Recurrent truncating mutations in alanine-glyoxylate aminotransferase gene in two South Indian families with primary hyperoxaluria type 1 causing later onset end-stage kidney disease

PubMed Central

Dutta, A. K.; Paulose, B. K.; Danda, S.; Alexander, S.; Tamilarasi, V.; Omprakash, S.

2016-01-01

Primary hyperoxaluria type 1 is an autosomal recessive inborn error of metabolism due to liver-specific peroxisomal enzyme alanine-glyoxylate transaminase deficiency. Here, we describe two unrelated patients who were diagnosed to have primary hyperoxaluria. Homozygous c.445_452delGTGCTGCT (p.L151Nfs*14) (Transcript ID: ENST00000307503; human genome assembly GRCh38.p2) (HGMD ID CD073567) mutation was detected in both the patients and the parents were found to be heterozygous carriers. Our patients developed end-stage renal disease at 23 years and 35 years of age. However, in the largest series published from OxalEurope cohort, the median age of end-stage renal disease for null mutations carriers was 9.9 years, which is much earlier than our cases. Our patients had slower progressions as compared to three unrelated patients from North India and Pakistan, who had homozygous c.302T>C (p.L101P) (HGMD ID CM093792) mutation in exon 2. Further, patients need to be studied to find out if c.445_452delGTGCTGCT mutation represents a founder mutation in Southern India. PMID:27512303

Gut microbiota and oxalate homeostasis

PubMed Central

2017-01-01

This perspective focuses on how the gut microbiota can impact urinary oxalate excretion in the context of hyperoxaluria, a major risk factor in kidney stone disease. In the genetic disease of Primary Hyperoxaluria Type 1 (PH1), an increased endogenous production of oxalate, due to a deficiency of the liver enzyme alanine-glyoxylate aminotransferase (AGT), results in hyperoxaluria and oxalate kidney stones. The constant elevation in urinary oxalate in PH1 patients ultimately leads to tissue deposition of oxalate, renal failure and death and the only known cure for PH1 is a liver or liver-kidney transplant. The potential impact of a probiotic/therapeutic approach may be clinically significant in PH1 and could also extend to a much larger population of idiopathic oxalate stone formers who comprise ~12% of Americans, individuals with enteric hyperoxaluria, and an emerging population of hyperoxaluric patients who have undergone bariatric surgery and develop kidney stone disease as a consequence. PMID:28217701

Gut microbiota and oxalate homeostasis.

PubMed

Hatch, Marguerite

2017-01-01

This perspective focuses on how the gut microbiota can impact urinary oxalate excretion in the context of hyperoxaluria, a major risk factor in kidney stone disease. In the genetic disease of Primary Hyperoxaluria Type 1 (PH1), an increased endogenous production of oxalate, due to a deficiency of the liver enzyme alanine-glyoxylate aminotransferase (AGT), results in hyperoxaluria and oxalate kidney stones. The constant elevation in urinary oxalate in PH1 patients ultimately leads to tissue deposition of oxalate, renal failure and death and the only known cure for PH1 is a liver or liver-kidney transplant. The potential impact of a probiotic/therapeutic approach may be clinically significant in PH1 and could also extend to a much larger population of idiopathic oxalate stone formers who comprise ~12% of Americans, individuals with enteric hyperoxaluria, and an emerging population of hyperoxaluric patients who have undergone bariatric surgery and develop kidney stone disease as a consequence.

Evaluation of mutation screening as a first line test for the diagnosis of the primary hyperoxalurias.

PubMed

Rumsby, Gill; Williams, Emma; Coulter-Mackie, Marion

2004-09-01

A definitive diagnosis of primary hyperoxaluria type 1 (PH1) and primary hyperoxaluria type 2 (PH2) requires the measurement of alanine:glyoxylate aminotransferase (AGT) and glyoxylate reductase (GR) activities, respectively, in a liver biopsy. We have evaluated a molecular genetic approach for the diagnosis of these autosomal-recessive diseases. Polymerase chain reaction (PCR) was used to detect three common mutations in the AGXT gene (c.33_34insC, c.508G>A, and c.731T>C) and one, c.103delG, in the GRHPR gene in DNA samples from 365 unrelated individuals referred for diagnosis of PH1 and/or PH2 by liver enzyme analysis. One or more of these mutations was found in 183 (68.8%) biopsy proven cases of PH1 and PH2 with a test negative predictive value of 62% and 2%, respectively. 102 (34.1%) patients were homozygous or compound heterozygous, making a molecular diagnosis possible. Age of onset and presenting features were similar in patients homozygous for any of the four mutations. Of the AGXT homozygotes, only the c.508G>A mutant was associated with significant AGT catalytic activity and in two of these activity was in the low normal range, possibly reflecting variation in mitochondrial content of the biopsy as this particular mutation is associated with mitochondrial mistargeting. Limited mutation analysis can provide a useful first line test for PH1 and PH2 in patients in whom primary hyperoxaluria is suspected and in whom secondary causes have been excluded. Those patients in whom a single mutation, or no mutation, is found can then be selectively targeted for liver biopsy.

[Primary hiperoxaluria: a new mutation in gen AGXT (R197Q) cause of neonatal convulsions].

PubMed

Guevara-Campos, José; Riverol, Débora; González-Guevara, Lucía; Tinedo, Rubin

2008-12-01

Primary hyperoxaluria is a congenital innate error of the metabolism of the amino acids, that is transmitted like an autosomal recessive character. Two types of hyperoxaluria exist: the primary type I, that corresponds to the peroxisomal enzymatic deficit of the alanine glyoxylate aminotransferase in the liver (AGT) and type II, due to the deficit of the glyoxylate reductase/hydroxypyruvate reductase deficiency (GRHPR). The primary type I (AGT) is the most frequenty. We report the case of a female infant of one month of age, that on her first day post birth, presented myoclonic convulsions and tonic spasms, both during wakefullness and sleep periods, that became more frequent and did not respond to the use of anticonvulsants. The ictal Electroencephalogram presented an intermittent activity of spikes and spike-waves of high voltage in the right hemisphere. Eight minutes after the intravenous administration of 150 mg of pyridoxine, it was observed a diminution of the epileptic activity, as well as the clinical manifestations. The determination of organic acids in urine revealed an increase in the concentration levels of oxalic acid (3064 mmol/mol of creatinine). The molecular genetic study of the AGXT gene, showed the existence of a R197Q mutation in exón 5 of the patient and her father. She received treatment with pyridoxine at a dose of 50 mg/day. When she reached the age of three months both a normal electroencephalogram and biochemistry were obtained. Although it is a rare cause of neonatal convulsions, hyperoxaluria, due to new mutations is an underdiagnosed disease by neonatologists and paediatricias.

Identification of new mutations in primary hyperoxaluria type 1 (PH1).

PubMed

von Schnakenburg, C; Rumsby, G

1998-01-01

Primary hyperoxaluria type 1 (PH1) is caused by deficiency of the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). The AGXT gene, which codes for the 392 amino acid protein, has been mapped to chromosome 2q37.3. In order to identify new mutations in the AGXT gene we studied 79 PH1 patients using single strand conformation polymorphism analysis. In addition to a cluster of new mutations in exon 7 we report five novel mutations in exons 2, 4, 5, 9 and 10. These are T444C, G640A, G690A, 1008-1010delGCG and G1171A. These five new mutations contribute to our knowledge of the AGXT gene. Their possible consequences for PH1 phenotype and enzyme activity are discussed.

Enteric oxalate elimination is induced and oxalate is normalized in a mouse model of primary hyperoxaluria following intestinal colonization with Oxalobacter

PubMed Central

Gjymishka, Altin; Salido, Eduardo C.; Allison, Milton J.; Freel, Robert W.

2011-01-01

Oxalobacter colonization of rat intestine was previously shown to promote enteric oxalate secretion and elimination, leading to significant reductions in urinary oxalate excretion (Hatch et al. Kidney Int 69: 691–698, 2006). The main goal of the present study, using a mouse model of primary hyperoxaluria type 1 (PH1), was to test the hypothesis that colonization of the mouse gut by Oxalobacter formigenes could enhance enteric oxalate secretion and effectively reduce the hyperoxaluria associated with this genetic disease. Wild-type (WT) mice and mice deficient in liver alanine-glyoxylate aminotransferase (Agxt) exhibiting hyperoxalemia and hyperoxaluria were used in these studies. We compared the unidirectional and net fluxes of oxalate across isolated, short-circuited large intestine of artificially colonized and noncolonized mice. In addition, plasma and urinary oxalate was determined. Our results demonstrate that the cecum and distal colon contribute significantly to enteric oxalate excretion in Oxalobacter-colonized Agxt and WT mice. In colonized Agxt mice, urinary oxalate excretion was reduced 50% (to within the normal range observed for WT mice). Moreover, plasma oxalate concentrations in Agxt mice were also normalized (reduced 50%). Colonization of WT mice was also associated with marked (up to 95%) reductions in urinary oxalate excretion. We conclude that segment-specific effects of Oxalobacter on intestinal oxalate transport in the PH1 mouse model are associated with a normalization of plasma oxalate and urinary oxalate excretion in otherwise hyperoxalemic and hyperoxaluric animals. PMID:21163900

Diagnosis of rare inherited glyoxalate metabolic disorders through in-situ analysis of renal stones

NASA Astrophysics Data System (ADS)

Jacob, D. E.; Grohe, B.; Hoppe, B.; Beck, B. B.; Tessadri, R.

2012-04-01

The primary hyperoxalurias type I - III constitute rare autosomal-recessive inherited disorders of the human glyoxylate metabolism. By mechanisms that are ill understood progressive nephrocalcinosis and recurrent urolithiasis (kidney stone formation) often starting in early childhood, along with their secondary complications results in loss of nephron mass which progresses to end-stage renal failure over time. In the most frequent form, end-stage renal failure (ESRF) is the rule and combined liver/kidney transplantation respectively pre-emptive liver transplantation are the only causative treatment today. Hence, this contributes significantly to healthcare costs and early diagnosis is extremely important for a positive outcome for the patient. We are developing a stone-based diagnostic method by in-detail multi-methods investigation of the crystalline moiety in concert with urine and stone proteomics. Stone analysis will allow faster analysis at low-impact for the patients in the early stages of the disease. First results from combined spectroscopic (Raman, FTIR)and geochemical micro-analyses (Electron Microprobe and Laser Ablation ICP-MS) are presented here that show significant differences between stones from hyperoxaluria patients and those formed by patients without this disorder (idiopathic stones). Major differences exist in chemistry as well as in morphology and phase composition of the stones. Ca/P ratios and Mg contents differentiate between oxalate-stones from hyperoxaluria patients and idiopathic stones. Results show that also within the different subtypes of primary hyperoxaluria significant differences can be found in stone composition. These imply differences in stone formation which could be exploited for new therapeutic pathways. Furthermore, the results provide important feedback for suspected but yet unconfirmed cases of primary hyperoxaluria when used in concert with the genetic methods routinely applied.

Molecular analysis of hyperoxaluria type 1 in Italian patients reveals eight new mutations in the alanine: glyoxylate aminotransferase gene.

PubMed

Pirulli, D; Puzzer, D; Ferri, L; Crovella, S; Amoroso, A; Ferrettini, C; Marangella, M; Mazzola, G; Florian, F

1999-06-01

Systematic screening using the SSCP technique followed by sequencing of bands with abnormal mobility derived from the AGXT exons of 15 unrelated Italian patients with primary hyperoxaluria type 1 (PH1) allowed us to characterize both the mutant alleles in each individual. Eight new mutations were identified: C155del, C156ins, G244T, C252T, GAG408ins, G468A, G588A and G1098del. This study demonstrates both the effectiveness of the screening strategy chosen to identify all the mutant alleles and the high degree of allelic heterogeneity in PH1.

Crystals in brain and meninges in primary hyperoxaluria and oxalosis.

PubMed Central

Haqqani, M T

1977-01-01

A case of primary hyperoxaluria and oxalosis with chronic renal failure, crystalline myocarditis, and disseminated calcium oxalate crystal deposition in various tissues including the brain and meninges is described. Deposition of crystals in brain and meninges is exceptionally rare in primary oxalosis. Images PMID:838867

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

A vertical (pseudodominant) pattern of inheritance in the autosomal recessive disease primary hyperoxaluria type 1: lack of relationship between genotype, enzymic phenotype, and disease severity.

PubMed

Hoppe, B; Danpure, C J; Rumsby, G; Fryer, P; Jennings, P R; Blau, N; Schubiger, G; Neuhaus, T; Leumann, E

1997-01-01

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disease caused by a deficiency of alanine:glyoxylate aminotransferase (encoded by the AGXT gene). Primary hyperoxaluria type 1 is characterized by the elevated urinary excretion of oxalate and glycolate, and the deposition of insoluble calcium oxalate in the renal parenchyma and urinary tract. In the present study, we investigated an unusual family containing four affected individuals in two different generations. Based on our genetic, enzymic, metabolic, and clinical analyses, we have come to the following conclusions. First, although the pattern of inheritance of PH1 is usually horizontal (ie, all patients in the same generation), as expected for an autosomal recessive disease, it can sometimes show a vertical (pseudodominant) pattern of inheritance (ie, patients in more than one generation) due to the segregation within a family of three, rather than two, mutant AGXT alleles. Second, affected members of such a family can manifest very different clinical phenotypes both within and between generations. Although the clinical differences between generations might be at least partly due to differences in AGXT genotype, differences can equally occur within the same generation in individuals who possess the same AGXT genotype. Finally, individuals with PH1 at the level of the AGXT genotype might remain asymptomatic and undiagnosed for many years. The consequences of these findings for the clinical management and genetic counseling of families with PH1 are profound and wide-ranging.

Genotype-phenotype correlation in primary hyperoxaluria type 1: the p.Gly170Arg AGXT mutation is associated with a better outcome.

PubMed

Harambat, Jérôme; Fargue, Sonia; Acquaviva, Cécile; Gagnadoux, Marie-France; Janssen, Françoise; Liutkus, Aurélia; Mourani, Chebl; Macher, Marie-Alice; Abramowicz, Daniel; Legendre, Christophe; Durrbach, Antoine; Tsimaratos, Michel; Nivet, Hubert; Girardin, Eric; Schott, Anne-Marie; Rolland, Marie-Odile; Cochat, Pierre

2010-03-01

We sought to ascertain the long-term outcome and genotype-phenotype correlations available for primary hyperoxaluria type 1 in a large retrospective cohort study. We examined the clinical history of 155 patients (129 families primarily from Western Europe, North Africa, or the Middle East) as well as the enzymatic or genetic diagnosis. The median age at first symptom was 4 years, and at diagnosis 7.7 years, at which time 43% had reached end-stage renal disease. Presentations included: (1) early nephrocalcinosis and infantile renal failure, (2) recurrent urolithiasis and progressive renal failure diagnosed during childhood, (3) late onset with occasional stone passage diagnosed in adulthood, (4) diagnosis occurring on post-transplantation recurrence, and (5) family screening. The cumulative patient survival was 95, 86, and 74% at ages 10, 30, and 50 years, respectively, with the cumulative renal survival of 81, 59, 41, and 10% at ages 10, 20, 30, and 50 years, respectively; 72 patients had undergone a total of 97 transplantations. Among the 136 patients with DNA analysis, the most common mutation was p.Gly170Arg (allelic frequency 21.5%), with a median age at end-stage renal disease of 47 years for homozygotes, 35 years for heterozygotes, and 21 years for other mutations. Our results underscore the severe prognosis of primary hyperoxaluria type 1 and the necessity for early diagnosis and treatment, as well as confirm a better prognosis of the p.Gly170Arg mutation.

Data from a large European study indicate that the outcome of primary hyperoxaluria type 1 correlates with the AGXT mutation type.

PubMed

Mandrile, Giorgia; van Woerden, Christiaan S; Berchialla, Paola; Beck, Bodo B; Acquaviva Bourdain, Cécile; Hulton, Sally-Anne; Rumsby, Gill

2014-12-01

Primary hyperoxaluria type 1 displays a heterogeneous phenotype, likely to be affected by genetic and non-genetic factors, including timeliness of diagnosis and quality of care. As previous genotype-phenotype studies were hampered by limited patient numbers the European OxalEurope Consortium was constituted. This preliminary retrospective report is based on 526 patients of which 410 have the AGXT genotype defined. We grouped mutations by the predicted effect as null, missense leading to mistargeting (G170R), and other missense, and analyzed their phenotypic correlations. Median age of end-stage renal disease increased from 9.9 for 88 homozygous null patients, 11.5 for 42 heterozygous null/missense, 16.9 for 116 homozygous missense patients, 25.1 for 61 G170R/null patients, 31.2 for 32 G170R/missense patients, and 33.9 years for 71 homozygous G170R patients. The outcome of some recurrent missense mutations (p.I244T, p.F152I, p.M195R, p.D201E, p.S81L, p.R36C) and an unprecedented number of G170R homozygotes is described in detail. Diagnosis is still delayed and actions aimed at increasing awareness of primary hyperoxaluria type 1 are recommended. Thus, in addition to G170R, other causative mutations are associated with later onset of end-stage renal disease. The OxalEurope registry will provide necessary tools for characterizing those genetic and non-genetic factors through a combination of genetic, functional, and biostatistical approaches.

Molecular insights into primary hyperoxaluria type 1 pathogenesis.

PubMed

Cellini, Barbara; Oppici, Elisa; Paiardini, Alessandro; Montioli, Riccardo

2012-01-01

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder of glyoxylate metabolism caused by the deficiency of liver peroxisomal alanine:glyoxylate aminotransferase (AGT), a pyridoxal 5'-phosphate (PLP)-dependent enzyme. The PH1 pathogenesis is mostly due to single point mutations (more than 150 so far identified) on the AGXT gene, and is characterized by a marked heterogeneity in terms of genotype, enzymatic and clinical phenotypes. This article presents an up to date review of selected aspects of the biochemical properties of the two allelic forms of AGT and of some PH1-causing variants. These recent discoveries highlight the effects at the protein level of the pathogenic mutations, and, together with previous cell biology and clinical data, (i) improve the understanding of the molecular basis of PH1 pathogenesis, and (ii) help to delineate perspectives for predicting the response to pyridoxine treatment or for suggesting new strategies for PH1 patients bearing the analyzed mutations.

Molecular analysis of the AGXT gene in Italian patients with primary hyperoxaluria type 1 (PH1).

PubMed

Ferrettini, C; Pirulli, D; Cosseddu, D; Marangella, M; Petrarulo, M; Mazzola, G; Vatta, S; Amoroso, A

1998-01-01

Specimens were collected from 22 Italian patients with primary hyperoxaluria type 1 (PH1). Ten of them had already been analyzed by molecular biology. To clarify the molecular characteristics of the AGXT gene disease responsible for PH1, DNA samples were examined for known mutations by hybridisation of PCR products with Sequence Specific Oligonucleotides (PCR-SSO). We planned to identify new mutations of the AGXT gene by heteroduplex analysis followed by direct sequencing. We had already standardized a) the conditions for the amplification of the 11 exons of AGXT, b) the PCR-SSO technique and c) the heteroduplex analysis of amplified products. Preliminary results demonstrated that the AGXT mutations described in previous studies were found only in 40% of the examined Italian patients with PH1. The remaining 60% of mutations should be characterised in future studies.

Chronic Nephropathy from Dietary Hyperoxaluria: Sustained Improvement of Renal Function after Dietary Intervention.

PubMed

Sun, Yijuan; Horowitz, Bruce L; Servilla, Karen S; Fair, Joanna R; Vigil, Darlene; Ganta, Kavitha; Massie, Larry; Tzamaloukas, Antonios H

2017-03-20

A 56-year-old man with stable chronic kidney disease (CKD) for two years following a single episode of calcium oxalate urolithiasis developed progressive elevation of his serum creatinine concentration. Urinalysis revealed pyuria and white cell casts, a few red blood cells, minimal proteinuria, and no crystals. Urine culture was sterile. Gallium scintigraphy was consistent with interstitial nephritis. Proton pump inhibitor intake was discontinued, and a short course of oral corticosteroids was initiated. Percutaneous kidney biopsy, performed because of the continued deterioration of renal function to a minimum estimated glomerular filtration rate (eGFR) value of 15 mL/min per 1.73 m 2 and persistent pyuria, revealed deposition of oxalate crystals in the tubules and interstitium, pronounced tubular changes, and interstitial nephritis and fibrosis. Urinary oxalate excretion was very high, in the range usually associated with primary hyperoxaluria. However, investigations for primary or enteric hyperoxaluria were negative. He reported a diet based on various nuts high in oxalate content. Estimated oxalate content in the diet was, for years, approximately four times higher than that in the average American diet. The institution of a diet low in oxalates resulted in the rapid normalization of urinary oxalate excretion and urinary sediment and in the slow, continuous improvement of renal function to near normal levels (eGFR 59 mL/min/1.73 m 2 ) before his death from a brain malignancy 3.5 years later. The manifestations of nephropathy secondary to dietary hyperoxaluria, including the urine findings, can be indistinguishable from other types of interstitial nephritis. The diagnosis of dietary hyperoxaluria requires careful dietary history and a kidney biopsy. Identifying dietary hyperoxaluria as the cause of CKD is important because the decrease in dietary oxalate intake without any other measures can lead to sustained improvement in renal function.

Chronic Nephropathy from Dietary Hyperoxaluria: Sustained Improvement of Renal Function after Dietary Intervention

PubMed Central

Sun, Yijuan; Horowitz, Bruce L; Servilla, Karen S; Fair, Joanna R; Vigil, Darlene; Ganta, Kavitha; Massie, Larry

2017-01-01

A 56-year-old man with stable chronic kidney disease (CKD) for two years following a single episode of calcium oxalate urolithiasis developed progressive elevation of his serum creatinine concentration. Urinalysis revealed pyuria and white cell casts, a few red blood cells, minimal proteinuria, and no crystals. Urine culture was sterile. Gallium scintigraphy was consistent with interstitial nephritis. Proton pump inhibitor intake was discontinued, and a short course of oral corticosteroids was initiated. Percutaneous kidney biopsy, performed because of the continued deterioration of renal function to a minimum estimated glomerular filtration rate (eGFR) value of 15 mL/min per 1.73 m2 and persistent pyuria, revealed deposition of oxalate crystals in the tubules and interstitium, pronounced tubular changes, and interstitial nephritis and fibrosis. Urinary oxalate excretion was very high, in the range usually associated with primary hyperoxaluria. However, investigations for primary or enteric hyperoxaluria were negative. He reported a diet based on various nuts high in oxalate content. Estimated oxalate content in the diet was, for years, approximately four times higher than that in the average American diet. The institution of a diet low in oxalates resulted in the rapid normalization of urinary oxalate excretion and urinary sediment and in the slow, continuous improvement of renal function to near normal levels (eGFR 59 mL/min/1.73 m2) before his death from a brain malignancy 3.5 years later. The manifestations of nephropathy secondary to dietary hyperoxaluria, including the urine findings, can be indistinguishable from other types of interstitial nephritis. The diagnosis of dietary hyperoxaluria requires careful dietary history and a kidney biopsy. Identifying dietary hyperoxaluria as the cause of CKD is important because the decrease in dietary oxalate intake without any other measures can lead to sustained improvement in renal function. PMID:28435765

Novel findings in patients with primary hyperoxaluria type III and implications for advanced molecular testing strategies

PubMed Central

Beck, Bodo B; Baasner, Anne; Buescher, Anja; Habbig, Sandra; Reintjes, Nadine; Kemper, Markus J; Sikora, Przemyslaw; Mache, Christoph; Pohl, Martin; Stahl, Mirjam; Toenshoff, Burkhard; Pape, Lars; Fehrenbach, Henry; Jacob, Dorrit E; Grohe, Bernd; Wolf, Matthias T; Nürnberg, Gudrun; Yigit, Gökhan; Salido, Eduardo C; Hoppe, Bernd

2013-01-01

Identification of mutations in the HOGA1 gene as the cause of autosomal recessive primary hyperoxaluria (PH) type III has revitalized research in the field of PH and related stone disease. In contrast to the well-characterized entities of PH type I and type II, the pathophysiology and prevalence of type III is largely unknown. In this study, we analyzed a large cohort of subjects previously tested negative for type I/II by complete HOGA1 sequencing. Seven distinct mutations, among them four novel, were found in 15 patients. In patients of non-consanguineous European descent the previously reported c.700+5G>T splice-site mutation was predominant and represents a potential founder mutation, while in consanguineous families private homozygous mutations were identified throughout the gene. Furthermore, we identified a family where a homozygous mutation in HOGA1 (p.P190L) segregated in two siblings with an additional AGXT mutation (p.D201E). The two girls exhibiting triallelic inheritance presented a more severe phenotype than their only mildly affected p.P190L homozygous father. In silico analysis of five mutations reveals that HOGA1 deficiency is causing type III, yet reduced HOGA1 expression or aberrant subcellular protein targeting is unlikely to be the responsible pathomechanism. Our results strongly suggest HOGA1 as a major cause of PH, indicate a greater genetic heterogeneity of hyperoxaluria, and point to a favorable outcome of type III in the context of PH despite incomplete or absent biochemical remission. Multiallelic inheritance could have implications for genetic testing strategies and might represent an unrecognized mechanism for phenotype variability in PH. PMID:22781098

Novel findings in patients with primary hyperoxaluria type III and implications for advanced molecular testing strategies.

PubMed

Beck, Bodo B; Baasner, Anne; Buescher, Anja; Habbig, Sandra; Reintjes, Nadine; Kemper, Markus J; Sikora, Przemyslaw; Mache, Christoph; Pohl, Martin; Stahl, Mirjam; Toenshoff, Burkhard; Pape, Lars; Fehrenbach, Henry; Jacob, Dorrit E; Grohe, Bernd; Wolf, Matthias T; Nürnberg, Gudrun; Yigit, Gökhan; Salido, Eduardo C; Hoppe, Bernd

2013-02-01

Identification of mutations in the HOGA1 gene as the cause of autosomal recessive primary hyperoxaluria (PH) type III has revitalized research in the field of PH and related stone disease. In contrast to the well-characterized entities of PH type I and type II, the pathophysiology and prevalence of type III is largely unknown. In this study, we analyzed a large cohort of subjects previously tested negative for type I/II by complete HOGA1 sequencing. Seven distinct mutations, among them four novel, were found in 15 patients. In patients of non-consanguineous European descent the previously reported c.700+5G>T splice-site mutation was predominant and represents a potential founder mutation, while in consanguineous families private homozygous mutations were identified throughout the gene. Furthermore, we identified a family where a homozygous mutation in HOGA1 (p.P190L) segregated in two siblings with an additional AGXT mutation (p.D201E). The two girls exhibiting triallelic inheritance presented a more severe phenotype than their only mildly affected p.P190L homozygous father. In silico analysis of five mutations reveals that HOGA1 deficiency is causing type III, yet reduced HOGA1 expression or aberrant subcellular protein targeting is unlikely to be the responsible pathomechanism. Our results strongly suggest HOGA1 as a major cause of PH, indicate a greater genetic heterogeneity of hyperoxaluria, and point to a favorable outcome of type III in the context of PH despite incomplete or absent biochemical remission. Multiallelic inheritance could have implications for genetic testing strategies and might represent an unrecognized mechanism for phenotype variability in PH.

Hyperoxaluria Requires TNF Receptors to Initiate Crystal Adhesion and Kidney Stone Disease.

PubMed

Mulay, Shrikant R; Eberhard, Jonathan N; Desai, Jyaysi; Marschner, Julian A; Kumar, Santhosh V R; Weidenbusch, Marc; Grigorescu, Melissa; Lech, Maciej; Eltrich, Nuru; Müller, Lisa; Hans, Wolfgang; Hrabě de Angelis, Martin; Vielhauer, Volker; Hoppe, Bernd; Asplin, John; Burzlaff, Nicolai; Herrmann, Martin; Evan, Andrew; Anders, Hans-Joachim

2017-03-01

Intrarenal crystals trigger inflammation and renal cell necroptosis, processes that involve TNF receptor (TNFR) signaling. Here, we tested the hypothesis that TNFRs also have a direct role in tubular crystal deposition and progression of hyperoxaluria-related CKD. Immunohistochemical analysis revealed upregulated tubular expression of TNFR1 and TNFR2 in human and murine kidneys with calcium oxalate (CaOx) nephrocalcinosis-related CKD compared with controls. Western blot and mRNA expression analyses in mice yielded consistent data. When fed an oxalate-rich diet, wild-type mice developed progressive CKD, whereas Tnfr1-, Tnfr2- , and Tnfr1/2- deficient mice did not. Despite identical levels of hyperoxaluria, Tnfr1-, Tnfr2- , and Tnfr1/2 -deficient mice also lacked the intrarenal CaOx deposition and tubular damage observed in wild-type mice. Inhibition of TNFR signaling prevented the induced expression of the crystal adhesion molecules, CD44 and annexin II, in tubular epithelial cells in vitro and in vivo , and treatment with the small molecule TNFR inhibitor R-7050 partially protected hyperoxaluric mice from nephrocalcinosis and CKD. We conclude that TNFR signaling is essential for CaOx crystal adhesion to the luminal membrane of renal tubules as a fundamental initiating mechanism of oxalate nephropathy. Furthermore, therapeutic blockade of TNFR might delay progressive forms of nephrocalcinosis in oxalate nephropathy, such as primary hyperoxaluria. Copyright © 2017 by the American Society of Nephrology.

Hyperoxaluria Requires TNF Receptors to Initiate Crystal Adhesion and Kidney Stone Disease

PubMed Central

Mulay, Shrikant R.; Eberhard, Jonathan N.; Desai, Jyaysi; Marschner, Julian A.; Kumar, Santhosh V.R.; Weidenbusch, Marc; Grigorescu, Melissa; Lech, Maciej; Eltrich, Nuru; Müller, Lisa; Hans, Wolfgang; Hrabě de Angelis, Martin; Vielhauer, Volker; Hoppe, Bernd; Asplin, John; Burzlaff, Nicolai; Herrmann, Martin; Evan, Andrew

2017-01-01

Intrarenal crystals trigger inflammation and renal cell necroptosis, processes that involve TNF receptor (TNFR) signaling. Here, we tested the hypothesis that TNFRs also have a direct role in tubular crystal deposition and progression of hyperoxaluria-related CKD. Immunohistochemical analysis revealed upregulated tubular expression of TNFR1 and TNFR2 in human and murine kidneys with calcium oxalate (CaOx) nephrocalcinosis-related CKD compared with controls. Western blot and mRNA expression analyses in mice yielded consistent data. When fed an oxalate-rich diet, wild-type mice developed progressive CKD, whereas Tnfr1-, Tnfr2-, and Tnfr1/2-deficient mice did not. Despite identical levels of hyperoxaluria, Tnfr1-, Tnfr2-, and Tnfr1/2-deficient mice also lacked the intrarenal CaOx deposition and tubular damage observed in wild-type mice. Inhibition of TNFR signaling prevented the induced expression of the crystal adhesion molecules, CD44 and annexin II, in tubular epithelial cells in vitro and in vivo, and treatment with the small molecule TNFR inhibitor R-7050 partially protected hyperoxaluric mice from nephrocalcinosis and CKD. We conclude that TNFR signaling is essential for CaOx crystal adhesion to the luminal membrane of renal tubules as a fundamental initiating mechanism of oxalate nephropathy. Furthermore, therapeutic blockade of TNFR might delay progressive forms of nephrocalcinosis in oxalate nephropathy, such as primary hyperoxaluria. PMID:27612997

Primary Hyperoxaluria Type 1 with Homozygosity for a Double-mutated AGXT Allele in a 2-year-old Child.

PubMed

Krishnamurthy, S; Kartha, G B; Venkateswaran, V S; Prasannakumar, M; Mahadevan, S; Gowda, M; Pelle, A; Giachino, D

2017-01-01

Primary hyperoxaluria (PH) Type 1 is a rare, genetic disorder caused by deficiency of the liver enzyme alanine-glyoxylate aminotransferase, which is encoded by AGXT gene. We report a 2-year-old South Indian Tamil child with nephrocalcinosis due to PH Type 1, in whom a homozygous genotype for two missense mutations in the AGXT gene was found: first, a C to G transversion (c. 32C>G) in exon 1 resulting in the amino acid substitution p.Pro11Arg; second, a T to A transversion (c. 167T>A) in exon 2 resulting in p.Ile56Asn. A therapy based on potassium citrate and pyridoxine was started. This is the first report of molecular testing-proven childhood onset-PH Type 1 from South India and is notable for the co-occurrence of two missense mutations in one AGXT allele, which might lead to different and more severe phenotype than each mutation alone. To the best of our knowledge, AGXT allele carrying two already known mutations has not been previously reported.

Primary Hyperoxaluria Type 1 with Homozygosity for a Double-mutated AGXT Allele in a 2-year-old Child

PubMed Central

Krishnamurthy, S.; Kartha, G. B.; Venkateswaran, V. S.; Prasannakumar, M.; Mahadevan, S.; Gowda, M.; Pelle, A.; Giachino, D.

2017-01-01

Primary hyperoxaluria (PH) Type 1 is a rare, genetic disorder caused by deficiency of the liver enzyme alanine-glyoxylate aminotransferase, which is encoded by AGXT gene. We report a 2-year-old South Indian Tamil child with nephrocalcinosis due to PH Type 1, in whom a homozygous genotype for two missense mutations in the AGXT gene was found: first, a C to G transversion (c. 32C>G) in exon 1 resulting in the amino acid substitution p.Pro11Arg; second, a T to A transversion (c. 167T>A) in exon 2 resulting in p.Ile56Asn. A therapy based on potassium citrate and pyridoxine was started. This is the first report of molecular testing-proven childhood onset-PH Type 1 from South India and is notable for the co-occurrence of two missense mutations in one AGXT allele, which might lead to different and more severe phenotype than each mutation alone. To the best of our knowledge, AGXT allele carrying two already known mutations has not been previously reported. PMID:28904440

Extreme intrafamilial variability of Saudi brothers with primary hyperoxaluria type 1.

PubMed

Alfadhel, Majid; Alhasan, Khalid A; Alotaibi, Mohammed; Al Fakeeh, Khalid

2012-01-01

Primary hyperoxaluria type 1 (PH1) is characterized by progressive renal insufficiency culminating in end-stage renal disease, and a wide range of clinical features related to systemic oxalosis in different organs. It is caused by autosomal recessive deficiency of alanine:glyoxylate aminotransferase due to a defect in AGXT gene. Two brothers (one 6 months old; the other 2 years old) presented with acute renal failure and urinary tract infection respectively. PH1 was confirmed by high urinary oxalate level, demonstration of oxalate crystals in bone biopsy, and pathogenic homozygous known AGXT gene mutation. Despite the same genetic background, same sex, and shared environment, the outcome of the two siblings differs widely. While one of them died earlier with end-stage renal disease and multiorgan failure caused by systemic oxalosis, the older brother is pyridoxine responsive with normal development and renal function. Clinicians should be aware of extreme intrafamilial variability of PH1 and international registries are needed to characterize the genotype-phenotype correlation in such disorder.

A novel mutation in the AGXT gene causing primary hyperoxaluria type I: genotype-phenotype correlation.

PubMed

M'Dimegh, Saoussen; Aquaviva-Bourdain, Cécile; Omezzine, Asma; M'Barek, Ibtihel; Souche, Geneviéve; Zellama, Dorsaf; Abidi, Kamel; Achour, Abdelattif; Gargah, Tahar; Abroug, Saoussen; Bouslama, Ali

2016-09-01

Primary hyperoxaluria type I (PH1) is an autosomal recessive metabolic disorder caused by inherited mutations in the AGXT gene encoding liver peroxisomal alanine : glyoxylate aminotransferase (AGT) which is deficient or mistargeted to mitochondria. PH1 shows considerable phenotypic and genotypic heterogeneity. The incidence and severity of PH1 varies in different geographic regions. DNA samples of the affected members from two unrelated Tunisian families were tested by amplifying and sequencing each of the AGXT exons and intron-exon junctions. We identified a novel frameshift mutation in the AGXT gene, the c.406_410dupACTGC resulting in a truncated protein (p.Gln137Hisfs*19). It is found in homozygous state in two nonconsanguineous unrelated families from Tunisia. These molecular findings provide genotype/phenotype correlations in the intrafamilial phenotypic and permit accurate carrier detection, and prenatal diagnosis. The novel p.Gln137Hisfs*19 mutation detected in our study extend the spectrum of known AGXT gene mutations in Tunisia.

Bifidobacterium animalis subsp. lactis decreases urinary oxalate excretion in a mouse model of primary hyperoxaluria

PubMed Central

Whittamore, Jonathan M.; Hatch, Marguerite

2015-01-01

Hyperoxaluria significantly increases the risk of calcium oxalate kidney stone formation. Since several bacteria have been shown to metabolize oxalate in vitro, including probiotic bifidobacteria, we focused on the efficiency and possible mechanisms by which bifidobacteria can infuence oxalate handling in vivo, especially in the intestines, and compared these results with the reported effects of Oxalobacter formigenes. Bifidobacterium animalis subsp. lactis DSM 10140 and B. adolescentis ATCC 15703 were administered to wild-type (WT) mice and to mice defcient in the hepatic enzyme alanine-glyoxylate aminotransferase (Agxt−/−, a mouse model of Primary Hyperoxaluria) that were fed an oxalate-supplemented diet. The administration of B. animalis subsp. lactis led to a significant decrease in urinary oxalate excretion in WT and Agxt−/− mice when compared to treatment with B. adolescent-is. Detection of B. animalis subsp. lactis in feces revealed that 3 weeks after oral gavage with the bacteria 64 % of WT mice, but only 37 % of Agxt−/− mice were colonized. Examining intestinal oxalate fuxes showed there were no significant changes to net oxalate secretion in colonized animals and were therefore not associated with the changes in urinary oxalate excretion. These results indicate that colonization with B. animalis subsp. lactis decreased urinary oxalate excretion by degrading dietary oxalate thus limiting its absorption across the intestine but it did not promote enteric oxalate excretion as reported for O. formigenes. Preventive or therapeutic administration of B. animalis subsp. lactis appears to have some potential to beneficially infuence dietary hyperoxaluria in mice. PMID:25269440

Hyperoxaluria

MedlinePlus

... such as gastric bypass, Crohn’s Disease, short bowel syndrome or other malabsorption disorders causing enteric hyperoxaluria . Avoiding, foods high in oxalate in particularly important. Learn more… Types ...

An Investigational RNAi Therapeutic Targeting Glycolate Oxidase Reduces Oxalate Production in Models of Primary Hyperoxaluria

PubMed Central

Li, Xingsheng; Racie, Timothy; Hettinger, Julia; Bettencourt, Brian R.; Najafian, Nader; Haslett, Patrick; Fitzgerald, Kevin; Holmes, Ross P.; Erbe, David; Querbes, William; Knight, John

2017-01-01

Primary hyperoxaluria type 1 (PH1), an inherited rare disease of glyoxylate metabolism, arises from mutations in the enzyme alanine-glyoxylate aminotransferase. The resulting deficiency in this enzyme leads to abnormally high oxalate production resulting in calcium oxalate crystal formation and deposition in the kidney and many other tissues, with systemic oxalosis and ESRD being a common outcome. Although a small subset of patients manages the disease with vitamin B6 treatments, the only effective treatment for most is a combined liver-kidney transplant, which requires life-long immune suppression and carries significant mortality risk. In this report, we discuss the development of ALN-GO1, an investigational RNA interference (RNAi) therapeutic targeting glycolate oxidase, to deplete the substrate for oxalate synthesis. Subcutaneous administration of ALN-GO1 resulted in potent, dose-dependent, and durable silencing of the mRNA encoding glycolate oxidase and increased serum glycolate concentrations in wild-type mice, rats, and nonhuman primates. ALN-GO1 also increased urinary glycolate concentrations in normal nonhuman primates and in a genetic mouse model of PH1. Notably, ALN-GO1 reduced urinary oxalate concentration up to 50% after a single dose in the genetic mouse model of PH1, and up to 98% after multiple doses in a rat model of hyperoxaluria. These data demonstrate the ability of ALN-GO1 to reduce oxalate production in preclinical models of PH1 across multiple species and provide a clear rationale for clinical trials with this compound. PMID:27432743

Primary Hyperoxaluria

PubMed Central

Harambat, Jérôme; Fargue, Sonia; Bacchetta, Justine; Acquaviva, Cécile; Cochat, Pierre

2011-01-01

Primary hyperoxalurias (PH) are inborn errors in the metabolism of glyoxylate and oxalate. PH type 1, the most common form, is an autosomal recessive disorder caused by a deficiency of the liver-specific enzyme alanine, glyoxylate aminotransferase (AGT) resulting in overproduction and excessive urinary excretion of oxalate. Recurrent urolithiasis and nephrocalcinosis are the hallmarks of the disease. As glomerular filtration rate decreases due to progressive renal damage, oxalate accumulates leading to systemic oxalosis. Diagnosis is often delayed and is based on clinical and sonographic findings, urinary oxalate assessment, DNA analysis, and, if necessary, direct AGT activity measurement in liver biopsy tissue. Early initiation of conservative treatment, including high fluid intake, inhibitors of calcium oxalate crystallization, and pyridoxine in responsive cases, can help to maintain renal function in compliant subjects. In end-stage renal disease patients, the best outcomes have been achieved with combined liver-kidney transplantation which corrects the enzyme defect. PMID:21748001

Stones, bones, and heredity.

PubMed

Milliner, Dawn S

2006-07-01

Genetic disorders of mineral metabolism cause urolithiasis, renal disease, and osteodystrophy. Most are rare, such that the full spectrum of clinical expression is difficult to appreciate. Diagnosis is further complicated by overlap of clinical features. Dent's disease and primary hyperoxaluria, inherited causes of calcium urolithiasis, are both associated with nephrocalcinosis and urolithiasis in early childhood and renal failure that can occur at any age but is seen more often in adulthood. Bone disease is an inconsistent feature of each. Dent's disease is caused by mutations of the CLCN-5 gene with impaired kidney-specific CLC-5 chloride channel expression in the proximal tubule, thick ascending limb of Henle, and the collecting ducts. Resulting hypercalciuria and proximal tubule dysfunction, including phosphate wasting, are primarily responsible for the clinical manifestations. Low-molecular-weight proteinuria is characteristic. Definitive diagnosis is made by DNA mutation analysis. Primary hyperoxaluria, type I, is due to mutations of the AGXT gene leading to deficient hepatic alanine-glyoxylate aminotransferase activity. Marked overproduction of oxalate by hepatic cells results in the hyperoxaluria responsible for clinical features. Definitive diagnosis is by liver biopsy with measurement of enzyme activity, with DNA mutation analysis used increasingly as mutations and their frequency are defined. These disorders of calcium urolithiasis illustrate the value of molecular medicine for diagnosis and the promise it provides for innovative and more effective future treatments.

Anemia in patient with primary hyperoxaluria and bone marrow involvement by oxalate crystals.

PubMed

Mykytiv, Vitaliy; Campoy Garcia, Fiz

2018-06-01

We present a rare case of anaemia secondary to bone marrow infiltration by oxalate crystals and renal failure in a patient diagnosed with primary hyperoxaluria. In our case, the anaemia was recovered after the double liver and kidney transplantation, the latter was performed on two occasions after the failure of the first graft. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

An overview of the role of genotyping in the diagnosis of the primary hyperoxalurias.

PubMed

Rumsby, Gill

2005-11-01

The aim of this paper is to give an overview of our current state of knowledge with respect to genotyping for the primary hyperoxalurias and the role of molecular genetics alongside the more traditional biochemical and enzymatic tests for the diagnosis and prognosis of these disorders. The published literature was reviewed to establish the frequency of different mutations and thus the value of testing for a limited number of these mutations in patients with clinical suspicion of primary hyperoxaluria (PH). This approach was compared with whole gene sequencing of the AGXT and GRHPR genes. A limited genetic screen can provide a first line test for PH1 and PH2 in symptomatic patients and can provide a full diagnosis in approximately a third of cases. Molecular genetic analysis is essential for carrier testing and prenatal diagnosis. The value of molecular genetics in prognosis requires a wider evidence base.

A double mutation in AGXT gene in families with primary hyperoxaluria type 1.

PubMed

Kanoun, Houda; Jarraya, Faiçal; Hadj Salem, Ikhlass; Mahfoudh, Hichem; Chaabouni, Yosr; Makni, Fatma; Hachicha, Jamil; Fakhfakh, Faiza

2013-12-01

Primary hyperoxaluria type 1 (PH1) is a severe autosomal recessive inherited disorder of glyoxylate metabolism caused by mutations in the AGXT gene on chromosome 2q37.3 that encodes the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase. These mutations are found throughout the entire gene and cause a wide spectrum of clinical severity. Rare in Europe, PH1 is responsible for 13% of the end stage renal failure in the Tunisian child. In the present work, we identified the double mutation c.32C>T (Pro11Leu) and c.731T>C (p.Ile244Thr) in AGXT gene in five unrelated Tunisian families with PH1 disease. Our results provide evidence regarding the potential involvement of c.32C>T, originally described as common polymorphism, on the resulting phenotype. We also reported an extreme intrafamilial heterogeneity in clinical presentation of PH1. Despite the same genetic background, the outcome of the affected members differs widely. The significant phenotypic heterogeneity observed within a same family, with a same genotype, suggests the existence of relevant modifier factors. © 2013.

Molecular etiology of primary hyperoxaluria type 1: new directions for treatment.

PubMed

Danpure, Christopher J

2005-01-01

Primary hyperoxaluria type 1 (PH1) is a rare autosomal-recessive disorder caused by a deficiency of the liver-specific enzyme alanine:glyoxylate aminotransferase (AGT). AGT deficiency results in increased synthesis and excretion of the metabolic end-product oxalate and deposition of insoluble calcium oxalate in the kidney and urinary tract. Classic treatments for PH1 have tended to address the more distal aspects of the disease process (i.e. the symptoms rather than the causes). However, advances in the understanding of the molecular etiology of PH1 over the past decade have shifted attention towards the more proximal aspects of the disease process (i.e. the causes rather than the symptoms). The determination of the crystal structure of AGT has enabled the effects of some of the most important missense mutations in the AGXT gene to be rationalised in terms of AGT folding, dimerization and stability. This has opened up new possibilities for the design pharmacological agents that might counteract the destabilizing effects of these mutations and which might be of use for the treatment of a potentially life-threatening and difficult-to-treat disease.

Extreme intrafamilial variability of Saudi brothers with primary hyperoxaluria type 1

PubMed Central

Alfadhel, Majid; Alhasan, Khalid A; Alotaibi, Mohammed; Al Fakeeh, Khalid

2012-01-01

Background Primary hyperoxaluria type 1 (PH1) is characterized by progressive renal insufficiency culminating in end-stage renal disease, and a wide range of clinical features related to systemic oxalosis in different organs. It is caused by autosomal recessive deficiency of alanine:glyoxylate aminotransferase due to a defect in AGXT gene. Case report Two brothers (one 6 months old; the other 2 years old) presented with acute renal failure and urinary tract infection respectively. PH1 was confirmed by high urinary oxalate level, demonstration of oxalate crystals in bone biopsy, and pathogenic homozygous known AGXT gene mutation. Despite the same genetic background, same sex, and shared environment, the outcome of the two siblings differs widely. While one of them died earlier with end-stage renal disease and multiorgan failure caused by systemic oxalosis, the older brother is pyridoxine responsive with normal development and renal function. Conclusion Clinicians should be aware of extreme intrafamilial variability of PH1 and international registries are needed to characterize the genotype-phenotype correlation in such disorder. PMID:22956877

Modeling the effect of 3 missense AGXT mutations on dimerization of the AGT enzyme in primary hyperoxaluria type 1.

PubMed

Robbiano, Angela; Frecer, Vladimir; Miertus, Jan; Zadro, Cristina; Ulivi, Sheila; Bevilacqua, Elena; Mandrile, Giorgia; De Marchi, Mario; Miertus, Stanislav; Amoroso, Antonio

2010-01-01

Mutations of the AGXT gene encoding the alanine:glyoxylate aminotransferase liver enzyme (AGT) cause primary hyperoxaluria type 1 (PH1). Here we report a molecular modeling study of selected missense AGXT mutations: the common Gly170Arg and the recently described Gly47Arg and Ser81Leu variants, predicted to be pathogenic using standard criteria. Taking advantage of the refined 3D structure of AGT, we computed the dimerization energy of the wild-type and mutated proteins. Molecular modeling predicted that Gly47Arg affects dimerization with a similar effect to that shown previously for Gly170Arg through classical biochemical approaches. In contrast, no effect on dimerization was predicted for Ser81Leu. Therefore, this probably demonstrates pathogenic properties via a different mechanism, similar to that described for the adjacent Gly82Glu mutation that affects pyridoxine binding. This study shows that the molecular modeling approach can contribute to evaluating the pathogenicity of some missense variants that affect dimerization. However, in silico studies--aimed to assess the relationship between structural change and biological effects--require the integrated use of more than 1 tool.

Variable presentation of primary hyperoxaluria type 1 in 2 patients homozygous for a novel combined deletion and insertion mutation in exon 8 of the AGXT gene.

PubMed

von Schnakenburg, C; Hulton, S A; Milford, D V; Roper, H P; Rumsby, G

1998-01-01

Two unrelated patients of Pakistani origin presented with primary hyperoxaluria type 1 (PH1) at 4 months and 3 years of age, respectively. While the younger patient failed to thrive and suffered from early renal failure, the older one showed a relatively benign history with urolithiasis as the main feature of the disease. In both patients the diagnosis was confirmed by assessment of alanine:glyoxylate aminotransferase catalytic and immunoreactivity in liver biopsy specimens. The underlying genetic defect was found to be a combined deletion and insertion in exon 8 which alters the reading frame of the protein. The nucleotide change introduces a Stu1 restriction site which facilitated typing of additional family members. Both patients and a further affected brother were homozygous for this mutation, while their parents were heterozygous for it. This mutation is the first deletion/insertion identified in PH1. Although rare in our PH1 patient cohort (2.5% of alleles), the finding of 2 homozygous apparently unrelated individuals of the same ethnic origin suggests that it may prove worthwhile to screen other Asian patients for this mutation. These PH1 cases present further evidence that factors other than genotype contribute significantly to the clinical presentation and severity of PH1.

Liver peroxisomal alanine:glyoxylate aminotransferase and the effects of mutations associated with Primary Hyperoxaluria Type I: An overview.

PubMed

Oppici, Elisa; Montioli, Riccardo; Cellini, Barbara

2015-09-01

Liver peroxisomal alanine:glyoxylate aminotransferase (AGT) (EC 2.6.1.44) catalyses the conversion of l-alanine and glyoxylate to pyruvate and glycine, a reaction that allows glyoxylate detoxification. Inherited mutations on the AGXT gene encoding AGT lead to Primary Hyperoxaluria Type I (PH1), a rare disorder characterized by the deposition of calcium oxalate crystals primarily in the urinary tract. Here we describe the results obtained on the biochemical features of AGT as well as on the molecular and cellular effects of polymorphic and pathogenic mutations. A complex scenario on the molecular pathogenesis of PH1 emerges in which the co-inheritance of polymorphic changes and the condition of homozygosis or compound heterozygosis are two important factors that determine the enzymatic phenotype of PH1 patients. All the reported data represent relevant steps toward the understanding of genotype/phenotype correlations, the prediction of the response of the patients to the available therapies, and the development of new therapeutic approaches. This article is part of a Special Issue entitled: Cofactor-dependent proteins: evolution, chemical diversity and bio-applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Primary hyperoxaluria type 1: is genotyping clinically helpful?

PubMed

Leumann, Ernst; Hoppe, Bernd

2005-05-01

There is some controversy about the value of mutation analysis in the management of primary hyperoxaluria type 1 (PH1). About 50 different mutations of the AGXT gene encoding the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT) are currently known. The three most common mutations in the Western population account for less than half of the mutant alleles, and no simple screening test is available. Does the genotype help in diagnosis, prognosis and therapy? Definitive diagnosis is indispensable if liver transplantation is considered and can under certain circumstances be established by mutation analysis, but a liver biopsy is still necessary to determine AGT activity in a number of cases. Prognosis is difficult to assess due to a large clinical variation, despite identical mutations. Although the homozygous 508G>A (Gly170Arg) mutation appears to be associated with a better (and 33insC with a worse) prognosis, there are too many exceptions for precise prediction. Pyridoxine responsiveness can be anticipated in some genotypes (508G>A (Gly170Arg) and 454T>A (Phe153Ile)), but it should still be tested for in all patients. Genetic testing is thus clinically helpful but has clear limitations.

Maternal isodisomy of the telomeric end of chromosome 2 is responsible for a case of primary hyperoxaluria type 1.

PubMed

Chevalier-Porst, Françoise; Rolland, Marie-Odile; Cochat, Pierre; Bozon, Dominique

2005-01-01

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder of glyoxylate metabolism, in which excessive oxalates are formed by the liver and excreted by the kidneys, causing a wide spectrum of disease, ranging from renal failure in infancy to mere renal stones in late adulthood. This disease is caused by a deficiency of alanine:glyoxylate aminotransferase (AGT), which is encoded by a single copy gene, AGXT, located in 2q37.3. We identified an apparently homozygous, loss-of-function, mutation in a patient; the gene defect was present in the heterozygous mother but not in the patient's father. We performed a microsatellite repeat analysis using 13 specific chromosome 2 markers and non-chromosome 2 minisatellites. Six specific chromosome 2 markers showed an apparently homozygous maternal inheritance while four showed a biparental transmission consistent with paternity (confirmed by minisatellite analysis). Quantitative PCR of AGXT exons 1 and 3 on the patient's and parents genomic DNA revealed the presence of two copies of the gene. This is the first case of PH1 caused by segmental maternal isodisomy of 2q37.3. (c) 2004 Wiley-Liss, Inc.

Severe periodontitis in a patient with hyperoxaluria and oxalosis: a case report and review of the literature.

PubMed

Panis, Vassilios; Tosios, Konstantinos I; Gagari, Eleni; Griffin, Terrence J; Damoulis, Petros D

2010-10-01

Hyperoxaluria is a metabolic disease with excessive urinary oxalate excretion that can be primary or secondary. Hyperoxaluria can result in chronic renal disease and renal failure. Calcium oxalate crystals can be deposited in oral tissues, and the disease can be associated with severe periodontitis and tooth loss. The periodontal condition of a 38-year-old patient with a diagnosis of hyperoxaluria and end-stage renal disease is presented. The patient's periodontal status was monitored over a period of several weeks, and extracted teeth were submitted for histopathologic evaluation. The patient was diagnosed with generalized severe periodontitis and external root resorption. Initial periodontal treatment consisting of oral-hygiene instructions and scaling and root planing was performed. However, despite an initial decrease of soft tissue inflammation, the patient's periodontal condition deteriorated, and eventually, all teeth had to be extracted. The deposition of calcium oxalate crystals in the periodontal tissues was confirmed histologically. Long-standing hyperoxaluria can be associated with severe periodontitis and external root resorption resulting in tooth loss. The pathogenetic mechanisms of hard tissue destruction are still unclear.

Renal function can be impaired in children with primary hyperoxaluria type 3.

PubMed

Allard, Lise; Cochat, Pierre; Leclerc, Anne-Laure; Cachat, François; Fichtner, Christine; De Souza, Vandréa Carla; Garcia, Clotilde Druck; Camoin-Schweitzer, Marie-Christine; Macher, Marie-Alice; Acquaviva-Bourdain, Cécile; Bacchetta, Justine

2015-10-01

Primary hyperoxaluria type 3 (PH3) is characterized by mutations in the 4-hydroxy-2-oxoglutarate aldolase (HOGA1) gene. PH3 patients are believed to present with a less severe phenotype than those with PH1 and PH2, but the clinical characteristics of PH3 patients have yet to be defined in sufficient detail. The aim of this study was to report our experience with PH3. Genetic analysis of HOGA1 was performed in patients with a high clinical suspicion of PH after the presence of mutations in the alanine-glyoxylate aminotransferase gene had been ruled out. Clinical, biochemical and genetic data of the seven patients identified with HOGA1 mutations were subsequently retrospectively reviewed. Among the seven patients identified with HOGA1 mutations the median onset of clinical symptoms was 1.8 (range 0.4-9.8) years. Five patients initially presented with urolithiasis, and two other patients presented with urinary tract infection. All patients experienced persistent hyperoxaluria. Seven mutations were found in HOGA1, including two previously unreported ones, c.834 + 1G > T and c.3G > A. At last follow-up, two patients had impaired renal function based on estimated glomerular filtration rates (GFRs) of 77 and 83 mL/min per 1.73 m(2), respectively. We found that the GFR was significantly impaired in two of our seven patients with PH3 diagnosed during childhood. This finding is in contrast to the early-impaired renal function in PH1 and PH2 and appears to refute to preliminary reassuring data on renal function in PH3.

Identification of compound heterozygous patients with primary hyperoxaluria type 1: clinical evaluations and in silico investigations.

PubMed

Kanoun, Houda; Jarraya, Faiçal; Maalej, Bayen; Lahiani, Amina; Mahfoudh, Hichem; Makni, Fatma; Hachicha, Jamil; Fakhfakh, Faiza

2017-10-02

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive inherited disorder of glyoxylate metabolism in which excessive oxalates are formed by the liver and excreted by the kidneys. Calcium oxalate crystallizes in the urine, leading to urolithiasis, nephrocalcinosis, and consequent renal failure if treatment is not initiated promptly. Mutations in the AGXT gene which encodes the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase are responsible of PH1. In the present work, we aimed to analyze AGXT gene and in silico investigations performed in four patients with PH1 among two non consanguineous families. Exhaustive gene sequencing was performed after PCR amplification of coding exons and introns boundaries. Bioinformatic tools were used to predict the impact of AGXT variants on gene expression as well as on the protein structure and function. Direct sequencing of all exons of AGXT gene revealed the emergence of multiple mutations in compound heterozygous state in the two studied families. Two patients were compound heterozygous for the c.731 T > C, c.32C > T, c.1020A > G and c.33_34insC and presented clinically with recurrent urinary tract infection, multiple urolithiasis and nephrocalcinosis under the age of 1 year and a persistent hyperoxaluria at the age of diagnosis. The two other patients presenting a less severe phenotypes were heterozygous for c.731 T > C and homozygous for the c.32C > T and c.1020A > G or compound heterozygous for c.26C > A and c.65A > G variants. In Summary, we provided relevance regarding the compound heterozygous mutations in non consanguineous PH1 families with variable severity.

Comprehensive mutation screening in 55 probands with type 1 primary hyperoxaluria shows feasibility of a gene-based diagnosis.

PubMed

Monico, Carla G; Rossetti, Sandro; Schwanz, Heidi A; Olson, Julie B; Lundquist, Patrick A; Dawson, D Brian; Harris, Peter C; Milliner, Dawn S

2007-06-01

Mutations in AGXT, a locus mapped to 2q37.3, cause deficiency of liver-specific alanine:glyoxylate aminotransferase (AGT), the metabolic error in type 1 primary hyperoxaluria (PH1). Genetic analysis of 55 unrelated probands with PH1 from the Mayo Clinic Hyperoxaluria Center, to date the largest with availability of complete sequencing across the entire AGXT coding region and documented hepatic AGT deficiency, suggests that a molecular diagnosis (identification of two disease alleles) is feasible in 96% of patients. Unique to this PH1 population was the higher frequency of G170R, the most common AGXT mutation, accounting for 37% of alleles, and detection of a new 3' end deletion (Ex 11_3'UTR del). A described frameshift mutation (c.33_34insC) occurred with the next highest frequency (11%), followed by F152I and G156R (frequencies of 6.3 and 4.5%, respectively), both surpassing the frequency (2.7%) of I244T, the previously reported third most common pathogenic change. These sequencing data indicate that AGXT is even more variable than formerly believed, with 28 new variants (21 mutations and seven polymorphisms) detected, with highest frequencies on exons 1, 4, and 7. When limited to these three exons, molecular analysis sensitivity was 77%, compared with 98% for whole-gene sequencing. These are the first data in support of comprehensive AGXT analysis for the diagnosis of PH1, obviating a liver biopsy in most well-characterized patients. Also reported here is previously unavailable evidence for the pathogenic basis of all AGXT missense variants, including evolutionary conservation data in a multisequence alignment and use of a normal control population.

NALP3-mediated inflammation is a principal cause of progressive renal failure in oxalate nephropathy

PubMed Central

Knauf, Felix; Asplin, John R.; Granja, Ignacio; Schmidt, Insa M.; Moeckel, Gilbert; David, Rachel; Flavell, Richard A.; Aronson, Peter S.

2013-01-01

Oxalate nephropathy with renal failure is caused by multiple disorders causing hyperoxaluria due to either overproduction of oxalate (primary hyperoxaluria) or excessive absorption of dietary oxalate (enteric hyperoxaluria). To study the etiology of renal failure in crystal-induced kidney disease, we created a model of progressive oxalate nephropathy by feeding mice a diet high in soluble oxalate (high oxalate in the absence of dietary calcium). Renal histology was characterized by intratubular calcium-oxalate crystal deposition with an inflammatory response in the surrounding interstitium. Oxalate nephropathy was not found in mice fed a high oxalate diet that also contained calcium. NALP3, also known as cryopyrin, has been implicated in crystal-associated diseases such as gout and silicosis. Mice fed the diet high in soluble oxalate demonstrated increased NALP3 expression in the kidney. Nalp3-null mice were completely protected from the progressive renal failure and death that occurred in wild-type mice fed the diet high in soluble oxalate. NALP3-deficiency did not affect oxalate homeostasis, thereby excluding differences in intestinal oxalate handling to explain the observed phenotype. Thus, progressive renal failure in oxalate nephropathy results primarily from NALP3-mediated inflammation. PMID:23739234

Clinical spectrum of primary hyperoxaluria type 1: Experience of a tertiary center

PubMed Central

Soliman, Neveen A.; Nabhan, Marwa M.; Abdelrahman, Safaa M.; Abdelaziz, Hanan; Helmy, Rasha; Ghanim, Khaled; Bazaraa, Hafez M.; Badr, Ahmed M.; Tolba, Omar A.; Kotb, Magd A.; Eweeda, Khaled M.; Fayez, Alaa

2018-01-01

Background and aim Primary hyperoxalurias are rare inborn errors of metabolism resulting in increased endogenous production of oxalate that leads to excessive urinary oxalate excretion. Diagnosis of primary hyperoxaluria type 1 (PH1) is a challenging issue and depends on diverse diagnostic tools including biochemical analysis of urine, stone analysis, renal biopsy, genetic studies and in some cases liver biopsy for enzyme assay. We characterized the clinical presentation as well as renal and extrarenal phenotypes in PH1 patients. Methods This descriptive cohort study included patients with presumable PH1 presenting with nephrolithiasis and/or nephrocalcinosis (NC). Precise clinical characterization of renal phenotype as well as systemic involvement is reported. AGXT mutational analysis was performed to confirm the diagnosis of PH1. Results The study cohort included 26 patients with presumable PH1 with male to female ratio of 1.4:1. The median age at time of diagnosis was 6 years, nevertheless the median age at initial symptoms was 3 years. Thirteen patients (50%) were diagnosed before the age of 5 years. Two patients had no symptoms and were diagnosed while screening siblings of index patients. Seventeen patients (65.4%) had reached end-stage renal disease (ESRD): 6/17 (35.3%) during infancy, 4/17 (23.5%) in early childhood and 7/17 (41.29%) in late childhood. Two patients (7.7%) had clinically manifest extra renal (retina, heart, bone, soft tissue) involvement. Mutational analysis of AGXT gene confirmed the diagnosis of PH1 in 15 out of 19 patients (79%) where analysis had been performed. Fifty percent of patients with maintained renal functions had projected 10 years renal survival. Conclusion PH1 is a heterogeneous disease with wide spectrum of clinical, imaging and functional presentation. More than two-thirds of patients presented prior to the age of 5 years; half of them with the stormy course of infantile PH1. ESRD was the commonest presenting manifestation in two-thirds of our cohort. PMID:28161266

[Biochemical and molecular diagnosis of primary hyperoxaluria type 1: Tunisian study about 15 cases].

PubMed

Belhaj, R; Hayder, N; Gargueh, T; Zorguati, M; Marrakchi, O; Abdelhak, S; Lakhoua, R; Abdelmoula, J

2011-08-01

The primary type 1 hyperoxaluria (HP1) is the most frequent and severe form of the primary hyperoxaluriae. It is related to an enzymatic deficit in alanine glyoxylate aminotransferase (AGT). It is a recessive autosomic disease. Rare in Europe, it is responsible for 13% of the end stage renal failure in the Tunisian child. The aim of this work is to evaluate the biological and molecular examinations contributing with the early diagnosis and the follow-up of the HP1 patients and to test their response to pyridoxin. A prospective study of 15 children who have oxaluria lower than 500 μmol/l and normal renal function is carried out. The cristalluria study, oxaluria and the glycolate-glycerate urinary ratio were carried out on all the patients. The so-called mutation maghrebean T853 (Ile244 Thr) was detected by direct sequencing of the exon 7 gene AGXT. The response to pyridoxin was tested among 13 patients. The oxaluria concentration was greater or equal to 1000 μmol/l in nine cases (60%) and ranging between 600 and 1000 μmol/l in the remaining cases. The oxaluria flow was significantly high depending on the age. The glycolaturia was high among eight patients (57%). In 61,5% of the cases, the most frequent crystalline species was whewellite (C1). The "maghrebin" mutation was identified in nine patients at the heterozygous state, showing 25% allelic frequency. The response to pyridoxin was observed in the 13 tested cases. The HP1 is frequent in our country from where the need for an early diagnosis. The use of simple biochemical tools such as the study of the cristalluria, the morphological analysis of stones and the oxaluria allow to direct the diagnosis towards a HP1, confirmed by the glycolaturia determination. The molecular biology is required in the atypical forms. Copyright © 2009. Published by Elsevier SAS.

Partial deletion of the AGXT gene (EX1_EX7del): A new genotype in hyperoxaluria type 1.

PubMed

Nogueira, P K; Vuong, T S; Bouton, O; Maillard, A; Marchand, M; Rolland, M O; Cochat, P; Bozon, D

2000-04-01

Primary hyperoxaluria type 1 (PH1) is a rare autosomal (2q37.3) recessive metabolic disease caused by a deficiency of the hepatic peroxisomal enzyme alanine:glyoxylate amino transferase. Molecular heterogeneity is important in PH1 as most of the patients (if the parents are unrelated) are compound heterozygotes for rare mutations. We describe the first large deletion in the AGXT gene, removing exons 1 to 7 (EX1_EX7del) that was responsible for one case of severe PH1. This 10 kb deletion was identified by Southern blotting of genomic DNA digested by Xba I and hybridized with different exonic probes. Both parents (from Turkey) are first cousin and carry the deletion. It is of note that the presently reported patient did not exhibit any AGT catalytic activity and even so, he progressed towards end-stage renal disease only at 19 years old. Copyright 2000 Wiley-Liss, Inc.

Cellular Transfection to Deliver Alanine-Glyoxylate Aminotransferase to Hepatocytes: A Rational Gene Therapy for Primary Hyperoxaluria-1 (PH-1)

PubMed Central

Koul, Sweaty; Johnson, Thomas; Pramanik, Saroj; Koul, Hari

2005-01-01

Background: Primary hyperoxaluria-type 1 (PH-1) is a rare autosomal recessive disorder of glyoxalate metabolism caused by deficiency in the liver-specific peroxisomal enzyme alanine-glyoxalate transaminase 1 (AGT) resulting in the increased oxidation of glyoxalate to oxalate. Accumulation of oxalate in the kidney and other soft tissues results in loss of renal function and significant morbidity. The present treatment options offer some relief in the short term, but they are not completely successful. In the present study, we tested the feasibility of corrective gene therapy for this metabolic disorder. Methods: A cDNA library was made from HepG2 cells. PCR primers were designed for the AGT sequence with modifications to preclude mistargeting during gene delivery. Amplified AGT cDNA was cloned as a fusion protein with green fluorescent protein (GFP) using the vector EGFP-C1 (Clontech) for monitoring subcellular distribution. Sequence and expression of the fusion protein was verified. Fusion protein vectors were transfected into hepatocytes by liposomal transfection. AGT expression and subcellular distribution was monitored by GFP fluorescence. Results: HepG2 cells express full-length mRNA coding for AGT as confirmed by insert size as well as sequence determination. Selective primers allowed us to generate a modified recombinant GFP-AGT fusion protein. Cellular transfections with Lipofectamine resulted in transfection efficiencies of 60–90%. The recombinant AGT did localize to peroxisomes as monitored by GFP fluorescence. Conclusions: The results demonstrate preliminary in vitro feasibility data for AGT transfection into the hepatocytes. To the best of our knowledge, this is the first study to attempt recombinant AGT gene therapy for treatment of primary hyperoxaluria-1. PMID:15849465

Kidney Stones in Primary Hyperoxaluria: New Lessons Learnt

PubMed Central

Jacob, Dorrit E.; Grohe, Bernd; Geßner, Michaela; Beck, Bodo B.; Hoppe, Bernd

2013-01-01

To investigate potential differences in stone composition with regard to the type of Primary Hyperoxaluria (PH), and in relation to the patient’s medical therapy (treatment naïve patients versus those on preventive medication) we examined twelve kidney stones from ten PH I and six stones from four PH III patients. Unfortunately, no PH II stones were available for analysis. The study on this set of stones indicates a more diverse composition of PH stones than previously reported and a potential dynamic response of morphology and composition of calculi to treatment with crystallization inhibitors (citrate, magnesium) in PH I. Stones formed by PH I patients under treatment are more compact and consist predominantly of calcium-oxalate monohydrate (COM, whewellite), while calcium-oxalate dihydrate (COD, weddellite) is only rarely present. In contrast, the single stone available from a treatment naïve PH I patient as well as stones from PH III patients prior to and under treatment with alkali citrate contained a wide size range of aggregated COD crystals. No significant effects of the treatment were noted in PH III stones. In disagreement with findings from previous studies, stones from patients with primary hyperoxaluria did not exclusively consist of COM. Progressive replacement of COD by small COM crystals could be caused by prolonged stone growth and residence times in the urinary tract, eventually resulting in complete replacement of calcium-oxalate dihydrate by the monohydrate form. The noted difference to the naïve PH I stone may reflect a reduced growth rate in response to treatment. This pilot study highlights the importance of detailed stone diagnostics and could be of therapeutic relevance in calcium-oxalates urolithiasis, provided that the effects of treatment can be reproduced in subsequent larger studies. PMID:23940605

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.

Primary hyperoxaluria type 1 and brachydactyly mental retardation syndrome caused by a novel mutation in AGXT and a terminal deletion of chromosome 2.

PubMed

Tammachote, Rachaneekorn; Kingsuwannapong, Nelawat; Tongkobpetch, Siraprapa; Srichomthong, Chalurmpon; Yeetong, Patra; Kingwatanakul, Pornchai; Monico, Carla G; Suphapeetiporn, Kanya; Shotelersuk, Vorasuk

2012-09-01

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder caused by mutations in the alanine:glyoxylate aminotransferase (AGXT) gene, located on chromosome 2q37. Mutant AGXT leads to excess production and excretion of oxalate, resulting in accumulation of calcium oxalate in the kidney, and progressive loss of renal function. Brachydactyly mental retardation syndrome (BDMR) is an autosomal dominant disorder, caused by haploinsufficiency of histone deacetylase 4 (HDAC4), also on chromosome 2q37. It is characterized by skeletal abnormalities and developmental delay. Here, we report on a girl who had phenotypes of both PH1 and BDMR. PCR-sequencing of the coding regions of AGXT showed a novel missense mutation, c.32C>G (p.Pro11Arg) inherited from her mother. Functional analyses demonstrated that it reduced the enzymatic activity to 31% of the wild-type and redirected some percentage of the enzyme away from the peroxisome. Microsatellite and array-CGH analyses indicated that the proband had a paternal de novo telomeric deletion of chromosome 2q, which included HDAC4. To our knowledge, this is the first report of PH1 and BDMR, with a novel AGXT mutation and a de novo telomeric deletion of chromosome 2q. Copyright © 2012 Wiley Periodicals, Inc.

A Novel Mutation of Human Liver Alanine:Glyoxylate Aminotransferase Causes Primary Hyperoxaluria Type 1: Immunohistochemical Quantification and Subcellular Distribution

PubMed Central

Kawai, Chikage; Minatogawa, Yohsuke; Akiyoshi, Hidetaka; Hirose, Shinichi; Suehiro, Tsunatoshi; Tone, Shigenobu

2012-01-01

A novel alanine:glyoxylate aminotransferase (AGT) mutation involved in primary hyperoxaluria type 1 (PH1) was studied in Japanese patients. Two mutations in exon 7, c.751T>A and c.752G>A, lead to a W251K amino acid substitution. Proband 1 (patient 1) was homozygous for the W251K mutation allele (DDBJ Accession No. AB292648), and AGT-specific activity in the patient’s liver was very low. To reveal the cause of the low enzymatic activity, the intracellular localization of AGT (W251K) was studied using immunohistochemistry and immunoelectron microscopy. The latter analysis showed that patient 2 had only one-fifth of the normal AGT expression per catalase, suggesting impairment of AGT (W251K) dependent transport into peroxisomes. Peroxisomal transport of human AGT is believed to be dependent on the presence of the type 1 peroxisomal targeting sequence. The C-terminal tripeptide of AGT, KKL is necessary for peroxisomal targeting. In cultured cells, EGFP-AGT (W251K) localized both in the peroxisome and cytosol. These results were consistent with the data obtained from liver analysis of patient 2. The subcellular distribution of AGT (W251K) and the results from a random mutagenesis study suggest that KKL is necessary for peroxisomal targeting of human AGT, but additional signal other than KKL may be necessary. PMID:22685354

Inhibition of Glycolate Oxidase With Dicer-substrate siRNA Reduces Calcium Oxalate Deposition in a Mouse Model of Primary Hyperoxaluria Type 1

PubMed Central

Dutta, Chaitali; Avitahl-Curtis, Nicole; Pursell, Natalie; Larsson Cohen, Marita; Holmes, Benjamin; Diwanji, Rohan; Zhou, Wei; Apponi, Luciano; Koser, Martin; Ying, Bo; Chen, Dongyu; Shui, Xue; Saxena, Utsav; Cyr, Wendy A; Shah, Anee; Nazef, Naim; Wang, Weimin; Abrams, Marc; Dudek, Henryk; Salido, Eduardo; Brown, Bob D; Lai, Chengjung

2016-01-01

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive, metabolic disorder caused by mutations of alanine-glyoxylate aminotransferase (AGT), a key hepatic enzyme in the detoxification of glyoxylate arising from multiple normal metabolic pathways to glycine. Accumulation of glyoxylate, a precursor of oxalate, leads to the overproduction of oxalate in the liver, which accumulates to high levels in kidneys and urine. Crystalization of calcium oxalate (CaOx) in the kidney ultimately results in renal failure. Currently, the only treatment effective in reduction of oxalate production in patients who do not respond to high-dose vitamin B6 therapy is a combined liver/kidney transplant. We explored an alternative approach to prevent glyoxylate production using Dicer-substrate small interfering RNAs (DsiRNAs) targeting hydroxyacid oxidase 1 (HAO1) mRNA which encodes glycolate oxidase (GO), to reduce the hepatic conversion of glycolate to glyoxylate. This approach efficiently reduces GO mRNA and protein in the livers of mice and nonhuman primates. Reduction of hepatic GO leads to normalization of urine oxalate levels and reduces CaOx deposition in a preclinical mouse model of PH1. Our results support the use of DsiRNA to reduce liver GO levels as a potential therapeutic approach to treat PH1. PMID:26758691

Molecular aetiology of primary hyperoxaluria type 1.

PubMed

Danpure, Christopher J

2004-01-01

Primary hyperoxaluria type 1 (PH1) is a rare autosomal-recessive disorder, caused by a deficiency of the liver-specific intermediary-metabolic enzyme alanine:glyoxylate aminotransferase (AGT). AGT deficiency results in increased synthesis and excretion of the metabolic end-product oxalate and the deposition of insoluble calcium oxalate in the kidney and urinary tract. Numerous mutations and polymorphisms have been identified in the gene (AGXT) that encodes AGT, some of which interact synergistically to cause a variety of complex enzyme phenotypes, including AGT intraperoxisomal aggregation, accelerated degradation, and peroxisome-to-mitochondrion mistargeting. The latter is the single most common cause of PH1 and results from the functional interaction between a common Pro11Leu polymorphism and a disease-specific Gly170Arg mutation. The recent solution of the crystal structure of AGT has enabled the effects of several mutations and polymorphisms to be rationalised in terms of their likely effects on AGT conformation. Increased understanding of the molecular aetiology of PH1 has led to significant improvements in all aspects of the clinical management of the disorder, including diagnosis (by enzyme assay of percutaneous needle liver biopsies), prenatal diagnosis (by DNA analysis of chorionic villus samples) and treatment (by liver transplantation as a form of enzyme replacement therapy). Copyright (c) 2004 S. Karger AG, Basel.

Primary hyperoxaluria type 1 in 18 children: genotyping and outcome.

PubMed

Al Riyami, Mohamed S; Al Ghaithi, Badria; Al Hashmi, Nadia; Al Kalbani, Naifain

2015-01-01

Background. Primary hyperoxaluria belongs to a group of rare metabolic disorders with autosomal recessive inheritance. It results from genetic mutations of the AGXT gene, which is more common due to higher consanguinity rates in the developing countries. Clinical features at presentation are heterogeneous even in children from the same family; this study was conducted to determine the clinical characteristics, type of AGXT mutation, and outcome in children diagnosed with PH1 at a tertiary referral center in Oman. Method. Retrospective review of children diagnosed with PH1 at a tertiary hospital in Oman from 2000 to 2013. Result. Total of 18 children were identified. Females composed 61% of the children with median presentation age of 7 months. Severe renal failure was initial presentation in 39% and 22% presented with nephrocalcinosis and/or renal calculi. Family screening diagnosed 39% of patients. Fifty percent of the children underwent hemodialysis. 28% of children underwent organ transplantation. The most common mutation found in Omani children was c.33-34insC mutation in the AGXT gene. Conclusion. Due to consanguinity, PH1 is a common cause of ESRD in Omani children. Genetic testing is recommended to help in family counseling and helps in decreasing the incidence and disease burden; it also could be utilized for premarital screening.

[From gene to disease; primary hyperoxaluria type I caused by mutations in the AGXT gene].

PubMed

van Woerden, C S; Groothof, J W; Wanders, R J A; Waterham, H R; Wijburg, F R

2006-07-29

Primary hyperoxaluria type I (PH1) is a congenital defect in glyoxylate metabolism caused by a deficiency in the liver-specific peroxisomal enzyme known as alanine glyoxylate aminotransferase (AGT). The deficiency is due to mutations in the AGXT gene, located on chromosome 2q37.3, and results in the conversion of glyoxylate to oxalate. The crystallisation of oxalate with calcium results in symptoms varying from a solitary kidney stone to end-stage renal disease with systemic oxalosis. The diagnosis is based on increased oxalate and glycolate excretion in the urine, reduced AGT activity in liver tissue, and confirmed mutations in the AGXT gene. Over 50 disease-causing mutations have been identified in PH1, which are associated with a wide range of effects on the AGT enzyme. Homozygous Gly170Arg or Phei52Ile mutations are associated with a reduction in urinary oxalate excretion upon pyridoxine administration and long-term preservation of renal function when treatment is initiated in a timely manner. Homozygous 33insC and Gly82Arg mutations result in a much poorer prognosis. Mutational analysis of the AGXT gene in PH1 patients can be a useful tool for establishing the diagnosis and choosing an appropriate therapeutic strategy.

Primary Hyperoxaluria Type 1 in 18 Children: Genotyping and Outcome

PubMed Central

Al Riyami, Mohamed S.; Al Ghaithi, Badria; Al Hashmi, Nadia; Al Kalbani, Naifain

2015-01-01

Background. Primary hyperoxaluria belongs to a group of rare metabolic disorders with autosomal recessive inheritance. It results from genetic mutations of the AGXT gene, which is more common due to higher consanguinity rates in the developing countries. Clinical features at presentation are heterogeneous even in children from the same family; this study was conducted to determine the clinical characteristics, type of AGXT mutation, and outcome in children diagnosed with PH1 at a tertiary referral center in Oman. Method. Retrospective review of children diagnosed with PH1 at a tertiary hospital in Oman from 2000 to 2013. Result. Total of 18 children were identified. Females composed 61% of the children with median presentation age of 7 months. Severe renal failure was initial presentation in 39% and 22% presented with nephrocalcinosis and/or renal calculi. Family screening diagnosed 39% of patients. Fifty percent of the children underwent hemodialysis. 28% of children underwent organ transplantation. The most common mutation found in Omani children was c.33-34insC mutation in the AGXT gene. Conclusion. Due to consanguinity, PH1 is a common cause of ESRD in Omani children. Genetic testing is recommended to help in family counseling and helps in decreasing the incidence and disease burden; it also could be utilized for premarital screening. PMID:25918646

Primary hyperoxaluria type I: a model for multiple mutations in a monogenic disease within a distinct ethnic group.

PubMed

Rinat, C; Wanders, R J; Drukker, A; Halle, D; Frishberg, Y

1999-11-01

Primary hyperoxaluria type 1 is an autosomal recessive inherited metabolic disease in which excessive oxalates are formed by the liver and excreted by the kidneys, causing a wide spectrum of phenotypes ranging from renal failure in infancy to mere renal stones in late adulthood. Mutations in the AGXT gene, encoding the liver-specific enzyme alanine:glyoxylate aminotransferase, are responsible for the disease. Seven mutations were detected in eight families in Israel. Four of these mutations are novel and three occur in children living in single-clan villages. The mutations are scattered along various exons (1, 4, 5, 7, 9, 10), and on different alleles comprising at least five different haplotypes. All but one of the mutations are in a homozygous pattern, reflecting the high rate of consanguinity in our patient population. Two affected brothers are homozygous for two different mutations expressed on the same allele. The patients comprise a distinct ethnic group (Israeli Arabs) residing in a confined geographic area. These results, which are supported by previous data, suggest for the first time that the phenomenon of multiple mutations in a relatively closed isolate is common and almost exclusive to the Israeli-Arab population. Potential mechanisms including selective advantage to heterozygotes, digenic inheritance, and the recent emergence of multiple mutations are discussed.

Primary hyperoxaluria type 1: update and additional mutation analysis of the AGXT gene.

PubMed

Williams, Emma L; Acquaviva, Cecile; Amoroso, Antonio; Chevalier, Francoise; Coulter-Mackie, Marion; Monico, Carla G; Giachino, Daniela; Owen, Tricia; Robbiano, Angela; Salido, Eduardo; Waterham, Hans; Rumsby, Gill

2009-06-01

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive, inherited disorder of glyoxylate metabolism arising from a deficiency of the alanine:glyoxylate aminotransferase (AGT) enzyme, encoded by the AGXT gene. The disease is manifested by excessive endogenous oxalate production, which leads to impaired renal function and associated morbidity. At least 146 mutations have now been described, 50 of which are newly reported here. The mutations, which occur along the length of the AGXT gene, are predominantly single-nucleotide substitutions (75%), 73 are missense, 19 nonsense, and 18 splice mutations; but 36 major and minor deletions and insertions are also included. There is little association of mutation with ethnicity, the most obvious exception being the p.Ile244Thr mutation, which appears to have North African/Spanish origins. A common, polymorphic variant encoding leucine at codon 11, the so-called minor allele, has significantly lower catalytic activity in vitro, and has a higher frequency in PH1 compared to the rest of the population. This polymorphism influences enzyme targeting in the presence of the most common Gly170Arg mutation and potentiates the effect of several other pathological sequence variants. This review discusses the spectrum of AGXT mutations and polymorphisms, their clinical significance, and their diagnostic relevance.

Primary hiperoxaluria diagnosed after kidney transplantation: report of 2 cases and literature review.

PubMed

Rios, John Fredy Nieto; Zuluaga, Monica; Higuita, Lina Maria Serna; Florez, Adriana; Bello-Marquez, Diana Carolina; Aristizábal, Arbey; Kohn, Catalina Ocampo; Zuluaga, Gustavo Adolfo

2017-01-01

Primary hyperoxaluria (PH) is a very rare genetic disorder; it is characterized by total or partial deficiency of the enzymes related to the metabolism of glyoxylate, with an overproduction of calcium oxalate that is deposited in different organs, mainly the kidney, leading to recurrent lithiasis, nephrocalcinosis and end stage renal disease (ESRD). In patients with ESRD that receive kidney transplantation alone, the disease has a relapse of 100%, with graft loss in a high percentage of patients in the first 5 years of transplantation. Three molecular disorders have been described in PH: mutation of the gene alanin glioxalate aminotransferase (AGXT); glyoxalate reductase/hydroxy pyruvate reductase (GRHPR) and 4-OH-2-oxoglutarate aldolase (HOGA1). We present two cases of patients with a history of renal lithiasis who were diagnosed with primary hyperoxaluria in the post-transplant period, manifested by early graft failure, with evidence of calcium oxalate crystals in renal biopsy, hyperoxaluria, hyperoxalemia, and genetic test compatible; they were managed with proper diet, abundant oral liquids, pyridoxine, hydrochlorothiazide and potassium citrate; however, they had slow but progressive deterioration of their grafts function until they reached end-stage chronic renal disease.

Clinical spectrum of primary hyperoxaluria type 1: Experience of a tertiary center.

PubMed

Soliman, Neveen A; Nabhan, Marwa M; Abdelrahman, Safaa M; Abdelaziz, Hanan; Helmy, Rasha; Ghanim, Khaled; Bazaraa, Hafez M; Badr, Ahmed M; Tolba, Omar A; Kotb, Magd A; Eweeda, Khaled M; Fayez, Alaa

2017-05-01

Primary hyperoxalurias are rare inborn errors of metabolism resulting in increased endogenous production of oxalate that leads to excessive urinary oxalate excretion. Diagnosis of primary hyperoxaluria type 1 (PH1) is a challenging issue and depends on diverse diagnostic tools including biochemical analysis of urine, stone analysis, renal biopsy, genetic studies and in some cases liver biopsy for enzyme assay. We characterized the clinical presentation as well as renal and extrarenal phenotypes in PH1 patients. This descriptive cohort study included patients with presumable PH1 presenting with nephrolithiasis and/or nephrocalcinosis (NC). Precise clinical characterization of renal phenotype as well as systemic involvement is reported. AGXT mutational analysis was performed to confirm the diagnosis of PH1. The study cohort included 26 patients with presumable PH1 with male to female ratio of 1.4:1. The median age at time of diagnosis was 6 years, nevertheless the median age at initial symptoms was 3 years. Thirteen patients (50%) were diagnosed before the age of 5 years. Two patients had no symptoms and were diagnosed while screening siblings of index patients. Seventeen patients (65.4%) had reached end-stage renal disease (ESRD): 6/17 (35.3%) during infancy, 4/17 (23.5%) in early childhood and 7/17 (41.29%) in late childhood. Two patients (7.7%) had clinically manifest extra renal (retina, heart, bone, soft tissue) involvement. Mutational analysis of AGXT gene confirmed the diagnosis of PH1 in 15 out of 19 patients (79%) where analysis had been performed. Fifty percent of patients with maintained renal functions had projected 10 years renal survival. PH1 is a heterogeneous disease with wide spectrum of clinical, imaging and functional presentation. More than two-thirds of patients presented prior to the age of 5 years; half of them with the stormy course of infantile PH1. ESRD was the commonest presenting manifestation in two-thirds of our cohort. Copyright © 2016 Association Société de néphrologie. Published by Elsevier Masson SAS. All rights reserved.

Bilateral native nephrectomy to reduce oxalate stores in children at the time of combined liver-kidney transplantation for primary hyperoxaluria type 1.

PubMed

Lee, Eliza; Ramos-Gonzalez, Gabriel; Rodig, Nancy; Elisofon, Scott; Vakili, Khashayar; Kim, Heung Bae

2018-05-01

Primary hyperoxaluria type-1 (PH-1) is a rare genetic disorder in which normal hepatic metabolism of glyoxylate is disrupted resulting in diffuse oxalate deposition and end-stage renal disease (ESRD). While most centers agree that combined liver-kidney transplant (CLKT) is the appropriate treatment for PH-1, perioperative strategies for minimizing recurrent oxalate-related injury to the transplanted kidney remain unclear. We present our management of children with PH-1 and ESRD on hemodialysis (HD) who underwent CLKT at our institution from 2005 to 2015. On chart review, three patients (2 girls, 1 boy) met study criteria. Two patients received deceased-donor split-liver grafts, while one patient received a whole liver graft. All patients underwent bilateral native nephrectomy at transplant to minimize the total body oxalate load. Median preoperative serum oxalate was 72 μmol/L (range 17.8-100). All patients received HD postoperatively until predialysis serum oxalate levels fell <20 μmol/L. All patients, at a median of 7.5 years of follow-up (range 6.5-8.9), demonstrated stable liver and kidney function. While CLKT remains the definitive treatment for PH-1, bilateral native nephrectomy at the time of transplant reduces postoperative oxalate stores and may mitigate damage to the renal allograft.

Two novel AGXT mutations identified in primary hyperoxaluria type-1 and distinct morphological and structural difference in kidney stones

PubMed Central

Wang, Cui; Lu, Jingru; Lang, Yanhua; Liu, Ting; Wang, Xiaoling; Zhao, Xiangzhong; Shao, Leping

2016-01-01

Primary hyperoxaluria type 1 (PH1) is a rare genetic disease characterized by excessive oxalate accumulation in plasma and urine, resulting in various phenotypes because of allelic and clinical heterogeneity. This study aimed to detect disease-associated genetic mutations in three PH1 patients in a Chinese family. All AGXT exons and 3 common polymorphisms which might synergistically interact with mutations, including P11L, I340 M and IVSI+74 bp were analyzed by direct sequencing in all family members. It demonstrated that in each of three patients, a previously reported nonsense mutation p.R333* was in cis with a novel missense mutation p.M49L in the minor allele characterized by the polymorphism of 74-bp duplication in intron 1, while the other novel missense mutation p.N72I was in trans with both p.R333* and P.M49L in the major allele. Kidney stones from two sibling patients were also observed though stereomicroscopic examination and scanning electron microscopy. Distinct morphological and inner-structure differences in calculi were noticed, suggesting clinical heterozygosity of PH1 to a certain extent. In brief, two novel missense mutations were identified probably in association with PH1, a finding which should provide an accurate tool for prenatal diagnosis, genetic counseling and screening for potential presymptomatic individuals. PMID:27644547

Mutation spectrum of primary hyperoxaluria type 1 in Tunisia: implication for diagnosis in North Africa.

PubMed

Nagara, Majdi; Tiar, Afaf; Ben Halim, Nizar; Ben Rhouma, Faten; Messaoud, Olfa; Bouyacoub, Yosra; Kefi, Rym; Hassayoun, Saida; Zouari, Noura; Ben Ammar, Mohamed Slim; Abdelhak, Sonia; Chemli, Jalel

2013-09-15

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive inherited metabolic disease, characterized by progressive kidney failure due to renal deposition of calcium oxalate. Mutations in the AGXT gene, encoding the liver-specific enzyme alanine glyoxylate aminotransferase, are responsible for the disease. We aimed to determine the mutational spectrum causing PH1 and to provide an accurate tool for diagnosis as well as for prenatal diagnosis in the affected families. Direct sequencing was used to detect mutations in the AGXT gene in DNA samples from 13 patients belonging to 12 Tunisian families. Molecular analysis revealed five mutations causing PH1 in Tunisia. The mutations were identified along exons 1, 2, 4, 5 and 7. The most predominant mutations were the Maghrebian "p.I244T" and the Arabic "p.G190R". Furthermore, three other mutations characteristic of different ethnic groups were found in our study population. These results confirm the mutational heterogeneity related to PH1 in Tunisian population. All the mutations are in a homozygous state, reflecting the high impact of endogamy in our population. Mutation analysis through DNA sequencing can provide a useful first line investigation for PH1. This identification could provide an accurate tool for prenatal diagnosis, genetic counseling and screen for potential presymptomatic individuals. © 2013 Elsevier B.V. All rights reserved.

Unusual clinical outcome of primary Hyperoxaluria type 1 in Tunisian patients carrying 33_34InsC mutation.

PubMed

Mbarek, Ibtihel Benhaj; Mdimeg, Saoussen; Moussa, Amira; Zellama, Dorsaf; Kaarout, Hayat; Abdelmoula, Jaouida; Achour, Abdellatif; Abroug, Saoussen; Omezzine, Asma; Bouslama, Ali

2017-06-15

Primary hyperoxaluria type 1 (PH1), is a rare and heterogeneous disease and one of major causes of renal insufficiency in Tunisia, caused by mutations in the AGXT gene. 33-34InsC mutation, was mainly described in children with a severe clinical feature leading to early death, but it was uncommonly reported in adult patients. Common mutations in AGXT were tested using PCR/RFLP technique in 111 patients (68 adult, 43 children) with suspected PH1. We described 16 cases (eight adult and eight children) with a 33-34InsC mutation with a median age of 24 years [6 months - 73 years]. All children were in end stage renal disease (ESRD) at the median age of 3 years due to lithiasis and/or nephrocalcinosis. Unfortunately, 75% of them died with a median age of 2.5 years. For the majority of adults only spontaneous elimination of urolithiasis were noted, 37.5% preserved until now a normal renal function and 62.5% of them reached ESRD at the median age of 55.8 ± 12.31 years old. In this study 33-34InsC mutation gives a controversial clinical effect in children and adults. The implication of other genetic and/or environmental factors can play a crucial role in determining the ultimate phenotype.

Primary hyperoxaluria type 1: a cluster of new mutations in exon 7 of the AGXT gene.

PubMed

von Schnakenburg, C; Rumsby, G

1997-06-01

Primary hyperoxaluria type 1 (PH1) is a severe autosomal recessive inborn error of glyoxylate metabolism caused by deficiency of the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase. This enzyme is encoded by the AGXT gene on chromosome 2q37.3. DNA samples from 79 PH1 patients were studied using single strand conformation polymorphism analysis to detect sequence variants, which were then characterised by direct sequencing and confirmed by restriction enzyme digestion. Four novel mutations were identified in exon 7 of AGXT: a point mutation T853C, which leads to a predicted Ile244Thr amino acid substitution, occurred in nine patients. Two other mutations in adjacent nucleotides, C819T and G820A, mutated the same codon at residue 233 from arginine to cysteine and histidine, respectively. The fourth mutation, G860A, introduced a stop codon at amino acid residue 246. Enzyme studies in these patients showed that AGT catalytic activity was either very low or absent and that little or no immunoreactive protein was present. Together with a new polymorphism in exon 11 (C1342A) these findings underline the genetic heterogeneity of the AGXT gene. The novel mutation T853C is the second most common mutation found to date with an allelic frequency of 9% and will therefore be of clinical importance for the diagnosis of PH1.

Sustained Pyridoxine Response in Primary Hyperoxaluria Type 1 Recipients of Kidney Alone Transplant

PubMed Central

Lorenz, Elizabeth C; Lieske, John C; Seide, Barbara M; Meek, Alicia M; Olson, Julie B; Bergstralh, Eric J; Milliner, Dawn S

2015-01-01

Combined kidney liver transplant is the preferred transplant option for most patients with primary hyperoxaluria type 1 (PH1) given that it removes the hepatic source of oxalate production and improves renal allograft survival. However, PH1 patients homozygous for the G170R mutation can develop normal urine oxalate levels with pyridoxine therapy and may be candidates for kidney alone transplant. We examined the efficacy of pyridoxine therapy following kidney alone transplant in five patients homozygous for G170R transplanted between 9/1999 and 7/2013. All patients were maintained on pyridoxine post-transplant. Median age at transplant was 39 years (range 33–67 years). Median follow-up post-transplant was 8.5 years (range 0.2–13.9 years). At the end of follow-up, 4 grafts were functioning. One graft failed 13.9 years post-transplant due to recurrent oxalate nephropathy following an acute medical illness. After tissue oxalate stores had cleared, post-transplant urine oxalate levels were < 0.5 mmol/24 hr the majority of times checked. Calcium oxalate crystals were noted in only 3/13 allograft biopsies. This series suggests that a subgroup of PH1 patients demonstrate sustained response to pyridoxine therapy following kidney alone transplant. Therefore, pyridoxine combined with kidney alone transplantation should be considered for PH1 patients with a homozygous G170R mutation. PMID:24797341

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.

A glycine-to-glutamate substitution abolishes alanine:glyoxylate aminotransferase catalytic activity in a subset of patients with primary hyperoxaluria type 1.

PubMed

Purdue, P E; Lumb, M J; Allsop, J; Minatogawa, Y; Danpure, C J

1992-05-01

We have synthesized and sequenced alanine:glyoxylate aminotransferase (AGT; HGMW-approved symbol for the gene--AGXT) cDNA from the liver of a primary hyperoxaluria type 1 (PH1) patient who had normal levels of hepatic peroxisomal immunoreactive AGT protein, but no AGT catalytic activity. This revealed the presence of a single point mutation (G----A at cDNA nucleotide 367), which is predicted to cause a glycine-to-glutamate substitution at residue 82 of the AGT protein. This mutation is located in exon 2 of the AGT gene and leads to the loss of an AvaI restriction site. Exon 2-specific PCR followed by AvaI digestion showed that this patient was homozygous for this mutation. In addition, three other PH1 patients, one related to and two unrelated to, but with enzymological phenotype similar to that of the first patient, were also shown to be homozygous for the mutation. However, one other phenotypically similar PH1 patient was shown to lack this mutation. The mechanism by which the glycine-to-glutamate substitution at residue 82 causes loss of catalytic activity remains to be resolved. However, the protein sequence in this region is highly conserved between different mammals, and the substitution at residue 82 is predicted to cause significant local structural alterations.

Molecular aetiology of primary hyperoxaluria and its implications for clinical management.

PubMed

Danpure, Christopher J; Rumsby, Gill

2004-01-09

The primary hyperoxalurias type 1 (PH1) and type 2 (PH2) are autosomal recessive calcium oxalate kidney stone diseases caused by deficiencies of the metabolic enzymes alanine:glyoxylate aminotransferase (AGT) and glyoxylate/hydroxypyruvate reductase (GR/HPR), respectively. Over 50 mutations have been identified in the AGXT gene (encoding AGT) in PH1, associated with a wide variety of effects on AGT, including loss of catalytic activity, aggregation, accelerated degradation, and peroxisome-to-mitochondrion mistargeting. Some of these mutations segregate and interact synergistically with a common polymorphism. Over a dozen mutations have been found in the GRHPR gene (encoding GR/HPR) in PH2, all associated with complete loss of glyoxylate reductase enzyme activity and immunoreactive protein. The crystal structure of human AGT, but not human GR/HPR, has been solved, allowing the effects of many of the mutations in PH1 to be rationalised in structural terms. Detailed analysis of the molecular aetiology of PH1 and PH2 has led to significant improvements in all aspects of their clinical management. Enzyme replacement therapy by liver transplantation can provide a metabolic cure for PH1, but it has yet to be tried for PH2. New treatments that aim to counter the effects of specific mutations on the properties of the enzymes could be feasible in the not-too-distant future.

Primary hyperoxaluria type 1: a cluster of new mutations in exon 7 of the AGXT gene.

PubMed Central

von Schnakenburg, C; Rumsby, G

1997-01-01

Primary hyperoxaluria type 1 (PH1) is a severe autosomal recessive inborn error of glyoxylate metabolism caused by deficiency of the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase. This enzyme is encoded by the AGXT gene on chromosome 2q37.3. DNA samples from 79 PH1 patients were studied using single strand conformation polymorphism analysis to detect sequence variants, which were then characterised by direct sequencing and confirmed by restriction enzyme digestion. Four novel mutations were identified in exon 7 of AGXT: a point mutation T853C, which leads to a predicted Ile244Thr amino acid substitution, occurred in nine patients. Two other mutations in adjacent nucleotides, C819T and G820A, mutated the same codon at residue 233 from arginine to cysteine and histidine, respectively. The fourth mutation, G860A, introduced a stop codon at amino acid residue 246. Enzyme studies in these patients showed that AGT catalytic activity was either very low or absent and that little or no immunoreactive protein was present. Together with a new polymorphism in exon 11 (C1342A) these findings underline the genetic heterogeneity of the AGXT gene. The novel mutation T853C is the second most common mutation found to date with an allelic frequency of 9% and will therefore be of clinical importance for the diagnosis of PH1. Images PMID:9192270

Two novel AGXT mutations identified in primary hyperoxaluria type-1 and distinct morphological and structural difference in kidney stones.

PubMed

Wang, Cui; Lu, Jingru; Lang, Yanhua; Liu, Ting; Wang, Xiaoling; Zhao, Xiangzhong; Shao, Leping

2016-09-20

Primary hyperoxaluria type 1 (PH1) is a rare genetic disease characterized by excessive oxalate accumulation in plasma and urine, resulting in various phenotypes because of allelic and clinical heterogeneity. This study aimed to detect disease-associated genetic mutations in three PH1 patients in a Chinese family. All AGXT exons and 3 common polymorphisms which might synergistically interact with mutations, including P11L, I340 M and IVSI+74 bp were analyzed by direct sequencing in all family members. It demonstrated that in each of three patients, a previously reported nonsense mutation p.R333(*) was in cis with a novel missense mutation p.M49L in the minor allele characterized by the polymorphism of 74-bp duplication in intron 1, while the other novel missense mutation p.N72I was in trans with both p.R333(*) and P.M49L in the major allele. Kidney stones from two sibling patients were also observed though stereomicroscopic examination and scanning electron microscopy. Distinct morphological and inner-structure differences in calculi were noticed, suggesting clinical heterozygosity of PH1 to a certain extent. In brief, two novel missense mutations were identified probably in association with PH1, a finding which should provide an accurate tool for prenatal diagnosis, genetic counseling and screening for potential presymptomatic individuals.

The clinical pattern of primary hyperoxaluria in pediatric patient at Queen Rania Abdulla Children Hospital.

PubMed

Almardini, Reham I; Alfarah, Mahdi G; Salaita, Ghazi M

2014-05-01

Hyperoxaluria is a metabolic disorder that can lead to end stage renal disease (ESRD). It can be either inherited or acquired. Primary hyperoxaluria (PHO) is more common and characterized by an excessive production of oxalate leading to recurrent urolithiasis and progressive nephrocalcinosis. Due to the high rate of consanguineous marriage in Jordan this disease is commonly diagnosed in pediatric nephrology clinics. We aimed to demonstrate the clinical pattern and progression to ESRD in pediatric patients with hyperoxaluria at Queen Rania Abdulla Children Hospital. Medical records of all patients followed up in the pediatric nephrology clinic with the diagnosis of PHO during the period between September 2007 and March 2013 were reviewed. There were 70 patients with the diagnosis of PHO, 52.9% were males. The median age at presentation was 3 years ± 3 months with the youngest child being two months old. Diagnosis was made in the first year of life in 15.7% of patients. The most common presenting symptom was hematuria, while 14% of patients were asymptomatic and detected by family screening after the diagnosis of an index case. At the time of initial presentation, 15.7% of patients had ESRD and 25% had impaired renal function. Kidney stones were found in 57% of cases and nephrocalcinosis was found in 37%. High index of suspicion is needed to diagnose PHO in children presenting with kidney stone or unexplained hematuria. Twenty-four hour urine collection for oxalate are required to make the proper diagnosis. Family screening, when appropriate, is indicated for early detection of PHO.

Updated genetic testing of Italian patients referred with a clinical diagnosis of primary hyperoxaluria.

PubMed

Pelle, Alessandra; Cuccurullo, Alessandra; Mancini, Cecilia; Sebastiano, Regina; Stallone, Giovanni; Negrisolo, Susanna; Benetti, Elisa; Peruzzi, Licia; Petrarulo, Michele; De Marchi, Mario; Marangella, Martino; Amoroso, Antonio; Giachino, Daniela; Mandrile, Giorgia

2017-04-01

Primary hyperoxaluria (PH) is a rare autosomal recessive disease commonly arising in childhood and presenting with nephrolithiasis, nephrocalcinosis and/or chronic renal failure. Three genes are currently known as responsible: alanine-glyoxylate aminotransferase (AGXT, PH type 1), glyoxylate reductase/hydroxypyruvate reductase (GRHPR, PH type 2), and 4-hydroxy-2-oxoglutarate aldolase (HOGA1, PH type 3). In our Centre, at the end of 2014 molecular diagnosis of PH1 had been performed in 80 patients, while one patient received a PH2 diagnosis. Fifteen patients referred to our Centre and suspected to have PH on clinical grounds were negative for pathogenic variants in the entire coding sequence and exon-intron boundaries of the AGXT gene. Therefore, we extended the analysis to the AGXT promoter region and the GRHPR and HOGA1 genes. Two patients were heterozygous for two novel AGXT-promoter variants (c.-647C > T, c.-424C > T) that were probably non pathogenic. One patient was homozygous for a novel HOGA1 variant of intron 2 (c.341-81delT), whose pathogenicity predicted by in silico splicing tools was not confirmed by a minigene splicing assay in COS-7 and HEK293T cells. New genetic subtypes of PH can be hypothesized in our patients, that may be caused by mutations in other gene encoding proteins of glyoxylate metabolism. Alternatively, some kind of mutations (e.g., deletions/duplications, deep intronic splicing regulatory variants) could be missed in a few cases, similarly to other genetic diseases.

Transplantation outcomes in primary hyperoxaluria.

PubMed

Bergstralh, E J; Monico, C G; Lieske, J C; Herges, R M; Langman, C B; Hoppe, B; Milliner, D S

2010-11-01

Optimal transplantation strategies are uncertain in primary hyperoxaluria (PH) due to potential for recurrent oxalosis. Outcomes of different transplantation approaches were compared using life-table methods to determine kidney graft survival among 203 patients in the International Primary Hyperoxaluria Registry. From 1976-2009, 84 kidney alone (K) and combined kidney and liver (K + L) transplants were performed in 58 patients. Among 58 first kidney transplants (32 K, 26 K + L), 1-, 3- and 5-year kidney graft survival was 82%, 68% and 49%. Renal graft loss occurred in 26 first transplants due to oxalosis in ten, chronic allograft nephropathy in six, rejection in five and other causes in five. Delay in PH diagnosis until after transplant favored early graft loss (p = 0.07). K + L had better kidney graft outcomes than K with death-censored graft survival 95% versus 56% at 3 years (p = 0.011). Among 29 year 2000-09 first transplants (24 K + L), 84% were functioning at 3 years compared to 55% of earlier transplants (p = 0.05). At 6.8 years after transplantation, 46 of 58 patients are living (43 with functioning grafts). Outcomes of transplantation in PH have improved over time, with recent K + L transplantation highly successful. Recurrent oxalosis accounted for a minority of kidney graft losses. ©2010 The Authors Journal compilation©2010 The American Society of Transplantation and the American Society of Transplant Surgeons.

Primary hyperoxaluria type 1: diagnostic relevance of mutations and polymorphisms in the alanine:glyoxylate aminotransferase gene (AGXT).

PubMed

Tarn, A C; von Schnakenburg, C; Rumsby, G

1997-09-01

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder of glyoxylate metabolism caused by deficiency of the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). The disease shows considerable phenotypic, enzymatic and genetic heterogeneity. To date, 7 polymorphisms and 11 point mutations have been described in the gene encoding AGT. We report on the prevalence of these polymorphisms and mutations in 79 patients with PH1 with the aim of assessing their diagnostic relevance. A strong association of the C154T, intron 1 insertion and C386T polymorphisms is confirmed and this linkage extends to include the type 1 variant of a polymorphic tandem repeat in intron 4. Only 64 of 158 (40%) PH1 alleles have one of the defined mutations, with the G630A mutation accounting for 39 of these and T853C for 14. Overall only 20 (25%) of the patients studied had the genetic basis of their disease fully explained: 7 were homozygous for the G630A mutation, 5 were homozygous for the T853C mutation, 1 was homozygous for the C819T mutation, and 7 had two different mutations identified and were presumed to be compound heterozygotes. Only the two more frequent G630A and T853C mutations are of general diagnostic relevance for mutation screening. It seems likely that there are a significant number of other mutations, perhaps family-specific, still to be described. There was no apparent difference in the types of mutations in patients presenting in the first year of life (36%), suggesting that other factors, such as periods of dehydration or urinary tract infections, might contribute more to the clinical manifestation than genotype.

AGXT Gene Mutations and Prevalence of Primary Hyperoxaluria Type 1 in Moroccan Population.

PubMed

Boualla, Lamiae; Tajir, Mariam; Oulahiane, Najat; Lyahyai, Jaber; Laarabi, Fatima Zahra; Chafai Elalaoui, Siham; Soulami, Kenza; Ait Ouamar, Hassan; Sefiani, Abdelaziz

2015-11-01

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder caused by deficiency of alanine glyoxylate aminotransferase, due to a defect in the AGXT gene. Several mutations in this gene have been reported and some of them have been observed in multiple populations. The aim of our study was to analyze the mutations causing PH1 in the Moroccan population and to estimate its prevalence in Morocco. Molecular studies of 29 unrelated Moroccan patients with PH were performed by direct sequencing of all exons of the AGXT gene. In addition, to estimate the prevalence of PH1, we screened for the recurrent p.Ile244Thr mutation in 250 unrelated Moroccan newborns using real-time polymerase chain reaction. Four pathogenic mutations were detected in 25 unrelated patients. The c.731T>C (p.Ile244Thr) was the most frequent mutation with a frequency of 84%. The other three mutations were c.33delC, c.976delG, and c.331C>T. The prevalence of the PH1 mutation among Moroccans was then estimated to range from 1/7267 to 1/6264. PH1 is one of the most prevalent genetic diseases in the Moroccan population and is probably underdiagnosed. Front line genetic testing for PH1 in Morocco should be initiated using an assay for the recurrent p.Ile244Thr mutation. This strategy would provide a useful tool for precocious diagnosis of presymptomatic individuals and to prevent their rapid progression to renal failure.

Mutational Analysis of Agxt in Tunisian Population with Primary Hyperoxaluria Type 1.

PubMed

M'dimegh, Saoussen; Omezzine, Asma; M'barek, Ibtihel; Moussa, Amira; Mabrouk, Sameh; Kaarout, Hayet; Souche, Geneviéve; Chemli, Jalel; Aloui, Sabra; Aquaviva-Bourdain, Cécile; Achour, Abdellatif; Abroug, Saoussen; Bouslama, Ali

2017-01-01

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive metabolic disorder caused by inherited mutations in the AGXT gene encoding liver peroxisomal alanine:glyoxylate aminotransferase (AGT). PH1 is a clinically and genetically heterogeneous disorder. The aim of our study was to analyze and characterize the mutational spectrum of PH1 in Tunisian patients. Molecular studies of 146 Tunisian patients suspected with PH were performed by PCR/Restriction fragment length polymorphism (RFLP) to detect seven mutations described as the most common. Direct sequencing for the 11 exons was performed in patients in whom any mutation was not identified. The genetic diagnosis of PH1 was confirmed in 62.3% of patients. The first molecular approach based on PCR/restriction enzyme test was positive in 37.6% of patients, whereas the second molecular approach based on whole gene sequencing was successful in 24% of cases. Twelve pathogenic mutations were detected in our cohort. Two mutations were novel, and five were detected for the first time in Tunisians. The three most frequent mutations were p.Ile244Thr, p.Gly190Arg, and c.33dupC, with a frequency of 43.4%, 21.4%, and 13.1%, respectively. The two novel mutations detected in our study extend the spectrum of known AGXT gene mutations. The screen for the mutations identified in this study can provide a useful, cost-effective, and first-line investigation in Tunisian PH1 patients. © 2016 John Wiley & Sons Ltd/University College London.

HOGA1 Gene Mutations of Primary Hyperoxaluria Type 3 in Tunisian Patients.

PubMed

M'dimegh, Saoussen; Aquaviva-Bourdain, Cécile; Omezzine, Asma; Souche, Geneviéve; M'barek, Ibtihel; Abidi, Kamel; Gargah, Tahar; Abroug, Saoussen; Bouslama, Ali

2017-05-01

Primary hyperoxaluria type 3 (PH3) is due to mutations in the recently identified 4-hydroxy-2-oxoglutarate aldolase (HOGA1) gene. PH3 might be the least severe form with a milder phenotype with good preservation of kidney function in most patients. The aim of this study was to report three PH3 cases carrying mutations in HOGA1. Genetic analysis of HOGA1 was performed in patients with a high clinical suspicion of PH after sequencing of AGXT and GRHPR genes, which was negative. Also, a complete AGXT/GRHPR MLPA was performed in these patients in order to detect large deletions/insertions. Two different HOGA1 gene mutations were identified: the p.Pro190Leu in a homozygous state and the p.Gly287Val in two patients in homozygous and heterozygous carriers. The median age at onset of clinical symptoms was 3.93 years. Most of the patients had a positive family history for recurrent urolithiasis. The p.Pro190Leu mutation was reported with impaired renal function at follow-up; however, the p.Gly287Val was presented with normal renal function. All patients were presented with urolithiasis, but only one had a nephrocalcinosis. This study expanded the number of PH3 patients from 63 to 66 cases. The p.Pro190Leu and the p.Gly287Val mutations found in this study can provide a first-line investigation in Tunisian PH1 patients. © 2016 Wiley Periodicals, Inc.

Effect of conservative treatment on the renal outcome of children with primary hyperoxaluria type 1.

PubMed

Fargue, Sonia; Harambat, Jérôme; Gagnadoux, Marie-France; Tsimaratos, Michel; Janssen, Françoise; Llanas, Brigitte; Berthélémé, Jean-Pierre; Boudailliez, Bernard; Champion, Gérard; Guyot, Claude; Macher, Marie-Alice; Nivet, Hubert; Ranchin, Bruno; Salomon, Rémi; Taque, Sophie; Rolland, Marie-Odile; Cochat, Pierre

2009-10-01

Primary hyperoxaluria type 1 results from alanine:glyoxylate aminotransferase deficiency. Due to genotype/phenotype heterogeneity in this autosomal recessive disorder, the renal outcome is difficult to predict in these patients and the long-term impact of conservative management in children is unknown. We report here a multicenter retrospective study on the renal outcome in 27 affected children whose biological diagnosis was based on either decreased enzyme activity or identification of mutations in the patient or his siblings. The median age at first symptoms was 2.4 years while that at initiation of conservative treatment was 4.1 years; 6 children were diagnosed upon family screening. The median follow-up was 8.7 years. At diagnosis, 15 patients had an estimated glomerular filtration rate (eGFR) below 90, and 7 children already had stage 2-3 chronic kidney disease. The median baseline eGFR was 74, which rose to 114 with management in the 22 patients who did not require renal replacement therapy. Overall, 20 patients had a stable eGFR, however, 7 exhibited a decline in eGFR of over 20 during the study period. In a Cox regression model, the only variable significantly associated with deterioration of renal function was therapeutic delay with a relative risk of 1.7 per year. Our study strongly suggests that early and aggressive conservative management may preserve renal function of compliant children with this disorder, thereby avoiding dialysis and postponing transplantation.

In vivo oxalate degradation by liposome encapsulated oxalate oxidase in rat model of hyperoxaluria

PubMed Central

Dahiya, Tulika; Pundir, C.S.

2013-01-01

Background & objectives: High level of urinary oxalate substantially increases the risk of hyperoxaluria, a significant risk factor for urolithiasis. The primary goal of this study was to reduce urinary oxalate excretion employing liposome encapsulated oxalate oxidase in animal model. Methods: A membrane bound oxalate oxidase was purified from Bougainvillea leaves. The enzyme in its native form was less effective at the physiological pH of the recipient animal. To increase its functional viability, the enzyme was immobilized on to ethylene maleic anhydride (EMA). Rats were injected with liposome encapsulated EMA- oxalate oxidase and the effect was observed on degradation of oxalic acid. Results: The enzyme was purified to apparent homogeneity with 60-fold purification and 31 per cent yield. The optimum pH of EMA-derivative enzyme was 6.0 and it showed 70 per cent of its optimal activity at pH 7.0. The EMA-bound enzyme encapsulated into liposome showed greater oxalate degradation in 15 per cent casein vitamin B6 deficient fed rats as compared with 30 per cent casein vitamin B6 deficient fed rats and control rats. Interpretation & conclusions: EMA-oxalate oxidase encapsulated liposome caused oxalate degradation in experimental hyperoxaluria indicating that the enzyme could be used as a therapeutic agent in hyperoxaluria leading to urinary stones. PMID:23481063

Hydroxyproline metabolism in mouse models of primary hyperoxaluria

PubMed Central

Holmes, Ross P.; Cramer, Scott D.; Takayama, Tatsuya; Salido, Eduardo

2012-01-01

Primary hyperoxaluria type 1 (PH1) and type 2 (PH2) are rare genetic diseases that result from deficiencies in glyoxylate metabolism. The increased oxalate synthesis that occurs can lead to kidney stone formation, deposition of calcium oxalate in the kidney and other tissues, and renal failure. Hydroxyproline (Hyp) catabolism, which occurs mainly in the liver and kidney, is a prominent source of glyoxylate and could account for a significant portion of the oxalate produced in PH. To determine the sensitivity of mouse models of PH1 and PH2 to Hyp-derived oxalate, animals were fed diets containing 1% Hyp. Urinary excretions of glycolate and oxalate were used to monitor Hyp catabolism and the kidneys were examined to assess pathological changes. Both strains of knockout (KO) mice excreted more oxalate than wild-type (WT) animals with Hyp feeding. After 4 wk of Hyp feeding, all mice deficient in glyoxylate reductase/hydroxypyruvate reductase (GRHPR KO) developed severe nephrocalcinosis in contrast to animals deficient in alanine-glyoxylate aminotransferase (AGXT KO) where nephrocalcinosis was milder and with a lower frequency. Plasma cystatin C measurements over 4-wk Hyp feeding indicated no significant loss of renal function in WT and AGXT KO animals, and significant and severe loss of renal function in GRHPR KO animals after 2 and 4 wk, respectively. These data suggest that GRHPR activity may be vital in the kidney for limiting the conversion of Hyp-derived glyoxylate to oxalate. As Hyp catabolism may make a major contribution to the oxalate produced in PH patients, Hyp feeding in these mouse models should be useful in understanding the mechanisms associated with calcium oxalate deposition in the kidney. PMID:22189945

Hyperoxaluria and Bariatric Surgery

NASA Astrophysics Data System (ADS)

Asplin, John R.

2007-04-01

Bariatric surgery as a means to treat obesity is becoming increasingly common in the United States. An early form of bariatric surgery, the jejunoileal bypass, had to be abandoned in 1980 due to numerous complications, including hyperoxaluria and kidney stones. Current bariatric procedures have not been systematically evaluated to determine if they cause hyperoxaluria. Presented here are data showing that hyperoxaluria is the major metabolic abnormality in patients with bariatric surgery who form kidney stones. Further studies are needed to assess the prevalence of hyperoxaluria in all patients with bariatric surgery.

Genetics Home Reference: primary hyperoxaluria

MedlinePlus

... Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): ... Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): ...

AGXT gene mutations and their influence on clinical heterogeneity of type 1 primary hyperoxaluria.

PubMed

Amoroso, A; Pirulli, D; Florian, F; Puzzer, D; Boniotto, M; Crovella, S; Zezlina, S; Spanò, A; Mazzola, G; Savoldi, S; Ferrettini, C; Berutti, S; Petrarulo, M; Marangella, M

2001-10-01

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder that is caused by a deficiency of alanine: glyoxylate aminotransferase (AGT), which is encoded by a single copy gene (AGXT). Molecular diagnosis was used in conjunction with clinical, biochemical, and enzymological data to evaluate genotype-phenotype correlation. Twenty-three unrelated, Italian PH1 patients were studied, 20 of which were grouped according to severe form of PH1 (group A), adult form (group B), and mild to moderate decrease in renal function (group C). All 23 patients were analyzed by using the single-strand conformation polymorphism technique followed by the sequencing of the 11 AGXT exons. Relevant chemistries, including plasma, urine and dialyzate oxalate and glycolate assays, liver AGT activity, and pyridoxine responsiveness, were performed. Both mutant alleles were found in 21 out of 23 patients, and 13 different mutations were recognized in exons 1, 2, 4, and 10. Normalized AGT activity was lower in the severe form than in the adult form (P < 0.05). Double heterozygous patients presented a lower age at the onset of the disease (P = 0.025), and they were more frequent in group A (75%) than in the group B (14%; P = 0.0406). The T444C mutation was more frequent in the severe form (P < 0.05), and the opposite was observed for G630A (P < 0.05). G630A mutation homozygotes had a higher AGT residual activity (P = 0.00001). This study confirms the allelic heterogeneity of the AGXT, which could to some extent be responsible for the phenotypic heterogeneity in PH1.

Two Novel HOGA1 Splicing Mutations Identified in a Chinese Patient with Primary Hyperoxaluria Type 3.

PubMed

Wang, Xinsheng; Zhao, Xiangzhong; Wang, Xiaoling; Yao, Jian; Zhang, Feifei; Lang, Yanhua; Tuffery-Giraud, Sylvie; Bottillo, Irene; Shao, Leping

2015-01-01

Twenty-six HOGA1 mutations have been reported in primary hyperoxaluria (PH) type 3 (PH3) patients with c.700 + 5G>T accounting for about 50% of the total alleles. However, PH3 has never been described in Asians. A Chinese child with early-onset nephrolithiasis was suspected of having PH. We searched for AGXT, GRHPR and HOGA1 gene mutations in this patient and his parents. All coding regions, including intron-exon boundaries, were analyzed using PCR followed by direct sequence analysis. Two heterozygous mutations not previously described in the literature about HOGA1 were identified (compound heterozygous). One mutation was a successive 2 bp substitution at the last nucleotide of exon 6 and at the first nucleotide of intron 6, respectively (c.834_834 + 1GG>TT), while the other one was a guanine to adenine substitution of the last nucleotide of exon 6 (c.834G>A). Direct sequencing analysis failed to find these mutations in 100 unrelated healthy subjects and the functional role on splicing of both variants found in this study was confirmed by a minigene assay based on the pSPL3 exon trapping vector. In addition, we found a SNP in this family (c.715G>A, p.V239I). There were no mutations detected in AGXT and GRHPR. Two novel HOGA1 mutations were identified in association with PH3. This is the first description and investigation on mutant gene analysis of PH3 in an Asian. © 2015 S. Karger AG, Basel

Specific Inhibition of Hepatic Lactate Dehydrogenase Reduces Oxalate Production in Mouse Models of Primary Hyperoxaluria.

PubMed

Lai, Chengjung; Pursell, Natalie; Gierut, Jessica; Saxena, Utsav; Zhou, Wei; Dills, Michael; Diwanji, Rohan; Dutta, Chaitali; Koser, Martin; Nazef, Naim; Storr, Rachel; Kim, Boyoung; Martin-Higueras, Cristina; Salido, Eduardo; Wang, Weimin; Abrams, Marc; Dudek, Henryk; Brown, Bob D

2018-06-15

Primary hyperoxalurias (PHs) are autosomal recessive disorders caused by the overproduction of oxalate leading to calcium oxalate precipitation in the kidney and eventually to end-stage renal disease. One promising strategy to treat PHs is to reduce the hepatic production of oxalate through substrate reduction therapy by inhibiting liver-specific glycolate oxidase (GO), which controls the conversion of glycolate to glyoxylate, the proposed main precursor to oxalate. Alternatively, diminishing the amount of hepatic lactate dehydrogenase (LDH) expression, the proposed key enzyme responsible for converting glyoxylate to oxalate, should directly prevent the accumulation of oxalate in PH patients. Using RNAi, we provide the first in vivo evidence in mammals to support LDH as the key enzyme responsible for converting glyoxylate to oxalate. In addition, we demonstrate that reduction of hepatic LDH achieves efficient oxalate reduction and prevents calcium oxalate crystal deposition in genetically engineered mouse models of PH types 1 (PH1) and 2 (PH2), as well as in chemically induced PH mouse models. Repression of hepatic LDH in mice did not cause any acute elevation of circulating liver enzymes, lactate acidosis, or exertional myopathy, suggesting further evaluation of liver-specific inhibition of LDH as a potential approach for treating PH1 and PH2 is warranted. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Molecular recognition of PTS-1 cargo proteins by Pex5p: implications for protein mistargeting in primary hyperoxaluria.

PubMed

Mesa-Torres, Noel; Tomic, Nenad; Albert, Armando; Salido, Eduardo; Pey, Angel L

2015-02-13

Peroxisomal biogenesis and function critically depends on the import of cytosolic proteins carrying a PTS1 sequence into this organelle upon interaction with the peroxin Pex5p. Recent structural studies have provided important insights into the molecular recognition of cargo proteins by Pex5p. Peroxisomal import is a key feature in the pathogenesis of primary hyperoxaluria type 1 (PH1), where alanine:glyoxylate aminotransferase (AGT) undergoes mitochondrial mistargeting in about a third of patients. Here, we study the molecular recognition of PTS1 cargo proteins by Pex5p using oligopeptides and AGT variants bearing different natural PTS1 sequences, and employing an array of biophysical, computational and cell biology techniques. Changes in affinity for Pex5p (spanning over 3-4 orders of magnitude) reflect different thermodynamic signatures, but overall bury similar amounts of molecular surface. Structure/energetic analyses provide information on the contribution of ancillary regions and the conformational changes induced in Pex5p and the PTS1 cargo upon complex formation. Pex5p stability in vitro is enhanced upon cargo binding according to their binding affinities. Moreover, we provide evidence that the rational modulation of the AGT: Pex5p binding affinity might be useful tools to investigate mistargeting and misfolding in PH1 by pulling the folding equilibria towards the native and peroxisomal import competent state.

Stroke in Primary Hyperoxaluria Type I

PubMed Central

Rao, Neal M.; Yallapragada, Anil; Winden, Kellen D.; Saver, Jeffrey; Liebeskind, David S.

2014-01-01

We report the case of a 27-year-old man with a history of previously undiagnosed renal disease that presented with multiple cerebrovascular infarctions. Workup for traditional causes of cerebrovascular infarction including cardiac telemetry, multiple echocardiograms, and hypercoagulative workup was negative. However, a transcranial Doppler detected circulating microemboli at the rate of 14 per hour. A serum oxalate level greater than the supersaturation point of calcium oxalate was detected, providing a potential source of the microemboli. Furthermore, serial imaging recorded rapid mineralization of the infarcted territories. In the absence of any proximal vessel irregularities, atherosclerosis, valvular abnormalities, arrhythmias, or systemic shunt as potential stroke etiology in this patient, we propose that circulating oxalate precipitate may be a potential mechanism for stroke in patients with primary oxalosis. PMID:23551880

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

A test of the hypothesis that oxalate secretion produces proximal tubule crystallization in primary hyperoxaluria type I

PubMed Central

Evan, Andrew P.; Coe, Fredric L.; Lingeman, James E.; Krambeck, Amy; Sommers, Andre; Phillips, Carrie L.; Milliner, Dawn

2013-01-01

The sequence of events by which primary hyperoxaluria type 1 (PH1) causes renal failure is unclear. We hypothesize that proximal tubule (PT) is vulnerable because oxalate secretion raises calcium oxalate (CaOx) supersaturation (SS) there, leading to crystal formation and cellular injury. We studied cortical and papillary biopsies from two PH1 patients with preserved renal function, and seven native kidneys removed from four patients at the time of transplant, after short-term (2) or longer term (2) dialysis. In these patients, and another five PH1 patients without renal failure, we calculated oxalate secretion, and estimated PT CaOx SS. Plasma oxalate was elevated in all PH1 patients and inverse to creatinine clearance. Renal secretion of oxalate was present in all PH1 but rare in controls. PT CaOx SS was >1 in all nonpyridoxine-responsive PH1 before transplant and most marked in patients who developed end stage renal disease (ESRD). PT from PH1 with preserved renal function had birefringent crystals, confirming the presence of CaOx SS, but had no evidence of cortical inflammation or scarring by histopathology or hyaluronan staining. PH1 with short ESRD showed CaOx deposition and hyaluronan staining particularly at the corticomedullary junction in distal PT while cortical collecting ducts were spared. Longer ESRD showed widespread cortical CaOx, and in both groups papillary tissue had marked intratubular CaOx deposits and fibrosis. CaOx SS in PT causes CaOx crystal formation, and CaOx deposition in distal PT appears to be associated with ESRD. Minimizing PT CaOx SS may be important for preserving renal function in PH1. PMID:24089413

Biochemical analyses are instrumental in identifying the impact of mutations on holo and/or apo-forms and on the region(s) of alanine:glyoxylate aminotransferase variants associated with Primary Hyperoxaluria Type I☆

PubMed Central

Oppici, Elisa; Montioli, Riccardo; Lorenzetto, Antonio; Bianconi, Silvia; Borri Voltattorni, Carla; Cellini, Barbara

2012-01-01

Primary Hyperoxaluria Type I (PH1) is a disorder of glyoxylate metabolism caused by mutations in the human AGXT gene encoding liver peroxisomal alanine:glyoxylate aminotransferase (AGT), a pyridoxal 5′-phosphate (PLP) dependent enzyme. Previous investigations highlighted that, although PH1 is characterized by a significant variability in terms of enzymatic phenotype, the majority of the pathogenic variants are believed to share both structural and functional defects, as mainly revealed by data on AGT activity and expression level in crude cellular extracts. However, the knowledge of the defects of the AGT variants at a protein level is still poor. We therefore performed a side-by-side comparison between normal AGT and nine purified recombinant pathogenic variants in terms of catalytic activity, coenzyme binding mode and affinity, spectroscopic features, oligomerization, and thermal stability of both the holo- and apo-forms. Notably, we chose four variants in which the mutated residues are located in the large domain of AGT either within the active site and interacting with the coenzyme or in its proximity, and five variants in which the mutated residues are distant from the active site either in the large or in the small domain. Overall, this integrated analysis of enzymatic activity, spectroscopic and stability information is used to (i) reassess previous data obtained with crude cellular extracts, (ii) establish which form(s) (i.e. holoenzyme and/or apoenzyme) and region(s) (i.e. active site microenvironment, large and/or small domain) of the protein are affected by each mutation, and (iii) suggest the possible therapeutic approach for patients bearing the examined mutations. PMID:22018727

Crystal structure of the S187F variant of human liver alanine: Aminotransferase associated with primary hyperoxaluria type I and its functional implications

PubMed Central

Oppici, Elisa; Fodor, Krisztian; Paiardini, Alessandro; Williams, Chris; Voltattorni, Carla Borri; Wilmanns, Matthias; Cellini, Barbara

2013-01-01

The substitution of Ser187, a residue located far from the active site of human liver peroxisomal alanine:glyoxylate aminotransferase (AGT), by Phe gives rise to a variant associated with primary hyperoxaluria type I. Unexpectedly, previous studies revealed that the recombinant form of S187F exhibits a remarkable loss of catalytic activity, an increased pyridoxal 5′-phosphate (PLP) binding affinity and a different coenzyme binding mode compared with normal AGT. To shed light on the structural elements responsible for these defects, we solved the crystal structure of the variant to a resolution of 2.9 Å. Although the overall conformation of the variant is similar to that of normal AGT, we noticed: (i) a displacement of the PLP-binding Lys209 and Val185, located on the re and si side of PLP, respectively, and (ii) slight conformational changes of other active site residues, in particular Trp108, the base stacking residue with the pyridine cofactor moiety. This active site perturbation results in a mispositioning of the AGT-pyridoxamine 5′-phosphate (PMP) complex and of the external aldimine, as predicted by molecular modeling studies. Taken together, both predicted and observed movements caused by the S187F mutation are consistent with the following functional properties of the variant: (i) a 300- to 500-fold decrease in both the rate constant of L-alanine half-transamination and the kcat of the overall transamination, (ii) a different PMP binding mode and affinity, and (iii) a different microenvironment of the external aldimine. Proposals for the treatment of patients bearing S187F mutation are discussed on the basis of these results. Proteins 2013; 81:1457–1465. © 2013 Wiley Periodicals, Inc. PMID:23589421

Primary hyperoxaluria type 1 in the Canary Islands: A conformational disease due to I244T mutation in the P11L-containing alanine:glyoxylate aminotransferase

PubMed Central

Santana, A.; Salido, E.; Torres, A.; Shapiro, L. J.

2003-01-01

Primary hyperoxaluria type 1 (PH1) is an inborn error of metabolism resulting from a deficiency of alanine:glyoxylate aminotransferase (AGXT; EC 2.6.1.44). Most of the PH1 alleles detected in the Canary Islands carry the Ile-244 → Thr (I244T) mutation in the AGXT gene, with 14 of 16 patients homozygous for this mutation. Four polymorphisms within AGXT and regional microsatellites also were shared in their haplotypes (AGXT*LTM), consistent with a founder effect. The consequences of these amino acid changes were investigated. Although I244T alone did not affect AGXT activity or subcellular localization, when present in the same protein molecule as Leu-11 → Pro (L11P), it resulted in loss of enzymatic activity in soluble cell extracts. Like its normal counterpart, the AGXT*LTM protein was present in the peroxisomes but it was insoluble in detergent-free buffers. The polymorphism L11P behaved as an intragenic modifier of the I244T mutation, with the resulting protein undergoing stable interaction with molecular chaperones and aggregation. This aggregation was temperature-sensitive. AGXT*LTM expressed in Escherichia coli, as a GST-fusion protein, and in insect cells could be purified and retained enzymatic activity. Among various chemical chaperones tested in cell culture, betaine substantially improved the solubility of the mutant protein and the enzymatic activity in cell lysates. In summary, I244T, the second most common mutation responsible for PH1, is a protein conformational disease that may benefit from new therapies with pharmacological chaperones or small molecules to minimize protein aggregation. PMID:12777626

Presentation and role of transplantation in adult patients with type 1 primary hyperoxaluria and the I244T AGXT mutation: Single-center experience.

PubMed

Lorenzo, V; Alvarez, A; Torres, A; Torregrosa, V; Hernández, D; Salido, E

2006-09-01

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder characterized by allelic and clinical heterogeneity. We aim to describe the presentation and full single-center experience of the management of PH1 patients bearing the mutation described in our community (I244T mutation+polymorphism P11L). Since 1983, 12 patients with recurrent renal lithiasis have been diagnosed with PH1 and renal failure in the Canary Islands, Spain. Diagnostic confirmation was based on the presence of oxalosis in undecalcified bone or kidney allograft biopsy, reduced alanine:glyoxylate aminotransferase activity in liver biopsy, and blood DNA analysis. Patients underwent different treatment modalities depending on individual clinical circumstances and therapeutic possibilities at the time of diagnosis: hemodialysis, isolated kidney, simultaneous liver-kidney, or pre-emptive liver transplantation. In all cases, the presentation of advanced renal disease was relatively late (>13 years) and no cases were reported during lactancy or childhood. The eight patients treated with hemodialysis or isolated kidney transplantation showed unfavorable evolution leading to death over a variable period of time. In contrast, the four patients undergoing liver transplantation (three liver+kidney and one pre-emptive liver alone) showed favorable long-term allograft and patient survival (up to 12 years follow-up). In conclusion, in this PH1 population, all bearing the I244T mutation, the development of end-stage renal disease was distinctive during late adolescence or adulthood. Our long-term results support pre-emptive liver transplantation at early stages of renal failure, and kidney-liver transplantation for those with advanced renal disease.

Primary hyperoxaluria type 1 in the Canary Islands: a conformational disease due to I244T mutation in the P11L-containing alanine:glyoxylate aminotransferase.

PubMed

Santana, A; Salido, E; Torres, A; Shapiro, L J

2003-06-10

Primary hyperoxaluria type 1 (PH1) is an inborn error of metabolism resulting from a deficiency of alanine:glyoxylate aminotransferase (AGXT; EC 2.6.1.44). Most of the PH1 alleles detected in the Canary Islands carry the Ile-244 --> Thr (I244T) mutation in the AGXT gene, with 14 of 16 patients homozygous for this mutation. Four polymorphisms within AGXT and regional microsatellites also were shared in their haplotypes (AGXT*LTM), consistent with a founder effect. The consequences of these amino acid changes were investigated. Although I244T alone did not affect AGXT activity or subcellular localization, when present in the same protein molecule as Leu-11 --> Pro (L11P), it resulted in loss of enzymatic activity in soluble cell extracts. Like its normal counterpart, the AGXT*LTM protein was present in the peroxisomes but it was insoluble in detergent-free buffers. The polymorphism L11P behaved as an intragenic modifier of the I244T mutation, with the resulting protein undergoing stable interaction with molecular chaperones and aggregation. This aggregation was temperature-sensitive. AGXT*LTM expressed in Escherichia coli, as a GST-fusion protein, and in insect cells could be purified and retained enzymatic activity. Among various chemical chaperones tested in cell culture, betaine substantially improved the solubility of the mutant protein and the enzymatic activity in cell lysates. In summary, I244T, the second most common mutation responsible for PH1, is a protein conformational disease that may benefit from new therapies with pharmacological chaperones or small molecules to minimize protein aggregation.

Clinical implications of mutation analysis in primary hyperoxaluria type 1.

PubMed

van Woerden, Christiaan S; Groothoff, Jaap W; Wijburg, Frits A; Annink, Carla; Wanders, Ronald J A; Waterham, Hans R

2004-08-01

Primary hyperoxaluria type 1 (PH1) is an inborn error of glyoxylate metabolism with an extensive clinical and genetic heterogeneity. Although over 50 disease-causing mutations have been identified, the relationship between genotype and clinical outcome remains unclear. The aim of this study was to determine this association in order to find clues for improvement of patient care. AGXT mutation analysis and assessment of biochemical characteristics and clinical outcome were performed on patients from a Dutch PH1 cohort. Thirty-three of a cohort of 57 PH1 patients, identified in The Netherlands over a period of 30 years, were analyzed. Ten different mutations were found. The most common mutations were the Gly170Arg, Phe152Ile, and the 33insC mutations, with an allele frequency of 43%, 19%, and 15%, respectively. Homozygous Gly170Arg and Phe152Ile mutations were associated with pyridoxine responsiveness and a preserved renal function over time when treatment was timely initiated. All patients homozygous for the 33insC mutation had end-stage renal disease (ESRD) before the first year of age. In two unrelated patients, a new Val336Asp mutation was found coupled with the Gly170Arg mutation on the minor allele. We also found 3 patients homozygous for a novel Gly82Arg mutation with adverse outcome in 2 of them. Early detection of Gly170Arg and Phe152Ile mutations in PH1 has important clinical implications because of their association with pyridoxine responsiveness and clinical outcome. The association of a homozygous 33insC mutation with severe infantile ESRD, resulting in early deaths in 2 out of 3 cases, warrants a choice for prenatal diagnostics in affected families.

Biochemical analyses are instrumental in identifying the impact of mutations on holo and/or apo-forms and on the region(s) of alanine:glyoxylate aminotransferase variants associated with primary hyperoxaluria type I.

PubMed

Oppici, Elisa; Montioli, Riccardo; Lorenzetto, Antonio; Bianconi, Silvia; Borri Voltattorni, Carla; Cellini, Barbara

2012-01-01

Primary Hyperoxaluria Type I (PH1) is a disorder of glyoxylate metabolism caused by mutations in the human AGXT gene encoding liver peroxisomal alanine:glyoxylate aminotransferase (AGT), a pyridoxal 5'-phosphate (PLP) dependent enzyme. Previous investigations highlighted that, although PH1 is characterized by a significant variability in terms of enzymatic phenotype, the majority of the pathogenic variants are believed to share both structural and functional defects, as mainly revealed by data on AGT activity and expression level in crude cellular extracts. However, the knowledge of the defects of the AGT variants at a protein level is still poor. We therefore performed a side-by-side comparison between normal AGT and nine purified recombinant pathogenic variants in terms of catalytic activity, coenzyme binding mode and affinity, spectroscopic features, oligomerization, and thermal stability of both the holo- and apo-forms. Notably, we chose four variants in which the mutated residues are located in the large domain of AGT either within the active site and interacting with the coenzyme or in its proximity, and five variants in which the mutated residues are distant from the active site either in the large or in the small domain. Overall, this integrated analysis of enzymatic activity, spectroscopic and stability information is used to (i) reassess previous data obtained with crude cellular extracts, (ii) establish which form(s) (i.e. holoenzyme and/or apoenzyme) and region(s) (i.e. active site microenvironment, large and/or small domain) of the protein are affected by each mutation, and (iii) suggest the possible therapeutic approach for patients bearing the examined mutations. Copyright © 2011 Elsevier Inc. All rights reserved.

S81L and G170R mutations causing Primary Hyperoxaluria type I in homozygosis and heterozygosis: an example of positive interallelic complementation

PubMed Central

Montioli, Riccardo; Roncador, Alessandro; Oppici, Elisa; Mandrile, Giorgia; Giachino, Daniela Francesca; Cellini, Barbara; Borri Voltattorni, Carla

2014-01-01

Primary Hyperoxaluria type I (PH1) is a rare disease due to the deficit of peroxisomal alanine:glyoxylate aminotransferase (AGT), a homodimeric pyridoxal-5′-phosphate (PLP) enzyme present in humans as major (Ma) and minor (Mi) allele. PH1-causing mutations are mostly missense identified in both homozygous and compound heterozygous patients. Until now, the pathogenesis of PH1 has been only studied by approaches mimicking homozygous patients, whereas the molecular aspects of the genotype-enzymatic-clinical phenotype relationship in compound heterozygous patients are completely unknown. Here, for the first time, we elucidate the enzymatic phenotype linked to the S81L mutation on AGT-Ma, relative to a PLP-binding residue, and how it changes when the most common mutation G170R on AGT-Mi, known to cause AGT mistargeting without affecting the enzyme functionality, is present in the second allele. By using a bicistronic eukaryotic expression vector, we demonstrate that (i) S81L-Ma is mainly in its apo-form and has a significant peroxisomal localization and (ii) S81L and G170R monomers interact giving rise to the G170R-Mi/S81L-Ma holo-form, which is imported into peroxisomes and exhibits an enhanced functionality with respect to the parental enzymes. These data, integrated with the biochemical features of the heterodimer and the homodimeric counterparts in their purified recombinant form, (i) highlight the molecular basis of the pathogenicity of S81L-Ma and (ii) provide evidence for a positive interallelic complementation between the S81L and G170R monomers. Our study represents a valid approach to investigate the molecular pathogenesis of PH1 in compound heterozygous patients. PMID:24990153

Genotype-phenotype variability of retinal manifestation in primary hyperoxaluria type 1.

PubMed

Dulz, S; Bigdon, E; Atiskova, Y; Schuettauf, F; Cerkauskiene, R; Oh, J; Brinkert, F

2018-04-01

Primary hyperoxaluria type 1 (PH1) is a rare congenital metabolic disorder of the glyoxylate pathway, which manifests with nephrocalcinosis, urolithiasis, and end-stage renal failure (ESRD) as well as deposition of oxalate crystals within ocular tissues. This report demonstrates classical ocular features of PH1 of the posterior pole and furthermore highlights the ocular genotype-phenotype variability among siblings with identical compound heterozygous alanine-glyoxylate aminotransferase (AGXT) mutations. Two siblings, an 8-year-old boy and an 18-year-old girl, with genetically confirmed AGXT mutation (c.364C>T (p.R122X) and c.33dupC), but different renal phenotype underwent an ophthalmic examination, including slit-lamp examination and funduscopy as well as optical coherence tomography (OCT), near-infrared autofluorescence (NIA), and microperimetry examination. The 8-year-old boy presented with a best-corrected visual acuity (BCVA) of 20/630. Fundus examination revealed bilateral, whitish oxalate deposits and prominent fibrotic macular scars. OCT imaging illustrated hyperdense deposits in all retinal layers and the choroid and the vitreous body along with a prominent dome-shaped macular fibrosis. NIA imaging outlined macular retinal pigment epithelium (RPE) atrophy with panretinal hyperreflective material. Bilateral symptomatic epiphora was putatively due to bilateral depositions of palpable nodular oxalate deposits at the level of the lacrimal sac. In contrary, the 18-year-old sister presented without any signs of ocular oxalate deposition and a BCVA of 20/20. PH1 is potentially accompanied with a considerable decline in visual acuity due to macular scaring and fibrosis, whereas a profound variability of ocular manifestations can be observed in PH1 patients with identical genotypes.

Allele-specific Characterization of Alanine: Glyoxylate Aminotransferase Variants Associated with Primary Hyperoxaluria

PubMed Central

Lage, Melissa D.; Pittman, Adrianne M. C.; Roncador, Alessandro; Cellini, Barbara; Tucker, Chandra L.

2014-01-01

Primary Hyperoxaluria Type 1 (PH1) is a rare autosomal recessive kidney stone disease caused by deficiency of the peroxisomal enzyme alanine: glyoxylate aminotransferase (AGT), which is involved in glyoxylate detoxification. Over 75 different missense mutations in AGT have been found associated with PH1. While some of the mutations have been found to affect enzyme activity, stability, and/or localization, approximately half of these mutations are completely uncharacterized. In this study, we sought to systematically characterize AGT missense mutations associated with PH1. To facilitate analysis, we used two high-throughput yeast-based assays: one that assesses AGT specific activity, and one that assesses protein stability. Approximately 30% of PH1-associated missense mutations are found in conjunction with a minor allele polymorphic variant, which can interact to elicit complex effects on protein stability and trafficking. To better understand this allele interaction, we functionally characterized each of 34 mutants on both the major (wild-type) and minor allele backgrounds, identifying mutations that synergize with the minor allele. We classify these mutants into four distinct categories depending on activity/stability results in the different alleles. Twelve mutants were found to display reduced activity in combination with the minor allele, compared with the major allele background. When mapped on the AGT dimer structure, these mutants reveal localized regions of the protein that appear particularly sensitive to interactions with the minor allele variant. While the majority of the deleterious effects on activity in the minor allele can be attributed to synergistic interaction affecting protein stability, we identify one mutation, E274D, that appears to specifically affect activity when in combination with the minor allele. PMID:24718375

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.

Urine oxalate biological variation in patients with primary hyperoxaluria.

PubMed

Clifford-Mobley, Oliver; Sjögren, Anna; Lindner, Elisabeth; Rumsby, Gill

2016-08-01

Hyperoxaluria is a well-recognised risk factor for urolithiasis and patients with primary hyperoxaluria (PH) gradually build up calcium oxalate deposits leading to chronic kidney disease. Efforts to improve treatment for PH have focused on reducing urine oxalate excretion and thus decreasing lithogenesis. To determine the efficacy of treatments designed to alter a biochemical parameter it is necessary to know the biological and analytical variation of that parameter. In this study, we estimated the intra-individual biological variation of urine oxalate excretion in patients with PH, and from this determined what would constitute a significant change in the form of a reference change value (RCV). Each patient collected four 24-h urines on consecutive weeks. The intra-individual biological variation of oxalate excretion calculated from these samples ranged from 0 to 36 % with a mean of 14 %. The corresponding RCVs were 4-84 % with a mean of 32 %. This result implies that, on average, a reduction of almost one-third in urine oxalate excretion is required to prove an effect from treatment. The wide range of biological variation between individuals may reflect other, as yet unknown, determinants of oxaluria in PH, as well as inaccuracies in urine collection. The data suggest that it is more appropriate to use individual RCVs established prior to treatment to determine its efficacy: a relatively small fall in urine oxalate excretion may be outside the biological variation of some patients but not of others.

Cardiac Abnormalities in Primary Hyperoxaluria

PubMed Central

Mookadam, Farouk; Smith, Travis; Jiamsripong, Panupong; Moustafa, Sherif E; Monico, Carla G.; Lieske, John C.; Milliner, Dawn S.

2018-01-01

Background In patients with primary hyperoxaluria (PH), oxalate overproduction can result in recurrent urolithiasis and nephrocalcinosis, which in some cases results in a progressive decline in renal function, oxalate retention, and systemic oxalosis involving bone, retina, arterial media, peripheral nerves, skin, and heart. Oxalosis involving the myocardium or conduction system can potentially lead to heart failure and fatal arrhythmias. Methods and Results A retrospective review of our institution’s database was conducted for all patients with a confirmed diagnosis of PH between 1/1948 and 1/2006 (n=103). Electrocardiogram (ECG) and echocardiography were used to identify cardiac abnormalities. Ninety-three patients fulfilled the inclusion criteria, 58% were male. Mean follow-up was 11.9 (median 8.8) years. In 38 patients who received an ECG or echocardiography, 31 were found to have any cardiac abnormalities. Cardiac findings correlated with decline in renal function. Conclusions Our data suggests that physicians caring for patients with PH should pay close attention to cardiac status, especially if renal function is impaired. PMID:20921818

Mutational analysis of AGXT gene in Libyan children with primary hyperoxaluria type 1 at Tripoli Children Hospital.

PubMed

Rhuma, Naziha R; Fituri, Omar A; Sabei, Laila T

2018-01-01

Primary hyperoxaluria type 1 (PH1) is an inborn error of glyoxylate metabolism. It results from genetic mutation of the AGXT gene. The study objective was to verify the clinical and epidemiological patterns of PH1 in Libyan children at Tripoli Children Hospital confirmed by AGXT gene mutation. A descriptive case series study of 53 children with PH1 diagnosed between 1994 and 2015 was carried out in the Nephrology Unit at Tripoli Children Hospital. Diagnosis of PH1 was based on the clinical presentation (renal stones or nephrocalcinosis), positive family history of PH1, and high 24 h urinary oxalate. Sampling for AGXT gene mutation was collected from April 2012 to December. 2015. Among the 53 children included, males composed of 62.3% of patients. Their age at presentation ranged between two months and 20 years with a mean age of 55.4 ± 48 months. The parents of 81.1% of these patients had positive consanguinity. Forty (75.5%) patients were from South West (mountain area), and 16 (40%) of them were from Yefrin. The most common mutation found in this study was c.731T>C (p.lle244thr) seen in 32 (71%) of children, and interestingly, among these patients, 87.1% were homozygous in gene typing, 86.2% had positive history of consanguinity, 71.4% were from South West (mountain area), 96.6% had family history of PH1, and 20% presented with impaired renal function. The patients with this mutation were younger at presentation than that with other genes, and it was more prevalent among boys (61.3%). Thus, the most common gene mutation found in Libyan children with PH1 was c.731T>C (p.lle244thr) and this is more likely due to the strong genetic pooling caused by the high consanguinity rate which requires an extensive genetic counseling.

Selected exonic sequencing of the AGXT gene provides a genetic diagnosis in 50% of patients with primary hyperoxaluria type 1.

PubMed

Williams, Emma; Rumsby, Gill

2007-07-01

Definitive diagnosis of primary hyperoxaluria type 1 (PH1) requires analysis of alanine:glyoxylate aminotransferase (AGT) activity in the liver. We have previously shown that targeted screening for the 3 most common mutations in the AGXT gene (c.33_34insC, c.508G>A, and c.731T>C) can provide a molecular diagnosis in 34.5% of PH1 patients, eliminating the need for a liver biopsy. Having reviewed the distribution of all AGXT mutations, we have evaluated a diagnostic strategy that uses selected exon sequencing for the molecular diagnosis of PH1. We sequenced exons 1, 4, and 7 for 300 biopsy-confirmed PH1 patients and expressed the identified missense mutations in vitro. Our identification of at least 1 mutation in 224 patients (75%) and 2 mutations in 149 patients increased the diagnostic sensitivity to 50%. We detected 29 kinds of sequence changes, 15 of which were novel. Four of these mutations were in exon 1 (c.2_3delinsAT, c.30_32delCC, c.122G>A, c.126delG), 7 were in exon 4 (c.447_454delGCTGCTGT, c.449T>C, c.473C>T, c.481G>A, c.481G>T, c.497T>C, c.424-2A>G), and 4 were in exon 7 (c.725insT, c.737G>A, c.757T>C, c.776 + 1G>A). The missense changes were associated with severely decreased AGT catalytic activity and negative immunoreactivity when expressed in vitro. Missense mutation c.26C>A, previously described as a pathological mutation, had activity similar to that of the wild-type enzyme. Selective exon sequencing can allow a definitive diagnosis in 50% of PH1 patients. The test offers a rapid turnaround time (15 days) with minimal risk to the patient. Demonstration of the expression of missense changes is essential to demonstrate pathogenicity.

Primary hyperoxaluria: genotype-phenotype correlation.

PubMed

Pirulli, Doroti; Marangella, Martino; Amoroso, Antonio

2003-01-01

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder caused by a deficiency of alanine-glyoxylate aminotransferase (AGT), which is encoded by a single copy gene (AGXT). Molecular diagnosis was used in conjunction with clinical, biochemical and enzymological data to evaluate genotype-phenotype correlation. Patients can present a severe form of PH1, an adult form and a mild to moderate decrease in renal function. Biochemical diagnosis is made by plasma, urine and dialyzate oxalate and glycolate assays, and by liver AGT activity and pyridoxine responsitivity. Molecular genetic diagnosis can be made using different techniques, for example, the single strand conformation polymorphism technique (SSCP), followed by the sequencing of the 11 AGXT exons. The disease is clinically and genetically classified as highly heterogeneous. Mutant alleles can be recognised in 80- 90% of chromosomes, depending on the techniques used. Mutations in exons 1, 2, 4 and 10 are more frequent in Italian patients. Normalized AGT activity seems to be lower in the severe form than in the adult form. Double heterozygous patients present a lower age at disease onset and they were more frequent in the more severe than in mild severe disease. The 444T>C mutation was more frequent in the severe form, while the opposite was observed for 630G>A. 630G>A mutation homozygotes had a higher AGT residual activity. The presence of allelic heterogeneity of the AGXT could be responsible, to some extent, for the phenotypic heterogeneity in PH1. Homozygous genotypes were more frequent than expected and were associated with a less severe form of the disease.

Four of the Most Common Mutations in Primary Hyperoxaluria Type 1 Unmask the Cryptic Mitochondrial Targeting Sequence of Alanine:glyoxylate Aminotransferase Encoded by the Polymorphic Minor Allele*

PubMed Central

Fargue, Sonia; Lewin, Jackie; Rumsby, Gill; Danpure, Christopher J.

2013-01-01

The gene encoding the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT, EC. 2.6.1.44) exists as two common polymorphic variants termed the “major” and “minor” alleles. The P11L amino acid replacement encoded by the minor allele creates a hidden N-terminal mitochondrial targeting sequence, the unmasking of which occurs in the hereditary calcium oxalate kidney stone disease primary hyperoxaluria type 1 (PH1). This unmasking is due to the additional presence of a common disease-specific G170R mutation, which is encoded by about one third of PH1 alleles. The P11L and G170R replacements interact synergistically to reroute AGT to the mitochondria where it cannot fulfill its metabolic role (i.e. glyoxylate detoxification) effectively. In the present study, we have reinvestigated the consequences of the interaction between P11L and G170R in stably transformed CHO cells and have studied for the first time whether a similar synergism exists between P11L and three other mutations that segregate with the minor allele (i.e. I244T, F152I, and G41R). Our investigations show that the latter three mutants are all able to unmask the cryptic P11L-generated mitochondrial targeting sequence and, as a result, all are mistargeted to the mitochondria. However, whereas the G170R, I244T, and F152I mutants are able to form dimers and are catalytically active, the G41R mutant aggregates and is inactive. These studies open up the possibility that all PH1 mutations, which segregate with the minor allele, might also lead to the peroxisome-to-mitochondrion mistargeting of AGT, a suggestion that has important implications for the development of treatment strategies for PH1. PMID:23229545

Primary hyperoxaluria in populations of Pakistan origin: results from a literature review and two major registries.

PubMed

Talati, Jamsheer Jehangir; Hulton, Sally-Anne; Garrelfs, Sander F; Aziz, Wajahat; Rao, Shoaib; Memon, Amanullah; Nazir, Zafar; Biyabani, Raziuddin; Qazi, Saqib; Azam, Iqbal; Khan, Aysha Habib; Ahmed, Jamil; Jafri, Lena; Zeeshan, Mohammad

2018-04-01

Primary hyperoxalurias (PH) are devastating, autosomal recessive diseases causing renal stones. Undifferentiated hyperoxaluria is seen in up to 43% of Pakistani paediatric stone patients. High rates of consanguinity in Pakistan suggest significant local prevalence. There is no detailed information regarding number of cases, clinical features, and genetics in Pakistan-origin (P-o) patients. We reviewed available information on P-o PH patients recorded in the literature as well as from two major PH registries (the Rare Kidney Stone Consortium PH Registry (RKSCPHR) and the OxalEurope PH Registry (OxER); and the Aga Khan University Hospital in Pakistan. After excluding overlaps, we noted 217 P-o PH subjects (42 in OxER and 4 in RKSCPHR). Presentations were protean. Details of mutations were available for 94 patients of 201 who had genetic analyses. Unique mutations were noted. Mutation [c.508G>A (p. Gly170Arg)] (present in up to 25% in the West) was reported in only one case. In one series, only 30% had mutations on exons 1,4,7 of AGXT. Of 42 P-o patients in OxER, 52.4% were PH1, 45.2% PH2, and 2.4% PH3. Of concern is that diagnosis was made after renal transplant rejection (four cases) and on bone-marrow aspiration (in five). Lack of consideration of PH as a diagnosis, late diagnosis, and loss of transplanted kidneys mandates that PH be searched for diligently. Mutation analysis will need to extend to all exons and include PH 1,2,3. There is a need to spread awareness and identify patients through a scoring or screening system that alerts physicians to consider a diagnosis of PH.

Enteric hyperoxaluria in chronic pancreatitis.

PubMed

Demoulin, Nathalie; Issa, Zaina; Crott, Ralph; Morelle, Johann; Danse, Etienne; Wallemacq, Pierre; Jadoul, Michel; Deprez, Pierre H

2017-05-01

Chronic pancreatitis may lead to steatorrhea, enteric hyperoxaluria, and kidney damage. However, the prevalence and determinants of hyperoxaluria in chronic pancreatitis patients as well as its association with renal function decline have not been investigated.We performed an observational study. Urine oxalate to creatinine ratio was assessed on 2 independent random urine samples in consecutive adult patients with chronic pancreatitis followed at the outpatient clinic from March 1 to October 31, 2012. Baseline characteristics and annual estimated glomerular filtration rate (eGFR) change during follow-up were compared between patients with hyper- and normo-oxaluria.A total of 48 patients with chronic pancreatitis were included. The etiology of the disease was toxic (52%), idiopathic (27%), obstructive (11%), autoimmune (6%), or genetic (4%). Hyperoxaluria (defined as urine oxalate to creatinine ratio >32 mg/g) was found in 23% of patients. Multivariate regression analysis identified clinical steatorrhea, high fecal acid steatocrit, and pancreatic atrophy as independent predictors of hyperoxaluria. Taken together, a combination of clinical steatorrhea, steatocrit level >31%, and pancreatic atrophy was associated with a positive predictive value of 100% for hyperoxaluria. On the contrary, none of the patients with a fecal elastase-1 level >100 μg/g had hyperoxaluria. Longitudinal evolution of eGFR was available in 71% of the patients, with a mean follow-up of 904 days. After adjustment for established determinants of renal function decline (gender, diabetes, bicarbonate level, baseline eGFR, and proteinuria), a urine oxalate to creatinine ratio >32 mg/g was associated with a higher risk of eGFR decline.Hyperoxaluria is highly prevalent in patients with chronic pancreatitis and associated with faster decline in renal function. A high urine oxalate to creatinine ratio in patients with chronic pancreatitis is best predicted by clinical steatorrhea, a high acid steatocrit, and pancreatic atrophy. Further studies will need to investigate the mechanisms of renal damage in chronic pancreatitis and the potential benefits of therapies reducing oxaluria.

Hydroxyproline Metabolism and Oxalate Synthesis in Primary Hyperoxaluria.

PubMed

Fargue, Sonia; Milliner, Dawn S; Knight, John; Olson, Julie B; Lowther, W Todd; Holmes, Ross P

2018-06-01

Background Endogenous oxalate synthesis contributes to calcium oxalate stone disease and is markedly increased in the inherited primary hyperoxaluria (PH) disorders. The incomplete knowledge regarding oxalate synthesis complicates discovery of new treatments. Hydroxyproline (Hyp) metabolism results in the formation of oxalate and glycolate. However, the relative contribution of Hyp metabolism to endogenous oxalate and glycolate synthesis is not known. Methods To define this contribution, we performed primed, continuous, intravenous infusions of the stable isotope [ 15 N, 13 C 5 ]-Hyp in nine healthy subjects and 19 individuals with PH and quantified the levels of urinary 13 C 2 -oxalate and 13 C 2 -glycolate formed using ion chromatography coupled to mass detection. Results The total urinary oxalate-to-creatinine ratio during the infusion was 73.1, 70.8, 47.0, and 10.6 mg oxalate/g creatinine in subjects with PH1, PH2, and PH3 and controls, respectively. Hyp metabolism accounted for 12.8, 32.9, and 14.8 mg oxalate/g creatinine in subjects with PH1, PH2, and PH3, respectively, compared with 1.6 mg oxalate/g creatinine in controls. The contribution of Hyp to urinary oxalate was 15% in controls and 18%, 47%, and 33% in subjects with PH1, PH2, and PH3, respectively. The contribution of Hyp to urinary glycolate was 57% in controls, 30% in subjects with PH1, and <13% in subjects with PH2 or PH3. Conclusions Hyp metabolism differs among PH types and is a major source of oxalate synthesis in individuals with PH2 and PH3. In patients with PH1, who have the highest urinary excretion of oxalate, the major sources of oxalate remain to be identified. Copyright © 2018 by the American Society of Nephrology.

Phenotype-Genotype Correlations and Estimated Carrier Frequencies of Primary Hyperoxaluria

PubMed Central

Hopp, Katharina; Cogal, Andrea G.; Bergstralh, Eric J.; Seide, Barbara M.; Olson, Julie B.; Meek, Alicia M.; Lieske, John C.; Milliner, Dawn S.

2015-01-01

Primary hyperoxaluria (PH) is a rare autosomal recessive disease characterized by oxalate accumulation in the kidneys and other organs. Three loci have been identified: AGXT (PH1), GRHPR (PH2), and HOGA1 (PH3). Here, we compared genotype to phenotype in 355 patients in the Rare Kidney Stone Consortium PH registry and calculated prevalence using publicly available whole-exome data. PH1 (68.4% of families) was the most severe PH type, whereas PH3 (11.0% of families) showed the slowest decline in renal function but the earliest symptoms. A group of patients with disease progression similar to that of PH3, but for whom no mutation was detected (11.3% of families), suggested further genetic heterogeneity. We confirmed that the AGXT p.G170R mistargeting allele resulted in a milder PH1 phenotype; however, other potential AGXT mistargeting alleles caused more severe (fully penetrant) disease. We identified the first PH3 patient with ESRD; a homozygote for two linked, novel missense mutations. Population analysis suggested that PH is an order of magnitude more common than determined from clinical cohorts (prevalence, approximately 1:58,000; carrier frequency, approximately 1:70). We estimated PH to be approximately three times less prevalent among African Americans than among European Americans because of a limited number of common European origin alleles. PH3 was predicted to be as prevalent as PH1 and twice as common as PH2, indicating that PH3 (and PH2) cases are underdiagnosed and/or incompletely penetrant. These results highlight a role for molecular analyses in PH diagnostics and prognostics and suggest that wider analysis of the idiopathic stone-forming population may be beneficial. PMID:25644115

Phenotype-Genotype Correlations and Estimated Carrier Frequencies of Primary Hyperoxaluria.

PubMed

Hopp, Katharina; Cogal, Andrea G; Bergstralh, Eric J; Seide, Barbara M; Olson, Julie B; Meek, Alicia M; Lieske, John C; Milliner, Dawn S; Harris, Peter C

2015-10-01

Primary hyperoxaluria (PH) is a rare autosomal recessive disease characterized by oxalate accumulation in the kidneys and other organs. Three loci have been identified: AGXT (PH1), GRHPR (PH2), and HOGA1 (PH3). Here, we compared genotype to phenotype in 355 patients in the Rare Kidney Stone Consortium PH registry and calculated prevalence using publicly available whole-exome data. PH1 (68.4% of families) was the most severe PH type, whereas PH3 (11.0% of families) showed the slowest decline in renal function but the earliest symptoms. A group of patients with disease progression similar to that of PH3, but for whom no mutation was detected (11.3% of families), suggested further genetic heterogeneity. We confirmed that the AGXT p.G170R mistargeting allele resulted in a milder PH1 phenotype; however, other potential AGXT mistargeting alleles caused more severe (fully penetrant) disease. We identified the first PH3 patient with ESRD; a homozygote for two linked, novel missense mutations. Population analysis suggested that PH is an order of magnitude more common than determined from clinical cohorts (prevalence, approximately 1:58,000; carrier frequency, approximately 1:70). We estimated PH to be approximately three times less prevalent among African Americans than among European Americans because of a limited number of common European origin alleles. PH3 was predicted to be as prevalent as PH1 and twice as common as PH2, indicating that PH3 (and PH2) cases are underdiagnosed and/or incompletely penetrant. These results highlight a role for molecular analyses in PH diagnostics and prognostics and suggest that wider analysis of the idiopathic stone-forming population may be beneficial. Copyright © 2015 by the American Society of Nephrology.

Selected AGXT gene mutations analysis provides a genetic diagnosis in 28% of Tunisian patients with primary hyperoxaluria.

PubMed

Benhaj Mbarek, Ibtihel; Abroug, Saoussen; Omezzine, Asma; Zellama, Dorsaf; Achour, Abdellatif; Harbi, Abdelaziz; Bouslama, Ali

2011-05-25

Primary hyperoxaluria type I (PH1) is a rare genetic disorder characterized by allelic and clinical heterogeneity. Four mutations (G170R, 33_34insC, I244T and F152I) account for more than 50% of PH1 alleles and form the basis for diagnostic genetic screening for PH1. We aimed to analyze the prevalence of these specific mutations causing PH1, and to provide an accurate tool for diagnosis of presymptomatic patients as well as for prenatal diagnosis in the affected families. Polymerase chain reaction/Restriction Fragment Length Polymorphism, were used to detect the four mutations in the AGXT gene in DNA samples from 57 patients belonging to 40 families. Two mutations causing PH1 were detected in 24 patients (42.1%), with a predominance of the I244T mutation (68% of patients) and 33_34insC (in the remaining 32%). In 92% of cases, mutated alleles were in homozygous state. The presented clinical features were similar for the two mutations. The age of onset was heterogeneous with a higher frequency of the pediatric age. In 58.3% of cases, the presentation corresponded to advanced renal disease which occurred early (< 5 years) in the two mutations. In adolescents, only the I244T mutation was detected (41.1%). I244T and 33_34insC mutations were observed in adult patients, with 17.6% and 12.5% respectively. Limited mutation analysis can provide a useful first line investigation for PH1. I244T and 33_34insC presented 28.2% of identified mutations causing disease in our cohort. This identification could provide an accurate tool for prenatal diagnosis in the affected families, for genetic counselling and for detection of presymptomatic individuals.

Etiology of chronic renal failure in Jenin district, Palestine.

PubMed

Abumwais, Jamal Qasem

2012-01-01

A study was conducted on chronic renal failure patients treated by medications or by hemodialysis at The Martyr Dr. Khalil Sulaiman Hospital in Jenin city, Palestine, from 1/8/2005 to 1/8/2006 to know the underlying etiology of chronic renal failure. The subjects included were 84 patients. The information was obtained from files of the patients. The diagnosis was based on medical history, laboratory tests, X-rays, CT scans, ultrasound and renal biopsies. The results showed that the three most common causes of chronic renal failure in Jenin district were diabetes mellitus (33.32%), hypertension (16.7%), and chronic glomerulonephritis (13.1%). Inherited kidney diseases formed an important percentage (17.85%) and included primary hyperoxaluria (10.71%), Alport's syndrome (5.95%), and adult polycystic kidney disease (1.19%). These results differ from what is found in most developing countries including many Arab countries where the principal causes of chronic renal failure are chronic glomerulonephritis and interstitial nephritis. The high prevalence of inherited kidney diseases in some families (primary hyperoxaluria and Alport's) syndrome may be explained by the very high prevalence of consanguineous marriage especially among cousins in these families.

Crystal structure and confirmation of the alanine:glyoxylate aminotransferase activity of the YFL030w yeast protein.

PubMed

Meyer, Philippe; Liger, Dominique; Leulliot, Nicolas; Quevillon-Cheruel, Sophie; Zhou, Cong-Zhao; Borel, Franck; Ferrer, Jean-Luc; Poupon, Anne; Janin, Joël; van Tilbeurgh, Herman

2005-12-01

We have determined the three-dimensional crystal structure of the protein encoded by the open reading frame YFL030w from Saccharomyces cerevisiae to a resolution of 2.6 A using single wavelength anomalous diffraction. YFL030w is a 385 amino-acid protein with sequence similarity to the aminotransferase family. The structure of the protein reveals a homodimer adopting the fold-type I of pyridoxal 5'-phosphate (PLP)-dependent aminotransferases. The PLP co-factor is covalently bound to the active site in the crystal structure. The protein shows close structural resemblance with the human alanine:glyoxylate aminotransferase (EC 2.6.1.44), an enzyme involved in the hereditary kidney stone disease primary hyperoxaluria type 1. In this paper we show that YFL030w codes for an alanine:glyoxylate aminotransferase, highly specific for its amino donor and acceptor substrates.

Primary hyperoxaluria in Coton de Tulear.

PubMed

Vidgren, G; Vainio-Siukola, K; Honkasalo, S; Dillard, K; Anttila, M; Vauhkonen, H

2012-06-01

Primary hyperoxaluria (PH) is a rare autosomal recessive disorder of glyoxylate metabolism in humans. It is characterized by the accumulation of oxalate and subsequent precipitation of calcium oxalate crystals, primarily in the kidneys. Deficiencies in glyoxylate-metabolizing enzymes alanine-glyoxylate aminotransferase (AGXT) or glyoxylate reductase/hydroxypyruvate reductase (GRHPR) occur in 95% of PH cases. Seven Coton de Tulear puppies from four apparently unrelated litters were examined owing to sudden illness at the age of 3-4 weeks. A complete necropsy was performed. The typical finding was tubular necrosis with extensive oxalate crystal deposition. Based on history and necropsy findings, PH was suspected. Eight microsatellite loci flanking AGXT and GRHPR were analysed, and based on segregation results, AGXT was suspected as to be the candidate gene. AGXT exon sequencing revealed a single base change (c.996G>A) that changed one conserved residue (p.Gly102Ser). The mutation was tested in of 118 Finnish Coton de Tulear dogs, ten (8.5%) of which were revealed as carriers. This preliminary study reports PH as a cause of neonatal death in Finnish Coton de Tulear and suggests that genetic testing of dogs be carried out before breeding to prevent the birth of affected offspring. © 2011 The Authors, Animal Genetics © 2011 Stichting International Foundation for Animal Genetics.

Performance evaluation of Sanger sequencing for the diagnosis of primary hyperoxaluria and comparison with targeted next generation sequencing

PubMed Central

Williams, Emma L; Bagg, Eleanor A L; Mueller, Michael; Vandrovcova, Jana; Aitman, Timothy J; Rumsby, Gill

2015-01-01

Definitive diagnosis of primary hyperoxaluria (PH) currently utilizes sequential Sanger sequencing of the AGXT, GRPHR, and HOGA1 genes but efficacy is unproven. This analysis is time-consuming, relatively expensive, and delays in diagnosis and inappropriate treatment can occur if not pursued early in the diagnostic work-up. We reviewed testing outcomes of Sanger sequencing in 200 consecutive patient samples referred for analysis. In addition, the Illumina Truseq custom amplicon system was evaluated for paralleled next-generation sequencing (NGS) of AGXT,GRHPR, and HOGA1 in 90 known PH patients. AGXT sequencing was requested in all patients, permitting a diagnosis of PH1 in 50%. All remaining patients underwent targeted exon sequencing of GRHPR and HOGA1 with 8% diagnosed with PH2 and 8% with PH3. Complete sequencing of both GRHPR and HOGA1 was not requested in 25% of patients referred leaving their diagnosis in doubt. NGS analysis showed 98% agreement with Sanger sequencing and both approaches had 100% diagnostic specificity. Diagnostic sensitivity of Sanger sequencing was 98% and for NGS it was 97%. NGS has comparable diagnostic performance to Sanger sequencing for the diagnosis of PH and, if implemented, would screen for all forms of PH simultaneously ensuring prompt diagnosis at decreased cost. PMID:25629080

Reduced active transcellular intestinal oxalate secretion contributes to the pathogenesis of obesity-associated hyperoxaluria.

PubMed

Amin, Ruhul; Asplin, John; Jung, Daniel; Bashir, Mohamed; Alshaikh, Altayeb; Ratakonda, Sireesha; Sharma, Sapna; Jeon, Sohee; Granja, Ignacio; Matern, Dietrich; Hassan, Hatim

2018-05-01

Most kidney stones are composed of calcium oxalate, and minor changes in urine oxalate affect the stone risk. Obesity is a risk factor for kidney stones and a positive correlation of unknown etiology between increased body size, and elevated urinary oxalate excretion has been reported. Here, we used obese ob/ob (ob) mice to elucidate the pathogenesis of obesity-associated hyperoxaluria. These ob mice have significant hyperoxaluria (3.3-fold) compared with control mice, which is not due to overeating as shown by pair-feeding studies. Dietary oxalate removal greatly ameliorated this hyperoxaluria, confirming that it is largely enteric in origin. Transporter SLC26A6 (A6) plays an essential role in active transcellular intestinal oxalate secretion, and ob mice have significantly reduced jejunal A6 mRNA (- 80%) and total protein (- 62%) expression. While net oxalate secretion was observed in control jejunal tissues mounted in Ussing chambers, net absorption was seen in ob tissues, due to significantly reduced secretion. We hypothesized that the obesity-associated increase in intestinal and systemic inflammation, as reflected by elevated proinflammatory cytokines, suppresses A6-mediated intestinal oxalate secretion and contributes to obesity-associated hyperoxaluria. Indeed, proinflammatory cytokines (elevated in ob mice) significantly decreased intestinal oxalate transport in vitro by reducing A6 mRNA and total protein expression. Proinflammatory cytokines also significantly reduced active mouse jejunal oxalate secretion, converting oxalate transport from net secretion in vehicle-treated tissues to net absorption in proinflammatory cytokines-treated tissues. Thus, reduced active intestinal oxalate secretion, likely secondary to local and systemic inflammation, contributes to the pathogenesis of obesity-associated hyperoxaluria. Hence, proinflammatory cytokines represent potential therapeutic targets. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

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.

[Oliguria and acute renal dysfunction in a six-month-old infant].

PubMed

Cui, Ya-Jie; Song, Chun-Lan; Cheng, Yi-Bing

2017-02-01

The infant (a girl aged 6 months) was admitted to the hospital because of oliguria and acute renal dysfunction. The laboratory examination results showed serious metabolic acidosis and increased blood urea nitrogen and serum creatinine levels. The patient continued to be anuric after 10 days of treatment with continuous renal replacement therapy (CRRT). she died a day later. The family history showed that the patient's sister died of acute renal failure 6 months after birth. The genomic sequencing results showed AGXT mutation in the patient and confirmed the diagnosis of primary hyperoxaluria type 1 (PH1). Her parents were heterozygous carriers. PH1 should be considered when the children have abnormal renal function or recurrent renal calculi or have a family history of these symptoms. AGXT gene analysis is an important method for PH1 diagnosis.

Identification of 5 novel mutations in the AGXT gene.

PubMed

Basmaison, O; Rolland, M O; Cochat, P; Bozon, D

2000-06-01

In order to identify additional genotypes in primary hyperoxaluria type 1, we sequenced the AGXT genes of 9 patients. We report 5 new mutations. Three are splice-site mutations situated at the end of intron 4 and 8 (647-1G>A, 969-1G>C, 969-3C>G), one is a missense mutation in exon 5 (D183N), and one is a short duplication in exon 2 (349ins7). Their consequence is always a lack of enzymatic activity of the Alanine-Glyoxylate Aminotransferase (AGT); for 4 of them, we were able to deduce that they were associated to the absence of AGT protein. These mutations are rare, as they have been found on one allele in our study (except 969-3C>G present in 2 unrelated families), and have not been previously reported.

Selected AGXT gene mutations analysis provides a genetic diagnosis in 28% of Tunisian patients with primary hyperoxaluria

PubMed Central

2011-01-01

Background Primary hyperoxaluria type I (PH1) is a rare genetic disorder characterized by allelic and clinical heterogeneity. Four mutations (G170R, 33_34insC, I244T and F152I) account for more than 50% of PH1 alleles and form the basis for diagnostic genetic screening for PH1. We aimed to analyze the prevalence of these specific mutations causing PH1, and to provide an accurate tool for diagnosis of presymptomatic patients as well as for prenatal diagnosis in the affected families. Methods Polymerase chain reaction/Restriction Fragment Length Polymorphism, were used to detect the four mutations in the AGXT gene in DNA samples from 57 patients belonging to 40 families. Results Two mutations causing PH1 were detected in 24 patients (42.1%), with a predominance of the I244T mutation (68% of patients) and 33_34insC (in the remaining 32%). In 92% of cases, mutated alleles were in homozygous state. The presented clinical features were similar for the two mutations. The age of onset was heterogeneous with a higher frequency of the pediatric age. In 58.3% of cases, the presentation corresponded to advanced renal disease which occurred early (< 5 years) in the two mutations. In adolescents, only the I244T mutation was detected (41.1%). I244T and 33_34insC mutations were observed in adult patients, with 17.6% and 12.5% respectively. Conclusion Limited mutation analysis can provide a useful first line investigation for PH1. I244T and 33_34insC presented 28.2% of identified mutations causing disease in our cohort. This identification could provide an accurate tool for prenatal diagnosis in the affected families, for genetic counselling and for detection of presymptomatic individuals. PMID:21612638

A Human Strain of Oxalobacter (HC-1) Promotes Enteric Oxalate Secretion in the Small Intestine of Mice and Reduces Urinary Oxalate Excretion

PubMed Central

Hatch, Marguerite; Freel, Robert W.

2013-01-01

Enteric oxalate secretion that correlated with reductions in urinary oxalate excretion was previously reported in a mouse model of Primary Hyperoxaluria, and in wild type (WT) mice colonized with a wild rat strain (OXWR) of Oxalobacter (Am J Physiol 300: G461-G469, 2011). Since a human strain of the bacterium is more likely to be clinically used as a probiotic therapeutic, we tested the effects of HC-1 in WT. Following artificial colonization of WT mice with HC-1, the bacteria were confirmed to be present in the large intestine and, unexpectedly, detected in the small intestine for varying periods of time. The main objective of the present study was to determine whether the presence of HC-1 promoted intestinal secretion in the more proximal segments of the gastrointestinal tract. In addition, we determined whether HC-1 colonization led to reductions in urinary oxalate excretion in these mice. The results show that the human Oxalobacter strain promotes a robust net secretion of oxalate in the distal ileum as well as in the caecum and distal colon and these changes in transport correlate with the beneficial effect of reducing renal excretion of oxalate. We conclude that OXWR effects on intestinal oxalate transport and oxalate homeostasis are not unique to the wild rat strain and that, mechanistically, HC-1 has significant potential for use as a probiotic treatment for hyperoxaluria especially if it is also targeted to the upper and lower gastrointestinal tract. PMID:23959075

Chronic dietary oxalate nephropathy after intensive dietary weight loss regimen

PubMed Central

Khneizer, Gebran; Al-Taee, Ahmad; Mallick, Meher S; Bastani, Bahar

2017-01-01

Background: Hyperoxaluria has been associated with nephrolithiasis as well as acute and chronic kidney disease. We present a case of end stage renal failure caused by excessive dietary oxalate intake in a dietary weight loss regimen. Case Presentation: A 51-year-old Caucasian male with the past medical history of type 2 diabetes mellitus, gout, hypertension and morbid obesity was referred to the primary care clinic after being found pale and easily fatigued. The patient had lost 36 kg over a 7-month period by implementing exercise and intense dietary measures that included 6 meals of spinach, kale, berries, and nuts. Physical examination revealed a blood pressure of 188/93 mm Hg with sunken eyes and dry mucus membranes. Laboratory workup was notable for blood urea nitrogen of 122 mg/dL, creatinine of 12 mg/dL, and estimated glomerular filtration rate (eGFR) of 4.4 mL/min/1.73m2. Patient denied any history of renal disease or renal stones, or taking herbal products, non-steroidal anti-inflammatory drugs, antifreeze (ethylene glycol), or any type of "diet pills." Family history was unremarkable for any renal diseases. After failing intravenous fluid resuscitation, patient was started on maintenance hemodialysis. Abdominal imaging was consistent with chronic renal parenchymal disease with no evidence of nephrolithiasis. Renal biopsy revealed numerous polarized oxalate crystal deposition and diabetic nephropathy class IIA. At this point the patient was instructed to adopt a low oxalate diet. A 24-hour urine collection was remarkable for pH 4.7, citrate <50 mg, and oxalate 46 mg. Importantly, serum oxalate level was undetectable. Repeat renal biopsy 5 months later while patient was still on maintenance hemodialysis revealed persistence of extensive oxalate crystal deposition. Patient has been referred for evaluation for renal transplantation. Conclusions: Clinicians need to maintain a high index of suspicion for dietary hyperoxaluria as a potential etiology for acute or chronic kidney failure, particularly in patients pursuing intensive dietary weight loss intervention PMID:28975090

Primary hyperoxaluria in an adult presenting with end-stage renal failure together with hypercalcemia and hypothyroidism.

PubMed

Karadag, Serhat; Gursu, Meltem; Aydin, Zeki; Uzun, Sami; Dogan, Oner; Ozturk, Savas; Kazancioglu, Rumeyza

2011-10-01

Primary hyperoxaluria (PH) is a rare genetic disorder characterized by overproduction of oxalate due to specific enzyme deficiencies in glyoxylate metabolism. The primary clinical presentation is in the form of recurrent urolithiasis, progressive nephrocalcinosis, end-stage renal disease, and systemic oxalosis. Herein, we present a case of PH who was diagnosed at 47 years of age after 6 years on hemodialysis. He presented with fatigue, anorexia, weight loss, and was found to have cachexia, diffuse edema, hepatomegaly, ascites, hypercalcemia, hyperphosphatemia, hypoalbuminemia, low parathyroid hormone levels, lytic and resorptive areas in the vertebrae, diffusely increased echogenity of the liver, multiple renal stones, and bilateral nephrocalcinosis. Bone marrow biopsy showed calcium oxalate crystals and crystal granulomas. The liver biopsy could not be performed. The absence of an identifiable reason for secondary forms, the severity of the clinical presentation, and pathological findings led to the diagnosis of PH2. He died while waiting for a potential liver and kidney donor. The presented case is consistent with the literature as he had renal stone disease in the third decade and end-stage renal disease in the fifth decade. Hypercalcemia was thought to be due to osteoclast-stimulating activity of macrophages constituting the granuloma. Erythropoietin-resistant anemia and hypothyroidism were thought to be due to accumulation of oxalate in the bone marrow and thyroid gland, respectively. It is very important to keep in mind the possibility of PH when faced with a patient with nephrocalcinosis and oxalate stone disease. © 2011 The Authors; Hemodialysis International © 2011 International Society for Hemodialysis.

Partial trypsin digestion as an indicator of mis-folding of mutant alanine:glyoxylate aminotransferase and chaperone effects of specific ligands. Study of a spectrum of missense mutants.

PubMed

Coulter-Mackie, M B; Lian, Q

2008-07-01

Alanine:glyoxylate aminotransferase (AGT) is a liver peroxisomal enzyme whose deficiency results in primary hyperoxaluria type 1 (PH1). More than 75 PH1 mutations are now documented in the AGT gene (AGXT), of which about 50% are missense. We have previously demonstrated that many such mutants expressed by transcription/translation are subject to generalized degradation by the proteasome and a specific limited trimming by an endogenous ATP-independent protease activity. Here, we report the results of partial digestion using trypsin as a mimic for the endogenous non-proteasomal protease and the use of N-terminal protein sequencing to determine the sensitive site. Partial trypsin digestion also provided an indicator of proper folding of the mutant enzyme. For selected mutations the sensitivity to trypsin could be ameliorated by addition of pyridoxal phosphate or aminooxy acetic acid as specific pharmacological chaperones.

Oxalobacter formigenes–Derived Bioactive Factors Stimulate Oxalate Transport by Intestinal Epithelial Cells

PubMed Central

Arvans, Donna; Jung, Yong-Chul; Antonopoulos, Dionysios; Koval, Jason; Granja, Ignacio; Bashir, Mohamed; Karrar, Eltayeb; Roy-Chowdhury, Jayanta; Musch, Mark; Asplin, John; Chang, Eugene

2017-01-01

Hyperoxaluria is a major risk factor for kidney stones and has no specific therapy, although Oxalobacter formigenes colonization is associated with reduced stone risk. O. formigenes interacts with colonic epithelium and induces colonic oxalate secretion, thereby reducing urinary oxalate excretion, via an unknown secretagogue. The difficulties in sustaining O. formigenes colonization underscore the need to identify the derived factors inducing colonic oxalate secretion. We therefore evaluated the effects of O. formigenes culture conditioned medium (CM) on apical 14C-oxalate uptake by human intestinal Caco-2-BBE cells. Compared with control medium, O. formigenes CM significantly stimulated oxalate uptake (>2.4-fold), whereas CM from Lactobacillus acidophilus did not. Treating the O. formigenes CM with heat or pepsin completely abolished this bioactivity, and selective ultrafiltration of the CM revealed that the O. formigenes–derived factors have molecular masses of 10–30 kDa. Treatment with the protein kinase A inhibitor H89 or the anion exchange inhibitor 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid completely blocked the CM-induced oxalate transport. Knockdown of the oxalate transporter SLC26A6 also significantly restricted the induction of oxalate transport by CM. In a mouse model of primary hyperoxaluria type 1, rectal administration of O. formigenes CM significantly reduced (>32.5%) urinary oxalate excretion and stimulated (>42%) distal colonic oxalate secretion. We conclude that O. formigenes–derived bioactive factors stimulate oxalate transport in intestinal cells through mechanisms including PKA activation. The reduction in urinary oxalate excretion in hyperoxaluric mice treated with O. formigenes CM reflects the in vivo retention of biologic activity and the therapeutic potential of these factors. PMID:27738124

Oxalate quantification in hemodialysate to assess dialysis adequacy for primary hyperoxaluria

PubMed Central

Tang, Xiaojing; Voskoboev, Nikolay V.; Wannarka, Stacie L.; Olson, Julie B.; Milliner, Dawn S.; Lieske, John C.

2015-01-01

Background Patients with primary hyperoxaluria (PH) overproduce oxalate which is eliminated via the kidneys. If end stage kidney disease develops they are at high risk for systemic oxalosis, unless adequate oxalate is removed during hemodialysis to equal or exceed ongoing oxalate production. The purpose of this study was to validate a method to measure oxalate removal in this unique group of dialysis patients. Methods Fourteen stable patients with a confirmed diagnosis of PH on hemodialysis were included in the study. Oxalate was measured serially in hemodialysate and plasma samples in order to calculate rates of oxalate removal. Hemodialysis regimens were adjusted according to a given patient's historical oxalate production, amount of oxalate removal at dialysis, residual renal clearance of oxalate, and plasma oxalate levels. Results After a typical session of hemodialysis, plasma oxalate was reduced by 78.4±7.7%. Eight patients performed hemodialysis 6 times a week, two patients 5 times a week and three patients 3 times a week. Combined oxalate removal by hemodialysis and the kidneys was sufficient to match or exceed endogenous oxalate production. After a median period of 9 months, pre-dialysis plasma oxalate was significantly lower than initially (75.1±33.4 mmol/L vs. 54.8±46.6 mmol/L, P=0.02). Conclusion This methodology can be used to individualize the dialysis prescription of PH patients to prevent oxalosis during the time they are maintained on hemodialysis, and to reduce risk of oxalate injury to a transplanted kidney. PMID:24776840

Bariatric Surgery and Stone Disease

NASA Astrophysics Data System (ADS)

Lieske, John C.; Kumar, Rajiv

2008-09-01

Bariatric surgery is an effective treatment strategy for patients with morbid obesity that can result in effective weight loss, resolution of diabetes mellitus and other weight related complications, and even improved mortality. However, it also appears that hyperoxaluria is common after modern bariatric surgery, perhaps occurring in up to 50% of patients after Rouxen-Y gastric bypass. Although increasing numbers of patients are being seen with calcium oxalate kidney stones after bariatric surgery, and even a few with oxalosis and renal failure, the true risk of these outcomes remains unknown. The mechanisms that contribute to this enteric hyperoxaluria are also incompletely defined, although fat malabsorption may be an important component. Since increasing numbers of these procedures are likely to be performed in the coming years, further study regarding the prevalence and mechanisms of hyperoxaluria and kidney stones after bariatric surgery is needed to devise effective methods of treatment in order to prevent such complications.

Bone metabolism in oxalosis: a single-center study using new imaging techniques and biomarkers.

PubMed

Bacchetta, Justine; Fargue, Sonia; Boutroy, Stéphanie; Basmaison, Odile; Vilayphiou, Nicolas; Plotton, Ingrid; Guebre-Egziabher, Fitsum; Dohin, Bruno; Kohler, Rémi; Cochat, Pierre

2010-06-01

The deposition of calcium oxalate crystals in the kidney and bone is a hallmark of primary hyperoxaluria type 1 (PH1). We report here an evaluation of the bone status of 12 PH1 children based on bone biomarkers [parathyroid hormone, vitamin D, fibroblast growth factor 23 (FGF23)] and radiological assessments (skeletal age, three-dimensional high-resolution peripheral quantitative computed tomography, HR-pQCT) carried out within the framework of a cross-sectional single-center study. The controls consisted of healthy and children with chronic kidney disease already enrolled in local bone and mineral metabolism studies. The mean age (+ or - standard deviation) age of the patients was 99 (+ or - 63) months. Six children suffered from fracture. Bone maturation was accelerated in five patients, four of whom were <5 years. The combination of new imaging techniques and biomarkers highlighted new and unexplained features of PH1: advanced skeletal age in young PH1 patients, increased FGF23 levels and decreased total volumetric bone mineral density with bone microarchitecture alteration.

Frequency of the AGT Pro11Leu polymorphism in humans: Does diet matter?

PubMed

Ségurel, Laure; Lafosse, Sophie; Heyer, Evelyne; Vitalis, Renaud

2010-01-01

The Pro11Leu substitution in the AGXT gene, which causes primary hyperoxaluria type 1, is found with high frequency in some human populations (e.g., 5-20% in Caucasians). It has been suggested that this detrimental mutation could have been positively selected in populations with a meat-rich diet. In order to test this hypothesis, we investigated the occurrence of Pro11Leu in both herder and agriculturalist populations from Central Asia. We found a lower frequency of this detrimental mutation in herders, whose diet is more meat-rich, as compared to agriculturalists, which therefore challenges the universality of the previous claim. Furthermore, when combining our original data with previously published results, we could show that the worldwide genetic differentiation measured at the Pro11Leu polymorphism does not depart from neutrality. Hence, the distribution of the variation observed in the AGXT gene could be due to demographic history, rather than local adaptation to diet.

Pre-emptive liver transplantation for primary hyperoxaluria (PH-I) arrests long-term renal function deterioration.

PubMed

Perera, M Thamara P R; Sharif, Khalid; Lloyd, Carla; Foster, Katharine; Hulton, Sally A; Mirza, Darius F; McKiernan, Patrick J

2011-01-01

Primary hyperoxaluria-I (PH-I) is a serious metabolic disease resulting in end-stage renal disease. Pre-emptive liver transplantation (PLT) for PH-I is an option for children with early diagnosis. There is still little information on its effect on long-term renal function in this situation. Long-term assessment of renal function was conducted using Schwartz's formula (estimated glomerular filtration rate-eGFR) in four children (Group A) undergoing PLT between 2002 and 2008, and a comparison was done with eight gender- and sex-matched controls (Group B) having liver transplantation for other indications. All patients received a liver graft from a deceased donor. Median follow-up for the two groups was 64 and 94 months, respectively. One child in Group A underwent re-transplantation due to hepatic artery thrombosis, while acute rejection was seen in one. A significant difference was seen in eGFR at transplant (81 vs 148 mL/min/1.73 m(2)) with greater functional impairment seen in the study population. In Group A, renal function reduced by 21 and 11% compared with 37 and 35% in Group B at 12 and 24 months, respectively. At 2 years post-transplantation, there was no significant difference in eGFR between the two groups (72 vs 100 mL/min/1.73 m(2), respectively; P = 0.06). Renal function remains relatively stable following pre-emptive LTx for PH-I. With early diagnosis of PH-I, isolated liver transplantation may prevent progression to end-stage renal disease and the need for renal transplantation.

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.

The comparability of oxalate excretion and oxalate:creatinine ratio in the investigation of primary hyperoxaluria: review of data from a referral centre.

PubMed

Clifford-Mobley, Oliver; Tims, Christopher; Rumsby, Gill

2015-01-01

Urine oxalate measurement is an important investigation in the evaluation of renal stone disease. Primary hyperoxaluria (PH) is a rare inherited metabolic disease characterised by persistently elevated urine oxalate, but the diagnosis may be missed in adults until renal failure has developed. Urine oxalate results were reviewed to compare oxalate:creatinine ratio and oxalate excretion, and to estimate the potential numbers of undiagnosed PH. Urine oxalate results from August 2011 to April 2013 were reviewed. Oxalate excretion and oxalate:creatinine ratio were evaluated for 24 h collections and ratio alone for spot urine samples. Oxalate:creatinine ratio and oxalate excretion were moderately correlated (R=0.63) in 24-h urine collections from patients aged 18 years and above. Sex-related differences were found requiring implementation of male and female reference ranges for oxalate:creatinine ratio. Of samples with both ratio and excretion above the reference range, 7% came from patients with confirmed PH. There were 24 patients with grossly elevated urine oxalate who had not been evaluated for PH. Oxalate:creatinine ratio and oxalate excretion were discordant in many patients, which is likely to be a result of intra-individual variation in creatinine output and imprecision in the collection itself. Some PH patients had urine oxalate within the reference range on occasion, and therefore it is not possible to exclude PH on the finding of a single normal result. A significant number of individuals had urine oxalate results well above the reference range who potentially have undiagnosed PH and are consequently at risk of renal failure. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Effect of aqueous extract of Tribulus terrestris on oxalate-induced oxidative stress in rats

PubMed Central

Kamboj, P.; Aggarwal, M.; Puri, S.; Singla, S. K.

2011-01-01

The present study was aimed at studying the effect of Tribulus terrestris on different parameters of oxidative stress and gene expression profiles of antioxidant enzymes in renal tissues of male wistar rats after induction of hyperoxaluria. The animals were divided into three groups. The animals in group I (control) were administered vehicle only. In group II, the animals were treated with ethylene glycol (hyperoxaluric agent) and those in group III were administered T. terrestris plant extract in addition to ethylene glycol. All treatments were continued for a period of seven weeks. Ethylene glycol feeding resulted in hyperoxaluria as well as increased excretion of calcium and phosphate. Serum creatinine, uric acid and blood urea nitrogen levels were also altered in hyperoxaluric animals. Various oxidative stress parameters viz. lipid peroxidation and activity of antioxidant enzymes were used to confirm the peroxidant state. Reverse transcription-polymerase chain reaction (RT-PCR) analysis was used to confirm whether steady-state transcription level of different antioxidant enzymes was altered. T. terrestris significantly reduced the excretion of oxalate, calcium, and phosphate along with decreased levels of blood urea nitrogen, uric acid and creatinine in serum. T. terrestris also reduced hyperoxaluria- caused oxidative stress, and restored antioxidant enzyme activity and their expression profile in kidney tissue. Histological analysis depicted that T. terrestris treatment decreased renal epithelial damage, inflammation, and restored normal glomerular morphology. PMID:21886973

Characteristics of renal papillae in kidney stone formers.

PubMed

Marien, Tracy P; Miller, Nicole L

2016-12-01

The mechanism of kidney stone formation is not well understood. In order to better understand the pathophysiology for specific kidney stone compositions and systemic diseases associated with kidney stones, endoscopic papillary mapping studies with concurrent biopsies have been conducted. This review will summarize the findings of these studies and proposed mechanisms for thirteen disease processes associated with kidney stones. A review of the literature was performed identifying thirteen studies that endoscopically mapped and biopsied renal papillae of different stone formers. These studies characterized renal papillae based on amount of Randall's plaque, Bellini's duct pathology, papillary contour changes, presence of attached stones, pitting, and frequently papillary and cortical biopsies. The groups studied and reviewed here are kidney stone formers who have a history of idiopathic calcium oxalate stone formation, cystinuria, brushite stones, gastric bypass, ileostomy, small bowel resection, primary hyperparathyroidism, distal renal tubular acidosis (dRTA), primary hyperoxaluria, idiopathic calcium phosphate stone formation, medullary sponge kidney (MSK), uric acid stones, and struvite stones. A proposed standardized scoring system for papillary pathology was also reviewed. The series showed various degrees and types of changes to the renal papillae and corresponding histopathologic changes for each type of stone former reviewed. Those with predominantly alone Randall's plaque pathology had less tissue damage versus those with extensive Bellini's duct lesions who had more interstitial fibrosis and cortical pathology. Randall's plaques are associated with stone formers who have low urinary volume, high urinary calcium, and acidic urine and thus are frequently seen in those with brushite stones, primary hyperparathyroidism, small bowel resection, and idiopathic calcium phosphate stone formers. Bellini's duct plugging and pathology is theorized to occur via free solution crystallization, ductal obstruction, inflammation, cellular injury, fibrosis, and acidification defects. Ureteroscopic manifestations of stone disease can vary from normal appearing papillae to significantly diseased appearing papillae. Some diseases have very characteristic papillary changes. Further studies are necessary to fully elucidate the mechanisms of stone formation in patients with nephrolithiasis.

Autophagy inhibition attenuates hyperoxaluria-induced renal tubular oxidative injury and calcium oxalate crystal depositions in the rat kidney.

PubMed

Duan, Xiaolu; Kong, Zhenzhen; Mai, Xin; Lan, Yu; Liu, Yang; Yang, Zhou; Zhao, Zhijian; Deng, Tuo; Zeng, Tao; Cai, Chao; Li, Shujue; Zhong, Wen; Wu, Wenqi; Zeng, Guohua

2018-06-01

Hyperoxaluria-induced oxidative injury of renal tubular epithelial cell is a casual and essential factor in kidney calcium oxalate (CaOx) stone formation. Autophagy has been shown to be critical for the regulation of oxidative stress-induced renal tubular injury; however, little is known about its role in kidney CaOx stone formation. In the present study, we found that the autophagy antagonist chloroquine could significantly attenuate oxalate-induced autophagy activation, oxidative injury and mitochondrial damage of renal tubular cells in vitro and in vivo, as well as hyperoxaluria-induced CaOx crystals depositions in rat kidney, whereas the autophagy agonist rapamycin exerted contrasting effects. In addition, oxalate-induced p38 phosphorylation was significantly attenuated by chloroquine pretreatment but was markedly enhanced by rapamycin pretreatment, whereas the protective effect of chloroquine on rat renal tubular cell oxidative injury was partly reversed by a p38 protein kinase activator anisomycin. Furthermore, the knockdown of Beclin1 represented similar effects to chloroquine on oxalate-induced cell oxidative injury and p38 phosphorylation in vitro. Taken together, our results revealed that autophagy inhibition could attenuate oxalate-induced oxidative injury of renal tubular cell and CaOx crystal depositions in the rat kidney via, at least in part, inhibiting the activation of p38 signaling pathway, thus representing a novel role of autophagy in the regulation of oxalate-induced renal oxidative injury and CaOx crystal depositions for the first time. Copyright © 2018. Published by Elsevier B.V.

Changes of Klotho protein and Klotho mRNA expression in a hydroxy-L-proline induced hyperoxaluric rat model.

PubMed

Jaturakan, Orapun; Buranakarl, Chollada; Dissayabutra, Thasinas; Chaiyabutr, Narongsak; Kijtawornrat, Anusak; Rungsipipat, Anudep

2017-11-17

Klotho protein is recognized as having a renoprotective effect and is used as a biomarker for kidney injury. We investigated the level of Klotho protein in hyperoxaluria-induced kidney injury and the effects of vitamin E (Vit E) and vitamin C (Vit C) supplementation. Hyperoxaluria was induced by feeding 2% (w/v) Hydroxy-L-proline (HLP) in the drinking water for 21 days. Rats were divided into 5 groups; control (Group 1, n=7), HLP treated rats that received nothing else (Group 2, n=7), Vit E (Group 3, n=6), Vit C (Group 4, n=6) and both Vit E and Vit C (Group 5, n=7). Vit E (200 mg/kg) was injected on days 1, 6, 11 and 16, while Vit C (500 mg/kg) was given intravenously on days 1 and 11. The Klotho protein levels and oxidative status were measured. The expression level of kidney Klotho protein expression was significantly reduced by HLP-treatment, while the mRNA expression was higher (P<0.05), the plasma and kidney malondialdehyde and kidney superoxide dismutase activities were increased, and the kidney reduced glutathione and urinary total antioxidant status were decreased (P<0.05). All of these changes were ameliorated by administration of Vit E, Vit C or especially the co-administration of both. In conclusion, HLP-induced hyperoxaluria reduced the kidney Klotho protein level, which could be restored by Vit E and/or Vit C.

Changes of Klotho protein and Klotho mRNA expression in a hydroxy-L-proline induced hyperoxaluric rat model

PubMed Central

JATURAKAN, Orapun; BURANAKARL, Chollada; DISSAYABUTRA, Thasinas; CHAIYABUTR, Narongsak; KIJTAWORNRAT, Anusak; RUNGSIPIPAT, Anudep

2017-01-01

Klotho protein is recognized as having a renoprotective effect and is used as a biomarker for kidney injury. We investigated the level of Klotho protein in hyperoxaluria-induced kidney injury and the effects of vitamin E (Vit E) and vitamin C (Vit C) supplementation. Hyperoxaluria was induced by feeding 2% (w/v) Hydroxy-L-proline (HLP) in the drinking water for 21 days. Rats were divided into 5 groups; control (Group 1, n=7), HLP treated rats that received nothing else (Group 2, n=7), Vit E (Group 3, n=6), Vit C (Group 4, n=6) and both Vit E and Vit C (Group 5, n=7). Vit E (200 mg/kg) was injected on days 1, 6, 11 and 16, while Vit C (500 mg/kg) was given intravenously on days 1 and 11. The Klotho protein levels and oxidative status were measured. The expression level of kidney Klotho protein expression was significantly reduced by HLP-treatment, while the mRNA expression was higher (P<0.05), the plasma and kidney malondialdehyde and kidney superoxide dismutase activities were increased, and the kidney reduced glutathione and urinary total antioxidant status were decreased (P<0.05). All of these changes were ameliorated by administration of Vit E, Vit C or especially the co-administration of both. In conclusion, HLP-induced hyperoxaluria reduced the kidney Klotho protein level, which could be restored by Vit E and/or Vit C. PMID:28943597

Structure of GroEL in Complex with an Early Folding Intermediate of Alanine Glyoxylate Aminotransferase*

PubMed Central

Albert, Armando; Yunta, Cristina; Arranz, Rocío; Peña, Álvaro; Salido, Eduardo; Valpuesta, José María; Martín-Benito, Jaime

2010-01-01

Primary hyperoxaluria type 1 is a rare autosomal recessive disease caused by mutations in the alanine glyoxylate aminotransferase gene (AGXT). We have previously shown that P11L and I340M polymorphisms together with I244T mutation (AGXT-LTM) represent a conformational disease that could be amenable to pharmacological intervention. Thus, the study of the folding mechanism of AGXT is crucial to understand the molecular basis of the disease. Here, we provide biochemical and structural data showing that AGXT-LTM is able to form non-native folding intermediates. The three-dimensional structure of a complex between the bacterial chaperonin GroEL and a folding intermediate of AGXT-LTM mutant has been solved by cryoelectron microscopy. The electron density map shows the protein substrate in a non-native extended conformation that crosses the GroEL central cavity. Addition of ATP to the complex induces conformational changes on the chaperonin and the internalization of the protein substrate into the folding cavity. The structure provides a three-dimensional picture of an in vivo early ATP-dependent step of the folding reaction cycle of the chaperonin and supports a GroEL functional model in which the chaperonin promotes folding of the AGXT-LTM mutant protein through forced unfolding mechanism. PMID:20056599

Structure of GroEL in complex with an early folding intermediate of alanine glyoxylate aminotransferase.

PubMed

Albert, Armando; Yunta, Cristina; Arranz, Rocío; Peña, Alvaro; Salido, Eduardo; Valpuesta, José María; Martín-Benito, Jaime

2010-02-26

Primary hyperoxaluria type 1 is a rare autosomal recessive disease caused by mutations in the alanine glyoxylate aminotransferase gene (AGXT). We have previously shown that P11L and I340M polymorphisms together with I244T mutation (AGXT-LTM) represent a conformational disease that could be amenable to pharmacological intervention. Thus, the study of the folding mechanism of AGXT is crucial to understand the molecular basis of the disease. Here, we provide biochemical and structural data showing that AGXT-LTM is able to form non-native folding intermediates. The three-dimensional structure of a complex between the bacterial chaperonin GroEL and a folding intermediate of AGXT-LTM mutant has been solved by cryoelectron microscopy. The electron density map shows the protein substrate in a non-native extended conformation that crosses the GroEL central cavity. Addition of ATP to the complex induces conformational changes on the chaperonin and the internalization of the protein substrate into the folding cavity. The structure provides a three-dimensional picture of an in vivo early ATP-dependent step of the folding reaction cycle of the chaperonin and supports a GroEL functional model in which the chaperonin promotes folding of the AGXT-LTM mutant protein through forced unfolding mechanism.

Oxalosis and Hyperoxaluria Foundation

MedlinePlus

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Calcium oxalate crystal related kidney injury in a patient receiving Roux-en Y hepaticojejunostomy due to gall bladder cancer.

PubMed

Tsai, Jun-Li; Tsai, Shang-Feng

2017-03-29

Calcium oxalate nephropathy is rare in current practice. It was a common complication during jejunoileal bypass, but much less seen in modern gastric bypass surgery for morbid obesity. The major cause of it is enteric hyperoxaluria. We report on a patient here with acute kidney disease due to calcium oxalate nephropathy, rather than the conditions mentioned above. The male patient received a Roux-en Y hepaticojejunostomy and common bile duct drainage. In addition to enteric hyperoxaluria, chronic kidney disease related metabolic acidosis, chronic diarrhea related volume depletion, a high oxalate and low potassium diet, long term ascorbic acid intake and long term exposure to antibiotics, all predisposed him to having oxalate nephropathy. This is the first case with such conditions and we recommend that similarly diagnosed patients avoid all these predisposing factors, in order to avoid this rare disease and its undesired outcome.

Hereditary Causes of Kidney Stones and Chronic Kidney Disease

PubMed Central

Edvardsson, Vidar O.; Goldfarb, David S.; Lieske, John C.; Beara-Lasic, Lada; Anglani, Franca; Milliner, Dawn S.; Palsson, Runolfur

2013-01-01

Adenine phosphoribosyltransferase (APRT) deficiency, cystinuria, Dent disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) and primary hyperoxaluria (PH) are rare but important causes of severe kidney stone disease and/or chronic kidney disease in children. Recurrent kidney stone disease and nephrocalcinosis, particularly in pre-pubertal children, should alert the physician to the possibility of an inborn error of metabolism as the underlying cause. Unfortunately, the lack of recognition and knowledge of the five disorders has frequently resulted in an unacceptable delay in diagnosis and treatment, sometimes with grave consequences. A high index of suspicion coupled with early diagnosis may reduce or even prevent the serious long-term complications of these diseases. In this paper, we review the epidemiology, clinical features, diagnosis, treatment and outcome of patients with APRT deficiency, cystinuria, Dent disease, FHHNC and PH with emphasis on childhood manifestations. PMID:23334384

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

Dietary hyperoxaluria is not reduced by treatment with lactic acid bacteria

PubMed Central

2013-01-01

Background Secondary hyperoxaluria either based on increased intestinal absorption of oxalate (enteric), or high oxalate intake (dietary), is a major risk factor of calcium oxalate urolithiasis. Oxalate-degrading bacteria might have beneficial effects on urinary oxalate excretion resulting from decreased intestinal oxalate concentration and absorption. Methods Twenty healthy subjects were studied initially while consuming a diet normal in oxalate. Study participants were then placed on a controlled oxalate-rich diet for a period of 6 weeks. Starting with week 2 of the oxalate-rich diet, participants received 2.6 g/day of a lactic acid bacteria preparation for 5 weeks. Finally, subjects were examined 4 weeks after treatment while consuming again a normal-oxalate diet. Participants provided weekly 24-hour urine specimens. Analyses of blood samples were performed before and at the end of treatment. Results Urinary oxalate excretion increased significantly from 0.354 ± 0.097 at baseline to 0.542 ± 0.163 mmol/24 h under the oxalate-rich diet and remained elevated until the end of treatment, as did relative supersaturation of calcium oxalate. Plasma oxalate concentration was significantly higher after 5 weeks of treatment compared to baseline. Four weeks after treatment, urinary oxalate excretion and relative supersaturation of calcium oxalate fell to reach initial values. Conclusions Persistent dietary hyperoxaluria and increased plasma oxalate concentration can already be induced in healthy subjects without disorders of oxalate metabolism. The study preparation neither reduced urinary oxalate excretion nor plasma oxalate concentration. The preparation may be altered to select for lactic acid bacteria strains with the highest oxalate-degrading activity. PMID:24330782

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.

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.

Chronic Kidney Disease in Kidney Stone Formers

PubMed Central

Krambeck, Amy E.; Lieske, John C.

2011-01-01

Summary Recent population studies have found symptomatic kidney stone formers to be at increased risk for chronic kidney disease (CKD). Although kidney stones are not commonly identified as the primary cause of ESRD, they still may be important contributing factors. Paradoxically, CKD can be protective against forming kidney stones because of the substantial reduction in urine calcium excretion. Among stone formers, those with rare hereditary diseases (cystinuria, primary hyperoxaluria, Dent disease, and 2,8 dihydroxyadenine stones), recurrent urinary tract infections, struvite stones, hypertension, and diabetes seem to be at highest risk for CKD. The primary mechanism for CKD from kidney stones is usually attributed to an obstructive uropathy or pyelonephritis, but crystal plugs at the ducts of Bellini and parenchymal injury from shockwave lithotripsy may also contribute. The historical shift to less invasive surgical management of kidney stones has likely had a beneficial impact on the risk for CKD. Among potential kidney donors, past symptomatic kidney stones but not radiographic stones found on computed tomography scans were associated with albuminuria. Kidney stones detected by ultrasound screening have also been associated with CKD in the general population. Further studies that better classify CKD, better characterize stone formers, more thoroughly address potential confounding by comorbidities, and have active instead of passive follow-up to avoid detection bias are needed. PMID:21784825

Active site and loop 4 movements within human glycolate oxidase: implications for substrate specificity and drug design.

PubMed

Murray, Michael S; Holmes, Ross P; Lowther, W Todd

2008-02-26

Human glycolate oxidase (GO) catalyzes the FMN-dependent oxidation of glycolate to glyoxylate and glyoxylate to oxalate, a key metabolite in kidney stone formation. We report herein the structures of recombinant GO complexed with sulfate, glyoxylate, and an inhibitor, 4-carboxy-5-dodecylsulfanyl-1,2,3-triazole (CDST), determined by X-ray crystallography. In contrast to most alpha-hydroxy acid oxidases including spinach glycolate oxidase, a loop region, known as loop 4, is completely visible when the GO active site contains a small ligand. The lack of electron density for this loop in the GO-CDST complex, which mimics a large substrate, suggests that a disordered to ordered transition may occur with the binding of substrates. The conformational flexibility of Trp110 appears to be responsible for enabling GO to react with alpha-hydroxy acids of various chain lengths. Moreover, the movement of Trp110 disrupts a hydrogen-bonding network between Trp110, Leu191, Tyr134, and Tyr208. This loss of interactions is the first indication that active site movements are directly linked to changes in the conformation of loop 4. The kinetic parameters for the oxidation of glycolate, glyoxylate, and 2-hydroxy octanoate indicate that the oxidation of glycolate to glyoxylate is the primary reaction catalyzed by GO, while the oxidation of glyoxylate to oxalate is most likely not relevant under normal conditions. However, drugs that exploit the unique structural features of GO may ultimately prove to be useful for decreasing glycolate and glyoxylate levels in primary hyperoxaluria type 1 patients who have the inability to convert peroxisomal glyoxylate to glycine.

Enhanced vulnerability of human proteins towards disease-associated inactivation through divergent evolution.

PubMed

Medina-Carmona, Encarnación; Fuchs, Julian E; Gavira, Jose A; Mesa-Torres, Noel; Neira, Jose L; Salido, Eduardo; Palomino-Morales, Rogelio; Burgos, Miguel; Timson, David J; Pey, Angel L

2017-09-15

Human proteins are vulnerable towards disease-associated single amino acid replacements affecting protein stability and function. Interestingly, a few studies have shown that consensus amino acids from mammals or vertebrates can enhance protein stability when incorporated into human proteins. Here, we investigate yet unexplored relationships between the high vulnerability of human proteins towards disease-associated inactivation and recent evolutionary site-specific divergence of stabilizing amino acids. Using phylogenetic, structural and experimental analyses, we show that divergence from the consensus amino acids at several sites during mammalian evolution has caused local protein destabilization in two human proteins linked to disease: cancer-associated NQO1 and alanine:glyoxylate aminotransferase, mutated in primary hyperoxaluria type I. We demonstrate that a single consensus mutation (H80R) acts as a disease suppressor on the most common cancer-associated polymorphism in NQO1 (P187S). The H80R mutation reactivates P187S by enhancing FAD binding affinity through local and dynamic stabilization of its binding site. Furthermore, we show how a second suppressor mutation (E247Q) cooperates with H80R in protecting the P187S polymorphism towards inactivation through long-range allosteric communication within the structural ensemble of the protein. Our results support that recent divergence of consensus amino acids may have occurred with neutral effects on many functional and regulatory traits of wild-type human proteins. However, divergence at certain sites may have increased the propensity of some human proteins towards inactivation due to disease-associated mutations and polymorphisms. Consensus mutations also emerge as a potential strategy to identify structural hot-spots in proteins as targets for pharmacological rescue in loss-of-function genetic diseases. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Inhibition of calcium oxalate crystal deposition on kidneys of urolithiatic rats by Hibiscus sabdariffa L. extract.

PubMed

Laikangbam, Reena; Damayanti Devi, M

2012-06-01

The present study aims at systematic evaluation of the calyces of Hibiscus sabdariffa to establish its scientific validity for anti-urolithiatic property using ethylene glycol-induced hyperoxaluria model in male albino rats. Administration of a mixture of 0.75% ethylene glycol and 2% ammonium chloride resulted in hyperoxaluria as well as increased renal excretion of calcium and phosphate. The decrease in the serum calcium concentration indicates an increased calcium oxalate formation. Supplementation of aqueous extract of H. sabdariffa at different doses (250, 500 and 750 mg/kg body weight) significantly lowered the deposition of stone-forming constituents in the kidneys and serum of urolithiatic rats. These findings have been confirmed through histological investigations. Results of in vivo genotoxicity testing showed no significant chromosomal aberrations in the bone marrow cells of ethylene glycol-induced rats. The plant extracts at the doses investigated induced neither toxic nor lethal effects and are safe. It can be concluded that the calyces of H. sabdariffa are endowed with anti-urolithiatic activity and do not have genotoxic effects. Thus, it can be introduced in clinical practices and medicine in the form of orally administered syrup after further investigations and clinical trials.

Oxalate, inflammasome, and progression of kidney disease

PubMed Central

Ermer, Theresa; Eckardt, Kai-Uwe; Aronson, Peter S.; Knauf, Felix

2016-01-01

Purpose of review Oxalate is an end product of metabolism excreted via the kidney. Excess urinary oxalate, whether from primary or enteric hyperoxaluria, can lead to oxalate deposition in the kidney. Oxalate crystals are associated with renal inflammation, fibrosis and progressive renal failure. It has long been known that as glomerular filtration rate (GFR) becomes reduced in chronic kidney disease (CKD), there is striking elevation of plasma oxalate. Taken together, these findings raise the possibility that elevation of plasma oxalate in CKD may promote renal inflammation and more rapid progression of CKD independent of primary etiology. Recent findings The inflammasome has recently been identified to play a critical role in oxalate-induced renal inflammation. Oxalate crystals have been shown to activate the nucleotide-binding domain, leucine-rich repeat inflammasome 3 (also known as NALP3, NLRP3 or cryopyrin), resulting in release of Interleukin-1β and macrophage infiltration. Deletion of inflammasome proteins in mice protects from oxalate-induced renal inflammation and progressive renal failure. Summary The findings reviewed in this article expand our understanding of the relevance of elevated plasma oxalate levels leading to inflammasome activation. We propose that inhibiting oxalate-induced inflammasome activation, or lowering plasma oxalate, may prevent or mitigate progressive renal damage in CKD, and warrants clinical trials. PMID:27191349

An update and practical guide to renal stone management.

PubMed

Johri, Nikhil; Cooper, Bruce; Robertson, William; Choong, Simon; Rickards, David; Unwin, Robert

2010-01-01

Renal stone disease covers kidney and lower urinary tract stones caused by a variety of conditions, including metabolic and inherited disorders, and anatomical defects with or without chronic urinary infection. Most cases are idiopathic, in which there is undoubtedly a genetic predisposition, but where environmental and lifestyle factors play an important role. Indeed, it is becoming apparent that renal stone disease is often part of a larger 'metabolic picture' commonly associated with type 2 diabetes, obesity, dyslipidaemia, and hypertension. Renal stone disease is a growing problem in the UK (and other developed and developing populations) with a cross-sectional prevalence of ∼1.2%. This means that there are currently ∼720,000 individuals with a history of kidney stones in the UK. Almost 40% of first-time stone formers will form a second stone within 3 years of the first episode if no prophylactic measures are instituted to prevent stone recurrence, since removal or disintegration of the first stone does not treat the underlying cause of stones in the majority of patients. The age of onset is getting younger and the sex ratio (until recently more men than women) is becoming almost even. Metabolic screening remains an important part of investigating renal stone disease, but to the disappointment and frustration of many doctors, medical treatment is still essentially pragmatic, except perhaps in cystinuria, and to a limited extent in primary hyperoxaluria (if pyridoxine-sensitive); although newer treatments may be emerging. This review summarizes current thinking and provides a practical basis for the management of renal stone disease. Copyright © 2010 S. Karger AG, Basel.

Familial mixed nephrocalcinosis as a cause of chronic kidney failure: two case reports.

PubMed

de Arruda, Pedro Francisco Ferraz; Gatti, Márcio; de Arruda, José Germano Ferraz; Fácio, Fernando Nestor; Spessoto, Luis Cesar Fava; de Arruda, Laísa Ferraz; de Godoy, José Maria Pereira; Godoy, Moacir Fernandes

2014-10-27

Nephrocalcinosis consists of the deposition of calcium salts in the renal parenchyma and is considered the mixed form when it involves the renal cortex and medulla. The main etiological agents of this condition are primary hyperparathyroidism, renal tubular acidosis, medullary sponge kidney, hyperoxaluria and taking certain drugs. These factors can lead to hypercalcemia and/or hypercalciuria, which can give rise to nephrocalcinosis. Patient 1 was a 48-year-old Caucasian woman with a history of bilateral nephrocalcinosis causing chronic kidney failure. Imaging examinations (X-ray, ultrasound and computed tomography of the abdomen) revealed extensive calcium deposits in the renal parenchyma, indicating nephrocalcinosis as the causal factor of the disease. Patient 2 is the 45-year-old brother of patient 1. He exhibited an advanced stage of chronic kidney failure. As nephrocalcinosis is considered to have a genetic component, a family investigation revealed this condition in patient 2. Nephrocalcinosis may be detected incidentally through diagnostic imaging studies. Whenever possible, treatment should include the base disease that caused the appearance of the calcification, as the precise etiological determination is extremely important.

Intestinal Adaptations in Chronic Kidney Disease and the Influence of Gastric Bypass Surgery

PubMed Central

Hatch, Marguerite

2015-01-01

Studies have shown that compensatory adaptations in gastrointestinal oxalate transport can impact the amount of oxalate excreted by the kidney. Hyperoxaluria is a major risk factor in the formation of kidney stones and oxalate is derived from both the diet as well as from liver metabolism of glyoxylate. Although the intestine generally absorbs oxalate from dietary sources, and can contribute as much as 50% of urinary oxalate, enteric oxalate elimination plays a significant role when renal function is compromised. While the mechanistic basis for these changes in the direction of intestinal oxalate movements in chronic renal failure involves an up-regulation of angiotensin II (ANG) receptors in the large intestine, enteric secretion/excretion of oxalate can also occur by mechanisms that are independent of ANG II. Most notably, the commensal bacterium Oxalobacter sp. interacts with the host enterocyte and promotes the movement of oxalate from blood into the lumen resulting in the beneficial effect of significantly lowering urinary oxalate excretion. Changes in the passive permeability of the intestine such as in steatorrhea and following gastric bypass also promote oxalate absorption and hyperoxaluria. In summary, this report highlights the two-way physiological signaling between the gut and the kidney which may help to alleviate the consequences of certain kidney diseases. PMID:24951497

Frequency of metabolic abnormalities in urinary stones patients

PubMed Central

Ahmad, Iftikhar; Pansota, Mudassar Saeed; Tariq, Muhammad; Tabassum, Shafqat Ali

2013-01-01

Objective: To determine the frequency of metabolic abnormalities in the serum and urine of patients with urinary stones disease. Methods: Two hundred patients with either multiple or recurrent urolithiasis diagnosed on ultrasonography and intravenous urography were included in this study. 24 hour urine sample were collected from each patient and sent for PH, specific gravity, Creatinine, uric acid, calcium, phosphate, oxalate, citrate and magnesium. In addition, blood sample of each patient was also sent for serum levels of urea, creatinine, uric acid, phosphate and calcium. Results: Mean age of patients was 38 ± 7.75 years with male to female ratio of 2:1. The main presenting complaint was lumber pain and 82.5% patients were found to have calcium oxalate stones on chemical analysis. Metabolic abnormalities were found in 90.5% patients, whereas there were no metabolic abnormalities in 19 (9.5%) patients. Forty patients (21.5%) only had one metabolic abnormality and 157 (78.5%) patients had multiple metabolic abnormalities. Hyperoxaluria was the most commonly observed metabolic abnormality and was found in 64.5% patients. Other significant metabolic abnormalities were hypercalciuria, Hypercalcemia, hypocitraturia and hyperuricemia. Conclusion: This study concludes that frequency of metabolic abnormalities is very high in patients with urolithiasis and hyperoxaluria, hypercalciuria and hypocitraturia are the most important metabolic abnormalities observed in these patients. PMID:24550954

Frequency of metabolic abnormalities in urinary stones patients.

PubMed

Ahmad, Iftikhar; Pansota, Mudassar Saeed; Tariq, Muhammad; Tabassum, Shafqat Ali

2013-11-01

To determine the frequency of metabolic abnormalities in the serum and urine of patients with urinary stones disease. Two hundred patients with either multiple or recurrent urolithiasis diagnosed on ultrasonography and intravenous urography were included in this study. 24 hour urine sample were collected from each patient and sent for PH, specific gravity, Creatinine, uric acid, calcium, phosphate, oxalate, citrate and magnesium. In addition, blood sample of each patient was also sent for serum levels of urea, creatinine, uric acid, phosphate and calcium. Mean age of patients was 38 ± 7.75 years with male to female ratio of 2:1. The main presenting complaint was lumber pain and 82.5% patients were found to have calcium oxalate stones on chemical analysis. Metabolic abnormalities were found in 90.5% patients, whereas there were no metabolic abnormalities in 19 (9.5%) patients. Forty patients (21.5%) only had one metabolic abnormality and 157 (78.5%) patients had multiple metabolic abnormalities. Hyperoxaluria was the most commonly observed metabolic abnormality and was found in 64.5% patients. Other significant metabolic abnormalities were hypercalciuria, Hypercalcemia, hypocitraturia and hyperuricemia. This study concludes that frequency of metabolic abnormalities is very high in patients with urolithiasis and hyperoxaluria, hypercalciuria and hypocitraturia are the most important metabolic abnormalities observed in these patients.

Vitamin D Supplementation in Submariners

DTIC Science & Technology

2008-12-02

prevalence of over 10% in men.71 Most stones are composed of calcium oxalate or calcium phosphate.72 It is the composition of these stones that...urine that combine with calcium to form calcium oxalate stones.77 One of the major factors that reduce hyperoxaluria is calcium in the diet. The... calcium in the intestinal lumen forms insoluble calcium salts with the oxalates and is not absorbed. A diet low in calcium will allow more oxalates to be

Consequences of missense mutations for dimerization and turnover of alanine:glyoxylate aminotransferase: study of a spectrum of mutations.

PubMed

Coulter-Mackie, M B; Lian, Q

2006-12-01

Alanine:glyoxylate aminotransferase (AGT) is a liver peroxisomal enzyme, deficiency of which results in primary hyperoxaluria type 1 (PH1). More than 65 PH1-related mutations are now documented in the AGT gene (AGXT), of which about 50% are missense. We have generated a spectrum of 15 missense changes including the most common PH1 mutation, G170R, and expressed them on the appropriate background of the major or minor allele, in an Escherichia coli overexpression system and in a rabbit reticulocyte transcription/translation system. We have investigated their effects on enzyme activity, dimerization, aggregation, and turnover. The effect of pyridoxal phosphate (PLP) on dimerization and stability was also investigated. Although all 15 mutant AGTs were expressed as intact proteins in E. coli, only three: G41R and G41V on the major allele, and the common mutation G170R, resulted in significant amounts of enzymatic activity. Dimerization failure was a frequent observation (13/15) except for G41V and D183N. Dimerization was poor with S187F but was substantially improved with PLP. Proteasome-mediated protein degradation was observed for all the mutations except G41R on the major allele, G41V, D183N, G170R, and S218L. Increases in the stability of the mutant enzymes in the presence of PLP were small; however, G41R on the minor allele showed a direct relationship between its half life and the concentration of PLP. The minor allele AGT product and many of the mutants were subject to a limited non-proteasomal proteolytic cleavage when ATP was depleted.

Caenorhabditis elegans AGXT-1 is a mitochondrial and temperature-adapted ortholog of peroxisomal human AGT1: New insights into between-species divergence in glyoxylate metabolism.

PubMed

Mesa-Torres, Noel; Calvo, Ana C; Oppici, Elisa; Titelbaum, Nicholas; Montioli, Riccardo; Miranda-Vizuete, Antonio; Cellini, Barbara; Salido, Eduardo; Pey, Angel L

2016-09-01

In humans, glyoxylate is an intermediary product of metabolism, whose concentration is finely balanced. Mutations in peroxisomal alanine:glyoxylate aminotransferase (hAGT1) cause primary hyperoxaluria type 1 (PH1), which results in glyoxylate accumulation that is converted to toxic oxalate. In contrast, glyoxylate is used by the nematode Caenorhabditis elegans through a glyoxylate cycle to by-pass the decarboxylation steps of the tricarboxylic acid cycle and thus contributing to energy production and gluconeogenesis from stored lipids. To investigate the differences in glyoxylate metabolism between humans and C. elegans and to determine whether the nematode might be a suitable model for PH1, we have characterized here the predicted nematode ortholog of hAGT1 (AGXT-1) and compared its molecular properties with those of the human enzyme. Both enzymes form active PLP-dependent dimers with high specificity towards alanine and glyoxylate, and display similar three-dimensional structures. Interestingly, AGXT-1 shows 5-fold higher activity towards the alanine/glyoxylate pair than hAGT1. Thermal and chemical stability of AGXT-1 is lower than that of hAGT1, suggesting temperature-adaptation of the nematode enzyme linked to the lower optimal growth temperature of C. elegans. Remarkably, in vivo experiments demonstrate the mitochondrial localization of AGXT-1 in contrast to the peroxisomal compartmentalization of hAGT1. Our results support the view that the different glyoxylate metabolism in the nematode is associated with the divergent molecular properties and subcellular localization of the alanine:glyoxylate aminotransferase activity. Copyright © 2016 Elsevier B.V. All rights reserved.

The chaperone role of the pyridoxal 5'-phosphate and its implications for rare diseases involving B6-dependent enzymes.

PubMed

Cellini, Barbara; Montioli, Riccardo; Oppici, Elisa; Astegno, Alessandra; Voltattorni, Carla Borri

2014-02-01

The biologically active form of the B6 vitamers is pyridoxal 5'-phosphate (PLP), which plays a coenzymatic role in several distinct enzymatic activities ranging from the synthesis, interconversion and degradation of amino acids to the replenishment of one-carbon units, synthesis and degradation of biogenic amines, synthesis of tetrapyrrolic compounds and metabolism of amino-sugars. In the catalytic process of PLP-dependent enzymes, the substrate amino acid forms a Schiff base with PLP and the electrophilicity of the PLP pyridine ring plays important roles in the subsequent catalytic steps. While the essential role of PLP in the acquisition of biological activity of many proteins is long recognized, the finding that some PLP-enzymes require the coenzyme for refolding in vitro points to an additional role of PLP as a chaperone in the folding process. Mutations in the genes encoding PLP-enzymes are causative of several rare inherited diseases. Patients affected by some of these diseases (AADC deficiency, cystathionuria, homocystinuria, gyrate atrophy, primary hyperoxaluria type 1, xanthurenic aciduria, X-linked sideroblastic anaemia) can benefit, although at different degrees, from the administration of pyridoxine, a PLP precursor. The effect of the coenzyme is not limited to mutations that affect the enzyme-coenzyme interaction, but also to those that cause folding defects, reinforcing the idea that PLP could play a chaperone role and improve the folding efficiency of misfolded variants. In this review, recent biochemical and cell biology studies highlighting the chaperoning activity of the coenzyme on folding-defective variants of PLP-enzymes associated with rare diseases are presented and discussed. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Sat1 is dispensable for active oxalate secretion in mouse duodenum

PubMed Central

Ko, Narae; Knauf, Felix; Jiang, Zhirong; Markovich, Daniel

2012-01-01

Mice deficient for the apical membrane oxalate transporter SLC26A6 develop hyperoxalemia, hyperoxaluria, and calcium oxalate stones due to a defect in intestinal oxalate secretion. However, the nature of the basolateral membrane oxalate transport process that operates in series with SLC26A6 to mediate active oxalate secretion in the intestine remains unknown. Sulfate anion transporter-1 (Sat1 or SLC26A1) is a basolateral membrane anion exchanger that mediates intestinal oxalate transport. Moreover, Sat1-deficient mice also have a phenotype of hyperoxalemia, hyperoxaluria, and calcium oxalate stones. We, therefore, tested the role of Sat1 in mouse duodenum, a tissue with Sat1 expression and SLC26A6-dependent oxalate secretion. Although the active secretory flux of oxalate across mouse duodenum was strongly inhibited (>90%) by addition of the disulfonic stilbene DIDS to the basolateral solution, secretion was unaffected by changes in medium concentrations of sulfate and bicarbonate, key substrates for Sat1-mediated anion exchange. Inhibition of intracellular bicarbonate production by acetazolamide and complete removal of bicarbonate from the buffer also produced no change in oxalate secretion. Finally, active oxalate secretion was not reduced in Sat1-null mice. We conclude that a DIDS-sensitive basolateral transporter is involved in mediating oxalate secretion across mouse duodenum, but Sat1 itself is dispensable for this process. PMID:22517357

Intestinal adaptations in chronic kidney disease and the influence of gastric bypass surgery.

PubMed

Hatch, Marguerite

2014-09-01

Studies have shown that compensatory adaptations in gastrointestinal oxalate transport can impact the amount of oxalate excreted by the kidney. Hyperoxaluria is a major risk factor in the formation of kidney stones, and oxalate is derived from both the diet and the liver metabolism of glyoxylate. Although the intestine generally absorbs oxalate from dietary sources and can contribute as much as 50% of urinary oxalate, enteric oxalate elimination plays a significant role when renal function is compromised. While the mechanistic basis for these changes in the direction of intestinal oxalate movements in chronic renal failure involves an upregulation of angiotensin II receptors in the large intestine, enteric secretion/excretion of oxalate can also occur by mechanisms that are independent of angiotensin II. Most notably, the commensal bacterium Oxalobacter sp. interacts with the host enterocyte and promotes the movement of oxalate from the blood into the lumen, resulting in the beneficial effect of significantly lowering urinary oxalate excretion. Changes in the passive permeability of the intestine, such as in steatorrhoea and following gastric bypass, also promote oxalate absorption and hyperoxaluria. In summary, this report highlights the two-way physiological signalling between the gut and the kidney, which may help to alleviate the consequences of certain kidney diseases. © 2014 The Author. Experimental Physiology © 2014 The Physiological Society.

Diagnostic examination of the child with urolithiasis or nephrocalcinosis.

PubMed

Hoppe, Bernd; Kemper, Markus J

2010-03-01

Urolithiasis and nephrocalcinosis are more frequent in children then currently anticipated, but still remain under- or misdiagnosed in a significant proportion of patients, since symptoms and signs may be subtle or misleading. All children with colicky abdominal pain or macroscopic hematuria should be examined thoroughly for urolithiasis. Also, other, more general, abdominal manifestations can be the first symptoms of renal stones. The patients and their family histories, as well as physical examination, are important initial steps for diagnostic evaluation. Thereafter, diagnostic imaging should be aimed at the location of calculi but also at identification of urinary tract anomalies or acute obstruction due to stone disease. This can often be accomplished by ultrasound examination alone, but sometimes radiological methods such as plain abdominal films or more sensitive non-enhanced computed tomography are necessary. Since metabolic causes are frequent in children, diagnostic evaluation should be meticulous so that metabolic disorders that cause recurrent urolithiasis or even renal failure, such as the primary hyperoxalurias and others, can be ruled out. The stone is not the disease itself; it is only one serious sign! Therefore, thorough and early diagnostic examination is mandatory for every infant and child with the first stone event, or with nephrocalcinosis.

The role of intestinal oxalate transport in hyperoxaluria and the formation of kidney stones in animals and man

PubMed Central

Whittamore, Jonathan M.; Hatch, Marguerite

2016-01-01

The intestine exerts a considerable influence over urinary oxalate in two ways, through the absorption of dietary oxalate and by serving as an adaptive extra-renal pathway for elimination of this waste metabolite. Knowledge of the mechanisms responsible for oxalate absorption and secretion by the intestine therefore have significant implications for understanding the etiology of hyperoxaluria, as well as offering potential targets for future treatment strategies for calcium oxalate kidney stone disease. In this review, we present the recent developments and advances in this area over the past 10 years, and put to the test some of the new ideas that have emerged during this time, using human and mouse models. A key focus for our discussion are the membrane-bound anion exchangers, belonging to the SLC26 gene family, some of which have been shown to participate in transcellular oxalate absorption and secretion. This has offered the opportunity to not only examine the roles of these specific transporters, revealing their importance to oxalate homeostasis, but to also probe the relative contributions made by the active transcellular and passive paracellular components of oxalate transport across the intestine. We also discuss some of the various physiological stimuli and signaling pathways which have been suggested to participate in the adaptation and regulation of intestinal oxalate transport. Finally, we offer an update on research into Oxalobacter formigenes, alongside recent investigations of other oxalate-degrading gut bacteria, in both laboratory animals and humans. PMID:27913853

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®

Relative hyperoxaluria, crystalluria and haematuria after megadose ingestion of vitamin C.

PubMed

Auer, B L; Auer, D; Rodgers, A L

1998-09-01

Long-term or high-dosage consumption of vitamin C may play a role in calcium oxalate kidney stone formation. The present study was undertaken to determine the biochemical and physicochemical risk factors in a male subject who developed haematuria and calcium oxalate crystalluria after ingestion of large doses of ascorbic acid for 8 consecutive days. Twenty-four-hour urine samples were collected before and during the ascorbic acid ingestion period as well as after the detection of haematuria. A special procedure was implemented for urine collections to allow for oxalate, ascorbate and other urinalysis. Oxalate was determined in the presence of EDTA to prevent in vitro conversion to ascorbic acid, whereas ascorbate itself was determined by manual titration in a redox method using the dye dichlorophenolindophenol. Urinalysis data were used to compute calcium oxalate relative supersaturations and Tiselius risk indices, whereas scanning electron microscopy was used to examine urinary deposits. Oxalate excretion increased by about 350% during ascorbate ingestion before haematuria. Ascorbate concentrations also increased dramatically but appeared to reach a plateau maximum. Increasing calcium excretion was accompanied by decreasing potassium and phosphate values. The calcium oxalate relative supersaturation and Tiselius risk index increased during vitamin C ingestion and large aggregates of calcium oxalate dihydrate crystals were observed by scanning electron microscopy immediately after the detection of haematuria. High percentage metabolic conversion of ascorbate to oxalate in this subject caused relative hyperoxaluria and crystalluria, the latter manifesting itself as haematuria. Clinicians need to be alerted to the potential dangers of large dose ingestion of vitamin C in some individuals.

Combination of vitamin E and vitamin C alleviates renal function in hyperoxaluric rats via antioxidant activity.

PubMed

Jaturakan, Orapun; Dissayabutra, Thasinas; Chaiyabutr, Narongsak; Kijtawornrat, Anusak; Tosukhowong, Piyaratana; Rungsipipat, Anudep; Nhujak, Thumnoon; Buranakarl, Chollada

2017-05-18

Hyperoxaluria and oxidative stress are risk factors in calcium oxalate (CaOx) stone formation. Supplement with antioxidant could be effective in prevention of recurrent stone formation. The present study aims to evaluate the protective effects of vitamin E and vitamin C in hyperoxaluric rat. The experiment was performed in rats for 21 days. Rats were divided into 5 groups as follows: control (group 1, n=8), hyperoxaluric rats (group 2, n=8), hyperoxaluric rats with vitamin E supplement (group 3, n=7), hyperoxaluric rats with vitamin C supplement (group 4, n=7) and hyperoxaluric rats with vitamin E and C supplement (group 5, n=7). Hyperoxaluria was induced by feeding hydroxyl L-proline (HLP) 2% w/v dissolved in drinking water. Intraperitoneal 200 mg/kg of vitamin E was given in groups 3 and 5 on days 1, 6, 11 and 16, while 500 mg of vitamin C was injected intravenously in groups 4 and 5 on days 1 and 11. Renal functions and oxidative status were measured. The urinary oxalate excretion was increased in HLP supplement rats, while glomerular filtration rate, proximal water and sodium reabsorption were significantly lower in group 2 compared with a control (P<0.05). Giving antioxidants significantly lower urinary calcium oxalate crystals (P<0.05). Hyperoxaluric rats had higher plasma malondialdehyde (PMDA) and lower urinary total antioxidant status (UTAS), which were alleviated by vitamin E and/or vitamin C supplement. In conclusion, giving combination of vitamin E and vitamin C exerts a protective role against HLP-induced oxalate nephropathy.

Combination of vitamin E and vitamin C alleviates renal function in hyperoxaluric rats via antioxidant activity

PubMed Central

JATURAKAN, Orapun; DISSAYABUTRA, Thasinas; CHAIYABUTR, Narongsak; KIJTAWORNRAT, Anusak; TOSUKHOWONG, Piyaratana; RUNGSIPIPAT, Anudep; NHUJAK, Thumnoon; BURANAKARL, Chollada

2017-01-01

Hyperoxaluria and oxidative stress are risk factors in calcium oxalate (CaOx) stone formation. Supplement with antioxidant could be effective in prevention of recurrent stone formation. The present study aims to evaluate the protective effects of vitamin E and vitamin C in hyperoxaluric rat. The experiment was performed in rats for 21 days. Rats were divided into 5 groups as follows: control (group 1, n=8), hyperoxaluric rats (group 2, n=8), hyperoxaluric rats with vitamin E supplement (group 3, n=7), hyperoxaluric rats with vitamin C supplement (group 4, n=7) and hyperoxaluric rats with vitamin E and C supplement (group 5, n=7). Hyperoxaluria was induced by feeding hydroxyl L-proline (HLP) 2% w/v dissolved in drinking water. Intraperitoneal 200 mg/kg of vitamin E was given in groups 3 and 5 on days 1, 6, 11 and 16, while 500 mg of vitamin C was injected intravenously in groups 4 and 5 on days 1 and 11. Renal functions and oxidative status were measured. The urinary oxalate excretion was increased in HLP supplement rats, while glomerular filtration rate, proximal water and sodium reabsorption were significantly lower in group 2 compared with a control (P<0.05). Giving antioxidants significantly lower urinary calcium oxalate crystals (P<0.05). Hyperoxaluric rats had higher plasma malondialdehyde (PMDA) and lower urinary total antioxidant status (UTAS), which were alleviated by vitamin E and/or vitamin C supplement. In conclusion, giving combination of vitamin E and vitamin C exerts a protective role against HLP-induced oxalate nephropathy. PMID:28392511

gene2drug: a computational tool for pathway-based rational drug repositioning.

PubMed

Napolitano, Francesco; Carrella, Diego; Mandriani, Barbara; Pisonero-Vaquero, Sandra; Sirci, Francesco; Medina, Diego L; Brunetti-Pierri, Nicola; di Bernardo, Diego

2018-05-01

Drug repositioning has been proposed as an effective shortcut to drug discovery. The availability of large collections of transcriptional responses to drugs enables computational approaches to drug repositioning directly based on measured molecular effects. We introduce a novel computational methodology for rational drug repositioning, which exploits the transcriptional responses following treatment with small molecule. Specifically, given a therapeutic target gene, a prioritization of potential effective drugs is obtained by assessing their impact on the transcription of genes in the pathway(s) including the target. We performed in silico validation and comparison with a state-of-art technique based on similar principles. We next performed experimental validation in two different real-case drug repositioning scenarios: (i) upregulation of the glutamate-pyruvate transaminase (GPT), which has been shown to induce reduction of oxalate levels in a mouse model of primary hyperoxaluria, and (ii) activation of the transcription factor TFEB, a master regulator of lysosomal biogenesis and autophagy, whose modulation may be beneficial in neurodegenerative disorders. A web tool for Gene2drug is freely available at http://gene2drug.tigem.it. An R package is under development and can be obtained from https://github.com/franapoli/gep2pep. dibernardo@tigem.it. Supplementary data are available at Bioinformatics online.

Biopsy of small kidneys: A safe and a useful guide to potentially treatable kidney disease.

PubMed

El-Reshaid, Kamel; El-Reshaid, Wael; Al-Bader, Dalal; Varro, Jozsef; Madda, John; Sallam, Hosameldin Tawfik

2017-01-01

Over the past four years, all patients with unexplained rapid progression of their renal disease were subjected to kidney biopsy, despite their small size (<9 cm), to define its etiology. Children, pregnant women, morbidly obese patients, and those with an unstable cardiovascular state, septicemia, bleeding diathesis as well as those kidney size with size <6 cm were excluded from the study. Doppler ultrasound was used to exclude renovascular/ischemic nephropathy. The procedure was performed by an interventional radiologist using a biopsy gun technique and under ultrasound guidance. The actual diagnosis was established in 29 cases while seven had advanced sclerosing glomerulonephritis. Eleven cases had evidence of vasculitis, of which two were due to polyarteritis nodosa and two were due to crescentic immunoglobulin A disease. The remaining patients had a secondary form of focal segmental glomerulosclerosis (n = 4), interstitial nephritis (n = 4), malignant nephro-angiosclerosis (n = 2), and single patient with primary hyperoxaluria, light chain cast nephropathy, amyloidosis, and thrombotic microangiopathy. All, except eight with advanced glomerulosclerosis, had improved or became stable with specific treatment. Our study shows that biopsy of small-sized kidneys, in patients with unexplained renal deterioration, is safe, and its diagnostic value can improve their morbidity and even mortality.

Vitamin C with metabolites reduce oxalate levels compared to ascorbic acid: a preliminary and novel clinical urologic finding.

PubMed

Moyad, Mark A; Combs, Maile A; Crowley, David C; Baisley, Joshua E; Sharma, Prachi; Vrablic, Angelica S; Evans, Malkanthi

2009-01-01

The incidence and prevalence of kidney stones are notable and are projected to increase over the next decade. Risk factors for kidney stones abound, but a prominent risk factor is hyperoxaluria, which has numerous etiologies, including vitamin C (ascorbic acid) dietary supplement intake. This randomized, double-blind, crossover study examined the effects of two different vitamin C formulations and found that vitamin C with metabolites (Ester-C) significantly reduced urine oxalate levels compared to ascorbic acid. This is a potential novel finding that requires further clinical evaluation.

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.

Response to Dietary Oxalate after Bariatric Surgery

PubMed Central

Froeder, Leila; Arasaki, Carlos Haruo; Malheiros, Carlos Alberto; Baxmann, Alessandra Calábria

2012-01-01

Summary Background and objectives Bariatric surgery (BS) may be associated with increased oxalate excretion and a higher risk of nephrolithiasis. This study aimed to investigate urinary abnormalities and responses to an acute oxalate load as an indirect assessment of the intestinal absorption of oxalate in this population. Design, setting, participants, & measurements Twenty-four–hour urine specimens were collected from 61 patients a median of 48 months after BS (post-BS) as well as from 30 morbidly obese (MO) participants; dietary information was obtained through 24-hour food recalls. An oral oxalate load test (OLT), consisting of 2-hour urine samples after overnight fasting and 2, 4, and 6 hours after consuming 375 mg of oxalate (spinach juice), was performed on 21 MO and 22 post-BS patients 12 months after BS. Ten post-BS patients also underwent OLT before surgery (pre-BS). Results There was a higher percentage of low urinary volume (<1.5 L/d) in post-BS versus MO (P<0.001). Hypocitraturia and hyperoxaluria (P=0.13 and P=0.36, respectively) were more frequent in BS versus MO patients. The OLT showed intragroup (P<0.001 for all periods versus baseline) and intergroup differences (P<0.001 for post-BS versus MO; P=0.03for post-BS versus pre-BS). The total mean increment in oxaluria after 6 hours of load, expressed as area under the curve, was higher in both post-BS versus MO and in post-BS versus pre-BS participants (P<0.001 for both). Conclusions The mean oxaluric response to an oxalate load is markedly elevated in post-bariatric surgery patients, suggesting that increased intestinal absorption of dietary oxalate is a predisposing mechanism for enteric hyperoxaluria. PMID:23024163

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.

Effect of cinnamon and turmeric on urinary oxalate excretion, plasma lipids, and plasma glucose in healthy subjects.

PubMed

Tang, Minghua; Larson-Meyer, D Enette; Liebman, Michael

2008-05-01

High oxalate intake resulting from consuming supplemental doses of cinnamon and turmeric may increase risk of hyperoxaluria, a significant risk factor for urolithiasis. This study assessed urinary oxalate excretion from supplemental doses of cinnamon and turmeric as well as changes in fasting plasma glucose, cholesterol, and triacylglycerol concentrations. Eleven healthy subjects, aged 21-38 y, participated in an 8-wk, randomly assigned, crossover study that involved the ingestion of supplemental doses of cinnamon and turmeric for 4-wk periods that provided 55 mg oxalate/d. Oxalate load tests, which entailed the ingestion of a 63-mg dose of oxalate from the test spices, were performed after each 4-wk experimental period and at the study onset with water only (control treatment). Fasting plasma glucose and lipid concentrations were also assessed at these time points. Compared with the cinnamon and control treatments, turmeric ingestion led to a significantly higher urinary oxalate excretion during the oxalate load tests. There were no significant changes in fasting plasma glucose or lipids in conjunction with the 4-wk periods of either cinnamon or turmeric supplementation. The percentage of oxalate that was water soluble differed markedly between cinnamon (6%) and turmeric (91%), which appeared to be the primary cause of the greater urinary oxalate excretion/oxalate absorption from turmeric. The consumption of supplemental doses of turmeric, but not cinnamon, can significantly increase urinary oxalate levels, thereby increasing risk of kidney stone formation in susceptible individuals.

Renal calcinosis and stone formation in mice lacking osteopontin, Tamm-Horsfall protein, or both.

PubMed

Mo, Lan; Liaw, Lucy; Evan, Andrew P; Sommer, Andre J; Lieske, John C; Wu, Xue-Ru

2007-12-01

Although often supersaturated with mineral salts such as calcium phosphate and calcium oxalate, normal urine possesses an innate ability to keep them from forming harmful crystals. This inhibitory activity has been attributed to the presence of urinary macromolecules, although controversies abound regarding their role, or lack thereof, in preventing renal mineralization. Here, we show that 10% of the mice lacking osteopontin (OPN) and 14.3% of the mice lacking Tamm-Horsfall protein (THP) spontaneously form interstitial deposits of calcium phosphate within the renal papillae, events never seen in wild-type mice. Lack of both proteins causes renal crystallization in 39.3% of the double-null mice. Urinalysis revealed elevated concentrations of urine phosphorus and brushite (calcium phosphate) supersaturation in THP-null and OPN/THP-double null mice, suggesting that impaired phosphorus handling may be linked to interstitial papillary calcinosis in THP- but not in OPN-null mice. In contrast, experimentally induced hyperoxaluria provokes widespread intratubular calcium oxalate crystallization and stone formation in OPN/THP-double null mice, while completely sparing the wild-type controls. Whole urine from OPN-, THP-, or double-null mice all possessed a dramatically reduced ability to inhibit the adhesion of calcium oxalate monohydrate crystals to renal epithelial cells. These data establish OPN and THP as powerful and functionally synergistic inhibitors of calcium phosphate and calcium oxalate crystallization in vivo and suggest that defects in either molecule may contribute to renal calcinosis and stone formation, an exceedingly common condition that afflicts up to 12% males and 5% females.

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.

Human SLC26A1 gene variants: a pilot study.

PubMed

Dawson, Paul A; Sim, Pearl; Mudge, David W; Cowley, David

2013-01-01

Kidney stones are a global health problem, incurring massive health costs annually. Why stones recur in many patients remains unknown but likely involves environmental, physiological, and genetic factors. The solute linked carrier (SLC) 26A1 gene has previously been linked to kidney stones in mice. SLC26A1 encodes the sulfate anion transporter 1 (SAT1) protein, and its loss in mice leads to hyperoxaluria and calcium oxalate renal stones. To investigate the possible involvement of SAT1 in human urolithiasis, we screened the SLC26A1 gene in a cohort of 13 individuals with recurrent calcium oxalate urolithiasis, which is the commonest type. DNA sequence analyses showed missense mutations in seven patients: one individual was heterozygous R372H; 4 individuals were heterozygous Q556R; one patient was homozygous Q556R; and one patient with severe nephrocalcinosis (requiring nephrectomy) was homozygous Q556R and heterozygous M132T. The M132 amino acid in human SAT1 is conserved with 15 other species and is located within the third transmembrane domain of the predicted SAT1 protein structure, suggesting that this amino acid may be important for SAT1 function. These initial findings demonstrate genetic variants in SLC26A1 of recurrent stone formers and warrant wider independent studies of SLC26A1 in humans with recurrent calcium oxalate stones.

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.

Net Intestinal Transport of Oxalate Reflects Passive Absorption and SLC26A6-mediated Secretion

PubMed Central

Knauf, Felix; Ko, Narae; Jiang, Zhirong; Robertson, William G.; Van Itallie, Christina M.; Anderson, James M.

2011-01-01

Mice lacking the oxalate transporter SLC26A6 develop hyperoxalemia, hyperoxaluria, and calcium-oxalate stones as a result of a defect in intestinal oxalate secretion, but what accounts for the absorptive oxalate flux remains unknown. We measured transepithelial absorption of [14C]oxalate simultaneously with the flux of [3H]mannitol, a marker of the paracellular pathway, across intestine from wild-type and Slc26a6-null mice. We used the anion transport inhibitor DIDS to investigate other members of the SLC26 family that may mediate transcellular oxalate absorption. Absorptive flux of oxalate in duodenum was similar to mannitol, insensitive to DIDS, and nonsaturable, indicating that it is predominantly passive and paracellular. In contrast, in wild-type mice, secretory flux of oxalate in duodenum exceeded that of mannitol, was sensitive to DIDS, and saturable, indicating transcellular secretion of oxalate. In Slc26a6-null mice, secretory flux of oxalate was similar to mannitol, and no net flux of oxalate occurred. Absorptive fluxes of both oxalate and mannitol varied in parallel in different segments of small and large intestine. In epithelial cell lines, modulation of the charge selectivity of the claudin-based pore pathway did not affect oxalate permeability, but knockdown of the tight-junction protein ZO-1 enhanced permeability to oxalate and mannitol in parallel. Moreover, formation of soluble complexes with cations did not affect oxalate absorption. In conclusion, absorptive oxalate flux occurs through the paracellular “leak” pathway, and net absorption of dietary oxalate depends on the relative balance between absorption and SLC26A6-dependent transcellular secretion. PMID:22021714

Oxalate absorption and endogenous oxalate synthesis from ascorbate in calcium oxalate stone formers and non-stone formers.

PubMed

Chai, Weiwen; Liebman, Michael; Kynast-Gales, Susan; Massey, Linda

2004-12-01

Increased rates of either oxalate absorption or endogenous oxalate synthesis can contribute to hyperoxaluria, a primary risk factor for the formation of calcium oxalate-containing kidney stones. This study involves a comparative assessment of oxalate absorption and endogenous oxalate synthesis in subpopulations of stone formers (SFs) and non-stone formers (NSFs) and an assessment of the effect of ascorbate supplementation on oxalate absorption and endogenous oxalate synthesis. Twenty-nine individuals with a history of calcium oxalate kidney stones (19 men, 10 women) and 19 age-matched NSFs (8 men, 11 women) participated in two 6-day controlled feeding experimental periods: ascorbate-supplement (2 g/d) and no-supplement treatments. An oxalate load consisting of 118 mg of unlabeled oxalate and 18 mg of 13C2 -oxalic acid was administered the morning of day 6 of each experimental period. Mean 13C2 -oxalic acid absorption averaged across the ascorbate and no-supplement treatments was significantly greater in SFs (9.9%) than NSFs (8.0%). SFs also had significantly greater 24-hour post-oxalate load urinary total oxalate and endogenous oxalate levels with both treatments. Twenty-four-hour urinary total oxalate level correlated strongly with both 13C2 -oxalic acid absorption (SFs, r = 0.76; P < 0.01; NSFs, r = 0.62; P < 0.01) and endogenous oxalate synthesis (SFs, r = 0.95; P < 0.01; NSFs, r = 0.92; P < 0.01). SFs are characterized by greater rates of both oxalate absorption and endogenous oxalate synthesis, and both these factors contribute to the hyperoxaluric state. The finding that ascorbate supplementation increased urinary total and endogenous oxalate levels suggested that this practice is a risk factor for individuals predisposed to kidney stones.

Determination of Oxalate Content in Herbal Remedies and Dietary Supplements Based on Plant Extracts.

PubMed

Siener, Roswitha; López-Mesas, Montserrat; Valiente, Manuel; Blanco, Francisco

2016-02-01

Lifestyle, especially diet, is a prominent risk factor that affects the formation of calcium oxalate stones. Urinary oxalate excretion is directly related to the amount of oral intake and intestinal absorption rate of oxalate. This work evaluated the possibility of increasing oxalate ingestion, which could lead to secondary hyperoxaluria, associated with the intake of herbal remedies and dietary supplements containing plant extracts. A wide variety of 17 commercially available drugs and dietary supplements were analyzed using ion chromatography. The results showed remarkable differences in oxalate contents of the extracts. Total oxalate concentrations ranged from 0.03 to 2.2 mg/g in solid samples and from 0.005 to 0.073 mg/mL in liquid samples. The selected herbal remedies and dietary supplements containing plant extracts represent only a low risk for calcium oxalate stone formers, if the recommended daily dose is not exceeded.

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.

Externalization of phosphatidylserine via multidrug resistance 1 (MDR1)/P-glycoprotein in oxalate-treated renal epithelial cells: implications for calcium oxalate urolithiasis.

PubMed

Li, Yu-Hang; Yu, Shi-Liang; Gan, Xiu-Guo; Pan, Shang-Ha; Teng, Yue-Qiu; An, Rui-Hua

2016-02-01

We investigated the possible involvement of multidrug resistance protein 1 P-glycoprotein (MDR1 P-gp) in the oxalate-induced redistribution of phosphatidylserine in renal epithelial cell membranes. Real-time PCR and western blotting were used to examine MDR1 expression in Madin-Darby canine kidney cells at the mRNA and protein levels, respectively, whereas surface-expressed phosphatidylserine was detected by the annexin V-binding assay. Oxalate treatment resulted in increased synthesis of MDR1, which resulted in phosphatidylserine (PS) externalization in the renal epithelial cell membrane. Treatment with the MDR1 inhibitor PSC833 significantly attenuated phosphatidylserine externalization. Transfection of the human MDR1 gene into renal epithelial cells significantly increased PS externalization. To our knowledge, this study is the first to show that oxalate increases the synthesis of MDR1 P-gp, which plays a key role in hyperoxaluria-promoted calcium oxalate urolithiasis by facilitating phosphatidylserine redistribution in renal epithelial cells.

Transcellular oxalate and Cl− absorption in mouse intestine is mediated by the DRA anion exchanger Slc26a3, and DRA deletion decreases urinary oxalate

PubMed Central

Freel, Robert W.; Whittamore, Jonathan M.

2013-01-01

Active transcellular oxalate transport in the mammalian intestine contributes to the homeostasis of this important lithogenic anion. Several members of the Slc26a gene family of anion exchangers have a measurable oxalate affinity and are expressed along the gut, apically and basolaterally. Mouse Slc26a6 (PAT1) targets to the apical membrane of enterocytes in the small intestine, and its deletion results in net oxalate absorption and hyperoxaluria. Apical exchangers of the Slc26a family that mediate oxalate absorption have not been established, yet the Slc26a3 [downregulated in adenoma (DRA)] protein is a candidate mediator of oxalate uptake. We evaluated the role of DRA in intestinal oxalate and Cl− transport by comparing unidirectional and net ion fluxes across short-circuited segments of small (ileum) and large (cecum and distal colon) intestine from wild-type (WT) and DRA knockout (KO) mice. In WT mice, all segments demonstrated net oxalate and Cl− absorption to varying degrees. In KO mice, however, all segments exhibited net anion secretion, which was consistently, and solely, due to a significant reduction in the absorptive unidirectional fluxes. In KO mice, daily urinary oxalate excretion was reduced 66% compared with that in WT mice, while urinary creatinine excretion was unchanged. We conclude that DRA mediates a predominance of the apical uptake of oxalate and Cl− absorbed in the small and large intestine of mice under short-circuit conditions. The large reductions in urinary oxalate excretion underscore the importance of transcellular intestinal oxalate absorption, in general, and, more specifically, the importance of the DRA exchanger in oxalate homeostasis. PMID:23886857

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.

High resolution crystal structure of rat long chain hydroxy acid oxidase in complex with the inhibitor 4-carboxy-5-[(4-chlorophenyl)sulfanyl]-1, 2, 3-thiadiazole. Implications for inhibitor specificity and drug design.

PubMed

Chen, Zhi-wei; Vignaud, Caroline; Jaafar, Adil; Lévy, Bernard; Guéritte, Françoise; Guénard, Daniel; Lederer, Florence; Mathews, F Scott

2012-05-01

Long chain hydroxy acid oxidase (LCHAO) is responsible for the formation of methylguanidine, a toxic compound with elevated serum levels in patients with chronic renal failure. Its isozyme glycolate oxidase (GOX), has a role in the formation of oxalate, which can lead to pathological deposits of calcium oxalate, in particular in the disease primary hyperoxaluria. Inhibitors of these two enzymes may have therapeutic value. These enzymes are the only human members of the family of FMN-dependent l-2-hydroxy acid-oxidizing enzymes, with yeast flavocytochrome b(2) (Fcb2) among its well studied members. We screened a chemical library for inhibitors, using in parallel rat LCHAO, human GOX and the Fcb2 flavodehydrogenase domain (FDH). Among the hits was an inhibitor, CCPST, with an IC(50) in the micromolar range for all three enzymes. We report here the crystal structure of a complex between this compound and LCHAO at 1.3 Å resolution. In comparison with a lower resolution structure of this enzyme, binding of the inhibitor induces a conformational change in part of the TIM barrel loop 4, as well as protonation of the active site histidine. The CCPST interactions are compared with those it forms with human GOX and those formed by two other inhibitors with human GOX and spinach GOX. These compounds differ from CCPST in having the sulfur replaced with a nitrogen in the five-membered ring as well as different hydrophobic substituents. The possible reason for the ∼100-fold difference in affinity between these two series of inhibitors is discussed. The present results indicate that specificity is an issue in the quest for therapeutic inhibitors of either LCHAO or GOX, but they may give leads for this quest. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Flexible ureteroscopic laser lithotripsy for upper urinary tract stone disease in patients with spinal cord injury.

PubMed

Tepeler, Abdulkadir; Sninsky, Brian C; Nakada, Stephen Y

2015-11-01

The objective of this study is to present the outcomes of flexible ureteroscopic laser lithotripsy (URS) for upper urinary tract stone disease in spinal cord injury (SCI) patients performed by a single surgeon. A retrospective analysis was performed for SCI patients treated with flexible URS for proximal ureter and kidney stone disease by a single surgeon between 2003 and 2013. Patient characteristics, operative outcomes, metabolic evaluation, and stone analyses were assessed in detail. A total of 27 URS procedures were performed for urolithiasis in 21 renal units of 19 patients. The mean age was 52.1 ± 15.6 years (16-72) and mean BMI was 29.2 ± 7.3 kg/m(2) (20-45.7). Etiology of SCI was trauma (n: 10), multiple sclerosis (n: 6), cerebrovascular accident (n: 1), or undetermined (n: 2). The mean stone size was 15.9 ± 8.6 (6-40) mm. In the 27 URS procedures, stones were located in the ureter (n: 5), the kidney (n: 14), and both areas (n: 8). Mean hospitalization time was 2.0 ± 2.4 (0-10) days. Postoperative complications were observed in 6 cases (22.2%). Three major complications included urosepsis (n: 1) and respiratory failure (n: 2), that were observed postoperatively and required admission to the intensive care unit. The 2 minor complications were hypotension, fever and UTI, and required medical treatment. Fourteen (66.6%) of the 21 renal units were stone free. Calcium phosphate carbonate (n: 9) and struvite (n: 5) were the primary stone compositions detected. Hypocitraturia (n: 6), hypercalciuria (n: 5), hypernaturia (n: 5), hyperoxaluria (n: 4), and hyperuricosuria (n: 1) were common abnormalities in 24-h urine analysis. Ureteroscopic laser lithotripsy can be an effective treatment modality for SCI patients with upper urinary tract calculi.

Optimization of OSPF Routing in IP Networks

NASA Astrophysics Data System (ADS)

Bley, Andreas; Fortz, Bernard; Gourdin, Eric; Holmberg, Kaj; Klopfenstein, Olivier; Pióro, Michał; Tomaszewski, Artur; Ümit, Hakan

The Internet is a huge world-wide packet switching network comprised of more than 13,000 distinct subnetworks, referred to as Autonomous Systems (ASs) autonomous system AS . They all rely on the Internet Protocol (IP) internet protocol IP for transport of packets across the network. And most of them use shortest path routing protocols shortest path routing!protocols , such as OSPF or IS-IS, to control the routing of IP packets routing!of IP packets within an AS. The idea of the routing is extremely simple — every packet is forwarded on IP links along the shortest route between its source and destination nodes of the AS. The AS network administrator can manage the routing of packets in the AS by supplying the so-called administrative weights of IP links, which specify the link lengths that are used by the routing protocols for their shortest path computations. The main advantage of the shortest path routing policy is its simplicity, allowing for little administrative overhead. From the network engineering perspective, however, shortest path routing can pose problems in achieving satisfactory traffic handling efficiency. As all routing paths depend on the same routing metric routing!metric , it is not possible to configure the routing paths for the communication demands between different pairs of nodes explicitly or individually; the routing can be controlled only indirectly and only as a whole by modifying the routing metric. Thus, one of the main tasks when planning such networks is to find administrative link weights that induce a globally efficient traffic routing traffic!routing configuration of an AS. It turns out that this task leads to very difficult mathematical optimization problems. In this chapter, we discuss and describe exact integer programming models and solution approaches as well as practically efficient smart heuristics for such shortest path routing problems shortest path routing!problems .

Optimizing the Primary Prevention of Type-2 Diabetes in Primary Health Care

ClinicalTrials.gov

2017-08-18

Interprofessional Relations; Primary Health Care/Organization & Administration; Diabetes Mellitus, Type 2/Prevention & Control; Primary Prevention/Methods; Risk Reduction Behavior; Randomized Controlled Trial; Life Style

NADPH Oxidase as a Therapeutic Target for Oxalate Induced Injury in Kidneys

PubMed Central

Peck, Ammon B.; Khan, Saeed R.

2013-01-01

A major role of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes is to catalyze the production of superoxides and other reactive oxygen species (ROS). These ROS, in turn, play a key role as messengers in cell signal transduction and cell cycling, but when they are produced in excess they can lead to oxidative stress (OS). Oxidative stress in the kidneys is now considered a major cause of renal injury and inflammation, giving rise to a variety of pathological disorders. In this review, we discuss the putative role of oxalate in producing oxidative stress via the production of reactive oxygen species by isoforms of NADPH oxidases expressed in different cellular locations of the kidneys. Most renal cells produce ROS, and recent data indicate a direct correlation between upregulated gene expressions of NADPH oxidase, ROS, and inflammation. Renal tissue expression of multiple NADPH oxidase isoforms most likely will impact the future use of different antioxidants and NADPH oxidase inhibitors to minimize OS and renal tissue injury in hyperoxaluria-induced kidney stone disease. PMID:23840917

Urolithiasis in Tennessee: an occupational window into a regional problem.

PubMed Central

Thun, M J; Schober, S

1991-01-01

BACKGROUND: Urinary tract stones (stones) are believed to be unusually common in the southeastern United States but neither the incidence of nor the risk factors for stones are known. METHODS: In three well-defined occupational populations in eastern Tennessee, we assessed the prevalence, incidence, and cumulative incidence of stones and measured biochemical risk factors for lithogenesis. RESULTS: The age-adjusted prevalence of stones was 18.5 percent in Tennessee compared to 7.7 percent among White males in US NHANES (prevalence ratio 2.4, 95% CI 1.7, 3.3). The cumulative incidence (risk) was 27.8 percent by age 65, higher than in any other reported population. Risk factors were age, a family history, and urinary saturation with calcium-oxalate (COAX). Persons with a positive family history and the highest measured CAOX index had a predicted lifetime risk of 88.8 percent. Biochemical factors affecting lithogenesis were hypercalciuria, hyperoxaluria, and low urine volume. CONCLUSION: Future research should characterize the geographic boundaries of a southeastern "stone-belt" and explore genetic and dietary hypotheses that might explain it. PMID:2014858

Limitation of HIF-1α with pentoxifillyne on renal tubular ischemia result of hiperoxaluria and ESWL.

PubMed

Erturhan, Sakip; Bayrak, Omer; Seckiner, Ilker; Celik, Mehmet; Karakok, Metin

2014-03-01

To evaluate hypoxia-inducible factor 1 subunit α (HIF-1α) expression during the performance of extracorporeal shock wave lithotripsy (ESWL) and to investigate the effects of pentoxyphylline on HIF-1α expression. One hundred New Zealand Albino rabbit were used in the study divided in 5 groups. There were 20 rabbits in each group. The groups were divided in two parts: early (7 days) and late period (14 days) according to follow up duration. Immunohistochemical analyses were performed using nuclear staining to show HIF-1α expression in rabbit renal tissue sample. HIF-1α expression was higher in rabbits undergoing ESWL (group 4). In the hyperoxaluria group taking pentoxyphylline before ESWL (group 5), HIF-1α expression was lower in both early and late period subgroups (p < 0.05) CONCLUSION: In this study we evaluated HIF-1α expression and showed that ESWL may cause renal cell injury. Our results suggest that pentoxyphylline, as a circulatory regulator agent, may prevent renal cell injury induced by ESWL.

Characteristics of microRNAs enriched in specific cell types and primary tissue types in solid organs.

PubMed

Kriegel, Alison J; Liu, Yong; Liu, Pengyuan; Baker, Maria Angeles; Hodges, Matthew R; Hua, Xing; Liang, Mingyu

2013-12-01

Knowledge of miRNA expression and function in specific cell types in solid organs is limited because of difficulty in obtaining appropriate specimens. We used laser capture microdissection to obtain nine tissue regions from rats, including the nucleus of the solitary tract, hypoglossal motor nucleus, ventral respiratory column/pre-Bötzinger complex, and midline raphe nucleus from the brain stem, myocardium and coronary artery from the heart, and glomerulus, proximal convoluted tubule, and medullary thick ascending limb from the kidney. Each tissue region consists of or is enriched for a specific cell type. Differential patterns of miRNA expression obtained by deep sequencing of minute amounts of laser-captured cells were highly consistent with data obtained from real-time PCR analysis. miRNA expression patterns correctly clustered the specimens by tissue regions and then by primary tissue types (neural, muscular, or epithelial). The aggregate difference in miRNA profiles between tissue regions that contained the same primary tissue type was as large as one-half of the aggregate difference between primary tissue types. miRNAs differentially expressed between primary tissue types are more likely to be abundant miRNAs, while miRNAs differentially expressed between tissue regions containing the same primary tissue type were distributed evenly across the abundance spectrum. The tissue type-enriched miRNAs were more likely to target genes enriched for specific functional categories compared with either cell type-enriched miRNAs or randomly selected miRNAs. These data indicate that the role of miRNAs in determining characteristics of primary tissue types may be different than their role in regulating cell type-specific functions in solid organs.

Age-related variation in primary care-type presentations to emergency departments.

PubMed

Freed, Gary; Gafforini, Sarah; Carson, Norman

2015-08-01

A significant amount of attention has been paid to the increase in emergency department (ED) presentations in Australia. Questions have arisen regarding whether all of those presenting to the ED are actually in need of true emergency services. Under-standing the characteristics of those patients who may be cared for in non-emergency settings is important for future health system strategies. The aim of this study was to identify age-related variation in primary care type emergency department (ED) presentations over time. A secondary analysis of data from the Victorian emergency minimum dataset (VEMD) between 2002-13 was conducted. The main outcomes were patterns of primary care type ED presentations for different ages groups over time, age-specific patterns of specific primary care type exclusion criteria and primary care type ED presentations by residents from aged care facilities. The proportion of triage category 4 or 5 ED presentations that met the criteria for a primary care type visit was greatest in the 0-4-year age group and tended to decrease as the age of the patient increased. Triage category 4 or 5 presentation by ambulance was uncommon in the younger age groups, surpassed 10% in the 50-54-year age group, and was >70% for those aged >90 years. The greater proportion of residential aged care facility patients who arrived by ambulance resulted in a much smaller proportion of primary care type visits. There are marked differences by age in the proportion of triage category 4 or 5 ED presentations that met the criteria for primary care type visits. These results indicate it was primarily younger patients who presented to the ED with non-urgent conditions. Most might be able to safely receive care in a primary care setting.

Treat early, treat appropriately.

PubMed

Liebl, Andreas; Rutten, Guy; Abraira, Carlos

2010-04-01

The treatment of type 2 diabetes is shifting from secondary specialist centres to the primary care setting. However, for this shift to be sustainable and successful, primary care physicians (PCPs) must effectively provide aspects of diabetes care traditionally supplied by specialists. In particular, the early and appropriate use of insulin in type 2 diabetes will increasingly become the responsibility of PCPs. This review examines how patients with type 2 diabetes are currently managed across several European countries, and explores the evidence around insulin use in type 2 diabetes and the implications for primary care. 2010 Primary Care Diabetes Europe. Published by Elsevier Ltd.. All rights reserved.

Patho-physiological evaluation of Duranta erecta for the treatment of urolithiasis.

PubMed

Agawane, Sachin B; Gupta, Vidya S; Kulkarni, Mahesh J; Bhattacharya, Asish K; Koratkar, Santosh S; Rao, Vamkudoth Koteswara

2018-04-07

Urolithiasis is the third common disorder of the urinary system affecting 10-15% of the general population. In recent years, search for new antilithiatic drugs from natural sources has assumed greater importance. This study was performed to investigate the anti-urolithiatic activity of methanolic extract of Duranta erecta leaves by in vitro and in vivo analysis. The study was designed to determine presence of phytochemicals in D. erecta, its yield in percentage, antioxidant activity against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and anti-microbial property against few bacteria. In vitro analysis was carried out study anti-urolithiatic property of D. erecta by nucleation assay and synthetic urine assay for inhibition of calcium oxalate and calcium oxalate monohydrate crystals formation. An in vivo experiment was performed on Wistar rats for confirmation of anti-urolithiatic property of D. erecta in animal model. D. erecta has the presence of primary and secondary metabolites like glycoside, saponins, sterols, flavonoids, phenols, tannins, alkaloids, carbohydrates and proteins. Methanolic extract of D. erecta gave a very good yield (60%). D. erecta proved its antioxidant potential by 93.51% inhibition of DPPH radical at a concentration of 1000 μg/mL where ascorbic showed 94.71% of DPPH radical at the same concentration. In vitro tests like nucleation assay and synthetic urine assay showed that D. erecta inhibits formation of calcium oxalate and calcium oxalate monohydrate crystals. It also showed the anti-microbial property by formation of zone of inhibition against few bacteria. An in vivo experiment on Wistar rat animal model confirmed the anti-urolithiatic property of D. erecta L. leaves extract. Based on the results, we reported that D. erecta may treat calcium oxalate crystal deposition in the kidney by preventing hyperoxaluria-induced peroxidative damage to the renal tubular membrane surface (lipid peroxidation). It has anti-microbial potential so it may also inhibit the secondary bacterial infection in kidney. Based on the data, it can be concluded that this herb can be used as a potential anti-urolithiasis agent for kidney stone removal. Copyright © 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

Aluminum Citrate Prevents Renal Injury from Calcium Oxalate Crystal Deposition

PubMed Central

Besenhofer, Lauren M.; Cain, Marie C.; Dunning, Cody

2012-01-01

Calcium oxalate monohydrate crystals are responsible for the kidney injury associated with exposure to ethylene glycol or severe hyperoxaluria. Current treatment strategies target the formation of calcium oxalate but not its interaction with kidney tissue. Because aluminum citrate blocks calcium oxalate binding and toxicity in human kidney cells, it may provide a different therapeutic approach to calcium oxalate-induced injury. Here, we tested the effects of aluminum citrate and sodium citrate in a Wistar rat model of acute high-dose ethylene glycol exposure. Aluminum citrate, but not sodium citrate, attenuated increases in urea nitrogen, creatinine, and the ratio of kidney to body weight in ethylene glycol–treated rats. Compared with ethylene glycol alone, the addition of aluminum citrate significantly increased the urinary excretion of both crystalline calcium and crystalline oxalate and decreased the deposition of crystals in renal tissue. In vitro, aluminum citrate interacted directly with oxalate crystals to inhibit their uptake by proximal tubule cells. These results suggest that treating with aluminum citrate attenuates renal injury in rats with severe ethylene glycol toxicity, apparently by inhibiting calcium oxalate’s interaction with, and retention by, the kidney epithelium. PMID:23138489

Fourier Transform Infrared Analysis of Urinary Calculi and Metabolic Studies in a Group of Sicilian Children.

PubMed

D'Alessandro, Maria Michela; Gennaro, Giuseppe; Tralongo, Pietro; Maringhini, Silvio

2017-05-01

Prevalence of urinary calculi in children has been increasing in the past years. We performed an analysis of the chemical composition of stones formers of the pediatric population in our geographical area over the years 2005 to 2013. Fourier transform infrared spectroscopy was employed for the determination of the calculus composition of a group of Sicilian children, and metabolic studies were performed to formulate the correct diagnosis and establish therapy. The prevalence of stone formation was much higher for boys than for girls, with a sex ratio of 1.9:1. The single most frequent component was found to be calcium oxalate monohydrate, and calcium oxalates (pure or mixed calculi) were the overall most frequent components. Calcium phosphates ranked 2nd for frequency, most often in mixed calculi, while urates ranked 3rd. The metabolic disorder most often associated with pure calcium oxalate monohydrate calculi was hypocitraturia, while hyperoxaluria was predominantly associated with calcium oxalate dihydrate calculi. Mixed calculi had the highest prevalence in our pediatric population. Our data showed that Fourier transform infrared spectroscopy was a useful tool for the determination of the calculi composition.

Diet, but not oral probiotics, effectively reduces urinary oxalate excretion and calcium oxalate supersaturation.

PubMed

Lieske, John C; Tremaine, William J; De Simone, Claudio; O'Connor, Helen M; Li, Xujian; Bergstralh, Eric J; Goldfarb, David S

2010-12-01

We examined the effect of a controlled diet and two probiotic preparations on urinary oxalate excretion, a risk factor for calcium oxalate kidney stone formation, in patients with mild hyperoxaluria. Patients were randomized to a placebo, a probiotic, or a synbiotic preparation. This tested whether these probiotic preparations can increase oxalate metabolism in the intestine and/or decrease oxalate absorption from the gut. Patients were maintained on a controlled diet to remove the confounding variable of differing oxalate intake from food. Urinary oxalate excretion and calcium oxalate supersaturation on the controlled diet were significantly lower compared with baseline on a free-choice diet. Neither study preparation reduced urinary oxalate excretion nor calcium oxalate supersaturation. Fecal lactobacilli colony counts increased on both preparations, whereas enterococcal and yeast colony counts were increased on the synbiotic. Total urine volume and the excretion of oxalate and calcium were all strong independent determinants of urinary calcium oxalate supersaturation. Hence, dietary oxalate restriction reduced urinary oxalate excretion, but the tested probiotics did not influence urinary oxalate levels in patients on a restricted oxalate diet. However, this study suggests that dietary oxalate restriction is useful for kidney stone prevention.

[Secondary hyperoxaluria and nephrocalcinosis due to ethylene glycol poisoning].

PubMed

Monet, C; Richard, E; Missonnier, S; Rebouissoux, L; Llanas, B; Harambat, J

2013-08-01

We report the case of a 3-year-old boy admitted to the pediatric emergency department for ethylene glycol poisoning. During hospitalization, he presented dysuria associated with crystalluria. Blood tests showed metabolic acidosis with an elevated anion gap. A renal ultrasound performed a few weeks later revealed bilateral medullary hyperechogenicity. Urine microscopic analysis showed the presence of weddellite crystals. Secondary nephrocalcinosis due to ethylene glycol intoxication was diagnosed. Hyperhydration and crystallization inhibition by magnesium citrate were initiated. Despite this treatment, persistent weddellite crystals and nephrocalcinosis were seen more than 2years after the intoxication. Ethylene glycol is metabolized in the liver by successive oxidations leading to its final metabolite, oxalic acid. Therefore, metabolic acidosis with an elevated anion gap is usually found following ethylene glycol intoxication. Calcium oxalate crystal deposition may occur in several organs, including the kidneys. The precipitation of calcium oxalate in renal tubules can lead to nephrocalcinosis and acute kidney injury. The long-term renal prognosis is related to chronic tubulointerstitial injury caused by nephrocalcinosis. Treatment of ethylene glycol intoxication is based on specific inhibitors of alcohol dehydrogenase and hemodialysis in the most severe forms, and should be started promptly. Copyright © 2013. Published by Elsevier SAS.

[Etiological orientation from the analysis morphological and constitutional of urinary stones in Conakry].

PubMed

Kaba, M L; Bah, O R; Baldé, N M; Bigot, J C; Bah, A O; Diakité, M; Baldé, I; Panzo, D A; Touré, Y I; Diallo, M B; Carré, J L

2007-01-01

The epidemiological profile of urinary stones varies from region of the world to another according to food habit and certain enviromental factors. The aim of our study was to establish an etiological approach of the urinary lithiasis collected in Conakry by morphological and constitutional analysis. It was a prospective study from january 1 rst 2003 to january 1 rst 2004 concerning all the stones collected. They were analysed by binocular magnifying glass and infra red spectrophotometry of Fourier. During the period, 18 patients were observed (14 male, 4 femele) of 27.4 +/- 4 years old (from 2 to 69) living mainly in urban environment. From these patients 28 stones were collected; 12 spontaneously and 16 surgicaly. Their composition were whewellite (36%), struvite (29%), carbapatite (14%), urates (14%) and weddellite (7%). In Conakry stones come mainly from hyperoxaluria and urinary tract infection; hypercalciuria is uncomon. The urinary calculations examined among patients show in the adult a prevalence of elements in favour of a hyperoxalurie and a notable context of urinary infections in particular in the child; the pure hypercalciurie remains negligible in Conakry, we plan to lead a thorough work to the national scales.

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

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.

[Traditional and Complementary Medicine in Brazil: inclusion in the Brazilian Unified National Health System and integration with primary care].

PubMed

Sousa, Islandia Maria Carvalho de; Tesser, Charles Dalcanale

2017-01-23

This study aimed to analyze the inclusion of Traditional and Complementary Medicine in Brazilian Unified National Health System (SUS) and its integration with primary healthcare (PHC). A qualitative study drew on institutional data, indexed articles, and case studies in selected Brazilian cities: Campinas (São Paulo State), Florianópolis (Santa Catarina State), Recife (Pernambuco State), Rio de Janeiro, and São Paulo. The analysis adopted the perspective of inclusion of Traditional and Complementary Medicine in the healthcare network and its integration with primary healthcare, based on the following dimensions: presence of Traditional and Complementary Medicine on the municipal agenda; position in the services; mode of access to Traditional and Complementary Medicine; Traditional and Complementary Medicine practitioners; types of practices; demand profile; and potential for expansion in the SUS. The authors identified and characterized four types of inclusion and integration of Traditional and Complementary Medicine, whether in association or not: Type 1 - in primary healthcare via professionals from the family health teams - Integrated; Type 2 - in primary healthcare via professionals with full-time employment - Juxtaposed; Type 3 - in primary healthcare via matrix-organized teams - Matrix Organization; Type 4 - in specialized services - Without Integration. The combination of types 1 and 3 was considered a potential guideline for the expansion of Traditional and Complementary Medicine in the SUS and can orient the growth and integration of Traditional and Complementary Medicine with primary healthcare. The growing presence of Traditional and Complementary Medicine in the SUS requires conceiving its strategic expansion, while existing experiences should not be wasted.

Movement as Medicine for Type 2 Diabetes: protocol for an open pilot study and external pilot clustered randomised controlled trial to assess acceptability, feasibility and fidelity of a multifaceted behavioural intervention targeting physical activity in primary care.

PubMed

Avery, Leah; Sniehotta, Falko F; Denton, Sarah J; Steen, Nick; McColl, Elaine; Taylor, Roy; Trenell, Michael I

2014-02-03

Physical activity (PA) and nutrition are the cornerstones of diabetes management. Several reviews and meta-analyses report that PA independently produces clinically important improvements in glucose control in people with Type 2 diabetes. However, it remains unclear what the optimal strategies are to increase PA behaviour in people with Type 2 diabetes in routine primary care. This study will determine whether an evidence-informed multifaceted behaviour change intervention (Movement as Medicine for Type 2 Diabetes) targeting both consultation behaviour of primary healthcare professionals and PA behaviour in adults with Type 2 diabetes is both acceptable and feasible in the primary care setting. An open pilot study conducted in two primary care practices (phase one) will assess acceptability, feasibility and fidelity. Ongoing feedback from participating primary healthcare professionals and patients will provide opportunities for systematic adaptation and refinement of the intervention and study procedures. A two-arm parallel group clustered pilot randomised controlled trial with patients from participating primary care practices in North East England will assess acceptability, feasibility, and fidelity of the intervention (versus usual clinical care) and trial processes over a 12-month period. Consultation behaviour involving fidelity of intervention delivery, diabetes and PA related knowledge, attitudes/beliefs, intentions and self-efficacy for delivering a behaviour change intervention targeting PA behaviour will be assessed in primary healthcare professionals. We will rehearse the collection of outcome data (with the focus on data yield and quality) for a future definitive trial, through outcome assessment at baseline, one, six and twelve months. An embedded qualitative process evaluation and treatment fidelity assessment will explore issues around intervention implementation and assess whether intervention components can be reliably and faithfully delivered in routine primary care. Movement as Medicine for Type 2 Diabetes will address an important gap in the evidence-base, that is, the need for interventions to increase free-living PA behaviour in adults with Type 2 diabetes. The multifaceted intervention incorporates an online accredited training programme for primary healthcare professionals and represents, to the best of our knowledge, the first of its kind in the United Kingdom. This study will establish whether the multifaceted behavioural intervention is acceptable and feasible in routine primary care. Movement as Medicine for Type 2 Diabetes (MaMT2D) was registered with Current Controlled Trials on the 14th January 2012: ISRCTN67997502. The first primary care practice was randomised on the 5th October 2012.

Racial/Ethnic Disparities in Primary Care Quality Among Type 2 Diabetes Patients, Medical Expenditure Panel Survey, 2012.

PubMed

Hu, Ruwei; Shi, Leiyu; Liang, Hailun; Haile, Geraldine Pierre; Lee, De-Chih

2016-08-04

Racial and ethnic disparities exist in diabetes prevalence, access to diabetes care, diabetes-related complications and mortality rates, and the quality of diabetes care among Americans. We explored racial and ethnic disparities in primary care quality among Americans with type 2 diabetes. We analyzed data on adults with type 2 diabetes derived from the household component of the 2012 Medical Expenditure Panel Survey. Multiple regression and multivariate logistic regressions were used to examine the association between race/ethnicity and primary care attributes related to first contact, longitudinality, comprehensiveness, and coordination, and clusters of confounding factors were added sequentially. Preliminary findings indicated differences in primary care quality between racial/ethnic minorities and whites across measures of first contact, longitudinality, comprehensiveness, and coordination. After controlling for confounding factors, these differences were no longer apparent; all racial/ethnic categories showed similar rates of primary care quality according to the 4 primary care domains of interest in the study. Results indicate equitable primary care quality for type 2 diabetes patients across 4 key domains of primary care after controlling for socioeconomic characteristics. Additional research is necessary to support these findings, particularly when considering smaller racial/ethnic groups and investigating outcomes related to diabetes.

Double-hit or dual expression of MYC and BCL2 in primary cutaneous large B-cell lymphomas.

PubMed

Menguy, Sarah; Frison, Eric; Prochazkova-Carlotti, Martina; Dalle, Stephane; Dereure, Olivier; Boulinguez, Serge; Dalac, Sophie; Machet, Laurent; Ram-Wolff, Caroline; Verneuil, Laurence; Gros, Audrey; Vergier, Béatrice; Beylot-Barry, Marie; Merlio, Jean-Philippe; Pham-Ledard, Anne

2018-03-26

In nodal diffuse large B-cell lymphoma, the search for double-hit with MYC and BCL2 and/or BCL6 rearrangements or for dual expression of BCL2 and MYC defines subgroups of patients with altered prognosis that has not been evaluated in primary cutaneous large B-cell lymphoma. Our objectives were to assess the double-hit and dual expressor status in a cohort of 44 patients with primary cutaneous large B-cell lymphoma according to the histological subtype and to evaluate their prognosis relevance. The 44 cases defined by the presence of more than 80% of large B-cells in the dermis corresponded to 21 primary cutaneous follicle centre lymphoma with large cell morphology and 23 primary cutaneous diffuse large B-cell lymphoma, leg type. Thirty-one cases (70%) expressed BCL2 and 29 (66%) expressed MYC. Dual expressor profile was observed in 25 cases (57%) of either subtypes (n = 6 or n = 19, respectively). Only one primary cutaneous follicle centre lymphoma, large-cell case had a double-hit status (2%). Specific survival was significantly worse in primary cutaneous diffuse large B-cell lymphoma, leg type than in primary cutaneous follicle centre lymphoma, large cell (p = 0.021) and for the dual expressor primary cutaneous large B-cell lymphoma group (p = 0.030). Both overall survival and specific survival were worse for patients belonging to the dual expressor primary cutaneous diffuse large B-cell lymphoma, leg type subgroup (p = 0.001 and p = 0.046, respectively). Expression of either MYC and/or BCL2 negatively impacted overall survival (p = 0.017 and p = 0.018 respectively). As the differential diagnosis between primary cutaneous follicle centre lymphoma, large cell and primary cutaneous diffuse large B-cell lymphoma, leg type has a major impact on prognosis, dual-expression of BCL2 and MYC may represent a new diagnostic criterion for primary cutaneous diffuse large B-cell lymphoma, leg type subtype and further identifies patients with impaired survival. Finally, the double-hit assessment does not appear clinically relevant in primary cutaneous large B-cell lymphoma.

7 CFR 801.5 - Tolerance for diverter-type mechanical samplers.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Tolerance for diverter-type mechanical samplers. 801.5 Section 801.5 Agriculture Regulations of the Department of Agriculture (Continued) GRAIN INSPECTION... mechanical samplers. The maintenance tolerance for diverter-type mechanical samplers (primary, or primary and...

[Better coordination between primary care, community settings and diabetes outpatient clinic for patients with type 2 diabetes].

PubMed

Gjessing, Hans Jørgen; Jørgensen, Ulla Linding; Møller, Charlotte Chrois; Huge, Lis; Dalgaard, Anne Mette; Nielsen, Kristian Wendelboe; Thomsen, Lis; Buch, Martin Sandberg

2014-06-02

Integrated care programmes for patients with type 2 diabetes can be successfully implemented by planning the programmes in coordination between the sectors primary care, community settings and diabetes outpatient clinic, and with involvement of leaders and employees. Our project has resulted in: 1) more patients with type 2 diabetes receiving diabetes management courses, 2) improved diabetes management of primary care, and 3) improved confidence and respect between sectors involved in diabetes care.

Movement as Medicine for Type 2 Diabetes: protocol for an open pilot study and external pilot clustered randomised controlled trial to assess acceptability, feasibility and fidelity of a multifaceted behavioural intervention targeting physical activity in primary care

PubMed Central

2014-01-01

Background Physical activity (PA) and nutrition are the cornerstones of diabetes management. Several reviews and meta-analyses report that PA independently produces clinically important improvements in glucose control in people with Type 2 diabetes. However, it remains unclear what the optimal strategies are to increase PA behaviour in people with Type 2 diabetes in routine primary care. Methods This study will determine whether an evidence-informed multifaceted behaviour change intervention (Movement as Medicine for Type 2 Diabetes) targeting both consultation behaviour of primary healthcare professionals and PA behaviour in adults with Type 2 diabetes is both acceptable and feasible in the primary care setting. An open pilot study conducted in two primary care practices (phase one) will assess acceptability, feasibility and fidelity. Ongoing feedback from participating primary healthcare professionals and patients will provide opportunities for systematic adaptation and refinement of the intervention and study procedures. A two-arm parallel group clustered pilot randomised controlled trial with patients from participating primary care practices in North East England will assess acceptability, feasibility, and fidelity of the intervention (versus usual clinical care) and trial processes over a 12-month period. Consultation behaviour involving fidelity of intervention delivery, diabetes and PA related knowledge, attitudes/beliefs, intentions and self-efficacy for delivering a behaviour change intervention targeting PA behaviour will be assessed in primary healthcare professionals. We will rehearse the collection of outcome data (with the focus on data yield and quality) for a future definitive trial, through outcome assessment at baseline, one, six and twelve months. An embedded qualitative process evaluation and treatment fidelity assessment will explore issues around intervention implementation and assess whether intervention components can be reliably and faithfully delivered in routine primary care. Discussion Movement as Medicine for Type 2 Diabetes will address an important gap in the evidence-base, that is, the need for interventions to increase free-living PA behaviour in adults with Type 2 diabetes. The multifaceted intervention incorporates an online accredited training programme for primary healthcare professionals and represents, to the best of our knowledge, the first of its kind in the United Kingdom. This study will establish whether the multifaceted behavioural intervention is acceptable and feasible in routine primary care. Trial registration Movement as Medicine for Type 2 Diabetes (MaMT2D) was registered with Current Controlled Trials on the 14th January 2012: ISRCTN67997502. The first primary care practice was randomised on the 5th October 2012. PMID:24491134

A Typological Analysis of South Korean Primary Teachers' Awareness of Primary Geography Education

ERIC Educational Resources Information Center

Lee, Dong-min

2018-01-01

This study illuminates primary teachers' awareness of geography education. Data were collected through interviews with twenty-one teachers and analyzed using Straussian-grounded theory. A total of 210 concepts were categorized into twenty-two categories. The participants were categorized into three types. Many participating teachers (type 1 and 2)…

Turkish EFL Teachers' Perceptions and Practices of Foreign Language Assessment in Primary Education

ERIC Educational Resources Information Center

Kirkgoz, Yasemin; Babanoglu, Muzaffer Pinar; Agçam, Reyhan

2017-01-01

The present study aimed to investigate perceptions of EFL teachers working at state primary schools on core language skills, assessment types and question types used in assessing student's foreign language development and proficiency during an academic year. Data were gathered from 56 EFL teachers working at 42 primary state schools in Turkey…

Is Team-Based Primary Care Associated with Less Access Problems and Self-Reported Unmet Need in Canada?

PubMed

Zygmunt, Austin; Asada, Yukiko; Burge, Frederick

2017-10-01

As in many jurisdictions, the delivery of primary care in Canada is being transformed from solo practice to team-based care. In Canada, team-based primary care involves general practitioners working with nurses or other health care providers, and it is expected to improve equity in access to care. This study examined whether team-based care is associated with fewer access problems and less unmet need and whether socioeconomic gradients in access problems and unmet need are smaller in team-based care than in non-team-based care. Data came from the 2008 Canadian Survey of Experiences with Primary Health Care (sample size: 10,858). We measured primary care type as team-based or non-team-based and socioeconomic status by income and education. We created four access problem variables and four unmet need variables (overall and three specific components). For each, we ran separate logistic regression models to examine their associations with primary care type. We examined socioeconomic gradients in access problems and unmet need stratified by primary care type. Primary care type had no statistically significant, independent associations with access problems or unmet need. Among those with non-team-based care, a statistically significant education gradient for overall access problems existed, whereas among those with team-based care, no statistically significant socioeconomic gradients existed.

Cytogenetic and morphologic typing of 58 papillary renal cell carcinomas: evidence for a cytogenetic evolution of type 2 from type 1 tumors.

PubMed

Gunawan, Bastian; von Heydebreck, Anja; Fritsch, Thekla; Huber, Wolfgang; Ringert, Rolf-Hermann; Jakse, Gerhard; Füzesi, László

2003-10-01

We evaluated clinical characteristics, patient outcome (mean follow-up, 47 months), and cytogenetic abnormalities in the largest as yet reported cytogenetic series of 47 primary and 11 secondary papillary renal cell carcinomas for differences between the recently proposed type 1 and type 2 subtypes. Secondary tumors were more often of type 2 morphology (P = 0.02), whereas primary type 2 tumors were associated with higher clinical stage (P = 0.001) and worse patient outcome (P = 0.02). Although both subtypes had at least one of the primary chromosomal gains at 17q, 7, and 16q, type 2 tumors had moderately lower frequencies of primary gains at 17p (61 versus 94%; P = 0.007) and 17q (72 versus 97%; P = 0.02). On the other hand, type 2 tumors overall had more chromosomal alterations than type 1 tumors (P = 0.01), particularly gains of 1q (28 versus 3%; P = 0.02) and losses of 8p (33 versus 0%; P = 0.001), 11 (28 versus 3%; P = 0.02), and 18 (44 versus 9%; P = 0.01). Hierarchical clustering suggested cytogenetic patterns common but not restricted to type 2 morphology, one characterized by multiple additional gains, and another predominantly showing additional losses. These findings provide genetic evidence that type 1 and type 2 tumors arise from common cytogenetic pathways and that type 2 tumors evolve from type 1 tumors. Independently of type, losses of 9p were statistically correlated with advanced disease (P = 0.0008) and may serve as a potential adverse prognostic marker in papillary renal cell carcinomas.

Prevalence of enamel defects in primary and permanent teeth in a group of schoolchildren from Granada (Spain).

PubMed

Robles, Maria-Jesús; Ruiz, Matilde; Bravo-Perez, Manuel; González, Encarnación; Peñalver, Maria-Angustias

2013-03-01

The purpose of this study was to determine and compare the prevalence and presentations of developmental defects of the enamel (DDE) in the primary and permanent dentitions of a group of healthy schoolchildren residing in Granada (Spain). A total of 1,414 healthy schoolchildren were examined using modified DDE criteria for recording enamel defects. The prevalence of DDE of any type was 40.2% in primary dentition and 52% in permanent dentition (p<0.033). Of the 31,820 primary and permanent teeth examined in the study, 699 (4.1%) primary and 1,232 (8.3%) permanent teeth had some form of DDE. Diffuse opacity was the most common type of DDE observed in primary teeth, and demarcated opacity in the permanent teeth. Enamel hypoplasia was the least prevalent defect in both dentition types. The study population showed a high prevalence of DDE in primary as well as in permanent dentition, reflecting the current increasing trend of this condition, which should be considered as a significant public health problem.

Does the Psychological Type of Primary Caregivers Relate to the Number of Books They Read to Their Children?

ERIC Educational Resources Information Center

Calahan, Charles A.

1995-01-01

Investigates whether the psychological type of 23 female primary caregivers related to the amount of reading they will do with their children. Finds a significant correlation between the personality-temperament type of mothers and the number of books they read to their children during an eight-week period. (RS)

The Relationship Between True Colors Temperament Types of Primary Caregivers and Literacy Development: An Exploratory Analysis.

ERIC Educational Resources Information Center

Calahan, Charles A.

1996-01-01

Examines the relationship between the "True Colors" temperament type of the primary caregiver and the readiness to involve her child in the social context of extracurricular reading activities (a summer reading program) intended to promote literacy development. Finds that the "Gold" and "Blue" types involved their children in organized, structured…

Types and rates of forest disturbance in Brazilian Legal Amazon, 2000–2013

PubMed Central

Tyukavina, Alexandra; Hansen, Matthew C.; Potapov, Peter V.; Stehman, Stephen V.; Smith-Rodriguez, Kevin; Okpa, Chima; Aguilar, Ricardo

2017-01-01

Deforestation rates in primary humid tropical forests of the Brazilian Legal Amazon (BLA) have declined significantly since the early 2000s. Brazil’s national forest monitoring system provides extensive information for the BLA but lacks independent validation and systematic coverage outside of primary forests. We use a sample-based approach to consistently quantify 2000–2013 tree cover loss in all forest types of the region and characterize the types of forest disturbance. Our results provide unbiased forest loss area estimates, which confirm the reduction of primary forest clearing (deforestation) documented by official maps. By the end of the study period, nonprimary forest clearing, together with primary forest degradation within the BLA, became comparable in area to deforestation, accounting for an estimated 53% of gross tree cover loss area and 26 to 35% of gross aboveground carbon loss. The main type of tree cover loss in all forest types was agroindustrial clearing for pasture (63% of total loss area), followed by small-scale forest clearing (12%) and agroindustrial clearing for cropland (9%), with natural woodlands being directly converted into croplands more often than primary forests. Fire accounted for 9% of the 2000–2013 primary forest disturbance area, with peak disturbances corresponding to droughts in 2005, 2007, and 2010. The rate of selective logging exploitation remained constant throughout the study period, contributing to forest fire vulnerability and degradation pressures. As the forest land use transition advances within the BLA, comprehensive tracking of forest transitions beyond primary forest loss is required to achieve accurate carbon accounting and other monitoring objectives. PMID:28439536

Role of amine structure on carbon dioxide adsorption from ultradilute gas streams such as ambient air.

PubMed

Didas, Stephanie A; Kulkarni, Ambarish R; Sholl, David S; Jones, Christopher W

2012-10-01

A fundamental study on the adsorption properties of primary, secondary, and tertiary amine materials is used to evaluate what amine type(s) are best suited for ultradilute CO(2) capture applications. A series of comparable materials comprised of primary, secondary, or tertiary amines ligated to a mesoporous silica support via a propyl linker are used to systematically assess the role of amine type. Both CO(2) and water adsorption isotherms are presented for these materials in the range relevant to CO(2) capture from ambient air and it is demonstrated that primary amines are the best candidates for CO(2) capture from air. Primary amines possess both the highest amine efficiency for CO(2) adsorption as well as enhanced water affinity compared to other amine types or the bare silica support. The results suggest that the rational design of amine adsorbents for the extraction of CO(2) from ambient air should focus on adsorbents rich in primary amines. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

MitoTEMPO Prevents Oxalate Induced Injury in NRK-52E Cells via Inhibiting Mitochondrial Dysfunction and Modulating Oxidative Stress

PubMed Central

Yu, Xiao; Liu, Jihong

2017-01-01

As one of the major risks for urolithiasis, hyperoxaluria can be caused by genetic defect or dietary intake. And high oxalate induced renal epithelial cells injury is related to oxidative stress and mitochondrial dysfunction. Here, we investigated whether MitoTEMPO, a mitochondria-targeted antioxidant, could protect against oxalate mediated injury in NRK-52E cells via inhibiting mitochondrial dysfunction and modulating oxidative stress. MitoSOX Red was used to determine mitochondrial ROS (mtROS) production. Mitochondrial membrane potential (Δψm) and quantification of ATP synthesis were measured to evaluate mitochondrial function. The protein expression of Nox4, Nox2, and p22 was also detected to explore the effect of oxalate and MitoTEMPO on NADPH oxidase. Our results revealed that pretreatment with MitoTEMPO significantly inhibited oxalate induced lactate dehydrogenase (LDH) and malondialdehyde (MDA) release and decreased oxalate induced mtROS generation. Further, MitoTEMPO pretreatment restored disruption of Δψm and decreased ATP synthesis mediated by oxalate. In addition, MitoTEMPO altered the protein expression of Nox4 and p22 and decreased the protein expression of IL-6 and osteopontin (OPN) induced by oxalate. We concluded that MitoTEMPO may be a new candidate to protect against oxalate induced kidney injury as well as urolithiasis. PMID:28116040

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.

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.

Prevalence of primary headache disorders in a population aged 60 years and older in a rural area of Northern China.

PubMed

Zhang, Yajing; Shi, Zhihong; Hock, Duncan; Yue, Wei; Liu, Shuling; Zhang, Ying; Liu, Shuai; Zhao, Lei; Lu, Hui; Guan, Yalin; Wang, Xiaodan; Wsiniewski, Thomas; Ji, Yong

2016-12-01

Primary headache disorders are among the most common neurological complaints worldwide, and are significant causes of disability. Data are limited on the prevalence of primary headaches among individuals aged 60 years and older in China. The purpose of our study was to investigate the prevalence and characteristics of primary headaches among people aged 60 years and older in a rural area of northern China. A door-to-door survey was conducted in Ji County of Tianjin Province. A total of 5248 residents aged 60 years and older were visited from 2014 to 2015, unannounced, and basic sociodemographic and headache diagnostic information was collected via a questionnaire. Primary headache was classified tension-type headaches, migraines, chronic headache, and unclassified headache. The 1-year prevalence for primary headaches in Ji county is 10.30 %. The 1-year prevalence of tension-type headaches, migraines, chronic headache, and unclassified headache is 2.02 %, 0.85 %, 3.79 %, and 3.63 %. The 1-year prevalence of primary headache was higher in women than in men. The 1-year prevalence of primary headache was decreased with increasing age. The 1-year prevalence of tension-type headaches and chronic headache were decreased with higher education. Headache in the elderly was mild to moderate and not serious. In a population older than 60 years of age in rural, northern China, we found the 1-year prevalence of primary headache was 10.30 %, of tension-type headaches was 2.02 %, of migraines was 0.85 %, of chronic headache was 3.79 %, and of unclassified headache was 3.63 %. The prevalence of all of these was much lower than those observed in previous studies examining prevalence rates in the general population. The results of our study also indicated that women are more likely to have primary headache than men. We also found that chronic headache was frequent among the elderly. Participants with higher education levels were more predisposed than healthy participants to tension-type headaches. We also found that respondents who did not participate in social activities had a decreased predisposition for primary headache in general, as well as for unclassified headache. Lastly, we found that participants who had heart disease were more likely than healthy participants to experience primary headache, tension-type headache, chronic headache, and unclassified headache.

Academic Achievement in Primary School in Offspring Born to Mothers With Type 1 Diabetes (the EPICOM Study): A Register-Based Prospective Cohort Study.

PubMed

Knorr, Sine; Clausen, Tine D; Vlachová, Zuzana; Bytoft, Birgitte; Damm, Peter; Beck-Nielsen, Henning; Jensen, Dorte M; Juul, Svend; Gravholt, Claus Højbjerg

2015-07-01

This study examined the effect of maternal pregestational type 1 diabetes on offspring primary school performance. We performed a prospective combined clinical and register-based cohort study comparing primary school performance in offspring (n = 707) of women with pregestational type 1 diabetes with matched control offspring (n = 60,341). We also examined the association between HbA1c levels during pregnancy and later school performance among offspring born to women with pregestational type 1 diabetes. Offspring of mothers with pregestational type 1 diabetes obtained similar school grades as control offspring when finishing primary school (regression coefficient [β] = -0.13; 95% CI = -0.30 to 0.03; P = 0.12). Adjusting for parental education also resulted in an insignificant difference between the two groups (β = -0.07; 95% CI = -0.23 to 0.09; P = 0.37). Among offspring of women with type 1 diabetes, increasing maternal HbA1c pregestationally and throughout the pregnancy was associated with lower average school grades. Offspring born to mothers with good glycemic control in the third trimester obtained higher average school grades compared with control offspring. The opposite applied to offspring born to mothers with inadequate glycemic control, who obtained significantly lower average school grades compared with control offspring. Offspring of mothers with pregestational type 1 diabetes obtained similar average grades when finishing primary school compared with matched control offspring. Among offspring of women with type 1 diabetes, we found a consistent negative association between maternal HbA1c in pregnancy and primary school grades. However, whether this association reflects a direct causal influence of intrauterine hyperglycemia is uncertain. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

77 FR 31410 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-25

.... Eastern Time. As proposed the order type would be renamed the ``Primary After 3:55 Order.'' Other than the time change, the Exchange does not propose any changes to the order type. The Exchange is proposing... type to obtain an Exchange execution before it is routed to the primary market. In particular, because...

Gravitropism in lateral roots of Arabidopsis pgm-1 mutants is indistinguishable from that of wild-type

PubMed Central

Bai, Hanwen

2011-01-01

The majority of understanding of root gravity responses comes from the study of primary roots, even though lateral roots make a far greater contribution to root system architecture. The focus of this report is the analysis of gravitropic responses in lateral roots of wild-type background and pgm-1 mutants. Despite the significant reduction in gravitropic response of primary roots of pgm-1 mutants, the lateral roots of this mutant demonstrate wild-type rates of gravitropism, suggesting a significant difference in gravity signal transduction between primary and lateral roots. PMID:21921698

Gravitropism in lateral roots of Arabidopsis pgm-1 mutants is indistinguishable from that of wild-type.

PubMed

Bai, Hanwen; Wolverton, Chris

2011-10-01

The majority of understanding of root gravity responses comes from the study of primary roots, even though lateral roots make a far greater contribution to root system architecture. The focus of this report is the analysis of gravitropic responses in lateral roots of wild-type background and pgm-1 mutants. Despite the significant reduction in gravitropic response of primary roots of pgm-1 mutants, the lateral roots of this mutant demonstrate wild-type rates of gravitropism, suggesting a significant difference in gravity signal transduction between primary and lateral roots.

Transcriptomic and anatomical complexity of primary, seminal, and crown roots highlight root type-specific functional diversity in maize (Zea mays L.)

PubMed Central

Tai, Huanhuan; Lu, Xin; Opitz, Nina; Marcon, Caroline; Paschold, Anja; Lithio, Andrew; Nettleton, Dan; Hochholdinger, Frank

2016-01-01

Maize develops a complex root system composed of embryonic and post-embryonic roots. Spatio-temporal differences in the formation of these root types imply specific functions during maize development. A comparative transcriptomic study of embryonic primary and seminal, and post-embryonic crown roots of the maize inbred line B73 by RNA sequencing along with anatomical studies were conducted early in development. Seminal roots displayed unique anatomical features, whereas the organization of primary and crown roots was similar. For instance, seminal roots displayed fewer cortical cell files and their stele contained more meta-xylem vessels. Global expression profiling revealed diverse patterns of gene activity across all root types and highlighted the unique transcriptome of seminal roots. While functions in cell remodeling and cell wall formation were prominent in primary and crown roots, stress-related genes and transcriptional regulators were over-represented in seminal roots, suggesting functional specialization of the different root types. Dynamic expression of lignin biosynthesis genes and histochemical staining suggested diversification of cell wall lignification among the three root types. Our findings highlight a cost-efficient anatomical structure and a unique expression profile of seminal roots of the maize inbred line B73 different from primary and crown roots. PMID:26628518

A morphometric analysis of cellular differentiation in caps of primary and lateral roots of Helianthus annuus

NASA Technical Reports Server (NTRS)

Moore, R.

1985-01-01

In order to determine if patterns of cell differentiation are similar in primary and lateral roots, I performed a morphometric analysis of the ultrastructure of calyptrogen, columella, and peripheral cells in primary and lateral roots of Helianthus annuus. Each cell type is characterized by a unique ultrastructure, and the ultrastructural changes characteristic of cellular differentiation in root caps are organelle specific. No major structural differences exist in the structures of the composite cell types, or in patterns of cell differentiation in caps of primary vs. lateral roots.

Method for solid state crystal growth

DOEpatents

Nolas, George S.; Beekman, Matthew K.

2013-04-09

A novel method for high quality crystal growth of intermetallic clathrates is presented. The synthesis of high quality pure phase crystals has been complicated by the simultaneous formation of both clathrate type-I and clathrate type-II structures. It was found that selective, phase pure, single-crystal growth of type-I and type-II clathrates can be achieved by maintaining sufficient partial pressure of a chemical constituent during slow, controlled deprivation of the chemical constituent from the primary reactant. The chemical constituent is slowly removed from the primary reactant by the reaction of the chemical constituent vapor with a secondary reactant, spatially separated from the primary reactant, in a closed volume under uniaxial pressure and heat to form the single phase pure crystals.

Pregnancy outcomes in women with type 1 and type 2 diabetes mellitus in a retrospective multi-institutional study in Japan.

PubMed

Sato, Takahiro; Sugiyama, Takashi; Kurakata, Michiyo; Saito, Masatoshi; Sugawara, Junichi; Yaegashi, Nobuo; Sagawa, Norimasa; Sanaka, Mayumi; Akazawa, Shoichi; Anazawa, Sonoko; Waguri, Masako; Sameshima, Hiroshi; Hiramatsu, Yuji; Toyoda, Nagayasu

2014-01-01

The present study was performed to evaluate pregnancy outcomes in women with type 1 and type 2 diabetes mellitus (DM) in Japan. This multi-institutional retrospective study was conducted in 40 general hospitals in Japan during 2003-2009. We evaluated 369 and 579 pregnant women with type 1 and type 2 DM, respectively, and compared pregnancy outcomes between the two groups. Glycosylated hemoglobin levels in the first trimester did not differ significantly between the studied groups. Gestational weight gain was lower in type 2 DM than in type 1 DM. Although there were no significant differences in perinatal outcomes between the groups, the primary cesarean section rate was higher in type 2 DM than in type 1 DM. Multiple logistic regression analysis revealed that primigravida status, pre-gestational body mass index (BMI), gestational weight gain, chronic hypertension, and microvascular disease including diabetic retinopathy or nephropathy were associated with onset of pregnancy-induced hypertension. Further, pre-gestational BMI was associated with the need for primary cesarean section. This study demonstrated that no differences were observed in the rates of perinatal mortality and congenital malformation between pregnant women with type 1 DM and type 2 DM; however, women with type 2 DM displayed a higher risk of primary cesarean section.

[MRI findings and pathological features of occult breast cancer].

PubMed

Zhang, J J; Yang, X T; Du, X S; Zhang, J X; Hou, L N; Niu, J L

2018-01-23

Objective: To investigate the magnetic resonance imaging (MRI) findings and clinicopathological features of primary lesions in patients with occult breast cancer (OBC). Methods: The imaging reports from the Breast Imaging Reporting and Data System in 2013 were retrospectively analyzed to investigate the morphology and the time signal intensity curve (TIC) of breast lesions in patients with OBC. The clinical and pathological characteristics of these patients were also included. Results: A total of 34 patients were enrolled. Among these patients, 24 patients underwent modified radical mastectomy and 18 of them had primary breast carcinoma in pathological sections. MRI detected 17 cases of primary lesions, including six masse lesions with a diameter of 0.6-1.2 cm (average 0.9 cm), and 11 non-mass lesions with four linear distributions, three segmental distributions, three focal distributions, and one regions distribution. Five patients had TIC typeⅠprimary lesions, ten had TIC type Ⅱ primary lesions, and two had TIC type Ⅲ primary lesions. Among all 34 cases, 23 of them had complete results of immunohistochemistry: 11 estrogen receptor (ER) positive lesions (47.8%), tenprogesterone receptor (PR) positive lesions (43.5%), seven human epidermal growth factor receptor 2 (HER-2) positive lesions (30.4%), and 20high expression(>14%) of Ki-67 (87.0%). The proportion of type luminal A was 4.3%, type luminal B was 43.5%, triple negative breast cancer (TNBC) was 30.4%, and HER-2 over expression accounted for 21.7%. Conclusions: The primary lesions of OBC usually manifested as small mass lesions, or focal, linear or segmental distribution of non-mass lesions. The positive rate of ER and PR was low, but the positive rate of HER-2 and the proliferation index of Ki-67 was high. Type luminal B is the most common molecular subtype.

[Fundus fluorescein angiography in metastatic choroidal carcinomas and differentiating metastatic choroidal carcinomas from primary choroidal melanomas].

PubMed

Li, Lei; Wang, Wen-Ji; Chen, Rong-Jia; Qian, Jiang; Luo, Chuan-Qi; Zhang, Yong-Jin; Shen, Ying; Ye, Xiao-Feng; Gao, Qiao-Yun

2011-01-01

To investigate the characteristics of fundus fluorescein angiography (FFA) in metastatic choroidal carcinomas and determine the value of FFA in differentiating metastatic choroidal carcinomas from primary choroidal melanomas. It was a retrospective case series. The retrospective analysis of clinical data and FFA findings was performed in 23 eyes of 22 patients with metastatic choroidal carcinomas and 31 eyes of 31 patients with primary choroidal melanomas as the control. Ocular fundus findings of metastatic choroidal carcinomas were divided into three types: solitary flat (tumor thickness less than 3 mm), solitary elevated (tumor thickness more than 3 mm) or diffuse type. FFA of the three types showed hypofluorescence during the arterial phase and progressive hyperfluorescence during the subsequent phases. The border of the lesions revealed retinal capillary dilation during the arteriovenous phase and persistent pinpoint leakage throughout the angiogram. Retinal capillary dilation and pinpoint leakage were more frequently presented in the solitary flat type. Simultaneous visualization of retinal and tumor circulation (the so called double circulation) was more frequently presented in the solitary elevated type. Pinpoint leakage could be detected in 17 (73.91%) eyes of metastatic choroidal carcinomas and in 5 (16.13%) eyes of primary choroidal melanomas. The difference between the visibility of pinpoint leakage in metastatic choroidal carcinomas and primary choroidal melanomas was statistically significant (P = 0.0000). When pinpoint leakage of FFA was used to differentiate metastatic choroidal carcinomas from primary choroidal melanomas, the sensitivity, specificity, accuracy, positive and negative predictive values were 73.91%, 83.87%, 79.63%, 77.27%, 81.25% respectively. FFA is helpful for the diagnosis of metastatic choroidal carcinomas. Pinpoint leakage on the border of lesions has some value in differentiating metastatic choroidal carcinomas from primary choroidal melanomas.

Primary cilia: cellular sensors for the skeleton.

PubMed

Anderson, Charles T; Castillo, Alesha B; Brugmann, Samantha A; Helms, Jill A; Jacobs, Christopher R; Stearns, Tim

2008-09-01

The primary cilium is a solitary, immotile cilium that is present in almost every mammalian cell type. Primary cilia are thought to function as chemosensors, mechanosensors, or both, depending on cell type, and have been linked to several developmental signaling pathways. Primary cilium malfunction has been implicated in several human diseases, the symptoms of which include vision and hearing loss, polydactyly, and polycystic kidneys. Recently, primary cilia have also been implicated in the development and homeostasis of the skeleton. In this review, we discuss the structure and formation of the primary cilium and some of the mechanical and chemical signals to which it could be sensitive, with a focus on skeletal biology. We also raise several unanswered questions regarding the role of primary cilia as mechanosensors and chemosensors and identify potential research avenues to address these questions.

Primary Cilia: Cellular Sensors for the Skeleton

PubMed Central

Anderson, Charles T.; Castillo, Alesha B.; Brugmann, Samantha A.; Helms, Jill A.; Jacobs, Christopher R.; Stearns, Tim

2010-01-01

The primary cilium is a solitary, immotile cilium that is present in almost every mammalian cell type. Primary cilia are thought to function as chemosensors, mechanosensors, or both, depending on cell type, and have been linked to several developmental signaling pathways. Primary cilium malfunction has been implicated in several human diseases, the symptoms of which include vision and hearing loss, polydactyly, and polycystic kidneys. Recently, primary cilia have also been implicated in the development and homeostasis of the skeleton. In this review, we discuss the structure and formation of the primary cilium and some of the mechanical and chemical signals to which it could be sensitive, with a focus on skeletal biology. We also raise several unanswered questions regarding the role of primary cilia as mechanosensors and chemosensors and identify potential research avenues to address these questions. PMID:18727074

Primary types of Chinese longhorned woodboring beetles (Coleoptera: Cerambycidae: and Disteniidae) of the Smithsonian Institution

USDA-ARS?s Scientific Manuscript database

The primary types of Chinese (mainland China, Taiwan, and Tibet) longhorned woodboring beetles (Coleoptera: Cerambycidae, Disteniidae) of the Smithsonian Institution are catalogued and figured, current through 2012. Data on the original combination, current name, current tribal classification, and ...

Primary types of longhorned woodboring beetles (Coleoptera: Cerambycidae and Disteniidae) of the Smithsonian Institution

USDA-ARS?s Scientific Manuscript database

The primary types of longhorned woodboring beetles (Coleoptera: Cerambycidae, Disteniidae) of the National Museum of Natural History (Smithsonian Institution) are catalogued and figured, current through 2012 (but also including some 2013 holotypes). Data on the original combination, current combina...

Primary battery design and safety guidelines handbook

NASA Technical Reports Server (NTRS)

Bragg, Bobby J.; Casey, John E.; Trout, J. Barry

1994-01-01

This handbook provides engineers and safety personnel with guidelines for the safe design or selection and use of primary batteries in spaceflight programs. Types of primary batteries described are silver oxide zinc alkaline, carbon-zinc, zinc-air alkaline, manganese dioxide-zionc alkaline, mercuric oxide-zinc alkaline, and lithium anode cells. Along with typical applications, the discussions of the individual battery types include electrochemistry, construction, capacities and configurations, and appropriate safety measures. A chapter on general battery safety covers hazard sources and controls applicable to all battery types. Guidelines are given for qualification and acceptance testing that should precede space applications. Permissible failure levels for NASA applications are discussed.

Transcriptomic and anatomical complexity of primary, seminal, and crown roots highlight root type-specific functional diversity in maize (Zea mays L.).

PubMed

Tai, Huanhuan; Lu, Xin; Opitz, Nina; Marcon, Caroline; Paschold, Anja; Lithio, Andrew; Nettleton, Dan; Hochholdinger, Frank

2016-02-01

Maize develops a complex root system composed of embryonic and post-embryonic roots. Spatio-temporal differences in the formation of these root types imply specific functions during maize development. A comparative transcriptomic study of embryonic primary and seminal, and post-embryonic crown roots of the maize inbred line B73 by RNA sequencing along with anatomical studies were conducted early in development. Seminal roots displayed unique anatomical features, whereas the organization of primary and crown roots was similar. For instance, seminal roots displayed fewer cortical cell files and their stele contained more meta-xylem vessels. Global expression profiling revealed diverse patterns of gene activity across all root types and highlighted the unique transcriptome of seminal roots. While functions in cell remodeling and cell wall formation were prominent in primary and crown roots, stress-related genes and transcriptional regulators were over-represented in seminal roots, suggesting functional specialization of the different root types. Dynamic expression of lignin biosynthesis genes and histochemical staining suggested diversification of cell wall lignification among the three root types. Our findings highlight a cost-efficient anatomical structure and a unique expression profile of seminal roots of the maize inbred line B73 different from primary and crown roots. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Creatinine plasma at uncontrolled type 2 diabetes mellitus and controlled type 2 diabetes mellitus patients at primary health care in Binjai city, Indonesia

NASA Astrophysics Data System (ADS)

Rusdiana; Savira, M.; Syahputra, M.; Santoso, A.

2018-03-01

The aim of the study knowing the comparison creatinine plasma levels at uncontrolled type 2 diabetes mellitus and controlled type 2 diabetes mellitus patients at Primary Health Care in Binjai city of North Sumatera in Indonesia. This cross-sectional study was conductedon 40 type 2 Diabetes Mellitus patients who attended Primary Health Care in Binjai. Patients with age > 40 years old, (both sexes) were included in the study. We recorded different demographic parameter as age, Body Mass Index, Blood Pressure, and personal history status. And we examined the biochemicalparameters including Hba1c, Fasting Blood Sugar Levels (FBL) and creatinine serum. We separated into two groups base on HbA1c test, controlled type 2 diabetes mellitus and uncontrolled type 2 diabetes mellitus. We measured FBL by using the portable measuring instrument, and Thamrin clinical laboratory measured Hba1c, andwe measured creatinine plasmaby spectrophotometry in Biochemistry laboratory. With statistical analysis using T-test found that there was asignificant differencein creatinine plasma levels between uncontrolled type 2 diabetes mellitus with controlled type 2 diabetes mellitus (p<0.005).

Primary mucinous adenocarcinoma of the vulva, intestinal type

PubMed Central

Lee, In Ho; Kim, Mi Kyung; Lee, Yoo Kyung; Hong, Sung Ran

2017-01-01

Primary vulva malignancy is a rare gynecologic malignancy. Most of them are squamous cell carcinomas and adenocarcinomas are much less common. Intestinal type is a rare variant of primary adenocarcinoma of the vulva. It histologically resembles mucinous colonic carcinomas. Origin from cloacal remnants has been suggested but remains speculative. A 64-year-old woman was referred to our clinic with a 1-month history of an itching vulva mass. An incisional biopsy was performed at other hospital and disclosed adenocarcinoma of intestinal type. Extensive workups were performed to detect other underlying carcinomas but revealed nothing abnormal. She underwent wide local excision without lymph node dissection for a primary vulva carcinoma. She received no adjuvant therapy and has been free from recurrent disease for 12 months after surgery. The authors report a rare case and review the relevant literature. PMID:28791269

Type-2 diabetes mellitus reduces cortical thickness and decreases oxidative metabolism in sensorimotor regions after stroke.

PubMed

Ferris, Jennifer K; Peters, Sue; Brown, Katlyn E; Tourigny, Katherine; Boyd, Lara A

2018-05-01

Individuals with type-2 diabetes mellitus experience poor motor outcomes after ischemic stroke. Recent research suggests that type-2 diabetes adversely impacts neuronal integrity and function, yet little work has considered how these neuronal changes affect sensorimotor outcomes after stroke. Here, we considered how type-2 diabetes impacted the structural and metabolic function of the sensorimotor cortex after stroke using volumetric magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). We hypothesized that the combination of chronic stroke and type-2 diabetes would negatively impact the integrity of sensorimotor cortex as compared to individuals with chronic stroke alone. Compared to stroke alone, individuals with stroke and diabetes had lower cortical thickness bilaterally in the primary somatosensory cortex, and primary and secondary motor cortices. Individuals with stroke and diabetes also showed reduced creatine levels bilaterally in the sensorimotor cortex. Contralesional primary and secondary motor cortex thicknesses were negatively related to sensorimotor outcomes in the paretic upper-limb in the stroke and diabetes group such that those with thinner primary and secondary motor cortices had better motor function. These data suggest that type-2 diabetes alters cerebral energy metabolism, and is associated with thinning of sensorimotor cortex after stroke. These factors may influence motor outcomes after stroke.

UK GPs' and practice nurses' views of continuity of care for patients with type 2 diabetes.

PubMed

Alazri, Mohammed H; Heywood, Philip; Neal, Richard D; Leese, Brenda

2007-04-01

Continuity of care is widely regarded as a core value of primary care. Type 2 diabetes is a common chronic disease with major health, social and economic impacts. Primary health care professionals in many countries are involved in the management of patients with type 2 diabetes, but their perspectives on continuity remain neglected in research. To explore UK GPs' and nurses' experiences of continuity of care for patients with type 2 diabetes in primary care settings. Semi-structured individual interviews were conducted with 16 GPs and 18 practice nurses who manage patients with type 2 diabetes recruited from 20 practices with various organizational structures in Leeds, UK. Three types of continuities were identified: relational continuity from the same health care professional, team continuity from a group of health care professionals and cross-boundary continuity across primary-secondary care settings. Relational continuity was influenced by the quality of the patient-health care professional relationship, policy of the National Health Service (NHS) in the UK (new General Medical Services contract), walk-in centres, the behaviour of receptionists and the structure and systems of the practice. Team and cross-boundary continuities were influenced by the relationship between team members and by effective communication. Relational continuity contributed to more 'personal care', but the usual health care professional might know less about diabetes. Team continuity was important in providing 'physical care', but patients could be confused by conflicting advice from different professionals. Cross-boundary continuity helps to provide 'expert advice', but is dependent upon effective communication. GPs and practice nurses dealing with patients with type 2 diabetes identified three types of continuities, each influenced by several factors. Relational continuity deals better with psychosocial care while team continuity promotes better physical care; therefore, imposing one type of continuity may inhibit good diabetic care. Cross-boundary continuity between primary and secondary care is fundamental to contemporary diabetic services and ways should be found to achieve more effective communication.

Systematic development of a theory-informed multifaceted behavioural intervention to increase physical activity of adults with type 2 diabetes in routine primary care: Movement as Medicine for Type 2 Diabetes.

PubMed

Avery, Leah; Charman, Sarah J; Taylor, Louise; Flynn, Darren; Mosely, Kylie; Speight, Jane; Lievesley, Matthew; Taylor, Roy; Sniehotta, Falko F; Trenell, Michael I

2016-07-19

Despite substantial evidence for physical activity (PA) as a management option for type 2 diabetes, there remains a lack of PA behavioural interventions suitable for delivery in primary care. This paper describes the systematic development of an evidence-informed PA behavioural intervention for use during routine primary care consultations. In accordance with the Medical Research Council Framework for the Development and Evaluation of Complex Interventions, a four-stage systematic development process was undertaken: (1) exploratory work involving interviews and workshop discussions identified training needs of healthcare professionals and support needs of adults with type 2 diabetes; (2) a systematic review with meta- and moderator analyses identified behaviour change techniques and optimal intervention intensity and duration; (3) usability testing identified strategies to increase implementation of the intervention in primary care and (4) an open pilot study in two primary care practices facilitated intervention optimisation. Healthcare professional training needs included knowledge about type, intensity and duration of PA sufficient to improve glycaemic control and acquisition of skills to promote PA behaviour change. Patients lacked knowledge about type 2 diabetes and skills to enable them to make sustainable changes to their level of PA. An accredited online training programme for healthcare professionals and a professional-delivered behavioural intervention for adults with type 2 diabetes were subsequently developed. This multifaceted intervention was informed by the theory of planned behaviour and social cognitive theory and consisted of 15 behaviour change techniques. Intervention intensity and duration were informed by a systematic review. Usability testing resolved technical problems with the online training intervention that facilitated use on practice IT systems. An open pilot study of the intervention with fidelity of delivery assessment informed optimisation and identified mechanisms to enhance implementation of the intervention during routine diabetes consultations. Movement as Medicine for Type 2 diabetes represents an evidence-informed multifaceted behavioural intervention targeting PA for management of type 2 diabetes developed for delivery in primary care. The structured development process undertaken enhances transparency of intervention content, replicability and scalability. Movement as Medicine for Type 2 diabetes is currently undergoing evaluation in a pilot RCT. ISRCTN67997502.

Mobile group II intron based gene targeting in Lactobacillus plantarum WCFS1.

PubMed

Sasikumar, Ponnusamy; Paul, Eldho; Gomathi, Sivasamy; Abhishek, Albert; Sasikumar, Sundaresan; Selvam, Govindan Sadasivam

2016-10-01

The usage of recombinant lactic acid bacteria for delivery of therapeutic proteins to the mucosa has been emerging. In the present study, an attempt was made to engineer a thyA mutant of Lactobacillus plantarum (L. plantarum) using lactococcal group II intron Ll.LtrB for the development of biologically contained recombinant L. plantarum for prevention of calcium oxalate stone disease. The 3 kb Ll.LtrB intron donor cassettes from the source vector pACD4C was PCR amplified, ligated into pSIP series of lactobacillus vector pLp_3050sAmyA, yielding a novel vector pLpACD4C (8.6 kb). The quantitative real-time PCR experiment shows 94-fold increased expression of Ll.LtrB intron and 14-fold increased expression of ltrA gene in recombinant L. plantarum containing pLpACD4C. In order to target the thyA gene, the potential intron RNA binding sites in the thyA gene of L. plantarum was predicted with help of computer algorithm. The insertion location 188|189s of thyA gene (lowest E-0.134) was chosen and the wild type intron Ll.LtrB was PCR modified, yielding a retargeted intron of pLpACDthyA. The retargeted intron was expressed by using induction peptide (sppIP), subsequently the integration of intron in thyA gene was identified by PCR screening and finally ThyA - mutant of L. plantarum (ThyA18) was detected. In vitro growth curve result showed that in the absence of thymidine, colony forming units of mutant ThyA18 was decreased, whereas high thymidine concentration (10 μM) supported the growth of the culture until saturation. In conclusion, ThyA - mutant of L. plantarum (ThyA18) constructed in this study will be used as a biologically contained recombinant probiotic to deliver oxalate decarboxylase into the lumen for treatment of hyperoxaluria and calcium oxalate stone deposition. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

47 CFR 52.15 - Central office code administration.

Code of Federal Regulations, 2010 CFR

2010-10-01

... forecast data to the NANPA. (ii) Reporting shall be by separate legal entity and must include company name, company headquarters address, Operating Company Number (OCN), parent company OCN, and the primary type of... headquarters address, OCN, parent company's OCN(s), and the primary type of business in which the numbering...

A Longitudinal Study of the Presence of Dental Anomalies in the Primary and Permanent Dentitions of Cleft Lip and/or Palate Patients.

PubMed

Suzuki, Akira; Nakano, Masayuki; Yoshizaki, Keigo; Yasunaga, Atsushi; Haruyama, Naoto; Takahashi, Ichiro

2017-05-01

  The aim is to survey primary and permanent dental anomalies: hypodontia, microdontia, a supernumerary tooth, and fused teeth in patients with cleft lip and/or palate.   Retrospective longitudinal study Subjects :  The subjects were selected from all 1724 patients with cleft lip and/or palate who were registered at the orthodontic clinic of Kyushu University Hospital, Fukuoka, Japan, from 1970 to 2009. Finally, 994 subjects were evaluated for primary dentition, 1352 for permanent dentition, and 871 for the longitudinal changes from primary to permanent dentition.   The prevalence of dental anomalies was compared for each tooth type, among various cleft types, between males and females, and between the alveolar cleft area and the noncleft area.   The prevalence of hypodontia was 16.2% for primary dentition and 52.7% for permanent dentition in the subjects with cleft lip and/or palate. Hypodontia increased with the severity of the cleft type. Multiple hypodontia was found more frequently in the subjects with bilateral cleft lip and palate and the subjects with unilateral cleft lip and palate. Microformed lateral incisors were found in 22.7% of permanent lateral incisors but not in primary dentition. Supernumerary teeth were found in 17.7% of the subjects with cleft lip and/or palate for primary maxillary dentition and in 5.7% for permanent maxillary dentition.   The prevalence of hypodontia was greater in permanent dentition than in primary dentition; although, it was not much different between males and females or between the right and left sides. The prevalence of dental anomalies was significantly different among four groups by cleft type: cleft lip, cleft lip and alveolus, cleft lip and palate, and cleft palate.

Insurance-related disparities in primary care quality among U.S. Type 2 diabetes patients.

PubMed

Lee, De-Chih; Liang, Hailun; Shi, Leiyu

2016-08-02

This study explored insurance-related disparities in primary care quality among Americans with type 2 diabetes. Data came from the household component of the 2012 Medical Expenditure Panel Survey (MEPS). Analysis focused on adult subjects with type 2 diabetes. Logistic regressions were performed to investigate the associations between insurance status and primary care attributes related to first contact, longitudinality, comprehensiveness, and coordination, while controlling for confounding factors. Preliminary findings revealed differences among three insurance groups in the first contact domain of primary care quality. After controlling for confounding factors, these differences were no longer apparent, with all insurance groups reporting similar primary care quality according to the four domains of interest in the study. There were significant differences in socioeconomic status among different insurance groups. This study reveals equitable primary care quality for diabetes patients despite their health insurance status. In addition to insurance-related differences, the other socioeconomic stratification factors are assumed to be the root cause of disparities in care. This research emphasizes the crucial role that primary care plays in the accessibility and quality of care for chronically ill patients. Policy makers should continue their commitment to reduce gaps in insurance coverage and improve access as well as quality of diabetic care.

Group Patient Education: Effectiveness of a Brief Intervention in People with Type 2 Diabetes Mellitus in Primary Health Care in Greece: A Clinically Controlled Trial

ERIC Educational Resources Information Center

Merakou, K.; Knithaki, A.; Karageorgos, G.; Theodoridis, D.; Barbouni, A.

2015-01-01

This study aims to assess the impact of a brief patient group education intervention in people with type 2 diabetes mellitus. The sample, 193 people with type 2 diabetes mellitus who were patients at the diabetic clinic of a primary health care setting in Attica, was assigned to two groups, intervention (138 individuals) and control group (55…

Comparative characteristics of primary hyperparathyroidism in pediatric and young adult patients.

PubMed

Nicholson, Kristina J; McCoy, Kelly L; Witchel, Selma F; Stang, Michael T; Carty, Sally E; Yip, Linwah

2016-10-01

Primary hyperparathyroidism is rare in pediatric patients. Our study aim was to compare primary hyperparathyroidism in pediatric (<19 years) and young adult (19-29 years) patients. A prospectively collected database from a single, high-volume institution was queried for all patients age <30 years who had initial parathyroidectomy for primary hyperparathyroidism yielding 126/4,546 (2.7%) primary hyperparathyroidism patients representing 39 pediatric and 87 young adult patients. Presenting symptoms, operative data, and postoperative course were compared for patients age 0-19 years and 20-29 years. Sporadic primary hyperparathyroidism was present in 81.7% and occurred less often in pediatric patients than young adult patients (74.4% vs 86.2%, P = .12). Among patients with hereditary primary hyperparathyroidism, multiple endocrine neoplasia type 1 was the most common type. Multiglandular disease was common in both pediatric (30.7%) and young adult (21.8%) patients. Following parathyroidectomy, 3 (2.3%) patients had permanent hypoparathyroidism and none had permanent recurrent laryngeal nerve paralysis. Biochemical cure at 6 months was equally likely in pediatric and young adult patients (97.1% vs 93.6%, P = .44) with comparable follow-up (78.4 months vs 69.1 months, P = .66) and rates of recurrent disease (5.9% vs 10.3%, P = .46). Recurrence was due to multiple endocrine neoplasia 1-related primary hyperparathyroidism in all cases. Although primary hyperparathyroidism is sporadic in most patients <19 years, they are more likely to have multiple endocrine neoplasia type 1-associated primary hyperparathyroidism (23%). Parathyroidectomy for primary hyperparathyroidism can be performed safely in pediatric patients with a high rate of cure. Follow-up for patients with hereditary disease is necessary. Copyright © 2016 Elsevier Inc. All rights reserved.

Language Teacher Burnout and School Type

ERIC Educational Resources Information Center

Mukundan, Jayakaran; Zare, Pezhman; Zarifi, Abdolvahed; Manaf, Umi Kalthom Abdul; Sahamid, Husniah

2015-01-01

The present study was an attempt to explore the level of burnout among primary school teachers in Malaysia. In addition, the study tried to determine if the school type has any significant influence on teachers' burnout level. To this end, 714 primary school teachers participated in the study. They were teaching at Malay (SK), Tamil (SJKT), and…

TEFL Textbook Evaluation: From Teachers' Perspectives

ERIC Educational Resources Information Center

Tok, Hidayet

2010-01-01

This study aims to examine the advantages and disadvantages of one type of TEFL materials, English language textbook "Spot On", used in state primary schools in Turkey. Sample of the research consists of 46 English teachers chosen randomly from state primary schools in Malatya and Adiyaman city centres. A five-likert type scale was used…

Job Satisfaction of Primary-Care Workers Who Assist the Elderly.

ERIC Educational Resources Information Center

Carter, Travis A.

1988-01-01

Used Job Descriptive Index to appraise level of job satisfaction of 111 primary-care employees. The results revealed that varied personality types chose occupations in the caregiving field; satisfaction tended to be independent of personality type. Issues such as pay, promotion, and relationships with supervisors and co-workers were important…

Checklist of Cerambycidae, Disteniidae and Vesperidae (Coleoptera) primary types of the Museu de Zoologia, Universidade de São Paulo, São Paulo, Brazil.

PubMed

Monné, Miguel A; Santos-Silva, Antonio; Casari, Sônia A; Monné, Marcela L

2017-03-31

A checklist of the 1164 primary types of Cerambycidae, Disteniidae and Vesperidae (Coleoptera) deposited in the Museu de Zoologia, Universidade de São Paulo, São Paulo, Brazil is provided. Lectotype designations for 97 species are proposed.

Seeking History: Teaching with Primary Sources in Grades 4-6.

ERIC Educational Resources Information Center

Edinger, Monica

This book offers ideas about using primary sources to enhance students' understandings of history. It discusses the following resources, methods, and ideas: types of primary sources; tips on finding and preparing primary sources for student use; personal, local, and remote history activities; detailed descriptions of diverse projects; guidelines…

Type 2 diabetes mellitus and hypothyroidism: the possible influence of metformin therapy.

PubMed

Distiller, L A; Polakow, E S; Joffe, B I

2014-02-01

To evaluate the frequency with which hypothyroidism is associated with Type 2 diabetes, to examine gender and ethnic group differences, and to assess the possible impact of metformin therapy. To compare the prevalence of hypothyroidism in a cohort of people with Type 2 diabetes with a previously published cohort of people with Type 1 diabetes from the same centre. We randomly surveyed the records of 922 people with Type 2 diabetes (576 men and 342 women) to identify diagnoses of hypothyroidism, based on current thyroxin replacement therapy (with previous biochemical confirmation). Four subjects had secondary hypothyroidism after radio-iodine therapy for primary hyperthyroidism and were excluded from the analysis. The prevalence of primary hypothyroidism was documented in the remaining 918 subjects. We assessed the association of metformin therapy with hypothyroidism. The overall prevalence of primary hypothyroidism was 11.8% (women: 22.5%; men: 5.4%, P < 0.001) in subjects with Type 2 diabetes. Inter-ethnic differences were noted, with the highest prevalence among white subjects. The prevalence of hypothyroidism was lower in subjects with Type 2 diabetes who were receiving metformin therapy (P < 0.01), and this difference was greater when assessing those who developed primary hypothyroidism after starting metformin therapy (P < 0.001) CONCLUSIONS: Our results support a relatively close association between diabetes and hypothyroidism. Hypothyroidism was more common in the cohort of white subjects than in other ethnic groups. The use of metformin therapy in people with Type 2 diabetes was associated with a significantly lower prevalence of diagnosed hypothyroidism. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

9 CFR 146.41 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

...-Type Turkey Slaughter Plants § 146.41 Definitions. Meat-type turkey. A domesticated turkey grown for the primary purpose of producing meat. Meat-type turkey slaughter plant. A meat-type turkey slaughter...

9 CFR 146.41 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

...-Type Turkey Slaughter Plants § 146.41 Definitions. Meat-type turkey. A domesticated turkey grown for the primary purpose of producing meat. Meat-type turkey slaughter plant. A meat-type turkey slaughter...

9 CFR 146.41 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

...-Type Turkey Slaughter Plants § 146.41 Definitions. Meat-type turkey. A domesticated turkey grown for the primary purpose of producing meat. Meat-type turkey slaughter plant. A meat-type turkey slaughter...

9 CFR 146.41 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

...-Type Turkey Slaughter Plants § 146.41 Definitions. Meat-type turkey. A domesticated turkey grown for the primary purpose of producing meat. Meat-type turkey slaughter plant. A meat-type turkey slaughter...

A rapid chemiluminescent slot blot immunoassay for the detection and quantification of Clostridium botulinum neurotoxin type E, in cultures.

PubMed

Cadieux, Brigitte; Blanchfield, Burke; Smith, James P; Austin, John W

2005-05-01

A simple, rapid, cost-effective in vitro slot blot immunoassay was developed for the detection and quantification of botulinum neurotoxin type E (BoNT/E) in cultures. Culture supernatants of 36 strains of clostridia, including 12 strains of Clostridium botulinum type E, 12 strains of other C. botulinum neurotoxin serotypes, and 12 strains of other clostridial species were tested. Samples containing BoNT/E were detected using affinity-purified polyclonal rabbit antisera prepared against BoNT/E with subsequent detection of secondary antibodies using chemiluminescence. All strains of C. botulinum type E tested positive, while all non C. botulinum type E strains tested negative. The sensitivity of the slot blot immunoassay for detection of BoNT/E was approximately four mouse lethal doses (MLD). The intensity of chemiluminescence was directly correlated with the concentration of BoNT/E up to 128 MLD, allowing quantification of BoNT/E between 4 and 128 MLD. The slot blot immunoassay was compared to the mouse bioassay for detection of BoNT/E using cultures derived from fish samples inoculated with C. botulinum type E, and cultures derived from naturally contaminated environmental samples. A total of 120 primary enrichment cultures derived from fish samples, of which 103 were inoculated with C. botulinum type E, and 17 were uninoculated controls, were assayed. Of the 103 primary enrichment cultures derived from inoculated fish samples, all were positive by mouse bioassay, while 94 were also positive by slot blot immunoassay, resulting in a 7.5% false-negative rate. All 17 primary enrichment cultures derived from the uninoculated fish samples were negative by both mouse bioassay and slot blot immunoassay. A total of twenty-six primary enrichment cultures derived from environmental samples were tested by mouse bioassay and slot blot immunoassay. Of 13 primary enrichment cultures positive by mouse bioassay, 12 were also positive by slot blot immunoassay, resulting in a 3.8% false-negative rate. All 13 primary enrichment cultures that tested negative by mouse bioassay also tested negative by slot blot immunoassay. The slot blot immunoassay could be used routinely as a positive screen for BoNT/E in primary enrichment cultures, and could be used as a replacement for the mouse bioassay for pure cultures.

Muscle layer histopathology and manometry pattern of primary esophageal motility disorders including achalasia.

PubMed

Nakajima, N; Sato, H; Takahashi, K; Hasegawa, G; Mizuno, K; Hashimoto, S; Sato, Y; Terai, S

2017-03-01

Histopathology of muscularis externa in primary esophageal motility disorders has been characterized previously. We aimed to correlate the results of high-resolution manometry with those of histopathology. During peroral endoscopic myotomy, peroral esophageal muscle biopsy was performed in patients with primary esophageal motility disorders. Immunohistochemical staining for c-kit was performed to assess the interstitial cells of Cajal (ICCs). Hematoxylin Eosin and Azan-Mallory staining were used to detect muscle atrophy, inflammation, and fibrosis, respectively. Slides from 30 patients with the following motility disorders were analyzed: achalasia (type I: 14, type II: 5, type III: 3), one diffuse esophageal spasm (DES), two outflow obstruction (OO), four jackhammer esophagus (JE), and one nutcracker esophagus (NE). ICCs were preserved in high numbers in type III achalasia (n=9.4±1.2 cells/high power field [HPF]), compared to types I (n=3.7±0.3 cells/HPF) and II (n=3.5±1.0 cells/HPF). Moreover, severe fibrosis was only observed in type I achalasia and not in other types of achalasia, OO, or DES. Four of five patients with JE and NE had severe inflammation with eosinophilic infiltration of the esophageal muscle layer (73.8±50.3 eosinophils/HPF) with no epithelial eosinophils. One patient with JE showed a visceral myopathy pattern. Compared to types I and II, type III achalasia showed preserved ICCs, with variable data regarding DES and OO. In disorders considered as primary esophageal motility disorders, a disease category exists, which shows eosinophilic infiltration in the esophageal muscle layer with no eosinophils in the epithelium. © 2016 John Wiley & Sons Ltd.

Socioeconomic status and geographical factors associated with active listing in primary care: a cross-sectional population study accounting for multimorbidity, age, sex and primary care

PubMed Central

Ranstad, Karin; Midlöv, Patrik; Halling, Anders

2017-01-01

Background Socioeconomic status and geographical factors are associated with health and use of healthcare. Well-performing primary care contributes to better health and more adequate healthcare. In a primary care system based on patient’s choice of practice, this choice (listing) is a key to understand the system. Objective To explore the relationship between population and practices in a primary care system based on listing. Methods Cross-sectional population-based study. Logistic regressions of the associations between active listing in primary care, income, education, distances to healthcare and geographical location, adjusting for multimorbidity, age, sex and type of primary care practice. Setting and subjects Population over 15 years (n=123 168) in a Swedish county, Blekinge (151 731 inhabitants), in year 2007, actively or passively listed in primary care. The proportion of actively listed was 68%. Main outcome measure Actively listed in primary care on 31 December 2007. Results Highest ORs for active listing in the model including all factors according to income had quartile two and three with OR 0.70 (95% CI 0.69 to 0.70), and those according to education less than 9 years of education had OR 0.70 (95% CI 0.68 to 0.70). Best odds for geographical factors in the same model had municipality C with OR 0.85 (95% CI 0.85 to 0.86) for active listing. Akaike’s Information Criterion (AIC) was 124 801 for a model including municipality, multimorbidity, age, sex and type of practice and including all factors gave AIC 123 934. Conclusions Higher income, shorter education, shorter distance to primary care or longer distance to hospital is associated with active listing in primary care. Multimorbidity, age, geographical location and type of primary care practice are more important to active listing in primary care than socioeconomic status and distance to healthcare. PMID:28601827

The influence of registered nurses and nurse practitioners on patient experience with primary care: results from the Canadian QUALICO-PC study.

PubMed

Ammi, Mehdi; Ambrose, Sarah; Hogg, Bill; Wong, Sabrina

2017-12-01

Nurses, whether registered nurses (RNs) or nurse practitioners (NPs), are becoming key providers of primary care services. While evidence for the influence of NPs on patient experience in primary care is mounting, this is less so for RNs. We use the Canadian component of the international Quality and Costs of Primary Care 2013/14 survey to investigate the mechanisms by which nurses can affect patients' experience in primary care, focusing on accessibility and appropriateness of care. The data allow us to distinguish between family practice RNs, specialised RNs and NPs, and covers all types of patients visiting a primary care clinic in a variety of contexts in all Canadian provinces. In addition to the types of nurses and full-time equivalent (FTE) numbers, we explore the role of nurse autonomy and collaboration. Our regression results show that one of the most important predictors of patient experience is the collaboration between health professionals, whereas nurse staffing in terms of FTE numbers has little influence by itself. Different types of nurses influence different dimensions of accessibility, and the association between patient experience and nurse staffing depends on the number of physicians in the clinic. Our results can inform decision-makers on how to strengthen primary care provision, and particularly in Canadian context, the adaptation of the recently implemented interprofessional primary care teams. Copyright © 2017 Elsevier B.V. All rights reserved.

Screening of Indigenous Oxalate Degrading Lactic Acid Bacteria from Human Faeces and South Indian Fermented Foods: Assessment of Probiotic Potential

PubMed Central

Kavitha, Murugan; Selvi, M. S.; Selvam, Govindan Sadasivam

2014-01-01

Lactic acid bacteria (LAB) have the potential to degrade intestinal oxalate and this is increasingly being studied as a promising probiotic solution to manage kidney stone disease. In this study, oxalate degrading LAB were isolated from human faeces and south Indian fermented foods, subsequently assessed for potential probiotic property in vitro and in vivo. Based on preliminary characteristics, 251 out of 673 bacterial isolates were identified as LAB. A total of 17 strains were found to degrade oxalate significantly between 40.38% and 62.90% and were subjected to acid and bile tolerance test. Among them, nine strains exhibited considerable tolerance up to pH 3.0 and at 0.3% bile. These were identified as Lactobacillus fermentum and Lactobacillus salivarius using 16S rDNA sequencing. Three strains, Lactobacillus fermentum TY5, Lactobacillus fermentum AB1, and Lactobacillus salivarius AB11, exhibited good adhesion to HT-29 cells and strong antimicrobial activity. They also conferred resistance to kanamycin, rifampicin, and ampicillin, but were sensitive to chloramphenicol and erythromycin. The faecal recovery rate of these strains was observed as 15.16% (TY5), 6.71% (AB1), and 9.3% (AB11) which indicates the colonization ability. In conclusion, three efficient oxalate degrading LAB were identified and their safety assessments suggest that they may serve as good probiotic candidates for preventing hyperoxaluria. PMID:24723820

Predisposing factors for infantile urinary calculus in south-west of Iran.

PubMed

Alemzadeh-Ansari, Mohammad Hasan; Valavi, Ehsan; Ahmadzadeh, Ali

2014-01-01

Urinary calculi in infants are relatively infrequent, but their incidence has increased in the recent decades. The aim of this study was to investigate the clinical presentation, metabolic risk factors, and urinary tract abnormalities in infants suffering from kidney calculus. A total of 152 infants were admitted between 2009 and 2012 with ultrasonography-proven urolithiasis. A Foley catheter was fixed and 24-hour urine samples were analyzed for calcium, citrate, oxalate, uric acid, and magnesium. For detecting cystinuria, qualitative measurement of urinary cystine was done by nitroprusside test. Urinary tract structural abnormalities were also evaluated. The mean age at the diagnosis of kidney calculus was 5.46 months (range, 15 days to 12 months). The most common clinical findings were restlessness and urinary tract infection. A family history of calculi was found in 67.1% of the patients and 68.4% were born to consanguineous marriages. Metabolic abnormalities and urinary tract abnormalities were found in 96.1% and 15.1% of children, respectively. Urinary tract abnormalities were more common in girls. The most common metabolic risk factors were hypercalciuria (79.6%) and hypocitraturia (40.9%). Hyperoxaluria and hypomagnesuria were found in about 28% of patients, both of which were associated with bilateral urolithiasis. These findings show that urinary metabolic abnormalities are very common in infants with urolithiasis. Appropriate evaluation of urinary metabolic parameters can lead us to proper diagnosis and treatment.

The Effect of Text Types on Reading Comprehension

ERIC Educational Resources Information Center

Sahin, Ayfer

2013-01-01

Aim of this study is to determine the effect of narrative and informative text types on Reading Comprehension levels of Primary Education 4th and 5th grade students. Application was fulfilled in 2011-2012 academic year with 134 students in a primary education school in Province Kirsehir. Reading comprehension tests prepared according to text types…

Evidence for a primary autoimmune type of diabetes mellitus.

PubMed

Bottazzo, G F; Cudworth, A G; Moul, D J; Doniach, D; Festenstein, H

1978-11-04

Sixty-eight patients with longstanding diabetes and persistent islet-cell antibody and 35 with coexistent diabetes and Graves's disease or primary myxoedema were studied with particular reference to the HLA system and autoantibody patterns. A higher incidence of HLA-B8 than normal was observed in the two groups. An additive relative risk exists when type I diabetes and autoimmune thyroid disease coexist, indicating that different HLA-linked genes may confer susceptibility to the pancreatic and thyroid disorders. Other characteristics, including female predominance, a later onset of diabetes, and a strong family history of autoimmune endocrinopathy, provide further evidence that this form of diabetes is aetiologically distinct from that generally seen in children. These results support the hypothesis of a primary autoimmune type of diabetes mellitus.

Recognizing and managing type 2 diabetes mellitus in children: an algorithm for primary care providers.

PubMed

Sunni, Muna; Mays, Rita; Kaup, Tara; Nathan, Brandon

2011-08-01

During the last two decades, type 2 diabetes mellitus increasingly has been seen in children. Although still not as common as type 1 diabetes among children, it has become the leading form of diabetes among adolescents of certain ethnicities. It is imperative that primary care providers recognize the risk factors, perform appropriate screening tests, and initiate therapy for children who have type 2 diabetes or prediabetes. This article discusses the epidemiology and pathogenesis of the disease, complications, and treatments, and includes a concise, easy-to-follow algorithm to assist providers in diagnosing and treating young patients.

Cell-type-specific and differentiation-status-dependent variations in cytotoxicity of tributyltin in cultured rat cerebral neurons and astrocytes.

PubMed

Oyanagi, Koshi; Tashiro, Tomoko; Negishi, Takayuki

2015-08-01

Tributyltin (TBT) is an organotin used as an anti-fouling agent for fishing nets and ships and it is a widespread environmental contaminant at present. There is an increasing concern about imperceptible but serious adverse effect(s) of exposure to chemicals existing in the environment on various organs and their physiological functions, e.g. brain and mental function. Here, so as to contribute to improvement of and/or advances in in vitro cell-based assay systems for evaluating brain-targeted adverse effect of chemicals, we tried to evaluate cell-type-specific and differentiation-status-dependent variations in the cytotoxicity of TBT towards neurons and astrocytes using the four culture systems differing in the relative abundance of these two types of cells; primary neuron culture (> 95% neurons), primary neuron-astrocyte (2 : 1) mix culture, primary astrocyte culture (> 95% astrocytes), and passaged astrocyte culture (100% proliferative astrocytes). Cell viability was measured at 48 hr after exposure to TBT in serum-free medium. IC50's of TBT were 198 nM in primary neuron culture, 288 nM in primary neuron-astrocyte mix culture, 2001 nM in primary astrocyte culture, and 1989 nM in passaged astrocyte culture. Furthermore, in primary neuron-astrocyte mix culture, vulnerability of neurons cultured along with astrocytes to TBT toxicity was lower than that of neurons cultured purely in primary neuron culture. On the other hand, astrocytes in primary neuron-astrocyte mix culture were considered to be more vulnerable to TBT than those in primary or passaged astrocyte culture. The present study demonstrated variable cytotoxicity of TBT in neural cells depending on the culture condition.

A fluid inclusion study of blueschist-facies lithologies from the Indus suture zone, Ladakh (India): Implications for the exhumation of the subduction related Sapi-Shergol ophiolitic mélange

NASA Astrophysics Data System (ADS)

Sachan, Himanshu Kumar; Kharya, Aditya; Singh, P. Chandra; Rolfo, Franco; Groppo, Chiara; Tiwari, Sameer K.

2017-09-01

The best occurrence of blueschist-facies lithologies in Himalaya is that of the Shergol Ophiolitic Mélange along the Indus suture zone in Ladakh region of north-western India. These lithologies are characterized by well preserved lawsonite-glaucophane-garnet-quartz assemblages. This paper presents for the first time the results of a detailed fluid inclusion study on these lithologies, in order to understand the fluid P-T evolution and its tectonic implications. The blueschist rocks from Shergol Ophiolitic Mélange record metamorphic peak conditions at ∼19 kbar, 470 °C. Several types of fluid inclusions are trapped in quartz and garnet, most of them being two-phase at room temperature. Three types of fluid inclusions have been recognised, basing on microtextures and fluid composition: Type-I are primary two-phase carbonic-aqueous fluid inclusions (VCO2 - LH2O); Type-II are two-phase (LH2O - VH2O) aqueous fluid inclusions, either primary (Type-IIa) or secondary (Type-IIb); Type-III are re-equilibrated fluid inclusions. In the Type-I primary carbonic-aqueous inclusions, H2O is strongly predominant with respect to CO2; the homogenization temperature of CO2 range from -7 to -2 °C. The clathrate melting temperature in such inclusions varies in between +7.1 and +8.6 °C. Type-II two-phase aqueous fluid inclusions show a wide range of salinity, from 7.8-14 wt.% NaCleq (Type-IIa) to 1.65-6.37 wt.% NaCleq (Type-IIb) with accuracy ±0.4 wt.% NaCleq. Type-I and Type-IIa primary fluid inclusions are hosted in peak minerals (garnet and quartz included in garnet), therefore they were likely entrapped at, or near to, peak P-T conditions. The dominantly aqueous fluid of both Type-I and Type-IIa inclusions was most likely produced through metamorphic devolatilization reactions occurring in the subducting slab. Despite their primary nature, the isochores of Type-I and Type-IIa inclusions do not intersect the peak metamorphic conditions of the blueschist mineral assemblage, suggesting that these inclusions stretched or re-equilibrated during nearly isothermal decompression from 19 kbar to 3 kbar or less, at T = 290 °C. This conclusion is further supported by their large variability in shapes and sizes which range from irregular inclusions ('C'/arc shaped, hook shape and satellite type). This decompression stage was followed by nearly isobaric cooling, testified by the occurrence of dendritic networks of decrepitated and 'imploded' fluid inclusions.

An unusual presentation of primary malignant B-cell-type dural lymphoma

PubMed Central

Low, Yin Yee Sharon; Lai, Siang Hui; Ng, Wai Hoe

2014-01-01

Primary malignant B-cell-type dural lymphoma is a rare subtype of primary central nervous system lymphoma (PCNSL). We herein report an unusual case of diffuse B-cell lymphoma that presents as a chronic subdural haematoma without extracranial involvement. The notable aspects of this case include the patient’s immunocompetence, a short clinical history of symptom onset, rapid neurological deterioration and a final diagnosis of high-grade PCNSL. This case highlights the challenges neurosurgeons face, especially in the emergency setting, when the disease manifests in varied presentations. PMID:25631982

A simulation study on few parameters of Cherenkov photons in extensive air showers of different primaries incident at various zenith angles over a high altitude observation level

NASA Astrophysics Data System (ADS)

Das, G. S.; Hazarika, P.; Goswami, U. D.

2018-07-01

We have studied the distribution patterns of lateral density, arrival time and angular position of Cherenkov photons generated in Extensive Air Showers (EASs) initiated by γ-ray, proton and iron primaries incident with various energies and at various zenith angles. This study is the extension of our earlier work [1] to cover a wide energy range of ground based γ-ray astronomy with a wide range of zenith angles (≤40°) of primary particles, as well as the extension to study the angular distribution patterns of Cherenkov photons in EASs. This type of study is important for distinguishing the γ-ray initiated showers from the hadronic showers in the ground based γ-ray astronomy, where Atmospheric Cherenkov Technique (ACT) is being used. Importantly, such study gives an insight on the nature of γ-ray and hadronic showers in general. In this work, the CORSIKA 6.990 simulation code is used for generation of EASs. Similarly to the case of Ref. [1], this study also revealed that, the lateral density and arrival time distributions of Cherenkov photons vary almost in accordance with the functions: ρch(r) =ρ0e-βr and tch(r) =t0eΓ/rλ respectively by taking different values of the parameters of functions for the type, energy and zenith angle of the primary particle. The distribution of Cherenkov photon's angular positions with respect to shower axis shows distinctive features depending on the primary type, its energy and the zenith angle. As a whole this distribution pattern for the iron primary is noticeably different from those for γ-ray and proton primaries. The value of the angular position at which the maximum number of Cherenkov photons are concentrated, increases with increase in energy of vertically incident primary, but for inclined primary it lies within a small value (≤1°) for almost all energies and primary types. No significant difference in the results obtained by using the high energy hadronic interaction models, viz., QGSJETII and EPOS has been observed.

Spontaneous delayed sealing in selected patients with a primary type-Ia endoleak after endovascular aneurysm repair.

PubMed

Bastos Gonçalves, F; Verhagen, H J M; Vasanthananthan, K; Zandvoort, H J A; Moll, F L; van Herwaarden, J A

2014-07-01

Direct additional therapy is advised for type-Ia endoleaks detected on completion angiography after endovascular aneurysm repair (EVAR). Additional intraoperative endovascular procedures are, however, often challenging or not possible, and direct open conversion is unattractive. The results of a selective, conservative strategy for patients with primary type-Ia endoleak has been analysed. This was a retrospective, single-centre study (UMC, Utrecht, NL). From 2004 to 2008, all patients with a primary type-Ia endoleak and suitable anatomy for EVAR, stentgraft oversizing ≥15%, and optimal deployment were included. Complications during follow-up were studied and all sequential CTA scans were reviewed. These were compared with the remaining patients, treated during the same period. Fifteen patients were included (14 male, median age 77, range 67-85) with a median aneurysm diameter of 60 mm (48-80), an aneurysm neck diameter of 26 mm (21-32), a neck length of 29 mm (11-39), and infrarenal angulation of 49° (31-90). One patient suffered rupture 2 days after EVAR - leading to the only AAA-related death. Eight of the 15 type-Ia endoleaks disappeared spontaneously on the first postoperative CTA, obtained within 1 week of EVAR. On the second postoperative CTA, obtained a median of 5 months (1-12) after EVAR, all remaining endoleaks had sealed. One recurrence occurred at 4.85 years. During a median follow-up of 3.3 years, there were five secondary interventions. Compared with controls, there were more secondary (or recurrent) type-1a endoleaks (13% vs. 4%), endograft migrations (13% vs. 3%), sac growths (33% vs. 16%), and secondary interventions (33% vs. 23%). None of these differences however, were statistically significant. All but one of the primary type-Ia endoleaks sealed spontaneously. Until sealing, the risk of rupture persisted, but subsequently only one recurrence of type-Ia endoleak was seen. In selected patients, a conservative approach for primary type-Ia endoleaks may be justified. Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

[Type IIb primary hyperlipoproteinemia. An homogenous series of 412 cases].

PubMed

Rouffy, J; Loeper, J; Dreux, C; Lemogne, M; Loeper, J; Pestel, M; Dakkak, R

1976-03-20

On the basis of a homogeneous series of 412 cases of type IIb primary hyperlipoproteinaemia, the authors compare their experience with findings in the literature. The prevalence of this type of hyperlipoproteinaemia in the general population has been underestimated at 3%. Biological diagnosis remains simple (identification of a double and distinct excess in beta and pre beta lipoproteins). Extravascular lipid deposits (gerontoxon, xanthelasma, tendon xanthomata) are not type specific. Hyperlipidaemic syndrome is rare. Above all, the importance of type IIb in atheromatous disease in the young subject now seems obvious. The mode of hereditary transmission of the familial anomaly is not certain but would appear to be often associated with a double heterozygote condition.

Power and type I error results for a bias-correction approach recently shown to provide accurate odds ratios of genetic variants for the secondary phenotypes associated with primary diseases.

PubMed

Wang, Jian; Shete, Sanjay

2011-11-01

We recently proposed a bias correction approach to evaluate accurate estimation of the odds ratio (OR) of genetic variants associated with a secondary phenotype, in which the secondary phenotype is associated with the primary disease, based on the original case-control data collected for the purpose of studying the primary disease. As reported in this communication, we further investigated the type I error probabilities and powers of the proposed approach, and compared the results to those obtained from logistic regression analysis (with or without adjustment for the primary disease status). We performed a simulation study based on a frequency-matching case-control study with respect to the secondary phenotype of interest. We examined the empirical distribution of the natural logarithm of the corrected OR obtained from the bias correction approach and found it to be normally distributed under the null hypothesis. On the basis of the simulation study results, we found that the logistic regression approaches that adjust or do not adjust for the primary disease status had low power for detecting secondary phenotype associated variants and highly inflated type I error probabilities, whereas our approach was more powerful for identifying the SNP-secondary phenotype associations and had better-controlled type I error probabilities. © 2011 Wiley Periodicals, Inc.

Assessment of oral hygiene and periodontal health around posterior primary molars after their restoration with various crown types.

PubMed

Beldüz Kara, Nihal; Yilmaz, Yucel

2014-07-01

To compare the time-dependent changes in oral hygiene and periodontal health after restoring primary posterior molars with a traditional stainless steel crown (SSC) or an aesthetic crown using various measures of periodontal health and oral hygiene. This investigation was a randomized, non-blinded prospective controlled clinical trial in which 264 crowns of different types were fitted onto the first and/or second primary molars of 76 children. The oral hygiene and the gingival health of the restored teeth and the antagonistic teeth were evaluated clinically and radiographically at 3- and 6-month intervals for 18 months after fitting the crowns. The periodontal health of the control teeth was better than that of the remaining 215 restored teeth. The oral hygiene, as measured by the simplified oral hygiene index, and gingival health, as measured by the gingival index and the volume of gingival crevicular fluid, of the restored teeth, irrespective of crown type, progressively increased during the 18-month study period. Oral hygiene and gingival health around a restored primary tooth deteriorate with time. Our results suggest that SSC, an open-faced SSC, or a NuSmile(®) pediatric crown should be the preferred crown type for restoring posterior primary teeth. © 2013 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Oral microbial community typing of caries and pigment in primary dentition.

PubMed

Li, Yanhui; Zou, Cheng-Gang; Fu, Yu; Li, Yanhong; Zhou, Qing; Liu, Bo; Zhang, Zhigang; Liu, Juan

2016-08-05

Black extrinsic discoloration in primary dentition is a common clinical and aesthetic problem that can co-occur with dental caries, the most common oral diseases in childhood. Although the role of bacteria in the formation of pigment and caries in primary dentition is important, their basic features still remain a further mystery. Using targeted sequencing of the V1-V3 hypervariable regions of bacterial 16S ribosomal RNA (rRNA) genes, we obtained a dataset consisting of 831,381 sequences from 111 saliva samples and 110 supragingival plaque samples from 40 patients with pigment (black extrinsic stain), 20 with caries (obvious decay), and 25 with both pigment and caries and from 26 healthy individuals. We applied a Dirichlet multinomial mixture (DMM)-based community typing approach to investigate oral microbial community types. Our results revealed significant structural segregation of microbial communities, as indicated by the identification of two plaque community types (A and B) and three saliva community types (C-E). We found that the independent occurrence of the two plaque community types, A and B, was potentially associated with our oral diseases of interest. For type A, three co-occurring bacterial genus pairs could separately play a potential role in the formation of pigment (Leptotrichia and Fusobacterium), caries (unclassified Gemellales and Granulicatella), and mixed caries and pigment (Streptococcus and Mogibacterium). For type B, three co-occurring bacterial genera (unclassified Clostridiaceae, Peptostreptococcus, and Clostridium) were related to mixed pigment and caries. Three dominant bacterial genera (Selenomonas, Gemella, and Streptobacillus) were linked to the presence of caries. Our study demonstrates that plaque-associated oral microbial communities could majorly contribute to the formation of pigment and caries in primary dentition and suggests potential clinical applications of monitoring oral microbiota as an indicator for disease diagnosis and prognosis.

Primary care of female adolescents with type 1 diabetes mellitus and disordered eating.

PubMed

McCarvill, Rachael; Weaver, Kathryn

2014-09-01

To identify the role of the nurse practitioner in caring for female adolescents with type 1 diabetes mellitus at risk for disordered eating behaviour and to formulate clinical recommendations for nurse practitioners in the primary care setting. Transition into adulthood can be difficult for female adolescents with type 1 diabetes mellitus. Challenges associated with management of this illness may place adolescent females at an increased risk for disordered eating. Discussion paper. Sourced literature from 1991-2013, located through CINAHL, Health Source, Proquest, PubMed, PsychInfo, Web of Science and Medline databases. Nurses involved in the primary care of female adolescents with type 1 diabetes mellitus need to be aware of the increased risk for disordered eating behaviours and develop the competencies to care for both the adolescent and her family to reduce the serious consequences of these behaviours. Awareness and acquisition of the skills required to intervene will enable nurse practitioners to recognize clients at risk for disordered eating, gain appreciation of the motivation of female adolescents with type 1 diabetes mellitus towards disordered eating behaviours and give optimal opportunity for education, counselling and recovery. Future direction for research includes exploration of the experiences of adolescents with type 1 diabetes mellitus; early interventions in the primary care setting; effective educational, preventative or supportive services for adolescents with this illness and their families; and outcomes to emerging technologies for insulin therapy on disordered eating occurrence. © 2014 John Wiley & Sons Ltd.

Hierarchical Robot Control System and Method for Controlling Select Degrees of Freedom of an Object Using Multiple Manipulators

NASA Technical Reports Server (NTRS)

Platt, Robert (Inventor); Wampler, II, Charles W. (Inventor); Abdallah, Muhammad E. (Inventor)

2013-01-01

A robotic system includes a robot having manipulators for grasping an object using one of a plurality of grasp types during a primary task, and a controller. The controller controls the manipulators during the primary task using a multiple-task control hierarchy, and automatically parameterizes the internal forces of the system for each grasp type in response to an input signal. The primary task is defined at an object-level of control, e.g., using a closed-chain transformation, such that only select degrees of freedom are commanded for the object. A control system for the robotic system has a host machine and algorithm for controlling the manipulators using the above hierarchy. A method for controlling the system includes receiving and processing the input signal using the host machine, including defining the primary task at the object-level of control, e.g., using a closed-chain definition, and parameterizing the internal forces for each of grasp type.

5 CFR 591.211 - What are the categories of consumer expenditures?

Code of Federal Regulations, 2011 CFR

2011-01-01

... furnishings and supplies, medical, education and communication, recreation, and miscellaneous. (b) Primary expenditure groups. OPM subdivides each MEG into primary expenditure groups (PEGs). There are approximately 40... different types of categories: Major expenditure groups, primary expenditure groups, and detailed...

5 CFR 591.211 - What are the categories of consumer expenditures?

Code of Federal Regulations, 2013 CFR

2013-01-01

... furnishings and supplies, medical, education and communication, recreation, and miscellaneous. (b) Primary expenditure groups. OPM subdivides each MEG into primary expenditure groups (PEGs). There are approximately 40... different types of categories: Major expenditure groups, primary expenditure groups, and detailed...

5 CFR 591.211 - What are the categories of consumer expenditures?

Code of Federal Regulations, 2014 CFR

2014-01-01

... furnishings and supplies, medical, education and communication, recreation, and miscellaneous. (b) Primary expenditure groups. OPM subdivides each MEG into primary expenditure groups (PEGs). There are approximately 40... different types of categories: Major expenditure groups, primary expenditure groups, and detailed...

5 CFR 591.211 - What are the categories of consumer expenditures?

Code of Federal Regulations, 2012 CFR

2012-01-01

... furnishings and supplies, medical, education and communication, recreation, and miscellaneous. (b) Primary expenditure groups. OPM subdivides each MEG into primary expenditure groups (PEGs). There are approximately 40... different types of categories: Major expenditure groups, primary expenditure groups, and detailed...

Issues in Primary Care: The Academic Perspective

ERIC Educational Resources Information Center

Petersdorf, Robert G.

1975-01-01

Outlines the problems requiring restructuring of programs to prepare two new types of primary care physicians: a family physician who is predominantly an ambulatory care specialist and a primary care internist, pediatrician, or obstetrician who cares for most diseases in office and hospital. (JT)

Checklist of Cerambycidae (Coleoptera) primary types of the Coleção Entomológica Pe. Jesus Santiago Moure, Departamento de Zoologia, Universidade Federal do Paraná, Curitiba, Paraná, Brazil, Instituto Nacional de Pesquisas da Amazônia, Amazonas, Manaus, Brazil, and of the Museu Paraense Emílio Goeldi, Pará, Belém, Brazil.

PubMed

Monné, Miguel A; Almeida, Lucia M; Oliveira, Marcio L; Viana, Jéssica Herzog; Monné, Marcela L

2017-01-17

The primary types of Cerambycidae (Coleoptera) deposited in the Coleção Entomológica Pe. Jesus Santiago Moure, Departamento de Zoologia, Universidade Federal do Paraná, Curitiba, Paraná, Brazil (DZUP), Instituto Nacional de Pesquisas da Amazônia, Amazonas, Manaus, Brazil (INPA), and in the Museu Paraense Emílio Goeldi, Pará, Belém,Brazil (MPEG) are catalogued. There are 54 primary types of Cerambycidae in the DZUP, 48 in the INPA, and 25 in the MPEG.

Prevalence and burden of primary headache in Akaki textile mill workers, Ethiopia.

PubMed

Takele, Getahun Mengistu; Tekle Haimanot, Redda; Martelletti, Paolo

2008-04-01

Headache disorders are the most common complaints worldwide. Migraine, tension-type and cluster headaches account for majority of primary headaches and impose a substantial burden on the individual, family or society at large. The burden is immense on workers, women and children in terms of missing work and school days. There are few studies that show relatively lower prevalence of primary headaches in Africa as compared to Europe and America. There might be many reasons for this lower prevalence. The objective of this study is to determine the prevalence and burden of primary headaches among the Akaki textile factory workers, which may provide data for the local and international level toward the campaign of lifting the burden of headache worldwide. The overall 1-year prevalence of all types of primary headaches was found to be 16.4%, and that of migraine was 6.2%. The prevalence of migraine in females was 10.1% while it was 3.7% in males. The prevalence of tension-type headaches was found to be 9.8%. This was 16.3 % in females as compared to 5.7% in males. The burden of the primary headaches in terms of lost workdays, gross under recognition and absence of effective treatment is tremendous. In conclusion, the prevalence of primary headaches in the Akaki textile mill workers is significant, particularly in females, and the burden is massive, in a place of poverty and ignorance. We recommend the availability and administration of specific therapy to the factory workers with primary headaches, and community based well-designed study for the whole nation's rural and urban population.

Early prophylactic autogenous bone grafting in type III open tibial fractures.

PubMed

Kesemenli, Cumhur C; Kapukaya, Ahmet; Subaşi, Mehmet; Arslan, Huseyin; Necmioğlu, Serdar; Kayikçi, Cuma

2004-08-01

The authors report the results achieved in patients with type III open tibial fractures who underwent primary autogenous bone grafting at the time of debridement and skeletal stabilisation. Twenty patients with a mean age of 35.8 years (range, 24-55) were treated between 1996 and 1999. Eight fractures were type IIIA, 11 were type IIIB, and 1 was type IIIC. At the index procedure, wound debridement, external fixation and autogenous bone grafting with bone coverage were achieved. The mean follow-up period was 46 months (range, 34-55). The mean time to fixator removal was 21 weeks (range, 14-35), and the mean time to union was 28 weeks (range, 19-45). Skin coverage was achieved by a myocutaneous flap in 2 patients, late primary closure in 4, and split skin grafting in 14. One (5%) of the patients experienced delayed union, and 1 (5%) developed infection. In tibial type III open fractures, skin coverage may be delayed, using the surrounding soft tissue to cover any exposed bone after thorough débridement and wound cleansing. Primary prophylactic bone grafting performed at the same time reduces the rate of delayed union, shortens the time to union, and does not increase the infection rate.

Culturally appropriate organization of water and sewerage projects built through public private partnerships

PubMed Central

2017-01-01

This paper contributes to the pursuit of socially sustainable water and sanitation infrastructure for all people by discovering statistically robust relationships between Hofstede’s dimensions of cross-cultural comparison and the choice of contract award types, project type, and primary revenue sources. This analysis, which represents 973 projects distributed across 24 low- and middle-income nations, uses a World Bank dataset describing high capital cost water and sewerage projects funded through private investment. The results show that cultural dimensions explain variation in the choice of contract award types, project type, and primary revenue sources. These results provide empirical evidence that strategies for water and sewerage project organization are not culturally neutral. The data show, for example, that highly individualistic contexts are more likely to select competitive contract award types and to depend on user fees to provide the primary project revenue stream post-construction. By selecting more locally appropriate ways to organize projects, project stakeholders will be better able to pursue the construction of socially sustainable water and sewerage infrastructure. PMID:29200432

A Comparative Evaluation between Cheiloscopic Patterns and Terminal Planes in Primary Dentition.

PubMed

Vignesh, R; Rekha, C Vishnu; Annamalai, Sankar; Norouzi, Parisa; Sharmin, Ditto

2017-01-01

To assess the correlation between different cheiloscopic patterns with the terminal planes in deciduous dentition. Three hundred children who are 3-6 years old with complete primary dentition were recruited, and the pattern of molar terminal plane was recorded in the pro forma. Lip prints of these children were recorded with lipstick-cellophane method, and the middle 10 mm of lower lip was analyzed for the lip print pattern as suggested by Sivapathasundharam et al . The pattern was classified based on Tsuchihashi and Suzuki classification. Type II (branched) pattern was the most predominant cheiloscopic pattern. The predominant patterns which related to the terminal planes were as follows: Type IV (reticular) and Type V (irregular) pattern for mesial step, Type IV (reticular) pattern for distal step, and Type I (complete vertical) pattern for flush terminal plane. No significant relationship was obtained on gender comparison. Lip prints can provide an alternative to dermatoglyphics to predict the terminal plane in primary dentition. Further studies with larger sample size are required to provide an insight into its significant correlations.

A Comparative Evaluation between Cheiloscopic Patterns and Terminal Planes in Primary Dentition

PubMed Central

Vignesh, R; Rekha, C Vishnu; Annamalai, Sankar; Norouzi, Parisa; Sharmin, Ditto

2017-01-01

Objective: To assess the correlation between different cheiloscopic patterns with the terminal planes in deciduous dentition. Materials and Methods: Three hundred children who are 3–6 years old with complete primary dentition were recruited, and the pattern of molar terminal plane was recorded in the pro forma. Lip prints of these children were recorded with lipstick-cellophane method, and the middle 10 mm of lower lip was analyzed for the lip print pattern as suggested by Sivapathasundharam et al. The pattern was classified based on Tsuchihashi and Suzuki classification. Results: Type II (branched) pattern was the most predominant cheiloscopic pattern. The predominant patterns which related to the terminal planes were as follows: Type IV (reticular) and Type V (irregular) pattern for mesial step, Type IV (reticular) pattern for distal step, and Type I (complete vertical) pattern for flush terminal plane. No significant relationship was obtained on gender comparison. Conclusion: Lip prints can provide an alternative to dermatoglyphics to predict the terminal plane in primary dentition. Further studies with larger sample size are required to provide an insight into its significant correlations. PMID:29326500

Divergence in Forest-Type Response to Climate and Weather: Evidence for Regional Links Between Forest-Type Evenness and Net Primary Productivity

USGS Publications Warehouse

Bradford, J.B.

2011-01-01

Climate change is altering long-term climatic conditions and increasing the magnitude of weather fluctuations. Assessing the consequences of these changes for terrestrial ecosystems requires understanding how different vegetation types respond to climate and weather. This study examined 20 years of regional-scale remotely sensed net primary productivity (NPP) in forests of the northern Lake States to identify how the relationship between NPP and climate or weather differ among forest types, and if NPP patterns are influenced by landscape-scale evenness of forest-type abundance. These results underscore the positive relationship between temperature and NPP. Importantly, these results indicate significant differences among broadly defined forest types in response to both climate and weather. Essentially all weather variables that were strongly related to annual NPP displayed significant differences among forest types, suggesting complementarity in response to environmental fluctuations. In addition, this study found that forest-type evenness (within 8 ?? 8 km2 areas) is positively related to long-term NPP mean and negatively related to NPP variability, suggesting that NPP in pixels with greater forest-type evenness is both higher and more stable through time. This is landscape- to subcontinental-scale evidence of a relationship between primary productivity and one measure of biological diversity. These results imply that anthropogenic or natural processes that influence the proportional abundance of forest types within landscapes may influence long-term productivity patterns. ?? 2011 Springer Science+Business Media, LLC (outside the USA).

The Patient-Centered Medical Home (PCMH) Framing Typology for Understanding the Structure, Function, and Outcomes of PCMHs.

PubMed

Kieber-Emmons, Autumn M; Miller, William L

2017-01-01

Patient-centered medical homes (PCHMs) aspire to transform today's challenged primary care services. However, it is unclear which PCMH characteristics produce specific outcomes of interest for care delivery. This study tested a novel typology of PCMH practice transformation, the PCMH framing typology, and evaluated measurable outcomes by each type. Using the Patient-Centered Primary Care Collaborative 2012 to 2013 Annual Review, this secondary analysis of the published PCMH literature extracted data from publications of 59 PCMHs. Each of the 59 sites was categorized as 1 of 4 PCMH types: add-on, renovated, hybrid, or integrated. Six outcome measures (cost reductions, decreased emergency department/hospital utilization, improved quality, improved access, increased preventive services, and improved patient satisfaction) were independently coded for each site. Practices were combined based on type, and mean outcomes scores for each measure were displayed on radar graphs for comparison. While each type showed a characteristic pattern of success, only the integrated type improved in all 6 outcomes. No type achieved high success in all measures. There seem to be 4 types of PCMH, each of which shows a distinctive outcomes profile. Within the PCMH framing typology, direction is emerging for how best to transform primary care to achieve the greatest success. © Copyright 2017 by the American Board of Family Medicine.

Primary and secondary precipitates in a hierarchical-precipitate-strengthened ferritic alloy

DOE PAGES

Song, Gian; Sun, Zhiqian; Poplawsky, Jonathan D.; ...

2017-02-27

The microstructures of a hierarchical-precipitate-strengthened ferritic alloy are characterized, using transmission-electron microscopy (TEM) and atom-probe tomography (APT). The alloy shows duplex precipitates. The primary precipitate with an average edge length of 90 nm consists of NiAl- and Ni2TiAl-type phases, while the secondary precipitate with an average radius of 2 nm is a NiAl-type phase. Based on the APT results, the volume fractions of the primary and secondary precipitates were calculated, using the lever rule to be 17.3 and 2.3 %, respectively.

Management of obesity in patients with type 2 diabetes mellitus in primary care.

PubMed

Mohammad, Shoaib; Ahmad, Jamal

2016-01-01

Obesity and being overweight is the most powerful risk factor accounting for 80-90% of patients with type 2 diabetes mellitus (T2DM). The epidemic of obesity is driving the diabetes epidemic to alarming levels and primary care is becoming an important setting for obesity management in T2DM in India. Yet many primary care providers feel ill-equipped or inadequately supported to address obesity in patients with diabetes. This article reviews the most recent and strongest evidence-based strategies that may aid physicians in management of obesity in patients with T2DM in primary care. A systematic literature search of MEDLINE using the search terms Obesity, Obesity in T2DM, weight loss and Primary Care was conducted. The American Diabetes Association, National Institute for Health, National Institute of Health and Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN) and World Health Organization websites were also searched. Most studies in this area are observational in design with few randomized controlled trials (RCTs). Articles and studies involving meta-analysis or RCTs were preferred over other types. Effective weight management treatment in T2DM patient can be implemented in the primary care setting. Evidence based individualized lifestyle and pharmacologic measures supported by behavioral intervention and counseling with appropriate and informed surgical referrals has the potential to improve the success of weight management within primary care. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Low resolution spectroscopy of selected Algol systems

NASA Astrophysics Data System (ADS)

Devarapalli, Shanti Priya; Jagirdar, Rukmini; Parthasarathy, M.; Sahu, D. K.; Mohan, Vijay; Bhatt, B. C.; Thomas, Vineet S.

2018-04-01

The analysis of spectroscopic data for 30 Algol-type binaries is presented. All these systems are short period Algols having primaries with spectral types B and A. Dominant spectral lines were identified for the spectra collected and their equivalent widths were calculated. All the spectra were examined to understand presence of mass transfer, a disk or circumstellar matter and chromospheric emission. We also present first spectroscopic and period study for few Algols and conclude that high resolution spectra within and outside the primary minimum are needed for better understanding of these Algol type close binaries.

Psychological Types of Female Primary School Teachers in Anglican State-Maintained Schools in England and Wales: Implications for Continuing Professional Development

ERIC Educational Resources Information Center

Francis, Leslie J.; Lankshear, David W.; Robbins, Mandy

2011-01-01

A sample of 221 female primary school teachers in Anglican state-maintained schools in England and Wales completed the Francis Psychological Type Scales (FPTS). The data demonstrated clear preferences for Extraversion (E) over Introversion (I), for Sensing (S) over Intuition (N), for Feeling (F) over Thinking (T) and for Judging (J) over…

Good imaging with very fast paraboloidal primaries - An optical solution and some applications. [performance improvement of astronomical telescopes

NASA Technical Reports Server (NTRS)

Angel, J. R. P.; Woolf, N. J.; Epps, N. W.

1982-01-01

Attention is given to the imaging performance improvement obtainable in telescopes with fast parabolic primaries by means of two-mirror correctors of the Paul-Baker type. Images with 80 percent of the energy concentrated within 0.2 arcsec are projected for an f/1 primary relaying to an f/2 final focus, over a 1 deg-diameter field. It is noted that the mechanical structure and enclosure of a large telescope built with these fast optics should be significantly smaller and less expensive than those for conventional optics. The application of the Paul-Baker corrector system is explored for such diverse telescope types as those employing six off-axis primary mirrors, UV astronomy telescopes with no chromatic aberration, a low emissivity IR astronomy instrument with an off-axis f/1 parent primary mirror part, and thin rectangular aperture telescopes which are useful for spectroscopy and photometry.

Socioeconomic status and geographical factors associated with active listing in primary care: a cross-sectional population study accounting for multimorbidity, age, sex and primary care.

PubMed

Ranstad, Karin; Midlöv, Patrik; Halling, Anders

2017-06-09

Socioeconomic status and geographical factors are associated with health and use of healthcare. Well-performing primary care contributes to better health and more adequate healthcare. In a primary care system based on patient's choice of practice, this choice (listing) is a key to understand the system. To explore the relationship between population and practices in a primary care system based on listing. Cross-sectional population-based study. Logistic regressions of the associations between active listing in primary care, income, education, distances to healthcare and geographical location, adjusting for multimorbidity, age, sex and type of primary care practice. Population over 15 years (n=123 168) in a Swedish county, Blekinge (151 731 inhabitants), in year 2007, actively or passively listed in primary care. The proportion of actively listed was 68%. Actively listed in primary care on 31 December 2007. Highest ORs for active listing in the model including all factors according to income had quartile two and three with OR 0.70 (95% CI 0.69 to 0.70), and those according to education less than 9 years of education had OR 0.70 (95% CI 0.68 to 0.70). Best odds for geographical factors in the same model had municipality C with OR 0.85 (95% CI 0.85 to 0.86) for active listing. Akaike's Information Criterion (AIC) was 124 801 for a model including municipality, multimorbidity, age, sex and type of practice and including all factors gave AIC 123 934. Higher income, shorter education, shorter distance to primary care or longer distance to hospital is associated with active listing in primary care.Multimorbidity, age, geographical location and type of primary care practice are more important to active listing in primary care than socioeconomic status and distance to healthcare. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Elevated production of NH4NO3 from the photochemical processing of vehicle exhaust: Implications for air quality in the Seoul Metropolitan Region

NASA Astrophysics Data System (ADS)

Link, Michael F.; Kim, Jounghwa; Park, Gyutae; Lee, Taehyoung; Park, Taehyun; Babar, Zaeem Bin; Sung, Kijae; Kim, Pilho; Kang, Seokwon; Kim, Jeong Soo; Choi, Yongjoo; Son, Jihawn; Lim, Ho-Jin; Farmer, Delphine K.

2017-05-01

A vehicle fleet representative of passenger vehicles driven in the Seoul Metropolitan Region was investigated for primary emissions and secondary chemistry. Exhaust was photochemically oxidized in a flow reactor to determine the ammonium nitrate (NH4NO3) aerosol formation potential from vehicles of gasoline, diesel and liquid petroleum gasoline (LPG) fuel types. Secondary formation of aerosol NH4NO3, was larger than primary emissions for all vehicle fuel types except diesel, for which negligible secondary NH4NO3 production was observed. Although diesel vehicles emitted more primary nitrogen oxides than other vehicle types, ammonia emitted from gasoline and liquid petroleum gasoline fuels types limited the secondary production of NH4NO3. The results suggest that gasoline and liquid petroleum gasoline vehicles with three-way catalysts could be an important source of ammonia for NH4NO3 aerosol formation in ammonia-limited environments, including the Seoul Metropolitan Region.

Surgical recurrence in Crohn's disease: a comparison between different types of bowel resections.

PubMed

Aaltonen, Gisele; Carpelan-Holmström, Monika; Keränen, Ilona; Lepistö, Anna

2018-04-01

To compare recurrence frequency and location between different types of bowel resections in Crohn's disease patients. This was a retrospective study of consecutive patients undergoing bowel resection for Crohn's disease between 2006 and 2016. Type of primary operation was recorded and grouped as ileocolic resection, small bowel resection, segmental colon resection with colocolic anastomosis or colorectal anastomosis, colectomy with ileorectal anastomosis, or end stoma operation. Binary logistic regression was used to compare surgical recurrence frequency between groups. We also investigated how Crohn's disease location at reoperations was related to the primary bowel resection type. Altogether, 218 patients with a median follow-up of 4.7 years were included in our study. Reoperation was performed in 42 (19.3%) patients. The risk of reoperation using the ileocolic resection group as reference was the following: small bowel resection (odds ratio (OR) 2.95, 95% confidence interval (CI) 1.01-8.66; P = 0.049), segmental colon resection with colocolic or colorectal anastomosis (OR 6.20, 95% CI 2.04-18.87; P = 0.001), colectomy with ileorectal anastomosis (OR 26.57, 95% CI 2.59-273.01; P = 0.006), and end stoma operation (OR 4.62, 95% CI 1.90-11.26; P = 0.001). In case of surgical recurrence, the reoperation type and location correlated with the primary bowel resection type. Reoperation frequency in Crohn's disease is lower after ileocolic resection than after other types of bowel resections. Surgical recurrence in Crohn's disease tends to maintain the disease location of the primary operation. One third of Crohn's patients undergoing an end stoma operation will still need new bowel resections due to recurrence.

Velopharyngeal function of patients with cleft palate after primary palatoplasty: relevance of sex, age, and cleft type.

PubMed

Yang, Yunqiang; Li, Yang; Wu, Yeke; Gu, Yifei; Yin, Heng; Long, Hu; Shi, Bing; Zheng, Qian

2013-05-01

The aim of this study was to investigate the relevance of sex, age, and cleft type to velopharyngeal function after primary Sommerlad palatoplasty so as to improve velopharyngeal function after the procedure. Records of 503 patients with nonsyndromic cleft palate after primary Sommerlad palatoplasty were included in the retrospective study. Relevance between their velopharyngeal function and sex, age, and cleft type was analyzed. Statistical analysis was performed using SPSS 13.0 (SPSS Inc., Chicago, IL). There were no significant differences of velopharyngeal competence (VPC) rates between different sexes (P = 0.635). Specifically, VPC rates were significantly higher in younger-than-2-years groups than in older age groups (P < 0.05) and significantly lower in 6-years-or-older group (P < 0.05). No differences were found among 2- to 6-year-old groups (P > 0.05). The VPC rates were significantly lower in the bilateral complete cleft palate and the unilateral complete cleft palate than in the incomplete cleft palate before 2 years old (P < 0.05), whereas there were no significant differences totally (P = 0.875). Results showed that the disparity of the VPC rate among different cleft types would decrease with age. Moreover, results of multivariate logistic regression also indicated that operation age and cleft type are factors influencing velopharyngeal function. Primary palatoplasty should be completed before 2 years old, and the postoperative velopharygeal function will greatly decreases after 6 years old. The influence of cleft type on velopharyngeal function is limited to young patients. For those who have missed the best surgical timing, appropriate delay of operation age is reasonable, especially for patients with complete cleft palate. For patients 4 to 6 years old, the first choice is still simple palatoplasty no matter which cleft type they are classified into.

Cryopreservation and in vitro culture of primary cell types from lung tissue of a stranded pygmy sperm whale (Kogia breviceps).

PubMed

Annalaura Mancia; Spyropoulos, Demetri D; McFee, Wayne E; Newton, Danforth A; Baatz, John E

2012-01-01

Current models for in vitro studies of tissue function and physiology, including responses to hypoxia or environmental toxins, are limited and rely heavily on standard 2-dimensional (2-D) cultures with immortalized murine or human cell lines. To develop a new more powerful model system, we have pursued methods to establish and expand cultures of primary lung cell types and reconstituted tissues from marine mammals. What little is known about the physiology of the deep-sea diving pygmy sperm whale (PSW), Kogia breviceps, comes primarily from stranding events that occur along the coast of the southeastern United States. Thus, development of a method for preserving live tissues and retrieving live cells from deceased stranded individuals was initiated. This report documents successful cryopreservation of PSW lung tissue. We established in vitro cultures of primary lung cell types from tissue fragments that had been cryopreserved several months earlier at the stranding event. Dissociation of cryopreserved lung tissues readily provides a variety of primary cell types that, to varying degrees, can be expanded and further studied/manipulated in cell culture. In addition, PSW-specific molecular markers have been developed that permitted the monitoring of fibroblast, alveolar type II, and vascular endothelial cell types. Reconstitution of 3-D cultures of lung tissues with these cell types is now underway. This novel system may facilitate the development of rare or disease-specific lung tissue models (e.g., to test causes of PSW stranding events and lead to improved treatments for pulmonary hypertension or reperfusion injury in humans). Also, the establishment of a "living" tissue bank biorepository for rare/endangered species could serve multiple purposes as surrogates for freshly isolated samples. Copyright © 2011 Elsevier Inc. All rights reserved.

Violence at work and depressive symptoms in primary health care teams: a cross-sectional study in Brazil.

PubMed

da Silva, Andréa Tenório Correia; Peres, Maria Fernanda Tourinho; Lopes, Claudia de Souza; Schraiber, Lilia Blima; Susser, Ezra; Menezes, Paulo Rossi

2015-09-01

Implementation of primary care has long been a priority in low- and middle-income countries. Violence at work may hamper progress in this field. Hence, we examined the associations between violence at work and depressive symptoms/major depression in primary care teams (physicians, nurses, nursing assistants, and community health workers). A cross-sectional study was undertaken in the city of Sao Paulo, Brazil. We assessed a random sample of Family Health Program teams. We investigated depressive symptoms and major depression using the nine-item Patient Health Questionnaire (PHQ-9), and exposure to violence at work in the previous 12 months using a standardized questionnaire. Associations between exposure to violence and depressive symptoms/major depression were analyzed using multinomial logistic regression. Of 3141 eligible workers, 2940 (93 %) completed the interview. Of these, 36.3 % (95 % CI 34.6-38.1) presented intermediate depressive symptoms, and 16 % (95 % CI 14.6-17.2), probable major depression. The frequencies of exposure to the different types of violence at work were: insults (44.9 %), threats (24.8 %), physical aggression (2.3 %), and witnessing violence (29.5 %). These exposures were strongly and progressively associated with depressive symptoms (adjusted odds ratio 1.67 for exposure to one type of violence; and 5.10 for all four types), and probable major depression (adjusted odds ratio 1.84 for one type; and 14.34 for all four types). Primary care workers presenting depressive symptoms and those who have experienced violence at work should be assisted. Policy makers should prioritize strategies to prevent these problems, since they can threaten primary care sustainability.

The Epidemiology and National Trends of Bearing Surface Usage in Primary Total Hip Arthroplasty in Korea

PubMed Central

Yoon, Pil Whan; Kim, Yunjung; Yoo, Seungmi; Lee, Sahnghoon; Kim, Hee Joong

2016-01-01

Background We analyzed the data for primary total hip arthroplasty (THA) in the Korean nationwide database to assess (1) the epidemiology and national trends of bearing surface usage in THAs and (2) the prevalence of each type of bearing surface according to age, gender, hospital type, primary payer, and hospital procedure volume. Methods A total of 30,881 THAs were analyzed using the Korean Health Insurance Review and Assessment Service database for 2007 through 2011. Bearing surfaces were sub-grouped according to device code for national health insurance claims and consisted of ceramic-on-ceramic (CoC), metal-on-polyethylene (MoP), ceramic-on-polyethylene (CoP), and metal-on-metal (MoM). The prevalence of each type of bearing surface was calculated and stratified by age, gender, hospital type, primary payer, and procedure volume of each hospital. Results CoC was the most frequently used bearing surface (76.7%), followed by MoP (11.9%), CoP (7.3%), and MoM (4.1%). The proportion of THAs using a CoC bearing surface increased steadily from 71.6% in 2007 to 81.4% in 2011, whereas the proportions using CoP, MoP, and MoM bearing surfaces decreased. The order of prevalence was identical to that in the general population regardless of age, gender, hospital type, primary payer, and hospital procedure volume. Conclusions The trends and epidemiology of bearing surface usage in THAs in Korea are different from those in other countries, and the CoC bearing surface is the most prevalent articulation. In future, the results of a large-scale study using nationwide data of THAs involving a CoC bearing surface will be reported in Korea. PMID:26929796

Lipid Profiles, Inflammatory Markers, and Insulin Therapy in Youth with Type 2 Diabetes.

PubMed

Levitt Katz, Lorraine E; Bacha, Fida; Gidding, Samuel S; Weinstock, Ruth S; El Ghormli, Laure; Libman, Ingrid; Nadeau, Kristen J; Porter, Kristin; Marcovina, Santica

2018-05-01

Data regarding atherogenic dyslipidemia and the inflammation profile in youth with type 2 diabetes is limited and the effect of insulin therapy on these variables has not previously been studied in youth. We determined the impact of insulin therapy on lipid and inflammatory markers in youth with poorly controlled type 2 diabetes. In the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) multicenter trial, 285 participants failed to sustain glycemic control on randomized treatment (primary outcome, glycated hemoglobin A1c [HbA1c] at ≥8% for 6 months); 363 maintained glycemic control (never reached primary outcome). Statins were used for a low-density lipoprotein cholesterol of ≥130 mg/dL. Upon reaching the primary outcome, insulin was started. Changes in lipids and inflammatory markers (slopes over time) were examined. Progression of dyslipidemia was related to glycemic control. In those with the primary outcome, insulin therapy impacted HbA1c modestly, and dampened the increase in total cholesterol, low-density lipoprotein cholesterol, and total apolipoprotein B, although statin use increased from 8.6% to 22% year after the primary outcome. The increase in triglycerides and plasma nonesterified fatty acids stabilized after insulin was started, independent of HbA1c. There was an increase in high-sensitivity C-reactive protein that continued after insulin initiation, related to HbA1c and percent overweight. Worsening dyslipidemia and inflammation over time raise concern regarding premature development of atherosclerosis in youth with type 2 diabetes. Insulin therapy has a limited benefit in the absence of glycemic control. Strategies to achieve better glycemic control are needed. ClinicalTrials.gov: NCT00081328. Copyright © 2017 Elsevier Inc. All rights reserved.

The Epidemiology and National Trends of Bearing Surface Usage in Primary Total Hip Arthroplasty in Korea.

PubMed

Yoon, Pil Whan; Yoo, Jeong Joon; Kim, Yunjung; Yoo, Seungmi; Lee, Sahnghoon; Kim, Hee Joong

2016-03-01

We analyzed the data for primary total hip arthroplasty (THA) in the Korean nationwide database to assess (1) the epidemiology and national trends of bearing surface usage in THAs and (2) the prevalence of each type of bearing surface according to age, gender, hospital type, primary payer, and hospital procedure volume. A total of 30,881 THAs were analyzed using the Korean Health Insurance Review and Assessment Service database for 2007 through 2011. Bearing surfaces were sub-grouped according to device code for national health insurance claims and consisted of ceramic-on-ceramic (CoC), metal-on-polyethylene (MoP), ceramic-on-polyethylene (CoP), and metal-on-metal (MoM). The prevalence of each type of bearing surface was calculated and stratified by age, gender, hospital type, primary payer, and procedure volume of each hospital. CoC was the most frequently used bearing surface (76.7%), followed by MoP (11.9%), CoP (7.3%), and MoM (4.1%). The proportion of THAs using a CoC bearing surface increased steadily from 71.6% in 2007 to 81.4% in 2011, whereas the proportions using CoP, MoP, and MoM bearing surfaces decreased. The order of prevalence was identical to that in the general population regardless of age, gender, hospital type, primary payer, and hospital procedure volume. The trends and epidemiology of bearing surface usage in THAs in Korea are different from those in other countries, and the CoC bearing surface is the most prevalent articulation. In future, the results of a large-scale study using nationwide data of THAs involving a CoC bearing surface will be reported in Korea.

Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas

ClinicalTrials.gov

2018-06-11

ALK-Positive Large B-Cell Lymphoma; Atypical Burkitt/Burkitt-Like Lymphoma; Burkitt-Like Lymphoma With 11q Aberration; Diffuse Large B-Cell Lymphoma Activated B-Cell Type; Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation; Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; EBV-Positive Mucocutaneous Ulcer; High-Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements; Human Herpesvirus 8-Positive Neoplastic Cells Present; Intravascular Large B-Cell Lymphoma; Large B-Cell Lymphoma With IRF4 Rearrangement; Plasmablastic Lymphoma; Primary Cutaneous Diffuse Large B-Cell Lymphoma; Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type; Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System; Primary Effusion Lymphoma; Recurrent B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Lymphomatoid Granulomatosis; Recurrent Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Small Intestinal High Grade B-Cell Lymphoma, Not Otherwise Specified; T-Cell/Histiocyte-Rich Large B-Cell Lymphoma

The diagnostic characteristics of a group of patients with primary gastric lymphoma: macroscopic, histopathological and immunohistochemical aspects.

PubMed

Rotaru, Ionela; Ciurea, T; Foarfă, Camelia; Tănase, Alina Daniela; Găman, G

2012-01-01

Primary gastric lymphoma is defined as the malignant lymphoproliferative disease with initial symptoms located in the stomach, or tumor mass located in the stomach. This paper aims to present the macroscopic, histopathological and immunohistochemical aspects encountered in a group of patients with primary gastric lymphoma, diagnosed between 2005 and 2010 in the Hematology Clinic of Craiova and the Hematology Clinic of "Fundeni" Institute in Bucharest. This study was performed on a group of 65 patients diagnosed with primary gastric lymphoma. The positive diagnosis in primary gastric lymphoma is established by the histopathological and immunohistochemical analysis of gastric biopsies, taken during the upper gastrointestinal endoscopy, or of gastric resection samples. We used the monoclonal antibodies CD20, CD10, CD5, k light chain, PCNA (proliferating cell nuclear antigen) and Ki67. The average age of the patients enrolled in the study was 52.55 years. The most common macroscopic feature encountered was the mixed ulcerative-vegetative one. We found two histological types, represented by diffuse large B-cell lymphoma (with or without MALT component), and marginal zone lymphoma (MALT type). Both the MALT type lymphoma and the diffuse large B-cell lymphoma revealed B-cell phenotype. A correct diagnosis is very important in terms of therapeutic approach. The characteristics of the group of patients were: a higher number of the aggressive histological type; an excessive use of gastric resection; none of the cases was a T-lymphoproliferation.

The effects of surgical preparation techniques and implant macro-geometry on primary stability: An in vitro study

PubMed Central

Severino, Marco; Rastelli, Claudio; Bernardi, Sara; Caruso, Silvia; Galli, Massimo; Lamazza, Luca; Di Paolo, Carlo

2017-01-01

Background The attainment of a good primary stability is a necessary condition to ensure the success of osseointegration in implantology. In type IV cancellous bone, however, it is possible that a reduced primary stability can lead to an increased rate of failure. The aim of this study was therefore to determine, with the help of the resonance frequency (Osstell mentor), which technique of implant site preparation (piezo surgery, conventional, under-preparation, bone compaction, osteodistraction) and macro-geometry is able to improve implant stability in type IV cancellous bone. Material and Methods 10 pig ribs were prepared with a surgical pre-drilled guide, calibrated for a correct implant positioning. On each rib, 5 implant sites (one for each technique) were prepared. Successively, 50 conical implants (Tekka Global D) were inserted and measured with the resonance frequency to evaluate the primary stability. Data collected were analyzed by analysis of variance (ANOVA) to test whether the Implant Stability Quotient (ISQ) values of the five techniques were significantly different. Results The results showed that no significant differences among the ISQ values of the five techniques used were found. Also, no significant differences in the macro-geometry of the two types of compared implants were observed. However, the macro-geometry of Tekka implants, characterized by a double condensing thread, seems to provide greater ISQ values than those of single thread implants when using the same technique. Conclusions In light of these preliminary data, it is conceivable that in cases of reduced stability, such as those occurring with a type IV bone, all means ameliorating the primary stability and accelerating the osseointegration can be utilized. Key words:Implant primary stability, resonance frequency analysis, implant site preparation. PMID:28160577

The Relationship Between Neutrophil–Lymphocyte Ratio and Primary Patency of Percutaneous Transluminal Angioplasty in Hemodialysis Arteriovenous Fistula Stenosis When Using Conventional and Drug-Eluting Balloons

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

Çildağ, Mehmet Burak, E-mail: mbcildag@yahoo.com; Çildağ, Songül, E-mail: songulcildag@yahoo.com; Köseoğlu, Ömer Faruk Kutsi, E-mail: kutsikoseoglu@yahoo.com

ObjectiveThe aim of this study is to investigate the potential association of neutrophil–lymphocyte ratio (NLR) between primary patency of percutaneous transluminal angioplasty (PTA) in hemodialysis arteriovenous fistula stenosis and type (Conventional and Drug-Eluting) of balloons used in PTA.Material-MethodThis retrospective study consists of 78 patients with significant arteriovenous fistulas stenosis who were treated with PTA by using Drug-Eluting Balloon (DEB) (n = 29) or Conventional Balloon (CB) (n = 49). NLR was calculated from preinterventional blood samples. All patients were classified into two groups. Group A; primary patency <12 months (43/78), Group B; primary patency ≥12 months (35/78). Cox regression analysis and Kaplan–Meier method were used to determine respectivelymore » independent factors affecting the primary patency and to compare the primary patency for the two balloon types.ResultsNLR ratio and balloon type of the two groups were significantly different (p = 0.002, p = 0.010). The cut-off value of NLR was 3.18 for determination of primary patency, with sensitivity of 81.4 % and specificity of 51.4 %. Primary patency rates between PTA with DEB and CB displayed statistically significant differences (p < 0.05). The cut-off value was 3.28 for determination of 12-month primary patency with the conventional balloon group; sensitivity was 81.8 % and specificity was 81.3 %. There was no statistical relation between NLR levels and the drug-eluting balloon group in 12-month primary patency (p = 0.927).ConclusionIncreased level of NLR may be a risk factor in the development of early AVF restenosis after successful PTA. Preferring Drug-Eluting Balloon at an increased level of NLR can be beneficial to prolong patency.« less

Pain and Function Recovery Trajectories following Revision Hip Arthroplasty: Short-Term Changes and Comparison with Primary Hip Arthroplasty in the ADAPT Cohort Study.

PubMed

Lenguerrand, Erik; Whitehouse, Michael R; Wylde, Vikki; Gooberman-Hill, Rachael; Blom, Ashley W

2016-01-01

Patients report similar or better pain and function before revision hip arthroplasty than before primary arthroplasty but worse results are reported after revision surgery than after primary surgery. The trajectory of post-operative recovery during the first months and any differences by type of surgery have received little attention. We explored the trajectories of change in pain and function after revision hip arthroplasty to 12-months post-operatively and compare them with those observed after primary hip arthroplasty. This study is a prospective cohort study of patients undergoing primary (n = 80 with 92% for an indication of osteoarthritis) and revision (n = 43) hip arthroplasties. WOMAC pain and function scores and walking speed were collected pre-operatively, at 3 and 12-months post-operatively. Multilevel regression models were used to chart and compare the trajectories of change (0-3 months and 3-12 months) between types of surgery. The improvements in pain and function following revision arthroplasty occurred within the first 3-months with no evidence of further change beyond this initial period. While the pattern of recovery was similar to the one observed after primary arthroplasty, improvements in the first 3-months were smaller after revision compared to primary arthroplasty. Patients listed for revision surgery reported lower pre-operative pain levels but similar post-operative levels compared to those undergoing primary surgery. At 12-months post-operation patients who underwent a revision arthroplasty had not reached the same level of function achieved by those who underwent primary arthroplasty. The post-operative improvements in pain and function are larger following primary hip arthroplasty than following revision hip arthroplasty. Irrespectively of surgery type, most of the improvements occur in the first three post-operative months. More research is required to identify whether the recovery following revision surgery could be improved with specific post-operative interventions.

Comparative assessment of the polypeptide profiles from lateral and primary roots of Phaseolus vulgaris L

NASA Technical Reports Server (NTRS)

Westberg, J.; Odom, W. R.; Guikema, J. A.; Spooner, B. S. (Principal Investigator)

1994-01-01

In Phaseolus vulgaris, primary roots show gravitational sensitivity soon after emerging from the seed. In contrast, lateral roots are agravitropic during early development, and become gravitropic after several cm growth. Primary and lateral root tissues were examined by polyacrylamide gel electrophoresis, coupled with western blotting techniques, to compare proteins which may contribute to the acquisition of gravitational sensitivity. Root tips and zones of cell elongation were compared for each root type, using immunological probes for calmodulin, alpha-actin, alpha-tubulin, and proteins of the plastid envelope. Lateral roots contained qualitatively less calmodulin, and showed a slightly different pattern of actin-related epitope proteins, than did primary root tissues, suggesting that polypeptide differences may contribute to the gravitational sensitivity which these root types express.

Pursuing equity: contact with primary care and specialist clinicians by demographics, insurance, and health status.

PubMed

Ferrer, Robert L

2007-01-01

Long-term shifts in specialty choice and health workforce policy have raised concern about the future of primary care in the United States. The objective of this study was to examine current use of primary and specialty care across the US population for policy-relevant subgroups, such as disadvantaged populations and persons with chronic illness. Data from the Medical Expenditure Panel Survey from 2004 were analyzed using a probability sample patients or other participants from the noninstitutionalized US population in 2004 (N = 34,403). The main and secondary outcome measures were the estimates of the proportion of Americans who accessed different types of primary care and specialty physicians and midlevel practitioners, as well as the fraction of ambulatory visits accounted for by the different clinician types. Data were disaggregated by income, health insurance status, race/ethnicity, rural or urban residence, and presence of 5 common chronic diseases. Family physicians were the most common clinician type accessed by adults, seniors, and reproductive-age women, and they were second to pediatricians for children. Disadvantaged adults with 3 markers of disadvantage (poverty, disadvantaged minority, uninsured) received 45.6% (95% CI, 40.4%-50.7%) of their ambulatory visits from family physicians vs 30.5% (95% CI, 30.0%-32.1%) for adults with no markers. For children with 3 vs 0 markers of disadvantage, the proportion of visits from family physicians roughly doubled from 16.5% (95% CI, 14.4%-18.6%) to 30.1% (95% CI, 18.8%-41.2%). Family physicians constitute the only clinician group that does not show income disparities in access. Multivariate analyses show that patterns of access to family physicians and nurse-practitioners are more equitable than for other clinician types. Primary care clinicians, especially family physicians, deliver a disproportionate share of ambulatory care to disadvantaged populations. A diminished primary care workforce will leave considerable gaps in US health care equity. Health care workforce policy should reflect this important population-level function of primary care.

Primary health care registered nurses' types in implementation of health promotion practices.

PubMed

Maijala, Virpi; Tossavainen, Kerttu; Turunen, Hannele

2016-09-01

Aim This study aimed to identify and reach consensus among primary health care participants [registered nurses (RNs) who receive clients, directors of nursing, senior physicians, health promotion officers, and local councillors] on the types of service provider that RNs who receive clients represent in the implementation of health promotion practices in primary health care in Eastern Finland. There is an increasing focus on public health thinking in many countries as the population ages. To meet the growing needs of the health promotion practices of populations, advance practice has been recognized as effective in the primary health care setting. The advance practice nurses share many common features, such as being RNs with additional education, possessing competencies to work independently, treating clients in both acute and primary care settings, and applying a variety of health promotion practices into nursing. The two-stage modified Delphi method was applied. In round one, semi-structured interviews were conducted among primary health care participants (n=42) in 11 health centres in Eastern Finland. In round two, a questionnaire survey was conducted in the same health centres. The questionnaire was answered by 64% of those surveyed (n=56). For data analysis, content analysis and descriptive statistics were used. Findings This study resulted in four types of service provider that RNs who receive clients represented in the implementation of health promotion practices in the primary health care setting in Eastern Finland. First, the client-oriented health promoter demonstrated four dimensions, which reached consensus levels ranging between 82.1 and 89.3%. Second, the developer of health promotion practices comprised four dimensions, which reached consensus levels between 71.4 and 85.7%. Third, the member of multi-professional teams of health promotion practices representing three dimensions, with consensus levels between 69.6 and 82.1%. Fourth, the type who showed interest towards health policy reached a consensus level of 55.4% in this study.

Multi-walled carbon nanotube length as a critical determinant of bioreactivity with primary human pulmonary alveolar cells

PubMed Central

Sweeney, Sinbad; Berhanu, Deborah; Misra, Superb K.; Thorley, Andrew J.; Valsami-Jones, Eugenia; Tetley, Teresa D.

2015-01-01

Multiwalled carbon nanotube (MWCNT) length is suggested to critically determine their pulmonary toxicity. This stems from in vitro and in vivo rodent studies and in vitro human studies using cell lines (typically cancerous). There is little data using primary human lung cells. We addressed this knowledge gap, using highly relevant, primary human alveolar cell models exposed to precisely synthesized and thoroughly characterized MWCNTs. In this work, transformed human alveolar type-I-like epithelial cells (TT1), primary human alveolar type-II epithelial cells (ATII) and alveolar macrophages (AM) were treated with increasing concentrations of MWCNTs before measuring cytotoxicity, inflammatory mediator release and MAP kinase signalling. Strikingly, we observed that short MWCNTs (~0.6 µm in length) induced significantly greater responses from the epithelial cells, whilst AM were particularly susceptible to long MWCNTs (~20 µm). These differences in the pattern of mediator release were associated with alternative profiles of JNK, p38 and ERK1/2 MAP kinase signal transduction within each cell type. This study, using highly relevant target human alveolar cells and well defined and characterized MWCNTs, shows marked cellular responses to the MWCNTs that vary according to the target cell type, as well as the aspect ratio of the MWCNT. PMID:25780270

First siRNA library screening in hard-to-transfect HUVEC cells

PubMed Central

Zumbansen, Markus; Altrogge, Ludger M; Spottke, Nicole UE; Spicker, Sonja; Offizier, Sheila M; Domzalski, Sandra BS; St Amand, Allison L; Toell, Andrea; Leake, Devin; Mueller-Hartmann, Herbert A

2010-01-01

Meaningful RNAi-based data for target gene identification are strongly dependent on the use of a biologically relevant cell type and efficient delivery of highly functional siRNA reagents into the selected cell type. Here we report the use of the Amaxa® Nucleofector® 96-well Shuttle® System for siRNA screening in primary cells. Lonza's Clonetics® HUVEC-Human Umbilical Vein Endothelial Cells were transfected with Thermo Scientific Dharmacon siGENOME® siRNA Libraries targeting protein kinases and cell cycle related genes and screened for genes important for cell viability. Of the 37 primary hits, down-regulation of 33 led to reduced proliferation or increased cell death, while down-regulation of two allowed for better cell viability. The validated four genes out of the 16 strongest primary hits (COPB2, PYCS, CDK4 and MYC) influenced cell proliferation to varying degrees, reflecting differing importance for survival of HUVEC cells. Our results demonstrate that the Nucleofector® 96-well Shuttle® System allows the delivery of siRNA libraries in cell types previously considered to be difficult to transfect. Thus, identification and validation of gene targets can now be conducted in primary cells, as the selection of cell types is not limited to those accessible by lipid-mediated transfection. PMID:20628494

Multidisciplinary coordinated care for Type 2 diabetes: A qualitative analysis of patient perspectives.

PubMed

Berkowitz, Seth A; Eisenstat, Stephanie A; Barnard, Lily S; Wexler, Deborah J

2018-06-01

To explore the patient perspective on coordinated multidisciplinary diabetes team care among a socioeconomically diverse group of adults with type 2 diabetes. Qualitative research design using 8 focus groups (n=53). We randomly sampled primary care patients with type 2 diabetes and conducted focus groups at their primary care clinic. Discussion prompts queried current perceptions of team care. Each focus group was audio recorded, transcribed verbatim, and independently coded by three reviewers. Coding used an iterative process. Thematic saturation was achieved. Data were analyzed using content analysis. Most participants believed that coordinated multidisciplinary diabetes team care was a good approach, feeling that diabetes was too complicated for any one care team member to manage. Primary care physicians were seen as too busy to manage diabetes alone, and participants were content to be treated by other care team members, especially if there was a single point of contact and the care was coordinated. Participants suggested that an ideal multidisciplinary approach would additionally include support for exercise and managing socioeconomic challenges, components perceived to be missing from the existing approach to diabetes care. Coordinated, multidisciplinary diabetes team care is understood by and acceptable to patients with type 2 diabetes. Copyright © 2018 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Evaluation of the enterovirus laboratory surveillance system in Denmark, 2010 to 2013.

PubMed

Condell, Orla; Midgley, Sofie; Christiansen, Claus Bohn; Chen, Ming; Chen Nielsen, Xiaohui; Ellermann-Eriksen, Svend; Mølvadgaard, Mette; Schønning, Kristian; Vermedal Hoegh, Silje; Andersen, Peter Henrik; Voldstedlund, Marianne; Fischer, Thea Kølsen

2016-05-05

The primary aim of the Danish enterovirus (EV) surveillance system is to document absence of poliovirus infection. The conflict in Syria has left many children unvaccinated and movement from areas with polio cases to Europe calls for increased awareness to detect and respond to virus-transmission in a timely manner. We evaluate the national EV laboratory surveillance, to generate recommendations for system strengthening. The system was analysed for completeness of viral typing analysis and clinical information and timeliness of specimen collection, laboratory results and reporting of clinical information. Of 23,720 specimens screened, 2,202 (9.3%) were EV-positive. Submission of cerebrospinal fluid and faecal specimens from primary diagnostic laboratories was 79.5% complete (845/1,063), and varied by laboratory and patient age. EV genotypes were determined in 68.5% (979/1,430) of laboratory-confirmed cases, clinical information was available for 63.1% (903/1,430). Primary diagnostic results were available after a median of 1.4 days, typing results after 17 days, detailed clinical information after 33 days. The large number of samples typed demonstrated continued monitoring of EV-circulation in Denmark. The system could be strengthened by increasing the collection of supplementary faecal specimens, improving communication with primary diagnostic laboratories, adapting the laboratory typing methodology and collecting clinical information with electronic forms.

Primary Progressive Aphasia

MedlinePlus

... condition has three types, which cause different symptoms. Semantic variant primary progressive aphasia Symptoms include these difficulties: ... a not-for-profit organization and proceeds from Web advertising help support our mission. Mayo Clinic does ...

Combined human papillomavirus typing and TP53 mutation analysis in distinguishing second primary tumors from lung metastases in patients with head and neck squamous cell carcinoma.

PubMed

Daher, Tamas; Tur, Mehmet Kemal; Brobeil, Alexander; Etschmann, Benjamin; Witte, Biruta; Engenhart-Cabillic, Rita; Krombach, Gabriele; Blau, Wolfgang; Grimminger, Friedrich; Seeger, Werner; Klussmann, Jens Peter; Bräuninger, Andreas; Gattenlöhner, Stefan

2018-06-01

In head and neck squamous cell carcinoma (HNSCC), the occurrence of concurrent lung malignancies poses a significant diagnostic challenge because metastatic HNSCC is difficult to discern from second primary lung squamous cell carcinoma (SCC). However, this differentiation is crucial because the recommended treatments for metastatic HNSCC and second primary lung SCC differ profoundly. We analyzed the origin of lung tumors in 32 patients with HNSCC using human papillomavirus (HPV) typing and targeted next generation sequencing of all coding exons of tumor protein 53 (TP53). Lung tumors were clearly identified as HNSCC metastases or second primary tumors in 29 patients, thus revealing that 16 patients had received incorrect diagnoses based on clinical and morphological data alone. The HPV typing and mutation analysis of all TP53 coding exons is a valuable diagnostic tool in patients with HNSCC and concurrent lung SCC, which can help to ensure that patients receive the most suitable treatment. © 2018 Wiley Periodicals, Inc.

A model of regional primary production for use with coarse resolution satellite data

NASA Technical Reports Server (NTRS)

Prince, S. D.

1991-01-01

A model of crop primary production, which was originally developed to relate the amount of absorbed photosynthetically active radiation (APAR) to net production in field studies, is discussed in the context of coarse resolution regional remote sensing of primary production. The model depends on an approximately linear relationship between APAR and the normalized difference vegetation index. A more comprehensive form of the conventional model is shown to be necessary when different physiological types of plants or heterogeneous vegetation types occur within the study area. The predicted variable in the new model is total assimilation (net production plus respiration) rather than net production alone or harvest yield.

Germinal centre frequency is decreased in pancreatic lymph nodes from individuals with recent-onset type 1 diabetes.

PubMed

Willcox, Abby; Richardson, Sarah J; Walker, Lucy S K; Kent, Sally C; Morgan, Noel G; Gillespie, Kathleen M

2017-07-01

Pancreatic lymph nodes (PLNs) are critical sites for the initial interaction between islet autoantigens and autoreactive lymphocytes, but the histology of PLNs in tissue from individuals with type 1 diabetes has not been analysed in detail. The aim of this study was to examine PLN tissue sections from healthy donors compared with those at risk of, or with recent-onset and longer-duration type 1 diabetes. Immunofluorescence staining was used to examine PLN sections from the following donor groups: non-diabetic (n=15), non-diabetic islet autoantibody-positive (n=5), recent-onset (≤1.5 years duration) type 1 diabetes (n=13), and longer-duration type 1 diabetes (n=15). Staining for CD3, CD20 and Ki67 was used to detect primary and secondary (germinal centre-containing) follicles and CD21 and CD35 to detect follicular dendritic cell networks. The frequency of secondary follicles was lower in the recent-onset type 1 diabetes group compared with the non-diabetic control group. The presence of insulitis (as evidence of ongoing beta cell destruction) and diagnosis of type 1 diabetes at a younger age, however, did not appear to be associated with a lower frequency of secondary follicles. A higher proportion of primary B cell follicles were observed to lack follicular dendritic cell networks in the recent-onset type 1 diabetes group. Histological analysis of rare PLNs from individuals with type 1 diabetes suggests a previously unrecognised phenotype comprising decreased primary B cell follicle frequency and fewer follicular dendritic cell networks in recent-onset type 1 diabetes.

Basal insulin initiation in primary vs. specialist care: similar glycaemic control in two different patient populations.

PubMed

Orozco-Beltran, D; Pan, C; Svendsen, A L; Faerch, L; Caputo, S

2016-03-01

To investigate the effect of healthcare provider (HCP) type (primary vs. specialist) on glycaemic control and other treatment parameters. Study of Once-Daily Levemir (SOLVE(™) ) is an international, 24-week, observational study of insulin initiation in people with type 2 diabetes. A total of 17,374 subjects were included, comprising 4144 (23.9%) primary care subjects. Glycaemic control improved in both HCP groups from baseline to final visit [glycated haemoglobin (HbA1c) -1.2 ± 1.4% (-13.1 ± 15.3 mmol/mol) and -1.3 ± 1.6% (-14.2 ± 17.5 mmol/mol), respectively]. After adjustment for known confounders, there was no statistically significant effect of HCP group on final HbA1c [-0.04%, 95% confidence interval (CI) -0.09 to -0.01 (-0.4 mmol/mol, 95% CI -1.0-0.1 mmol/mol), p = 0.1590]. However, insulin doses at the final visit were higher in primary care patients (+0.06, 95% CI 0.06-0.07 U/kg, p < 0.0001). Logistic regression demonstrated a significant effect of HCP type (primary vs. specialist care) on hypoglycaemia risk [odds ratio (OR) 0.75, 95% CI 0.64-0.87, p = 0.0002]. Primary care physicians took more time to train patients and had more frequent contact with patients than specialists (both p < 0.0001). Primary care physicians and specialists achieved comparable improvements in glycaemic control following insulin initiation. © 2016 The Authors. International Journal of Clinical Practice Published by John Wiley & Sons Ltd.

Type of primary education is associated with condom use at sexual debut among Chilean adolescents.

PubMed

Huneeus, Andrea; Deardorff, Julianna; Lahiff, Maureen; Guendelman, Sylvia

2014-05-01

Although condom use in adolescence is related to higher lifetime educational attainment, the association between primary education (from kindergarten to eighth grade) and adolescent sexual behavior is not well understood. This study examined the association between type of school in which primary education was completed-public, charter, or private-and condom use at sexual debut among Chilean adolescents. Drawing on the 2009 Chilean National Youth Survey, a population-based sample of general community youth aged 15 to 29 years, we conducted a study of the 4217 participants who reported onset of sexual activity during adolescence. Bivariate and multple logistic regression was used to examine the relationship between type of primary school attended (60.1% public, 30.3% charter, and 9.6% private) and condom use at sexual debut while controlling for sociodemographic characteristics and sexual behavior. Compared with students who completed their primary education in private or charter schools, students who completed their primary education in public schools had 1.85 (95% confidence interval, 1.12-3.04) and 1.67 (95% confidence interval, 1.26-2.23) higher odds, respectively, of not using condoms at sexual debut. Odds were similar for students living in urban settings, whereas there were too few students attending private schools in rural areas to allow meaningful estimates. Independent of household income, primary schooling is associated with sexual health behaviors among Chilean adolescents living in urban areas and can serve as a target for public health interventions designed to prevent sexually transmitted infections in adolescence.

Antihypertensive drugs for elderly patients: a cross- sectional study

PubMed Central

Lim, Ka Keat; Sivasampu, Sheamini; Khoo, Ee Ming

2015-01-01

INTRODUCTION As the population ages, the prevalence of hypertension also increases. Although primary care is usually the patient’s first point of contact for healthcare, little is known about the management of hypertension among elderly patients at the primary care level. This study aimed to determine the antihypertensive prescription trend for elderly patients, the predictors of antihypertensive use and any inappropriate prescribing practices in both public and private primary care settings. METHODS Data on patient demographics, diagnosis, prescription pattern, payment mode and follow-up was extracted from a cross-sectional study involving 122 public primary care clinics and 652 private primary care clinics in Malaysia. Encounters with hypertensive patients aged ≥ 60 years were included. RESULTS A total of 1,017 antihypertensive medications were prescribed – calcium channel blockers (27.1%), beta blockers (25.5%), diuretics (23.3%), angiotensin-converting enzyme inhibitors (14.9%) and angiotensin receptor blockers (6.3%). Out of the 614 patient encounters, 53.1% of the patients were prescribed monotherapy, 31.6% were prescribed dual therapy, 12.2% triple therapy, 2.8% quadruple therapy and 0.3% quintuple therapy. Type of primary care clinic and payment mode were significant predictors for the prescription of combination therapy and fixed-dose combination therapy, respectively. Four types of inappropriate prescriptions were identified. CONCLUSION Calcium channel blockers were the most common antihypertensive drug prescribed and more than half of the elderly patients were on monotherapy. Antihypertensive drug prescription was found to be associated with the type of primary care clinic and the payment mode, suggesting that prescription is influenced by the cost of the drug. PMID:25597751

Botulinum toxin type A in treatment of bilateral primary axillary hyperhidrosis: randomised, parallel group, double blind, placebo controlled trial

PubMed Central

Naumann, M; Lowe, N J

2001-01-01

Objectives To evaluate the safety and efficacy of botulinum toxin type A in the treatment of bilateral primary axillary hyperhidrosis. Design Multicentre, randomised, parallel group, placebo controlled trial. Setting 17 dermatology and neurology clinics in Belgium, Germany, Switzerland, and the United Kingdom. Participants Patients aged 18-75 years with bilateral primary axillary hyperhidrosis sufficient to interfere with daily living. 465 were screened, 320 randomised, and 307 completed the study. Interventions Patients received either botulinum toxin type A (Botox) 50 U per axilla or placebo by 10-15 intradermal injections evenly distributed within the hyperhidrotic area of each axilla, defined by Minor's iodine starch test. Main outcome measures Percentage of responders (patients with ⩾50% reduction from baseline of spontaneous axillary sweat production) at four weeks, patients' global assessment of treatment satisfaction score, and adverse events. Results At four weeks, 94% (227) of the botulinum toxin type A group had responded compared with 36% (28) of the placebo group. By week 16, response rates were 82% (198) and 21% (16), respectively. The results for all other measures of efficacy were significantly better in the botulinum toxin group than the placebo group. Significantly higher patient satisfaction was reported in the botulinum toxin type A group than the placebo group (3.3 v 0.8, P<0.001 at 4 weeks). Adverse events were reported by only 27 patients (11%) in the botulinum toxin group and four (5%) in the placebo group (P>0.05). Conclusion Botulinum toxin type A is a safe and effective treatment for primary axillary hyperhidrosis and produces high levels of patient satisfaction. What is already known on this topicPrimary hyperhidrosis is a chronic disorder that can affect any part of the body, especially the axillas, palms, feet, and faceCurrent treatments are often ineffective, short acting, or poorly toleratedWhat this study addsBotulinum toxin type A was significantly better than placebo on all measures of sweatingPatient satisfaction was high and few adverse events were reportedEffects of treatment remained apparent at 16 weeks PMID:11557704

Exploring the impact of the care sport connector in the Netherlands.

PubMed

Leenaars, Karlijn E F; Smit, Eva; Wagemakers, Annemarie; Molleman, Gerard R M; Koelen, Maria A

2017-10-16

Regular physical activity (PA) is deemed to contribute to the primary and secondary prevention of several chronic diseases, like diabetes mellitus, cancer, cardiovascular diseases, and osteoporosis. In 2012, Care Sport Connectors (CSC), to whom a broker has been ascribed, were introduced in the Netherlands to stimulate PA and guide primary care patients towards local sport facilities. The aim of this study was to explore which structural embedding is the most promising for CSCs' work. In three rounds of interviews, 13 CSCs were followed for 2 years in their work. In these interviews, a network survey was used to identify organisations in the CSCs' network, whether they collaborated with these organisations, and the role of the organisations in the connection. Data from the network survey were analysed using the RE-AIM framework and disaggregated into how CSCs were structurally embedded (Type A: only PA sector; Type B: different sectors; Type C: partnership). A related samples Wilcoxon signed rank test was performed to study how the CSCs' network developed between 2014 and 2016. All CSCs established a connection between the primary care and the PA sector in which the average number of organisations with which CSCs collaborated increased significantly between 2014 (8.3) and 2016 (19.8) (p = 0.002). However, differences were identified in the way CSCs were structurally embedded and in the way they established the connection. Type A CSCs established the connection mostly around their own activities, supported PA organisations with their activities, and collaborated with primary care and welfare professionals around their own activities. Type B and Type C CSCs established the connection by organising, supporting, and implementing different kinds of activities targeting different kinds of audiences, and collaborated mostly with primary care professionals around the referral of professionals' patients. The results of this study suggest that adopting an integral approach (Type B and C) for the structural embedding of the CSC is more promising for reaching the desired outcomes. Whether CSCs really improve the target groups' PA level and health needs to be further studied. Dutch Trial Register NTR4986 . Registered 14 December 2014.

Virasoro constraints for D 2n + 1 -, E 6 -, E 7 -, E 8 -type minimal models coupled to 2D gravity

NASA Astrophysics Data System (ADS)

Yen, Tim

1990-12-01

We find Virasoro constraints for D 2 n + 1 -, E 6 -, E 7 -, E 8 -type models analogous to the recently discovered Virasoro constraints for A n-type models by Fukuma et al., and Dijkgraaf et al. We verify that the proposed Virasoro constraints give operator scaling dimensions identical to those found by Kostov. We check that these Virasoro constraints and, more generally, W-algebra constraints can be used to express correlation functions with non-primary operator in terms of correlation functions of primary operators only.

Comparative characteristics of electron energy spectrum in PIG and arc type discharge plasmas

NASA Technical Reports Server (NTRS)

Romanyuk, L. I.; Suavilnyy, N. Y.

1978-01-01

The electron distribution functions relative to the velocity component directed along the magnetic field are compared for PIG and arc type discharges. The identity of these functions for the plasma region pierced by the primary electron beam and their difference in the peripheral part of the discharge are shown. It is concluded that the electron distribution function in the PIG type discharge is formed during one transit of the primary electron through the discharge gap. The mechanisms of electron energy spectrum formation in both the axis region and the peripheral region of the discharge are discussed.

Primary midgut, salivary gland, and ovary cultures from Boophilus microplus.

PubMed

Mosqueda, Juan; Cossío-Bayugar, Raquel; Rodríguez, Elba; Falcón, Alfonso; Ramos, Alberto; Figueroa, Julio V; Alvarez, Antonio

2008-12-01

Primary cell cultures from different tick organs are a valuable tool for host parasite research in the study of the protozoan Babesia sp., which infects different organs of the tick. In this work we describe the generation of midgut, salivary gland, and ovary primary cell cultures from dissections of Boophilus microplus. Midguts, salivary glands, and ovaries were dissected from B. microplus ticks on different days after bovine infestation; different enzymatic disaggregating protocols were tested in the presence of proteolytic enzymes, such as trypsin and collagenase type I and II, for tissue disaggregation and primary cell culture generation. The dissected tick organs obtained 18-20 days after bovine infestation showed a major cellular differentiation and were easier to identify by cellular morphology. The enzymatic disaggregation results showed that each tissue required a different proteolytic enzyme for optimal disaggregation; collagenase type I produced the most complete disaggregation for ovaries but not for midgut or salivary glands. Collagenase type II was effective for salivary glands but performed poorly on ovaries and midgets, and typsin was effective for midguts only. The midgut and ovary primary cell cultures were maintained for 4 weeks in optimal conditions after the cells were no longer viable. The salivary gland cell cultures were viable for 8 months.

Risk factors leading to mucoperiosteal flap necrosis after primary palatoplasty in patents with cleft palate.

PubMed

Rossell-Perry, Percy; Figallo-Hudtwalcker, Olga; Vargas-Chanduvi, Roberto; Calderon-Ayvar, Yvette; Romero-Narvaez, Carolina

2017-10-01

Few studies have been published reporting risk factors for flap necrosis after primary palatoplasty in patients with cleft palate. This complication is rare, and the event is a disaster for both the patient and the surgeon. This study was performed to explore the associations between different risk factors and the development of flap necrosis after primary palatoplasty in patients with cleft palate. This is a case-control study. A 20 years retrospective analysis (1994-2015) of patients with nonsyndromic cleft palate was identified from medical records and screening day registries). Demographical and risk factor data were collected using a patient´s report, including information about age at surgery, gender, cleft palate type, and degree of severity. Odds ratios and 95% confident intervals were derived from logistic regression analysis. All cases with diagnoses of flap necrosis after primary palatoplasty were included in the study (48 patients) and 156 controls were considered. In multivariate analysis, female sex, age (older than 15 years), cleft type (bilateral and incomplete), and severe cleft palate index were associated with significantly increased risk for flap necrosis. The findings suggest that female sex, older age, cleft type (bilateral and incomplete), and severe cleft palatal index may be associated with the development of flap necrosis after primary palatoplasty in patients with cleft palate.

Ensenanzas en un gimnasio: an investigation of modeling and verbal rehearsal on the motor performance of Hispanic limited English proficient children.

PubMed

Meaney, K S; Edwards, R

1996-03-01

This study investigated the effects of modeling and verbal rehearsal on the motor performance of English-speaking and limited English proficient (LEP) children. Children (N = 64) in 4th-grade classes were randomly assigned to conditions in a 2 x 2 x 2 x 2 (Gender x Primary Language x Model Type x Rehearsal) factorial design. Boys and girls whose primary language was English or Spanish were assigned to either a verbal model or no-model condition as well as to a verbal rehearsal or no-rehearsal condition of the motor skills required to be performed. Analysis of variance revealed a significant Model Type x Primary Language interaction as well as a significant Rehearsal x Primary Language interaction. Follow-up analyses revealed that English-speaking children provided with a verbal rehearsal strategy recalled significantly more skills than English-speaking children in the no-rehearsal condition; for LEP children, there were no differences due to rehearsal. Moreover, LEP children presented with a verbal model recalled significantly more skills than LEP children in the no-model condition; for English-speaking children, there were no differences attributed to model type. These results indicate that effective modeling conditions that are provided with verbal cues in English are related to children's primary language.

Primary intrathoracic liposarcoma: a clinicopathologic study and prognostic analysis of 23 cases

PubMed Central

2014-01-01

Background Primary intrathoracic liposarcoma is an extremely rare malignancy as well as a rare histologic subtype of intrathoracic sarcoma. Relatively few reports appear in the world literatures. We explored the clinicopathologic features and prognostic factors of this tumor in this study. Methods We retrospectively analyzed the clinicopathological data of 23 patients with primary intrathoracic liposarcoma who were treated in Shanghai chest Hospital affiliated to Jiao Tong University, from January 2003 to March 2013. These patients were classified into three groups according to the distinct tumor locations, including mediastinum, pleura and lung liposarcoma. Also, these patients could be divided into four types, including well-differentiated, myxoid, dedifferentiated and pleomorphic liposarcoma. The influences of age, sex, tumor size, tumor location, tumor histologic type and therapy on the prognosis of the patients were analyzed. Results There were no significant difference for survival among distinct liposarcoma locations. However, significant difference for survival among distinct liposarcoma types were observed. Poor disease-free survival (DFS) was observed in the myxoid, pleomorphic and dedifferentiated types as compared to well-differentiated type (P = 0.038). Inferior overall-survival (OS) was observed in dedifferentiated, pleomorphic and myxoid types relative to well-differentiated type (P = 0.027). The radical surgery was a favorable prognostic factor for OS, as demonstrated by the better OS of the radical surgery group as compared to that of the non-radical surgery group ( P = 0.029). Notably, there were no significant differences for DFS and OS in other clinical parameters including tumor size, gender and age. In addition, radiotherapy and/or chemotherapy could not improve the prognosis of the patients receiving non-radical surgery or suffering from relapse. Conclusions The histological type and the radical surgery are the factors that influence the behavior and prognosis of liposarcoma. In general, radiotherapy and chemotherapy are believed to be ineffective therapeutic modalities for survival. So it is essential to completely resect the primary intrathoracic liposarcoma as radical cure of the disease. PMID:24993036

The Primary Duct of Bothrops jararaca Glandular Apparatus Secretes Toxins

PubMed Central

Sakai, Fernanda; Portes-Junior, José Antonio; Godoy Viana, Luciana; Mendes Carneiro, Sylvia; Perales, Jonas; Yamanouye, Norma

2018-01-01

Despite numerous studies concerning morphology and venom production and secretion in the main venom gland (and some data on the accessory gland) of the venom glandular apparatus of Viperidae snakes, the primary duct has been overlooked. We characterized the primary duct of the Bothrops jararaca snake by morphological analysis, immunohistochemistry and proteomics. The duct has a pseudostratified epithelium with secretory columnar cells with vesicles of various electrondensities, as well as mitochondria-rich, dark, basal, and horizontal cells. Morphological analysis, at different periods after venom extraction, showed that the primary duct has a long cycle of synthesis and secretion, as do the main venom and accessory glands; however, the duct has a mixed mode venom storage, both in the lumen and in secretory vesicles. Mouse anti-B. jararaca venom serum strongly stained the primary duct’s epithelium. Subsequent proteomic analysis revealed the synthesis of venom toxins—mainly C-type lectin/C-type lectin-like proteins. We propose that the primary duct’s toxin synthesis products complement the final venom bolus. Finally, we hypothesize that the primary duct and the accessory gland (components of the venom glandular apparatus) are part of the evolutionary path from a salivary gland towards the main venom gland. PMID:29533989

Cell lines, Md108 and Md66, from the hemocytes of Malacosoma disstria (Lepidoptera) display aspects of plasma-free innate non-self activities.

PubMed

Lapointe, Jason F; Dunphy, Gary B; Giannoulis, Paschalis; Mandato, Craig A; Nardi, James B; Gharib, Osama H; Niven, Donald F

2011-11-01

The innate non-self response systems of the deciduous tree pest, the forest tent caterpillar, Malacosoma disstria has been documented by us in terms of in vitro and in vivo reactions towards the Gram-positive nonpathogenic bacterium, Bacillus subtilis and Gram-negative pathogenic microbe, Xenorhabdus nematophila and their respective surface antigens, lipopoteichoic acids (LTA) and lipopolysaccharides (LPS). These studies, often conducted in whole and diluted hemolymph, preclude examination of plasma-free cellular (hemocyte) responses. Plasma-free hemocytes as primary cultures are difficult to obtain. The floating cell line Md66 and attached cell line Md108 from M. disstria hemocytes were examined as a model for plasma-free M. disstria hemocyte non-self responses. Herein, it was established that although both lines differed from each other and from the primary hemocyte cultures of M. disstria in growth parameters, cell composition and sizes both cell lines displayed granular cell-like (GL) cells and plasmatocyte-like (PL) cells according to morphological criteria and to some extent antigenic similarities based on labeling with anti-Chrysodeixis includens hemocyte monoclonal antibodies. Hemocyte-specific neuroglian-like protein was detected on cells of both cell lines and in the primary hemocyte cultures albeit with staining patterns differing according to culture and cell types, confluency levels and cell-cell adhesion. Both cell lines bound B. subtilis and X. nematophila, the reaction extent varying with the cell line and its cell types. LPS damaged both cell types in the two cell lines whereas LTA enhanced the adhesion of Md66 GL cells to flask surfaces followed by PL cell adhesion. PL cells of both lines, like the primary cultures, phagocytosed FITC-labeled B. subtilis; only Md108 GL cells phagocytosed B. subtilis. In either case phagocytosis was always less in frequency and intensity than the primary cultures. Proteins released from the cell lines differed in pattern and magnitude but contained bacterial binding proteins that enhanced differential bacterial adhesion to both cell types in both cell lines: the GL cells both cultures, and those of granular cells in primary cultures, were more involved than the primary plasmatocytes and PL cells. Only Md66 cells possessed lysozyme and both cell types of both lines contained phenoloxidase. Neither enzyme type was released during early phase reaction with the bacteria. LPS inhibited phenoloxidase activity. The similarities and differences between the lines and primary cultures make Md66 and Md108 useful for the systematic examination of plasma-free cellular non-self reactions. Copyright © 2011 Elsevier Inc. All rights reserved.

A Phenomenographic Study of Greek Primary School Students' Representations Concerning Technology in Daily Life

ERIC Educational Resources Information Center

Solomonidou, Christina; Tassios, Athanassios

2007-01-01

The present research investigated and studied students' representations about daily life technologies, in a prospect of studying technology in Greek primary education. In the research participated 60 Greek primary school students aged 9 to 12 years old. Research data were collected through semi-structured, personal, clinical-type interviews. Each…

Primary renal diffuse large B-cell lymphoma with central nervous system involvement: a rare case report and literature review.

PubMed

Wang, Ying; Guo, Shuangshuang

2015-01-01

Primary renal lymphoma is a rare entity. Of these, diffuse large B-cell lymphoma is the most common pathological type and, R-CHOP regimen was the preferred chemotherapy for it. Here we present an adult case of primary renal diffuse large B-cell lymphoma.

Majewski osteodysplastic primordial dwarfism type II: clinical findings and dental management of a child patient

PubMed Central

Terlemez, Arslan; Altunsoy, Mustafa; Celebi, Hakki

2015-01-01

Majewski osteodysplastic primordial dwarfism type II (MOPD II) is an unusual autosomal recessive inherited form of primordial dwarfism, which is characterized by a small head diameter at birth, but which also progresses to severe microcephaly, progressive bony dysplasia, and characteristic facies and personality. This report presents a case of a five-year-old girl with MOPD II syndrome. The patient was referred to our clinic with the complaint of severe tooth pain at the left mandibular primary molar teeth. Clinical examination revealed that most of the primary teeth had been decayed and all primary teeth were hypoplastic. Patient’s history revealed delayed development in the primary dentition and radiographic examination showed rootless primary molar teeth and short-rooted incisors. The treatment was not possible due to the lack of root of the left mandibular primary molars; so the teeth were extracted. Thorough and timely dental evaluation is crucial for the prevention of dental problems and the maintenance of oral health in patients with MOPD II syndrome is of utmost importance. PMID:28955524

Majewski osteodysplastic primordial dwarfism type II: clinical findings and dental management of a child patient.

PubMed

Terlemez, Arslan; Altunsoy, Mustafa; Celebi, Hakki

2015-01-01

Majewski osteodysplastic primordial dwarfism type II (MOPD II) is an unusual autosomal recessive inherited form of primordial dwarfism, which is characterized by a small head diameter at birth, but which also progresses to severe microcephaly, progressive bony dysplasia, and characteristic facies and personality. This report presents a case of a five-year-old girl with MOPD II syndrome. The patient was referred to our clinic with the complaint of severe tooth pain at the left mandibular primary molar teeth. Clinical examination revealed that most of the primary teeth had been decayed and all primary teeth were hypoplastic. Patient's history revealed delayed development in the primary dentition and radiographic examination showed rootless primary molar teeth and short-rooted incisors. The treatment was not possible due to the lack of root of the left mandibular primary molars; so the teeth were extracted. Thorough and timely dental evaluation is crucial for the prevention of dental problems and the maintenance of oral health in patients with MOPD II syndrome is of utmost importance.

Identifying Southern Forest Types on Aerial Photographs

Treesearch

Gene Avery

1960-01-01

This booklet has been prepared to assist photo interpreters in recognizing broad forest types on aerial photographs of the South, and to illustrate primary differences between panchromatic and infrared photography from the standpoint of timber type-mapping.

Small bowel volvulus with jejunal diverticulum: Primary or secondary?

PubMed

Shen, Xiao-Fei; Guan, Wen-Xian; Cao, Ke; Wang, Hao; Du, Jun-Feng

2015-09-28

Small bowel volvulus, which is torsion of the small bowel and its mesentery, is a medical emergency, and is categorized as primary or secondary type. Primary type often occurs without any apparent intrinsic anatomical anomalies, while the secondary type is common clinically and could be caused by numerous factors including postoperative adhesions, intestinal diverticulum, and/or tumors. Here, we report a rare case of a 60-year-old man diagnosed with small bowel volvulus using multidetector computed tomography (MDCT) angiography. Further discovery by laparotomy showed one jejunal diverticulum, longer corresponding mesentery with a narrower insertion, and a lack of mesenteric fat. This case report includes several etiological factors of small bowel volvulus, and we discuss the possible cause of small bowel volvulus in this patient. We also highlight the importance of MDCT angiography in the diagnosis of volvulus and share our experience in treating this disease.

Small bowel volvulus with jejunal diverticulum: Primary or secondary?

PubMed Central

Shen, Xiao-Fei; Guan, Wen-Xian; Cao, Ke; Wang, Hao; Du, Jun-Feng

2015-01-01

Small bowel volvulus, which is torsion of the small bowel and its mesentery, is a medical emergency, and is categorized as primary or secondary type. Primary type often occurs without any apparent intrinsic anatomical anomalies, while the secondary type is common clinically and could be caused by numerous factors including postoperative adhesions, intestinal diverticulum, and/or tumors. Here, we report a rare case of a 60-year-old man diagnosed with small bowel volvulus using multidetector computed tomography (MDCT) angiography. Further discovery by laparotomy showed one jejunal diverticulum, longer corresponding mesentery with a narrower insertion, and a lack of mesenteric fat. This case report includes several etiological factors of small bowel volvulus, and we discuss the possible cause of small bowel volvulus in this patient. We also highlight the importance of MDCT angiography in the diagnosis of volvulus and share our experience in treating this disease. PMID:26420976

The primary culture of mirror carp snout and caudal fin tissues and the isolation of Koi herpesvirus.

PubMed

Zhou, Jingxiang; Wang, Hao; Zhu, Xia; Li, Xingwei; Lv, Wenliang; Zhang, Dongming

2013-10-01

The explosive Koi herpesvirus (KHV) epidemic has caused the deaths of a large number of carp and carp variants and has produced serious economic losses. The mirror carp (Cyprinus carpio var. specularis) exhibits strong environmental adaptability and its primary cells can be used to isolate KHV. This study utilized the tissue explant method to systematically investigate primary cell culture conditions for mirror carp snout and caudal fin tissues. We demonstrated that cells from these two tissue types had strong adaptability, and when cultured in Medium 199 (M199) containing 20% serum at 26 to 30°C, the cells from the snout and caudal fin tissues exhibited the fastest egress and proliferation. Inoculation of these two cell types with KHV-infected fish kidney tissues produced typical cytopathic effects; additionally, identification by electron microscopy, and PCR indicated that KHV could be isolated from both cell types.

The neotype barcode of the cotton aphid (Hemiptera: Aphididae: Aphis gossypii Glover, 1877) and a proposal for type barcodes

USDA-ARS?s Scientific Manuscript database

A type barcode is a DNA barcode unequivocally tied to an authoritatively identified specimen, preferably the primary type specimen. Type barcodes are analogous, albeit subordinate, to type specimens, providing a stable reference to which other barcodes can be compared. We here designate and describe...

The Difficulties Experienced by Teachers in the Process of Primary Reading and Writing Instruction and Their Solution Offers for Eliminating These Difficulties

ERIC Educational Resources Information Center

Gündogmus, Hatice Degirmenci

2018-01-01

The purpose of the current research is to identify the difficulties that primary school teachers experience in the primary reading and writing instruction, and to find out their solution offers for eliminating these difficulties. The study group of the research is composed of 51 primary school teachers selected by criterion sampling as a type of…

Are Binary Separations related to their System Mass?

NASA Astrophysics Data System (ADS)

Sterzik, M. F.; Durisen, R. H.

2004-08-01

We compile most recent multiplicity fractions and binary separation distributions for different primary masses, including very low-mass and brown dwarf primaries, and compare them with dynamical decay models of small-N clusters. The model predictions are based on detailed numerical calculations of the internal cluster dynamics, as well as on Monte-Carlo methods. Both observations and models reflect the same trends: (1) The multiplicity fraction is an increasing function of the primary mass. (2) The mean binary separations are increasing with the system mass in the sense that very low-mass binaries have average separations around ≈ 4AU, while the binary separation distribution for solar-type primaries peaks at ≈ 40AU. M-type binary systems apparently preferentially populate intermediate separations. Similar specific energy at the time of cluster formation for all cluster masses can possibly explain this trend.

Vaginal type-II mucosa is an inductive site for primary CD8+ T-cell mucosal immunity

PubMed Central

Wang, Yichuan; Sui, Yongjun; Kato, Shingo; Hogg, Alison E.; Steel, Jason C.; Morris, John C.; Berzofsky, Jay A.

2014-01-01

The structured lymphoid tissues are considered the only inductive sites where primary T cell immune responses occur. The naïve T cells in structured lymphoid tissues, once being primed by antigen -bearing dendritic cells, differentiate into memory T cells and traffic back to the mucosal sites through the bloodstream. Contrary to this belief, here we show that the vaginal type-II mucosa itself, despite lack of structured lymphoid tissues, can act as an inductive site during primary CD8+ T cell immune responses. We provide evidence that the vaginal mucosa supports both the local immune priming of naïve CD8+ T cells and the local expansion of antigen-specific CD8+ T cells, thereby demonstrating a different paradigm for primary mucosal T cell immune induction. PMID:25600442

Epidemiological features and control of an outbreak of scarlet fever in a Perth primary school.

PubMed

Feeney, Kynan T; Dowse, Gary K; Keil, Anthony D; Mackaay, Christine; McLellan, Duncan

2005-01-01

Scarlet fever was associated with feared outbreaks and mortality in the 19th Century. It occurs sporadically in modern society and infection is readily treated with antibiotics. We report on a scarlet fever outbreak in children attending a primary school in Perth, Western Australia, in late 2003. A total of 13 cases were identified over a five week period. Six of the cases were pre-primary children (ages 4 to 5) from the same class of 26 children (attack rate 23.1%). Three of the remaining seven cases were older siblings of pre-primary cases who developed scarlet fever after their younger siblings. Screening of the children and teachers from the two pre-primary classes at the school yielded 12 positive pharyngeal swabs for group A Streptococcus. Emm-typing of the screening isolates indicated that a common strain was circulating within the outbreak pre-primary class, with four of six isolates identified as emm-type 3. The overall group A Streptococcus carriage rate in screened students in this class was 31.6 per cent and the carriage rate for emm-type 3 was 21.1 per cent. Carriers were treated with oral penicillin V to eradicate carriage and control the outbreak. No further cases of scarlet fever were reported after the treatment of pharyngeal carriers. Outbreaks of scarlet fever still occur in young children and identification and treatment of carriers may still be valuable.

A novel antilithiatic protein from Tribulus terrestris having cytoprotective potency.

PubMed

Aggarwal, Anshu; Tandon, Simran; Singla, Surinder Kumar; Tandon, Chanderdeep

2012-08-01

Adhesion of calcium oxalate (CaOx) crystals to kidney cells is a key event in kidney stones associated with marked hyperoxaluria. As the propensity of stone recurrence and persistent side effects are not altered by surgical techniques available, phytotherapeutic agents could be useful as an adjuvant therapy. The present study is aimed at examining the antilithiatic potency of the protein biomolecules of Tribulus terrestris, a plant which is a common constituent of herbal marketed preparations to treat urolithiasis. Various biochemical methods with mass spectrometry were used to purify and characterize the purified protein. The protective potency of the protein was tested on the oxalate induced injury on renal epithelial cell lines (NRK 52E). An antilithiatic protein having molecular weight of ~ 60kDa was purified. This purified protein showed similarities with Carotenoid cleavage dioxygenase 7 (CCD7) of Arabidopsis thaliana after matching peptide mass fingerprints in MASCOT search engine. An EF hand domain was identified in CCD7 by SCAN PROSITE. Presence of an EF hand domain, a characteristic feature of calcium binding proteins and a role in the synthesis of retinol which is transported by retinol binding protein, a protein found in kidney stone matrix; of CCD7 support the role of TTP as an antilithiatic protein. The protective potency of TTP on NRK 52E was quite comparable to the aqueous extract of cystone. Our findings suggest that this purified protein biomolecule from Tribulus terrestris could open new vista in medical management of urolithiasis.

Alteration in Oxidative/nitrosative imbalance, histochemical expression of osteopontin and antiurolithiatic efficacy of Xanthium strumarium (L.) in ethylene glycol induced urolithiasis.

PubMed

Panigrahi, Padma Nibash; Dey, Sahadeb; Sahoo, Monalisa; Choudhary, Shyam Sundar; Mahajan, Sumit

2016-12-01

Xanthium strumarium has traditionally been used in the treatment of urolitiasis especially by the rural people in India, but its antiurolithiatic efficacy was not explored scientifically till now. Therefore, the present study was designed to validate the ethnic practice scientifically, and explore the possible antiurolithiatic effect to rationalize its medicinal use. Urolitiasis was induced in hyperoxaluric rat model by giving 0.75% ethylene glycol (EG) for 28days along with 1% ammonium chloride (AC) for first 14days. Antiurolithiatic effect of aqueous-ethanol extract of Xanthium strumarium bur (xanthium) was evaluated based on urine and serum biochemistry, oxidative/nitrosative stress indices, histopathology, kidney calcium and calcium oxalate content and immunohistochemical expression of matrix glycoprotein, osteopontin (OPN). Administration of EG and AC resulted in hyperoxaluria, crystalluria, hypocalciuria, polyurea, raised serum urea, creatinine, erythrocytic lipid peroxidise and nitric oxide, kidney calcium content as well as crystal deposition in kidney section in lithiatic group rats. However, xanthium treatment significantly restored the impairment in above kidney function test as that of standard treatment, cystone. The up-regulation of OPN was also significantly decreased after xanthium treatment. The present findings demonstrate the curative efficacy of xanthium in ethylene glycol induced urolithiasis, possibly mediated through inhibition of various pathways involved in renal calcium oxalate formation, antioxidant property and down regulation of matrix glycoprotein, OPN. Therefore, future studies may be established to evaluate its efficacy and safety for clinical use. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Oxalate nephropathy associated with chronic pancreatitis.

PubMed

Cartery, Claire; Faguer, Stanislas; Karras, Alexandre; Cointault, Olivier; Buscail, Louis; Modesto, Anne; Ribes, David; Rostaing, Lionel; Chauveau, Dominique; Giraud, Patrick

2011-08-01

Enteric overabsorption of oxalate may lead to hyperoxaluria and subsequent acute oxalate nephritis (AON). AON related to chronic pancreatitis is a rare and poorly described condition precluding early recognition and treatment. We collected the clinical characteristics, treatment, and renal outcome of 12 patients with chronic pancreatitis-associated AON followed in four French renal units. Before AON, mild to moderate chronic kidney disease was present in all patients, diabetes mellitus in eight (insulin [n = 6]; oral antidiabetic drugs [n = 2]), and known chronic pancreatitis in only eight. At presentation, pancreas imaging showed gland atrophy/heterogeneity, Wirsung duct dilation, calcification, or pseudocyst. Renal findings consisted of rapidly progressive renal failure with tubulointerstitial profile. Acute modification of glomerular filtration preceded the AON (i.e., diarrhea and diuretics). Increase in urinary oxalate excretion was found in all tested patients and hypocalcemia in nine (<1.5 mmol/L in four patients). Renal biopsy showed diffuse crystal deposits, highly suggestive of oxalate crystals, with tubular necrosis and interstitial inflammatory cell infiltrates. Treatment consisted of pancreatic enzyme supplementation, oral calcium intake, and an oxalate-free diet in all patients and renal replacement therapy in five patients. After a median follow-up of 7 months, three of 12 patients reached end-stage renal disease. AON is an under-recognized severe crystal-induced renal disease with features of tubulointerstitial nephritis that may occur in patients with a long history of chronic pancreatitis or reveal the pancreatic disease. Extrinsic triggering factors should be prevented.

Similarity of urinary risk factors among stone-forming patients in five regions of the United States

NASA Technical Reports Server (NTRS)

Harvey, J. A.; Hill, K. D.; Pak, C. Y.

1990-01-01

Study Objective: To compare urinary biochemical risk factors among stone-forming patients in the Southeast (SE) or "stone belt" versus four other regions of the United States. Design: Prospective biochemical survey for regional comparisons. Setting: Referral-based nephrolithiasis clinics, urologists, nephrologists, and family practitioners. Patients: Consecutive sample of 3473 stone-forming patients who submitted 24-hour urine collections for biochemical analyses of stone-forming risk factors. Interventions: None. Subjects taking medication known to interfere with stone-forming risk factors were deleted from the final data compilation. Measurements and Main Results: Overall, the mean values for each urinary parameter spanned a narrow range without significant difference between the five regions. Among "metabolic" factors, 40% in the SE had hypercalciuria (> 6.25 mmol/d), compared to 35%-43% in other regions, and hyperuricosuria (> 4.2 mmol/d) was found in 16% in the SE versus 17%-19% elsewhere. Among "environmental" factors, low urine volume ( < 2 L/d) was found in 77% patients in the SE compared to 69%-78% elsewhere, and high sodium was encountered in 27% in the SE versus 24%-29% elsewhere. No differences were noted in occurrence of other abnormal risk factors: hyperoxaluria, hypocitraturia, low pH, high sulfate, high phosphorus, or low magnesium. Conclusions: Despite expected regional differences in nutritional and environmental influences, the results of this study showed a striking similarity in urinary biochemical risk factor profiles of stone-formers in all five regions of the United States.

Antiurolithic effect of Bergenia ligulata rhizome: an explanation of the underlying mechanisms.

PubMed

Bashir, Samra; Gilani, Anwar H

2009-02-25

Bergenia ligulata is widely used plant in South Asia, mainly India and Pakistan, as a traditional medicine for treatment of urolithiasis. To rationalize the Bergenia ligulata use in kidney stones and to explain the underlying mechanisms. The crude aqueous-methanolic extract of Bergenia ligulata rhizome (BLR) was studied using in vitro and in vivo methods. BLR inhibited calcium oxalate (CaC(2)O(4)) crystal aggregation as well as crystal formation in the metastable solutions and exhibited antioxidant effect against 1,1-diphenyl-2-picrylhydrazyl free radical and lipid peroxidation in the in vitro. BLR caused diuresis in rats accompanied by a saluretic effect. In an animal model of urolithiasis, developed in male Wistar rats by adding 0.75% ethylene glycol (EG) in drinking water, BLR (5-10 mg/kg) prevented CaC(2)O(4) crystal deposition in the renal tubules. The lithogenic treatment caused polyuria, weight loss, impairment of renal function and oxidative stress, manifested as increased malondialdehyde and protein carbonyl contents, depleted reduced glutathione and decreased antioxidant enzyme activities of the kidneys, which were prevented by BLR. Unlike the untreated animals, EG intake did not cause excessive hyperoxaluria and hypocalciuria in BLR treated groups and there was a significant increase in the urinary Mg(2+), instead of a slight decrease. These data indicate the antiurolithic activity in Bergenia ligulata mediated possibly through CaC(2)O(4) crystal inhibition, diuretic, hypermagneseuric and antioxidant effects and this study rationalizes its medicinal use in urolithiasis.

Health-Related Quality of Life in Primary Care: Which Aspects Matter in Multimorbid Patients with Type 2 Diabetes Mellitus in a Community Setting?

PubMed

Kamradt, Martina; Krisam, Johannes; Kiel, Marion; Qreini, Markus; Besier, Werner; Szecsenyi, Joachim; Ose, Dominik

2017-01-01

Knowledge about predictors of health-related quality of life for multimorbid patients with type 2 diabetes mellitus in primary care could help to improve quality and patient-centeredness of care in this specific group of patients. Thus, the aim of this study was to investigate the impact of several patient characteristics on health-related quality of life of multimorbid patients with type 2 diabetes mellitus in a community setting. A cross-sectional study with 32 primary care practice teams in Mannheim, Germany, and randomly selected multimorbid patients with type 2 diabetes mellitus (N = 495) was conducted. In order to analyze associations of various patient characteristics with health-related quality of life (EQ-5D index) a multilevel analysis was applied. After excluding patients with missing data, the cohort consisted of 404 eligible patients. The final multilevel model highlighted six out of 14 explanatory patient variables which were significantly associated with health-related quality of life: female gender (r = -0.0494; p = .0261), school education of nine years or less (r = -0.0609; p = .0006), (physical) mobility restrictions (r = -0.1074; p = .0003), presence of chronic pain (r = -0.0916; p = .0004), diabetes-related distress (r = -0.0133; p < .0001), and BMI (r = -0.0047; p = .0045). The findings of this study suggest that increased diabetes-related distress, chronic pain, restrictions in (physical) mobility, female gender, as well as lower education and, increased BMI have a noteworthy impact on health-related quality of life in multimorbid patients with type 2 diabetes mellitus seen in primary care practices in a community setting. The highlighted aspects should gain much more attention when treating multimorbid patients with type 2 diabetes mellitus.

Cell wall polysaccharides from fern leaves: evidence for a mannan-rich Type III cell wall in Adiantum raddianum.

PubMed

Silva, Giovanna B; Ionashiro, Mari; Carrara, Thalita B; Crivellari, Augusto C; Tiné, Marco A S; Prado, Jefferson; Carpita, Nicholas C; Buckeridge, Marcos S

2011-12-01

Primary cell walls from plants are composites of cellulose tethered by cross-linking glycans and embedded in a matrix of pectins. Cell wall composition varies between plant species, reflecting in some instances the evolutionary distance between them. In this work the monosaccharide compositions of isolated primary cell walls of nine fern species and one lycophyte were characterized and compared with those from Equisetum and an angiosperm dicot. The relatively high abundance of mannose in these plants suggests that mannans may constitute the major cross-linking glycan in the primary walls of pteridophytes and lycophytes. Pectin-related polysaccharides contained mostly rhamnose and uronic acids, indicating the presence of rhamnogalacturonan I highly substituted with galactose and arabinose. Structural and fine-structural analyses of the hemicellulose fraction of leaves of Adiantum raddianum confirmed this hypothesis. Linkage analysis showed that the mannan contains mostly 4-Man with very little 4,6-Man, indicating a low percentage of branching with galactose. Treatment of the mannan-rich fractions with endo-β-mannanase produced characteristic mannan oligosaccharides. Minor amounts of xyloglucan and xylans were also detected. These data and those of others suggest that all vascular plants contain xyloglucans, arabinoxylans, and (gluco)mannans, but in different proportions that define cell wall types. Whereas xyloglucan and pectin-rich walls define Type I walls of dicots and many monocots, arabinoxylans and lower proportion of pectin define the Type II walls of commelinoid monocots. The mannan-rich primary walls with low pectins of many ferns and a lycopod indicate a fundamentally different wall type among land plants, the Type III wall. Copyright © 2011 Elsevier Ltd. All rights reserved.

Closed-form model for the analysis of W-type shaped charges

NASA Astrophysics Data System (ADS)

Mahdian, A.; Ghayour, M.; Liaghat, G. H.

2013-09-01

This paper presents a closed-form model for the analysis of symmetric planar W-type shaped charges (WSCs) with two V-sections, which produce two primary cores and two primary jets. If these two V-sections have proper asymmetry, these primary cores will force two primary jets into a secondary core formed on the axis of symmetry of a planar symmetric WSC. For the analysis of such a planar WSC, a complete generalized model for an asymmetric planar V-shaped charge (VSC) with any desired order of asymmetry is mandatory. In this paper, the model is applied to describe the secondary jet formation in the WSC. By presenting a closed-form analysis of the WSC, the secondary jet specifications can be easily evaluated and, thus, can be compared with respect to the jet quantities in symmetric or asymmetric VSCs. Finally, for the primary and secondary jets, the coherency conditions are investigated, and the critical parameters responsible for these conditions are determined.

Basement domain map of the conterminous United States and Alaska

USGS Publications Warehouse

Lund, Karen; Box, Stephen E.; Holm-Denoma, Christopher S.; San Juan, Carma A.; Blakely, Richard J.; Saltus, Richard W.; Anderson, Eric D.; DeWitt, Ed

2015-01-01

The tectonic settings for crustal types represented in the basement domains are subdivided into constituent geologic environments and the types of primary metals endowments and deposits in them are documented. The compositions, architecture, and original metals endowments are potentially important to assessments of primary mineral deposits and to the residence and recycling of metals in the crust of the United States portion of the North American continent. The databases can be configured to demonstrate the construction of the United States through time, to identify specific types of crust, or to identify domains potentially containing metal endowments of specific genetic types or endowed with specific metals. The databases can also be configured to illustrate other purposes chosen by users.

Survey on treatments for primary headaches in 13 specialized juvenile Headache Centers: The first multicenter Italian study.

PubMed

Toldo, Irene; Rattin, Martina; Perissinotto, Egle; De Carlo, Debora; Bolzonella, Barbara; Nosadini, Margherita; Rossi, Livia Nicoletta; Vecchio, Angelo; Simonati, Alessandro; Carotenuto, Marco; Scalas, Cinzia; Sciruicchio, Vittorio; Raieli, Vincenzo; Mazzotta, Giovanni; Tozzi, Elisabetta; Valeriani, Massimiliano; Cianchetti, Carlo; Balottin, Umberto; Guidetti, Vincenzo; Sartori, Stefano; Battistella, Pier Antonio

2017-05-01

The purpose of this retrospective multicenter study was to evaluate the use and the self-perceived efficacy and tolerability of pharmacological and non-pharmacological treatments in children and adolescents with primary headaches. Study of a cohort of children and adolescents diagnosed with primary headache, consecutively referred to 13 juvenile Italian Headache Centers. An ad hoc questionnaire was used for clinical data collection. Among 706 patients with primary headaches included in the study, 637 cases with a single type of headache (migraine 76% - with and without aura in 10% and 67% respectively; tension-type headache 24%) were selected (mean age at clinical interview: 12 years). Acetaminophen and non-steroidal anti-inflammatory drugs (in particular ibuprofen) were commonly used to treat attacks, by 76% and 46% of cases respectively. Triptans were used overall by 6% of migraineurs and by 13% of adolescents with migraine, with better efficacy than acetaminophen and non-steroidal anti-inflammatory drugs. Preventive drugs were used by 19% of migraineurs and by 3% of subjects with tension-type headache. In migraineurs, flunarizine was the most frequently used drug (18%), followed by antiepileptic drugs (7%) and pizotifen (6%), while cyproheptadine, propanolol and amitriptyline were rarely used. Pizotifen showed the best perceived efficacy and tolerability. Melatonin and nutraceuticals were used by 10% and 32% of subjects, respectively, both for migraine and tension-type headache, with good results in terms of perceived efficacy and tolerability. Non-pharmacological preventive treatments (i.e. relaxation techniques, biofeedback, cognitive-behavioral therapy, acupuncture) were used only by 10% of cases (migraine 9%, tension-type headache 15%). Non-steroidal anti-inflammatory drugs, especially ibuprofen, should be preferred to acetaminophen for acute attacks of migraine or tension-type headache, because they were usually more effective and well tolerated. Triptans could be used more frequently as first or almost second choice for treating migraine attack in adolescents. Non-pharmacological preventive treatments are recommended by some pediatric guidelines as first-line interventions for primary headaches and their use should be implemented in clinical practice. Prospective multicenter studies based on larger series are warranted to better understand the best treatment strategies for young people with primary headaches. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Primary care physician beliefs about insulin initiation in patients with type 2 diabetes

PubMed Central

Hayes, R P; Fitzgerald, J T; Jacober, S J

2008-01-01

Background Insulin is the most effective drug available to achieve glycaemic goals in patients with type 2 diabetes. Yet, there is reluctance among physicians, specifically primary care physicians (PCPs) in the USA, to initiate insulin therapy in these patients. Aims To describe PCPs’ attitudes about the initiation of insulin in patients with type 2 diabetes and identify areas in which there is a clear lack of consensus. Methods Primary care physicians practicing in the USA, seeing 10 or more patients with type 2 diabetes per week, and having > 3 years of clinical practice were surveyed via an internet site. The survey was developed through literature review, qualitative study and expert panel. Results Primary care physicians (n = 505, mean age = 46 years, 81% male, 62% with > 10 years practice; 52% internal medicine) showed greatest consensus on attitudes regarding risk/benefits of insulin therapy, positive experiences of patients on insulin and patient fears or concerns about initiating insulin. Clear lack of consensus was seen in attitudes about the metabolic effects of insulin, need for insulin therapy, adequacy of self-monitoring blood glucose, time needed for training and potential for hypoglycaemia in elderly patients. Conclusions The beliefs of some PCPs are inconsistent with their diabetes treatment goals (HbA1c ≤ 7%). Continuing medical education programmes that focus on increasing primary care physician knowledge about the progression of diabetes, the physiological effects of insulin, and tools for successfully initiating insulin in patients with type 2 diabetes are needed. Disclosures Drs Hayes and Jacober are employees and stockholders of Eli Lilly and Company. Dr Fitzgerald is a consultant to Eli Lilly and Company. What's known Insulin is the most effective drug available to achieve glycaemic goals in patients with type 2 diabetes, yet there is reluctance among many physicians to initiate insulin therapy in these patients. Diabetes specialists tend to be more aggressive than primary care physicians (PCPs) with insulin initiation in patients with type 2 diabetes, and US physicians are more disposed to delay insulin than physicians in other countries. What's new This article confirms that US PCPs lack consensus on some beliefs about insulin initiation. Consensus was seen regarding insulin risk/benefits, positive patient experiences of insulin and patient fears about initiating insulin. No consensus was seen regarding insulin's metabolic effects, need for insulin, adequacy of self-monitoring blood glucose, time needed for training and potential for hypoglycaemia in elderly patients. Some PCPs have beliefs inconsistent with their diabetes treatment goals (HbA1c ≤ 7%). PMID:18393965

LH response to GnRH blood test

MedlinePlus

... to tell the difference between primary and secondary hypogonadism . Hypogonadism is a condition in which the sex glands ... are the ovaries. Depending on the type of hypogonadism: Primary hypogonadism starts in the testicle or ovary ...

Effect of genetic testing for risk of type 2 diabetes mellitus on health behaviors and outcomes: study rationale, development and design.

PubMed

Cho, Alex H; Killeya-Jones, Ley A; O'Daniel, Julianne M; Kawamoto, Kensaku; Gallagher, Patrick; Haga, Susanne; Lucas, Joseph E; Trujillo, Gloria M; Joy, Scott V; Ginsburg, Geoffrey S

2012-01-18

Type 2 diabetes is a prevalent chronic condition globally that results in extensive morbidity, decreased quality of life, and increased health services utilization. Lifestyle changes can prevent the development of diabetes, but require patient engagement. Genetic risk testing might represent a new tool to increase patients' motivation for lifestyle changes. Here we describe the rationale, development, and design of a randomized controlled trial (RCT) assessing the clinical and personal utility of incorporating type 2 diabetes genetic risk testing into comprehensive diabetes risk assessments performed in a primary care setting. Patients are recruited in the laboratory waiting areas of two primary care clinics and enrolled into one of three study arms. Those interested in genetic risk testing are randomized to receive either a standard risk assessment (SRA) for type 2 diabetes incorporating conventional risk factors plus upfront disclosure of the results of genetic risk testing ("SRA+G" arm), or the SRA alone ("SRA" arm). Participants not interested in genetic risk testing will not receive the test, but will receive SRA (forming a third, "no-test" arm). Risk counseling is provided by clinic staff (not study staff external to the clinic). Fasting plasma glucose, insulin levels, body mass index (BMI), and waist circumference are measured at baseline and 12 months, as are patients' self-reported behavioral and emotional responses to diabetes risk information. Primary outcomes are changes in insulin resistance and BMI after 12 months; secondary outcomes include changes in diet patterns, physical activity, waist circumference, and perceived risk of developing diabetes. The utility, feasibility, and efficacy of providing patients with genetic risk information for common chronic diseases in primary care remain unknown. The study described here will help to establish whether providing type 2 diabetes genetic risk information in a primary care setting can help improve patients' clinical outcomes, risk perceptions, and/or their engagement in healthy behavior change. In addition, study design features such as the use of existing clinic personnel for risk counseling could inform the future development and implementation of care models for the use of individual genetic risk information in primary care. ClinicalTrials.gov: NCT00849563.

Apple-peel intestinal atresia: enteroplasty for intestinal lengthening and primary anastomosis.

PubMed

Onofre, Luciano Silveira; Maranhão, Renato Frota de Albuquerque; Martins, Elaine Cristina Soares; Fachin, Camila Girardi; Martins, Jose Luiz

2013-06-01

Apple-peel atresia (or Type-IIIb intestinal atresia) is an unusual type of jejunoileal atresia. They present with jejunal atresia near the ligament of Treitz and a foreshortened small bowel. Many surgical options have been used, but the optimal method of repair remains unclear. We present a case of a newborn with apple-peel intestinal atresia managed by enteroplasty for intestinal lengthening and primary anastomosis. Copyright © 2013 Elsevier Inc. All rights reserved.

Prognostic value of fluorine-18 fludeoxyglucose positron emission tomography parameters differs according to primary tumour location in small-cell lung cancer.

PubMed

Nobashi, Tomomi; Koyasu, Sho; Nakamoto, Yuji; Kubo, Takeshi; Ishimori, Takayoshi; Kim, Young H; Yoshizawa, Akihiko; Togashi, Kaori

2016-01-01

To investigate the prognostic value of fluorine-18 fludeoxyglucose (FDG) positron emission tomography (PET) parameters for small-cell lung cancer (SCLC), according to the primary tumour location, adjusted by conventional prognostic factors. From 2008 to 2013, we enrolled consecutive patients with histologically proven SCLC, who had undergone FDG-PET/CT prior to initial therapy. The primary tumour location was categorized into central or peripheral types. PET parameters and clinical variables were evaluated using univariate and multivariate analysis. A total of 69 patients were enrolled in this study; 28 of these patients were categorized as having the central type and 41 patients as having the peripheral type. In univariate analysis, stage, serum neuron-specific enolase, whole-body metabolic tumour volume (WB-MTV) and whole-body total lesion glycolysis (WB-TLG) were found to be significant in both types of patients. In multivariate analysis, the independent prognostic factor was found to be stage in the central type, but WB-MTV and WB-TLG in the peripheral type. Kaplan-Meier analysis demonstrated that patients with peripheral type with limited disease and low WB-MTV or WB-TLG showed significantly better overall survival than all of the other groups (p < 0.0083). The FDG-PET volumetric parameters were demonstrated to be significant and independent prognostic factors in patients with peripheral type of SCLC, while stage was the only independent prognostic factor in patients with central type of SCLC. FDG-PET is a non-invasive method that could potentially be used to estimate the prognosis of patients, especially those with peripheral-type SCLC.

Store turnover as a predictor of food and beverage provider turnover and associated dietary intake estimates in very remote Indigenous communities.

PubMed

Wycherley, Thomas; Ferguson, Megan; O'Dea, Kerin; McMahon, Emma; Liberato, Selma; Brimblecombe, Julie

2016-12-01

Determine how very-remote Indigenous community (RIC) food and beverage (F&B) turnover quantities and associated dietary intake estimates derived from only stores, compare with values derived from all community F&B providers. F&B turnover quantity and associated dietary intake estimates (energy, micro/macronutrients and major contributing food types) were derived from 12-months transaction data of all F&B providers in three RICs (NT, Australia). F&B turnover quantities and dietary intake estimates from only stores (plus only the primary store in multiple-store communities) were expressed as a proportion of complete F&B provider turnover values. Food types and macronutrient distribution (%E) estimates were quantitatively compared. Combined stores F&B turnover accounted for the majority of F&B quantity (98.1%) and absolute dietary intake estimates (energy [97.8%], macronutrients [≥96.7%] and micronutrients [≥83.8%]). Macronutrient distribution estimates from combined stores and only the primary store closely aligned complete provider estimates (≤0.9% absolute). Food types were similar using combined stores, primary store or complete provider turnover. Evaluating combined stores F&B turnover represents an efficient method to estimate total F&B turnover quantity and associated dietary intake in RICs. In multiple-store communities, evaluating only primary store F&B turnover provides an efficient estimate of macronutrient distribution and major food types. © 2016 Public Health Association of Australia.

Primary Education in the United Arab Republic, Its Development and Organization.

ERIC Educational Resources Information Center

Mehrez, Zainab

This document is an English-language abstract (approximately 1,500 words) of a comprehensive survey describing the growth of primary schooling in the UAR during the 19th and 20th centuries. Different types of elementary schools were unified in 1951 into one category, and in 1953, all fees were abolished and primary certificate examinations were…

Inservice Science Courses for Primary Teachers: Implementation of Different Types of Inservice Training Courses in Finland.

ERIC Educational Resources Information Center

Asunta, Tuula

1997-01-01

Reports on the effects of six different primary inservice training courses aimed at teachers' motivation, anxieties, hands-on working skills, and support needs. Results showed that primary teachers felt they needed more continuous support in the area of improving their knowledge and understanding of the subject, especially in chemistry and…

Using Primary Sources on the Internet To Teach and Learn History. ERIC Digest.

ERIC Educational Resources Information Center

Shiroma, Deanne

The Internet enables teachers to enhance the teaching and learning of history through quick and extensive access to primary sources. Introducing and using primary sources in the history classroom will almost certainly lead to active learning and development of critical thinking, reasoning, and problem solving. This Digest discusses: (1) types and…

78 FR 24584 - Imposition of Special Measures Against Halawi Exchange Co. as a Financial Institution of Primary...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-25

... financial institution operating outside of the United States that is of primary money laundering concern... international money laundering and the financing of terrorism. Regulations implementing the BSA appear at 31 CFR..., class of transaction, or type of account is of ``primary money laundering concern,'' to require domestic...

Leading Curriculum Innovation in Primary Schools Project: A Final Report

ERIC Educational Resources Information Center

Brundrett, Mark; Duncan, Diane

2015-01-01

This article provides the final report on a research project that investigated the ways in which curriculum innovation can be led successfully in primary schools. Data gathering included 40 semi-structured interviews in 10 successful primary schools in England of varying sizes and types and in a range of geographical and social locations. Findings…

Undesired Teacher Behaviours According to the Studentship Memories of Prospective Teachers in Primary School

ERIC Educational Resources Information Center

Polat, Hüseyin

2015-01-01

The purpose of this study is to explore the types of undesired behaviours observed by prospective primary school teachers during their studentship at primary school. 35 voluntary prospective teachers studying at the faculty of education in Adiyaman University participated into the study, which was conducted within qualitative research techniques.…

Performance of primary repair on colon injuries sustained from low-versus high-energy projectiles.

PubMed

Lazovic, Ranko; Radojevic, Nemanja; Curovic, Ivana

2016-04-01

Among various reasons, colon injuries may be caused by low- or high-energy firearm bullets, with the latter producing a temporary cavitation phenomenon. The available treatment options include primary repair and two-stage management, but recent studies have shown that primary repair can be widely used with a high success rate. This paper investigates the differences in performance of primary repair on these two types of colon injuries. Two groups of patients who sustained colon injuries due to single gunshot wounds, were retrospectively categorized based on the type of bullet. Primary colon repair was performed in all patients selected based on the inclusion and exclusion criteria (Stone and Fabian's criteria). An almost absolute homogeneity was attained among the groups in terms of age, latent time before surgery, and four trauma indexes. Only one patient from the low-energy firearm projectile group (4%) developed a postsurgical complication versus nine patients (25.8%) from the high-energy group, showing statistically significant difference (p = 0.03). These nine patients experienced the following postsurgical complications: pneumonia, abscess, fistula, suture leakage, and one multiorgan failure with sepsis. Previous studies concluded that one-stage primary repair is the best treatment option for colon injuries. However, terminal ballistics testing determined the projectile's path through the body and revealed that low-energy projectiles caused considerably lesser damage than their high-energy counterparts. Primary colon repair must be performed definitely for low-energy short firearm injuries but very carefully for high-energy injuries. Given these findings, we suggest that the treatment option should be determined based not only on the bullet type alone but also on other clinical findings. Copyright © 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Organotropism and prognostic marker discordance in distant metastases of breast carcinoma: fact or fiction? A clinicopathologic analysis.

PubMed

St Romain, Paul; Madan, Rashna; Tawfik, Ossama W; Damjanov, Ivan; Fan, Fang

2012-03-01

Prior studies have suggested that the type of breast cancer influences the location of distant metastases ("organotropism") and that there may be discordance of estrogen receptor and human epidermal growth factor receptor 2 (Her2) expression between primaries and metastases. Our aims were to investigate the relationship between tumor type and metastatic site and to compare biomarker expression between primary and metastatic tumors. We retrospectively reviewed 102 biopsy-proven cases of breast cancer metastatic to distant sites from 2000 to 2010 and 34 corresponding primaries for histologic subtype, grade, lymphovascular invasion, lymph node metastasis, and expression of estrogen receptor and Her2. Most metastases were of ductal (88) and lobular (11) histologic types. Available data on primaries indicated that the majority were grade III with positive lymph node metastasis and lymphovascular invasion. Biomarkers on 73 metastases showed 37 estrogen receptor positive/Her2-, 6 estrogen receptor positive/Her2+, 8 estrogen receptor negative/Her2+, and 22 estrogen receptor negative/Her2-. The most common metastatic sites were the lung (26%), bone (32%), and liver (21%). We found no association between estrogen receptor/Her2 profile and metastatic site (P = .16). When compared with ductal carcinoma, lobular carcinoma showed a unique metastatic pattern to gastrointestinal tract/gynecologic sites (P = .014). Of 34 cases with paired prognostic markers for primary and metastatic sites, 7 (20%) demonstrated discordance in estrogen receptor-positive/Her2 profile between the primary and the metastasis. Because the estrogen receptor-positive/Her2 profile of metastatic breast cancer did not always match that of the primary tumor, it is important to repeat the prognostic markers of metastasis. Copyright © 2012 Elsevier Inc. All rights reserved.

COST-UTILITY ANALYSIS OF PRIMARY PROPHYLAXIS, COMPARED WITH ON-DEMAND TREATMENT, FOR PATIENTS WITH SEVERE HEMOPHILIA TYPE A IN COLOMBIA.

PubMed

Castro Jaramillo, Héctor Eduardo; Moreno Viscaya, Mabel; Mejia, Aurelio E

2016-01-01

This article presents a cost-utility analysis from the Colombian health system perspective comparing primary prophylaxis to on-demand treatment using exogenous clotting factor VIII (FVIII) for patients with severe hemophilia type A. We developed a Markov model to estimate expected costs and outcomes (measured as quality-adjusted life-years, QALYs) for each strategy. Transition probabilities were estimated using published studies; utility weights were obtained from a sample of Colombian patients with hemophilia and costs were gathered using local data. Both deterministic and probabilistic sensitivity analysis were performed to assess the robustness of results. The additional cost per QALY gained of primary prophylaxis compared with on-demand treatment was 105,081,022 Colombian pesos (COP) (55,204 USD), and thus not considered cost-effective according to a threshold of up to three times the current Colombian gross domestic product (GDP) per-capita. When primary prophylaxis was provided throughout life using recombinant FVIII (rFVIII), which is much costlier than FVIII, the additional cost per QALY gained reached 174,159,553 COP (91,494 USD). using a decision rule of up to three times the Colombian GDP per capita, primary prophylaxis (with either FVIII or rFVIII) would not be considered as cost-effective in this country. However, a final decision on providing or preventing patients from primary prophylaxis as a gold standard of care for severe hemophilia type A should also consider broader criteria than the incremental cost-effectiveness ratio results itself. Only a price reduction of exogenous FVIII of 50 percent or more would make primary prophylaxis cost-effective in this context.

Performance of primary repair on colon injuries sustained from low-versus high-energy projectiles

PubMed Central

Lazovic, Ranko; Radojevic, Nemanja; Curovic, Ivana

2017-01-01

Among various reasons, colon injuries may be caused by low- or high-energy firearm bullets, with the latter producing a temporary cavitation phenomenon. The available treatment options include primary repair and two-stage management, but recent studies have shown that primary repair can be widely used with a high success rate. This paper investigates the differences in performance of primary repair on these two types of colon injuries. Two groups of patients who sustained colon injuries due to single gunshot wounds, were retrospectively categorized based on the type of bullet. Primary colon repair was performed in all patients selected based on the inclusion and exclusion criteria (Stone and Fabian's criteria). An almost absolute homogeneity was attained among the groups in terms of age, latent time before surgery, and four trauma indexes. Only one patient from the low-energy firearm projectile group (4%) developed a postsurgical complication versus nine patients (25.8%) from the high-energy group, showing statistically significant difference (p = 0.03). These nine patients experienced the following postsurgical complications: pneumonia, abscess, fistula, suture leakage, and one multiorgan failure with sepsis. Previous studies concluded that one-stage primary repair is the best treatment option for colon injuries. However, terminal ballistics testing determined the projectile's path through the body and revealed that low-energy projectiles caused considerably lesser damage than their high-energy counterparts. Primary colon repair must be performed definitely for low-energy short firearm injuries but very carefully for high-energy injuries. Given these findings, we suggest that the treatment option should be determined based not only on the bullet type alone but also on other clinical findings. PMID:26874437

Decreased endothelin receptor B expression in large primary uveal melanomas is associated with early clinical metastasis and short survival

PubMed Central

Smith, S L; Damato, B E; Scholes, A G M; Nunn, J; Field, J K; Heighway, J

2002-01-01

The most devastating aspect of cancer is the metastasis of tumour cells to organs distant from the original tumour site. The major problem facing oncologists treating uveal melanoma, the most common cancer of the eye, is metastatic disease. To lower mortality, it is necessary to increase our understanding of the molecular genetic alterations involved in this process. Using suppression subtractive hybridisation, we have analysed differential gene expression between four primary tumours from patients who have developed clinical metastasis and four primary tumours from patients with no evidence of metastasis to date. We have identified endothelin receptor type B as differentially expressed between these tumours and confirmed this observation using comparative multiplex RT–PCR. In a further 33 tumours, reduced endothelin receptor type B expression correlated with death from metastatic disease. Reduced expression also correlated with other known prognostic indicators, including the presence of epithelioid cells, chromosome 3 allelic imbalance and chromosome 8q allelic imbalance. Endothelin receptor type B expression was also reduced in four out of four primary small cell lung carcinomas compared to normal bronchial epithelium. We also show that the observed down-regulation of endothelin receptor type B in uveal melanoma was not due to gene deletion. Our findings suggest a role for endothelin receptor type B in the metastasis of uveal melanoma and, potentially, in the metastasis of other neural crest tumours. British Journal of Cancer (2002) 87, 1308–1313. doi:10.1038/sj.bjc.6600620 www.bjcancer.com © 2002 Cancer Research UK PMID:12439722

A landscape-scale assessment of above- and belowground primary production in coastal wetlands: Implications for climate change-induced community shifts

USGS Publications Warehouse

Stagg, Camille L.; Schoolmaster, Donald R.; Piazza, Sarai C.; Snedden, Gregg; Steyer, Gregory D.; Fischenich, Craig J; McComas, Robert W.

2017-01-01

Above- and belowground production in coastal wetlands are important contributors to carbon accumulation and ecosystem sustainability. As sea level rises, we can expect shifts to more salt-tolerant communities, which may alter these ecosystem functions and services. Although the direct influence of salinity on species-level primary production has been documented, we lack an understanding of the landscape-level response of coastal wetlands to increasing salinity. What are the indirect effects of sea-level rise, i.e., how does primary production vary across a landscape gradient of increasing salinity that incorporates changes in wetland type? This is the first study to measure both above- and belowground production in four wetland types that span an entire coastal gradient from fresh to saline wetlands. We hypothesized that increasing salinity would limit rates of primary production, and saline marshes would have lower rates of above- and belowground production than fresher marshes. However, along the Northern Gulf of Mexico Coast in Louisiana, USA, we found that aboveground production was highest in brackish marshes, compared with fresh, intermediate, and saline marshes, and belowground production was similar among all wetland types along the salinity gradient. Multiple regression analysis indicated that salinity was the only significant predictor of production, and its influence was dependent upon wetland type. We concluded that (1) salinity had a negative effect on production within wetland type, and this relationship was strongest in the fresh marsh (0–2 PSU) and (2) along the overall landscape gradient, production was maintained by mechanisms at the scale of wetland type, which were likely related to plant energetics. Regardless of wetland type, we found that belowground production was significantly greater than aboveground production. Additionally, inter-annual variation, associated with severe drought conditions, was observed exclusively for belowground production, which may be a more sensitive indicator of ecosystem health than aboveground production.

Development and status of Arkansas' primary forest products industry

Treesearch

Dennis M. May

1990-01-01

The development of Arkansas' primary forest products industry is presented by following the changes in numbers and types of mills operating through time as well as the State's production of roundwood to supply the changing industry.

Clinical coaching in primary care: Capable of improving control in patients with type 2 diabetes mellitus?

PubMed

González-Guajardo, Eduardo Enrique; Salinas-Martínez, Ana María; Botello-García, Antonio; Mathiew-Quiros, Álvaro

2016-06-01

Few clinical coaching studies are both endorsed by real cases and focused on reducing suboptimal diabetes control. We evaluated the effectiveness of coaching on improving type 2 diabetes goals after 3 years of implementation in primary care. A cross-sectional study with follow up was conducted during 2008-2011. Coaching consisted of guiding family doctors to improve their clinical abilities, and it was conducted by a medical doctor trained in skill building, experiential learning, and goal setting. Effectiveness was assessed by means of fasting plasma glucose and glycosylated hemoglobin outcomes. The main analysis consisted of 1×3 and 2×3 repeated measures ANOVAs. A significant coaching×time interaction was observed, indicating that the difference in glucose between primary care units with and without coaching increased over time (Wilks' lambda multivariate test, P<0.0001). Coaching increased 1.4 times (95%CI 1.3, 1.5) the possibility of reaching the fasting glucose goal after controlling for baseline values. There was also a significant improvement in glycosylated hemoglobin (Bonferroni-corrected p-value for pairwise comparisons, P<0.0001). A correctible and even preventable contributing component in diabetes care corresponds to physicians' performance. After 3 years of implementation, coaching was found to be worth the effort to improve type 2 diabetes control in primary care. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

The Prevalence and Treatment Outcomes of Primary Tooth Injuries

PubMed Central

Arikan, Volkan; Sari, Saziye; Sonmez, Hayriye

2010-01-01

Objectives: The aim of the present study was to evaluate the type and prevalence of primary tooth injuries, as well as their treatment and treatment outcomes, among children referred to the Department of Pedodontics at the Ankara University Faculty of Dentistry in Turkey. Methods: The study population consisted of patients applying to the department with a primary tooth injury over a period of 21 months. Fifty-one patients presented with trauma to 99 primary teeth. Clinical and radiographic examinations were conducted on each patient. Age, sex, time, cause of injury, and number of teeth affected were recorded, and the type of trauma was identified according to Andreasen’s classification. The teeth were treated by one of the authors. Results: The majority of trauma occurred between the ages of 2 and 4. The most common type of injury was lateral luxation (33.3%). Most injuries (33.3%) presented during May. The most common form of treatment was follow-up only (39.4%), followed by extraction (29.3%) and root canal treatment (12.1%). The average follow-up period was 11 months. During the follow-up period, complications were observed in 4 teeth. Conclusions: The study results show that in the absence of acute symptoms, parents tend not to apply to a dental clinic for children’s injuries. This finding highlights the importance of informing the public about primary tooth injuries and their consequences. PMID:20922165

Influence of Drilling Speed on Stability of Tapered Dental Implants: An Ex Vivo Experimental Study.

PubMed

Almeida, Karen P; Delgado-Ruiz, Rafael; Carneiro, Leandro G; Leiva, Alberto Bordonaba; Calvo-Guirado, Jose Luis; Gómez-Moreno, Gerardo; Malmström, Hans; Romanos, Georgios E

2016-01-01

The aim of this study was to evaluate whether the drilling speed used during implant site preparation influences primary stability. Eighty tapered designed implants (3.8 × 10 mm) were inserted following osteotomies created in solid rigid polyurethane foam (simulating bone type II) and cellular rigid polyurethane foam (simulating bone type IV). Half were prepared using drilling speeds of 800 rpm (low speed), and the other half were prepared using speeds of 1,500 rpm (high speed). Following insertion, implant primary stability was measured using Periotest and Osstell (resonance frequency analysis [RFA]) devices. Two-way analysis of variance (ANOVA) used for this study found that the drilling speed used to create the osteotomies appeared to have no significant impact on primary stability. The bone quality and not the osteotomy drilling speed seems to influence the implant primary stability.

Cognitive radio based optimal channel sensing and resources allocation

NASA Astrophysics Data System (ADS)

Vijayasarveswari, V.; Khatun, S.; Fakir, M. M.; Nayeem, M. N.; Kamarudin, L. M.; Jakaria, A.

2017-03-01

Cognitive radio (CR) is the latest type of wireless technoloy that is proposed to mitigate spectrum saturation problem. İn cognitve radio, secondary user will use primary user's spectrum during primary user's absence without interupting primary user's transmission. This paper focuses on practical cognitive radio network development process using Android based smart phone for the data transmission. Energy detector based sensing method was proposed and used here because it doesnot require primary user's information. Bluetooth and Wi-fi are the two available types of spectrum that was sensed for CR detection. Simulation showed cognitive radio network can be developed using Android based smart phones. So, a complete application was developed using Java based Android Eclipse program. Finally, the application was uploaded and run on Android based smart phone to form and verify CR network for channel sensing and resource allocation. The observed efficiency of the application was around 81%.

Three cases of pigmented cosmetic dermatitis-like eruptions associated with primary Sjögren's syndrome or anti-SSA antibody.

PubMed

Takeo, Naoko; Sakai, Takashi; Saito-Shono, Tomoko; Ishikawa, Kazushi; Hatano, Yutaka; Katagiri, Kazumoto; Takahashi, Yoshihiro; Kawano, Kenji; Kimoto, Kenichi; Kubota, Toshiaki; Eshima, Nobuoki; Kojima, Hiroto; Fujiwara, Sakuhei

2016-08-01

Pigmented cosmetic dermatitis-like (Riehl's melanosis-like) pigmentation was reported in three of 27 patients with primary Sjögren's syndrome. But case reports of such eruptions are rare. We describe three cases of such eruptions associated with primary Sjögren's syndrome or anti-SSA antibody and possible associations with specific types of human leukocyte antigen (HLA) and infiltrating lymphocytes. These middle-aged Japanese women had reticular facial pigmentation and histopathological examination revealed interface dermatitis, melanophages, and dense lymphocytic infiltration around hair follicles and sweat ducts. HLA typing revealed common antigenic equivalents or genetic typing of HLA-A2, DR52, DPA1(02:02) and DPB1(05:01). Immunohistochemical staining revealed major subsets of T cells to be CD8 and CD45RO. Some Foxp3- and few IL17-positive cells were found in strong contrast to the major CD4 subset of infiltrated T cells in annular erythema associated with Sjögren's syndrome. Apparently, our patients' pigmentation represented a specific etiology associated with primary Sjögren's syndrome or anti-SSA antibody. © 2016 Japanese Dermatological Association.

Which anxiety disorders may differentiate attention deficit hyperactivity disorder, combined type with dysthymic disorder from attention deficit hyperactivity disorder, combined type alone?

PubMed

Vance, Alasdair; Harris, Katrina; Boots, Marilyn; Talbot, Jessica; Karamitsios, Mary

2003-10-01

Attention deficit hyperactivity disorder, combined type (ADHD-CT), dysthymic disorder, and anxiety disorders frequently co-occur in primary school age children, although there have been no published data describing their association. We investigated the association of anxiety, defined from a parent or child perspective, with primary school-age children with ADHD-CT with and without dysthymic disorder. One hundred and forty-six medication naïve children with ADHD-CT were studied. Two groups with and without dysthymic disorder were formed to compare parent and child reports of anxiety, using categorical and continuous measures of anxiety, using logistic regression. Separation anxiety disorder and social phobia were associated with primary school-age children with ADHD-CT and dysthymic disorder, compared to children with ADHD-CT without dysthymic disorder. The recognition of dysthymic disorder and anxiety disorders and their management in primary school-age children with ADHD-CT is generally poorly understood. The identification and elucidation of composite anxiety and depressive phenomena that may be systematically investigated through longitudinal studies of epidemiologically derived samples is needed in this particular group of children.

Calculation of natural convection test at Phenix using the NETFLOW++ code

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

Mochizuki, H.; Kikuchi, N.; Li, S.

2012-07-01

The present paper describes modeling and analyses of a natural convection of the pool-type fast breeder reactor Phenix. The natural convection test was carried out as one of the End of Life Tests of the Phenix. Objective of the present study is to assess the applicability of the NETFLOW++ code which has been verified thus far using various water facilities and validated using the plant data of the loop-type FBR 'Monju' and the loop-type experimental fast reactor 'Joyo'. The Phenix primary heat transport system is modeled based on the benchmark documents available from IAEA. The calculational model consists of onlymore » the primary heat transport system with boundary conditions on the secondary-side of IHX. The coolant temperature at the primary pump inlet, the primary coolant temperature at the IHX inlet and outlet, the secondary coolant temperatures and other parameters are calculated by the code where the heat transfer between the hot and cold pools is explicitly taken into account. A model including the secondary and tertiary systems was prepared, and the calculated results also agree well with the measured data in general. (authors)« less

Association between refill adherence to lipid-lowering medications and the risk of cardiovascular disease and mortality in Swedish patients with type 2 diabetes mellitus: a nationwide cohort study

PubMed Central

Hero, Christel; Svensson, Ann-Marie; Franzén, Stefan; Miftaraj, Mervete; Gudbjörnsdottir, Soffia; Eeg-Olofsson, Katarina; Eliasson, Björn; Andersson Sundell, Karolina

2018-01-01

Objectives To analyse the association between refill adherence to lipid-lowering medications, and the risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes mellitus. Design Cohort study. Setting National population-based cohort of Swedish patients with type 2 diabetes mellitus. Participants 86 568 patients aged ≥18 years, registered with type 2 diabetes mellitus in the Swedish National Diabetes Register, who filled at least one prescription for lipid-lowering medication use during 2007–2010, 87% for primary prevention. Exposure and outcome measures Refill adherence of implementation was assessed using the medication possession ratio (MPR), representing the proportion of days with medications on hand during an 18-month exposure period. MPR was categorised by five levels (≤20%, 21%–40%, 41%–60%, 61%–80% and >80%). Patients without medications on hand for ≥180 days were defined as non-persistent. Risk of CVD (myocardial infarction, ischaemic heart disease, stroke and unstable angina) and mortality by level of MPR and persistence was analysed after the exposure period using Cox proportional hazards regression and Kaplan-Meier, adjusted for demographics, socioeconomic status, concurrent medications and clinical characteristics. Results The hazard ratios for CVD ranged 1.33–2.36 in primary prevention patients and 1.19–1.58 in secondary prevention patients, for those with MPR ≤80% (p<0.0001). The mortality risk was similar regardless of MPR level. The CVD risk was 74% higher in primary prevention patients and 33% higher in secondary prevention patients, for those who were non-persistent (p<0.0001). The mortality risk was 6% higher in primary prevention patients and 18% higher in secondary prevention patients, for non-persistent patients (p<0.0001). Conclusions Higher refill adherence to lipid-lowering medications was associated with lower risk of CVD in primary and secondary prevention patients with type 2 diabetes mellitus. PMID:29602853

Individual risk factors for deep infection and compromised fracture healing after intramedullary nailing of tibial shaft fractures: a single centre experience of 480 patients.

PubMed

Metsemakers, W-J; Handojo, K; Reynders, P; Sermon, A; Vanderschot, P; Nijs, S

2015-04-01

Despite modern advances in the treatment of tibial shaft fractures, complications including nonunion, malunion, and infection remain relatively frequent. A better understanding of these injuries and its complications could lead to prevention rather than treatment strategies. A retrospective study was performed to identify risk factors for deep infection and compromised fracture healing after intramedullary nailing (IMN) of tibial shaft fractures. Between January 2000 and January 2012, 480 consecutive patients with 486 tibial shaft fractures were enrolled in the study. Statistical analysis was performed to determine predictors of deep infection and compromised fracture healing. Compromised fracture healing was subdivided in delayed union and nonunion. The following independent variables were selected for analysis: age, sex, smoking, obesity, diabetes, American Society of Anaesthesiologists (ASA) classification, polytrauma, fracture type, open fractures, Gustilo type, primary external fixation (EF), time to nailing (TTN) and reaming. As primary statistical evaluation we performed a univariate analysis, followed by a multiple logistic regression model. Univariate regression analysis revealed similar risk factors for delayed union and nonunion, including fracture type, open fractures and Gustilo type. Factors affecting the occurrence of deep infection in this model were primary EF, a prolonged TTN, open fractures and Gustilo type. Multiple logistic regression analysis revealed polytrauma as the single risk factor for nonunion. With respect to delayed union, no risk factors could be identified. In the same statistical model, deep infection was correlated with primary EF. The purpose of this study was to evaluate risk factors of poor outcome after IMN of tibial shaft fractures. The univariate regression analysis showed that the nature of complications after tibial shaft nailing could be multifactorial. This was not confirmed in a multiple logistic regression model, which only revealed polytrauma and primary EF as risk factors for nonunion and deep infection, respectively. Future strategies should focus on prevention in high-risk populations such as polytrauma patients treated with EF. Copyright © 2014 Elsevier Ltd. All rights reserved.

Experiences of violence and deficits in academic achievement among urban primary school children in Jamaica.

PubMed

Baker-Henningham, Helen; Meeks-Gardner, Julie; Chang, Susan; Walker, Susan

2009-05-01

The aim of this study was to examine the relationship between children's experiences of three different types of violence and academic achievement among primary school children in Kingston, Jamaica. A cross-sectional study of 1300 children in grade 5 [mean (S.D.) age: 11 (0.5) years] from 29 government primary schools in urban areas of Kingston and St. Andrew, Jamaica, was conducted. Academic achievement (mathematics, reading, and spelling) was assessed using the Wide Range Achievement Test. Children's experiences of three types of violence - exposure to aggression among peers at school, physical punishment at school, and exposure to community violence - were assessed by self-report using an interviewer administered questionnaire. Fifty-eight percent of the children experienced moderate or high levels of all three types of violence. Boys had poorer academic achievement and experienced higher levels of aggression among peers and physical punishment at school than girls. Children's experiences of the three types of violence were independently associated with all three indices of academic achievement. There was a dose-response relationship between children's experiences of violence and academic achievement with children experiencing higher levels of violence having the poorest academic achievement and children experiencing moderate levels having poorer achievement than those experiencing little or none. Exposure to three different types of violence was independently associated with poor school achievement among children attending government, urban schools in Jamaica. Programs are needed in schools to reduce the levels of aggression among students and the use of physical punishment by teachers and to provide support for children exposed to community violence. Children in Jamaica and the wider Caribbean experience significant amounts of violence in their homes, communities, and schools. In this study, we demonstrate a dose-response relationship between primary school children's experiences of three different types of violence and their academic achievement. The study points to the need for validated violence prevention programs to be introduced in Jamaican primary schools. Such programs need to train teachers in appropriate classroom management and discipline strategies and to promote children's social and emotional competence and prevent aggression.

Relationship between self-efficacy, self-care behaviour and glycaemic control among patients with type 2 diabetes mellitus in the Malaysian primary care setting.

PubMed

Tharek, Zahirah; Ramli, Anis Safura; Whitford, David Leonard; Ismail, Zaliha; Mohd Zulkifli, Maryam; Ahmad Sharoni, Siti Khuzaimah; Shafie, Asrul Akmal; Jayaraman, Thevaraajan

2018-03-09

Self-efficacy has been shown to be positively correlated with self-care behaviour and glycaemic control among patients with type 2 diabetes mellitus. However, such evidence is lacking in the Malaysian primary care setting. The objectives of this study were to i) determine the levels of self-efficacy, self-care behaviour and glycaemic control among patients with type 2 diabetes mellitus in the Malaysian primary care setting ii) determine the relationship between self-efficacy, self-care behaviour and glycaemic control iii) determine the factors associated with glycaemic control. This was a cross-sectional study involving patients with type 2 diabetes mellitus from two public primary care clinics in Malaysia. Self-efficacy and self-care behaviour levels were measured using previously translated and validated DMSES and SDSCA questionnaires in Malay versions, respectively. Glycaemic control was measured using HbA 1c. RESULTS: A total of 340 patients with type 2 diabetes mellitus were recruited. The total mean (±SD) of self-efficacy and self-care behaviour scores were 7.33 (±2.25) and 3.76 (±1.87), respectively. A positive relationship was found between self-efficacy and self-care behaviour (r 0.538, P < 0.001). Higher self-efficacy score was shown to be correlated with lower HbA 1c (r - 0.41, P < 0.001). Multiple linear regression analysis demonstrated that higher self-efficacy scores (b - 0.398; 95% CI: -0.024, - 0.014; P < 0.001), shorter duration of diabetes (b 0.177; 95% CI: 0.002, 0.007; P < 0.001) and smaller waist circumference (b 0.135; 95% CI: 0.006, 0.035; P = 0.006), were significantly associated with good glycaemic control. This study demonstrated that higher self-efficacy was correlated with improved self-care behaviour and better glycaemic control. Findings of this study suggest the importance of including routine use of self-efficacy measures in the management of type 2 diabetes mellitus in primary care.

The Type 3 Adenylyl Cyclase is Required for Novel Object Learning and Extinction of Contextual Memory: Role of cAMP Signaling in Primary Cilia

PubMed Central

Wang, Zhenshan; Phan, Trongha; Storm, Daniel R.

2011-01-01

Although primary cilia are found on neurons throughout the brain, their physiological function remains elusive. Human ciliopathies are associated with cognition defects and transgenic mice lacking proteins expressed in primary cilia exhibit defects in learning and memory. Recently, it was reported that mice lacking the G-protein coupling receptor somatostatin receptor-3 (SSTR3), a protein expressed predominately in the primary cilia of neurons, have defective memory for novel object recognition and lower cAMP levels in the brain. Since SSTR3 is coupled to regulation of adenylyl cyclase this suggests that adenylyl cyclase activity in primary cilia of CNS neurons may be critical for some forms of learning and memory. Because the type 3 adenylyl cyclase (AC3) is expressed in primary cilia of hippocampal neurons, we examined AC3−/− mice for several forms of learning and memory. Here, we report that AC3−/− mice show no short-term memory for novel objects and fail to exhibit extinction of contextual fear conditioning. They also show impaired learning and memory for temporally dissociated passive avoidance (TDPA). Since AC3 is exclusively expressed in primary cilia we conclude that cAMP signals generated within primary cilia contribute to some forms of learning and memory including extinction of contextual fear conditioning. PMID:21490195

The type 3 adenylyl cyclase is required for novel object learning and extinction of contextual memory: role of cAMP signaling in primary cilia.

PubMed

Wang, Zhenshan; Phan, Trongha; Storm, Daniel R

2011-04-13

Although primary cilia are found on neurons throughout the brain, their physiological function remains elusive. Human ciliopathies are associated with cognition defects, and transgenic mice lacking proteins expressed in primary cilia exhibit defects in learning and memory. Recently, it was reported that mice lacking the G-protein-coupling receptor somatostatin receptor-3 (SSTR3), a protein expressed predominately in the primary cilia of neurons, have defective memory for novel object recognition and lower cAMP levels in the brain. Since SSTR3 is coupled to regulation of adenylyl cyclase, this suggests that adenylyl cyclase activity in primary cilia of CNS neurons may be critical for some forms of learning and memory. Because the type 3 adenylyl cyclase (AC3) is expressed in primary cilia of hippocampal neurons, we examined AC3(-/-) mice for several forms of learning and memory. Here, we report that AC3(-/-) mice show no short-term memory for novel objects and fail to exhibit extinction of contextual fear conditioning. They also show impaired learning and memory for temporally dissociative passive avoidance. Since AC3 is exclusively expressed in primary cilia, we conclude that cAMP signals generated within primary cilia contribute to some forms of learning and memory, including extinction of contextual fear conditioning.

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

Song, Gian; Sun, Zhiqian; Poplawsky, Jonathan D.

The microstructures of a hierarchical-precipitate-strengthened ferritic alloy are characterized, using transmission-electron microscopy (TEM) and atom-probe tomography (APT). The alloy shows duplex precipitates. The primary precipitate with an average edge length of 90 nm consists of NiAl- and Ni2TiAl-type phases, while the secondary precipitate with an average radius of 2 nm is a NiAl-type phase. Based on the APT results, the volume fractions of the primary and secondary precipitates were calculated, using the lever rule to be 17.3 and 2.3 %, respectively.

Paper-based device for rapid typing of secondary human blood groups.

PubMed

Li, Miaosi; Then, Whui Lyn; Li, Lizi; Shen, Wei

2014-01-01

We report the use of bioactive paper for typing of secondary human blood groups. Our recent work on using bioactive paper for human blood typing has led to the discovery of a new method for identifying haemagglutination of red blood cells. The primary human blood groups, i.e., ABO and RhD groups, have been successfully typed with this method. Clinically, however, many secondary blood groups can also cause fatal blood transfusion accidents, despite the fact that the haemagglutination reactions of secondary blood groups are generally weaker than those of the primary blood groups. We describe the design of a user-friendly sensor for rapid typing of secondary blood groups using bioactive paper. We also present mechanistic insights into interactions between secondary blood group antibodies and red blood cells obtained using confocal microscopy. Haemagglutination patterns under different conditions are revealed for optimization of the assay conditions.

The effects of surgical preparation techniques and implant macro-geometry on primary stability: An in vitro study.

PubMed

Falisi, G; Severino, M; Rastelli, C; Bernardi, S; Caruso, S; Galli, M; Lamazza, L; Di Paolo, C

2017-03-01

The attainment of a good primary stability is a necessary condition to ensure the success of osseointegration in implantology. In type IV cancellous bone, however, it is possible that a reduced primary stability can lead to an increased rate of failure. The aim of this study was therefore to determine, with the help of the resonance frequency (Osstell mentor), which technique of implant site preparation (piezo surgery, conventional, under-preparation, bone compaction, osteodistraction) and macro-geometry is able to improve implant stability in type IV cancellous bone. 10 pig ribs were prepared with a surgical pre-drilled guide, calibrated for a correct implant positioning. On each rib, 5 implant sites (one for each technique) were prepared. Successively, 50 conical implants (Tekka Global D) were inserted and measured with the resonance frequency to evaluate the primary stability. Data collected were analyzed by analysis of variance (ANOVA) to test whether the Implant Stability Quotient (ISQ) values of the five techniques were significantly different. The results showed that no significant differences among the ISQ values of the five techniques used were found. Also, no significant differences in the macro-geometry of the two types of compared implants were observed. However, the macro-geometry of Tekka implants, characterized by a double condensing thread, seems to provide greater ISQ values than those of single thread implants when using the same technique. In light of these preliminary data, it is conceivable that in cases of reduced stability, such as those occurring with a type IV bone, all means ameliorating the primary stability and accelerating the osseointegration can be utilized.

Primary tumor location predicts poor clinical outcome with cetuximab in RAS wild-type metastatic colorectal cancer.

PubMed

Kim, Dalyong; Kim, Sun Young; Lee, Ji Sung; Hong, Yong Sang; Kim, Jeong Eun; Kim, Kyu-Pyo; Kim, Jihun; Jang, Se Jin; Yoon, Young-Kwang; Kim, Tae Won

2017-11-23

In metastatic colorectal cancer, the location of the primary tumor has been suggested to have biological significance. In this study, we investigated whether primary tumor location affects cetuximab efficacy in patients with RAS wild-type metastatic colorectal cancer. Genotyping by the SequenomMassARRAY technology platform (OncoMap) targeting KRAS, NRAS, PIK3CA, and BRAF was performed in tumors from 307 patients who had been given cetuximab as salvage treatment. Tumors with mutated RAS (KRAS or NRAS; n = 127) and those with multiple primary location (n = 10) were excluded. Right colon cancer was defined as a tumor located in the proximal part to splenic flexure. A total of 170 patients were included in the study (right versus left, 23 and 147, respectively). Patients with right colon cancer showed more mutated BRAF (39.1% vs. 5.4%), mutated PIK3CA (13% vs. 1.4%), poorly differentiated tumor (17.4% vs. 3.4%), and peritoneal involvement (26.1% vs. 8.8%) than those with left colon and rectal cancer. Right colon cancer showed poorer progression-free survival (2.0 vs.5.0 months, P = 0.002) and overall survival (4.1 months and 13.0 months, P < 0.001) than the left colon and rectal cancer. By multivariable analysis, BRAF mutation, right colon primary, poorly differentiated histology, and peritoneal involvement were associated with risk of death. In RAS wild-type colon cancer treated with cetuximab as salvage treatment, right colon primary was associated with poorer survival outcomes than left colon and rectal cancer.

Primary and Specialty Medical Care Among Ethnically Diverse, Older Rural Adults With Type 2 Diabetes: The ELDER Diabetes Study

ERIC Educational Resources Information Center

Bell, Ronny A.; Quandt, Sara A.; Arcury, Thomas A.; Snively, Beverly M.; Stafford, Jeanette M.; Smith, Shannon L.; Skelly, Anne H.

2005-01-01

Purpose: Residents in rural communities in the United States, especially ethnic minority group members, have limited access to primary and specialty health care that is critical for diabetes management. This study examines primary and specialty medical care utilization among a rural, ethnically diverse, older adult population with diabetes.…

Primary and Specialty Medical Care among Ethnically Diverse, Older Rural Adults with Type 2 Diabetes: The ELDER Diabetes Study

ERIC Educational Resources Information Center

Bell, Ronny A.; Quandt, Sara A.; Arcury, Thomas A.; Snively, Beverly M.; Stafford, Jeanette M.; Smith, Shannon L.; Skelly, Anne H.

2005-01-01

Purpose: Residents in rural communities in the United States, especially ethnic minority group members, have limited access to primary and specialty health care that is critical for diabetes management. This study examines primary and specialty medical care utilization among a rural, ethnically diverse, older adult population with diabetes.…

What Do Children Write in Science? A Study of the Genre Set in a Primary Science Classroom

ERIC Educational Resources Information Center

Honig, Sheryl

2010-01-01

This article reports on the types of scientific writing found in two primary grade classrooms. These results are part of a larger two-year study whose purpose was to examine the development of informational writing of second- and third-grade students as they participated in integrated science-literacy instruction. The primary purpose of the…

Experiences of Violence and Deficits in Academic Achievement among Urban Primary School Children in Jamaica

ERIC Educational Resources Information Center

Baker-Henningham, Helen; Meeks-Gardner, Julie; Chang, Susan; Walker, Susan

2009-01-01

Objective: The aim of this study was to examine the relationship between children's experiences of three different types of violence and academic achievement among primary school children in Kingston, Jamaica. Methods: A cross-sectional study of 1300 children in grade 5 [mean (S.D.) age: 11 (0.5) years] from 29 government primary schools in urban…

The Primary Schoolteacher and Physical Education: A Review of Research and Implications for Irish Physical Education

ERIC Educational Resources Information Center

Fletcher, Tim; Mandigo, James

2012-01-01

This article reviews research on primary physical education (PE). In primary schools around the world PE is taught by the classroom teacher rather than by a PE specialist. Most classroom teachers feel poorly prepared to teach PE programmes that are meaningful to pupils and provide the types of experiences that lead to lifelong participation. This…

A Multidimensional Approach to Determinants of Computer Use in Primary Education: Teacher and School Characteristics

ERIC Educational Resources Information Center

Tondeur, J.; Valcke, M.; van Braak, J.

2008-01-01

The central aim of this study was to test a model that integrates determinants of educational computer use. In particular, the article examines teacher and school characteristics that are associated with different types of computer use by primary school teachers. A survey was set up, involving 527 teachers from 68 primary schools in Flanders. A…

GeoGebra Workshop for the Initial Teacher Training in Primary Education

ERIC Educational Resources Information Center

Lopez, Natalia Ruiz

2011-01-01

The GeoGebra Workshop for the degree "Teacher in Primary Education" has been designed to work the main geometric competencies that primary pre-service teachers need to develop. In this paper, some case studies are included in which we analyse the development of geometric skills and the use of GeoGebra dynamic tools in three types of activities:…

Immunogenicity and safety of primary and booster vaccination with 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens in a hexavalent DTPa-HBV-IPV/Hib combination vaccine in comparison with the licensed Infanrix hexa.

PubMed

Vesikari, Timo; Rivera, Luis; Korhonen, Tiina; Ahonen, Anitta; Cheuvart, Brigitte; Hezareh, Marjan; Janssens, Winnie; Mesaros, Narcisa

2017-07-03

Safety and immunogenicity of 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens of the combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Hib vaccine (DTPa-HBV-IPV/Hib) were evaluated in a Primary (NCT01248884) and a Booster vaccination (NCT01453998) study. In the Primary study, 721 healthy infants (randomized 1:1:1) received 3 doses of DTPa-HBV-IPV/Hib formulation A (D A T A Pa-HBV-IPV/Hib), or B (D B T B Pa-HBV-IPV/Hib) or the licensed DTPa-HBV-IPV/Hib vaccine (Infanrix hexa, GSK; control group) at 2, 3, 4 months of age. Infants were planned to receive a booster dose at 12-15 months of age with the same formulation received in the Primary study; however, following high incidence of fever associated with the investigational formulations in the Primary study, the Booster study protocol was amended and all infants yet to receive a booster dose (N = 385) received the licensed vaccine. In the Primary study, non-inferiority of 3-dose vaccination with investigational formulations compared with the licensed vaccine was not demonstrated due to anti-pertactin failing to meet the non-inferiority criterion. Post-primary vaccination, most infants had seroprotective levels of anti-diphtheria (100% of infants), anti-tetanus antigens (100%), against hepatitis B (≥ 97.5% across groups), polyribosyl-ribitol-phosphate (≥ 88.0%) and poliovirus types 1-3 (≥ 90.5%). Seropositivity rates for each pertussis antigen were 100% in all groups. Higher incidence of fever (> 38°C) was reported in infants receiving the investigational formulations (Primary study: 75.0% [A] and 72.1% [B] vs 58.8% [control]; Booster study, before amendment: 49.4% and 46.6% vs 37.4%, respectively). The development of the investigational formulations was not further pursued.

Immunogenicity and safety of primary and booster vaccination with 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens in a hexavalent DTPa-HBV-IPV/Hib combination vaccine in comparison with the licensed Infanrix hexa

PubMed Central

Vesikari, Timo; Rivera, Luis; Korhonen, Tiina; Ahonen, Anitta; Cheuvart, Brigitte; Hezareh, Marjan; Janssens, Winnie; Mesaros, Narcisa

2017-01-01

ABSTRACT Safety and immunogenicity of 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens of the combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Hib vaccine (DTPa-HBV-IPV/Hib) were evaluated in a Primary (NCT01248884) and a Booster vaccination (NCT01453998) study. In the Primary study, 721 healthy infants (randomized 1:1:1) received 3 doses of DTPa-HBV-IPV/Hib formulation A (DATAPa-HBV-IPV/Hib), or B (DBTBPa-HBV-IPV/Hib) or the licensed DTPa-HBV-IPV/Hib vaccine (Infanrix hexa, GSK; control group) at 2, 3, 4 months of age. Infants were planned to receive a booster dose at 12–15 months of age with the same formulation received in the Primary study; however, following high incidence of fever associated with the investigational formulations in the Primary study, the Booster study protocol was amended and all infants yet to receive a booster dose (N = 385) received the licensed vaccine. In the Primary study, non-inferiority of 3-dose vaccination with investigational formulations compared with the licensed vaccine was not demonstrated due to anti-pertactin failing to meet the non-inferiority criterion. Post-primary vaccination, most infants had seroprotective levels of anti-diphtheria (100% of infants), anti-tetanus antigens (100%), against hepatitis B (≥ 97.5% across groups), polyribosyl-ribitol-phosphate (≥ 88.0%) and poliovirus types 1–3 (≥ 90.5%). Seropositivity rates for each pertussis antigen were 100% in all groups. Higher incidence of fever (> 38°C) was reported in infants receiving the investigational formulations (Primary study: 75.0% [A] and 72.1% [B] vs 58.8% [control]; Booster study, before amendment: 49.4% and 46.6% vs 37.4%, respectively). The development of the investigational formulations was not further pursued. PMID:28340322

Association between registered nurse staffing and management outcomes of patients with type 2 diabetes within primary care: a cross-sectional linkage study

PubMed Central

Lukewich, Julia; Edge, Dana S.; VanDenKerkhof, Elizabeth; Williamson, Tyler; Tranmer, Joan

2016-01-01

Background: As the organization of primary care continues to evolve toward more interdisciplinary team structures, demonstrating effectiveness of care delivery is becoming important, particularly for nonphysician providers. Nurses are the most common nonphysician provider within primary care. The purpose of this study was to examine the relation between primary care delivery models that incorporate registered nurses and clinical outcomes of patients with type 2 diabetes. Methods: Patient data from the Canadian Primary Care Sentinel Surveillance Network were matched with survey data from 15 Family Health Team practices in southeastern Ontario. Included patients were adults with type 2 diabetes mellitus who had at least 1 primary care encounter at a Family Health Team practice that completed the organizational survey between Apr. 1, 2013, and Mar. 31, 2014. The clinical outcomes explored included hemoglobin A1c, fasting plasma glucose, blood pressure, low-density lipoprotein cholesterol and urine albumin:creatinine ratio. Results: Of the 15 practices, 13 (86.7%) had at least 1 registered nurse. The presence of 1 or more registered nurses in the practice was associated with increased odds of patients' having their hemoglobin A1c, fasting plasma glucose, blood pressure and low-density lipoprotein cholesterol values meet recommended targets. Practices with the lowest ratios of patients with diabetes to registered nurse had a significantly greater proportion of patients with hemoglobin A1c and fasting plasma glucose values on target than did practices with the highest ratios of patients to registered nurse (p < 0.01 and p = 0.03, respectively). Interpretation: The findings suggest that registered nurse staffing within primary care practice teams contributes to better diabetic care, as measured by diabetes management indicators. This study sets the groundwork for further exploration of nursing and organizational contributions to patient care in the primary care setting. PMID:27398372

Efficient Immortalization of Primary Nasopharyngeal Epithelial Cells for EBV Infection Study

PubMed Central

Yip, Yim Ling; Pang, Pei Shin; Deng, Wen; Tsang, Chi Man; Zeng, Musheng; Hau, Pok Man; Man, Cornelia; Jin, Yuesheng; Yuen, Anthony Po Wing; Tsao, Sai Wah

2013-01-01

Nasopharyngeal carcinoma (NPC) is common among southern Chinese including the ethnic Cantonese population living in Hong Kong. Epstein-Barr virus (EBV) infection is detected in all undifferentiated type of NPC in this endemic region. Establishment of stable and latent EBV infection in premalignant nasopharyngeal epithelial cells is an early event in NPC development and may contribute to its pathogenesis. Immortalized primary nasopharyngeal epithelial cells represent an important tool for investigation of EBV infection and its tumorigenic potential in this special type of epithelial cells. However, the limited availability and small sizes of nasopharyngeal biopsies have seriously restricted the establishment of primary nasopharyngeal epithelial cells for immortalization. A reliable and effective method to immortalize primary nasopharyngeal epithelial cells will provide unrestricted materials for EBV infection studies. An earlier study has reported that Bmi-1 expression could immortalize primary nasopharyngeal epithelial cells. However, its efficiency and actions in immortalization have not been fully characterized. Our studies showed that Bmi-1 expression alone has limited ability to immortalize primary nasopharyngeal epithelial cells and additional events are often required for its immortalization action. We have identified some of the key events associated with the immortalization of primary nasopharyngeal epithelial cells. Efficient immortalization of nasopharyngeal epithelial cells could be reproducibly and efficiently achieved by the combined actions of Bmi-1 expression, activation of telomerase and silencing of p16 gene. Activation of MAPK signaling and gene expression downstream of Bmi-1 were detected in the immortalized nasopharyngeal epithelial cells and may play a role in immortalization. Furthermore, these newly immortalized nasopharyngeal epithelial cells are susceptible to EBV infection and supported a type II latent EBV infection program characteristic of EBV-infected nasopharyngeal carcinoma. The establishment of an efficient method to immortalize primary nasopharyngeal epithelial cells will facilitate the investigation into the role of EBV infection in pathogenesis of nasopharyngeal carcinoma. PMID:24167620

9 CFR 145.72 - Participation.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE LIVESTOCK IMPROVEMENT NATIONAL POULTRY IMPROVEMENT PLAN FOR BREEDING POULTRY Special Provisions for Primary Egg-Type Chicken Breeding Flocks and Products § 145.72 Participation. Participating flocks of primary...

9 CFR 145.82 - Participation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE LIVESTOCK IMPROVEMENT NATIONAL POULTRY IMPROVEMENT PLAN FOR BREEDING POULTRY Special Provisions for Primary Meat-Type Chicken Breeding Flocks and Products § 145.82 Participation. Participating flocks of primary...

9 CFR 145.72 - Participation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE LIVESTOCK IMPROVEMENT NATIONAL POULTRY IMPROVEMENT PLAN FOR BREEDING POULTRY Special Provisions for Primary Egg-Type Chicken Breeding Flocks and Products § 145.72 Participation. Participating flocks of primary...

9 CFR 145.82 - Participation.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE LIVESTOCK IMPROVEMENT NATIONAL POULTRY IMPROVEMENT PLAN FOR BREEDING POULTRY Special Provisions for Primary Meat-Type Chicken Breeding Flocks and Products § 145.82 Participation. Participating flocks of primary...

9 CFR 145.82 - Participation.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE LIVESTOCK IMPROVEMENT NATIONAL POULTRY IMPROVEMENT PLAN FOR BREEDING POULTRY Special Provisions for Primary Meat-Type Chicken Breeding Flocks and Products § 145.82 Participation. Participating flocks of primary...

9 CFR 145.82 - Participation.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE LIVESTOCK IMPROVEMENT NATIONAL POULTRY IMPROVEMENT PLAN FOR BREEDING POULTRY Special Provisions for Primary Meat-Type Chicken Breeding Flocks and Products § 145.82 Participation. Participating flocks of primary...

9 CFR 145.82 - Participation.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE LIVESTOCK IMPROVEMENT NATIONAL POULTRY IMPROVEMENT PLAN FOR BREEDING POULTRY Special Provisions for Primary Meat-Type Chicken Breeding Flocks and Products § 145.82 Participation. Participating flocks of primary...

9 CFR 145.72 - Participation.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE LIVESTOCK IMPROVEMENT NATIONAL POULTRY IMPROVEMENT PLAN FOR BREEDING POULTRY Special Provisions for Primary Egg-Type Chicken Breeding Flocks and Products § 145.72 Participation. Participating flocks of primary...

9 CFR 145.72 - Participation.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE LIVESTOCK IMPROVEMENT NATIONAL POULTRY IMPROVEMENT PLAN FOR BREEDING POULTRY Special Provisions for Primary Egg-Type Chicken Breeding Flocks and Products § 145.72 Participation. Participating flocks of primary...

9 CFR 145.72 - Participation.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE LIVESTOCK IMPROVEMENT NATIONAL POULTRY IMPROVEMENT PLAN FOR BREEDING POULTRY Special Provisions for Primary Egg-Type Chicken Breeding Flocks and Products § 145.72 Participation. Participating flocks of primary...

Genetics Home Reference: Joubert syndrome

MedlinePlus

... sensing the physical environment and in chemical signaling. Primary cilia are important for the structure and function of many types of cells, including brain cells (neurons) and certain cells in the kidneys and liver. Primary cilia are also necessary for the perception ...

Primary site and regional lymph node involvement are independent prognostic factors for early-stage extranodal nasal-type natural killer/T cell lymphoma.

PubMed

Niu, Shao-Qing; Yang, Yong; Li, Yi-Yang; Wen, Ge; Wang, Liang; Li, Zhi-Ming; Wang, Han-Yu; Zhang, Lu-Lu; Xia, Yun-Fei; Zhang, Yu-Jing

2016-04-04

Nasal-type extranodal natural killer/T-cell lymphoma (ENKTCL) originates primarily in the nasal cavity or extra-nasal sites within the upper aerodigestive tract. However, it is unclear whether the primary site can serve as an independent prognostic factor or whether the varying clinical outcomes observed with different primary sites can be attributed merely to their propensities of regional lymph node involvement. The aim of this study was to investigate the prognostic implications of the primary site and regional lymph node involvement in patients with early-stage nasal-type ENKTCL. To develop a nomogram, we reviewed the clinical data of 215 consecutively diagnosed patients with early-stage nasal-type ENKTCL who were treated in Sun Yat-sen University Cancer Center with chemotherapy and radiotherapy between 2000 and 2011. The predictive accuracy and discriminative ability of the nomogram were determined using a concordance index (C-index) and calibration curve. The 5-year overall survival (OS) and progression-free survival (PFS) rates of patients with nasal ENKTCL were higher than those of patients with extra-nasal ENKTCL (OS: 68.2% vs. 46.0%, P = 0.030; PFS: 53.4% vs. 26.6%, P = 0.010). The 5-year OS and PFS rates of patients with Ann Arbor stage IE ENKTCL were higher than those of patients with Ann Arbor stage IIE ENKTCL (OS: 66.3% vs. 59.2%, P = 0.003; PFS: 51.4% vs. 40.3%, P = 0.009). Multivariate analysis showed that age >60 years, ECOG performance status score ≥2, elevated lactate dehydrogenase (LDH) level, extra-nasal primary site, and regional lymph node involvement were significantly associated with lower 5-year OS rate; age >60 years, elevated LDH level, extra-nasal primary site, and regional lymph node involvement were significantly associated with lower 5-year PFS rate. The nomogram included the primary site and regional lymph node involvement based on multivariate analysis. The calibration curve showed good agreement between the predicted and actual 5-year OS and PFS rates, and the C-indexes of the nomogram for the OS and PFS rates were 0.697 and 0.634, respectively. The primary site and regional lymph node involvement are independent prognostic factors for early-stage ENKTCL treated with chemotherapy followed by definitive radiotherapy.

Study protocol of EMPOWER participatory action research (EMPOWER-PAR): a pragmatic cluster randomised controlled trial of multifaceted chronic disease management strategies to improve diabetes and hypertension outcomes in primary care.

PubMed

Ramli, Anis S; Lakshmanan, Sharmila; Haniff, Jamaiyah; Selvarajah, Sharmini; Tong, Seng F; Bujang, Mohamad-Adam; Abdul-Razak, Suraya; Shafie, Asrul A; Lee, Verna K M; Abdul-Rahman, Thuhairah H; Daud, Maryam H; Ng, Kien K; Ariffin, Farnaza; Abdul-Hamid, Hasidah; Mazapuspavina, Md-Yasin; Mat-Nasir, Nafiza; Miskan, Maizatullifah; Stanley-Ponniah, Jaya P; Ismail, Mastura; Chan, Chun W; Abdul-Rahman, Yong R; Chew, Boon-How; Low, Wilson H H

2014-09-13

Chronic disease management presents enormous challenges to the primary care workforce because of the rising epidemic of cardiovascular risk factors. The chronic care model was proven effective in improving chronic disease outcomes in developed countries, but there is little evidence of its effectiveness in developing countries. The aim of this study was to evaluate the effectiveness of the EMPOWER-PAR intervention (multifaceted chronic disease management strategies based on the chronic care model) in improving outcomes for type 2 diabetes mellitus and hypertension using readily available resources in the Malaysian public primary care setting. This paper presents the study protocol. A pragmatic cluster randomised controlled trial using participatory action research is underway in 10 public primary care clinics in Selangor and Kuala Lumpur, Malaysia. Five clinics were randomly selected to provide the EMPOWER-PAR intervention for 1 year and another five clinics continued with usual care. Each clinic consecutively recruits type 2 diabetes mellitus and hypertension patients fulfilling the inclusion and exclusion criteria over a 2-week period. The EMPOWER-PAR intervention consists of creating/strengthening a multidisciplinary chronic disease management team, training the team to use the Global Cardiovascular Risks Self-Management Booklet to support patient care and reinforcing the use of relevant clinical practice guidelines for management and prescribing. For type 2 diabetes mellitus, the primary outcome is the change in the proportion of patients achieving HbA1c < 6.5%. For hypertension without type 2 diabetes mellitus, the primary outcome is the change in the proportion of patients achieving blood pressure < 140/90 mmHg. Secondary outcomes include the proportion of patients achieving targets for serum lipid profile, body mass index and waist circumference. Other outcome measures include medication adherence levels, process of care and prescribing patterns. Patients' assessment of their chronic disease care and providers' perceptions, attitudes and perceived barriers in care delivery and cost-effectiveness of the intervention are also evaluated. Results from this study will provide objective evidence of the effectiveness and cost-effectiveness of a multifaceted intervention based on the chronic care model in resource-constrained public primary care settings. The evidence should instigate crucial primary care system change in Malaysia. ClinicalTrials.gov NCT01545401.

Rat coronaviruses infect rat alveolar type I epithelial cells and induce expression of CXC chemokines

PubMed Central

Miura, Tanya A.; Wang, Jieru; Holmes, Kathryn V.; Mason, Robert J.

2007-01-01

We analyzed the ability of two rat coronavirus (RCoV) strains, sialodacryoadenitis virus (SDAV) and Parker’s RCoV (RCoV-P), to infect rat alveolar type I cells and induce chemokine expression. Primary rat alveolar type II cells were transdifferentiated into the type I cell phenotype. Type I cells were productively infected with SDAV and RCoV-P, and both live virus and UV-inactivated virus induced mRNA and protein expression of three CXC chemokines: CINC-2, CINC-3, and LIX, which are neutrophil chemoattractants. Dual immunolabeling of type I cells for viral antigen and CXC chemokines showed that chemokines were expressed primarily by uninfected cells. Virus-induced chemokine expression was reduced by the IL-1 receptor antagonist, suggesting that IL-1 produced by infected cells induces uninfected cells to express chemokines. Primary cultures of alveolar epithelial cells are an important model for the early events in viral infection that lead to pulmonary inflammation. PMID:17804032

Binary progenitors of supernovae

NASA Astrophysics Data System (ADS)

Trimble, V.

1984-12-01

Among the massive stars that are expected to produce Type II, hydrogen-rich supernovae, the presence of a close companion can increase the main sequence mass needed to yield a collapsing core. In addition, due to mass transfer from the primary to the secondary, the companion enhances the stripping of the stellar hydrogen envelope produced by single star winds and thereby makes it harder for the star to give rise to a typical SN II light curve. Among the less massive stars that may be the basis for Type I, hydrogen-free supernovae, a close companion could be an innocent bystander to carbon detonation/deflagration in the primary. It may alternatively be a vital participant which transfers material to a white dwarf primary and drives it to explosive conditions.

Primary hyperparathyroidism and proximal renal tubular acidosis: Report of two cases

PubMed Central

Siddiqui, Abdullah A.; Wilson, Douglas R.

1972-01-01

Two cases of primary hyperparathyroidism due to single parathyroid adenomas presented with the additional feature of hyperchloremic acidosis. The defect in urinary acidification responsible was not of the distal or gradient-limited type since both patients could lower urine pH adequately. However, there was a defect of bicarbonate reabsorption, an abnormality referred to as the proximal or rate-limited type of renal tubular acidosis. It is suggested that this defect represents an exaggeration of the physiological effect of parathormone on bicarbonate reabsorption and may be responsible for the frequent finding of hyperchloremia in association with primary hyperparathyroidism as well as for the urinary bicarbonate-wasting associated with a variety of causes of secondary hyperparathyroidism. PMID:5012229

Forecasting of primary energy consumption data in the United States: A comparison between ARIMA and Holter-Winters models

NASA Astrophysics Data System (ADS)

Rahman, A.; Ahmar, A. S.

2017-09-01

This research has a purpose to compare ARIMA Model and Holt-Winters Model based on MAE, RSS, MSE, and RMS criteria in predicting Primary Energy Consumption Total data in the US. The data from this research ranges from January 1973 to December 2016. This data will be processed by using R Software. Based on the results of data analysis that has been done, it is found that the model of Holt-Winters Additive type (MSE: 258350.1) is the most appropriate model in predicting Primary Energy Consumption Total data in the US. This model is more appropriate when compared with Holt-Winters Multiplicative type (MSE: 262260,4) and ARIMA Seasonal model (MSE: 723502,2).

Mycorrhiza of plants in different vegetation types in tropical ecosystems of Xishuangbanna, southwest China.

PubMed

Muthukumar, T; Sha, Liqing; Yang, Xiaodong; Cao, Min; Tang, Jianwei; Zheng, Zheng

2003-12-01

We examined plants growing in four tropical vegetation types (primary forest, secondary forest, limestone forest and a slash and burn field) in Xishuangbanna, southwest China for mycorrhizal associations. Of the 103 plant species examined (belonging to 47 families), 81 had arbuscular mycorrhizal (AM) associations, while three species possessed orchid mycorrhiza. AM colonization levels ranged between 6% and 91% and spore numbers ranged between 1.36 spores and 25.71 spores per 10 g soil. Mean AM colonization level was higher in primary and secondary forest species than in plant species from limestone forests and a slash and burn field. In contrast, mean AM fungal spore numbers of the primary and limestone forest were lower than in the secondary forest or the slash and burn field. AM fungal spores belonging to Glomus and Acaulospora were the most frequent in soils of Xishuangbanna. AM fungal colonization and spore numbers were significantly correlated to each other and were significantly influenced by vegetation type.

Centaurus X-3. [early x-ray binary star spectroscopy

NASA Technical Reports Server (NTRS)

Hutchings, J. B.; Cowley, A. P.; Crampton, D.; Van Paradus, J.; White, N. E.

1979-01-01

Spectroscopic observations of Krzeminski's star at dispersions 25-60 A/mm are described. The primary is an evolved star of type O6-O8(f) with peculiarities, some of which are attributable to X-ray heating. Broad emission lines at 4640A (N III), 4686 A(He II) and H-alpha show self-absorption and do not originate entirely from the region near the X-ray star. The primary is not highly luminous (bolometric magnitude about -9) and does not show signs of an abnormally strong stellar wind. The X-ray source was 'on' at the time of optical observations. Orbital parameters are presented for the primary, which yield masses of 17 + or - 2 and 1.0 + or - 3 solar masses for the stars. The optical star is undermassive for its luminosity, as are other OB-star X-ray primaries. The rotation is probably synchronized with the orbital motion. The distance to Cen X-3 is estimated to be 10 + or - 1 kpc. Basic data for 12 early-type X-ray primaries are discussed briefly

In situ observation of ultrasonic cavitation-induced fragmentation of the primary crystals formed in Al alloys.

PubMed

Wang, Feng; Tzanakis, Iakovos; Eskin, Dmitry; Mi, Jiawei; Connolley, Thomas

2017-11-01

The cavitation-induced fragmentation of primary crystals formed in Al alloys were investigated for the first time by high-speed imaging using a novel experimental approach. Three representative primary crystal types, Al 3 Ti, Si and Al 3 V with different morphologies and mechanical properties were first extracted by deep etching of the corresponding Al alloys and then subjected to ultrasonic cavitation processing in distilled water. The dynamic interaction between the cavitation bubbles and primary crystals was imaged in situ and in real time. Based on the recorded image sequences, the fragmentation mechanisms of primary crystals were studied. It was found that there are three major mechanisms by which the primary crystals were fragmented by cavitation bubbles. The first one was a slow process via fatigue-type failure. A cyclic pressure exerted by stationary pulsating bubbles caused the propagation of a crack pre-existing in the primary crystal to a critical length which led to fragmentation. The second mechanism was a sudden process due to the collapse of bubbles in a passing cavitation cloud. The pressure produced upon the collapse of the cloud promoted rapid monotonic crack growth and fast fracture in the primary crystals. The third observed mechanism was normal bending fracture as a result of the high pressure arising from the collapse of a bubble cloud and the crack formation at the branch connection points of dendritic primary crystals. The fragmentation of dendrite branches due to the interaction between two freely moving dendritic primary crystals was also observed. A simplified fracture analysis of the observed phenomena was performed. The specific fragmentation mechanism for the primary crystals depended on their morphology and mechanical properties. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Genetics Home Reference: blepharophimosis, ptosis, and epicanthus inversus syndrome

MedlinePlus

... features. Type I is also associated with an early loss of ovarian function (primary ovarian insufficiency) in women, which causes their menstrual periods to become less frequent and eventually stop before age 40. Primary ovarian insufficiency can lead to difficulty ...

[The OPTIMISE study (Optimal Type 2 Diabetes Management Including Benchmarking and Standard Treatment]. Results for Luxembourg].

PubMed

Michel, G

2012-01-01

The OPTIMISE study (NCT00681850) has been run in six European countries, including Luxembourg, to prospectively assess the effect of benchmarking on the quality of primary care in patients with type 2 diabetes, using major modifiable vascular risk factors as critical quality indicators. Primary care centers treating type 2 diabetic patients were randomized to give standard care (control group) or standard care with feedback benchmarked against other centers in each country (benchmarking group). Primary endpoint was percentage of patients in the benchmarking group achieving pre-set targets of the critical quality indicators: glycated hemoglobin (HbAlc), systolic blood pressure (SBP) and low-density lipoprotein (LDL) cholesterol after 12 months follow-up. In Luxembourg, in the benchmarking group, more patients achieved target for SBP (40.2% vs. 20%) and for LDL-cholesterol (50.4% vs. 44.2%). 12.9% of patients in the benchmarking group met all three targets compared with patients in the control group (8.3%). In this randomized, controlled study, benchmarking was shown to be an effective tool for improving critical quality indicator targets, which are the principal modifiable vascular risk factors in diabetes type 2.

T-Cell Tropism of Simian Varicella Virus during Primary Infection

PubMed Central

Ouwendijk, Werner J. D.; Mahalingam, Ravi; de Swart, Rik L.; Haagmans, Bart L.; van Amerongen, Geert; Getu, Sarah; Gilden, Don; Osterhaus, Albert D. M. E.; Verjans, Georges M. G. M.

2013-01-01

Varicella-zoster virus (VZV) causes varicella, establishes a life-long latent infection of ganglia and reactivates to cause herpes zoster. The cell types that transport VZV from the respiratory tract to skin and ganglia during primary infection are unknown. Clinical, pathological, virological and immunological features of simian varicella virus (SVV) infection of non-human primates parallel those of primary VZV infection in humans. To identify the host cell types involved in virus dissemination and pathology, we infected African green monkeys intratracheally with recombinant SVV expressing enhanced green fluorescent protein (SVV-EGFP) and with wild-type SVV (SVV-wt) as a control. The SVV-infected cell types and virus kinetics were determined by flow cytometry and immunohistochemistry, and virus culture and SVV-specific real-time PCR, respectively. All monkeys developed fever and skin rash. Except for pneumonitis, pathology produced by SVV-EGFP was less compared to SVV-wt. In lungs, SVV infected alveolar myeloid cells and T-cells. During viremia the virus preferentially infected memory T-cells, initially central memory T-cells and subsequently effector memory T-cells. In early non-vesicular stages of varicella, SVV was seen mainly in perivascular skin infiltrates composed of macrophages, dendritic cells, dendrocytes and memory T-cells, implicating hematogenous spread. In ganglia, SVV was found primarily in neurons and occasionally in memory T-cells adjacent to neurons. In conclusion, the data suggest the role of memory T-cells in disseminating SVV to its target organs during primary infection of its natural and immunocompetent host. PMID:23675304

Caries and salivary status in young adults with type 1 diabetes.

PubMed

Edblad, E; Lundin, S A; Sjödin, B; Aman, J

2001-01-01

The aim of this study was to evaluate the salivary status, prevalence of caries and the status of primary dentition, when primary teeth were exfoliated, in 41 patients, 18-24 years of age, with type 1 diabetes since childhood in comparison with age- and sex-matched non-diabetic controls. The blood glucose and glycosylated haemoglobin concentration (HbA1c), dosage of daily insulin and retinal fundus photography was recorded for the diabetic group. According to the concentration of HbA1c, the diabetic patients were divided into well and poorly controlled groups. The study was based on three intra-oral photos, dental examination including intra-oral radiographs, flow rate and buffering capacity of the saliva and amount of Streptococcus mutans and Lactobacilli. Retrospective data regarding the primary dentition was found in the dental files of each patient, and are based on the last registration for respective tooth before exfoliation. The patients with type 1 diabetes, without any relationship to metabolic control, displayed more initial buccal caries compared to healthy controls (p<0.01). No significant differences concerning the status of saliva (neither flow rate, buffering capacity nor amount of Streptococcus mutans and Lactobacilli), manifest caries or the status of the primary dentition were seen. We conclude that initial, but not manifest caries seems to be overrepresented in young adults with type 1 diabetes. These patients, thus, need more intense efforts regarding dental health care to prevent the development from initial to manifest caries.

Low-carbohydrate diets for type 1 diabetes mellitus: A systematic review.

PubMed

Turton, Jessica L; Raab, Ron; Rooney, Kieron B

2018-01-01

Type 1 diabetes is an autoimmune condition characterised by pancreatic beta cell destruction and absolute insulin deficiency. The strongest predictor of diabetes complications is glycaemic control and achieving HbA1c ≤ 7.0% is the primary management target. However, standard treatment appears to be lacking and adjunctive strategies require consideration. A systematic review was conducted to examine the effect of low-carbohydrate diets on type 1 diabetes management. Four databases were searched from inception until 28 March 2017: MEDLINE; CINAHL; Cochrane Library; and EMBASE. All primary studies containing a methods section (excluding cross-sectional) were included. Reports had to quantitatively measure the effect(s) of a dietary intervention or observed intake over at least two weeks where carbohydrate is below 45% total energy in adults and/or children with type 1 diabetes. The primary outcome was HbA1c and secondary outcomes were severe hypoglycaemia, total daily insulin, BMI, quality of life and mean daily glucose. Seventy-nine full-text articles were assessed for eligibility and nine were included (two randomised controlled trials, four pre-post interventions, two case-series, one case-report). Eight studies reported a mean change in HbA1c with a low-carbohydrate diet. Of these, four reported a non-significant change (P ≥ 0.05) and three reported statistically significant reductions (P < 0.05). Two studies reported severe hypoglycaemia, five reported total insulin, three reported BMI, and one reported blood glucose. Due to the significant heterogeneity of included studies, an overall effect could not be determined. This review presents all available evidence on low-carbohydrate diets for type 1 diabetes and suggests an urgent need for more primary studies.

vif-negative human immunodeficiency virus type 1 persistently replicates in primary macrophages, producing attenuated progeny virus.

PubMed Central

Chowdhury, I H; Chao, W; Potash, M J; Sova, P; Gendelman, H E; Volsky, D J

1996-01-01

The vif gene of human immunodeficiency virus type 1 (HIV-1) is required for efficient infection of primary T lymphocytes. In this study, we investigated in detail the role of vif in productive infection of primary monocyte-derived macrophages (MDM). Viruses carrying missense or deletion mutations in vif were constructed on the background of the monocytotropic recombinant NLHXADA-GP. Using MDM from multiple donors, we found that vif mutants produced in complementing or partially complementing cell lines were approximately 10% as infectious as wild-type virus when assayed for incomplete, complete, and circularized viral DNA molecules by quantitative PCR amplification or for viral core antigen p24 production by enzyme-linked immunosorbent assay. We then determined the structure and infectivity of vif mutant HIV-1 by using MDM exclusively both for virus production and as targets for infection. Biosynthetic labeling and immunoprecipitation analysis of sucrose cushion-purified vif-negative HIV-1 made in MDM revealed that the virus had reduced p24 content compared with wild-type HIV-1. Cell-free MDM-derived vif mutant HIV-1 was infectious in macrophages as determined by the synthesis and maintenance of full-length viral DNA and by the produc- tion of particle-associated viral RNA, but its infectivity was approximately 2,500-fold lower than that of wild-type virus whose titer was determined in parallel by measurement of the viral DNA burden. MDM infected with MDM-derived vif-negative HIV-1 were able to transmit the virus to uninfected MDM by cocultivation, confirming the infectiousness of this virus. We conclude that mutations in vif significantly reduce but do not eliminate the capacity of HIV-1 to replicate and produce infectious progeny virus in primary human macrophages. PMID:8764044

vif-negative human immunodeficiency virus type 1 persistently replicates in primary macrophages, producing attenuated progeny virus.

PubMed

Chowdhury, I H; Chao, W; Potash, M J; Sova, P; Gendelman, H E; Volsky, D J

1996-08-01

The vif gene of human immunodeficiency virus type 1 (HIV-1) is required for efficient infection of primary T lymphocytes. In this study, we investigated in detail the role of vif in productive infection of primary monocyte-derived macrophages (MDM). Viruses carrying missense or deletion mutations in vif were constructed on the background of the monocytotropic recombinant NLHXADA-GP. Using MDM from multiple donors, we found that vif mutants produced in complementing or partially complementing cell lines were approximately 10% as infectious as wild-type virus when assayed for incomplete, complete, and circularized viral DNA molecules by quantitative PCR amplification or for viral core antigen p24 production by enzyme-linked immunosorbent assay. We then determined the structure and infectivity of vif mutant HIV-1 by using MDM exclusively both for virus production and as targets for infection. Biosynthetic labeling and immunoprecipitation analysis of sucrose cushion-purified vif-negative HIV-1 made in MDM revealed that the virus had reduced p24 content compared with wild-type HIV-1. Cell-free MDM-derived vif mutant HIV-1 was infectious in macrophages as determined by the synthesis and maintenance of full-length viral DNA and by the produc- tion of particle-associated viral RNA, but its infectivity was approximately 2,500-fold lower than that of wild-type virus whose titer was determined in parallel by measurement of the viral DNA burden. MDM infected with MDM-derived vif-negative HIV-1 were able to transmit the virus to uninfected MDM by cocultivation, confirming the infectiousness of this virus. We conclude that mutations in vif significantly reduce but do not eliminate the capacity of HIV-1 to replicate and produce infectious progeny virus in primary human macrophages.

Walking Away from Type 2 diabetes: a cluster randomized controlled trial.

PubMed

Yates, T; Edwardson, C L; Henson, J; Gray, L J; Ashra, N B; Troughton, J; Khunti, K; Davies, M J

2017-05-01

This study aimed to investigate whether an established behavioural intervention, Walking Away from Type 2 Diabetes, is effective at promoting and sustaining increased walking activity when delivered within primary care. Cluster randomized controlled trial involving 10 general practices recruited from Leicestershire, UK, in 2009-2010. Eight hundred and eight (36% female) individuals with a high risk of Type 2 diabetes mellitus, identified through a validated risk score, were included. Participants in five practices were randomized to Walking Away from Type 2 Diabetes, a pragmatic 3-h group-based structured education programme incorporating pedometer use with annual follow-on refresher sessions. The primary outcome was accelerometer assessed ambulatory activity (steps/day) at 12 months. Longer term maintenance was assessed at 24 and 36 months. Results were analysed using generalized estimating equation models, accounting for clustering. Complete accelerometer data for the primary outcome were available for 571 (71%) participants. Increases in ambulatory activity of 411 steps/day [95% confidence interval (CI): 117, 704] and self-reported vigorous-intensity physical activity of 218 metabolic equivalent min/week (95% CI: 6, 425) at 12 months were observed in the intervention group compared with control; differences between groups were not sustained at 36 months. No differences between groups were observed for markers of cardiometabolic health. Replacing missing data with multiple imputation did not affect the results. A pragmatic low-resource group-based structured education programme with pedometer use resulted in modest increases in ambulatory activity compared with control conditions after 12 months when implemented within a primary care setting to those at high risk of Type 2 diabetes mellitus; however, the results were not maintained over 36 months. © 2016 Diabetes UK.

Evaluation of the need for longitudinal median joints in bridge decks on dual structures.

DOT National Transportation Integrated Search

2015-09-01

The primary objective of this project was to determine the effect of bridge width on deck cracking in bridges. Other parameters, : such as bridge skew, girder spacing and type, abutment type, pier type, and number of bridge spans, were also studied. ...

Efficient Transformation of Primary Human Mesenchymal Stromal Cells by Adenovirus Early Region 1 Oncogenes.

PubMed

Speiseder, Thomas; Hofmann-Sieber, Helga; Rodríguez, Estefanía; Schellenberg, Anna; Akyüz, Nuray; Dierlamm, Judith; Spruss, Thilo; Lange, Claudia; Dobner, Thomas

2017-01-01

Previous observations that human amniotic fluid cells (AFC) can be transformed by human adenovirus type 5 (HAdV-5) E1A/E1B oncogenes prompted us to identify the target cells in the AFC population that are susceptible to transformation. Our results demonstrate that one cell type corresponding to mesenchymal stem/stroma cells (hMSCs) can be reproducibly transformed by HAdV-5 E1A/E1B oncogenes as efficiently as primary rodent cultures. HAdV-5 E1-transformed hMSCs exhibit all properties commonly associated with a high grade of oncogenic transformation, including enhanced cell proliferation, anchorage-independent growth, increased growth rate, and high telomerase activity as well as numerical and structural chromosomal aberrations. These data confirm previous work showing that HAdV preferentially transforms cells of mesenchymal origin in rodents. More importantly, they demonstrate for the first time that human cells with stem cell characteristics can be completely transformed by HAdV oncogenes in tissue culture with high efficiency. Our findings strongly support the hypothesis that undifferentiated progenitor cells or cells with stem cell-like properties are highly susceptible targets for HAdV-mediated cell transformation and suggest that virus-associated tumors in humans may originate, at least in part, from infections of these cell types. We expect that primary hMSCs will replace the primary rodent cultures in HAdV viral transformation studies and are confident that these investigations will continue to uncover general principles of viral oncogenesis that can be extended to human DNA tumor viruses as well. It is generally believed that transformation of primary human cells with HAdV-5 E1 oncogenes is very inefficient. However, a few cell lines have been successfully transformed with HAdV-5 E1A and E1B, indicating that there is a certain cell type which is susceptible to HAdV-mediated transformation. Interestingly, all those cell lines have been derived from human embryonic tissue, albeit the exact cell type is not known yet. We show for the first time the successful transformation of primary human mesenchymal stromal cells (hMSCs) by HAdV-5 E1A and E1B. Further, we show upon HAdV-5 E1A and E1B expression that these primary progenitor cells exhibit features of tumor cells and can no longer be differentiated into the adipogenic, chondrogenic, or osteogenic lineage. Hence, primary hMSCs represent a robust and novel model system to elucidate the underlying molecular mechanisms of adenovirus-mediated transformation of multipotent human progenitor cells. Copyright © 2016 American Society for Microbiology.

Habitability in Binary Systems: The Role of UV Reduction and Magnetic Protection

NASA Astrophysics Data System (ADS)

Clark, Joni; Mason, P. A.; Zuluaga, J. I.; Cuartas, P. A.; Bustamonte, S.

2013-06-01

The number of planets found in binary systems is growing rapidly and the discovery of many more planets in binary systems appears inevitable. We use the newly refined and more restrictive, single star habitable zone (HZ) models of Kopparapu et al. (2013) and include planetary magnetic protection calculations in order to investigate binary star habitability. Here we present results on circumstellar or S-type planets, which are planets orbiting a single star member of a binary. P-type planets, on the other hand, orbit the center of mass of the binary. Stable planetary orbits exist in HZs for both types of binaries as long as the semi-major axis of the planet is either greater than (P-type) or less than (S-type) a few times the semi-major axis of the binary. We define two types of S-type binaries for this investigation. The SA-type is a circumstellar planet orbiting the binary’s primary star. In this case, the limits of habitability are dominated by the primary being only slightly affected by the presence of the lower mass companion. Thus, the SA-type planets have habitability characteristics, including magnetic protection, similar to single stars of the same type. The SB-type is a circumstellar planet orbiting the secondary star in a wide binary. An SB-type planet needs to orbit slightly outside the secondary’s single star HZ and remain within the primary’s single star HZ at all times. We explore the parameter space for which this is possible. We have found that planets lying in the combined HZ of SB binaries can be magnetically protected against the effects of stellar winds from both primary and secondary stars in a limited number of cases. We conclude that habitable conditions exist for a subset of SA-type, and a smaller subset of SB-type binaries. However, circumbinary planets (P-types) provide the most intriguing possibilities for the existence of complex life due to the effect of synchronization of binaries with periods in the 20-30 day range which allows for planets with significant magnetic protection.

Self Efficacy and Some Demographic Variables as Predictors of Occupational Stress among Primary School Teachers in Delta State of Nigeria

ERIC Educational Resources Information Center

Akpochafo, G. O.

2014-01-01

This study investigated self efficacy and some demographic variables as predictors of occupational stress among primary school teachers in Delta State. Three hypotheses were formulated to guide the study. The study adopted a descriptive survey design that utilized an expost-facto research type. A sample of one hundred and twenty primary school…

The Pattern of Electronic Game Use and Related Bodily Discomfort in Hong Kong Primary School Children

ERIC Educational Resources Information Center

Lui, Donald P. Y.; Szeto, Grace P. Y.; Jones, Alice Y. M.

2011-01-01

The present study examined the usage pattern of electronic game devices among primary school children in Hong Kong. Commonly used types of games devices were grouped into three main categories: large-screen/TV-based games, small handheld game devices and active game devices. A survey was conducted among 476 students in a local primary school, with…

An Evaluation of the Effectiveness of the New Primary School Mathematics Curriculum in Practice

ERIC Educational Resources Information Center

Gomleksiz, Mehmet Nuri; Bulut, Ilhami

2007-01-01

The aim of this study is to determine and compare the views of primary school teachers on the implementation and effectiveness of the new primary school mathematics curriculum. For that aim, a 32-item Likert-type Mathematics Curriculum Scale was developed. The reliability of the scale was tested through Cronbach Alpha (0.98), Spearman-Brown (0.93)…

Influence of age and fall type on head injuries in infants and toddlers

PubMed Central

Ibrahim, Nicole G.; Wood, Joanne; Margulies, Susan S.; Christian, Cindy W.

2011-01-01

Age-based differences in fall type and neuroanatomy in infants and toddlers may affect clinical presentations and injury patterns. Objective Our goal is to understand the influence of fall type and age on injuries to help guide clinical evaluation. Design/Setting/Participants Retrospectively, 285 children 0–48 months with accidental head injury from a fall and brain imaging between 2000–2006 were categorized by age (infant=<1 year and toddler=1–4 years) and fall type: low (≤3 ft), intermediate (>3 and <10 ft), high height falls (≥10 ft) and stair falls. Outcome Measures Clinical manifestations were noted and head injuries separated into primary (bleeding) and secondary (hypoxia, edema). The influence of age and fall type on head injuries sustained was evaluated. Results Injury patterns in children <4 yrs varied with age. Despite similar injury severity scores, infants sustained more skull fractures than toddlers (71% v. 39%). Of children with skull fractures, 11% had no evidence of scalp/facial soft tissue swelling. Of the patients with primary intracranial injury, 30% had no skull fracture and 8% had neither skull fracture nor cranial soft tissue injury. Low height falls resulted in primary intracranial injury without soft tissue or skull injury in infants (6%) and toddlers (16%). Conclusions Within a given fall type, age-related differences in injuries exist between infants and toddlers. When interpreting a fall history, clinicians must consider the fall type and influence of age on resulting injury. For young children, intracranial injury is not always accompanied by external manifestations of their injury. PMID:22079853

Ovarian Germ Cell Tumors Treatment

MedlinePlus

... Tube, & Primary Peritoneal Cancer Screening Research Ovarian Germ Cell Tumors Treatment (PDQ®)–Patient Version Treatment Option Overview ... types of treatment for patients with ovarian germ cell tumors. Different types of treatment are available for ...

Fuelwood production and sources in Wisconsin, 1981.

Treesearch

James E. Blyth; E. Michael Bailey; W. Brad Smith

1984-01-01

Discusses and analyzes the 1981 Wisconsin fuelwood production from roundwood and primary wood-using mill residue. Analyzes production by geographic area, type of producer, species, landowner class, type of land, and tree source.

Effect of cage design, supplemental posterior instrumentation and approach on primary stability of a lumbar interbody fusion - A biomechanical in vitro study.

PubMed

Schmoelz, Werner; Sandriesser, Sabrina; Loebl, Oded; Bauer, Marlies; Krappinger, Dietmar

2017-10-01

There are various techniques and approaches for lumbar interbody fusion differing in access, cage type and type of supplemental posterior instrumentation. While a transforaminal access usually includes a hemifacetectomy, the facet joint can be preserved with a more lateral extraforaminal access. The supplemental posterior instrumentation required for both fusion techniques is still debated. The purpose of the present study was to compare primary stability of the two accesses for two different cage types with none, unilateral and bilateral supplemental posterior instrumentation. Six monosegmental lumbar functional spinal units (FSUs) were included in each of the two groups, and subjected to a flexibility test. As cages, a newly designed cage was compared to a standard cage in the following states: (a) native, (b) stand-alone cage, (c) bilateral internal fixator, (d) unilateral internal fixator, (e) unilateral facetectomy+bilateral internal fixator, (f) unilateral facetectomy+unilateral internal fixator and (g) unilateral facetectomy with stand-alone cage. For comparison the range of motion was normalized to the native state and the effects of the facetectomy, cage type, and supplemental instrumentation was compared. Within the subject comparison showed a significantly higher flexibility for the unilateral facetectomy in all motion directions (p<0.001). In between subject comparison showed a significant effect of cage type on flexibility in flexion/extension (p=0.002) and lateral bending (p=0.028) but not in axial rotation (p=0.322). The type of supplemental posterior fixation had a significant effect on the flexibility in all motion directions (stand-alone>unilateral fixator>bilateral fixator). Cage design and approach type are affecting the primary stability of lumbar interbody fusion procedures while the type of posterior instrumentation is the most influencing factor. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hashimoto's thyroiditis with heterogeneous antithyrotropin receptor antibodies: unique epitopes may contribute to the regulation of thyroid function by the antibodies.

PubMed

Akamizu, T; Kohn, L D; Hiratani, H; Saijo, M; Tahara, K; Nakao, K

2000-06-01

Blocking-type TSH-binding inhibitor Igs (TBIIs) are known to cause hypothyroidism and an atrophic thyroid gland in patients with primary myxedema. They can block the activity of thyroid-stimulating antibodies (TSAbs) in Graves' patients as well as the activity of TSH. The majority of the epitopes for these blocking-type TBIIs have been, and are shown herein, to be present on the C-terminal region of the extracellular domain of the human TSH receptor (TSHR), whereas those for Graves' TSAbs are on the N-terminus. We report on a patient with Hashimoto's thyroiditis who suffered from mild hypothyroidism and a moderately sized goiter. Her serum had a potent blocking-type TBII and a weak TSAb in human and porcine TSHR systems. Using human TSHR/lutropin-CG receptor chimeras, we determined that the functional epitope of her blocking-type TBII was uniquely present on the N-terminal, rather than the C-terminal, region of the extracellular domain of the TSHR, unlike the case for blocking-type TBIIs in primary myxedema patients. The epitope of her TSAb was also unusual. Although the functional epitopes of most TSAbs are known to involve the N-terminal region of the receptor, her TSAb epitope did not seem to be present solely on the N- or C-terminus of the extracellular domain of the receptor. Blocking-type TBIIs from patients with primary myxedema blocked her TSAb activity as well as stimulation by TSH; her blocking-type TBII was able to only partially block her TSAb. In contrast, her blocking-type TBII almost completely blocked TSAbs from Graves' patients. Thus, we suggest that the unique epitopes of this patient's heterogeneous population of TSH receptor antibodies, at least in part, contribute to regulation of her thyroid function.

Distribution of Porphyromonas gingivalis fimA genotypes in primary endodontic infections.

PubMed

Rôças, Isabela N; Siqueira, José F

2010-03-01

Long fimbriae (FimA) are important virulence factors of Porphyromonas gingivalis. Based on the diversity of the fimA gene, this species is classified into 6 genotypes. This study surveyed samples from primary endodontic infections for the presence of these P. gingivalis fimA variants. Genomic DNA isolated from samples taken from 25 root canals of teeth with chronic apical periodontitis and 25 aspirates from acute apical abscess was used as template in polymerase chain reaction (PCR) assays directed toward the detection of the different P. gingivalis fimA genotypes. Porphyromonas gingivalis was detected by a 16S rRNA gene-based PCR in 36% of the total number of cases sampled (44% of chronic apical periodontitis and 28% of abscess aspirates). In cases of chronic apical periodontitis, P. gingivalis variant type IV was the most prevalent (24%), followed by types I (20%), II (16%), and III (8%). In acute abscess samples, variant type II was the most prevalent (12%), followed by types III and IV (8% of each) and type I (4%). Combinations of up to 3 different genotypes were detected in a few cases. No single fimA genotype variant or combination thereof was significantly associated with symptoms. Overall, fimA types IV (16%), II (14%), and I (12%) were the most prevalent. Findings demonstrated that different P. gingivalis fimA genotypes can be present in primary endodontic infections. Copyright 2010 Mosby, Inc. All rights reserved.

Characterization and prevalence of cataracts in Labrador Retrievers in The Netherlands.

PubMed

Kraijer-Huver, Ingrid M G; Gubbels, Ed J; Scholten, Janneke; Djajadiningrat-Laanen, Sylvia C; Boevé, Michael H; Stades, Frans C

2008-10-01

To assess the prevalence and distribution of types of cataract, investigate the effects of selective breeding on cataract development, and identify the relationship between posterior polar cataract and other types of cortical cataracts in Labrador Retrievers in The Netherlands. 9,017 Labrador Retrievers. Records of 18,283 ophthalmic examinations performed by veterinary ophthalmologists from 1977 through 2005 were reviewed. There were 522 dogs affected by hereditary cataracts in 1 or both eyes without progressive retinal atrophy (PRA) and 166 PRA-affected dogs with cataracts. These cataracts were divided into 3 groups: posterior polar (triangular) cataract, extensive immature and mature cataract, and a miscellaneous group. Dogs with PRA were analyzed separately. From 1980 through 2000, the prevalence of hereditary cataracts was stable at 8%. The prevalence of cataracts in offspring of cataract-affected dogs was significantly increased, compared with the prevalence in offspring of nonaffected dogs. The distribution of types of cataract was significantly different between dogs with primary cataracts and PRA-affected dogs. Dogs with posterior polar (triangular) cataracts produced affected offspring with the same distribution of types of cataracts as the entire population of primary cataract-affected dogs. Cataract development in the Labrador Retriever population in The Netherlands appears to be a predominantly genetic disorder. Posterior polar (triangular) cataracts appear to be related to other types of hereditary cataract. Although there is no conclusive evidence, it seems valid to continue exclusion of all Labrador Retrievers affected by any type of primary cataract from breeding.

Deep lateral wall orbital decompression following strabismus surgery in patients with Type II ophthalmic Graves' disease.

PubMed

Ellis, Michael P; Broxterman, Emily C; Hromas, Alan R; Whittaker, Thomas J; Sokol, Jason A

2018-01-10

Surgical management of ophthalmic Graves' disease traditionally involves, in order, orbital decompression, followed by strabismus surgery and eyelid surgery. Nunery et al. previously described two distinct sub-types of patients with ophthalmic Graves' disease; Type I patients exhibit no restrictive myopathy (no diplopia) as opposed to Type II patients who do exhibit restrictive myopathy (diplopia) and are far more likely to develop new-onset worsening diplopia following medial wall and floor decompression. Strabismus surgery involving extra-ocular muscle recession has, in turn, been shown to potentially worsen proptosis. Our experience with Type II patients who have already undergone medial wall and floor decompression and strabismus surgery found, when additional decompression is necessary, deep lateral wall decompression (DLWD) appears to have a low rate of post-operative primary-gaze diplopia. A case series of four Type II ophthalmic Graves' disease patients, all of whom had already undergone decompression and strabismus surgery, and went on to develop worsening proptosis or optic nerve compression necessitating further decompression thereafter. In all cases, patients were treated with DLWD. Institutional Review Board approval was granted by the University of Kansas. None of the four patients treated with this approach developed recurrent primary-gaze diplopia or required strabismus surgery following DLWD. While we still prefer to perform medial wall and floor decompression as the initial treatment for ophthalmic Graves' disease, for proptosis following consecutive strabismus surgery, DLWD appears to be effective with a low rate of recurrent primary-gaze diplopia.

PACAP receptor pharmacology and agonist bias: analysis in primary neurons and glia from the trigeminal ganglia and transfected cells

PubMed Central

Walker, C S; Sundrum, T; Hay, D L

2014-01-01

Background and Purpose A major challenge in the development of new medicines targeting GPCRs is the ability to quantify drug action in physiologically relevant models. Primary cell models that closely resemble the clinically relevant in vivo site of drug action are important translational tools in drug development. However, pharmacological studies in these models are generally very limited due to the methodology used. Experimental Approach We used a neuropeptide system to demonstrate the applicability of using highly sensitive signalling assays in primary cells. We quantified the action of pituitary adenylate cyclase-activating peptide (PACAP)-38, PACAP-27 and vasoactive intestinal polypeptide in primary cultures of neurons and glia derived from rat trigeminal ganglia (TG), comparing our observations to transfected cells. Key Results PACAP-responsive receptors in rat trigeminal neurons, glia and transfected PAC1n receptors were pharmacologically distinct. PACAP-38, but not PACAP-27, activated ERK in glia, while both forms stimulated cellular cAMP production. PACAP(6–38) also displayed cell-type-dependent, agonist-specific, antagonism. Conclusions and Implications The complexity of PACAP pharmacology in the TG may help to direct, more effectively, the development of disease treatments targeting the PACAP receptor. We suggest that these methodologies are broadly applicable to other primary cell types of human or animal origin, and that our approach may allow more thorough characterization of ligand properties in physiologically relevant cell types. PMID:24303997

Ovarian, Fallopian Tube, & Primary Peritoneal Cancer Prevention (PDQ®)—Health Professional Version

Cancer.gov

Ovarian, fallopian tube, and primary peritoneal cancer prevention involves understanding risk and protective factors, and the evidence behind them. Get detailed information about specific risk and protective factors and prevention strategies for these cancer types in this clinician summary.

40 CFR 86.085-2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... designed for rebuild. Rated horsepower generally ranges from 170 to 250. Vehicle body types in this group... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF... area. Primary intended service class means: (a) The primary service application group for which a heavy...

40 CFR 86.085-2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... designed for rebuild. Rated horsepower generally ranges from 170 to 250. Vehicle body types in this group... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF... area. Primary intended service class means: (a) The primary service application group for which a heavy...

40 CFR 86.085-2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... designed for rebuild. Rated horsepower generally ranges from 170 to 250. Vehicle body types in this group... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF... area. Primary intended service class means: (a) The primary service application group for which a heavy...

[Endovascular repair of primary retrograde Stanford type A aortic dissection].

PubMed

Wu, H W; Sun, L; Li, D M; Jing, H; Xu, B; Wang, C T; Zhang, L

2016-10-01

Objective: To summarize the short- and mid-term results on endovascular repair of primary retrograde Stanford type A aortic dissection with an entry tear in distal aortic arch or descending aorta. Methods: Between December 2009 and December 2014, 21 male patients of primary retrograde Stanford type A aortic dissection with a mean age of (52±9) years received endovascular repair in Department of Cardiothoracic Surgery, Jinling Hospital. Among the 21 cases, 17 patients were presented as ascending aortic intramural hematoma, 4 patients as active blood flow in false lumen and partial thrombosis, 8 patients as ulcer on descending aorta combined intramural hematoma in descending aorta, and 13 patients as typical dissection changes. All patients received endovascular stent-graft repair successfully, with 15 cases in acute phase and 6 cases in chronic phase. Results: Cone stent was implanted in 13 cases, while straight stent in 8 cases, including 1 case of left common carotid-left subclavian artery bypass surgery and 1 case of restrictive bare-metal stent implantation. No perioperative stroke, paraplegia, stent fracture or displacement, limbs or abdominal organ ischemia or other severe complications occured, except for tracheotomy in 2 patients. Active blood flow in ascending aorta or aortic arch disappeared, and intramural hematoma started being absorbed on CT angiography images before discharge. All patients were alive during follow-up (6 to 72 months), and intramural hematoma in ascending aorta and aortic arch was absorbed thoroughly. Type Ⅰ endoleak and ulcer expansion were found in 1 patient, and type Ⅳ endoleak in distal stent was found in another one patient. Secondary ascending aortic dissection was found in 1 case two years later, which was cured by hybrid procedure with cardiopulmonary bypass. Conclusion: Endovascular repair of primary retrograde Stanford type A aortic dissection was safe and effective, which correlated with favorable short- and mid-term results.

Mind Your Ps and Qs: The Interrelation between Period (P) and Mass-ratio (Q) Distributions of Binary Stars

NASA Astrophysics Data System (ADS)

Moe, Maxwell; Di Stefano, Rosanne

2017-06-01

We compile observations of early-type binaries identified via spectroscopy, eclipses, long-baseline interferometry, adaptive optics, common proper motion, etc. Each observational technique is sensitive to companions across a narrow parameter space of orbital periods P and mass ratios q = {M}{comp}/M 1. After combining the samples from the various surveys and correcting for their respective selection effects, we find that the properties of companions to O-type and B-type main-sequence (MS) stars differ among three regimes. First, at short orbital periods P ≲ 20 days (separations a ≲ 0.4 au), the binaries have small eccentricities e ≲ 0.4, favor modest mass ratios < q> ≈ 0.5, and exhibit a small excess of twins q > 0.95. Second, the companion frequency peaks at intermediate periods log P (days) ≈ 3.5 (a ≈ 10 au), where the binaries have mass ratios weighted toward small values q ≈ 0.2-0.3 and follow a Maxwellian “thermal” eccentricity distribution. Finally, companions with long orbital periods log P (days) ≈ 5.5-7.5 (a ≈ 200-5000 au) are outer tertiary components in hierarchical triples and have a mass ratio distribution across q ≈ 0.1-1.0 that is nearly consistent with random pairings drawn from the initial mass function. We discuss these companion distributions and properties in the context of binary-star formation and evolution. We also reanalyze the binary statistics of solar-type MS primaries, taking into account that 30% ± 10% of single-lined spectroscopic binaries likely contain white dwarf companions instead of low-mass stellar secondaries. The mean frequency of stellar companions with q > 0.1 and log P (days) < 8.0 per primary increases from 0.50 ± 0.04 for solar-type MS primaries to 2.1 ± 0.3 for O-type MS primaries. We fit joint probability density functions f({M}1,q,P,e)\

Influence of stem design on the primary stability of megaprostheses of the proximal femur.

PubMed

Kinkel, Stefan; Graage, Jan Dennis; Kretzer, Jan Philippe; Jakubowitz, Eike; Nadorf, Jan

2013-10-01

Extended bone defects of the proximal femur can be reconstructed by megaprostheses for which aseptic loosening constitutes one of the major failure modes. The basic requirement for long-term success of endoprostheses is primary stability. We therefore assessed whether sufficient primary stability can be achieved by four different megaprostheses in a standardised bone defect of the proximal femur and whether their different design leads to different fixation patterns. Four different designs of proximal femoral replacements were implanted into 16 Sawbones® after preparing segmental bone defects (AAOS type II). Primary rotational stability was analysed by application of a cyclic torque of ±7 Nm and measuring the relative micromotions between bone and implant at different levels. The main fixation zones and differences of fixation patterns of the stem designs were determined by an analysis of variance. All four implants exhibited micromotions below 150 μm, indicating adequate primary stability. Lowest micromotions for all designs were located near the femoral isthmus. The extent of primary stability and the global implant fixation pattern differed considerably and could be related to the different design concepts. All megaprostheses studied provided sufficient primary stability if the fixation conditions of the femoral isthmus were intact. The design characteristics of the different stems largely determined the extent of primary stability and fixation pattern. Understanding these different fixation types could help the surgeon to choose the most suitable implant if the fixation conditions in the isthmus are compromised.

Comparison of the microhardness of primary and permanent teeth after immersion in two types of carbonated beverages.

PubMed

Haghgou, Hamid R; Haghgoo, Roza; Asdollah, Fatemah Molla

2016-01-01

The consumption of carbonated beverages is one of the etiological factors that cause dental erosion. The purpose of this research was to compare changes in the microhardness of permanent and primary teeth after immersion in two types of carbonated beverages. This investigation was done on 30 healthy permanent molars and 30 healthy primary canines. Each group of primary and permanent teeth was subdivided into three groups of 10 teeth. The teeth was immersed in 40 ml of each of the three beverages for 5 min. One subgroup was immersed in water (as a control). The next was immersed in Lemon Delster and the last subgroup was immersed in Coca-Cola. The microhardness of enamel was measured using the Vickers method before and after immersion. Finally, the data was analyzed by paired t-test, one-way analysis of variance, and t-test. Microhardness reduction in the primary teeth was significant in both the Lemon Delster and Coca-Cola groups (P < 0.05). This reduction was also statistically significant in the permanent teeth (P < 0.05). A comparison of the enamel changes in the primary teeth with permanent teeth after immersion in both beverages showed a greater microhardness reduction in the primary teeth in both the experimental groups. Coca-Cola and Lemon Delster caused a significant reduction of microhardness in tooth enamel. This reduction was greater in primary teeth than in permanent teeth, and was also greater after immersion in Coca-Cola than after immersion in Lemon Delster.

40 CFR 161.20 - Overview.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... (1) The primary purpose of this part is to specify the types and minimum amounts of data and...)(7). (2) This part also specifies the types and minimum amounts of data and information the Agency...) Finally, this part specifies the types and minimum amounts of data and information that an applicant for...

Community governance in primary health care: towards an international Ideal Type.

PubMed

Meads, Geoffrey; Russell, Grant; Lees, Amanda

2017-10-01

Against a global background of increased resource management responsibilities for primary health care agencies, general medical practices, in particular, are increasingly being required to demonstrate the legitimacy of their decision making in market oriented environments. In this context a scoping review explores the potential utility for health managers in primary health care of community governance as a policy concept. The review of recent research suggests that applied learning from international health systems with enhanced approaches to public and patient involvement may contribute to meeting this requirement. Such approaches often characterise local health systems in Latin America and North West Europe where innovative models are beginning to respond effectively to the growing demands on general practice. The study design draws on documentary and secondary data analyses to identify common components of community governance from the countries in these regions, supplemented by other relevant international studies and sources where appropriate. Within a comprehensive framework of collaborative governance the components are aggregated in an Ideal Type format to provide a point of reference for possible adaptation and transferable learning across market oriented health systems. Each component is illustrated with international exemplars from recent organisational practices in primary health care. The application of community governance is considered for the particular contexts of GP led Clinical Commissioning Groups in England and Primary Health Networks in Australia. Some components of the Ideal Type possess potentially powerful negative as well as positive motivational effects, with PPI at practice levels sometimes hindering the development of effective local governance. This highlights the importance of careful and competent management of the growing resources attributed to primary health care agencies, which possess an increasingly diverse range of non-governmental status. Future policy and research priorities are outlined. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Predictors for additional anterior cruciate ligament reconstruction: data from the Swedish national ACL register.

PubMed

Fältström, Anne; Hägglund, Martin; Magnusson, Henrik; Forssblad, Magnus; Kvist, Joanna

2016-03-01

To identify predictors for additional anterior cruciate ligament (ACL) reconstruction. Patients from the Swedish national ACL register who underwent ACL reconstruction between January 2005 and February 2013 (follow-up duration 6-104 months) were included. Cox regression analyses included the following independent variables regarding primary injury: age, sex, time between injury and primary ACL reconstruction, activity at primary injury, concomitant injuries, injury side, graft type, and pre-surgery KOOS and EQ-5D scores. Among ACL reconstruction procedures, 93% involved hamstring tendon (HT) autografts. Graft type did not predict additional ACL reconstruction. Final regression models only included patients with HT autograft (n = 20,824). Of these, 702 had revision and 591 contralateral ACL reconstructions. The 5-year post-operative rates of revision and contralateral ACL reconstruction were 4.3 and 3.8%, respectively. Significant predictors for additional ACL reconstruction were age (fourfold increased rate for <16-year-old patients vs. >35-year-old patients), time between injury and primary surgery (two to threefold increased rate for ACL reconstruction within 0-90 days vs. >365 days), and playing football at primary injury. This study identified younger age, having ACL reconstruction early after the primary injury, and incurring the primary injury while playing football as the main predictors for revision and contralateral ACL reconstruction. This suggests that the rate of additional ACL reconstruction is increased in a selected group of young patients aiming to return to strenuous sports after primary surgery and should be taken into consideration when discussing primary ACL reconstruction, return to sports, and during post-surgery rehabilitation. II.

Regulation of CD4 T cells and their effects on immunopathological inflammation following viral infection.

PubMed

Bhattacharyya, Mitra; Madden, Patrick; Henning, Nathan; Gregory, Shana; Aid, Malika; Martinot, Amanda J; Barouch, Dan H; Penaloza-MacMaster, Pablo

2017-10-01

CD4 T cells help immune responses, but knowledge of how memory CD4 T cells are regulated and how they regulate adaptive immune responses and induce immunopathology is limited. Using adoptive transfer of virus-specific CD4 T cells, we show that naive CD4 T cells undergo substantial expansion following infection, but can induce lethal T helper type 1-driven inflammation. In contrast, memory CD4 T cells exhibit a biased proliferation of T follicular helper cell subsets and were able to improve adaptive immune responses in the context of minimal tissue damage. Our analyses revealed that type I interferon regulates the expansion of primary CD4 T cells, but does not seem to play a critical role in regulating the expansion of secondary CD4 T cells. Strikingly, blockade of type I interferon abrogated lethal inflammation by primary CD4 T cells following viral infection, despite that this treatment increased the numbers of primary CD4 T-cell responses. Altogether, these data demonstrate important aspects of how primary and secondary CD4 T cells are regulated in vivo, and how they contribute to immune protection and immunopathology. These findings are important for rational vaccine design and for improving adoptive T-cell therapies against persistent antigens. © 2017 John Wiley & Sons Ltd.

Prevalence of ADHD in primary school children in Vinh Long, Vietnam.

PubMed

Pham, Hoai Danh; Nguyen, Huu Bao Han; Tran, Diep Tuan

2015-10-01

Attention-deficit hyperactivity disorder (ADHD) is the most common behavioral disorder in children. It affects not only the subjects but also their families and society. The purpose of this study was to determine the prevalence of ADHD in primary school children in South Vietnam, especially Vinh Long province. Children were chosen randomly from primary schools in Vinh Long from February to March in 2009 in a cross-sectional study to determine the prevalence of ADHD using the ADHD Rating Scale-IV for parents/caregivers and teachers. ADHD Rating Scale-IV was based on DSM-IV for diagnosis of ADHD. A total of 600 children were chosen and 1200 reports were collected from parents/caregivers and teachers. The prevalence rate of ADHD was 7.7%. The rates of the predominantly inattentive type, predominantly hyperactive type and combined type were 1.7%, 5% and 1%, respectively. The difference in sex was not significant across all subtypes. The prevalence of ADHD in urban children was 2.2-fold that in rural children. The prevalence of ADHD in primary school children in Vinh Long, southern Vietnam, is in the same range as other regions in the world. Therefore, awareness of ADHD needs to be raised, to ensure suitable psychiatric care for children. © 2015 Japan Pediatric Society.

Assessment of Cell Line Models of Primary Human Cells by Raman Spectral Phenotyping

PubMed Central

Swain, Robin J.; Kemp, Sarah J.; Goldstraw, Peter; Tetley, Teresa D.; Stevens, Molly M.

2010-01-01

Abstract Researchers have previously questioned the suitability of cell lines as models for primary cells. In this study, we used Raman microspectroscopy to characterize live A549 cells from a unique molecular biochemical perspective to shed light on their suitability as a model for primary human pulmonary alveolar type II (ATII) cells. We also investigated a recently developed transduced type I (TT1) cell line as a model for alveolar type I (ATI) cells. Single-cell Raman spectra provide unique biomolecular fingerprints that can be used to characterize cellular phenotypes. A multivariate statistical analysis of Raman spectra indicated that the spectra of A549 and TT1 cells are characterized by significantly lower phospholipid content compared to ATII and ATI spectra because their cytoplasm contains fewer surfactant lamellar bodies. Furthermore, we found that A549 spectra are statistically more similar to ATI spectra than to ATII spectra. The spectral variation permitted phenotypic classification of cells based on Raman spectral signatures with >99% accuracy. These results suggest that A549 cells are not a good model for ATII cells, but TT1 cells do provide a reasonable model for ATI cells. The findings have far-reaching implications for the assessment of cell lines as suitable primary cellular models in live cultures. PMID:20409492

Primary prevention of type 2 diabetes: integrative public health and primary care opportunities, challenges and strategies

PubMed Central

Green, Lawrence W; Brancati, Frederick L; Albright, Ann

2012-01-01

Type 2 diabetes imposes a large and growing burden on the public’s health. This burden, combined with the growing evidence for primary prevention from randomized controlled trials of structured lifestyle programs leads to recommendations to include caloric reduction, increased physical activity and specific assistance to patients in problem solving to achieve modest weight loss as well as pharmacotherapy. These recommendations demand exploration of new ways to implement such primary prevention strategies through more integrated community organization, medical practice and policy. The US experience with control of tobacco use and high blood pressure offers valuable lessons for policy, such as taxation on products, and for practice in a variety of settings, such as coordination of referrals for lifestyle supports. We acknowledge also some notable exceptions to their generalizability. This paper presents possible actions proposed by an expert panel, summarized in Table 1 as recommendations for immediate action, strategic action and research. The collaboration of primary care and public health systems will be required to make many of these recommendations a reality. This paper also provides information on the progress made in recent years by the Division of Diabetes Translation at the US Centers for Disease Control and Prevention (CDC) to implement or facilitate such integration of primary care and public health for primary prevention. PMID:22399542

Global resistance and resilience of primary production following extreme drought are predicted by mean annual precipitation

NASA Astrophysics Data System (ADS)

Stuart-Haëntjens, E. J.; De Boeck, H. J.; Lemoine, N. P.; Gough, C. M.; Kröel-Dulay, G.; Mänd, P.; Jentsch, A.; Schmidt, I. K.; Bahn, M.; Lloret, F.; Kreyling, J.; Wohlgemuth, T.; Stampfli, A.; Anderegg, W.; Classen, A. T.; Smith, M. D.

2017-12-01

Extreme drought is increasing globally in frequency and intensity, with uncertain consequences for the resistance and resilience of key ecosystem functions, including primary production. Primary production resistance, the capacity of an ecosystem to withstand change in primary production following extreme climate, and resilience, the degree to which primary production recovers, vary among and within ecosystem types, obscuring global patterns of resistance and resilience to extreme drought. Past syntheses on resistance have focused climatic gradients or individual ecosystem types, without assessing interactions between the two. Theory and many empirical studies suggest that forest production is more resistant but less resilient than grassland production to extreme drought, though some empirical studies reveal that these trends are not universal. Here, we conducted a global meta-analysis of sixty-four grassland and forest sites, finding that primary production resistance to extreme drought is predicted by a common continuum of mean annual precipitation (MAP). However, grasslands and forests exhibit divergent production resilience relationships with MAP. We discuss the likely mechanisms underlying the mixed production resistance and resilience patterns of forests and grasslands, including different plant species turnover times and drought adaptive strategies. These findings demonstrate the primary production responses of forests and grasslands to extreme drought are mixed, with far-reaching implications for Earth System Models, ecosystem management, and future studies of extreme drought resistance and resilience.

Traumatic dental injuries to primary incisors and the terminal or occlusal plane relationship in Indian preschool children.

PubMed

Shekhar, M G; Mohan, R

2011-03-01

To determine the prevalence of traumatic dental injuries to primary incisors in 3-5 year-old preschool children and to study the relationship between dental injuries and age, gender and terminal plane relation. A cross-sectional study was conducted in 1,126 preschool children aged three to five years enrolled in eleven private and public nursery schools, randomly selected in Chennai, India. Data regarding the age, gender, cause and type of trauma and terminal plane relation were recorded. Maxillary and mandibular primary incisors were examined for traumatic injuries and were recorded according to the method described by Andreasen & Andreasen (1994). Data were analyzed through descriptive analysis and chi-square test. Traumatic injuries to primary incisors were identified in 6.2% of children. No significant gender differences in prevalence were seen (p > 0.05). Enamel fractures (57.3%) dominated amongst the type of injuries. Majority of children who sustained traumatic dental injuries to their primary incisors were associated with mesial step molar relation. Mesial step molar relation may be considered one of the possible predisposing factors to trauma in primary dentition. Further, there is need to intensify oral health education targeted at both parents and teachers at nursery schools to inform them about consequences of primary teeth injuries on permanent dentition and emphasize the importance of prevention of dental injuries in children.

State Electricity Profiles

EIA Publications

2017-01-01

The annual report presents data tables describing the electricity industry in each State. Data include: summary statistics; the 10 largest plants by generating capacity; the top five entities ranked by sector; electric power industry generating capacity by primary energy source; electric power industry generation by primary energy source; utility delivered fuel prices for coal, petroleum, and natural gas; electric power industry emissions estimates; retail sales, revenue, and average retail price by sector; retail electricity sales statistics; and supply and disposition of electricity; net metering counts and capacity by technology and customer type; and advanced metering counts by customer type.

Molecular characterization of primary humic-like substances in fine smoke particles by thermochemolysis-gas chromatography-mass spectrometry

NASA Astrophysics Data System (ADS)

Fan, Xingjun; Wei, Siye; Zhu, Mengbo; Song, Jianzhong; Peng, Ping'an

2018-05-01

In this study, the molecular structures of primary humic-like substances (HULIS) in fine smoke particles emitted from the combustion of biomass materials (including rice straw, corn straw, and pine branches) and coal, and atmospheric HULIS were determined by off-line tetramethylammonium hydroxide thermochemolysis coupled with gas chromatography and mass spectrometry (TMAH-GC/MS). A total of 89 pyrolysates were identified by the thermochemolysis of primary and atmospheric HULIS. The main groups were polysaccharide derivatives, N-containing compounds, lignin derivatives, aromatic acid methyl ester, aliphatic acid methyl ester, and diterpenoid derivatives. Both the type and distribution of pyrolysates among primary HULIS were comparable to those in atmospheric HULIS. This indicates that primary HULIS from combustion processes are important contributors to atmospheric HULIS. Some distinct differences were also observed. The aromatic compounds, including lignin derivatives and aromatic acid methyl ester, were the major pyrolysates (53.0%-84.9%) in all HULIS fractions, suggesting that primary HULIS significantly contributed aromatic structures to atmospheric HULIS. In addition, primary HULIS from biomass burning (BB) contained a relatively high abundance of lignin and polysaccharide derivatives, which is consistent with the large amounts of lignin and cellulose structures contained in biomass materials. Aliphatic acid methyl ester and benzyl methyl ether were prominent pyrolysates in atmospheric HULIS. Moreover, some molecular markers of specific sources were obtained from the thermochemolysis of primary and atmospheric HULIS. For example, polysaccharide derivatives, pyridine and pyrrole derivatives, and lignin derivatives can be used as tracers of fresh HULIS emitted from BB. Diterpenoid derivatives are important markers of HULIS from pine wood combustion sources. Finally, the differences in pyrolysate types and the distributions between primary and atmospheric HULIS suggested that the primary HULIS would undergo many atmospheric processes to reconstruct the macromolecular organic matter in atmospheric aerosols.

Treatment Option Overview (Ovarian Germ Cell Tumors)

MedlinePlus

... Tube, & Primary Peritoneal Cancer Screening Research Ovarian Germ Cell Tumors Treatment (PDQ®)–Patient Version Treatment Option Overview ... types of treatment for patients with ovarian germ cell tumors. Different types of treatment are available for ...

Treatment Options By Stage (Ovarian Germ Cell Tumors)

MedlinePlus

... Tube, & Primary Peritoneal Cancer Screening Research Ovarian Germ Cell Tumors Treatment (PDQ®)–Patient Version Treatment Option Overview ... types of treatment for patients with ovarian germ cell tumors. Different types of treatment are available for ...

Treatment Option Overview (Carcinoma of Unknown Primary)

MedlinePlus

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... cancer cells have places where hormones can attach ( receptors ), drugs, surgery, or radiation therapy are used to ...