography scans revealed nephrolithiasis and a homogeneous calcified mass between the pancreas and stomach and several para-pancreatic nodes. Direct visualization during exploratory laparotomy revealed a mass on the lesser curvature of the stomach. Pyloromyotomy and mass resection were performed. Biopsy showed reactive lymphoid hyperplasia consistent with the hyaline vascular variant of Castleman disease.

Castleman Disease Presenting as an Abdominal Mass

PubMed Central

Verter, Elizabeth; Chang, Wendy; Huang, Li; Joshi, Virendra

2017-01-01

Unicentric Castleman disease is a rare condition of lymphoid hyperplasia, of which only 15% of cases occur in the abdomen. We report a 66-year-old man who presented with complaints of abdominal pain. Computed tomography scans revealed nephrolithiasis and a homogeneous calcified mass between the pancreas and stomach and several para-pancreatic nodes. Direct visualization during exploratory laparotomy revealed a mass on the lesser curvature of the stomach. Pyloromyotomy and mass resection were performed. Biopsy showed reactive lymphoid hyperplasia consistent with the hyaline vascular variant of Castleman disease. PMID:28584844

Sensory Impairment and Head Circumference in Fragile X Syndrome, Down Syndrome and Idiopathic Intellectual Disability.

ERIC Educational Resources Information Center

Turk, Jeremy; Patton, Michael

2000-01-01

Eighteen boys with fragile X syndrome were compared with 42 with idiopathic intellectual disability, and 45 with Down syndrome. Boys with Down syndrome had more sensory problems and smaller head circumferences than normal. Head circumferences of boys with fragile X syndrome and with idiopathic intellectual disability were larger than normal.…

Screening for Adolescent Idiopathic Scoliosis: US Preventive Services Task Force Recommendation Statement.

PubMed

Grossman, David C; Curry, Susan J; Owens, Douglas K; Barry, Michael J; Davidson, Karina W; Doubeni, Chyke A; Epling, John W; Kemper, Alex R; Krist, Alex H; Kurth, Ann E; Landefeld, C Seth; Mangione, Carol M; Phipps, Maureen G; Silverstein, Michael; Simon, Melissa A; Tseng, Chien-Wen

2018-01-09

Adolescent idiopathic scoliosis, a lateral curvature of the spine of unknown cause with a Cobb angle of at least 10°, occurs in children and adolescents aged 10 to 18 years. Idiopathic scoliosis is the most common form and usually worsens during adolescence before skeletal maturity. Severe spinal curvature may be associated with adverse long-term health outcomes (eg, pulmonary disorders, disability, back pain, psychological effects, cosmetic issues, and reduced quality of life). Early identification and effective treatment of mild scoliosis could slow or stop curvature progression before skeletal maturity, thereby improving long-term outcomes in adulthood. To update the 2004 US Preventive Services Task Force (USPSTF) recommendation on screening for idiopathic scoliosis in asymptomatic adolescents. The USPSTF reviewed the evidence on the benefits and harms of screening for and treatment of adolescent idiopathic scoliosis. The USPSTF found no direct evidence on screening for adolescent idiopathic scoliosis and health outcomes and no evidence on the harms of screening. The USPSTF found inadequate evidence on treatment with exercise and surgery. It found adequate evidence that treatment with bracing may slow curvature progression in adolescents with mild or moderate curvature severity (Cobb angle <40° to 50°); however, evidence on the association between reduction in spinal curvature in adolescence and long-term health outcomes in adulthood is inadequate. The USPSTF found inadequate evidence on the harms of treatment. Therefore, the USPSTF concludes that the current evidence is insufficient and that the balance of benefits and harms of screening for adolescent idiopathic scoliosis cannot be determined. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for adolescent idiopathic scoliosis in children and adolescents aged 10 to 18 years. (I statement).

Idiopathic ventricular tachycardia and fibrillation.

PubMed

Belhassen, B; Viskin, S

1993-06-01

Important data have recently been added to our understanding of sustained ventricular tachyarrhythmias occurring in the absence of demonstrable heart disease. Idiopathic ventricular tachycardia (VT) is usually of monomorphic configuration and can be classified according to its site of origin as either right monomorphic (70% of all idiopathic VTs) or left monomorphic VT. Several physiopathological types of monomorphic VT can be presently individualized, according to their mode of presentation, their relationship to adrenergic stress, or their response to various drugs. The long-term prognosis is usually good. Idiopathic polymorphic VT is a much rarer type of arrhythmia with a less favorable prognosis. Idiopathic ventricular fibrillation may represent an underestimated cause of sudden cardiac death in ostensibly healty patients. A high incidence of inducibility of sustained polymorphic VT with programmed ventricular stimulation has been found by our group, but not by others. Long-term prognosis on Class IA antiarrhythmic medications that are highly effective at electrophysiologic study appears excellent.

Guidelines for the medical treatment of idiopathic pulmonary fibrosis.

PubMed

Xaubet, Antoni; Molina-Molina, María; Acosta, Orlando; Bollo, Elena; Castillo, Diego; Fernández-Fabrellas, Estrella; Rodríguez-Portal, José Antonio; Valenzuela, Claudia; Ancochea, Julio

2017-05-01

Idiopathic pulmonary fibrosis is defined as chronic fibrosing interstitial pneumonia limited to the lung, with poor prognosis. The incidence has been rising in recent years probably due to improved diagnostic methods and increased life expectancy. In 2013, the SEPAR guidelines for the diagnosis and treatment for idiopathic pulmonary fibrosis were published. Since then, clinical trials and meta-analyses have shown strong scientific evidence for the use of pirfenidone and nintedanib in the treatment of idiopathic pulmonary fibrosis. In 2015, the international consensus of 2011 was updated and new therapeutic recommendations were established, prompting us to update our recommendation for the medical treatment of idiopathic pulmonary fibrosis accordingly. Diagnostic aspects and non-pharmacological treatment will not be discussed as no relevant developments have emerged since the 2013 guidelines. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Comparison of Polysomnography and Multiple Sleep Latency Test Findings in Subjects with Narcolepsy and İdiopathic Hypersomnia.

PubMed

Erdem, Murat; Bolu, Abdullah; Ünlü, A Gazi; Alper, Mustafa; Yetkin, Sinan

2013-09-01

Both narcolepsy and idiopathic hypersomnia are the main causes of excessive daytime sleepiness. In this study, we aimed to compare polysomnography (PSG) and multiple sleep latency test (MSLT) findings in narcolepsy and idiopathic hypersomnia patients. The files of patients with narcolepsy and hypersomnia who were admitted between 1995 and 2009 were reviewed. We evaluated data from 94 patients with narcolepsy with cataplexy, 49 with narcolepsy without cataplexy and 140 patients with idiopathic hypersomnia. Sleep latency and REM latency were longer in idiopathic hypersomnia group than in narcolepsy with and without cataplexy group. Mean sleep latency in MSLT was the shortest in narcolepsy with cataplexy group. There was no difference in sleep efficiency, percentage of sleep stage and number of awakenings in PSG between three groups. The findings of the study indicated that narcolepsy patients differ from idiopathic hypersomnia patients in terms of sleep latency and REM latency in PSG.

Orthodontic treatment in patient with idiopathic root resorption: a case report.

PubMed

Rey, Diego; Smit, Rosana Martínez; Gamboa, Liliana

2015-01-01

Multiple idiopathic external root resorption is a rare pathological condition usually detected as an incidental radiographic finding. External root resorption of permanent teeth is a multifactorial process related to several local and systemic factors. If an etiological factor cannot be identified for root resorption, the term "idiopathic" is applied. This report presents a case of multiple idiopathic apical root resorption. The condition was found in a young female patient seeking orthodontic treatment due to malocclusion. This kind of resorption starts apically and progresses coronally, causing a gradual shortening and rounding of the remaining root. Patients with this condition are not the ideal candidates for orthodontic treatment; however, the aim of this report is to describe an unusual case of idiopathic root resorption involving the entire dentition, and to present the orthodontic treatment of this patient. It describes the progress and completion of orthodontic therapy with satisfactory end results.

Bayesian comparative effectiveness study of four consensus treatment plans for initial management of systemic juvenile idiopathic arthritis: FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST).

PubMed

Nigrovic, Peter A; Beukelman, Timothy; Tomlinson, George; Feldman, Brian M; Schanberg, Laura E; Kimura, Yukiko

2018-06-01

Systemic juvenile idiopathic arthritis is a rare febrile arthritis of childhood characterized by a potentially severe course, including prolonged glucocorticoid exposure, growth failure, destructive arthritis, and life-threatening macrophage activation syndrome. Early cytokine-blocking biologic therapy may improve long-term outcomes, although some systemic juvenile idiopathic arthritis patients respond well to non-biologic treatment, leaving optimal management undefined. Consequently, treatment of new-onset systemic juvenile idiopathic arthritis by expert clinicians varies widely. To describe a pragmatic, observational comparative effectiveness study that takes advantage of diversity in the management of a rare disease: FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST), comparing non-biologic and biologic consensus treatment plans for new-onset systemic juvenile idiopathic arthritis within the 60-center Childhood Arthritis and Rheumatology Research Alliance Registry (CARRA). FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST) is a multicenter, prospective, non-randomized study that compares four Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans for new-onset systemic juvenile idiopathic arthritis: (1) glucocorticoids alone, (2) methotrexate, (3) interleukin-1 blockade, and (4) interleukin-6 blockade. Patients consenting to participation in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry are started on one of four Consensus Treatment Plans at the discretion of the treating physician. The outcome of primary interest is clinically inactive disease off glucocorticoids at 9 months, comparing non-biologic (Consensus Treatment Plans 1 + 2) versus biologic (Consensus Treatment Plans 3 + 4) strategies. Bayesian analytic methods will be employed to evaluate response rates, using propensity scoring to balance treatment groups for potential confounding. With 200 patients in a 2:1 ratio of biologic to non-biologic, there is a >90% probability of finding biologic consensus treatment plans more effective if the rate of clinically inactive disease is 30% higher than for non-biologic therapy. Additional outcomes include Patient-Reported Outcomes Measurement Information System measures and other parent-/patient-reported outcomes reported in real time using smartphone technology. Routine operation of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry will allow assessment of outcomes over at least 10 years. FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST) began enrollment in November 2016. The observational design may not provide balance in measured and unmeasured confounders. Use of consensus treatment plan (CTP) strategies at frequencies more unbalanced than predicted could reduce the chance of finding differences in efficacy. FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST) will provide the first prospective comparison of Childhood Arthritis and Rheumatology Research Alliance's (CARRA's) consensus-derived non-biologic versus biologic management strategies in systemic juvenile idiopathic arthritis, performed in a real-world setting wherein each patient receives standard-of-care treatment selected by the treating physician. Outcomes include clinician- and patient-/family-reported outcomes, empowering both physician and patient decision making in new-onset systemic juvenile idiopathic arthritis.

Brief Report: Sensorimotor Gating in Idiopathic Autism and Autism Associated with Fragile X Syndrome

ERIC Educational Resources Information Center

Yuhas, Jennifer; Cordeiro, Lisa; Tassone, Flora; Ballinger, Elizabeth; Schneider, Andrea; Long, James M.; Ornitz, Edward M.; Hessl, David

2011-01-01

Prepulse inhibition (PPI) may useful for exploring the proposed shared neurobiology between idiopathic autism and autism caused by FXS. We compared PPI in four groups: typically developing controls (n = 18), FXS and autism (FXS+A; n = 15), FXS without autism spectrum disorder (FXS-A; n = 17), and idiopathic autism (IA; n = 15). Relative to…

Do adolescents with idiopathic scoliosis have body schema disorders? A cross-sectional study.

PubMed

Picelli, Alessandro; Negrini, Stefano; Zenorini, Andrea; Iosa, Marco; Paolucci, Stefano; Smania, Nicola

2016-01-01

To date etiology of adolescent idiopathic scoliosis appears complex and still remains unclear. A distorted body schema has been proposed to be a part of a sequence of pathological events in the development of adolescent idiopathic scoliosis. To investigate the awareness of trunk misalignment in adolescents with idiopathic scoliosis. Information about 44 adolescents with idiopathic scoliosis was collected as follows: age; sex; handedness; family history of scoliosis; back pain; sport practice; shoulder and waist line symmetry; leg length; dorsal kyphosis; back hump; rehabilitation; scoliotic curve; Risser sign. We evaluated awareness of trunk misalignment with a graphic table displaying pictures of progressively increasing scoliotic curves. Patients were asked to indicate which picture corresponded to their perceived own spinal alignment. Patients with thoracolumbar scoliosis overestimated their actual thoracic spine curve. Patients with thoracic-thoracolumbar scoliosis underestimated their actual thoracolumbar spine curve and overestimated their actual lumbar spine curve. Scoliotic curve > 15°, double curve, younger age, back pain, family history of scoliosis and lower Risser score related with a misperception of trunk alignment. Our results support the hypothesis that adolescents with idiopathic scoliosis have an altered corporeal awareness of their trunk alignment.

Treatment of the idiopathic scoliosis with brace and physiotherapy.

PubMed

Hundozi-Hysenaj, Hajrije; Dallku, Iliriana Boshnjaku; Murtezani, Ardiana; Rrecaj, Shkurte

2009-01-01

Scoliosis is a three-dimensional deformation of the spine with a lateral curvature or deviation greater than 10 degrees and associated with vertebral rotation. Many conservative treatments are available for adolescents with idiopathic scoliosis, but the evidence for their effectiveness is still questioned. The objective of this study was to define the effectiveness of braces and individual physiotherapy for the comprehensive treatment of idiopathic scoliosis in adolescents. A retrospective study of 57 children with idiopathic thoracic dextroscoliosis with the magnitude of the thoracic curve between 20 degrees-35 degrees, treated in Orthopedic and Physiatrist Clinic as well as National Ortho-prosthetic Center within University Clinical Center of Kosova in Prishtina, during the period of 2003-2006. Inclusion of kinesitherapy in the comprehensive management of idiopathic scoliosis varied in the improvement of the muscle strength (satisfied and moderate) in almost 80% of the children while the correction of the curve was small in approximately 42.1% of cases. For children with idiopathic scoliosis, who require braces, an exercise program helps chest mobility, muscle strength, proper breathing flexibility in the spine, correct posture and keeps muscles in tone so that the transition period after brace removal is easier.

Circulating irisin and chemerin levels as predictors of seizure control in children with idiopathic epilepsy.

PubMed

Elhady, Marwa; Youness, Eman R; Gafar, Heba S; Abdel Aziz, Ali; Mostafa, Rehab S I

2018-06-02

Irisin and chemerin peptides expression are triggered by hypoxia and involved in activation of inflammatory cascades in various organs including the brain; however, their role in epilepsy is not fully illustrated. This study aims to explore the predictive role of irisin and chemerin for seizure control in children with idiopathic epilepsy. This cross-sectional comparative study included 50 children with idiopathic epilepsy; 25 of them had controlled seizures over the previous 6 months and 30 age- and sex-matched healthy children as controls. Epilepsy characteristics, seizure severity Chalfont score, and response to medications were assessed in relation to serum irisin and chemerin levels. In comparison to healthy controls, serum chemerin and irisin levels were significantly higher in children with idiopathic epilepsy especially those with uncontrolled seizures. Serum chemerin and irisin levels had significant positive correlation with seizure severity Chalfont score and the duration of epilepsy. Elevated Chalfont score (OR 3.19), serum chemerin (OR 2.01), and irisin (OR 2.03) are predictors of uncontrolled seizures. Circulating chemerin and irisin have 80% and 76% sensitivity and 88% and 92% specificity at cutoff point > 191.38 ng/ml and > 151.2 ng/ml respectively for prediction of uncontrolled seizures in children with idiopathic epilepsy. Elevated circulating level of irisin and chemerin may predict poor seizure control in children with idiopathic epilepsy suggesting the role of hypoxia-triggered neuroinflammation in the pathogenesis of childhood idiopathic epilepsy.

Computed tomographic features of idiopathic fibrosing interstitial pneumonia: comparison with pulmonary fibrosis related to collagen vascular disease.

PubMed

Hwang, Jeong-Hwa; Misumi, Shigeki; Sahin, Hakan; Brown, Kevin K; Newell, John D; Lynch, David A

2009-01-01

To compare the computed tomographic (CT) features of idiopathic fibrosing interstitial pneumonia with those of pulmonary fibrosis related to collagen vascular disease (CVD). We reviewed the CT scans of 177 patients with diffuse interstitial pulmonary fibrosis, of which 97 had idiopathic fibrosing interstitial pneumonia and 80 had CVD. The CT images were systematically scored for the presence and extent of pulmonary and extrapulmonary abnormalities. Computed tomographic diagnosis of usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP) was assigned. A CT pattern of UIP was identified in 59 (60.8%) of patients with idiopathic fibrosing interstitial pneumonia compared with 15 (18.7%) of those patients with CVD; conversely, the CT diagnosis of NSIP was made in 51 (64%) of patients with CVD compared with 36 (37%) of patients with idiopathic disease (P < 0.01). In 113 patients who had lung biopsy, the CT diagnoses of UIP and NSIP were concordant with the histologic diagnoses in 36 of 50 patients and 34 of 41 patients, respectively. Pleural effusions, esophageal dilation, and pericardial abnormalities were more frequent in patients with CVD than in patients with idiopathic fibrosing interstitial pneumonia. Compared with patients with CVD, those patients with an idiopathic fibrosing interstitial pneumonia showed a higher prevalence of a UIP pattern and lower prevalence of an NSIP pattern as determined by CT. Identification of coexisting extrapulmonary abnormalities on CT can support a diagnosis of CVD.

Gastric mucin expression in Helicobacter pylori-related, nonsteroidal anti-inflammatory drug-related and idiopathic ulcers

PubMed Central

Boltin, Doron; Halpern, Marisa; Levi, Zohar; Vilkin, Alex; Morgenstern, Sara; Ho, Samuel B; Niv, Yaron

2012-01-01

AIM: To determine the pattern of secreted mucin expression in Helicobacter pylori (H. pylori)-related, nonsteroidal anti-inflammatory drug (NSAID)-related and idiopathic gastric ulcers. METHODS: We randomly selected 92 patients with H. pylori-associated (n = 30), NSAID-associated (n = 18), combined H. pylori and NSAID-associated gastric ulcers (n = 24), and patients with idiopathic gastric ulcers (n = 20). Immunohistochemistry for T-cell CD4/CD8, and for mucin 5AC (MUC5AC) and mucin 6 (MUC6), was performed on sections of the mucosa from the ulcer margin. Inflammation score was assessed according to the Sydney system. RESULTS: MUC5AC was expressed on the surface epithelium (98.9%) and neck glands (98.9%) with minimal expression in the deep glands (6.5%). MUC6 was strongly expressed in the deep glands (97.8%), variable in the neck glands (19.6%) and absent in the surface epithelium (0%). The pattern of mucin expression in idiopathic ulcer margins was not different from the expression in ulcers associated with H. pylori, NSAIDs, or combined H. pylori and NSAIDs. CD4/CD8 ratio was higher in H. pylori-positive patients (P = 0.009). Idiopathic ulcers are associated with hospitalized patients and have higher bleeding and mortality rates. CONCLUSION: Idiopathic ulcers have a unique clinical profile. Gastric mucin expression in idiopathic gastric ulcers is unchanged compared with H. pylori and/or NSAID-associated ulcers. PMID:22969235

Classification of Systemic and Localized Sweating Disorders.

PubMed

Ohshima, Yuichiro; Tamada, Yasuhiko

2016-01-01

Hyperhidrosis can be subdivided into generalized hyperhidrosis, with increased sweating over the entire body, and focal hyperhidrosis, in which the excessive sweating is restricted to specific parts of the body. Generalized hyperhidrosis may be either primary (idiopathic) or secondary. Secondary generalized hyperhidrosis may be caused by infections such as tuberculosis, hyperthyroidism, endocrine and metabolic disturbances such as pheochromocytoma, neurological disorders, or drugs. Focal hyperhidrosis may also be primary (idiopathic) or secondary. Frey's syndrome is one form of secondary focal hyperhidrosis that occurs during eating together with reddening of the area in front of the ear following parotid gland surgery or injury. Primary focal hyperhidrosis is particularly common on the palms and soles of the feet, in the axilla, and on the head. Anhidrosis may be either congenital/genetic or acquired. Some of the most typical forms of congenital/genetic anhidrosis include hypohidrotic ectodermal dysplasia, congenital insensitivity to pain and anhidrosis, and Fabry disease. Acquired anhidrosis is classified as secondary anhidrosis, which may be due to an underlying disorder such as a neurological disorder, an endocrine or metabolic disturbance, or the effect of drugs, or idiopathic anhidrosis for which the pathology, cause, and mechanism are unknown. Idiopathic anhidrosis is classified into acquired idiopathic generalized anhidrosis (AIGA), idiopathic segmental anhidrosis, and Ross syndrome. AIGA is divided into three categories according to differences in the site of disturbance: (1) sudomotor neuropathy, (2) idiopathic pure sudomotor failure, and (3) sweat gland failure. © 2016 S. Karger AG, Basel.

Possible association of FAS and FASLG polymorphisms with the risk of idiopathic azoospermia in southeast Turkey.

PubMed

Balkan, Mahmut; Atar, Murat; Erdal, Mehmet Emin; Rustemoğlu, Aydin; Yildiz, Ismail; Gunesacar, Ramazan; Hatipoğlu, Namık Kemal; Bodakçi, Mehmet Nuri; Ay, Ozlem Izci; Çevik, Kenan

2014-06-01

To investigate the association of the genetic variants of FAS/FASLG cell death pathway genes in male infertility, we genotyped the FAS -670A/G, -1377G/A, and FASLG -124A/G single-nucleotide polymorphisms (SNPs) by real-time polymerase chain reaction in 108 infertile men with idiopathic azoospermia and in 125 proven fertile controls. The distribution of genotypes and alleles for SNPs at FAS -1377G/A and FASLG -124A/G loci were determined not to be statistically different between the case and control groups. However, the genotype frequencies of SNPs, FAS -670AA and FAS -670AG, were found to be significantly different between the case and control groups. Whereas the FAS -670AA genotype might be regarded as a higher predisposition for idiopathic azoospermia, FAS -670AG could be interpreted to mean that this genotype provides protection against idiopathic azoospermia. The study of combined genotype and haplotype frequencies has found statistically significant differences between case and control subjects for some combinations. The AA-GG binary genotype for the FAS670 and FAS1377 loci couple, in particular, may have a high degree of predisposition to idiopathic azoospermia. Our results suggest that FAS -670A/G SNP may be a genetic predisposing factor of idiopathic azoospermia among southeastern Anatolian men. Larger studies are needed to verify these findings. Furthermore, our data indicated a possible linkage between the FAS and FASLG genes and idiopathic azoospermia.

Stone former urine proteome demonstrates a cationic shift in protein distribution compared to normal.

PubMed

Kolbach-Mandel, Ann M; Mandel, Neil S; Hoffmann, Brian R; Kleinman, Jack G; Wesson, Jeffrey A

2017-08-01

Many urine proteins are found in calcium oxalate stones, yet decades of research have failed to define the role of urine proteins in stone formation. This urine proteomic study compares the relative amounts of abundant urine proteins between idiopathic calcium oxalate stone forming and non-stone forming (normal) cohorts to identify differences that might correlate with disease. Random mid-morning urine samples were collected following informed consent from 25 stone formers and 14 normal individuals. Proteins were isolated from urine using ultrafiltration. Urine proteomes for each sample were characterized using label-free spectral counting mass spectrometry, so that urine protein relative abundances could be compared between the two populations. A total of 407 unique proteins were identified with the 38 predominant proteins accounting for >82% of all sample spectral counts. The most highly abundant proteins were equivalent in stone formers and normals, though significant differences were observed in a few moderate abundance proteins (immunoglobulins, transferrin, and epidermal growth factor), accounting for 13 and 10% of the spectral counts, respectively. These proteins contributed to a cationic shift in protein distribution in stone formers compared to normals (22% vs. 18%, p = 0.04). Our data showing only small differences in moderate abundance proteins suggest that no single protein controls stone formation. Observed increases in immunoglobulins and transferrin suggest increased inflammatory activity in stone formers, but cannot distinguish cause from effect in stone formation. The observed cationic shift in protein distribution would diminish protein charge stabilization, which could lead to protein aggregation and increased risk for crystal aggregation.

Temporal trends of acute nephrolithiasis in Auckland, New Zealand.

PubMed

Du, Jason; Johnston, Richard; Rice, Michael

2009-07-24

An increasing amount of evidence suggests that the occurrence of kidney stone disease has increased over the last 50 years. No data analysis on temporal trends in Auckland, New Zealand has ever been performed. The aim of this study was to investigate the changing pattern by age, ethnicity, and gender on stone incidence over a 10-year period. Demographic data was collected on all patients who presented with renal colic. Population numbers were provided by the New Zealand ministry of statistics using regular census data. The analysis was performed using Pearson's correlation coefficients and a Poisson regression model. From 1997 to 2007, 17,532 new stones were coded as nephrolithiasis with an age range of 1-97. Disease incidence amongst Auckland residents was greater in 2007 than 1997 (0.131% or 131 per 100,000 population vs 0.102% or 102 per 100,000 population. p=0.012). The male to female ratio changed over time with a greater proportion of females presenting in 2007 than 1997 (0.47 vs 0.41, p<0.05). Pacific, Asian, and Maori incidence increased faster compared to European whilst those from the Middle East were the only group to have a stable rate (0.26% or 260/100,000 per year) over the 10-year period. Incidence of kidney stone disease in the Auckland region has increased significantly from 1997 to 2007. Different ethnic groups had different rates of change, but all groups showed an increasing incidence over time, with the exception of those from the Middle East. A greater proportion of patients are female than 10 years ago.

Michelangelo: art, anatomy, and the kidney.

PubMed

Eknoyan, G

2000-03-01

Michelangelo (1475-1564) had a life-long interest in anatomy that began with his participation in public dissections in his early teens, when he joined the court of Lorenzo de' Medici and was exposed to its physician-philosopher members. By the age of 18, he began to perform his own dissections. His early anatomic interests were revived later in life when he aspired to publish a book on anatomy for artists and to collaborate in the illustration of a medical anatomy text that was being prepared by the Paduan anatomist Realdo Colombo (1516-1559). His relationship with Colombo likely began when Colombo diagnosed and treated him for nephrolithiasis in 1549. He seems to have developed gouty arthritis in 1555, making the possibility of uric acid stones a distinct probability. Recurrent urinary stones until the end of his life are well documented in his correspondence, and available documents imply that he may have suffered from nephrolithiasis earlier in life. His terminal illness with symptoms of fluid overload suggests that he may have sustained obstructive nephropathy. That this may account for his interest in kidney function is evident in his poetry and drawings. Most impressive in this regard is the mantle of the Creator in his painting of the Separation of Land and Water in the Sistine Ceiling, which is in the shape of a bisected right kidney. His use of the renal outline in a scene representing the separation of solids (Land) from liquid (Water) suggests that Michelangelo was likely familiar with the anatomy and function of the kidney as it was understood at the time.

Therapy-resistant nephrolithiasis following renal artery coil embolization

PubMed Central

2013-01-01

Background Transcatheter renal artery embolization is an effective and minimally invasive treatment option for acute renal bleeding. Early post-interventional complications include groin hematoma, incomplete embolization, coil misplacement and coil migration. Late complications are rare and mostly related to coil migration. Case presentation A 22-year-old woman with a history of recurrent stone disease and a lumbal meningomyelocele underwent bilateral open pyelolithotomy for bilateral staghorn calculi. Post-operatively, acute hemorrhage of the left kidney occurred and selective arterial coil embolization of a lower pole interlobular renal artery was performed twice. Four years after this intervention the patient presented with a new 15.4 mm stone in the lower calyx of the left kidney. After two extracorporeal shock wave lithotripsy treatments disintegration of the stone was not detectable. Therefore, flexible ureterorenoscopy was performed and revealed that the stone was adherent to a partially intraluminal metal coil in the lower renal calyx. The intracalyceal part of the coil and the adherent stone were successfully removed using the holmium laser. Conclusion Therapy-resistant nephrolithiasis was caused by a migrated metal coil, which was placed four years earlier for the treatment of acute post-operative renal bleeding. Renal coils in close vicinity to the renal pelvis can migrate into the collecting system and trigger renal stone formation. Extracorporeal shock wave lithotripsy seems to be inefficient for these composite stones. Identification of these rare stones is possible during retrograde intrarenal surgery. It also enables immediate stone disintegration and removal of the stone fragments and the intraluminal coil material. PMID:23758632

Xanthogranulomatous pyelonephritis presenting as acute pleuritic chest pain: a case report.

PubMed

Chow, Justin; Kabani, Rameez; Lithgow, Kirstie; Sarna, Magdalena A

2017-04-12

Xanthogranulomatous pyelonephritis is a rare and serious manifestation of chronic kidney inflammation that can be life-threatening if not recognized and treated appropriately, often with antibiotics and surgery. Affected patients are most commonly females in their fifth or sixth decade of life with a background of obstructive uropathy, nephrolithiasis, or recurrent urinary tract infections who present with vague nonspecific symptoms. A 43-year-old woman of Russian ethnicity with a history of nephrolithiasis presented to our emergency department with new left-sided pleuritic chest pain amid a 6-week history of constitutional symptoms including fevers, night sweats, and 7 kg of weight loss. Workup for acute coronary syndrome and pulmonary embolism in our emergency department was negative. Given that she was clinically unwell, she was admitted to internal medicine to expedite workup for the cause of her symptoms. A broad differential diagnosis for various infectious, inflammatory/autoimmune, and neoplastic processes was considered. Based on classic radiographic and histopathologic findings, she was ultimately diagnosed with xanthogranulomatous pyelonephritis of her left kidney, which was a direct consequence of chronic inflammation. This inflammation exhibited spread to local tissues and across her left hemidiaphragm, resulting in a unilateral pleural effusion which explained her chest discomfort. She was treated with antibiotics administered intravenously and urgent total nephrectomy with a good functional outcome. Our case illustrates an uncommon but clinically important do-not-miss diagnosis that underlies a common clinical presentation of pleuritic chest pain. The case underscores the importance of maintaining a broad differential diagnosis and organized approach when treating patients with undifferentiated clinical presentations.

Adults With Idiopathic Scoliosis Diagnosed at Youth Experience Similar Physical Activity and Fracture Rate as Controls.

PubMed

Diarbakerli, Elias; Grauers, Anna; Danielsson, Aina; Gerdhem, Paul

2017-04-01

Cross-sectional. To describe physical activity level and fracture rates in adults with idiopathic scoliosis, diagnosed before maturity, and to compare with a control group. A previous study found a lower level of sporting activities in adults treated for idiopathic scoliosis compared with controls. Other studies have shown a lower bone mass in adults with idiopathic scoliosis compared with controls. One thousand two hundred seventy-eight adults (aged 18-71 yr) with idiopathic scoliosis and 214 controls (aged 18-70 yr) were included and answered the International Physical Activity Questionnaire - Short Form (IPAQ-SF) and questions about previous fractures. The three scoliosis treatment groups (untreated n = 360, brace n = 460, and surgically treated n = 458) were compared. Furthermore, a comparison based on onset (juvenile n = 169 or adolescent n = 976) was performed. Achieved weekly moderate activity level and metabolic equivalent task (MET) minutes/week were assessed for patients and controls. Statistical comparisons were made with analysis of covariance with adjustments for age, body mass index, and sex. The proportion achieving weekly moderate activity level was 962 out of 1278 for individuals with idiopathic scoliosis (75%) and 157 out of 214 (73%) for controls (P = 0.40). The scoliosis patients reported 2016 MET-minutes/week (median value) and the controls 2456 (P = 0.06). Fracture rates did not differ (P = 0.72). Fewer surgically treated individuals achieved moderate activity level (P = 0.046) compared with the untreated and the previously braced individuals. No difference was seen regarding MET-minutes/week (P = 0.86). No differences were seen between individuals with a juvenile onset compared with individuals with an adolescent onset (all P ≥ 0.05). Adults with idiopathic scoliosis have similar physical activity level and do not sustain more fractures compared with controls. Adults with surgically treated idiopathic scoliosis have slightly lower physical activity level than previously braced and untreated patients. Onset of idiopathic scoliosis does not affect physical activity level. 2.

Aetiology of idiopathic granulomatous mastitis.

PubMed

Altintoprak, Fatih; Kivilcim, Taner; Ozkan, Orhan Veli

2014-12-16

Idiopathic granulomatous mastitis is a rare chronic inflammatory lesion of the breast that can clinically and radiographically mimic breast carcinoma. The most common clinical presentation is an unilateral, discrete breast mass, nipple retraction and even a sinus formation often associated with an inflammation of the overlying skin. The etiology of idiopathic granulomatous mastitis is still obscure. Its treatment remains controversial. The cause may be the autoimmune process, infection, a chemical reaction associated with oral contraceptive pills, or even lactation. Various factors, including hormonal imbalance, autoimmunity, unknown microbiological agents, smoking and α 1-antitrypsin deficiency have been suggested to play a role in disease aetiology. In this review, causing factors in the aetiology of idiopathic granulomatous mastitis are reviewed in detail.

Aetiology of idiopathic granulomatous mastitis

PubMed Central

Altintoprak, Fatih; Kivilcim, Taner; Ozkan, Orhan Veli

2014-01-01

Idiopathic granulomatous mastitis is a rare chronic inflammatory lesion of the breast that can clinically and radiographically mimic breast carcinoma. The most common clinical presentation is an unilateral, discrete breast mass, nipple retraction and even a sinus formation often associated with an inflammation of the overlying skin. The etiology of idiopathic granulomatous mastitis is still obscure. Its treatment remains controversial. The cause may be the autoimmune process, infection, a chemical reaction associated with oral contraceptive pills, or even lactation. Various factors, including hormonal imbalance, autoimmunity, unknown microbiological agents, smoking and α 1-antitrypsin deficiency have been suggested to play a role in disease aetiology. In this review, causing factors in the aetiology of idiopathic granulomatous mastitis are reviewed in detail. PMID:25516860

[Coincidence of juvenile idiopathic arthritis and multiple sclerosis: case report].

PubMed

Puszczewicz, Mariusz J; Tuchocka-Piotrowska, Aleksandra; Majewski, Dominik; Kołczewska, Aleksandra

2006-01-01

Juvenile idiopathic arthritis is a systemic pathology of connective tissue characterized by a chronic inflammatory process with an autoimmune background whereas multiple sclerosis is a demyelination disease with an important role of immune disorders in its pathogenesis. The etiology in both cases remains unknown. The coincidence of juvenile idiopathic arthritis and multiple sclerosis was described a just a few patients. We now report on a 31-year-old woman with juvenile idiopathic arthritis and multiple sclerosis. In the present case, the main problem was to find the right proper medication for a very, aggressive course of multiple sclerosis and for arthritis. Treatment with interferon-beta and methylprednisolone led to remission with just minor side-effects.

Pathogenesis, Newly Recognized Etiologies, and Management of Idiopathic Anaphylaxis

PubMed Central

Kuhlen, James L.; Virkud, Yamini V.

2018-01-01

Idiopathic anaphylaxis (IA) is a life-threatening allergic disease and the most common diagnosis given to patients following an anaphylactic event. The inability of the healthcare provider and the patient to identify the trigger for anaphylaxis makes standard allergen avoidance measures ineffectual. IA is diagnosed after other causes of anaphylaxis have been excluded. Mast cell activation syndromes (MCAS), mastocytosis, IgE to galactose-alpha-1,3-galactose (α-gal), and certain medications have recently been recognized as causes of anaphylaxis that were previously labeled idiopathic. This review will describe the epidemiology and proposed theories of pathogenesis for IA, its diagnostic approach, its clinical management, and examine newly recognized disorders that were previously labeled as idiopathic anaphylaxis. PMID:25725228

Inhibition of ileal bile acid transporter: An emerging therapeutic strategy for chronic idiopathic constipation.

PubMed

Mosińska, Paula; Fichna, Jakub; Storr, Martin

2015-06-28

Chronic idiopathic constipation is a common disorder of the gastrointestinal tract that encompasses a wide profile of symptoms. Current treatment options for chronic idiopathic constipation are of limited value; therefore, a novel strategy is necessary with an increased effectiveness and safety. Recently, the inhibition of the ileal bile acid transporter has become a promising target for constipation-associated diseases. Enhanced delivery of bile acids into the colon achieves an accelerated colonic transit, increased stool frequency, and relief of constipation-related symptoms. This article provides insight into the mechanism of action of ileal bile acid transporter inhibitors and discusses their potential clinical use for pharmacotherapy of constipation in chronic idiopathic constipation.

Idiopathic pulmonary fibrosis. A rare cause of scintigraphic ventilation-perfusion mismatch

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pochis, W.T.; Krasnow, A.Z.; Collier, B.D.

1990-05-01

A case of idiopathic pulmonary fibrosis with multiple areas of mismatch on ventilation-perfusion lung imaging in the absence of pulmonary embolism is presented. Idiopathic pulmonary fibrosis is one of the few nonembolic diseases producing a pulmonary ventilation-perfusion mismatch. In this condition, chest radiographs may not detect the full extent of disease, and xenon-133 ventilation imaging may be relatively insensitive to morbid changes in small airways. Thus, when examining patients with idiopathic pulmonary fibrosis, one should be aware that abnormal perfusion imaging patterns without matching ventilation abnormalities are not always due to embolism. In this setting, contrast pulmonary angiography is oftenmore » needed for accurate differential diagnosis.« less

Efficacy of high-dose intravenous immunoglobulins in two patients with idiopathic recurrent pericarditis refractory to previous immunosuppressive treatment.

PubMed

Tona, Francesco; Bellotto, Fabio; Laveder, Francesco; Meneghin, Alessia; Sinagra, Gianfranco; Marcolongo, Renzo

2003-01-01

Although idiopathic acute pericarditis is usually a self-limiting disease, in many patients it may recur over a period of months or years. Even if some evidence seems to suggest the possible role of a deranged immune reactivity in the pathogenesis of idiopathic recurrent pericarditis, the etiology of the disease is still unknown. Furthermore, while some trial data confirm the usefulness of colchicine, its medical treatment is not yet clearly established. We here report the clinical history of 2 patients with idiopathic recurrent pericarditis resistant to prednisone, colchicine and other immunosuppressive drugs, who have been successfully treated with high-dose intravenous immunoglobulins.

Adolescent idiopathic scoliosis and the single-nucleotide polymorphism of the growth hormone receptor and IGF-1 genes.

PubMed

Yang, Yong; Wu, Zhihong; Zhao, Taimao; Wang, Hai; Zhao, Dong; Zhang, Jianguo; Wang, Yipeng; Ding, Yaozhong; Qiu, Guixing

2009-06-01

The etiology of adolescent idiopathic scoliosis is undetermined despite years of research. A number of hypotheses have been postulated to explain its development, including growth abnormalities. The irregular expression of growth hormone and insulin-like growth factor-1 (IGF-1) may disturb hormone metabolism, result in a gross asymmetry, and promote the progress of adolescent idiopathic scoliosis. Initial association studies in complex diseases have demonstrated the power of candidate gene association. Prior to our study, 1 study in this field had a negative result. A replicable study is vital for reliability. To determine the relationship of growth hormone receptor and IGF-1 genes with adolescent idiopathic scoliosis, a population-based association study was performed. Single nucleotide polymorphisms with potential function were selected from candidate genes and a distribution analysis was performed. A conclusion was made confirming the insufficiency of an association between adolescent idiopathic scoliosis and the single-nucleotide polymorphism of the growth hormone receptor and IGF-1 genes in Han Chinese.

Idiopathic Inflammatory Myopathies

PubMed Central

Dimachkie, Mazen M.; Barohn, Richard J.

2012-01-01

The idiopathic inflammatory myopathies are a group of rare disorders including polymyositis (PM), dermatomyositis (DM), and autoimmune necrotizing myopathies (NMs). The idiopathic inflammatory myopathies share many similarities. They present acutely, subacutely, or chronically with marked proximal and symmetric muscle weakness, except for associated distal and asymmetric weakness in inclusion body myositis. The idiopathic inflammatory myopathies also share a variable degree of creatine kinase (CK) elevation and a nonspecifically abnormal electromyogram demonstrating an irritative myopathy. The muscle pathology demonstrates inflammatory exudates of variable distribution within the muscle fascicle. Despite these similarities, the idiopathic inflammatory myopathies are a heterogeneous group. The overlap syndrome (OS) refers to the association of PM, DM, or NM with connective tissue disease, such as scleroderma or systemic lupus erythematosus. In addition to elevated antinuclear antibodies (ANA), patients with OS may be weaker in the proximal arms than the legs mimicking the pattern seen in some muscular dystrophies. In this review, we focus on DM, PM, and NM and examine current and promising therapies. PMID:23117947

From bad to worse: when lung cancer complicates idiopathic pulmonary fibrosis.

PubMed

Strock, Stephen B; Alder, Jonathan K; Kass, Daniel J

2018-04-01

Patients with idiopathic pulmonary fibrosis have a significantly increased risk for the development of lung cancer. The morbidity and mortality of this disease combination are substantial, and, unfortunately, there are currently few data to help guide clinicians in its diagnosis and treatment. In a recent issue of this journal, Hwang et al presented one of the first studies to evaluate lung cancer in patients with idiopathic pulmonary fibrosis at the molecular level. They demonstrate variants in regulators of the cell cycle, which are known to be important in malignant transformation and may also be important in the pathogenesis of idiopathic pulmonary fibrosis. Further understanding of the pathogenic overlap between lung cancer and idiopathic pulmonary fibrosis could help point the direction to specific diagnostic modalities and targeted treatment of both conditions in the future. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Idiopathic orbital inflammatory disease successfully treated with rituximab.

PubMed

Schafranski, Marcelo Derbli

2009-02-01

We report a case of a 66-year-old Caucasian female with a diagnosis of idiopathic orbital inflammatory disease (OID) refractory to azathioprine therapy. The coexistence of diabetes mellitus represented a relative contraindication to chronic prednisone use. After two infusions of rituximab, a chimeric anti-CD20+ antibody, ophthalmic signs and symptoms remarkably improved. To our knowledge, this is the first case of idiopathic OID successfully treated with rituximab.

Perioperative Care of a Patient with Refractory Idiopathic Thrombocytopenic Purpura Undergoing Total Knee Arthroplasty

PubMed Central

Gudimetla, Veera; Stewart, Andrew; Luscombe, Karen L; Charalambous, Charalambos P

2012-01-01

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder leading to low platelet count and an increased risk of bleeding. Major joint replacement surgery in a patient with ITP can be associated with severe postoperative bleeding. We present our experience of perioperative management in a patient with severe refractory chronic idiopathic thrombocytopenic purpura who successfully underwent a cemented total knee replacement. PMID:23269964

Prognostic value of cardiovascular magnetic resonance imaging measurements corrected for age and sex in idiopathic pulmonary arterial hypertension.

PubMed

Swift, Andrew J; Rajaram, Smitha; Campbell, Michael J; Hurdman, Judith; Thomas, Steve; Capener, Dave; Elliot, Charlie; Condliffe, Robin; Wild, Jim M; Kiely, David G

2014-01-01

There are limited data on the prognostic value of cardiovascular magnetic resonance measurements in idiopathic pulmonary arterial hypertension, with no studies investigating the impact of correction of cardiovascular magnetic resonance indices for age and sex on prognostic value. Consecutive patients with idiopathic pulmonary arterial hypertension underwent cardiovascular magnetic resonance imaging at 1.5T. Steady-state free precession cardiac volumes and mass measurements were corrected for age, sex, and body surface area according to reference data and prognostic significance assessed. A total of 80 patients with idiopathic pulmonary arterial hypertension were identified, and 23 patients died during the mean follow-up of 32±14 months. Corrected for age, sex, and body surface area, right ventricular end-systolic volume (P=0.004) strongly predicted mortality, independent of World Health Organization functional class, mean right atrial pressure, cardiac index, and mixed venous oxygen saturations. Consideration should be given to correcting cardiovascular magnetic resonance measures for age, sex, and body surface area, particularly given the changing demographics of patients with idiopathic pulmonary arterial hypertension. Corrected right ventricular end-systolic volume is a strong prognostic marker in idiopathic pulmonary arterial hypertension, independent of invasively derived measurements, mean right atrial pressure cardiac index, and mixed venous oxygen saturations.

Risk for femoral fractures in Parkinson's disease patients with and without severe functional impairment.

PubMed

Benzinger, Petra; Rapp, Kilian; Maetzler, Walter; König, Hans-Helmut; Jaensch, Andrea; Klenk, Jochen; Büchele, Gisela

2014-01-01

Impaired balance is a major problem in patients with idiopathic Parkinson's disease (PD) resulting in an increased risk of falls and fall-related fractures. Most studies which analyzed the risk of femoral fractures in patients with idiopathic PD were performed either in specialized centers or excluded very frail patients. The current study used a large population-based dataset in order to analyze the risk of femoral fractures in patients with idiopathic PD. Data from more than 880.000 individuals aged 65 years or older and insured between 2004 and 2009 at a large German health insurance company were used for the analyses. Persons with idiopathic PD were identified by the dispensing of Parkinson-specific medication and by hospital diagnoses, if available. People without PD served as the reference group. Incident femoral fractures were obtained from hospital diagnoses. Analyses were stratified by gender and information on severe functional impairment (care need) as provided by reimbursement claims. Compared with the reference group, persons with idiopathic PD had a more than doubled risk to sustain a femoral fracture. The risk was higher in men (HR = 2.61; 95%-CI: 2.28-2.98) than in women (HR = 1.79; 95%-CI: 1.66-1.94). The increased risk was only observed in people without severe functional impairment. The sensitivity analysis using a refined definition of idiopathic PD patients yielded similar results. The findings confirm the increased risk of femoral fractures in patients with idiopathic PD. The relative risk is particularly high in male PD patients and in patients without severe functional impairment.

Enlarged Dural Sac in Idiopathic Bronchiectasis Implicates Heritable Connective Tissue Gene Variants

PubMed Central

Birchard, Katherine R.; Lowe, Jared R.; Patrone, Michael V.

2016-01-01

Rationale: Patients with idiopathic bronchiectasis are predominantly female and have an asthenic body morphotype and frequent nontuberculous mycobacterial respiratory infections. They also demonstrate phenotypic features (scoliosis, pectus deformity, mitral valve prolapse) that are commonly seen in individuals with heritable connective tissue disorders. Objectives: To determine whether lumbar dural sac size is increased in patients with idiopathic bronchiectasis as compared with control subjects, and to assess whether dural sac size is correlated with phenotypic characteristics seen in individuals with heritable connective tissue disorders. Methods: Two readers blinded to diagnosis measured anterior–posterior and transverse dural sac diameter using L1–L5 magnetic resonance images of 71 patients with idiopathic bronchiectasis, 72 control subjects without lung disease, 29 patients with cystic fibrosis, and 24 patients with Marfan syndrome. We compared groups by pairwise analysis of means, using Tukey’s method to adjust for multiple comparisons. Dural sac diameter association with phenotypic and clinical features was also tested. Measurements and Main Results: The L1–L5 (average) anterior–posterior dural sac diameter of the idiopathic bronchiectasis group was larger than those of the control group (P < 0.001) and the cystic fibrosis group (P = 0.002). There was a strong correlation between increased dural sac size and the presence of pulmonary nontuberculous mycobacterial infection (P = 0.007) and long fingers (P = 0.003). A trend toward larger dural sac diameter was seen in those with scoliosis (P = 0.130) and those with a family history of idiopathic bronchiectasis (P = 0.149). Conclusions: Individuals with idiopathic bronchiectasis have an enlarged dural sac diameter, which is associated with pulmonary nontuberculous mycobacterial infection, long fingers, and family history of idiopathic bronchiectasis. These findings support our hypothesis that “idiopathic” bronchiectasis development reflects complex genetic variation in heritable connective tissue and associated transforming growth factor-β–related pathway genes. PMID:27409985

IgG abnormality in narcolepsy and idiopathic hypersomnia.

PubMed

Tanaka, Susumu; Honda, Makoto

2010-03-05

A close association between narcolepsy and the Human Leukocyte Antigen (HLA)-DQB1*0602 allele suggests the involvement of the immune system, or possibly an autoimmune process. We investigated serum IgG levels in narcolepsy. We measured the serum total IgG levels in 159 Japanese narcolepsy-cataplexy patients positive for the HLA-DQB1*0602 allele, 28 idiopathic hypersomnia patients with long sleep time, and 123 healthy controls (the HLA-DQB1*0602 allele present in 45 subjects). The serum levels of each IgG subclass were subsequently measured. The distribution of serum IgG was significantly different among healthy controls negative for the HLA-DQB1*0602 allele (11.66+/-3.55 mg/ml), healthy controls positive for the HLA-DQB1*0602 allele (11.45+/-3.43), narcolepsy patients (9.67+/-3.38), and idiopathic hypersomnia patients (13.81+/-3.80). None of the following clinical variables, age, disease duration, Epworth Sleepiness Scale, smoking habit and BMI at the time of blood sampling, were associated with IgG levels in narcolepsy or idiopathic hypersomnia. Furthermore we found the decrease in IgG1 and IgG2 levels, stable expression of IgG3, and the increase in the proportion of IgG4 in narcolepsy patients with abnormally low IgG levels. The increase in the proportion of IgG4 levels was also found in narcolepsy patients with normal serum total IgG levels. Idiopathic hypersomnia patients showed a different pattern of IgG subclass distribution with high IgG3 and IgG4 level, low IgG2 level, and IgG1/IgG2 imbalance. Our study is the first to determine IgG abnormalities in narcolepsy and idiopathic hypersomnia by measuring the serum IgG levels in a large number of hypersomnia patients. The observed IgG abnormalities indicate humoral immune alterations in narcolepsy and idiopathic hypersomnia. Different IgG profiles suggest immunological differences between narcolepsy and idiopathic hypersomnia.

Perioperative Management of Pregnant Women With Idiopathic Pulmonary Arterial Hypertension: An Observational Case Series Study From China.

PubMed

Zhang, Jinglan; Lu, Jiakai; Zhou, Xiaorui; Xu, Xuefeng; Ye, Qing; Ou, Qitan; Li, Yanna; Huang, Jiapeng

2018-03-07

The mortality of pregnant women with idiopathic pulmonary arterial hypertension (PAH) is very high. There are limited data on the management of idiopathic PAH during pregnancy. The authors aimed to examine systematically the characteristics of parturient women with idiopathic PAH, to explore the adverse effects of idiopathic PAH on pregnancy outcomes, and to report the multidisciplinary perioperative management strategy from the largest comprehensive cardiac hospital in China. Observational case series study. Tertiary referral acute care hospital in Beijing, China. The cases of 17 consecutive pregnant idiopathic PAH patients undergoing abortion or parturition at Anzhen Hospital were reviewed retrospectively. Preoperative characteristics, anesthesia method, intensive care management, PAH-specific therapy, and maternal and neonatal outcomes were analyzed in this case series study. Maternal and neonatal outcomes were the main measures. The mean ages of the 17 parturient women with idiopathic PAH were 28.3 ± 5.4 years, and the mean systolic pulmonary arterial pressure was 97.9 ± 18.6 mmHg. Fifteen patients (88.2%) received PAH-specific therapy before delivery, including sildenafil, iloprost, and treprostinil. All except 1 parturient received epidural anesthesia for surgery due to an emergency Caesarean section. Three patients experienced pulmonary hypertension crisis that necessitated conversion to general anesthesia. Ten parturients underwent Caesarean delivery at a median gestational age of 31 weeks. Three patients developed acute pulmonary hypertensive crisis intraoperatively. Two patients underwent cardiopulmonary resuscitation and extracorporeal membrane oxygenation support. The maternal mortality was 17.6% (3/17). Of the 10 delivered neonates, 9 (90.0%) survived. The maternal mortality of the idiopathic PAH parturient was high in this case series from China. The authors applied epidural anesthesia, early management with multidisciplinary approaches, PAH-specific therapy, avoidance of oxytocin, and timely delivery or pregnancy termination to improve maternal and neonatal outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of pirfenidone on mortality: pooled analyses and meta-analyses of clinical trials in idiopathic pulmonary fibrosis.

PubMed

Nathan, Steven D; Albera, Carlo; Bradford, Williamson Z; Costabel, Ulrich; Glaspole, Ian; Glassberg, Marilyn K; Kardatzke, David R; Daigl, Monica; Kirchgaessler, Klaus-Uwe; Lancaster, Lisa H; Lederer, David J; Pereira, Carlos A; Swigris, Jeffrey J; Valeyre, Dominique; Noble, Paul W

2017-01-01

In clinical trials of idiopathic pulmonary fibrosis, rates of all-cause mortality are low. Thus prospective mortality trials are logistically very challenging, justifying the use of pooled analyses or meta-analyses. We did pooled analyses and meta-analyses of clinical trials of pirfenidone versus placebo to determine the effect of pirfenidone on mortality outcomes over 120 weeks. We did a pooled analysis of the combined patient populations of the three global randomised phase 3 trials of pirfenidone versus placebo-Clinical Studies Assessing Pirfenidone in Idiopathic Pulmonary Fibrosis: Research of Efficacy and Safety Outcomes (CAPACITY 004 and 006; trial durations 72-120 weeks) and Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND 016; 52 weeks)-for all-cause mortality, treatment-emergent all-cause mortality, idiopathic-pulmonary-fibrosis-related mortality, and treatment-emergent idiopathic-pulmonary-fibrosis-related mortality at weeks 52, 72, and 120. We also did meta-analyses of these data and data from two Japanese trials of pirfenidone versus placebo-Shionogi Phase 2 (SP2) and Shionogi Phase 3 (SP3; trial durations 36-52 weeks). At week 52, the relative risk of death for all four mortality outcomes was significantly lower in the pirfenidone group than in the placebo group in the pooled population (all-cause mortality hazard ratio [HR] 0·52 [95% CI 0·31-0·87; p=0·0107]; treatment-emergent all-cause mortality 0·45 [0·24-0·83; 0·0094]; idiopathic-pulmonary-fibrosis-related mortality 0·35 [0·17-0·72; 0·0029]; treatment-emergent idiopathic-pulmonary-fibrosis-related mortality 0·32 [0·14-0·76; 0·0061]). Consistent with the pooled analysis, meta-analyses for all-cause mortality at week 52 also showed a clinically relevant and significant risk reduction in the pirfenidone group compared with the placebo group. Over 120 weeks, we noted significant differences in the pooled analysis favouring pirfenidone therapy compared with placebo for treatment-emergent all-cause mortality (p=0·0420), idiopathic-pulmonary-fibrosis-related mortality (0·0237), and treatment-emergent idiopathic-pulmonary-fibrosis-related (0·0132) mortality; similar results were shown by meta-analyses. Several analytic approaches demonstrated that pirfenidone therapy is associated with a reduction in the relative risk of mortality compared with placebo over 120 weeks. F Hoffmann-La Roche/Genentech. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lack of evidence for central sensitization in idiopathic, non-traumatic neck pain: a systematic review.

PubMed

Malfliet, Annaleen; Kregel, Jeroen; Cagnie, Barbara; Kuipers, Mandy; Dolphens, Mieke; Roussel, Nathalie; Meeus, Mira; Danneels, Lieven; Bramer, Wichor M; Nijs, Jo

2015-01-01

Chronic neck pain is a common problem with a poorly understood pathophysiology. Often no underlying structural pathology can be found and radiological imaging findings are more related to age than to a patient's symptoms. Besides its common occurrence, chronic idiopathic neck pain is also very disabling with almost 50% of all neck pain patients showing moderate disability at long-term follow-up. Central sensitization (CS) is defined as "an amplification of neural signaling within the central nervous system that elicits pain hypersensitivity," "increased responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input," or "an augmentation of responsiveness of central neurons to input from unimodal and polymodal receptors." There is increasing evidence for involvement of CS in many chronic pain conditions. Within the area of chronic idiopathic neck pain, there is consistent evidence for the presence and clinical importance of CS in patients with traumatic neck pain, or whiplash-associated disorders. However, the majority of chronic idiopathic neck pain patients are unrelated to a traumatic injury, and hence are termed chronic idiopathic non-traumatic neck pain. When comparing whiplash with idiopathic non-traumatic neck pain, indications for different underlying mechanisms are found. The goal of this article was to review the existing scientific literature on the role of CS in patients with chronic idiopathic non-traumatic neck pain. Systematic review. All selected studies were case control studies. A systematic search of existing, relevant literature was performed via the electronic databases Medline, Embase, Web of Science, Cinahl, PubMed, and Google Scholar. All titles and abstracts were checked to identify relevant articles. An article was considered eligible if it met following inclusion criteria: (1) participants had to be human adults (> 18 years) diagnosed with idiopathic non-traumatic chronic (present for at least 3 months) neck pain; (2) papers had to report outcomes related to CS; and (3) articles had to be full-text reports or original research (no abstracts, case-reports, reviews, meta-analysis, letters, or editorials). Six articles were found eligible after screening the title, abstract and - when necessary - the full text for in- and exclusion criteria. All selected studies were case-control studies. Overall, results regarding the presence of CS were divergent. While the majority of patients with chronic traumatic neck pain (i.e. whiplash) are characterized by CS, this is not the case for patients with chronic idiopathic neck pain. The available evidence suggests that CS is not a major feature of chronic idiopathic neck pain. Individual cases might have CS pain, but further work should reveal how they can be characterized. Very few studies available. Literature about CS in patients with chronic idiopathic non-traumatic neck pain is rare and results from the available studies provide an inconclusive message. CS is not a characteristic feature of chronic idiopathic and non-traumatic neck pain, but can be present in some individuals of the population. In the future a subgroup with CS might be defined, but based on current knowledge it is not possible to characterize this subgroup. Such information is important in order to provide targeted treatment.

The cellular and humoral immunity assay in patients with complicated urolithiasis.

PubMed

Ceban, E; Banov, P; Galescu, A; Tanase, D

2017-01-01

Especially complicated, renal lithiasis contributes to the general inflammatory syndrome development that interferes with nonspecific, humoral and cellular immune system. The surgical treatment of nephrolithiasis is closely related to drug therapy of urinary infection, one of the reasons being the reduction of the immune status. The work is performed by evaluating the immunological status preoperatively in 58 patients with complicated lithiasis. The analysis of the status in these patients demonstrated that complicated urolithiasis results in significant changes in the immune system, these changes being expressed at the cellular and humoral level of immunity.

Urologic Emergencies.

PubMed

Manjunath, Adarsh S; Hofer, Matthias D

2018-03-01

Urologic emergencies can involve the kidneys, ureters, bladder, urethra, penis, scrotum, or testicles. History and physical examination are essential to diagnosis, whereas imaging is increasingly used to confirm diagnoses. Acute urinary retention should be relieved with Foley placement. Penile emergencies include paraphimosis, which can be treated by foreskin reduction, whereas penile fracture and priapism require urologic intervention. Fournier gangrene and testicular torsion are scrotal emergencies requiring emergent surgery. Nephrolithiasis, although painful, is not an emergency unless there is concern for concomitant urinary tract infection, both ureters are obstructed by stones, or there is an obstructing stone in a solitary kidney. Copyright © 2017 Elsevier Inc. All rights reserved.

[Neisser and the clap].

PubMed

Elbert, Niels J; van Gijn, Jan; Gijselhart, Joost P

2013-01-01

In 1879, during his specialization in dermatology, Albert Ludwig Sigesmund Neisser (1855-1916) discovered the bacterial cause of gonorrhoea. The gonococcus - Neisseria gonorrhoea - would, however, not bear his name until 1933. Neisser's early research focused primarily on venereal diseases, syphilis in particular, and on leprosy. Later, as a hygienist, he became a passionate advocate of public clinics for venereal diseases, regulated prostitution, and health education. In 1916, Neisser died of sepsis after lithotripsy for nephrolithiasis. His scientific inheritance includes many publications on a variety of venereal and skin diseases and public health-related topics, and textbooks such as Ikonographia dermatologica and Stereoskopischer Medizinischer Atlas.

Disease of the year: juvenile idiopathic arthritis--differential diagnosis.

PubMed

Hu-Torres, Sandra; Foster, C Stephen

2014-02-01

The purpose of this review is to comprehensively explain the differential diagnosis of juvenile idiopathic arthritis-associated uveitis. Web-based literature review. Main diagnostic decisions are made through a thorough anterior segment exam and a comprehensive exploration of past medical and family history. High clinical suspicion of other uveitic entities occurring in children is necessary and must be excluded by the practitioner before immediate diagnosis of juvenile idiopathic arthritis is made.

Idiopathic hemifacial spasm responsive to zonisamide: a case report.

PubMed

Siniscalchi, Antonio; Gallelli, Luca; Palleria, Caterina; De Sarro, Giovambattista

2009-01-01

We describe a patient with idiopathic hemifacial spasm (HFS) that was responsive to zonisamide treatment. A 65-year-old woman presented with a 4-year history of left-sided HFS developing gradually, starting from the upper facial muscles. After several analyses, the diagnosis of idiopathic HFS was made, and the clonazepam treatment (0.5 mg every 8 hours) was started, without a complete remission of symptoms. Therefore, zonisamide (150 mg twice a day for a 6-week period) was added, with a complete resolution. The rechallenge with zonisamide after its dechallenge confirmed its effectiveness. During follow-up, the patient remained symptom-free, with no adverse drug reactions. We suggest that zonisamide could represent a useful therapeutic option in the treatment of idiopathic HFS.

The Accuracy and Prognostic Value of Point-of-care Ultrasound for Nephrolithiasis in the Emergency Department: A Systematic Review and Meta-analysis.

PubMed

Wong, Charles; Teitge, Braden; Ross, Marshall; Young, Paul; Robertson, Helen Lee; Lang, Eddy

2018-06-01

Point-of-care ultrasound (POCUS) has been suggested as an initial investigation in the management of renal colic. Our objectives were: 1) to determine the accuracy of POCUS for the diagnosis of nephrolithiasis and 2) to assess its prognostic value in the management of renal colic. The review protocol was registered to the PROSPERO database (CRD42016035331). An electronic database search of MEDLINE, Embase, and PubMed was conducted utilizing subject headings, keywords, and synonyms that address our research question. Bibliographies of included studies and narrative reviews were manually examined. Studies of adult emergency department patients with renal colic symptoms were included. Any degree of hydronephrosis was considered a positive POCUS finding. Accepted criterion standards were computed tomography evidence of renal stone or hydronephrosis, direct stone visualization, or surgical findings. Screening of abstracts, quality assessment with the QUADAS-2 instrument, and data extraction were performed by two reviewers, with discrepancies resolved by consensus with a third reviewer. Test performance was assessed by pooled sensitivity and specificity, calculated likelihood ratios, and a summary receiver operator curve (SROC). The secondary objective of prognostic value was reported as a narrative summary. The electronic search yielded 627 unique titles. After relevance screening, 26 papers underwent full-text review, and nine articles met all inclusion criteria. Of these, five high-quality studies (N = 1,773) were included in the meta-analysis for diagnostic accuracy and the remaining yielded data on prognostic value. The pooled results for sensitivity and specificity were 70.2% (95% confidence interval [CI] = 67.1%-73.2%) and 75.4% (95% CI = 72.5%-78.2%), respectively. The calculated positive and negative likelihood ratios were 2.85 and 0.39. The SROC generated did not show evidence of a threshold effect. Two of the studies in the meta-analysis found that the finding of moderate or greater hydronephrosis yielded a specificity of 94.4% (95% CI = 92.7%-95.8%). Four studies examining prognostic value noted a higher likelihood of a large stone when positive POCUS findings were present. The largest randomized trial showed lower cumulative radiation exposure and no increase in adverse events in those who received POCUS investigation as the initial renal colic investigation. Point-of-care ultrasound has modest diagnostic accuracy for diagnosing nephrolithiasis. The finding of moderate or severe hydronephrosis is highly specific for the presence of any stone, and the presence of any hydronephrosis is suggestive of a larger (>5 mm) stone in those presenting with renal colic. © 2018 by the Society for Academic Emergency Medicine.

Endoscopic treatment of esophageal achalasia

PubMed Central

Esposito, Dario; Maione, Francesco; D’Alessandro, Alessandra; Sarnelli, Giovanni; De Palma, Giovanni D

2016-01-01

Achalasia is a motility disorder of the esophagus characterized by dysphagia, regurgitation of undigested food, chest pain, weight loss and respiratory symptoms. The most common form of achalasia is the idiopathic one. Diagnosis largely relies upon endoscopy, barium swallow study, and high resolution esophageal manometry (HRM). Barium swallow and manometry after treatment are also good predictors of success of treatment as it is the residue symptomatology. Short term improvement in the symptomatology of achalasia can be achieved with medical therapy with calcium channel blockers or endoscopic botulin toxin injection. Even though few patients can be cured with only one treatment and repeat procedure might be needed, long term relief from dysphagia can be obtained in about 90% of cases with either surgical interventions such as laparoscopic Heller myotomy or with endoscopic techniques such pneumatic dilatation or, more recently, with per-oral endoscopic myotomy. Age, sex, and manometric type by HRM are also predictors of responsiveness to treatment. Older patients, females and type II achalasia are better after treatment compared to younger patients, males and type III achalasia. Self-expandable metallic stents are an alternative in patients non responding to conventional therapies. PMID:26839644

Prevalence of vitamin D deficiency and rickets in children with cholestasis in Iran.

PubMed

Mohammadi, Bahram; Najafi, Mehri; Farahmand, Fateme; Motamed, Farzaneh; Ghajarzadeh, Mahsa; Mohammadi, Jamshid; Eshagh Roze, Mohammad

2012-01-01

This study was aimed to determine prevalence of vitamin D deficiency and rickets in children with cholestatic liver diseases. Forty eight children with established cholestatic liver disease who referred to gastrointestinal clinic of Children Medical Center (Tehran, Iran) between April 2010 and March 2011 were enrolled in a cross-sectional study. Laboratory analysis including calcium, phosphate, albumin, total and direct bilirubin, aminotransferases, alkalinephosphatase (ALP), prothrombin time (PT), parathyroid hormone (PTH), total protein determined by routine laboratory techniques. Mean age of participants was 299.1 ± 676.8 days (range 2-3600 days) whereas twenty one were female (43.8%) and 27 (56.3%) were male. Twenty two (45.8%) had evidences of rickets in X-ray evaluation. Three children with rickets and two with normal X-ray had vitamin D deficiency while ten in rickets group and 16 in normal group had vitamin D insufficiency. The main underlying diseases were anatomical biliary atresia in cases with rickets and idiopathic in other group. Rickets and vitamin D deficiency should be considered in chronic cholestatic children.

Endoscopic treatment of esophageal achalasia.

PubMed

Esposito, Dario; Maione, Francesco; D'Alessandro, Alessandra; Sarnelli, Giovanni; De Palma, Giovanni D

2016-01-25

Achalasia is a motility disorder of the esophagus characterized by dysphagia, regurgitation of undigested food, chest pain, weight loss and respiratory symptoms. The most common form of achalasia is the idiopathic one. Diagnosis largely relies upon endoscopy, barium swallow study, and high resolution esophageal manometry (HRM). Barium swallow and manometry after treatment are also good predictors of success of treatment as it is the residue symptomatology. Short term improvement in the symptomatology of achalasia can be achieved with medical therapy with calcium channel blockers or endoscopic botulin toxin injection. Even though few patients can be cured with only one treatment and repeat procedure might be needed, long term relief from dysphagia can be obtained in about 90% of cases with either surgical interventions such as laparoscopic Heller myotomy or with endoscopic techniques such pneumatic dilatation or, more recently, with per-oral endoscopic myotomy. Age, sex, and manometric type by HRM are also predictors of responsiveness to treatment. Older patients, females and type II achalasia are better after treatment compared to younger patients, males and type III achalasia. Self-expandable metallic stents are an alternative in patients non responding to conventional therapies.

Presynaptic Disorders: Lambert-Eaton Myasthenic Syndrome and Botulism.

PubMed

Gable, Karissa L; Massey, Janice M

2015-08-01

Lambert-Eaton myasthenic syndrome (LEMS) and botulism are acquired presynaptic nerve terminal disorders of the neuromuscular junction. Lambert-Eaton myasthenic syndrome is an idiopathic or paraneoplastic autoimmune syndrome in which autoantibodies of the P/Q-type voltage-gated calcium channel play a role in decreasing the release of acetylcholine, resulting in clinical symptoms of skeletal muscle weakness, diminished reflexes, and autonomic symptoms. Paraneoplastic LEMS is most often associated with small cell lung cancer. Diagnosis is confirmed by positive serologic testing and electrophysiological studies, which display characteristic features of low compound muscle action potentials, a decrement at 3Hz repetitive nerve stimulation, and facilitation with exercise or high-frequency repetitive stimulation. Treatment involves cancer monitoring and treatment, 3,4-diaminopyridine, immunosuppressive medications, and acetylcholinesterase inhibitors. Botulism is another presynaptic disorder of neuromuscular transmission. Clinical features classically involve cranial and bulbar palsies followed by descending weakness of the limbs, respiratory failure, and autonomic dysfunction. Electrodiagnostic testing is important in the evaluation and diagnosis. Treatment is supportive, and administration of antitoxin is beneficial in selected cases. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Genome-wide association analysis identifies 13 new risk loci for schizophrenia.

PubMed

Ripke, Stephan; O'Dushlaine, Colm; Chambert, Kimberly; Moran, Jennifer L; Kähler, Anna K; Akterin, Susanne; Bergen, Sarah E; Collins, Ann L; Crowley, James J; Fromer, Menachem; Kim, Yunjung; Lee, Sang Hong; Magnusson, Patrik K E; Sanchez, Nick; Stahl, Eli A; Williams, Stephanie; Wray, Naomi R; Xia, Kai; Bettella, Francesco; Borglum, Anders D; Bulik-Sullivan, Brendan K; Cormican, Paul; Craddock, Nick; de Leeuw, Christiaan; Durmishi, Naser; Gill, Michael; Golimbet, Vera; Hamshere, Marian L; Holmans, Peter; Hougaard, David M; Kendler, Kenneth S; Lin, Kuang; Morris, Derek W; Mors, Ole; Mortensen, Preben B; Neale, Benjamin M; O'Neill, Francis A; Owen, Michael J; Milovancevic, Milica Pejovic; Posthuma, Danielle; Powell, John; Richards, Alexander L; Riley, Brien P; Ruderfer, Douglas; Rujescu, Dan; Sigurdsson, Engilbert; Silagadze, Teimuraz; Smit, August B; Stefansson, Hreinn; Steinberg, Stacy; Suvisaari, Jaana; Tosato, Sarah; Verhage, Matthijs; Walters, James T; Levinson, Douglas F; Gejman, Pablo V; Kendler, Kenneth S; Laurent, Claudine; Mowry, Bryan J; O'Donovan, Michael C; Owen, Michael J; Pulver, Ann E; Riley, Brien P; Schwab, Sibylle G; Wildenauer, Dieter B; Dudbridge, Frank; Holmans, Peter; Shi, Jianxin; Albus, Margot; Alexander, Madeline; Campion, Dominique; Cohen, David; Dikeos, Dimitris; Duan, Jubao; Eichhammer, Peter; Godard, Stephanie; Hansen, Mark; Lerer, F Bernard; Liang, Kung-Yee; Maier, Wolfgang; Mallet, Jacques; Nertney, Deborah A; Nestadt, Gerald; Norton, Nadine; O'Neill, Francis A; Papadimitriou, George N; Ribble, Robert; Sanders, Alan R; Silverman, Jeremy M; Walsh, Dermot; Williams, Nigel M; Wormley, Brandon; Arranz, Maria J; Bakker, Steven; Bender, Stephan; Bramon, Elvira; Collier, David; Crespo-Facorro, Benedicto; Hall, Jeremy; Iyegbe, Conrad; Jablensky, Assen; Kahn, Rene S; Kalaydjieva, Luba; Lawrie, Stephen; Lewis, Cathryn M; Lin, Kuang; Linszen, Don H; Mata, Ignacio; McIntosh, Andrew; Murray, Robin M; Ophoff, Roel A; Powell, John; Rujescu, Dan; Van Os, Jim; Walshe, Muriel; Weisbrod, Matthias; Wiersma, Durk; Donnelly, Peter; Barroso, Ines; Blackwell, Jenefer M; Bramon, Elvira; Brown, Matthew A; Casas, Juan P; Corvin, Aiden P; Deloukas, Panos; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S; Mathew, Christopher G; Palmer, Colin N A; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J; Trembath, Richard C; Viswanathan, Ananth C; Wood, Nicholas W; Spencer, Chris C A; Band, Gavin; Bellenguez, Céline; Freeman, Colin; Hellenthal, Garrett; Giannoulatou, Eleni; Pirinen, Matti; Pearson, Richard D; Strange, Amy; Su, Zhan; Vukcevic, Damjan; Donnelly, Peter; Langford, Cordelia; Hunt, Sarah E; Edkins, Sarah; Gwilliam, Rhian; Blackburn, Hannah; Bumpstead, Suzannah J; Dronov, Serge; Gillman, Matthew; Gray, Emma; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T; Liddle, Jennifer; Potter, Simon C; Ravindrarajah, Radhi; Ricketts, Michelle; Tashakkori-Ghanbaria, Avazeh; Waller, Matthew J; Weston, Paul; Widaa, Sara; Whittaker, Pamela; Barroso, Ines; Deloukas, Panos; Mathew, Christopher G; Blackwell, Jenefer M; Brown, Matthew A; Corvin, Aiden P; McCarthy, Mark I; Spencer, Chris C A; Bramon, Elvira; Corvin, Aiden P; O'Donovan, Michael C; Stefansson, Kari; Scolnick, Edward; Purcell, Shaun; McCarroll, Steven A; Sklar, Pamela; Hultman, Christina M; Sullivan, Patrick F

2013-10-01

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

Clinical characteristics of Helicobacter pylori-negative drug-negative peptic ulcer bleeding

PubMed Central

Chung, Woo Chul; Jeon, Eun Jung; Kim, Dae Bum; Sung, Hea Jung; Kim, Yeon-Ji; Lim, Eun Sun; Kim, Min-ah; Oh, Jung Hwan

2015-01-01

AIM: To investigate the clinical characteristics and outcomes of idiopathic Helicobacter pylori (H. pylori)-negative and drug-negative] peptic ulcer bleeding (PUB). METHODS: A consecutive series of patients who experienced PUB between 2006 and 2012 was retrospectively analyzed. A total of 232 patients were enrolled in this study. The patients were divided into four groups according to the etiologies of PUB: idiopathic, H. pylori-associated, drug-induced and combined (H. pylori-associated and drug-induced) types. We compared the clinical characteristics and outcomes between the groups. When the silver stain or rapid urease tests were H. pylori-negative, we obtained an additional biopsy specimen by endoscopic re-examination and performed an H. pylori antibody test 6-8 wk after the initial endoscopic examination. For a diagnosis of idiopathic PUB, a negative result of an H. pylori antibody test was confirmed. In all cases, re-bleeding was confirmed by endoscopic examination. For the risk assessment, the Blatchford and the Rockall scores were calculated for all patients. RESULTS: For PUB, the frequency of H. pylori infection was 59.5% (138/232), whereas the frequency of idiopathic cases was 8.6% (20/232). When idiopathic PUB was compared to H. pylori-associated PUB, the idiopathic PUB group showed a higher rate of re-bleeding after initial hemostasis during the hospital stay (30% vs 7.4%, P = 0.02). When idiopathic PUB was compared to drug-induced PUB, the patients in the idiopathic PUB group showed a higher rate of re-bleeding after initial hemostasis upon admission (30% vs 2.7%, P < 0.01). When drug-induced PUB was compared to H. pylori-associated PUB, the patients in the drug-induced PUB were older (68.49 ± 14.76 years vs 47.83 ± 15.15 years, P < 0.01) and showed a higher proportion of gastric ulcer (77% vs 49%, P < 0.01). However, the Blatchford and the Rockall scores were not significantly different between the two groups. Among the patients who experienced drug-induced PUB, no significant differences were found with respect to clinical characteristics, irrespective of H. pylori infection. CONCLUSION: Idiopathic PUB has unique clinical characteristics such as re-bleeding after initial hemostasis upon admission. Therefore, these patients need to undergo close surveillance upon admission. PMID:26229405

Clinical characteristics of Helicobacter pylori-negative drug-negative peptic ulcer bleeding.

PubMed

Chung, Woo Chul; Jeon, Eun Jung; Kim, Dae Bum; Sung, Hea Jung; Kim, Yeon-Ji; Lim, Eun Sun; Kim, Min-Ah; Oh, Jung Hwan

2015-07-28

To investigate the clinical characteristics and outcomes of idiopathic Helicobacter pylori (H. pylori)-negative and drug-negative] peptic ulcer bleeding (PUB). A consecutive series of patients who experienced PUB between 2006 and 2012 was retrospectively analyzed. A total of 232 patients were enrolled in this study. The patients were divided into four groups according to the etiologies of PUB: idiopathic, H. pylori-associated, drug-induced and combined (H. pylori-associated and drug-induced) types. We compared the clinical characteristics and outcomes between the groups. When the silver stain or rapid urease tests were H. pylori-negative, we obtained an additional biopsy specimen by endoscopic re-examination and performed an H. pylori antibody test 6-8 wk after the initial endoscopic examination. For a diagnosis of idiopathic PUB, a negative result of an H. pylori antibody test was confirmed. In all cases, re-bleeding was confirmed by endoscopic examination. For the risk assessment, the Blatchford and the Rockall scores were calculated for all patients. For PUB, the frequency of H. pylori infection was 59.5% (138/232), whereas the frequency of idiopathic cases was 8.6% (20/232). When idiopathic PUB was compared to H. pylori-associated PUB, the idiopathic PUB group showed a higher rate of re-bleeding after initial hemostasis during the hospital stay (30% vs 7.4%, P = 0.02). When idiopathic PUB was compared to drug-induced PUB, the patients in the idiopathic PUB group showed a higher rate of re-bleeding after initial hemostasis upon admission (30% vs 2.7%, P < 0.01). When drug-induced PUB was compared to H. pylori-associated PUB, the patients in the drug-induced PUB were older (68.49 ± 14.76 years vs 47.83 ± 15.15 years, P < 0.01) and showed a higher proportion of gastric ulcer (77% vs 49%, P < 0.01). However, the Blatchford and the Rockall scores were not significantly different between the two groups. Among the patients who experienced drug-induced PUB, no significant differences were found with respect to clinical characteristics, irrespective of H. pylori infection. Idiopathic PUB has unique clinical characteristics such as re-bleeding after initial hemostasis upon admission. Therefore, these patients need to undergo close surveillance upon admission.

An electrocardiographic scoring system for distinguishing right ventricular outflow tract arrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy from idiopathic ventricular tachycardia.

PubMed

Hoffmayer, Kurt S; Bhave, Prashant D; Marcus, Gregory M; James, Cynthia A; Tichnell, Crystal; Chopra, Nagesh; Moxey, Laura; Krahn, Andrew D; Dixit, Sanjay; Stevenson, William; Calkins, Hugh; Badhwar, Nitish; Gerstenfeld, Edward P; Scheinman, Melvin M

2013-04-01

Ventricular arrhythmias in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) and idiopathic ventricular tachycardia (VT) can share a left bundle branch block/inferior axis morphology. We previously reported electrocardiogram characteristics during outflow tract ventricular arrhythmias that helped distinguish VT related to ARVD/C from idiopathic VT. To prospectively validate these criteria. We created a risk score by using a derivation cohort. Two experienced electrophysiologists blinded to the diagnosis prospectively scored patients with VT/premature ventricular contractions (PVCs) with left bundle branch block/inferior axis pattern in a validation cohort of 37 ARVD/C tracings and 49 idiopathic VT tracings. All patients with ARVD/C had their diagnosis confirmed based on the revised task force criteria. Patients with idiopathic VT were selected based on structurally normal hearts with documented right ventricular outflow tract VT successfully treated with ablation. The scoring system provides 3 points for sinus rhythm anterior T-wave inversions in leads V1-V3 and during ventricular arrhythmia: 2 points for QRS duration in lead I≥120 ms, 2 points for QRS notching, and 1 point for precordial transition at lead V5 or later. A score of 5 or greater was able to correctly distinguish ARVD/C from idiopathic VT 93% of the time, with a sensitivity of 84%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 91%. We describe a simple scoring algorithm that uses 12-lead electrocardiogram characteristics to effectively distinguish right ventricular outflow tract arrhythmias originating from patients with ARVD/C versus patients with idiopathic VT. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Facial morphology in children and adolescents with juvenile idiopathic arthritis and moderate to severe temporomandibular joint involvement.

PubMed

Hsieh, Yuh-Jia; Darvann, Tron A; Hermann, Nuno V; Larsen, Per; Liao, Yu-Fang; Bjoern-Joergensen, Jens; Kreiborg, Sven

2016-02-01

The aims of this study were to (1) assess lateral facial morphology in children and adolescents with juvenile idiopathic arthritis and moderate to severe temporomandibular joint (TMJ) involvement, (2) compare the lateral facial morphology of these subjects with and without TMJ involvement using cephalograms and 3-dimensional (3D) facial photographs, and (3) compare and correlate the results of the 3D photographic and cephalometric analyses. Sixty patients with juvenile idiopathic arthritis were included and grouped as follows: group 1, juvenile idiopathic arthritis patients without TMJ involvement; group 2, juvenile idiopathic arthritis patients with moderate to severe unilateral TMJ involvement; and group 3, juvenile idiopathic arthritis patients with moderate to severe bilateral TMJ involvement. Lateral cephalograms were used to assess and compare lateral facial morphologies between the groups. Lateral projections of oriented 3D photographs were superimposed on the lateral cephalograms. The results of the lateral 3D photographic analysis were correlated with those of lateral cephalometric analysis. Group 3 showed the most severe growth disturbances, including more retrognathic mandible and retruded chin, steep occlusal and mandibular planes, and more hyperdivergent type (P <0.01). Group 2 showed similar growth disturbances, but to a lesser extent than did group 3. Photographic variables were significantly correlated with the soft tissue and skeletal variables of cephalograms (0.5 < r < 0.9; P <0.001). Subjects with juvenile idiopathic arthritis and unilateral or bilateral moderate to severe TMJ involvement had significant growth disturbances. Early intervention is recommended for these patients to prevent unfavorable facial development. Furthermore, with proper orientation, 3D photographs can be used as an alternative to conventional lateral cephalograms and 2-dimensional photographs. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Risk for Femoral Fractures in Parkinson’s Disease Patients with and without Severe Functional Impairment

PubMed Central

Benzinger, Petra; Rapp, Kilian; Maetzler, Walter; König, Hans-Helmut; Jaensch, Andrea; Klenk, Jochen; Büchele, Gisela

2014-01-01

Background Impaired balance is a major problem in patients with idiopathic Parkinson’s disease (PD) resulting in an increased risk of falls and fall-related fractures. Most studies which analyzed the risk of femoral fractures in patients with idiopathic PD were performed either in specialized centers or excluded very frail patients. The current study used a large population-based dataset in order to analyze the risk of femoral fractures in patients with idiopathic PD. Methods Data from more than 880.000 individuals aged 65 years or older and insured between 2004 and 2009 at a large German health insurance company were used for the analyses. Persons with idiopathic PD were identified by the dispensing of Parkinson-specific medication and by hospital diagnoses, if available. People without PD served as the reference group. Incident femoral fractures were obtained from hospital diagnoses. Analyses were stratified by gender and information on severe functional impairment (care need) as provided by reimbursement claims. Results Compared with the reference group, persons with idiopathic PD had a more than doubled risk to sustain a femoral fracture. The risk was higher in men (HR = 2.61; 95%-CI: 2.28–2.98) than in women (HR = 1.79; 95%-CI: 1.66–1.94). The increased risk was only observed in people without severe functional impairment. The sensitivity analysis using a refined definition of idiopathic PD patients yielded similar results. Conclusion The findings confirm the increased risk of femoral fractures in patients with idiopathic PD. The relative risk is particularly high in male PD patients and in patients without severe functional impairment. PMID:24853110

Detection of equine herpesvirus in horses with idiopathic keratoconjunctivitis and comparison of three sampling techniques.

PubMed

Hollingsworth, Steven R; Pusterla, Nicola; Kass, Philip H; Good, Kathryn L; Brault, Stephanie A; Maggs, David J

2015-09-01

To determine the role of equine herpesvirus (EHV) in idiopathic keratoconjunctivitis in horses and to determine whether sample collection method affects detection of EHV DNA by quantitative polymerase chain reaction (qPCR). Twelve horses with idiopathic keratoconjunctivitis and six horses without signs of ophthalmic disease. Conjunctival swabs, corneal scrapings, and conjunctival biopsies were collected from 18 horses: 12 clinical cases with idiopathic keratoconjunctivitis and six euthanized controls. In horses with both eyes involved, the samples were taken from the eye judged to be more severely affected. Samples were tested with qPCR for EHV-1, EHV-2, EHV-4, and EHV-5 DNA. Quantity of EHV DNA and viral replicative activity were compared between the two populations and among the different sampling techniques; relative sensitivities of the sampling techniques were determined. Prevalence of EHV DNA as assessed by qPCR did not differ significantly between control horses and those with idiopathic keratoconjunctivitis. Sampling by conjunctival swab was more likely to yield viral DNA as assessed by qPCR than was conjunctival biopsy. EHV-1 and EHV-4 DNA were not detected in either normal or IKC-affected horses; EHV-2 DNA was detected in two of 12 affected horses but not in normal horses. EHV-5 DNA was commonly found in ophthalmically normal horses and horses with idiopathic keratoconjunctivitis. Because EHV-5 DNA was commonly found in control horses and in horses with idiopathic keratoconjunctivitis, qPCR was not useful for the etiological diagnosis of equine keratoconjunctivitis. Conjunctival swabs were significantly better at obtaining viral DNA samples than conjunctival biopsy in horses in which EHV-5 DNA was found. © 2015 American College of Veterinary Ophthalmologists.

Gastric neuromuscular histology in patients with refractory gastroparesis: Relationships to etiology, gastric emptying, and response to gastric electric stimulation.

PubMed

Heckert, J; Thomas, R M; Parkman, H P

2017-08-01

The aims of this study were to describe the histology in gastroparesis, specifically to relate histopathology to etiology of gastroparesis (idiopathic and diabetic gastroparesis), gastric emptying, and clinical response to gastric electric stimulation. Full thickness gastric body sections obtained during insertion of gastric stimulator in gastroparetics were stained with Hematoxylin & Eosin, Masson Trichrome and immunohistochemical stains for Neuron-Specific Enolase and c-Kit. In all, 145 gastroparetics (71 diabetics, 71 idiopathic, 2 post-surgical, and 1 chronic intestinal pseudo-obstruction) had full thickness gastric body biopsies. A lymphocytic infiltrate was seen in the intermyenteric plexus in 22 diabetic and 23 idiopathic gastroparesis patients. Fibrosis was present in the inner circular layer in 13 diabetic and 15 idiopathics and in the outer longitudinal layer in 46 diabetic and 51 idiopathics. Diabetic gastroparesis had less ganglion cells (3.27±1.82 vs 4.81±2.81/hpf; P<.01) and less ganglia (0.90±0.44 vs 1.10±0.50/hpf; P=.01) than idiopathic gastroparesis. Interstitial cells of Cajal (ICC) count was slightly lower in the inner circular layer in diabetic than idiopathics (2.77±1.47 vs 3.18±1.34/hpf; P=.08). Delayed gastric emptying was associated with reduced ICCs in the myenteric plexus. Global therapeutic response to gastric electric stimulation was inversely related to ganglia/hpf (R=-.22; P=.008). In diabetics, improvements in nausea, vomiting, and abdominal pain were inversely related to fibrosis. Histologic assessment of full thickness gastric biopsy specimens allows correlation of histopathology to the gastroparesis disease process, its etiology, gastric emptying, and response to gastric electric stimulation treatment. © 2017 John Wiley & Sons Ltd.

Alcohol and smoking as risk factors in an epidemiology study of patients with chronic pancreatitis.

PubMed

Coté, Gregory A; Yadav, Dhiraj; Slivka, Adam; Hawes, Robert H; Anderson, Michelle A; Burton, Frank R; Brand, Randall E; Banks, Peter A; Lewis, Michele D; Disario, James A; Gardner, Timothy B; Gelrud, Andres; Amann, Stephen T; Baillie, John; Money, Mary E; O'Connell, Michael; Whitcomb, David C; Sherman, Stuart

2011-03-01

Alcohol has been implicated in the development of chronic pancreatitis (CP) in 60%-90% of patients, although percentages in the United States are unknown. We investigated the epidemiology of alcohol-related CP at tertiary US referral centers. We studied data from CP patients (n = 539) and controls (n = 695) enrolled in the North American Pancreatitis Study-2 from 2000 to 2006 at 20 US referral centers. CP was defined by definitive evidence from imaging or histologic analyses. Subjects and physicians each completed a study questionnaire. Using physician-assigned diagnoses, patients were assigned to an etiology group: alcohol (with/without other diagnoses), nonalcohol (any etiology of CP from other than alcohol), or idiopathic (no etiology identified). The distribution of patients among etiology groups was: alcohol (44.5%), nonalcohol (26.9%), and idiopathic (28.6%). Physicians identified alcohol as the etiology more frequently in men (59.4% men vs 28.1% women), but nonalcohol (18% men vs 36.7% women) and idiopathic etiologies (22.6% men vs 35.2% women) more often in women (P < .01 for all comparisons). Nonalcohol etiologies were equally divided among obstructive, genetic, and other causes. Compared with controls, patients with idiopathic CP were more likely to have ever smoked (58.6% vs 49.7%, P < .05) or have a history of chronic renal disease or failure (5.2% vs 1.2%, P < .01). In multivariate analyses, smoking (ever, current, and amount) was independently associated with idiopathic CP. The frequency of alcohol-related CP at tertiary US referral centers is lower than expected. Idiopathic CP and nonalcohol etiologies represent a large subgroup, particularly among women. Smoking is an independent risk factor for idiopathic CP. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

[Effects of temporal lobe epilepsy and idiopathic epilepsy on cognitive function and emotion in children].

PubMed

Yang, Xiao-Yan; Long, Li-Li; Xiao, Bo

2016-07-01

To investigate the effects of temporal lobe epilepsy and idiopathic epilepsy on cognitive function and emotion in children and the risk factors for cognitive impairment. A retrospective analysis was performed for the clinical data of 38 children with temporal lobe epilepsy and 40 children with idiopathic epilepsy. The controls were 42 healthy children. All subjects received the following neuropsychological tests: Montreal Cognitive Assessment (MoCA) scale, verbal fluency test, digit span test, block design test, Social Anxiety Scale for Children (SASC), and Depression Self-rating Scale for Children (DSRSC). Compared with the control group, the temporal lobe epilepsy and idiopathic epilepsy groups showed significantly lower scores of MoCA, verbal fluency, digit span, and block design (P<0.05) and significantly higher scores on SASC and DSRSC (P<0.05). Compared with the idiopathic epilepsy group, the temporal lobe epilepsy group showed significantly lower scores of MoCA, verbal fluency, digit span, and block design (P<0.05) and significantly higher scores on SASC and DSRSC (P<0.05). In the temporal lobe epilepsy group, MoCA score was negatively correlated with SASC score, DSRSC score, and seizure frequency (r=-0.571, -0.529, and -0.545 respectively; P<0.01). In the idiopathic epilepsy group, MoCA score was also negatively correlated with SASC score, DSRSC score, and seizure frequency (r=-0.542, -0.487, and -0.555 respectively; P<0.01). Children with temporal lobe epilepsy and idiopathic epilepsy show impaired whole cognition, verbal fluency, memory, and executive function and have anxiety and depression, which are more significant in children with temporal lobe epilepsy. High levels of anxiety, depression, and seizure frequency are risk factors for impaired cognitive function.

Altered Regional Cerebral Blood Flow in Idiopathic Hypersomnia.

PubMed

Boucetta, Soufiane; Montplaisir, Jacques; Zadra, Antonio; Lachapelle, Francis; Soucy, Jean-Paul; Gravel, Paul; Dang-Vu, Thien Thanh

2017-10-01

Idiopathic hypersomnia is characterized by excessive daytime sleepiness, despite normal or long sleep time. Its pathophysiological mechanisms remain unclear. This pilot study aims at characterizing the neural correlates of idiopathic hypersomnia using single photon emission computed tomography. Thirteen participants with idiopathic hypersomnia and 16 healthy controls were scanned during resting wakefulness using a high-resolution single photon emission computed tomography scanner with 99mTc-ethyl cysteinate dimer to assess cerebral blood flow. The main analysis compared regional cerebral blood flow distribution between the two groups. Exploratory correlations between regional cerebral blood flow and clinical characteristics evaluated the functional correlates of those brain perfusion patterns. Significance was set at p < .05 after correction for multiple comparisons. Participants with idiopathic hypersomnia showed regional cerebral blood flow decreases in medial prefrontal cortex and posterior cingulate cortex and putamen, as well as increases in amygdala and temporo-occipital cortices. Lower regional cerebral blood flow in the medial prefrontal cortex was associated with higher daytime sleepiness. These preliminary findings suggest that idiopathic hypersomnia is characterized by functional alterations in brain areas involved in the modulation of vigilance states, which may contribute to the daytime symptoms of this condition. The distribution of regional cerebral blood flow changes was reminiscent of the patterns associated with normal non-rapid-eye-movement sleep, suggesting the possible presence of incomplete sleep-wake transitions. These abnormalities were strikingly distinct from those induced by acute sleep deprivation, suggesting that the patterns seen here might reflect a trait associated with idiopathic hypersomnia rather than a non-specific state of sleepiness. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Idiopathic Hypersomnia: Clinical Features and Response to Treatment

PubMed Central

Ali, Mohsin; Auger, R. Robert; Slocumb, Nancy L.; Morgenthaler, Timothy I.

2009-01-01

Objective: A recent American Academy of Sleep Medicine publication identified a need for research regarding idiopathic hypersomnia. We describe various clinical and polysomnographic features of patients with idiopathic hypersomnia, with an emphasis on response to pharmacotherapy. Methods: A retrospective review of our database initially identified 997 patients, utilizing “idiopathic hypersomnia,” “hypersomnia NOS,” and “primary hypersomnia” as keywords. The charts of eligible patients were examined in detail, and data were abstracted and analyzed. Response to treatment was graded utilizing an internally developed scale. Results: Eighty-five patients were ultimately identified (65% female). Median (interquartile range) ages of onset and diagnosis were 19.6 (15.5) and 33.7 (15.5), respectively. During a median follow-up duration of 2.4 (4.7) years, 65% of patients demonstrated a “complete response” to pharmacotherapy as assessed by the authors' grading schema. Methylphenidate was most commonly used as a first-line agent prior to December 1998, but subsequently, modafinil became the most common first drug. At the last recorded follow-up visit, 92% of patients were on monotherapy, with greater representation of methylphenidate versus modafinil (51% vs. 32%). Among these patients, methylphenidate produced a higher percentage of “complete” or “partial” responses than modafinil, although statistical significance was not reached (38/40 [ 95%] vs 22/25 [88%], respectively, p = 0.291). Conclusions: The majority of patients with idiopathic hypersomnia respond well to treatment. Methylphenidate is chosen more often than modafinil as final monotherapy in the treatment of idiopathic hypersomnia, despite the fact that it is less commonly used initially. Further prospective comparisons of medications should be explored. Citation: Ali M; Auger RR; Slocumb NL; Morgenthaler TI. Idiopathic hypersomnia: clinical features and response to treatment. J Clin Sleep Med 2009;5(6):562-568. PMID:20465024

Consanguineous marriage and increased risk of idiopathic congenital talipes equinovarus: a case-control study in a rural area.

PubMed

Sahin, Orcun; Yildirim, Cengiz; Akgun, Rahmi C; Haberal, Bahtiyar; Yazici, Ayse C; Tuncay, Ismail C

2013-01-01

The purpose of this study is to evaluate if there is any relationship between consanguineous marriages and idiopathic congenital talipes equinovarus (CTEV). A case-control study on CTEV screening was conducted in a rural eastern city of Turkey between 2009 and 2011 and a total of 28 cases (infants with idiopathic CTEV) and 575 controls (healthy infants) were recruited. Sociodemographic status of the infants, including gestational age and birth weights, maternal characteristics and, if any, the degree of consanguinity, were recorded. As an inclusion criterion, only singleton, full-term, live births were accepted. A backward stepwise logistic regression model was used to evaluate the relationship between idiopathic CTEV and parental consanguinity. Unadjusted and adjusted odds ratios (OR) with 95% confidence interval (CI) were calculated. Among maternal and infant characteristics, significant risk factors for idiopathic CTEV in the regression analysis were work status (employed), consanguineous marriage, sex (male), and gestational age (>42 wk). Babies born to first-cousin parents had >4 times the risk of idiopathic CTEV [OR, 4.138, (95% CI, 1.484, 11.538)] and the risk for those born to distant relatives was 2.9 times higher [OR, 2.941, (95% CI, 1.070, 8.087)] than for children of unrelated parents. Consanguineous marriage was significantly associated with an increased risk of idiopathic CTEV. This association remained significant even after adjusting for potential confounding variables. To obtain more accurate results, a population-based screening study with an increased number of cases and controls should be performed in future studies. Case-control study investigating the effect of a patient characteristic on the outcome of disease (level-III).

Molecular analysis of HLA-DPB1 alleles in idiopathic systemic sclerosis patients and uranium miners with systemic sclerosis.

PubMed

Rihs, H P; Conrad, K; Mehlhorn, J; May-Taube, K; Welticke, B; Frank, K H; Baur, X

1996-03-01

According to clinical mainifestation and autoantibody pattern [anti-Scl-70, anti-centromere antibodies (ACAs)], systemic sclerosis is a connective tissue disease with heterogenous subgroups. PCR-sequence-specific-oligonucleotide typing was used to study the genetic association of HLA-DPB1 alleles in 54 patients with idiopathic systemic sclerosis, 26 uranium miners with systemic sclerosis and 70 unrelated healthy control subjects. Systemic sclerosis patients with and without former employment in mines were divided into two subgroups according to their scleroderma-typical autoantibody specificities--anti-Scl-70 positive and ACA positive--and third subgroup comprising the rest. Statistical analysis revealed a significantly increased frequency of DPB1*1301(p=0.0001, corrected p=0.011) in idiopathic anti-Scl-70-positive systemic sclerosis cases when compared with unexposed controls. In the same group, we observed an enhanced frequency of DPB1*0601 and *1701 alleles. Since these three alleles carry the information for a glutamic acid residue in position 69 of DPB1, we tested the association of this residue with anti-Scl-70 expression. A strong association between anti-Scl-70 positivity in idiopathic systemic sclerosis patients and amino acid residue 69 of DPB1 was observed when compared with anti-Scl-70-negative idiopathic systemic sclerosis patients (p=0.0009) or unrelated controls (p=0.0007). ACA expression was not associated with the presence of any DPB1 allele tested. The data show that anti-Scl-70 expression in idiopathic systemic sclerosis patients is linked with DPB1*1301 whereas anti-Scl-70-positive miners do not show such a DPB1 association. Futhermore, the data indicate that glutamate 69 of DPB1 might be involved in the susceptibility to idiopathic anti-Scl-70 expression.

[Membranous glomerulonephritis. Experience at the Instituto Nacional de la Nutrición Salvador Zubirán].

PubMed

Correa-Rotter, R; Gamba, G; Ochoa, C; Onuma, L; Reyes, E; Tamayo, J A; Peña, J C

1990-01-01

The purpose of this retrospective study was to study the incidence of idiopathic and secondary forms of membranous nephropathy in our institution, its clinical course and progression to chronic renal failure, and the risk factors associated with it. Two hundred fourteen (16%) of the 1,287 renal biopsies obtained between 1962 and 1988 were primary glomerular diseases and 28 of this 214 (13%) were idiopathic membranous nephropathy. On the other hand 59 of 1,287 biopsies were membranous nephropathy of whom 28 were idiopathic, 27 secondary to systemic lupus erythematosus, 2 due to drugs, one associated with rheumatoid arthritis, and one more with breast cancer. The clinical picture was: nephrotic syndrome in 84%, hypertension in 15%, non-nephrotic proteinuria in 14%, chronic renal failure in 8.4%, and renal vein thrombosis in 6.3%. In the idiopathic group 75% of the patients were male while in the lupus group 85% were female. For the analysis of progression to chronic renal failure we excluded 5 patients with renal failure when the biopsy was taken, 2 because the nephropathy was due to drugs, one associated with breast cancer, and nine were within the first year of follow-up. Thus, for this analysis the group consisted of 22 patients with idiopathic form and 20 with systemic lupus erythematosus. The idiopathic and lupus groups were similar except for a lower serum albumin in the former. The progression to renal failure was seen in 9 patients: six in the idiopathic group and the other 3 in the lupus group; this difference was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

MR venography in idiopathic intracranial hypertension: unappreciated and misunderstood

PubMed Central

Higgins, J; Gillard, J; Owler, B; Harkness, K; Pickard, J

2004-01-01

Background: Venous sinus disease must be excluded before diagnosing idiopathic intracranial hypertension but is found only rarely in typical cases. Magnetic resonance venography (MRV) is the technique of choice for investigating this, and provides images that are diagnostic and easy to interpret. However, recent work using more invasive techniques has documented pressure gradients and stenoses in the lateral venous sinuses in many cases of idiopathic intracranial hypertension. Objective: To examine the reason for this discrepancy and to establish whether there are characteristic appearances on MRV in idiopathic intracranial hypertension that are routinely overlooked in clinical practice. Methods: MRVs from 20 patients with idiopathic intracranial hypertension were reviewed, unblinded, by two neuroradiologists, and their appearances rated for focal narrowings and signal gaps. A control group of 40 asymptomatic volunteers, matched for age and sex with the patient group, was recruited prospectively for MRV, and their scans rated in the same way. Results: The lateral sinuses presented a range of appearances with quite different distributions in the two groups (p<0.001). Bilateral lateral sinus flow gaps were seen in 13 of 20 patients with idiopathic intracranial hypertension and in none of 40 controls. Conclusions: A historical failure to use normal healthy controls to establish the boundaries between imaging artefact, normal anatomical variant, and disease means that the pathological significance of the different appearances of the lateral sinuses on MRV has not so far been appreciated. PMID:15026510

Auditory verbal memory and psychosocial symptoms are related in children with idiopathic epilepsy.

PubMed

Schaffer, Yael; Ben Zeev, Bruria; Cohen, Roni; Shuper, Avinoam; Geva, Ronny

2015-07-01

Idiopathic epilepsies are considered to have relatively good prognoses and normal or near normal developmental outcomes. Nevertheless, accumulating studies demonstrate memory and psychosocial deficits in this population, and the prevalence, severity and relationships between these domains are still not well defined. We aimed to assess memory, psychosocial function, and the relationships between these two domains among children with idiopathic epilepsy syndromes using an extended neuropsychological battery and psychosocial questionnaires. Cognitive abilities, neuropsychological performance, and socioemotional behavior of 33 early adolescent children, diagnosed with idiopathic epilepsy, ages 9-14years, were assessed and compared with 27 age- and education-matched healthy controls. Compared to controls, patients with stabilized idiopathic epilepsy exhibited higher risks for short-term memory deficits (auditory verbal and visual) (p<0.0001), working memory deficits (p<0.003), auditory verbal long-term memory deficits (p<0.0021), and more frequent psychosocial symptoms (p<0.0001). The severity of auditory verbal memory deficits was related to severity of psychosocial symptoms among the children with epilepsy but not in the healthy controls. Results suggest that deficient auditory verbal memory may be compromising psychosocial functioning in children with idiopathic epilepsy, possibly underscoring that cognitive variables, such as auditory verbal memory, should be assessed and treated in this population to prevent secondary symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

Short-term Clinical Results of Manipulation Under Ultrasound-Guided Brachial Plexus Block in Patients with Idiopathic Frozen Shoulder and Diabetic Secondary Frozen Shoulder.

PubMed

Ando, Akira; Hamada, Junichiro; Hagiwara, Yoshihiro; Sekiguchi, Takuya; Koide, Masashi; Itoi, Eiji

2018-01-01

This study examined the effectiveness of manipulation under ultrasound-guided brachial plexus block in patients with recalcitrant idiopathic frozen shoulder and diabetic secondary frozen shoulder (diabetic frozen shoulder). Forty-four idiopathic frozen shoulders and 10 diabetic frozen shoulders with failed conservative treatment for at least 3 months were included in this study. The manipulation was performed under ultrasound-guided brachial plexus block and visual analogue scale, range of motion, and Constant scores were measured before manipulation and at the last follow-up examination. No major complications were observed during the procedure. Sufficient improvement was not obtained in two patients during the procedure and to avoid complications, the procedure was discontinued and subsequently arthroscopic capsular release was performed. Visual analogue scale, range of motion towards all directions, and Constant scores were significantly improved after the manipulation in both the idiopathic frozen shoulder and diabetic frozen shoulder groups, however the diabetic group showed inferior results compared with those of the idiopathic group. This manipulation was effective and shortened the duration of symptoms in most of the idiopathic and diabetic frozen shoulders without major complications during the procedure. Diabetic frozen shoulder showed inferior clinical results and difficulty in recovery in range of motion, which indicated that diabetic frozen shoulder should be discussed as a different entity.

Determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis undergoing lung transplant evaluation.

PubMed

Porteous, Mary K; Rivera-Lebron, Belinda N; Kreider, Maryl; Lee, James; Kawut, Steven M

2016-03-01

Little is known about the physiologic determinants of 6-minute walk distance in idiopathic pulmonary fibrosis. We investigated the demographic, pulmonary function, echocardiographic, and hemodynamic determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis evaluated for lung transplantation. We performed a cross-sectional analysis of 130 patients with idiopathic pulmonary fibrosis who completed a lung transplantation evaluation at the Hospital of the University of Pennsylvania between 2005 and 2010. Multivariable linear regression analysis was used to generate an explanatory model for 6-minute walk distance. After adjustment for age, sex, race, height, and weight, the presence of right ventricular dilation was associated with a decrease of 50.9 m (95% confidence interval [CI], 8.4-93.3) in 6-minute walk distance ([Formula: see text]). For each 200-mL reduction in forced vital capacity, the walk distance decreased by 15.0 m (95% CI, 9.0-21.1; [Formula: see text]). For every increase of 1 Wood unit in pulmonary vascular resistance, the walk distance decreased by 17.3 m (95% CI, 5.1-29.5; [Formula: see text]). Six-minute walk distance in idiopathic pulmonary fibrosis depends in part on circulatory impairment and the degree of restrictive lung disease. Future trials that target right ventricular morphology, pulmonary vascular resistance, and forced vital capacity may potentially improve exercise capacity in patients with idiopathic pulmonary fibrosis.

Evaluation of Fitness and the Balance Levels of Children with a Diagnosis of Juvenile Idiopathic Arthritis: A Pilot Study

PubMed Central

Maggio, Maria Cristina; Corsello, Giovanni; Messina, Giuseppe; Iovane, Angelo; Palma, Antonio

2017-01-01

Background: Juvenile idiopathic arthritis is a main cause of physical disability and has high economic costs for society. The purpose of this study was to assess the fitness levels and the postural and balance deficits with a specific test battery. Methods: Fifty-six subjects were enrolled in this study. Thirty-nine healthy subjects were included in the control group and seventeen in the juvenile idiopathic arthritis group. All subjects were evaluated using a posturography system. The fitness level was evaluated with a battery of tests (Abalakov test, sit-up test, hand grip test, backsaver sit and reach, the toe touch test). An unpaired t-test was used to determine differences. Pearson’s correlation coefficient was used to evaluate the correlation between the tests. Results: The battery of tests demonstrated that subjects in the juvenile idiopathic arthritis group have lower fitness levels compared to the control group. The juvenile idiopathic arthritis group showed low postural control with respect to the control group. Pearson analysis of the juvenile idiopathic arthritis group data showed significant correlations between variables. Pearson’s results from the control group data showed a similar trend. Conclusions: The results suggest that the battery of tests used could be an appropriate tool. However, we highlight that these conclusions need to be supported by other studies with a larger population scale. PMID:28753965

Evaluation of Fitness and the Balance Levels of Children with a Diagnosis of Juvenile Idiopathic Arthritis: A Pilot Study.

PubMed

Patti, Antonino; Maggio, Maria Cristina; Corsello, Giovanni; Messina, Giuseppe; Iovane, Angelo; Palma, Antonio

2017-07-19

Background: Juvenile idiopathic arthritis is a main cause of physical disability and has high economic costs for society. The purpose of this study was to assess the fitness levels and the postural and balance deficits with a specific test battery. Methods: Fifty-six subjects were enrolled in this study. Thirty-nine healthy subjects were included in the control group and seventeen in the juvenile idiopathic arthritis group. All subjects were evaluated using a posturography system. The fitness level was evaluated with a battery of tests (Abalakov test, sit-up test, hand grip test, backsaver sit and reach, the toe touch test). An unpaired t -test was used to determine differences. Pearson's correlation coefficient was used to evaluate the correlation between the tests. Results: The battery of tests demonstrated that subjects in the juvenile idiopathic arthritis group have lower fitness levels compared to the control group. The juvenile idiopathic arthritis group showed low postural control with respect to the control group. Pearson analysis of the juvenile idiopathic arthritis group data showed significant correlations between variables. Pearson's results from the control group data showed a similar trend. Conclusions: The results suggest that the battery of tests used could be an appropriate tool. However, we highlight that these conclusions need to be supported by other studies with a larger population scale.

Associations Between Neuropsychological, Neurobehavioral and Emotional Functioning and Either Narcolepsy or Idiopathic Hypersomnia in Children and Adolescents.

PubMed

Ludwig, Beris; Smith, Simon; Heussler, Helen

2018-04-15

Narcolepsy and idiopathic hypersomnia are chronic neurological sleep disorders characterized by hypersomnolence or excessive daytime sleepiness. This review aims to systematically examine the scientific literature on the associations between narcolepsy and idiopathic hypersomnia and their effect on intellectual functioning, academic achievement, behavior, and emotion. Published studies that examined those associations in children and adolescents were included. Studies in which children or adolescents received a clinical diagnosis, and in which the associated function was measured with at least one objective instrument were included. Twenty studies published between 1968 and 2017 were eligible for inclusion in this review. There does not appear to be a clear association between intellectual functioning and narcolepsy or idiopathic hypersomnia; however, limited research is an obstacle to obtaining generalizability. The variability in results from studies investigating associations between academic achievement and these two hypersomnolence disorders suggests that further research using standardized and validated assessment instruments is required to determine if there is an association. Behavior and emotion appear to be significantly affected by narcolepsy. Only two studies included populations of children and adolescents with idiopathic hypersomnia. Further research using larger populations of children and adolescents with narcolepsy or idiopathic hypersomnia while utilizing standardized and validated instruments is required, because the effect of these conditions of hypersomnolence varies and is significant for each individual. © 2018 American Academy of Sleep Medicine.

Intraspinal anomalies in early-onset idiopathic scoliosis.

PubMed

Pereira, E A C; Oxenham, M; Lam, K S

2017-06-01

In the United Kingdom, lower incidences of intraspinal abnormalities in patients with early onset idiopathic scoliosis have been observed than in studies in other countries. We aimed to determine the rates of these abnormalities in United Kingdom patients diagnosed with idiopathic scoliosis before the age of 11 years. This retrospective study of patients attending an urban scoliosis clinic identified 71 patients satisfying a criteria of: clinical diagnosis of idiopathic scoliosis; age of onset ten years and 11 months or less; MRI screening for intraspinal abnormalities. United Kingdom census data combined with patient referral data was used to calculate incidence. Mean age at diagnosis was six years with 39 right-sided and 32 left-sided curves. Four patients (5.6%) were found to have intraspinal abnormalities on MRI. These consisted of: two combined Arnold-Chiari type 1 malformations with syrinx; one syrinx with a low lying conus; and one isolated syrinx. Overall annual incidence of early onset idiopathic scoliosis was one out of 182 000 (0.0006%). This study reports the lowest rates to date of intraspinal anomalies in patients with early onset idiopathic scoliosis, adding to knowledge regarding current incidences of these abnormalities as well as any geographical variation in the nature of the disease. Cite this article: Bone Joint J 2017;99-B:829-33. ©2017 The British Editorial Society of Bone & Joint Surgery.

Placental villous hypermaturation is associated with idiopathic preterm birth

PubMed Central

Morgan, Terry K.; Tolosa, Jorge E.; Mele, Lisa; Wapner, Ronald J.; Spong, Catherine Y.; Sorokin, Yoram; Dudley, Donald J.; Peaceman, Alan M.; Mercer, Brian M.; Thorp, John M.; O’Sullivan, Mary Jo; Ramin, Susan M.; Rouse, Dwight J.; Sibai, Baha

2014-01-01

Objective Pregnancy complications such as intra-amniotic infection, preeclampsia, and fetal intrauterine growth restriction (IUGR) account for most cases of preterm birth (PTB), but many spontaneous PTB cases do not have a clear etiology. We hypothesize that placental insufficiency may be a potential cause of idiopathic PTB. Methods Secondary analysis of 82 placental samples from women with PTB obtained from a multicenter trial of repeat versus single antenatal corticosteroids. Samples were centrally reviewed by a single placental pathologist masked to clinical outcomes. The histopathologic criterion for infection was the presence of acute chorioamnionitis defined as neutrophils marginating into the chorionic plate. Placental villous hypermaturation (PVH) was defined as a predominance of terminal villi (similar to term placenta) with extensive syncytial knotting. Idiopathic PTB comprised a group without another known etiology such as preeclampsia, IUGR or infection. Results Acute chorioamnionitis was observed in 33/82 (40%) cases. Other known causes of PTB were reported in 18/82 (22%). The remaining 31/82 (38%) were idiopathic. The frequency of PVH in idiopathic PTB (26/31=84%) was similar to cases with IUGR or preeclampsia (16/ 18=89%), but significantly more common than PVH in the group with acute chorioamnionitis (10/33=30%) (p<0.001). Conclusions PVH, which is a histologic marker of relative placental insufficiency, is a common finding in idiopathic PTB. PMID:23130816

Brain MRI findings in patients with idiopathic hypersomnia.

PubMed

Trotti, Lynn Marie; Bliwise, Donald L

2017-06-01

Proper diagnosis of idiopathic hypersomnia necessitates the exclusion of neurologic or medical causes of sleepiness that better explain the clinical syndrome. However, there are no formal guidelines regarding the use of neuroimaging to identify such secondary causes of symptoms. We sought to characterize brain MRI findings in a series of patients with idiopathic hypersomnia. We reviewed medical records on a consecutive series of 61 patients diagnosed with idiopathic hypersomnia to determine the frequency and results of brain magnetic resonance imaging (MRI). One-third of patients had undergone brain MRI, with focal neurologic signs or symptoms being the most common indication for neuroimaging. Although seven patients had an identifiable finding on neuroimaging (e.g., chronic microvascular ischemic changes), clinical management was changed as a result of imaging in only three cases. In all three, the imaging finding was predated by clear clinical abnormalities. Neuroimaging may be a complementary part of an idiopathic hypersomnia evaluation, but the decision to pursue imaging should be made on a case-by-case basis. Copyright © 2017 Elsevier B.V. All rights reserved.

Bell's palsy before Bell: Evert Jan Thomassen à Thuessink and idiopathic peripheral facial paralysis.

PubMed

van de Graaf, R C; IJpma, F F A; Nicolai, J-P A; Werker, P M N

2009-11-01

Bell's palsy is the eponym for idiopathic peripheral facial paralysis. It is named after Sir Charles Bell (1774-1842), who, in the first half of the nineteenth century, discovered the function of the facial nerve and attracted the attention of the medical world to facial paralysis. Our knowledge of this condition before Bell's landmark publications is very limited and is based on just a few documents. In 1804 and 1805, Evert Jan Thomassen à Thuessink (1762-1832) published what appears to be the first known extensive study on idiopathic peripheral facial paralysis. His description of this condition was quite accurate. He located several other early descriptions and concluded from this literature that, previously, the condition had usually been confused with other afflictions (such as 'spasmus cynicus', central facial paralysis and trigeminal neuralgia). According to Thomassen à Thuessink, idiopathic peripheral facial paralysis and trigeminal neuralgia were related, being different expressions of the same condition. Thomassen à Thuessink believed that idiopathic peripheral facial paralysis was caused by 'rheumatism' or exposure to cold. Many aetiological theories have since been proposed. Despite this, the cold hypothesis persists even today.

Debate: idiopathic short stature should be treated with growth hormone.

PubMed

Ambler, Geoffrey R; Fairchild, Jan; Wilkinson, Dominic J C

2013-03-01

In this paper we outline the case for and against the treatment of idiopathic short stature with growth hormone. Drs Ambler and Fairchild argue that many of those with 'idiopathic' short stature are not 'short, normal children' and will ultimately receive molecular diagnoses. They also argue that there is a subset of children who suffer negative psychosocial consequences of their stature for whom growth hormone therapy is effective. Growth hormone has a very good safety record and is likely to be as cost-effective in idiopathic short-stature as in some other conditions that are currently funded. Dr Wilkinson counters that short stature is not associated with physical or psychological illness, and that there is no evidence that growth hormone improves psychological or physical wellbeing. Moreover, growth hormone for idiopathic short stature represents a form of enhancement rather than treatment, and is not a fair use of resources. Socially mediated disadvantage should be treated by attention to prejudice and not by hormone treatment. © 2012 The Authors. Journal of Paediatrics and Child Health © 2012 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Adaptive Servo-Ventilation in "Real Life" Conditions : the OTRLASV Study

ClinicalTrials.gov

2017-03-27

Chronic Heart Failure and; Complex Sleep Apnea Syndrome; Obstructive Sleep Apnea Syndrome and; Idiopathic Central Sleep Apnea Syndrome; Idiopathic Induced Periodic Breathing; Central Sleep Apnea Syndrome

Idiopathic gingival fibromatosis rehabilitation: a case report with two-year followup.

PubMed

Jayachandran, Mahesh; Kapoor, Shalini; Mahesh, Rethi

2013-01-01

Gingival enlargements are quite common and may be either inflammatory, noninflammatory, or a combination of both. Gingival hyperplasia is a bizarre condition causing esthetic, functional, psychological, and masticatory disturbances of the oral cavity. Causes of gingival enlargement can be due to plaque accumulation, due to poor oral hygiene, inadequate nutrition, or systemic hormonal stimulation (Bakaeen and Scully, 1998). It can occur as an isolated disease or as part of a syndrome or chromosomal abnormality. A progressive fibrous enlargement of the gingiva is a facet of idiopathic fibrous hyperplasia of the gingiva (Carranza and Hogan, 2002; Gorlin et al., 1976). It is described variously as fibromatosis gingivae, gingivostomatitis, hereditary gingival fibromatosis, idiopathic fibromatosis, familial elephantiasis, and diffuse fibroma. We present a case of idiopathic gingival fibromatosis with its multidisciplinary approach of management.

The effect of myofascial release (MFR) on an adult with idiopathic scoliosis.

PubMed

LeBauer, Aaron; Brtalik, Robert; Stowe, Katherine

2008-10-01

The lack of evidence of conservative treatment has led to an interest in exploring myofascial release (MFR) as an effective means of controlling spinal curvature progression in adolescents with idiopathic scoliosis. The purpose of this case study is to measure the effects of MFR as a manual therapy technique in the treatment of idiopathic scoliosis. One 18-year-old female subject underwent 6 weeks of MFR treatment consisting of two sessions each week for 60min. Pain, pulmonary function, and quality of life were measured. Six goniometric measurements were taken encompassing trunk flexion, extension, and rotation. The subject improved with pain levels, trunk rotation, posture, quality of life, and pulmonary function. The results suggest further investigation is needed using MFR, as an effective manual therapy treatment for idiopathic scoliosis.

Do all patients with idiopathic pulmonary fibrosis warrant a trial of therapeutic intervention? A pro-con perspective.

PubMed

Moodley, Yuben; Corte, Tamera; Richeldi, Luca; King, Talmadge E

2015-04-01

Idiopathic pulmonary fibrosis (IPF) is an incurable condition that is characterized by progressive pulmonary fibrosis, architectural distortion of the lung and loss of gas exchange units. Until recently, there was no effective treatment for this condition. However, there were two landmark trials published earlier this year, which have changed the management of this condition. Pirfenidone (Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis trial) and nintedanib (Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis-1 and -2 trials) have both demonstrated positive outcomes in patients with IPF. In this perspective, we critically discuss the role of these agents in IPF and in the broader pulmonary fibrosis population. © 2015 Asian Pacific Society of Respirology.

Study on Treatment with Respect to Idiopathic Scoliosis

NASA Astrophysics Data System (ADS)

Takeuchi, Kenzen; Azegami, Hideyuki; Murachi, Shunji; Kitoh, Junzoh; Ishida, Yoshito; Kawakami, Noriaki; Makino, Mitsunori

A hypothesis that the thoracic idiopathic scoliosis is buckling phenomenon of the fourth mode induced by the growth of thoracic vertebral bodies was presented in the previous work by the authors using numerical simulations with finite element model of the spine. If the hypothesis is acceptable, sensitivity function with respect to the critical growth of thoracic vertebrae on the maximization problem of buckling load with the fourth buckling mode gives us useful information to improve and develop treatments for the idiopathic scoliosis. The numerical results analyzed by the finite element method demonstrated that the sensitivity function is high at the articular capsules of the intervertebral joints, the intervertebral disks, the costotransverse joints and the constovertebral joints around the apex of the curvature in the case of the thoracic idiopathic scoliosis.

The Use of IL-1 Receptor Antagonist (Anakinra) in Idiopathic Recurrent Pericarditis: A Narrative Review

PubMed Central

Baskar, Shankar; Klein, Allan L.; Zeft, Andrew

2016-01-01

Recurrent pericarditis is a complication of acute pericarditis in 20–30% of the patients and is usually idiopathic in nature. The underlying pathogenesis of this condition remains unclear, although immune-mediated mechanisms seem likely. A subgroup of these patients with refractory symptoms can be challenging to manage, and multiple immunosuppressive medications have been used without consistent benefit. Anakinra, an interleukin-1 receptor antagonist, has been used in treatment of rheumatoid arthritis and autoinflammatory syndromes. Preliminary evidence suggests that anakinra could be a promising therapy for idiopathic recurrent pericarditis. In this narrative review, we summarize the current understanding of the etiopathogenesis of idiopathic recurrent pericarditis, mechanism of action of anakinra, and the preliminary evidence, supporting the use of anakinra in pericarditis. PMID:26942035

High frequency of empty sella syndrome in children with growth hormone deficiency.

PubMed

Pocecco, M; de Campo, C; Marinoni, S; Tommasini, G; Basso, T; Muzzolini, C; Sacher, B

1989-02-01

Computer-assisted tomography (CT) with 2 mm axial sections and reconstructions was carried out in 31 children affected by GH deficiency (GHD): 18 with idiopathic complete isolated GHD, 3 with idiopathic partial isolated GHD, 2 with idiopathic panhypopituitarism, 4 with isolated acquired GHD and 4 with acquired panhypopituitarism. Density in the intrasellar area on CT corresponded to that of cerebrospinal fluid in 13/20 cases with idiopathic hypopituitarism and in 2/8 cases with acquired hypopituitarism. The overall incidence of primary empty sella syndrome (PESS) in the GH deficient patients studied was thus over 48%, while in children without endocrine dysfunction, it was only 5/213 (2.4%). It is concluded that PESS is more frequent in childhood than assumed until now and that it is frequently associated with GHD.

Eosinophilic Lung Disorders

MedlinePlus

... allergic or chemical reactions and certain infections. Eosinophilic Pneumonia Eosinophilic pneumonia describes a category of pneumonias that ... low oxygen in the bloodstream. Acute Idiopathic Eosinophilic Pneumonia Acute idiopathic eosinophilic pneumonia is a more sudden ...

Juvenile idiopathic arthritis

MedlinePlus

... www.ncbi.nlm.nih.gov/pubmed/21452260 . Long AR, Rouster-Stevens KA. The role of exercise therapy ... nlm.nih.gov/pubmed/21131338 . Wu EY, Bryan AR, Rabinovich CE. Juvenile idiopathic arthritis. In: Kliegman RM, ...

Hypocretin-1 CSF levels in anti-Ma2 associated encephalitis.

PubMed

Overeem, S; Dalmau, J; Bataller, L; Nishino, S; Mignot, E; Verschuuren, J; Lammers, G J

2004-01-13

Idiopathic narcolepsy is associated with deficient hypocretin transmission. Narcoleptic symptoms have recently been described in paraneoplastic encephalitis with anti-Ma2 antibodies. The authors measured CSF hypocretin-1 levels in six patients with anti-Ma2 encephalitis, and screened for anti-Ma antibodies in patients with idiopathic narcolepsy. Anti-Ma autoantibodies were not detected in patients with idiopathic narcolepsy. Four patients with anti-Ma2 encephalitis had excessive daytime sleepiness; hypocretin-1 was not detectable in their cerebrospinal fluid, suggesting an immune-mediated hypocretin dysfunction.

Recurrent urethral obstruction secondary to idiopathic renal hematuria in a puppy.

PubMed

Hawthorne, J C; deHaan, J J; Goring, R L; Randall, S R; Kennedy, F S; Stone, E; Zimmerman, K M; McAbee, S W

1998-01-01

A seven-month-old, neutered male Catahoula leopard dog cross was presented for recurrent urethral obstruction and intermittent hematuria. After exploratory laparotomy and ventral cystotomy, unilateral idiopathic renal hematuria was diagnosed based on gross observation of hematuria from the left ureteral catheter. The hematuria resolved after nephrectomy of the left kidney. The histopathological diagnosis was multifocal, acute congestion and intratubular hemorrhage. Although idiopathic renal hematuria has been described previously, this puppy was unique because the hematuria caused recurrent, complete urethral obstruction.

Idiopathic inflammatory myopathies overlapping with systemic diseases

PubMed Central

Lepreux, Sébastien; Hainfellner, Johannes A.; Vital, Anne

2018-01-01

A muscle biopsy is currently requested to assess the diagnosis of an idiopathic inflammatory myopathy overlapping with a systemic disease. During the past few years, the classification of inflammatory myopathy subtypes has been revisited progressively on the basis of correlations between clinical phenotypes, autoantibodies and histological data. Several syndromic entities are now more clearly defined, and the aim of the present review is to clarify the contribution of muscle biopsy in a setting of idiopathic inflammatory myopathies overlapping with systemic diseases. PMID:29154752

Stent-Graft Placement for Femoral Artery Pseudoaneurysm in a Patient with Idiopathic Multiple Arterial Aneurysmal Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koo, Bon Kwon; Choi, Donghoon; Kwon, Kihwan

2002-12-15

A 34-year-old man presenting with a left inguinal mass was diagnosed as having idiopathic multiple aneurysmal disease and pseudoaneurysm of a left superficial femoral artery. A stent-graft was successfully deployed percutaneously at the left superficial femoral artery pseudoaneurysm. Less invasive treatment should be used to avoid vascular complications in patients with idiopathic multiple aneurysmal disease, especially in those who have a progressive course or a history of prior complications after surgical repair.

Natural history of idiopathic abducens nerve paresis in a young adult.

PubMed

Hussaindeen, Jameel Rizwana; Mani, Revathy; Rakshit, Archayeeta; Ramasubramanian, Srikanth; Vittal Praveen, Smitha

2016-01-01

The natural history of idiopathic abducens nerve paresis and the role of conservative management such as vision training during the recovery process is not well documented in the literature to the best of our knowledge. This case report presents the natural recovery process of idiopathic abducens nerve paresis in a young adult and the role of vision therapy in the recovery process. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

Optimization of urinary dipstick pH: Are multiple dipstick pH readings reliably comparable to commercial 24-hour urinary pH?

PubMed

Abbott, Joel E; Miller, Daniel L; Shi, William; Wenzler, David; Elkhoury, Fuad F; Patel, Nishant D; Sur, Roger L

2017-09-01

Accurate measurement of pH is necessary to guide medical management of nephrolithiasis. Urinary dipsticks offer a convenient method to measure pH, but prior studies have only assessed the accuracy of a single, spot dipstick. Given the known diurnal variation in pH, a single dipstick pH is unlikely to reflect the average daily urinary pH. Our goal was to determine whether multiple dipstick pH readings would be reliably comparable to pH from a 24-hour urine analysis. Kidney stone patients undergoing a 24-hour urine collection were enrolled and took images of dipsticks from their first 3 voids concurrently with the 24-hour collection. Images were sent to and read by a study investigator. The individual and mean pH from the dipsticks were compared to the 24-hour urine pH and considered to be accurate if the dipstick readings were within 0.5 of the 24-hour urine pH. The Bland-Altman test of agreement was used to further compare dipstick pH relative to 24-hour urine pH. Fifty-nine percent of patients had mean urinary pH values within 0.5 pH units of their 24-hour urine pH. Bland-Altman analysis showed a mean difference between dipstick pH and 24-hour urine pH of -0.22, with an upper limit of agreement of 1.02 (95% confidence interval [CI], 0.45-1.59) and a lower limit of agreement of -1.47 (95% CI, -2.04 to -0.90). We concluded that urinary dipstick based pH measurement lacks the precision required to guide medical management of nephrolithiasis and physicians should use 24-hour urine analysis to base their metabolic therapy.

Late-onset hereditary hypophosphatemic rickets with hypercalciuria (HHRH) due to mutation of SLC34A3/NPT2c.

PubMed

Dhir, Gauri; Li, Dong; Hakonarson, Hakon; Levine, Michael A

2017-04-01

To identify a genetic basis for markedly reduced bone density and multiple fractures in an adult patient with hypophosphatemia and hypercalciuria. A 54-year-old Vietnamese man, his unaffected two daughters and wife. We performed biochemical studies and sequenced the SLC34A3 gene using genomic DNA from peripheral blood mononuclear cells. Biochemical evaluation of the proband revealed hypophosphatemia with increased renal phosphate wasting, hypercalciuria, low serum parathyroid hormone (PTH) and an elevated serum 1,25(OH) 2 D level. Mutation analysis of SLC34A3 gene revealed that the patient was a compound heterozygote for two nonsynonymous nucleotide substitutions: a novel c.571G>A (p.G191S) damaging mutation and the previously reported c.200G>A (p.R67H) polymorphism, consistent with the clinical diagnosis of late-onset hereditary hypophosphatemic rickets with hypercalciuria (HHRH). His wife and older daughter both carried the p.R67H polymorphism, while his younger daughter was compound heterozygous for p.R67H and p.G191S. HHRH is an uncommon autosomal recessive disease that generally manifests in childhood as rickets or nephrolithiasis, but an adult onset phenotype may occur in heterozygous carriers of SLC34A3 mutations. The severe presentation of this proband in adulthood with marked nephrolithiasis, multiple fractures and low bone density emphasizes the importance of measuring the serum phosphorus level in patients with suspected but unexplained osteoporosis and/or recurrent renal stones. The recognition of late-onset HHRH facilitates timely institution of appropriate therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Community-based study on CKD subjects and the associated risk factors.

PubMed

Chen, Nan; Wang, Weiming; Huang, Yanping; Shen, Pingyan; Pei, Daoling; Yu, Haijin; Shi, Hao; Zhang, Qianying; Xu, Jing; Lv, Yilun; Fan, Qishi

2009-07-01

The study was performed to investigate the prevalence, awareness and the risk factors of chronic kidney disease (CKD) in the community population in Shanghai, China. A total of 2596 residents were randomly recruited from the community population in Shanghai, China. All were screened for albuminuria, haematuria, morning spot urine albumin-to-creatinine ratio and renal function. Serum creatinine, uric acid, cholesterol, triglyceride and haemoglobin were assessed. A simplified MDRD equation was used to estimate the glomerular filtration rate (eGFR). All studied subjects were screened by kidney ultrasound. Haematuria, if present in the morning spot urine dipstick test, was confirmed by microscopy. The associations among the demographic characteristics, health characteristics and indicators of kidney damage were examined. Two thousand five hundred and fifty-four residents (n = 2554), after giving informed consent and with complete data, were entered into this study. Albuminuria and haematuria were detected in 6.3% and 1.2% of all the studied subjects, respectively, whereas decreased kidney function was found in 5.8% of all studied subjects. Approximately 11.8% of subjects had at least one indicator of kidney damage. The rate of awareness of CKD was 8.2%. The logistic regression model showed that age, central obesity, hypertension, diabetes, anaemia, hyperuricaemia and nephrolithiasis each contributed to the development of CKD. This is the first Shanghai community-based epidemiological study data on Chinese CKD patients. The prevalence of CKD in the community population in Shanghai is 11.8%, and the rate of awareness of CKD is 8.2%. All the factors including age, central obesity, hypertension, diabetes, anaemia, hyperuricaemia and nephrolithiasis are positively correlated with the development of CKD in our studied subjects.

Activity, energy intake, obesity, and the risk of incident kidney stones in postmenopausal women: a report from the Women's Health Initiative.

PubMed

Sorensen, Mathew D; Chi, Thomas; Shara, Nawar M; Wang, Hong; Hsi, Ryan S; Orchard, Tonya; Kahn, Arnold J; Jackson, Rebecca D; Miller, Joe; Reiner, Alex P; Stoller, Marshall L

2014-02-01

Obesity is a strong risk factor for nephrolithiasis, but the role of physical activity and caloric intake remains poorly understood. We evaluated this relationship in 84,225 women with no history of stones as part of the Women's Health Initiative Observational Study, a longitudinal, prospective cohort of postmenopausal women enrolled from 1993 to 1998 with 8 years' median follow-up. The independent association of physical activity (metabolic equivalents [METs]/wk), calibrated dietary energy intake, and body mass index (BMI) with incident kidney stone development was evaluated after adjustment for nephrolithiasis risk factors. Activity intensity was evaluated in stratified analyses. Compared with the risk in inactive women, the risk of incident stones decreased by 16% in women with the lowest physical activity level (adjusted hazard ratio [aHR], 0.84; 95% confidence interval [95% CI], 0.74 to 0.97). As activity increased, the risk of incident stones continued to decline until plateauing at a decrease of approximately 31% for activity levels ≥10 METs/wk (aHR, 0.69; 95% CI, 0.60 to 0.79). Intensity of activity was not associated with stone formation. As dietary energy intake increased, the risk of incident stones increased by up to 42% (aHR, 1.42; 95% CI, 1.02 to 1.98). However, intake <1800 kcal/d did not protect against stone formation. Higher BMI category was associated with increased risk of incident stones. In summary, physical activity may reduce the risk of incident kidney stones in postmenopausal women independent of caloric intake and BMI, primarily because of the amount of activity rather than exercise intensity. Higher caloric intake further increases the risk of incident stones.

Contemporary trends in urinary tract stone surgery, a regional perspective: Auckland, New Zealand.

PubMed

Acland, George; Zargar-Shoshtari, Kamran; Rice, Michael

2016-04-01

The aim of the study is to assess the contemporary patterns of utilization of various therapeutic options for the management of nephrolithiasis in our tertiary referral institution in Auckland, New Zealand. A retrospective audit was conducted for all urinary stone procedures between January 2007 and December 2013. Procedure-related information was collected for each year. All elective and emergency procedures were included. Data were collected on the elective waiting lists for each procedure. A total of 5512 stone-related cases were performed during the study period. Six hundred and fifty-three cases were performed in 2007 compared with 945 in 2013. Total number of percutaneous nephrolithotomy (PCNLs) performed, as well as the proportion of PCNL cases, demonstrated a significant decline from 84 (12.9%) in 2007 to 67 (7.1%) in 2013. While the annual numbers of extracorporeal shock wave lithotripsy (ESWLs) have increased, the percentage of ESWLs performed relative to total stone procedures has declined from 33% to 23% over the last 4 years of this audit. There has been a significant rise in the numbers of rigid and flexible ureteroscopies, with these now being the most utilized procedure. The number of patients awaiting elective procedures declined over the duration of this audit, with an associated improvement in meeting annual demand for treatment of nephrolithiasis from 78% in 2007 to 91% in 2013. A proportional decline in PCNL and ESWL utilization with a significant increase in flexible and rigid ureteroscopic procedures has been observed over this time and this pattern has been associated with improved adherence to surgical targets despite an increasing number of cases. © 2015 Royal Australasian College of Surgeons.

Urinary tract abnormalities in Chinese rural children who consumed melamine-contaminated dairy products: a population-based screening and follow-up study

PubMed Central

Liu, Jian-meng; Ren, Aiguo; Yang, Lei; Gao, Jinji; Pei, Lijun; Ye, Rongwei; Qu, Quangang; Zheng, Xiaoying

2010-01-01

Background Kidney damage related to consumption of melamine-contaminated dairy products by young children in China has been described. However, no studies have reported on the population-based prevalence of kidney damage among exposed children or on the condition of affected children after follow-up. Methods We conducted an ultrasound-based screening in September 2008 of 7933 children younger than 36 months of age who lived in a rural area in China where the dairy products most highly contaminated with melamine were sold. We monitored children who had evidence of nephrolithiasis or hydronephrosis at screening using renal ultrasonography after one, three and six months. We also collected information from the mothers of affected children about consumption of melamine-contaminated products between June and August 2008. Results The overall prevalence of urinary tract abnormalities among screened children was 0.61% (95% confidence interval [CI] 0.45%–0.80%). The mean exposure dose of melamine was estimated to be 116 (range 36–220) mg per day. Of the 48 affected children, 43 (89.6%) were asymptomatic, 2 had symptoms and were hospitalized, and 3 had symptoms but treatment had been not sought for them. Of the 46 children for whom six-month follow-up information was available, renal abnormalities persisted in 5 children and resolved in the remaining 41. Interpretation Among children who underwent screening, 0.61% showed ultrasonographic evidence of nephrolithiasis or hydronephrosis. Most of the affected children were asymptomatic. The majority of the affected children recovered from the toxic effects of melamine over time without specific treatment. Renal abnormalities remained in 12% of the affected children. PMID:20176755

Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia

PubMed Central

Schlingmann, Karl P.; Ruminska, Justyna; Kaufmann, Martin; Dursun, Ismail; Patti, Monica; Kranz, Birgitta; Pronicka, Ewa; Ciara, Elzbieta; Akcay, Teoman; Bulus, Derya; Cornelissen, Elisabeth A.M.; Gawlik, Aneta; Sikora, Przemysław; Patzer, Ludwig; Galiano, Matthias; Boyadzhiev, Veselin; Dumic, Miroslav; Vivante, Asaf; Kleta, Robert; Dekel, Benjamin; Levtchenko, Elena; Bindels, René J.; Rust, Stephan; Forster, Ian C.; Hernando, Nati; Jones, Glenville; Wagner, Carsten A.

2016-01-01

Idiopathic infantile hypercalcemia (IIH) is characterized by severe hypercalcemia with failure to thrive, vomiting, dehydration, and nephrocalcinosis. Recently, mutations in the vitamin D catabolizing enzyme 25-hydroxyvitamin D3-24-hydroxylase (CYP24A1) were described that lead to increased sensitivity to vitamin D due to accumulation of the active metabolite 1,25-(OH)2D3. In a subgroup of patients who presented in early infancy with renal phosphate wasting and symptomatic hypercalcemia, mutations in CYP24A1 were excluded. Four patients from families with parental consanguinity were subjected to homozygosity mapping that identified a second IIH gene locus on chromosome 5q35 with a maximum logarithm of odds (LOD) score of 6.79. The sequence analysis of the most promising candidate gene, SLC34A1 encoding renal sodium-phosphate cotransporter 2A (NaPi-IIa), revealed autosomal-recessive mutations in the four index cases and in 12 patients with sporadic IIH. Functional studies of mutant NaPi-IIa in Xenopus oocytes and opossum kidney (OK) cells demonstrated disturbed trafficking to the plasma membrane and loss of phosphate transport activity. Analysis of calcium and phosphate metabolism in Slc34a1-knockout mice highlighted the effect of phosphate depletion and fibroblast growth factor-23 suppression on the development of the IIH phenotype. The human and mice data together demonstrate that primary renal phosphate wasting caused by defective NaPi-IIa function induces inappropriate production of 1,25-(OH)2D3 with subsequent symptomatic hypercalcemia. Clinical and laboratory findings persist despite cessation of vitamin D prophylaxis but rapidly respond to phosphate supplementation. Therefore, early differentiation between SLC34A1 (NaPi-IIa) and CYP24A1 (24-hydroxylase) defects appears critical for targeted therapy in patients with IIH. PMID:26047794

Long-term outcome of cataract surgery in patients with idiopathic hypoparathyroidism and its relationship with their calcemic status.

PubMed

Saha, Soma; Gantyala, Shiva Prasad; Aggarwal, Sameer; Sreenivas, Vishnubhatla; Tandon, Radhika; Goswami, Ravinder

2017-07-01

Cataract is a cardinal manifestation of hypoparathyroidism. Although patients with hypoparathyroidism require cataract surgery at a younger age than individuals without hypoparathyroidism, there is limited information on the outcome of this surgery. We assessed long-term complications of cataract surgery in patients with idiopathic hypoparathyroidism (IH) and its relationship with their clinical and biochemical parameters. Twenty-seven patients with IH and 25 nonhypoparathyroid controls with a minimum follow-up of 2 years after cataract surgery were assessed for visual acuity, intraocular pressure, lens centricity, Nd:YAG laser capsulotomy, and the severity of posterior capsular opacification (PCO) and anterior capsular opacification. High-resolution optical slit-lamp images were analyzed by an ophthalmologist. Patients with IH had cataract surgery at a younger age than controls (34.0 ± 16.4 years vs 58.0 ± 11.2 years, P < 0.001). A higher proportion of IH patients had dense white PCO (75.0 % vs 39.4 %, P = 0.004), Nd:YAG laser capsulotomy (44.2 % vs 10.0 %, P = 0.001), anterior capsular opacification (97.7 % vs 84.2 %, P = 0.03), and a decentric lens (28.3% vs 2.6 %, P = 0.001) at a comparable time after surgery (8.6 ± 6.1 years vs 8.7 ± 6.8 years, P = 0.85). On regression analysis, the severity of PCO in IH correlated only with male sex and not with other factors, including serum total calcium and inorganic phosphorus levels at the baseline and during follow-up. To conclude, patients with IH are likelier than individuals without IH to develop PCO and to require Nd:YAG laser capsulotomy after cataract surgery. Proper precautions should be taken during surgery to minimize this complication in IH.

JAK2 mediates lung fibrosis, pulmonary vascular remodelling and hypertension in idiopathic pulmonary fibrosis: an experimental study.

PubMed

Milara, Javier; Ballester, Beatriz; Morell, Anselm; Ortiz, José L; Escrivá, Juan; Fernández, Estrella; Perez-Vizcaino, Francisco; Cogolludo, Angel; Pastor, Enrique; Artigues, Enrique; Morcillo, Esteban; Cortijo, Julio

2018-06-01

Pulmonary hypertension (PH) is a common disorder in patients with idiopathic pulmonary fibrosis (IPF) and portends a poor prognosis. Recent studies using vasodilators approved for PH have failed in improving IPF mainly due to ventilation ( V )/perfusion ( Q ) mismatching and oxygen desaturation. Janus kinase type 2 (JAK2) is a non-receptor tyrosine kinase activated by a broad spectrum of profibrotic and vasoactive mediators, but its role in PH associated to PH is unknown. The study of JAK2 as potential target to treat PH in IPF. JAK2 expression was increased in pulmonary arteries (PAs) from IPF (n=10; 1.93-fold; P=0.0011) and IPF+PH (n=9; 2.65-fold; P<0.0001) compared with PA from control subjects (n=10). PA remodelling was evaluated in human pulmonary artery endothelial cells (HPAECs) and human pulmonary artery smooth muscle cells (HPASMCs) from patients with IPF in vitro treated with the JAK2 inhibitor JSI-124 or siRNA-JAK2 and stimulated with transforming growth factor beta. Both JSI-124 and siRNA-JAK2 inhibited the HPAEC to mesenchymal transition and the HPASMCs to myofibroblast transition and proliferation. JAK2 inhibition induced small PA relaxation in precision-cut lung slice experiments. PA relaxation was dependent of the large conductance calcium-activated potassium channel (BK Ca ). JAK2 inhibition activated BK Ca channels and reduced intracellular Ca 2+ . JSI-124 1 mg/kg/day, reduced bleomycin-induced lung fibrosis, PA remodelling, right ventricular hypertrophy, PA hypertension and V / Q mismatching in rats. The animal studies followed the ARRIVE guidelines. JAK2 participates in PA remodelling and tension and may be an attractive target to treat IPF associated to PH. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Screening of differentially expressed genes in male idiopathic osteoporosis via RNA sequencing.

PubMed

Feng, Li; Wang, Yan; Zhou, Jing; Tian, Baofang; Xia, Bo

2018-05-07

As a type of osteoporosis (OP), male idiopathic OP (MIO) is a bone disorder that occurs in young males and is a public health problem worldwide. However, the detailed pathogenesis of MIO remains to be elucidated. In the present study, blood samples of patients with MIO, senile OP, postmenopausal OP and normal controls (NCs) were obtained for RNA sequencing. Compared with the NC group, differentially expressed genes (DEGs) in the three types of OP were identified. DEGs that were common among the three types of OP and the DEGs that were unique to patients with MIO were determined. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted. MIO‑specific and OP‑specific protein‑protein interaction (PPI) networks were constructed. Compared with NCs, a total of 519, 368 and 1,472 DEGs were identified in samples from MIO, senile OP and postmenopausal OP, respectively. Tetraspanin 5 (TSPAN5) and α‑synuclein (SNCA) were unique DEGs in MIO that were not identified in the other two types of OP compared with NCs. Furthermore, the expression of carbonic anhydrase 1 (CA1) and S100 calcium‑binding protein P (S100P) in MIO was significantly different compared with senile OP, postmenopausal OP and NC samples. 'MAPK signaling pathway', 'type I diabetes mellitus' and 'hematopoietic cell lineage' were among significantly enriched pathways of DEGs in MIO. SNCA and CDC‑like kinase 1 were the hub genes in the MIO‑specific PPI network. In conclusion, the mitogen‑activated protein kinase signaling and type I diabetes mellitus pathways may be involved in bone formation; SNCA and TSPAN5 may be associated with bone resorption. These two pathways and two genes may serve a role in MIO. CA1 and S100P may regulate the process of MIO by modulation of calcification and dysregulation of calcium binding. These findings may have provided an experimental basis for elucidating the underlying mechanisms and developing potential diagnostic biomarkers of MIO.

Quality of life in patients with an idiopathic rapid eye movement sleep behaviour disorder in Korea.

PubMed

Kim, Keun Tae; Motamedi, Gholam K; Cho, Yong Won

2017-08-01

There have been few quality of life studies in patients with idiopathic rapid eye movement sleep behaviour disorder. We compared the quality of life in idiopathic rapid eye movement sleep behaviour disorder patients to healthy controls, patients with hypertension, type 2 diabetes mellitus without complication and idiopathic restless legs syndrome. Sixty patients with idiopathic rapid eye movement sleep behaviour disorder (24 female; mean age: 61.43 ± 8.99) were enrolled retrospectively. The diagnosis was established based on sleep history, overnight polysomnography, neurological examination and Mini-Mental State Examination to exclude secondary rapid eye movement sleep behavior disorder. All subjects completed questionnaires, including the Short Form 36-item Health Survey for quality of life. The total quality of life score in idiopathic rapid eye movement sleep behaviour disorder (70.63 ± 20.83) was lower than in the healthy control group (83.38 ± 7.96) but higher than in the hypertension (60.55 ± 24.82), diabetes mellitus (62.42 ± 19.37) and restless legs syndrome (61.77 ± 19.25) groups. The total score of idiopathic rapid eye movement sleep behaviour disorder patients had a negative correlation with the Pittsburg Sleep Quality Index (r = -0.498, P < 0.001), Insomnia Severity Index (r = -0.645, P < 0.001) and the Beck Depression Inventory-2 (r = -0.694, P < 0.001). Multiple regression showed a negative correlation between the Short Form 36-item Health Survey score and the Insomnia Severity Index (β = -1.100, P = 0.001) and Beck Depression Inventory-2 (β = -1.038, P < 0.001). idiopathic rapid eye movement sleep behaviour disorder had a significant negative impact on quality of life, although this effect was less than that of other chronic disorders. This negative effect might be related to a depressive mood associated with the disease. © 2016 European Sleep Research Society.

The role of serial casting in early-onset scoliosis (EOS).

PubMed

Baulesh, David M; Huh, Jeannie; Judkins, Timothy; Garg, Sumeet; Miller, Nancy H; Erickson, Mark A

2012-01-01

Serial casting has demonstrated efficacy for idiopathic early-onset scoliosis (EOS). Results of casting in nonidiopathic (syndromic and congenital) EOS patients have not previously been well described. A total of 53 patients underwent serial casting for EOS from 2005 to 2010 at a single institution. Deformity was classified as idiopathic or nonidiopathic. Diagnosis, time in cast, number of casts, use of bracing, complications, and outcomes were recorded. Radiographic measures included Cobb angle and thoracic height (T1-T12). Thoracic height velocity was calculated and compared with established norms. A total of 36 patients, 19 idiopathic and 17 nonidiopathic (14 syndromic, 3 congenital), completed cast treatment and had >6-month follow-up and were therefore included. Of those, 17% (6/36) experienced resolution of their deformity, 53% (19/26) are currently in braces, and 31% (11/36) had undergone surgery. Surgery occurred on average at age 5.6 years and was delayed by an average of 2.1 years from time of first cast. A 19% complication was observed. There was no statistical difference in the rate of resolution of deformity between idiopathic (5/19) and nonidiopathic (1/17) patients (P=0.182), although there exists a trend toward greater curve correction in idiopathic patients. Surgery occurred in fewer patients (2/19) in the idiopathic group compared with the nonidiopathic group (9/17) (P=0.006). Significant improvements in Cobb angle was observed in the idiopathic group (12.2 degrees) during casting (P=0.003). Nonidiopathic patients did not maintain the correction gained during casting at the time of final follow-up. T1-T12 height increased across all study patients regardless of etiology during the period of casting at similar velocity to established norms of 1.4 cm/y for this age group. Serial casting offers modest deformity correction in idiopathic deformities compared with nonidiopathic deformities. Thoracic height growth continued throughout the casting period at normal velocity. Serial casting maintained normal longitudinal thoracic growth in all patients with EOS in this cohort. Although many required surgery, the increased thoracic height may have positive implications on ultimate pulmonary function. Therapeutic level III.

Efficacy of adalimumab in young children with juvenile idiopathic arthritis and chronic uveitis: a case series.

PubMed

La Torre, Francesco; Cattalini, Marco; Teruzzi, Barbara; Meini, Antonella; Moramarco, Fulvio; Iannone, Florenzo

2014-05-24

Juvenile idiopathic arthritis is a relatively common chronic disease of childhood, and is associated with persistent morbidity and extra-articular complications, one of the most common being uveitis. The introduction of biologic therapies, particularly those blocking the inflammatory mediator tumor necrosis factor-α, provided a new treatment option for juvenile idiopathic arthritis patients who were refractory to standard therapy such as non-steroidal anti-inflammatory drugs, corticosteroids and/or methotrexate. The first case was a 2-year-old girl with juvenile idiopathic arthritis and uveitis who failed to respond to treatment with anti-inflammatories, low-dose corticosteroids and methotrexate, and had growth retardation. Adalimumab 24 mg/m2 every 2 weeks and prednisone 0.5 mg/kg/day were added to methotrexate therapy; steroid tapering and withdrawal started after 1 month. After 2 months the patient showed good control of articular and ocular manifestations, and she remained in remission for 1 year, receiving adalimumab and methotrexate with no side effects, and showing significant improvement in growth. Case 2 was a 9-year-old boy with an 8-year history of juvenile idiopathic arthritis and uveitis that initially responded to infliximab, but relapse occurred after 2 years off therapy. After switching to adalimumab, and adjusting doses of both adalimumab and methotrexate based on body surface area, the patient showed good response and corticosteroids were tapered and withdrawn after 6 months; the patient remained in remission taking adalimumab and methotrexate. The final case was a 5-year-old girl with juvenile idiopathic arthritis for whom adalimumab was added to methotrexate therapy after three flares of uveitis. The patient had two subsequent episodes of uveitis that responded well to local therapy, but was then free of both juvenile idiopathic arthritis and uveitis symptoms, allowing methotrexate and then adalimumab to be stopped; the patient remained in drug-free remission. This report includes the first published case of the use of adalimumab in a child aged <3 years. Our clinical experience further supports the use of biologic therapy for the management of juvenile idiopathic arthritis and uveitis in children as young as two years of age.

Genome Wide Analysis of Differentially Expressed Genes in HK-2 Cells, a Line of Human Kidney Epithelial Cells in Response to Oxalate

PubMed Central

Koul, Sweaty; Khandrika, Lakshmipathi; Meacham, Randall B.; Koul, Hari K.

2012-01-01

Nephrolithiasis is a multi-factorial disease which, in the majority of cases, involves the renal deposition of calcium oxalate. Oxalate is a metabolic end product excreted primarily by the kidney. Previous studies have shown that elevated levels of oxalate are detrimental to the renal epithelial cells; however, oxalate renal epithelial cell interactions are not completely understood. In this study, we utilized an unbiased approach of gene expression profiling using Affymetrix HG_U133_plus2 gene chips to understand the global gene expression changes in human renal epithelial cells [HK-2] after exposure to oxalate. We analyzed the expression of 47,000 transcripts and variants, including 38,500 well characterized human genes, in the HK2 cells after 4 hours and 24 hours of oxalate exposure. Gene expression was compared among replicates as per the Affymetrix statistical program. Gene expression among various groups was compared using various analytical tools, and differentially expressed genes were classified according to the Gene Ontology Functional Category. The results from this study show that oxalate exposure induces significant expression changes in many genes. We show for the first time that oxalate exposure induces as well as shuts off genes differentially. We found 750 up-regulated and 2276 down-regulated genes which have not been reported before. Our results also show that renal cells exposed to oxalate results in the regulation of genes that are associated with specific molecular function, biological processes, and other cellular components. In addition we have identified a set of 20 genes that is differentially regulated by oxalate irrespective of duration of exposure and may be useful in monitoring oxalate nephrotoxicity. Taken together our studies profile global gene expression changes and provide a unique insight into oxalate renal cell interactions and oxalate nephrotoxicity. PMID:23028475

Vascular Disease and Kidney Stones: Abdominal Aortic Calcifications Are Associated with Low Urine pH and Hypocitraturia.

PubMed

Patel, Nishant D; Ward, Ryan D; Calle, Juan; Remer, Erick M; Monga, Manoj

2017-09-01

Vascular calcifications are associated with nephrolithiasis. Although studies have demonstrated correlations with vascular disease and calcium stones in kidney stone formers (KSF), an etiologic link has remained elusive. As a noncontrast CT (NCCT) scan is typically part of a stone evaluation, our objective was to evaluate the association of NCCT-based assessment of abdominal aortic calcifications (AACs) with 24-hour urine parameters and stone composition. Ninety-seven KSF were included with CT imaging and 24-hour urine studies. For each patient, semi-automated CT software was utilized to provide an AAC Agatston score from the celiac axis to the aortic bifurcation. Univariate analysis was performed to compare patients with or without AAC. Multivariate logistic regression was performed to assess for variables associated with 24-hour urine parameters and stone composition. The presence of AAC was associated with hypertension, diabetes, peripheral vascular disease, and coronary artery disease. Patients with any AAC showed lower 24-hour urine citrate (399 vs 593 mg/day, p < 0.001) and lower 24-hour urine pH (5.862 vs 6.328, p = 0.003). When controlling for age, system comorbidities, the presence of AAC was associated with low urine pH <6 (odds ratio [OR] 2.86, p = 0.032) and hypocitraturia <320 mg/day (OR 4.37, p = 0.005). The receiver operating characteristic curve showed that increasing AAC was associated with low urine pH (area under the curve [AUC] 0.683, p = 0.002) and uric acid stone formation (AUC 0.698, p = 0.045). NCCT-based diagnosis of AAC is associated with low urine pH, hypocitraturia, and uric acid stone formation. The presence of AAC could be considered an additional prognosticator for the utility of alkalinization therapy.

Secondary Cutaneous Amyloidosis Associated with Mycosis Fungoides

DTIC Science & Technology

2018-02-16

hypomelanosis, or idiopathic guttate hypomelanosis. Histologically. an atypical intraepidennallymphoid infiltrate was seen with scattered foci of g!obulat...fungoides, post-inflammatory hypomelanosis, or idiopathic guttate hypomelanosis. Histologically, an atypical intraepidermal lymphoid infiltrate was seen

Genetics Home Reference: idiopathic pulmonary fibrosis

MedlinePlus

... structures at the ends of chromosomes known as telomeres . It is not well understood how defects in ... Collard HR, Wolters PJ, Garcia CK. Effect of telomere length on survival in patients with idiopathic pulmonary ...

Idiopathic slow transit constipation and megacolon are not associated with neurturin mutations.

PubMed

Chen, B; Knowles, C H; Scott, M; Anand, P; Williams, N S; Milbrandt, J; Tam, P K H

2002-10-01

Chronic idiopathic slow-transit constipation (ISTC) and idiopathic megacolon (IMC) are early-onset gastrointestinal motility disorders of unknown aetiology. The gene encoding the neurotrophic factor neurturin may be a candidate for these disorders, as neurturin-deficient mice have a similar enteric phenotype. In the present study, we tested this hypothesis. Genomic DNA from 26 cases of chronic idiopathic STC [with a family history of constipation in 15 (58%) and Hirschsprung's disease in two (8%)], and five cases of IMC [two familial (40%)] was screened by direct DNA sequencing using the fluorescent dideoxy terminator method. Results were compared with published sequence data and 24 control DNAs. Our results revealed several previously unreported common sequence polymorphisms, but overall frequencies were comparable between patients and controls. We conclude that mutation of neurturin is not a frequent cause of ISTC or IMC.

McArdle's disease: A differential diagnosis of idiopathic toe walking.

PubMed

Pomarino, David; Martin, Stephan; Pomarino, Andrea; Morigeau, Stefanie; Biskup, Saskia

2018-06-01

Idiopathic toe walking (ITW) is a pathological gait pattern in which children walk on their tip toes with no orthopedic or neurological reason. Physiological characteristics of the gastrocnemius muscles, the Achilles tendon, and the foot of toe walkers differ from subjects with a plantigrade walking pattern. McArdle's disease is characterized by the inability to break down muscle glycogen. It is an autosomal-recessive condition, characterized by low exercise tolerance, muscular atrophy at the shoulder girdle, episodes of myoglobinuria after vigorous physical activities and the occurrence of the second wind phenomenon. The aim of this review is to present the case studies of two subjects who were originally diagnosed as idiopathic toe walkers, but were then found to have McArdle's disease. This review will describe some physical characteristics that distinguish McArdle´s disease from Idiopathic toe walkers.

[Juvenile idiopathic arthritis with dry synovitis: clinical case and review of literature].

PubMed

Dias, Bruno Leonardo Scofano; Imamura, Erica Ueno; Izumi, Ana Paula; Pinheiro, Lúcia Virgínia de Melo; Borigato, Eliana Valverde Magro

2009-01-01

Juvenile idiopathic arthritis is a term that encompasses all forms of arthritis that begin before the age of 16 years, persist for more than 6 weeks and are of unknown cause. Dry synovitis is still not completely understood nor commonly described. It is associated with juvenile idiopathic arthritis and must be considered in patients with minimal swelling but pain and stiffness along with flexion contractures as well as other evidence of an inflammatory process (lab changes and/or other symptoms, such as uveitis or rash), and often follow a destructive course. The authors present a case of a brazilian child with a rheumatoid factor- negative polyarthritis compatible with the subtype dry synovitis, who had great clinical and functional improvement after participation in rehabilitation activities and beginning of pharmacological treatment usually used in Juvenile idiopathic arthritis, including immunossuppressive therapy.

Idiopathic bile acid malabsorption: qualitative and quantitative clinical features and response to cholestyramine.

PubMed

Sinha, L; Liston, R; Testa, H J; Moriarty, K J

1998-09-01

Idiopathic bile acid malabsorption is a poorly recognized cause of chronic diarrhoea. The SeHCAT (75Selenium HomotauroCholic Acid Test) can accurately diagnose this condition. To identify patients with idiopathic bile acid malabsorption, to describe their clinical features, both qualitatively and quantitatively, and to assess the response to cholestyramine. Idiopathic bile acid malabsorption was considered in all patients complaining of chronic diarrhoea. They were included in the study if their SeHCATs were positive (< 15% retention) and secondary causes of bile acid malabsorption were excluded. The response to therapy with cholestyramine was assessed. Nine patients were diagnosed with idiopathic bile acid malabsorption (median SeHCAT retention 8%, range 3-12.6). Their median daily faecal weight was 285 g (range 85-676) and median faecal fat output was 17 mmol/24 h (range 8.3-38.8). Six patients had an immediate response to cholestyramine. There was a marked reduction in stool frequency (median stool frequency pre-treatment 5/day vs. 2/day post-treatment, P = 0.03). Five patients had large volume diarrhoea (faecal weight > 200 g/day) and three had steatorrhoea. Idiopathic bile acid malabsorption, once suspected, especially by documenting true 'large volume' watery diarrhoea or steatorrhoea, is easily diagnosed and response to therapy is often very good. There is often a previous history of gastrointestinal infection and this condition should be considered in patients with chronic diarrhoea of undetermined origin, especially before they are labelled as having irritable bowel syndrome.

Hypothalamic digoxin, hemispheric chemical dominance, and interstitial lung disease.

PubMed

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-10-01

The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. This was assessed in patients with idiopathic pulmonary fibrosis and in individuals of differing hemispheric dominance to find out the role of hemispheric dominance in the pathogenesis of idiopathic pulmonary fibrosis. All 15 cases of interstitial lung disease were right-handed/left hemispheric dominant by the dichotic listening test. The isoprenoidal metabolites--digoxin, dolichol, and ubiquinone, RBC membrane Na(+)-K+ ATPase activity, serum magnesium, tyrosine/tryptophan catabolic patterns, free radical metabolism, glycoconjugate metabolism, and RBC membrane composition--were assessed in idiopathic pulmonary fibrosis as well as in individuals with differing hemispheric dominance. In patients with idiopathic pulmonary fibrosis there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in patients with idiopathic pulmonary fibrosis. Isoprenoid pathway dysfunction con tributes to the pathogenesis of idiopathic pulmonary fibrosis. The biochemical patterns obtained in interstitial lung disease are similar to those obtained in left-handed/right hemispheric chemically dominant individuals by the dichotic listening test. However, all the patients with interstitial lung disease were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Interstitial lung disease occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.

Idiopathic diaphragmatic paralysis: Bell's palsy of the diaphragm?

PubMed

Crausman, Robert S; Summerhill, Eleanor M; McCool, F Dennis

2009-01-01

Idiopathic diaphragm paralysis is probably more common and responsible for more morbidity than generally appreciated. Bell's palsy, or idiopathic paralysis of the seventh cranial nerve, may be seen as an analogous condition. The roles of zoster sine herpete and herpes simplex have increasingly been recognized in Bell's palsy, and there are some data to suggest that antiviral therapy is a useful adjunct to steroid therapy. Thus, we postulated that antiviral therapy might have a positive impact on the course of acute idiopathic diaphragm paralysis which is likely related to viral infection. Three consecutive patients with subacute onset of symptomatic idiopathic hemidiaphragm paralysis were empirically treated with valacyclovir, 1,000 mg twice daily for 1 week. Prior to therapy, diaphragmatic function was assessed via pulmonary function testing and two-dimensional B-mode ultrasound, with testing repeated 1 month later. Diaphragmatic function pre- and post-treatment was compared to that of a historical control group of 16 untreated patients. All three subjects demonstrated ultrasound recovery of diaphragm function 4-6 weeks following treatment with valacyclovir. This recovery was accompanied by improvements in maximum inspiratory pressure (PI(max)) and vital capacity (VC). In contrast, in the untreated cohort, diaphragm recovery occurred in only 11 subjects, taking an average of 14.9 +/- 6.1 months (mean +/- SD). The results of this small, preliminary study suggest that antiviral therapy with valacyclovir may be helpful in the treatment of idiopathic diaphragm paralysis induced by a viral infection.

Significance of myositis autoantibody in patients with idiopathic interstitial lung disease.

PubMed

Song, Ju Sun; Hwang, Jiwon; Cha, Hoon-Suk; Jeong, Byeong-Ho; Suh, Gee Young; Chung, Man Pyo; Kang, Eun-Suk

2015-05-01

Some patients with interstitial lung disease (ILD) related to connective tissue disease (CTD) have a delayed diagnosis of the underlying CTD when the ILD is categorized as idiopathic. In this study, we evaluated the frequency of myositis autoantibodies in patients diagnosed with idiopathic ILD and investigated the clinical significance stemming from the presence of the antibodies. A total 32 patients diagnosed with idiopathic ILD were enrolled in this study. We analyzed a panel of 11 myositis autoantibody specificities in the patients using a line blot immunoassay. Then, we divided them into myositis autoantibody-positive and -negative groups and compared the clinical features and laboratory data between the two groups. Of the 32 idiopathic ILD patients, 12 patients had myositis autoantibodies encompassing 9 specificities, except for anti-Mi-2 and anti-PM-Scl 100 (12/32, 38%). Anti-synthetase autoantibodies including Jo-1, EJ, OJ, PL-7, and PL-12 were present in 7 patients (7/32, 22%). The group with myositis autoantibodies presented more frequently with the symptom of mechanic's hand and showed abnormal pulmonary function test results with low forced vital capacity, diffusing capacity for carbon monoxide, total lung capacity, and high lactate dehydrogenase values in blood when compared with the group without myositis antibodies. We strongly suggest that patients undergo an evaluation of myositis autoantibodies, if they are diagnosed with idiopathic ILD in the presence of clinical characteristics including mechanic's hand, arthralgia, and autoantibodies which are insufficient to make a diagnosis of a specific CTD category.

The effectiveness of core stabilization exercise in adolescent idiopathic scoliosis: A randomized controlled trial.

PubMed

Gür, Gözde; Ayhan, Cigdem; Yakut, Yavuz

2017-06-01

Core stabilization training is used to improve postural balance in musculoskeletal problems. The purpose of this study was to investigate the effectiveness of stabilization training in adolescent idiopathic scoliosis. A randomized controlled trial, pretest-posttest design. In total, 25 subjects with adolescent idiopathic scoliosis were randomly divided into two groups: stabilization group ( n = 12) and control group ( n = 13). The stabilization group received core stabilization in addition to traditional rehabilitation, and the control group received traditional rehabilitation for 10 weeks. Assessment included Cobb's angle on radiograph, apical vertebral rotation in Adam's test, trunk asymmetry (Posterior Trunk Symmetry Index), cosmetic trunk deformity (Trunk Appearance Perception Scale), and quality of life (Scoliosis Research Society-22 questionnaire). Inter-group comparisons showed significantly greater improvements in the mean change in lumbar apical vertebral rotation degree and the pain domain of Scoliosis Research Society-22 in the stabilization group than those in the control group ( p < 0.05). No significant differences were observed for other measurements between the groups; however, trends toward greater improvement were observed in the stabilization group. Core stabilization training in addition to traditional exercises was more effective than traditional exercises alone in the correction of vertebral rotation and reduction of pain in adolescent idiopathic scoliosis. Clinical relevance Stabilization exercises are more effective in reducing rotation deformity and pain than traditional exercises in the conservative rehabilitation of adolescent idiopathic scoliosis. These improvements suggest that stabilization training should be added to rehabilitation programs in adolescent idiopathic scoliosis.

Long-term efficacy of abatacept in pediatric patients with idiopathic uveitis: a case series.

PubMed

Marrani, Edoardo; Paganelli, Valeria; de Libero, Cinzia; Cimaz, Rolando; Simonini, Gabriele

2015-10-01

Non-infectious uveitis represents one of the most common causes of blindness, even at pediatric age; in particular, idiopathic chronic uveitis can pose significant difficulties during treatment, due to a partial response to TNF-α antagonists. To date, very few case series exist describing the treatment of idiopathic uveitis not adequately controlled by TNF-α antagonists. The aim of our study is to describe the role of abatacept in achieving remission in patients with idiopathic uveitis previously treated with TNF-α antagonists, and to assess how long abatacept efficacy is maintained during follow-up. The treatment's safety profile and tolerability were also specifically investigated. Three patients affected with chronic idiopathic uveitis, who have been treated with abatacept due to loss of efficacy of TNF-α antagonists, were reviewed. Details of the demographic and clinical characteristics were recorded, and a summary of the medical history was obtained. Patients were regularly reviewed in the ophthalmology and rheumatology clinics. Assessment of their ocular condition was characterized according to the Standardization of Uveitis Nomenclature (SUN) group. In our patients, abatacept was able to induce remission and to discontinue systemic corticosteroids after a mean of 30 weeks; the drug maintained its efficacy through a long follow-up period (42, 33, and 18 months respectively), with an excellent safety profile. Our small case series seems to suggest abatacept to be a promising therapy in children affected with chronic idiopathic uveitis not adequately controlled by TNF-α antagonists.

Crohn's disease mistaken for long-standing idiopathic mesenteric panniculitis: A case report and management algorithm.

PubMed

Nuzzo, Alexandre; Zappa, Magaly; Cazals-Hatem, Dominique; Bouhnik, Yoram

2016-09-01

Mesenteric panniculitis (MP) is mostly an associated sign of an intra-abdominal or systemic inflammatory primary disease. Nevertheless, etiological and differential diagnosis of idiopathic MP can be challenging when an associate primary cause is not in the foreground. We report here the case of an isolated small bowel Crohn's disease, long time considered as idiopathic MP. This patient presented to our department with a 10-year history of acute abdominal symptoms evolving with flare-up and remission. A diagnosis of idiopathic MP was made based on compatible CT-scan features along with normal laboratory tests and upper and lower bowel endoscopies. As symptoms recurred, a steroid course was proposed which dramatically improved his condition for years. Finally, an explorative laparoscopy was performed because of concern of malignancy when he returned to our unit with a steroid refractory flare-up and weight loss, along with MP nodes growing up to 10 mm. Crohn's disease was eventually diagnosed, based on histopathological middle-gut bowel resection and numerous granulomas in mesenteric nodes without necrosis. This case emphasizes the importance of excluding inflammatory intestinal lesions before making the diagnosis of idiopathic MP (fecal calprotectin, magnetic resonance enterography, wireless capsule endoscopy).

Severe neutropenia in children: a single institutional experience.

PubMed

Yilmaz, Deniz; Ritchey, Arthur Kim

2007-08-01

Severe neutropenia (SN) is a rare disorder in childhood. This study aimed to document the approach to diagnosis and treatment of children with SN in a single university-based children's hospital, determine the types of SN seen in a 4-year period, and determine outcomes of the subtypes of SN. Forty-five children with SN were identified between 2000 and 2004. Two patients had autoimmune, 3 congenital, 3 familial, 6 cyclic, and 31 idiopathic SN. The median age of the patients with idiopathic SN was 15 months (3 mo to 17 y). Thirteen patients with idiopathic SN received filgrastim and 18 were observed. The history of severe infection and hospitalization at presentation was significantly more common among the patients who received filgrastim than those observed, but was not different between the 2 groups during the follow-up period. SN resolved in 16 patients and persisted in 14 patients. One patient with idiopathic SN did not respond to filgrastim and died of sepsis while she was still neutropenic. In summary, the majority of patients with SN had idiopathic SN, the infection risk was variable, treatment was based on clinical judgment rather than absolute neutrophil count, and approximately half of the patients had complete recovery.

Non-Autoimmune Subclinical and Overt Hypothyroidism in Idiopathic Steroid-resistant Nephrotic Syndrome in Children.

PubMed

Marimuthu, Vidhya; Krishnamurthy, Sriram; Rajappa, Medha

2017-11-15

To evaluate the frequency of non-autoimmune subclinical and overt hypothyroidism in children with idiopathic steroid-resistant nephrotic syndrome (SRNS). This cross-sectional study recruited 30 children (age 1-18 y) with idiopathic SRNS; and 30 healthy controls. Serum T3, T4 and TSH were performed in cases as well as controls. Anti-thyroid peroxidase and anti-thyroglobulin antibody tests were performed in all cases. Non-autoimmune subclinical or overt hypothyroidism was detected in 10 out of 30 children with idiopathic SRNS; 2 had overt hypothyroidism, while 8 patients had subclinical hypothyroidism. Children with SRNS had a mean (SD) TSH value 4.55 (4.64) mIU/L that was higher as compared to controls (1.88 (1.04) mIU/L) (P<0.01). Focal segmental glomerulosclerosis (FSGS) was the commonest histopathological condition, seen in 13 (43.3%). Children with overt hypothyroidism (2 cases) and grade III subclinical hypothyroidism (1 case) were subsequently started on levothyroxine therapy. The prevalence of subclinical and overt hypothyroidism seems to be high in idiopathic SRNS, with almost one-third of children having overt or subclinical non-autoimmune hypothyroidism.