Asano, Takeshi; Sudoh, Mariko; Watanabe, Makoto; Fujino, Osamu
Although anemia frequently occurs in poststreptococcal acute glomerulonephritis (PSAGN), severe anemia is rare. We report severe normocytic, normochromic anemia (hematocrit, 19.8%) in PSAGN in a 6-year-old girl with edema, macrohematuria, and proteinuria for 1 month. The potential causes of severe anemia found in this case were: 1) longer duration of massive hematuria from onset of macrohemauria to treatment, 2) a level of erythropoietin much lower than that in cases of iron deficiency anemia, and 3) hemodilution. We speculate that these factors combined to cause an unusual case of severe anemia in PSAGN.
Yoshida, Masahiro; Yamakawa, Hideaki; Yabe, Masami; Ishikawa, Takeo; Takagi, Masamichi; Matsumoto, Kei; Hamaguchi, Akihiko; Ogura, Makoto; Kuwano, Kazuyoshi
We herein report a case of pulmonary renal syndrome with nephritis in a 17-year-old boy with diffuse alveolar hemorrhage (DAH) associated with acute poststreptococcal glomerulonephritis (APSGN). The patient exhibited hemoptysis two weeks after developing impetigo, and DAH was diagnosed on bronchoscopy. Respiratory failure progressed, and high-dose methylprednisolone therapy was administered; the respiratory failure regressed immediately after the onset of therapy. Streptococcus pyogenes was detected in an impetigo culture, and, together with the results of the renal biopsy, a diagnosis of APSGN was made. This case demonstrates the effects of high-dose methylprednisolone therapy in improving respiratory failure.
Horita, Yoshio; Tadokoro, Masato; Taura, Koichi; Suyama, Naofumi; Taguchi, Takashi; Miyazaki, Masanobu; Kohno, Shigeru
We describe a 39-year-old Japanese man with post-streptococcal acute glomerulonephritis (PSAGN) super-imposed on long-term immunoglobulin A nephropathy (IgA-N). The histological findings of the first renal biopsy, done at 21 years of age, revealed mild mesangial proliferative glomerulonephritis with mesangial IgA deposition. Nineteen years later, acute nephritic syndrome with hypocomplementemia and an increasing anti-streptolysin O (ASO) titer developed 2 weeks after the onset of an upper respiratory infection. A second renal biopsy revealed severe segmental endocapillary proliferative and exudative glomerulonephritis, with fibrocellular crescents in about 40% of the glomeruli. Immunofluorescence showed that more C3 than IgA was deposited in the mesangium and that the IgA deposits had decreased. Electron microscopy revealed "hump" electron-dense deposits on the epithelial side of the glomerular basement membrane. These features were consistent with PSAGN superimposed on IgA-N. After 2 weeks of observation, blood pressure, C3 level, and ASO titer had returned to normal, although the persisting nephritic syndrome necessitated steroid therapy. Six months after the onset of the acute nephritic syndrome, the patient remained asymptomatic, except for microhematuria.
Kuniyoshi, Yasutaka; Kamura, Azusa; Yasuda, Sumie; Tashiro, Makoto
Gouty arthritis is uncommon in childhood and adolescence. On the other hand, there has been no report of cases with development of gouty arthritis with post-streptococcal acute glomerulonephritis (PSAGN) in pediatric patients. Here we report the case of a mildly obese 12-year-old boy with PSAGN complicated by gouty arthritis of the left first metatarsophalangeal joint. On follow-up, it was confirmed that as serum C3 level returned to normal, urinary excretion of uric acid increased and serum uric acid level decreased, thereby resolving the burning pain of the left big toe. In this case, not only did renal insufficiency associate with PSAGN but also mild obesity may have led to hyperuricemia and gouty arthritis. In conclusion, clinicians should be aware that PSAGN may be complicated by gouty arthritis in obese pediatric patients.
Cronin, W; Deol, H; Azadegan, A; Lange, K
It is now generally accepted that acute post-streptococcal glomerulonephritis (PSGN) is the consequence of the formation of antigen-antibody-complement complexes on the basement membrane of the glomerulus and that the antigen is of streptococcal origin. In cases of acute PSGN a high titre of specific antibodies to a streptococcal cytoplasmic extract can be found at the very beginning of the disease. This cytoplasmic antigen which we called endostreptosin (ESS) is probably the pathogenetic antigen of glomerulonephritis. It is deposited on the subendothelial side of the basement membrane in the first few days of the disease and is rapidly covered by newly-formed and specific antibody and complement with resultant immune injury causing signs and symptoms of symptomatic but also frequently asymptomatic acute glomerulonephritis. To further characterize and isolate ESS we used immunoaffinity chromatography and Western blotting techniques. PAGE analysis of the affinity-isolated ESS revealed the major component to have a molecular weight of approximately 45 kD. Sera from patients with PSGN or sera of rabbits immunized with affinity-isolated ESS reacted by Western blotting with at least one antigenic component with a molecular weight of approximately 45 kD. Normal human sera or the sera of non-immunized rabbits failed to demonstrate activity against this antigen. The basement membranes of the glomeruli of patients with very early PSGN stain with fluorescein-labelled gammaglobulin of patients with glomerulonephritis. This staining can be prevented when these sera are pre-absorbed with ESS but not by pre-absorption with intact cells or cytoplasmic extracts of other bacteria. Images Fig. 1 Fig. 2 Fig. 3 Fig. 5 PMID:2667818
Rus, Rina R; Toplak, Nataša; Vizjak, Alenka; Mraz, Jerica; Ferluga, Dušan
There are only a few reports of the co-occurrence of acute poststreptococcal glomerulonephritis (APGN) and acute rheumatic fever. We report an unusual case of a 3-year-old boy with nephrotic syndrome and acute renal failure with the transitional need for peritoneal dialysis, biopsy-proven atypical IgA-dominant APGN, and concomitant acute rheumatic fever, successfully treated by steroids. Aggressive treatment with pulses of methylprednisolone proved to be successful and we recommend its use in this type of cases. PMID:26718763
Hisano, Satoshi; Matsushita, Misao; Fujita, Teizo; Takeshita, Morishige; Iwasaki, Hiroshi
The aim of the present study was to elucidate the correlation between complement pathways and clinicopathological findings in post-streptococcal acute glomerulonephritis (PSAGN). Immunohistological staining was performed on renal specimens obtained from 18 patients with PSAGN and 20 controls, using antibodies against IgG, IgA, IgM, C1q, C3c, C4, fibrinogen, factor B, C4-binding protein (C4-bp), C5b-9, CD59, mannose-binding lectin (MBL) and MBL-associated serine protease-1 (MASP-1). Controls showed no deposition of any antibody. In seven patients, glomerular deposits of C3c, C4, factor B, C4-bp, C5b-9, CD59, MBL and MASP-1 were found. In the remaining 11 patients, glomerular deposits of neither C4 nor MBL/MASP-1 were found, and glomerular deposits of C3c, factor B, C5b-9 and CD59 were evident. C4-bp was detected in seven of these 11 patients. Glomerular deposits of fibrinogen were detected in five of seven patients with MBL/MASP-1 deposits and in only two of 11 patients without MBL/MASP-1 deposits. Hematuria was prolonged in three of seven patients with MBL/MASP-1 deposits through follow up, whereas urinalysis was normal in all patients without MBL/MASP-1 deposits. However, the histological indicators were not different between the two groups. To the authors' knowledge this is the first report to show that complement activation through both the alternative and lectin pathways is evident in some patients with PSAGN. Complement activation is promoted in situ in the glomerulus.
Williams, R C; Zabriskie, J B; Mahros, F; Hassaballa, F; Abdin, Z H
Lymphocyte cell-surface markers were examined in forty children with acute rheumatic fever (ARF) and twelve with acute post-streptococal glomerulonephritis (AGN) and compared to thirty-six normal controls of similar age. Cell-surface-marker studies included surface Ig using fluorescein-labelled F(ab)2 anti-F(AB')2, IgG aggregate binding cells, and EAC rosettes. T cells were identified both as 'active' rosettes and total E-binding cells. Proportions and absolute numbers of cells bearing surface Ig and Fc receptors were elevated in subjects with AGN (Pless than0-01-0-5), whereas proportions of cells producing EAC rosettes were diminished. Patients with acute rheumatic carditis or chorea showed a substantial elevation in proportions and numbers of active T-cell rosettes (Pless than0-01). Streptococcal antigen binding cells capable of forming rosettes with autologous cells coated with group A streptococcal membranes were elevated in the acute phase of both rheumatic fever and acute glomerulonephritis(Pless than0-01). The majority of such cells were removed by passage over insolubilized Ig-anti-IgG columns and appeared to be B cells. PMID:300301
Bottinor, Wendy; Fronk, Daniel; Sadruddin, Salima; Foster, Harriet; Patel, Nilang; Prinz, Andreas; Jovin, Ion S
Pericarditis in conjunction with nephritis is an uncommon clinical scenario with a broad differential diagnosis. We present the case of a 58-year-old male who developed nephritis and pericardial effusion with tamponade physiology. In the following, we discuss the differential diagnosis for concomitant nephritis and pericarditis and discuss the work-up performed on our patient. We also review the epidemiology of postinfectious glomerulonephritis in adults and describe previous cases of Streptococcus pyogenes pericarditis in the literature. PMID:27826373
Chiu, Chih-Yung; Huang, Yhu-Chering; Wong, Kin-Sun; Hsia, Shao-Hsuan; Lin, Chi-Jen; Lin, Tzou-Yien
Acute poststreptococcal glomerulonephritis(PSGN) is characterized by an abrupt onset of edema,hypertension, and hematuria. Although the association of pulmonary edema with acute glomerulonephritis has been established, it is uncommon for children with PSGN to present with respiratory distress due to pulmonary edema. We encountered six such patients, aged 6-10 years, during a 10-month period. The demographic data, clinical manifestations, laboratory data, radiographic pictures, and clinical courses were collected. All patients presented to the primary pediatricians with dyspnea and alveolar infiltrates with bilateral pleural effusions on plain chest radiographs that were misinterpreted as pneumonia initially. The diagnosis of PSGN was de-layed until the awareness of the presence of pulmonary edema complicating PSGN. Subsequent urinalysis and blood pressure measurement all showed microscopic hematuria and hypertension. Elevated serum antistreptolysin 0 titers and depressed serum complement C3 levels confirmed the diagnosis of PSGN. Two patients progressed to respiratory failure because of a delayed diagnosis of PSGN. All patients recovered without sequelae following appropriate diuresis and antihypertensive therapy. We conclude that in preschool and school-age children who present with dyspneic respirations and a chest radiograph showing radiographic features of pulmonary edema, proper evaluation including blood pressure recording and urinalysis should be performed immediately. Prompt diagnosis and early therapy of PSGNmay avoid mortality and unnecessary therapeutic intervention.
Ulusoy, Sukru; Ozkan, Gulsum; Sonmez, Mehmet; Mungan, Sevdegül; Köseoğlu, Rahman; Cansız, Muammer; Kaynar, Kübra
In addition to being the main cause of glomerulonephritis in children, poststreptococcal glomerulonephritis (PSGN) has recently been shown in older patients, especially those with malignancy or diabetes mellitus. The pathogenesis of PSGN has been ascribed to activation of complement 3 (C3) of the alternative complement cascade which, along with immunoglobulin (Ig) G and IgM deposits, is observed in renal tissue. Our aim here is to discuss the probable causes of PSGN developing with isolated IgM deposition in a 52-year-old patient with essential thrombocytosis followed-up over the previous 3.5 years. These characteristics make our case the first to be reported in the literature.
Kanai, Hiroaki; Sawanobori, Emi; Koizumi, Keiichi; Ohashi, Ryuji; Higashida, Kosuke
Post-streptococcal glomerulonephritis (PSGN) generally has a good renal prognosis, and immunosuppressive therapies are not needed. However, a few patients present with severe acute kidney injury and extensive crescent formations. The etiology of such patients is not well known, and involvement of anti-neutrophil cytoplasmic antibodies is rarely reported. A 9-year-old girl with rapidly progressive nephritic syndrome was diagnosed with PSGN. A biopsy showed diffuse crescentic glomerulonephritis with immunoglobulin G and C3 deposits; moreover, humps were observed on electron microscopy. After she was administered methylprednisolone pulse therapy and intravenous cyclophosphamide, followed by prednisolone and azathioprine therapy, her urinary abnormalities improved and renal function normalized. However, the myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) titers gradually increased. We speculated that PSGN may be augmented by increased MPO-ANCA levels. Therefore, the patient is currently being treated with losartan, enalapril, azathioprine, and prednisolone. Although the MPO-ANCA titer remains high, urinary findings show mild proteinuria and her renal function has been norma for 18 months since onset. A progressive clinical course and severe histological findings may indicate the involvement of ANCA in deterioration of condition in patients with PSGN. Furthermore, in such cases immunosuppressive therapies should be considered even in pediatric PSGN.
Sebastian, Alphy A; Ahsan, Auswaf K
Hutchinson-Gilford progeria syndrome is a rare autosomal dominant disorder associated with skin fragility. It is characterized by craniofacial disproportion, delayed dentition, micrognathia, and plucked bird appearance. The genetic defect is mainly de nova mutation in the lamin A gene. This report describes a 16-year-old patient with classical features of progeria along with post-streptococcal glomerulonephritis. The symptoms of hepatomegaly were also present in the patient. The differential diagnoses of this lesion are also discussed in detail in this literature.
El Said, W; Awad, S; Farid, F; Maged, Z; Fattah, F A; El Maghraby, M
Twenty-one cases of acute glomerulonephritis in children with no previous history of renal disease were studied. Urinary infection with a rising titre of serum agglutinins against the organisms isolated from urine was found in 5 cases. No evidence of previous streptococcal infection was found in these cases. In the meantime all 8 cases with post-streptococcal glomerulonephritis remained without bacteriuria. In one case acute glomerulonephritis followed virus hepatitis, and in the remaining 7 cases the cause of glomerulonephritis was unknown. It is suggested that in predisposed patients the bacteria present in urinary infections might act as antigens starting immunologic reactions in the glomeruli, leading to glomerulonephritis. The final proof of this theory awaits immunofluorescence identification of these antigens in the glomeruli.
Underland, Lisa J; Villeda, Gerson A Vallencia; Pal, Abhijeet; Lam, Leslie
Thyroid storm has a high mortality rate and is often associated with a precipitating factor such as intercurrent illness or infection. It is rare in pediatric patients. Cardiac disease in hyperthyroidism mostly manifests itself as tachycardia but more serious cardiac findings have also been described. A 5-year-old male with recent strep throat infection presented with dilated cardiomyopathy, hematuria, and symptoms and lab findings consistent with severe hyperthyroidism. He was diagnosed with thyroid storm secondary to concurrent Graves' disease and poststreptococcal glomerulonephritis (PSGN). After starting the treatment with methimazole and a beta-blocker, his cardiac disease gradually improved and the PSGN resolved over time. There are no specific pediatric criteria for thyroid storm. Adult criteria can be difficult to apply to pediatric cases. Criteria for diagnosis of thyroid storm are less clear for pediatric patients. Dilated cardiomyopathy is a rare cardiac manifestation of hyperthyroidism. PSGN is due to glomerular immune complexes and can complicate group A strep infection. Providers should be aware of cardiac disease as a complication of hyperthyroidism. PSGN should not mechanistically be related to hyperthyroidism but can precipitate the signs of thyroid storm such as hypertension. This association has not been previously reported in the literature.
Kaarthigeyan, K; Vijayalakshmi, A M
The association between hypertensive encephalopathy and cortical blindness in children with acute glomerulonephritis is extremely rare. We report the case of a 9-year old girl who presented with headache, seizures, altered sensorium, hematuria, and transient cortical blindness as a complication of hypertensive encephalopathy which showed complete reversal following normalization of blood pressure and an underlying post-infectious acute glomerulonephritis was revealed.
... following: Decreased urine output Rust-colored urine Swelling (edema), general swelling, swelling of the abdomen, swelling of ... Exams and Tests A physical examination shows swelling (edema), especially in the face. Abnormal sounds may be ...
Kanodia, Kamal V; Vanikar, Aruna V; Kute, Vivek Balkrishna; Trivedi, Hargovind L
Malaria remains a major health problem in many parts of the world leading to high morbidity and mortality related to renal dysfunction and relapsing nature of Plasmodium vivax malaria. Acute renal failure occurs commonly in Plasmodium falciparum malaria, although its rare occurrences have been reported in P. vivax malaria also. We reported a rare case of P. vivax malaria monoinfection associated with acute post infectious glomerulonephritis.
Shimohata, Homare; Higuchi, Takashi; Ogawa, Yujiro; Fujita, Shogo; Nagai, Miho; Imaizumi, Masahiro; Maruyama, Hiroshi; Hirayama, Kouichi; Kobayashi, Masaki
Human parvovirus B19 (HPV B19) infection is well known as a cause of erythema infectiosum in children. Acute glomerulonephritis due to HPVB19 infection is rarely observed in adults. Here, we present the case of a 45-year-old female who showed acute glomerulonephritis induced by HPVB19 infection with various autoantibodies. She had proteinuria (175 mg/g creatinine) and hematuria (20-29 erythrocytes per high-power field) in a urinalysis, and various autoantibodies such as antinuclear antibodies, proteinase-3-antineutrophil cytoplasmic antibodies (PR3-ANCA), antiglomerular basement membrane (GBM) antibodies, and anticardiolipin antibodies in a blood examination. A renal biopsy showed that endocapillary proliferative glomerulonephritis comprised of mononuclear cell infiltration. By using immunofluorescence microscopy, IgG, IgA, IgM, C3, C4, and C1q deposits were detected mainly in glomerular capillaries. Electron-dense deposits were detected in the subendothelial area and mesangial area by using electron microscopy. All symptoms and abnormal laboratory data were self-improved. Our patient's case may provide a clue to the etiology of ANCA-associated vasculitis or lupus nephritis.
Welch, Thomas R
Acute glomerulonephritis (AGN) is a common condition in childhood. Many children with AGN can be managed in the primary care setting. The diagnosis is usually made on the basis of urinary findings, especially the presence of red blood cell casts. One of the most important initial investigations is determining the complement C3 level; hypocomplementemia is most characteristic of post streptococcal AGN, while normocomplementemia is most often seen with IgA nephropathy. Children whose AGN is accompanied by significant hypertension or renal insufficiency should be assessed by a specialist immediately. The presence of serious extrarenal signs or symptoms also merits urgent referral. Otherwise, serial followup in the primary care office is appropriate.
O'Donnell, D; Markowitz, S
Acute glomerulonephritis complicated secondary infection in a patient suffering from traumatic blisters caused by new footwear. This unlikely setting for acute glomerulonephritis was made more interesting by its occurrence in an adult in contrast with its more frequent recognition in a child. The age of the patient and the severity of the local symptoms masked the significance of the initial finding of haematuria until deteriorating renal function indicated the diagnosis of concomitant glomerular disease.
Zhang, Yong; Li, Junxia; Peng, Weihua; Yu, Guoqing; Wang, Liping; Chen, Jian; Zheng, Feng
Postinfectious acute glomerulonephritis (PIGN) may occur after various bacterial and viral infections. Hepatitis B virus (HBV) infection is a cause of chronic glomerulonephritis. We report here 10 cases (ages 7–20 years-old) of chronic HBV carriers with acute glomerulonephritis, with positive glomerular staining of hepatitis B surface antigen, and detectable presence of HBV DNA in the glomeruli. This form of PIGN, HBV-PIGN, has not been previously identified. To further characterize clinical and pathological features of HBV- PIGN, we selected 10 cases of age-matched non-HBV PIGN for comparison. While both HBV associated PIGN and non-HBV PIGN similarly presented as proteinuria, hematuria, and hypertension, there was a trend of higher acute kidney injury and worsened prognosis in HBV-PIGN. 6 months after the onset, 4 patients with HBV associated PIGN did not show improvement from the disease, whereas all patients with non-HBV PIGN had complete or partial recovery. Pathologically, both HBV associated PIGN and non-HBV PIGN showed typical diffuse glomerular endocapillary proliferation, but HBV associated PIGN differed from classical PIGN with much fewer sub-epithelial glomerular “hump-shape” immune complex depositions. In conclusion, we have identified a novel association of HBV infection with acute glomerulonephritis. PMID:27512989
Lu, Zeyuan; Yin, Jianyong; Bao, Hongda; Jiao, Qiong; Wu, Huijuan; Wu, Rui; Xue, Qin; Wang, Niansong; Zhang, Zhigang; Wang, Feng
Introduction IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder that may involve almost each organ or system. IgG4-related kidney disease (IgG4-RKD) refers to renal lesions associated with IgG4-RD. The most frequent morphological type of renal lesions is IgG4-related tubulointerstitial nephritis (IgG4-TIN) which is associated with increased IgG4-positive plasma cell infiltration and interstitial fibrosis. Case Report Herein, we present a rare case with coexisting IgG4-RKD and acute crescent glomerulonephritis with concomitant severe tubulointerstitial lesions instead of classic IgG4-TIN. Conclusion IgG4-RKD and acute crescent glomerulonephritis can occur in the same patient. This case may give us a clearer viewpoint of the disease. PMID:27504450
Nagy, J; Brasch, H; Süle, T; Hámori, A; Deák, G; Ambrus, M
Renal biopsy specimens from 204 patients with glomerulonephritis or nephrotic syndrome have been studied. In ten of the patients not suffering from acute poststreptococcal glomerulonephritis, systemic lupus erythematosus or Schönlein-Henoch syndrome, diffuse, selective mesangial IgA deposition was observed. Clinically, persistent microscopic haematuria, mild proteinuria and, except in one patient, normal renal function were found. Light microscopically the histological picture was dominated by a diffuse or focal increase in volume of the mesangial matrix, and mild mesangial cell proliferation. Exceptionally, there was also crescent formation. Immunofluorescence revealed large IgA, IgG and C3 deposits, as well as small IgM and fibrinogen deposits in the mesangial glomeruli. The authors' assumption that immunocomplexes containing a secretory component might be implicated in the pathomechanism of Berger's disease, could not be proved.
López-Gómez, Juan M.; Rivera, Francisco
Background and objectives: Renal biopsy in acute renal failure of unknown origin provides irreplaceable information for diagnosis, treatment, and prognosis. This study analyzed the frequency and clinicopathologic correlations of renal native biopsied acute renal failure in Spain during the period 1994 through 2006. Design, setting, participants, & measurements: Acute renal failure was defined as a rapid deterioration of glomerular filtration rate, with or without oligoanuria or rapidly progressive renal insufficiency, including acute-on-chronic renal failure. Patients who were younger than 15 yr were considered children, those between 15 and 65 yr adults, and those >65 elderly. Results: Between 1994 and 2006, data on 14,190 native renal biopsies were collected from 112 renal units in Spain. Of these, 16.1% (2281 biopsies) were diagnosed with acute renal failure. The prevalence of the main clinical syndromes was different in the three age groups: Biopsy-confirmed acute renal failure in children was 5.7%, in adults was 12.5%, and in elderly increased significantly to 32.9%. The prevalence of biopsy-confirmed acute renal failure according to cause was as follows: Vasculitis, 23.3%; acute tubulointerstitial nephritis, 11.3%; and crescentic glomerulonephritis types 1 and 2, 10.1%. The prevalence of the different causes differed significantly according to age group. Conclusions: The Spanish Registry of Glomerulonephritis provides useful information about renal histopathology in biopsy-confirmed acute renal failure. The prevalence of vasculitis and crescentic glomerulonephritis is high, especially in elderly patients. These data obtained from a national large registry highlight the value of renal biopsy in undetermined acute renal failure. PMID:18354075
Jardim, H M; Leake, J; Risdon, R A; Barratt, T M; Dillon, M J
Data on patients with crescentic glomerulonephritis (greater than 50% glomeruli with crescents), referred to the Hospital for Sick Children during the past 13 years, were reviewed. Thirty patients (13 male, 17 female) aged 3.7-15.7 years (mean 9.5) were evaluated. Initial clinical features included: oedema (24/30), hypertension (19/30), gross haematuria (15/30), oliguria (15/30) and a decreased glomerular filtration rate (GFR less than 30 ml/min per 1.73 m2) (22/30). Henoch-Schönlein purpura was present in 9 patients, microscopic polyarteritis in 3, polyarteritis nodosa in 1, Wegener's granulomatosis in 1, systemic lupus erythematosus in 1, post-streptococcal glomerulonephritis in 2, mesangiocapillary glomerulonephritis in 7, anti-glomerular basement membrane glomerulonephritis in 2, and 4 were idiopathic. In 10 patients 50%-79% of glomeruli were affected by crescentic changes (group 1) and in the remaining 20, 80% or more (group 2). The crescents were cellular, fibrocellular or fibrous, and the degree of sclerosis was assessed. Patients in both groups were treated with plasma exchange, corticosteroids, anticoagulants, cyclophosphamide and azathioprine in different combinations. On follow-up, 3 patients were dead, 1 was lost to follow-up, 12 were on dialysis/transplant programmes, 4 had a GFR of less than 30 and 10 a GFR of more than 30 ml/min per 1.73 m2. In our experience, 50% progressed to end-stage renal failure. The interval between disease onset and start of treatment was a prognostic factor for outcome. Fibrous crescents were associated with a worse outcome than fibrocellular crescents (P less than 0.05). Outcome was not, however, related to the percentage of glomeruli affected (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Salter, Tracey; Burton, Hannah; Douthwaite, Sam; Newsholme, William; Horsfield, Catherine; Hilton, Rachel
Hepatitis B virus (HBV) presents a risk to patients and staff in renal units. To minimise viral transmission, there are international and UK guidelines recommending HBV immunisation for patients commencing renal replacement therapy (RRT) and HBV surveillance in kidney transplant recipients. We report the case of a 56-year-old male who was immunised against HBV before starting haemodialysis. He received a deceased donor kidney transplant three years later, at which time there was no evidence of HBV infection. After a further six years he developed an acute kidney injury; allograft biopsy revealed an acute thrombotic microangiopathy (TMA) with glomerulitis, peritubular capillaritis, and C4d staining. Due to a "full house" immunoprofile, tests including virological screening were undertaken, which revealed acute HBV infection. Entecavir treatment resulted in an improvement in viral load and kidney function. HBV genotyping demonstrated a vaccine escape mutant, suggesting "past resolved" infection that reactivated with immunosuppression, though posttransplant acquisition cannot be excluded. This is the first reported case of acute HBV infection associated with immune complex mediated glomerulonephritis and TMA. Furthermore, it highlights the importance of HBV surveillance in kidney transplant recipients, which although addressed by UK guidelines is not currently practiced in all UK units.
Burton, Hannah; Douthwaite, Sam; Newsholme, William; Horsfield, Catherine
Hepatitis B virus (HBV) presents a risk to patients and staff in renal units. To minimise viral transmission, there are international and UK guidelines recommending HBV immunisation for patients commencing renal replacement therapy (RRT) and HBV surveillance in kidney transplant recipients. We report the case of a 56-year-old male who was immunised against HBV before starting haemodialysis. He received a deceased donor kidney transplant three years later, at which time there was no evidence of HBV infection. After a further six years he developed an acute kidney injury; allograft biopsy revealed an acute thrombotic microangiopathy (TMA) with glomerulitis, peritubular capillaritis, and C4d staining. Due to a “full house” immunoprofile, tests including virological screening were undertaken, which revealed acute HBV infection. Entecavir treatment resulted in an improvement in viral load and kidney function. HBV genotyping demonstrated a vaccine escape mutant, suggesting “past resolved” infection that reactivated with immunosuppression, though posttransplant acquisition cannot be excluded. This is the first reported case of acute HBV infection associated with immune complex mediated glomerulonephritis and TMA. Furthermore, it highlights the importance of HBV surveillance in kidney transplant recipients, which although addressed by UK guidelines is not currently practiced in all UK units. PMID:27800206
Stratta, Piero; Musetti, Claudio; Barreca, Antonella; Mazzucco, Gianna
The association between acute renal disease and infection has been known since the mid '800s: acute post-infectious glomerulonephritis (PIGN) is a reactive immunological process against the kidney secondary to an infection, classically caused by a Streptococcus. The typical clinical presentation of PIGN is an acute nephritic syndrome with macro- or microscopic hematuria, proteinuria, hypertension, edema and renal function impairment of variable degree. The histology is characterized by an intracapillary glomerular proliferation, but may rarely be associated with an extracapillary proliferation. The classical childhood form is still present nowadays, even with severe cases, in developing countries, while in the last decades it almost disappeared in industrialized countries, where post-infectious GN are often found in elderly patients with multiple comorbidities. These clinical variants are usually related to other infective agents, like Staphylococcus aureus, both methicillin resistant (MRSA) and susceptible, and may be characterized by an IgA-dominant deposition. Kidney biopsy is rarely needed, especially in the child, while in the adult or old patient a biopsy is warranted if there is an atypical presentation or evolution, like rapidly progressive renal failure, absent or delayed function recovery, persisting low C3, nephrotic range proteinuria and persisting high proteinuria. Current therapy strategies rely on culture-guided systemic antibiotics, especially in the old patient, in which MRSA are relatively frequent, support therapy and only in very selected cases on steroids. These latter cases include the rare PIGN with crescents and those with a severe interstitial inflammation.
Pathak, Himanshu; Marshall, Tarnya
A 35-year-old man presented with polyarthritis and constitutional symptoms, and a recent history of multiple tick bites and skin rash on trekking holiday. He did not respond to oral doxycycline and cephalexine for presumed Lyme's disease. Further investigation confirmed strongly positive streptococcal serology. There was absence of clinical or echocardiography evidence of heart involvement and immunological screening for inflammatory arthritis was negative. In the absence of other major Jones criteria for acute rheumatic fever, besides polyarthritis and the serological evidence of a recent streptococcal infection, a diagnosis of post-streptococcal reactive arthritis (PSRA) was also made. He responded well to penicillin therapy and has been started on oral penicillin prophylaxis as per available guidance. As streptococcal infections in the adult population are increasingly reported, it is a timely opportunity to revisit PSRA, and develop comprehensive treatment and antibiotic prophylaxis guidelines. PMID:27520996
Seggie, J; Davies, P G; Ninin, D; Henry, J
Ninety-eight Zimbabweans with glomerulonephritis characterised by nephrotic proteinuria were studied. There was no evidence to implicate Schistosoma mansoni or S. haemotobium in the aetiology, although schistosomiasis was diagnosed in 54 patients in the series. Similarly, Plasmodium malariae proved unimportant as a cause of the nephrotic syndrome, only one patient showing focal segmental glomerulosclerosis which was associated with subclinical quartan malarial infection. Nevertheless, infections were shown to play a major role in the genesis of glomerulonephritis which was associated with beta-haemolytic streptococcal, hepatitis B and syphilitic infection in 45 patients in the series. The major patterns of disease in childhood proved to be membranous glomerulopathy associated with hepatitis B antigenaemia. In young adults post-streptococcal proliferative glomerulonephritis constituted the commonest disease pattern. In older adult patients a miscellany of primary and secondary glomerulonephritides was encountered but proliferative glomerulonephritis, which was both idiopathic and streptococcus-related, predominated.
Daga, Mradul Kumar
Ruptured Sinus of Valsalva (RSOV) is a rarely seen disease condition. RSOV can have varied presentations from being asymptomatic with just a cardiac murmur to profound hypotension. There has been simultaneous occurrence of RSOV with Infective Endocarditis (IE) in literature. Glomerulonephritis has also been reported in approximately 20% patients with IE. Large amount of proteinuria or decline in kidney functions is rarely encountered and mostly this finding has been incidental on routine evaluation. The co-existence of all the three conditions in a single patient is rare. This case was diagnosed to have RSOV with IE and was also diagnosed with post-infectious glomerulonephritis on renal biopsy. Patient was advised corrective cardiac surgery, but due to financial constraints, patient could not be operated and he died. Here, we report for the first time an unusual presence of both RSOV and sub-aortic membrane with IE complicated by glomerulonephritis. PMID:27891383
Krishnamurthy, Sriram; Choudhary, Bharat; Rajesh, Nachiappa Ganesh; Ramesh, Ananthakrishnan; Srinivasan, Sadagopan
An 11-year-old girl with clinical features of Kartagener syndrome presented with signs of acute glomerulonephritis. Blood urea and creatinine were mildly elevated and anti-streptolysin O and C3 levels were normal. Renal biopsy demonstrated mesangial proliferation and direct immunofluorescence showed IgM and C3 deposits. This appears to be the first report of Kartagener syndrome in association with mesangioproliferative glomerulonephritis. The literature is reviewed and the possible mechanisms for this association are discussed.
Kim, Kyung Min; Sung, Kyoung; Yang, Hea Koung; Kim, Seong Heon; Kim, Hye Young; Ban, Gil Ho; Park, Su Eun; Lee, Hyoung Doo
Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal condition characterized by skin rash, fever, eosinophilia, and multiorgan involvement. Various drugs may be associated with this syndrome including carbamazepine, allopurinol, and sulfasalazine. Renal involvement in DRESS syndrome most commonly presents as acute kidney injury due to interstitial nephritis. An 11-year-old boy was referred to the Children's Hospital of Pusan National University because of persistent fever, rash, abdominal distension, generalized edema, lymphadenopathy, and eosinophilia. He previously received vancomycin and ceftriaxone for 10 days at another hospital. He developed acute kidney injury with nephrotic range proteinuria and hypocomplementemia. A subsequent renal biopsy indicated the presence of acute tubular necrosis (ATN) and late exudative phase of postinfectious glomerulonephritis (PIGN). Systemic symptoms and renal function improved with corticosteroid therapy after the discontinuation of vancomycin. Here, we describe a biopsy-proven case of severe ATN that manifested as a part of vancomycin-induced DRESS syndrome with coincident PIGN. It is important for clinicians to be aware of this syndrome due to its severity and potentially fatal nature. PMID:27186222
... salt, and potassium diuretics (medicines that increase urine production) medicines to lower blood pressure (if high blood pressure is a problem) antibiotics (if a bacterial infection is causing glomerulonephritis) steroids ...
Shah, H. H.; Thakkar, J.; Pullman, J. M.; Mathew, A. T.
Fibrillary glomerulonephritis (FGN) is a rare primary glomerular disease that commonly presents clinically with hypertension, proteinuria, microscopic hematuria, and varying degree of renal insufficiency. Histologically, FGN can present with different patterns of glomerular injury, more commonly mesangioproliferative, membranoproliferative, and membranous nephropathy. While crescent formation has been described in some kidney biopsy series of FGN, crescentic glomerulonephritis pattern of glomerular injury has been rarely described. Optimal therapy and outcomes in FGN presenting with crescentic GN is not currently known. We report an adult patient who presented with massive proteinuria and severe renal failure. The kidney biopsy revealed crescentic FGN (C-FGN). The patient remained dialysis dependent despite immunosuppressive therapy. We also briefly review FGN, and the few reported cases of C-FGN that presented as rapidly progressive or advanced renal failure in the literature. PMID:28356674
Elfenbein, I B; Baluarte, H J; Cubillos-Rojas, M; Gruskin, A B; Coté, M; Cornfeld, D
Histologic patterns in the glomerular tufts in "Glomerulonephritis with many crescents" take three main forms: (1) compression and sclerosis of glomeruli, (2) necrotizing glomerulitis, and (3) proliferation with or without exudation. In the third group, histologic differentiation between patients with poststreptococcal glomerulonephritis with many crescents (AGN) and those with nonstreptococcal rapidly progressive glomerulonephritis (RPGN) may be impossible. In a retrospective study, quantitative morphometry of glomeruli effectively separated three patients with AGN from two patients with RPGN after the usual histologic and electron microscopic observations had failed. Parameters studied were areas of tufts and crescents and total number of cells and granulocytes in tufts and crescents. Surface areas of tufts and crescents were separately determined by photographing glomeruli, projecting and tracing outlines of tufts and crescents, and cutting out and weighing the tracings. The cell density of glomerular tufts (cell per 1000-sq. mum. area) was significantly greater in AGN than in RPGN when either total cell densities (17.64 plus or minus 0.41 versus 13.63 plus or minus 0.30) or total cells minus granulocytes (16.39 plus or minus 0.50 versus 12.99 plus or minus 0.52) were compared. The cell density in the tufts was 120 and 70 per cent greater than controls in AGN and RPGN, respectively. Exudation of inflammatory cells is contributory but not the major cause of hypercellularity in AGN. Follow-up studies with biopsies showed marked resolution in two of three patients with AGN, with normal blood urea nitrogen levels and focal scarring in the third, whereas the two patients with RPGN had either extensive scarring and reduced renal function or required chronic hemodialysis.
Mágori, A; Sonkodi, S; Lászik, Z; Mohácsi, G
Diagnosis of glomerulonephritis (GN) is rare among diabetics and few data relevant to this issue can be found in literature. In Institute of Pathology of "Szent-Györgyi Albert" University of Medicine the presence of GN was found in cases during the examination of renal biopsy material of 36 diabetics. All patients have suffered from diabetes mellitus of 2nd type and of less than 10 year existence, requiring no insulin treatment. In 2 cases diffuse diabetic glomerulosclerosis associated with GN. It is emphasized that kidney biopsy and its complex--light and electronmicroscopic and immunhistological--examination are essential to the diagnosis of GN of diabetics.
Chronic glomerulonephritis (GN), which includes focal segmental glomerulosclerosis and proliferative forms of GN such as IgA nephropathy, increases the risk of hypertension. Hypertension in chronic GN is primarily volume dependent, and this increase in blood volume is not related to the deterioration of renal function. Patients with chronic GN become salt sensitive as renal damage including arteriolosclerosis progresses and the consequent renal ischemia causes the stimulation of the intrarenal renin-angiotensin-aldosterone system(RAAS). Overactivity of the sympathetic nervous system also contributes to hypertension in chronic GN. According to the KDIGO guideline, the available evidence indicates that the target BP should be ≤140mmHg systolic and ≤90mmHg diastolic in chronic kidney disease patients without albuminuria. In most patients with an albumin excretion rate of ≥30mg/24 h (i.e., those with both micro-and macroalbuminuria), a lower target of ≤130mmHg systolic and ≤80mmHg diastolic is suggested. The use of agents that block the RAAS system is recommended or suggested in all patients with an albumin excretion rate of ≥30mg/ 24 h. The combination of a RAAS blockade with a calcium channel blocker and a diuretic may be effective in attaining the target BP, and in reducing the amount of urinary protein excretion in patients with chronic GN. PMID:26848302
Aran, Adi; Weiner, Karin; Lin, Ling; Finn, Laurel Ann; Greco, Mary Ann; Peppard, Paul; Young, Terry; Ofran, Yanay; Mignot, Emmanuel
Post-streptococcal autoimmunity affects millions worldwide, targeting multiple organs including the heart, brain, and kidneys. To explore the post-streptococcal autoimmunity spectrum, we used western blot analyses, to screen 310 sera from healthy subjects with (33%) and without (67%) markers of recent streptococcal infections [anti-Streptolysin O (ASLO) or anti-DNAse B (ADB)]. A 58 KDa protein, reacting strongly with post-streptococcal sera, was identified as Protein Disulfide Isomerase (PDI), an abundant protein with pleiotropic metabolic, immunologic, and thrombotic effects. Anti-PDI autoantibodies, purified from human sera, targeted similar epitopes in Streptolysin O (SLO, P51-61) and PDI (P328-338). The correlation between post-streptococcal status and anti-human PDI auto-immunity was further confirmed in a total of 2987 samples (13.6% in 530 ASLO positive versus 5.6% in 2457 ASLO negative samples, p<0.0001). Finally, anti-PDI auto-antibodies inhibited PDI-mediated insulin degradation in vitro (n = 90, p<0.001), and correlated with higher serum insulin (14.1 iu/ml vs. 12.2 iu/ml, n = 1215, p = 0.039) and insulin resistance (Homeostatic Model Assessment (HOMA) 4.1 vs. 3.1, n = 1215, p = 0.004), in a population-based cohort. These results identify PDI as a major target of post-streptococcal autoimmunity, and establish a new link between infection, autoimmunity, and metabolic disturbances. PMID:20886095
Murphy, B F; Gonzales, M F; Ebeling, P; Fairley, K F; Kincaid-Smith, P
Two cases of idiopathic membranous glomerulonephritis associated with acute inflammatory demyelinating polyradiculoneuropathy (Landry-Guillian-Barre syndrome) are described. In both of the patients, the onset of the nephrotic syndrome coincided with the development of severe ascending sensorimotor neuropathy. Although this association has previously been reported in four other isolated cases, it is not generally recognized by nephrologists and may be of significance in the future understanding of the immunopathogenesis of both diseases.
Patel, Mohan P; Kute, Vivek B; Gumber, Manoj R; Gera, Dinesh N; Shah, Pankaj R; Patel, Himanshu V; Trivedi, Hargovind L; Vanikar, Aruna V
Plasmodium vivax infection is increasingly a major public health burden and the second most frequent human malaria. Higher levels of clinical severity and chloroquine resistance are major factors responsible for such increases. Malarial glomerular injury is uncommon and mainly observed in Plasmodium malariae-infected patients. Occasionally, transient immune complex-mediated glomerulonephritis is associated with Plasmodium falciparum infection. Coexistent crescentic glomerulonephritis and vivax malaria have not previously been reported. We report a fatal case of P. vivax malaria, who presented with acute renal failure. P. vivax monoinfection status was diagnosed with peripheral blood smear and rapid antigen test. Further evaluation for renal failure related to systemic illness and immunological markers were inconclusive. He was treated with antimalarial drugs, hemodialysis, and supportive therapy. Renal biopsy performed for nonrecovering renal failure reveled crescentic glomerulonephritis. This case highlights the need to thoroughly search for malaria-associated crescentic glomerulonephritis using renal biopsy after nonrecovering renal failure.
Yuste, Claudia; Rivera, Francisco; Moreno, Juan Antonio; López-Gómez, Juan Manuel
Recent studies suggest a pathogenic role for glomerular haematuria among renal function. However, there is no data on the prevalence of haematuria from a large renal biopsy registry. We analysed the prevalence of gross (GH) and microscopic (mH) haematuria in 19,895 patients that underwent native renal biopsies from the Spanish Registry of Glomerulonephritis. Haematuria’s overall incidence was 63% (GH 8.6% and mH 55.1%), being more frequent in males (64.7% vs. 62.4%). GH was more prevalent in patients <18 years (21.3% vs. 7.7%). The commonest clinical presentation associated with GH was acute kidney injury (31.5%) and IgA Nephropathy (IgAN) (33.6%) was the most frequent histological finding. GH patients showed a significantly (p < 0.05) lower eGFR and proteinuria levels as compared with patients with mH and without haematuria. Moreover, mH was more prevalent in adults (56.3%). Nephrotic syndrome was the commonest clinical presentation in mH patients (32.2%) and IgAN (18.5%) the most frequent histological finding. In conclusion, haematuria, is a frequent urinalysis finding in patients underwent native renal biopsy. The most frequent histological finding in both GH and mH is IgAN. Whereas, GH is more frequent in young males with acute kidney injury, mH is commoner among adults with nephrotic syndrome. PMID:26818712
Yuste, Claudia; Rivera, Francisco; Moreno, Juan Antonio; López-Gómez, Juan Manuel
Recent studies suggest a pathogenic role for glomerular haematuria among renal function. However, there is no data on the prevalence of haematuria from a large renal biopsy registry. We analysed the prevalence of gross (GH) and microscopic (mH) haematuria in 19,895 patients that underwent native renal biopsies from the Spanish Registry of Glomerulonephritis. Haematuria's overall incidence was 63% (GH 8.6% and mH 55.1%), being more frequent in males (64.7% vs. 62.4%). GH was more prevalent in patients <18 years (21.3% vs. 7.7%). The commonest clinical presentation associated with GH was acute kidney injury (31.5%) and IgA Nephropathy (IgAN) (33.6%) was the most frequent histological finding. GH patients showed a significantly (p < 0.05) lower eGFR and proteinuria levels as compared with patients with mH and without haematuria. Moreover, mH was more prevalent in adults (56.3%). Nephrotic syndrome was the commonest clinical presentation in mH patients (32.2%) and IgAN (18.5%) the most frequent histological finding. In conclusion, haematuria, is a frequent urinalysis finding in patients underwent native renal biopsy. The most frequent histological finding in both GH and mH is IgAN. Whereas, GH is more frequent in young males with acute kidney injury, mH is commoner among adults with nephrotic syndrome.
Radis, C D; Callis, K P
This report describes a 29-year-old bodybuilder taking anabolic steroids who presented with urinary retention, arthralgias, and peripheral edema, subsequently developed acute lower-extremity paralysis, and was diagnosed as having transverse myelitis and membranous glomerulonephritis secondary to systemic lupus erythematosus (SLE). The association of anabolic steroid use and hyperprolactinemia, and their possible link to the development of SLE, are reviewed.
... due to excess protein in the urine) Swelling (edema) of the face, eyes, ankles, feet, legs, or ... overload, including abnormal heart and lung sounds Swelling ( edema ) Imaging tests that may be done include: Abdominal ...
While antineutrophil cytoplasmic antibody (ANCA) positivity has been documented in some patients with postinfectious glomerulonephritis (PIGN) and is associated with more severe disease, antiphospholipid antibodies (APA) are not known to be a common occurrence. We describe a child with severe acute kidney injury who was noted to have prolonged positivity of both ANCA and APA; a renal biopsy showed noncrescentic immune complex mediated glomerulonephritis with subepithelial deposits compatible with PIGN. He recovered without maintenance immunosuppressive therapy and at last follow-up had normal renal function. We discuss the cooccurrence and implications of ANCA and APA in children with PIGN. PMID:28255306
Miadonna, A; Salmaso, C; Palazzi, P; Elli, A; Braidotti, P; Lambertenghi Deliliers, G
Castleman's disease is an uncommon lymph node disorder which can be associated with renal disease. In this report we describe a patient with fever, weight loss, anorexia, increase in inflammatory proteins, anemia and nephrotic syndrome. Castleman's disease, plasma cell type, was diagnosed by histologic analysis after surgical excision of a pelvic lymph node. The disease was considered localized, since further investigations did not show any other pathologic mass. After resection of the pelvic lymphoid mass, clinical remission of systemic symptoms and laboratory abnormalities was observed, with the exception of the nephrotic syndrome. Renal biopsy was performed and showed a pattern compatible with fibrillary glomerulonephritis. Progressive decline in renal function was observed, despite immunosuppressive therapy.
Peila, Elena; Mortara, Paolo; Cicerale, Alessandro; Pinessi, Lorenzo
We report a case of a 15-year-old boy presenting with sudden attacks of hyperkinetic movements of the limbs, trunk and neck. Clinical features were suggestive of paroxysmal non-kinesigenic dyskinesia, but the elevated antistreptolysin O antibody titre and history of recurrent upper airways infection led us to consider a post-streptococcal syndrome as a possible diagnosis. The patient started therapy with benzathine penicillin, sodium valproate and clonazepam without any significant improvement. A successive psychiatric assessment revealed the presence of a psychogenic movement disorder. Psychodynamic psychotherapy and individual counselling were started with progressive improvement of psychological symptoms and gradual resolution of hyperkinetic episodes, without any recurrence recorded during the follow-up (10 months). PMID:25795754
Peila, Elena; Mortara, Paolo; Cicerale, Alessandro; Pinessi, Lorenzo
We report a case of a 15-year-old boy presenting with sudden attacks of hyperkinetic movements of the limbs, trunk and neck. Clinical features were suggestive of paroxysmal non-kinesigenic dyskinesia, but the elevated antistreptolysin O antibody titre and history of recurrent upper airways infection led us to consider a post-streptococcal syndrome as a possible diagnosis. The patient started therapy with benzathine penicillin, sodium valproate and clonazepam without any significant improvement. A successive psychiatric assessment revealed the presence of a psychogenic movement disorder. Psychodynamic psychotherapy and individual counselling were started with progressive improvement of psychological symptoms and gradual resolution of hyperkinetic episodes, without any recurrence recorded during the follow-up (10 months).
Watson, Gabriella; Jallow, Bintou; Le Doare, Kirsty; Pushparajah, Kuberan; Anderson, Suzanne T
Poststreptococcal complications, such as acute rheumatic fever (ARF) and rheumatic heart disease (RHD), are common in resource-limited settings, with RHD recognised as the most common cause of paediatric heart disease worldwide. Managing these conditions in resource-limited settings can be challenging. We review the investigation and treatment options for ARF and RHD and, most importantly, prevention methods in an African setting.
Reich, Heather N.; Tritchler, David; Cattran, Daniel C.; Eichinger, Felix; Boucherot, Anissa; Henger, Anna; Berthier, Celine C.; Nair, Viji; Cohen, Clemens D.
Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 “albumin-regulated genes” differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n = 25) could be distinguished from those of control subjects (n = 6) based solely upon the expression of these 231 “albumin-regulated genes.” The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that all forms of primary glomerulonephritis (n = 33) can be distinguished from controls (n = 21) based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis. PMID:20976140
Sethi, Sanjeev; Rajkumar, S Vincent
Monoclonal gammopathy is characterized by circulating monoclonal immunoglobulin owing to clonal proliferation of immunoglobulin-producing B lymphocytes or plasma cells. Clonal proliferation of B lymphocytes is seen in B-cell lymphoma/leukemia, and clonal plasma cell proliferation is seen in multiple myeloma and monoclonal gammopathy of undetermined significance. The monoclonal immunoglobulin in the setting of a B-cell or plasma cell disorder can cause a proliferative glomerulonephritis via 2 mechanisms: (1) glomerular deposition of the monoclonal immunoglobulin with activation of the classical pathway of complement (direct mechanism), resulting in an immunoglobulin-positive C3-positive glomerulonephritis, and (2) glomerular deposition of complement factors of the alternative and terminal pathway via inhibition of alternative pathway-regulating proteins by the monoclonal immunoglobulin (indirect mechanism), resulting in immunoglobulin-negative C3-positive glomerulonephritis (C3 glomerulopathy). Evaluation should include serum and urine electrophoresis and immunofixation as well as serum-free light-chain assay. If a monoclonal immunoglobulin is detected on these tests, bone marrow biopsy or imaging is needed to exclude more advanced plasma cell dyscrasia. Evaluation of alternative pathway of complement should be done in patients with Ig-negative C3-positive glomerulonephritis. If monoclonal gammopathy is due to an underlying malignant disease such as myeloma, lymphoma, or chronic lymphocytic leukemia, then specific treatment should be aimed at treating the malignant disease, with the goal of eradicating the clonal cells producing the immunoglobulin. In contrast, if monoclonal gammopathy is due to a monoclonal gammopathy of undetermined significance, treatment options include bortezomib, cyclophosphamide, and dexamethasone for a non-IgM monoclonal immunoglobulin and rituximab alone or in combination with cyclophosphamide and dexamethasone for an IgM monoclonal
Kan'shina, N F; Rykov, V A; Lakhno, P A
Clinico-anatomical data of a rare condition congenital oligomeganephronic renal hypoplasia with a glomerulonephritis as a complication are available for a 13-year-old girl who died of chronic renal failure. Large aglomerular zones consisting of primitive canaliculi in a loose stroma were observed in kidneys that were decreased in size. The glomeruli were few in number, some of them of a large size (2-2.5-fold), firmly attached to the capsule, with pronounced extracapillary proliferation.
Forslund, Terje; Koistinen, Arvo; Anttinen, Jorma; Wagner, Bodo; Miettinen, Marja
We present a patient who had ingested sodium bicarbonate for treatment of alcoholic dyspepsia during forty years at increasing doses. During the last year he had used more than 50 grams daily. He presented with metabolic alkalosis, epileptic convulsions, subdural hematoma, hypertension and rhabdomyolysis with end stage renal failure, for which he had to be given regular intermittent hemodialysis treatment. Untreated hypertension and glomerulonephritis was probably present prior to all these acute incidents. Examination of the kidney biopsy revealed mesangial proliferative glomerulonephritis and arterial wall thickening causing nephrosclerosis together with interstitial calcinosis. The combination of all these pathologic changes might be responsible for the development of progressive chronic renal failure ending up with the need for continuous intermittent hemodialysis treatment.
Forslund, Terje; Koistinen, Arvo; Anttinen, Jorma; Wagner, Bodo; Miettinen, Marja
We present a patient who had ingested sodium bicarbonate for treatment of alcoholic dyspepsia during forty years at increasing doses. During the last year he had used more than 50 grams daily. He presented with metabolic alkalosis, epileptic convulsions, subdural hematoma, hypertension and rhabdomyolysis with end stage renal failure, for which he had to be given regular intermittent hemodialysis treatment. Untreated hypertension and glomerulonephritis was probably present prior to all these acute incidents. Examination of the kidney biopsy revealed mesangial proliferative glomerulonephritis and arterial wall thickening causing nephrosclerosis together with interstitial calcinosis. The combination of all these pathologic changes might be responsible for the development of progressive chronic renal failure ending up with the need for continuous intermittent hemodialysis treatment. PMID:24179353
Yabuuchi, Junko; Suwabe, Tatsuya; Ueno, Toshiharu; Hoshino, Junichi; Sekine, Akinari; Hayami, Noriko; Oguro, Masahiko; Kunisawa, Kyohei; Kawada, Masahiro; Yamanouchi, Masayuki; Sumida, Keiichi; Mizuno, Hiroki; Hasegawa, Eiko; Sawa, Naoki; Takaichi, Kenmei; Ohashi, Kenichi; Fujii, Takeshi; Ubara, Yoshifumi
We report a case of glomerulopathy in a 36-year-old Japanese woman with primary Sjögren syndrome (pSS). The first renal biopsy suggested membranous glomerulonephritis. However, repeat biopsy was performed after 16 years because of increased proteinuria, revealing membranoproliferative glomerulonephritis with mesangial deposits, subendothelial deposits, and subepithelial deposits. Immunofluorescent studies showed predominant deposition of IgG2 and IgG4. This patient was positive for antinuclear antibody and anti-SS-A antibody. Sicca syndrome was confirmed by a positive Schirmer test and positive Rose Bengal test. Therefore, pSS-related glomerulopathy was considered to be the most likely diagnosis. PMID:27904866
Mantan, M.; Sethi, G. R.; Batra, V. V.
Glomerulonephritis develops in about 20% patients with infective endocarditis (IE), but is mostly asymptomatic. Heavy proteinuria or derangement of kidney functions is uncommon. We report here a child with IE and proliferative glomerulonephritis who manifested as significant proteinuria that recovered on treatment with immunosupressants. PMID:24049276
Parker, M G; Atkins, M B; Ucci, A A; Levey, A S
Cytokines have been used in experimental and standard protocols for immune enhancement for cancer. The combination of interleukin-2 and interferon-alpha 2 beta has been used in experimental protocols for metastatic renal cell carcinoma. A man who developed rapidly progressive renal failure after receiving this combination therapy is reported. A renal biopsy revealed a pauci-immune crescentic glomerulonephritis. Antineutrophil cytoplasmic antibodies and antiglomerular basement membrane antibodies were absent. The spectrum of renal disease and potentially related extrarenal manifestations associated with interleukin-2 and inteferon-alpha are reviewed. A pathogenesis of altered cell-mediated immunity, consistent with abnormalities in extrarenal organs after immune enhancement, is proposed.
McAdoo, Stephen P; Bhangal, Gurjeet; Page, Theresa; Cook, H Terence; Pusey, Charles D; Tam, Frederick W K
Spleen tyrosine kinase (SYK) is an important component of the intracellular signaling pathway for various immunoreceptors. Inhibition of SYK has shown promise in preclinical models of autoimmune and glomerular disease. However, the description of SYK expression in human renal tissue, which would be desirable ahead of clinical studies, is lacking. Here we conducted immunohistochemical analysis for total and phosphorylated SYK in biopsy specimens from >120 patients with a spectrum of renal pathologies, including thin basement membrane lesion, minimal change disease, membranous nephropathy, IgA nephropathy, lupus nephritis, ANCA-associated glomerulonephritis, antiglomerular basement membrane disease, and acute tubular necrosis. We found significant SYK expression in proliferative glomerulonephritis and that glomerular expression levels correlated with presenting serum creatinine and histological features of disease activity that predict outcome in IgA nephropathy, lupus nephritis, ANCA-associated glomerulonephritis, and antiglomerular basement membrane disease. SYK was phosphorylated within pathological lesions, such as areas of extracapillary and endocapillary proliferation, and appeared to localize to both infiltrating leucocytes and to resident renal cells within diseased glomeruli. Thus SYK is associated with the pathogenesis of proliferative glomerulonephritides, suggesting that these conditions may respond to SYK inhibitor treatment.
Pillebout, Evangéline; Nochy, Dominique
IgA nephropathy is the primitive glomerulonephritis the most frequently encountered worldwide. In about one case out of three, it is responsible for the progression from progressive renal failure to end-stage renal failure. The pathophysiological mechanisms of this disease which is mediated by immune complexes remain unclear. The presentation, clinical progression and optical microscope aspect of the renal biopsy may widely vary, making any histological classification very difficult. Most therapeutic studies include the patients only on clinical criteria of severity. The only consensual management is that of patients with a nephropathy and mild glomerular lesions and a nephritic syndrome, or with an extracapillar glomerulonephritis and a rapidly progressive renal failure; corticoids are indicated in former cases while corticoids must be combined with immunosuppressive agents in the latter ones. Corticotherapy may be considered in patients with a proteinuria higher than 1g/day without renal failure. In any patient with primitive IgA nephropathy, the overall management used for chronic glomerulopathy must be initiated, including, in case of arterial hypertension or proteinuria, the renin-angiotensin system blockade.
Erlij, Daniel; Calderón, Beatriz; Rivera, Angela; Mella, Cristián; Valladares, Ximena; Roessler, Emilio; Rivera, María Teresa; Méndez, Gonzalo
Paraneoplastic syndromes can be presented in multiple ways, which include endocrinological, hematologic, rheumatologic and nephrologic manifestations. While most of the publications described solid tumors as responsible for these manifestations, hematologic neoplasms are important cause to consider as part of the differential diagnosis. We report the case of a 46 year-old man with seronegative symmetric polyarthritis of large and small joints associated with membranoproliferative glomerulonephritis with deposits of immune complexes and acute impairment of renal function, as part of a paraneoplastic syndrome secondary of a classical Hodgkin lymphoma with bone marrow invasion, which reversed completely with chemotherapy treatment.
Peces, R; Navascués, R A; Baltar, J; Seco, M; Alvarez, J
We report a case of rapidly progressive glomerulonephritis due to antiglomerular basement membrane (anti-GBM) antibodies that progressed to end-stage renal disease in a 35-year-old man who used intranasal cocaine on an occasional basis. In contrast to many prior reports of acute renal failure occurring with cocaine-associated rhabdomyolysis, this patient did not have any evidence of acute muscle damage and myoglobin release. Circulating anti-GBM antibodies and renal biopsy with linear IgG and C3 deposits confirmed the diagnosis of anti-GBM disease. The possibility of anti-GBM must be considered in the differential diagnosis of acute renal failure in cocaine addicts. This unusual combination raises complex questions regarding the pathogenesis of this type of renal injury.
Wagrowska-Danilewicz, M; Danilewicz, M; Fisiak, I; Piskorska, J
We report a case of IgA-dominant postinfectious glomerulonephritis in a 49-year-old man presenting with acute kidney injury, nephrotic range proteinuria and hematuria. He suffered from ischemic heart disease, cardiac insufficiency, mitral regurgitation, tricuspid insufficiency, septal aneurysm and hypertension. Renal biopsy revealed segmental and focal endocapillary and mesangial hypercellularity, and thickening of the glomerular capillary wall. Immunofluorescence showed co-dominant strong coarse granular immunostaining of IgA, IgG and C3 mainly along the glomerular capillary wall. On electron microscopy some large subepithelial hump-shaped deposits were present. In summary, this case demonstrates the presence of a broad spectrum of glomerular histological findings in postinfectious glomerulonephritis.
Al Wakeel, Jamal S; Mitwalli, Ahmed H; Tarif, Nauman; Alam, Awatif A; Hammad, Durdana; Abu-Aisha, Hassan; Memon, Nawaz; Sulimani, Fathia; Askar, Akram; Qudsi, Abdo
Glomerulonephritis (GN) is a major cause of chronic renal failure (CRF). To evaluate the trends and outcome with modern improved treatment strategies, we retrospectively reviewed the clinical records of 120 patients with biopsy proven primary GN at our center from January 1990 to June 2001. All the biopsy specimens were subjected to light, electron and immunofluorescent microscopy. The recorded clinical parameters included the presenting symptoms, blood pressure readings, complete blood count, urinalysis, 24-hr urinary protein excretion, creatinine clearance besides rendered therapy and the outcome. Focal segmental glomerulosclerosis was the most common GN and accounted for 56 (47.6%) cases. The frequency of other GN cases in our study included IgA GN in 21 (17.5%) patients, membranous GN in 20 (16.7%), minimal change disease (MCD) in 13 (10.8%), membranoproliferative GN in 4 (3.3%), post infection in 4 (3.3%) and rapidly progressive glomerulonephritis (RPGN) in 2 (1.7%). The type of nephropathy had great influence on outcome and response to therapy. The deterioration of patients with FSGS was the fastest of the glomerulopathies, and nine (16.1%) patients developed end-stage renal failure (ESRD). MCD and post infection GN had the best outcome. Corticosteroids alone along with supportive medication conferred good results in MCD, while combined therapies of mycophenolate mofetil (MMF) and/or cyclophosphamide with corticosteroids provided better outcomes in the rest of the GN. RPGN responded well to the cyclophosphamide and the patients did not develop ESRD. Hyperuricemia, high serum creatinine and hypertension predicted worse outcomes. The control of blood pressure and glucose, and treatment of hyperuricemia and hypoalbuminemia had salutary effect on the outcome. We conclude that due to the better delivered care the outcome of primary GN has improved over the years. However, FSGS is still the most frequently encountered primary GN and has the worst outcome. In the
Ghosh, Gopal Chandra; Sharma, Brijesh; Katageri, Bhimarey; Bhardwaj, Minakshi
Glomerulonephritis (GN) is an immunological phenomenon in bacterial endocarditis. These may be pauci-immune/vasculitic GN, post-infective GN, and sub-endothelial membranoproliferative glomerulonephritis. Each type of glomerulonephritis usually occurs in isolation. We report a case of infective endocarditis with dual existence of pauci-immune/vasculitic GN and post infective type of GN at the same time.
Danielsen, H; Kornerup, H J; Olsen, S; Posborg, V
310 cases of glomerulonephritis classified morphologically according to the criteria of the WHO were analyzed retrospectively in order to determine the frequency of arterial hypertension. The overall prevalence of arterial hypertension was 61%. Hypertension was most frequent and severe in membranoproliferative and sclerotic glomerulonephritis, but often mild and transient in extracapillary glomerulonephritis. Hypertension usually developed during the early stages of the disease when kidney function was well preserved and in only 16% was hypertension first seen during the uremic stage. No correlation was found between hypertension and the presence of the nephrotic syndrome. During dialysis, hypertension was present in 78%; in 90% of these patients hypertension was "controllable" and in 10% it was "uncontrollable".
Zand, Ladan; Fervenza, Fernando C; Nasr, Samih H; Sethi, Sanjeev
Membranoproliferative glomerulonephritis (MPGN) has been classified based on its pathogenesis into immune complex-mediated and complement-mediated MPGN. The immune complex-mediated type is secondary to chronic infections, autoimmune diseases or monoclonal gammopathy. There is a paucity of data on MPGN associated with autoimmune diseases. We reviewed the Mayo Clinic database over a 10-year period and identified 12 patients with MPGN associated with autoimmune diseases, after exclusion of systemic lupus erythematosus. The autoimmune diseases included rheumatoid arthritis, primary Sjögren's syndrome, undifferentiated connective tissue disease, primary sclerosing cholangitis and Graves' disease. Nine of the 12 patients were female, and the mean age was 57.9 years. C4 levels were decreased in nine of 12 patients tested. The serum creatinine at time of renal biopsy was 2.2 ± 1.0 mg/dl and the urinary protein was 2,850 ± 3,543 mg/24 h. Three patients required dialysis at the time of renal biopsy. Renal biopsy showed an MPGN in all cases, with features of cryoglobulins in six cases; immunoglobulin (Ig)M was the dominant Ig, and both subendothelial and mesangial electron dense deposits were noted. Median follow-up was 10.9 months. Serum creatinine and proteinuria improved to 1.6 ± 0.8 mg/dl and 428 ± 677 mg/24 h, respectively, except in 3 patients with end-stage renal disease. In summary, this study describes the clinical features, renal biopsy findings, laboratory evaluation, treatment and prognosis of MPGN associated with autoimmune diseases.
Jennette, J. C.; Wilkman, A. S.; Falk, R. J.
Anti-neutrophil cytoplasmic autoantibodies (ANCA) react with constituents of neutrophil primary granules and monocyte lysosomes. Indirect immunofluorescence microscopy using alcohol-fixed neutrophils demonstrates two ANCA types: one causing cytoplasmic staining (C-ANCA), and a second causing artifactual perinuclear staining (P-ANCA) that frequently has specificity for myeloperoxidase. Using indirect immunofluorescence microscopy (IIFM) and enzyme immunoassays (EIA), sera from over 300 patients with renal disease, with and without systemic vasculitis, were analyzed. Of 76 patients with pauci-immune glomerulonephritis with crescents or necrosis, 87% had ANCA by IIFM (38% of C-ANCA type, 49% of P-ANCA type), and 78% had ANCA by EIA. Of 55 patients with nonlupus immune complex-mediated glomerulonephritis, only 11% had ANCA by IIFM and 5% had ANCA by EIA. Of 24 patients with anti-GBM antibody-mediated glomerulonephritis, none had ANCA. Renal and extrarenal lesions were studied in 81 patients with ANCA-associated glomerulonephritis. These patients formed a pathologic continuum ranging from renal-limited to widespread systemic vascular injury, including patients with primary crescentic glomerulonephritis, Wegener's granulomatosis, and polyarteritis nodosa. In ANCA-positive patients the frequency of C-ANCA and P-ANCA correlated with disease distribution. P-ANCA was most frequent with renal-limited disease and C-ANCA was most frequent when there was lung and sinus involvement. It is proposed that ANCA are not only useful diagnostic markers, but may also be directly involved in a novel pathogenetic mechanism that is a frequent cause of crescentic glomerulonephritis and systemic necrotizing vasculitis. Images Figure 1 Figure 4 Figure 5 Figure 6 Figure 7 PMID:2683800
Liu, Chih-Hao; Du, Yong; Singh, Manmohan; Wu, Chen; Han, Zhaolong; Li, Jiasong; Chang, Anthony; Mohan, Chandra; Larin, Kirill V
Acute glomerulonephritis caused by antiglomerular basement membrane marked by high mortality. The primary reason for this is delayed diagnosis via blood examination, urine analysis, tissue biopsy, or ultrasound and X-ray computed tomography imaging. Blood, urine, and tissue-based diagnoses can be time consuming, while ultrasound and CT imaging have relatively low spatial resolution, with reduced sensitivity. Optical coherence tomography is a noninvasive and high-resolution imaging technique that provides superior spatial resolution (micrometer scale) as compared to ultrasound and CT. Changes in tissue properties can be detected based on the optical metrics analyzed from the OCT signals, such as optical attenuation and speckle variance. Furthermore, OCT does not rely on ionizing radiation as with CT imaging. In addition to structural changes, the elasticity of the kidney can significantly change due to nephritis. In this work, OCT has been utilized to quantify the difference in tissue properties between healthy and nephritic murine kidneys. Although OCT imaging could identify the diseased tissue, its classification accuracy is clinically inadequate. By combining optical metrics with elasticity, the classification accuracy improves from 76% to 95%. These results show that OCT combined with OCE can be a powerful tool for identifying and classifying nephritis. Therefore, the OCT/OCE method could potentially be used as a minimally invasive tool for longitudinal studies during the progression and therapy of glomerulonephritis as well as complement and, perhaps, substitute highly invasive tissue biopsies. Elastic-wave propagation in mouse healthy and nephritic kidneys.
Kunjal, Ryan; Makary, Raafat; Poenariu, Andreea
Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis rarely affects females of reproductive age. A 28-year-old African American woman presented at 8 weeks of gestation with intractable vomiting attributed to hyperemesis gravidarum. She was found to have acute kidney injury that was unresponsive to vigorous fluid resuscitation and urine sediment examination was suggestive of an underlying glomerulonephritis. Serum c-ANCA and PR3 were elevated and there was no peripheral eosinophilia. During her course she also developed one episode of small volume hemoptysis with right upper lobe infiltrates on CT Chest. There were no cutaneous manifestations of vasculitis or upper respiratory symptoms. Renal biopsy revealed a pauci-immune crescentic glomerulonephritis (PICGN). The diagnosis was consistent with granulomatosis with polyangiitis (GPA). Management initially comprised teratogen sparing agents; steroids, intravenous immunoglobulin; and plasma exchange. The response was suboptimal and she became dependent on daily renal replacement therapy. Ultimately the pregnancy was terminated allowing for traditional treatment approaches with dramatic effect. This is the first case of GPA presenting as PICGN in pregnancy and highlights the challenges of its management. PMID:27293925
Alexopoulos, Efstathios; Gionanlis, Lazaros; Papayianni, Ekaterini; Kokolina, Elizabeth; Leontsini, Maria; Memmos, Dimitrios
Background Small vessel vasculitides are known to follow a devastating course towards end-stage renal disease, unless treated with immunosuppressive regiments. We investigated the value of clinical, histological and immunohistochemical parameters as predictors of outcome at diagnosis in patients with pauci immune necrotizing glomerulonephritis. Methods In 34 patients the percentage and evolution stage of crescents, the presence of glomerular necrosis, the degree or severity of arteriosclerosis, as well as the extent of tubulointerstitial infiltration, interstial fibrosis and tubular atrophy were assessed. Monoclonal antibodies were used to identify infiltrating macrophages, α-SMA(+) and PCNA(+) cells, the expression of integrins α3β1 and LFA-1β, the adhesion molecule ICAM-1, the growth factor TGF-β1 and the terminal complement component C5b-9. Results 24 pts (70.6%) showed a complete or partial response to the treatment. The follow-up period was 20 ± 22 months. At multivariate analysis, serum CRP (p = 0.024), the intensity of tubular expression of C5b-9 (p < 0.0001) as well as the extent of glomerular and tubular expression of α3β1 integrin (p = 0.001 and 0.008 respectively) independently predicted the response to treatment. The response rate was better in ANCA(+) pts (p = 0.008). The extent of interstitial infiltrate (p < 0.0001), the severity of tubulointerstitial fibrosis (p < 0.0001) and the severity of tubular TGF-β1 expression (p < 0.0001) were independent predictors of long term outcome of renal function. Conclusion Patients with ANCA-associated renal vasculitis seem to respond better to the treatment. Acute phase reactants, such as CRP, implying a more intense parenchymal inflammatory reaction, as well as the intensity of the de novo expression of C5b-9 and the glomerular and tubular expression of α3β1 integrin predict the response to therapy. The severity of TIN lesions and of the tubulo-interstitial TGF-β1 and C5b-9 expression predict an
Gadde, Shilpa; Lee, Belinda; Kidd, Laura; Zhang, Rubin
Antineutrophil cytoplasmic antibodies (ANCA) are well known to be associated with several types of vasculitis, including pauci-immune crescentic glomerulonephritis, a form of rapid progressive glomerular nephritis (RPGN). ANCA vasculitis has also been reported after administration of propylthiouracil, hydralazine, cocaine (adulterated with levimasole), allopurinol, penicillamine and few other drugs. All previously reported cases of drug-associated ANCA glomerulonephritis were in native kidneys. Sofosbuvir is a new and effective drug for hepatitis C virus infection. Here, we report a case of ANCA vasculitis and RPGN following sofosbuvir administration in a kidney transplant recipient. It also represents the first case of drug-associated ANCA vasculitis in a transplanted kidney. Further drug monitoring is necessary to elucidate the degree of association and possible causal effect of sofosbuvir and perinuclear ANCA vasculitis. PMID:27872837
The publication of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines on the treatment of glomerular diseases in 2012 marked a milestone in this field, as it is the first time that comprehensive guidelines are provided for such disease entities. The current review focuses on major findings, both pathogenesis related and clinical, in the primary glomerulonephritis that have been made after the guidelines came into effect.
The publication of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines on the treatment of glomerular diseases in 2012 marked a milestone in this field, as it is the first time that comprehensive guidelines are provided for such disease entities. The current review focuses on major findings, both pathogenesis related and clinical, in the primary glomerulonephritis that have been made after the guidelines came into effect. PMID:26877924
Cherif, Mejda; Hedri, Hafedh; Ounissi, Mondher; Gergah, Taher; Goucha, Rim; Barbouch, Samia; Abderrahim, Ezzedine; Maiz, Hedi Ben; Kheder, Adel
Kidney disease is a rare complication in patients with the Down's syndrome. However, with increased survival, it appears that a growing number of these patients present with glomerulonephritis. Most cases have been reported as case reports and include lesions such as mesangiocapillary glomerulonephritis with hypo-complementemia, crescentic glomerulonephritis with anti-neutrophil cytoplasmic antibodies (ANCA), amyloidosis and immunotactoid glomerulopathy. We report the observation of a 38-year-old man with the Down's syndrome who presented with severe renal failure, proteinuria and microscopic hematuria evolving over two months. There was no history of congenital heart disease or urinary symptoms. Percutaneous renal biopsy revealed fibrous crescents, rupture of Bowman's capsule and peri-glomerular granuloma; there were no deposits on immunofluorescence study. Thoracic computerized tomography scan showed alveolar congestion. The patient tested negative for ANCA. At the time of reporting, the patient is on regular chronic hemodialysis. Our case illustrates a distinct entity that further expands the spectrum of renal disease known to occur in the Down's syndrome. Early detection of the renal disorders may prevent or slow down the progression.
Seelig, H P; Seelig, R; Fischer, K; Maurer, R; Safer, A; Schnitzlein, W
The nephrotic syndrome presumably caused by an immune complex glomerulonephritis constitutes a major side effect attendant upon chronic administration of penicillamine. The possible induction of an immune-complex glomerulonephritis by penicillamine and its further development after stopping the drug was investigated in rats. --60 rats were fed perorally 2000 mg D-Penicillamine/kg BW/die resp. for a period of 8--44 days. Following unilateral nephrectomy the animals were observed for further 5 weeks. --Dependent to the time of penicillamine application there was an increasing deposition of IgG and C3 in a granular pattern along the glomerular basement membrane and within the mesangium. The IgG deposits initially were focal and segmental later on diffuse and global in distribution. 5 weeks after stopping the penicillamine the immune globulin deposits had disappeared completely or at least in part as did the mild focal glomerulonephritis and the moderate proteinuria which developed in some animals after a 44 day treatment with penicillamine. --The results confirm the hitherto presumed immune complex pathogenesis of the penicillamine induced nephropathy. The disappearance of the immunoglobulins deposited and of proteinuria stopping penicillamine alludes the good prognosis of this kind of nephropathy.
Rabasco, Cristina; Cavero, Teresa; Román, Elena; Rojas-Rivera, Jorge; Olea, Teresa; Espinosa, Mario; Cabello, Virginia; Fernández-Juarez, Gema; González, Fayna; Ávila, Ana; Baltar, José María; Díaz, Montserrat; Alegre, Raquel; Elías, Sandra; Antón, Monserrat; Frutos, Miguel Angel; Pobes, Alfonso; Blasco, Miguel; Martín, Francisco; Bernis, Carmen; Macías, Manuel; Barroso, Sergio; de Lorenzo, Alberto; Ariceta, Gema; López-Mendoza, Manuel; Rivas, Begoña; López-Revuelta, Katia; Campistol, José María; Mendizábal, Santiago; de Córdoba, Santiago Rodríguez; Praga, Manuel
C3 glomerulonephritis is a clinicopathologic entity defined by the presence of isolated or dominant deposits of C3 on immunofluorescence. To explore the effect of immunosuppression on C3 glomerulonephritis, we studied a series of 60 patients in whom a complete registry of treatments was available over a median follow-up of 47 months. Twenty patients had not received immunosuppressive treatments. In the remaining 40 patients, 22 had been treated with corticosteroids plus mycophenolate mofetil while 18 were treated with other immunosuppressive regimens (corticosteroids alone or corticosteroids plus cyclophosphamide). The number of patients developing end-stage renal disease was significantly lower among treated compared with untreated patients (3 vs. 7 patients, respectively). No patient in the corticosteroids plus mycophenolate mofetil group doubled serum creatinine nor developed end-stage renal disease, as compared with 7 (significant) and 3 (not significant), respectively, in patients treated with other immunosuppressive regimens. Renal survival (100, 80, and 72% at 5 years) and the number of patients achieving clinical remission (86, 50, and 25%) were significantly higher in patients treated with corticosteroids plus mycophenolate mofetil as compared with patients treated with other immunosuppressive regimens and untreated patients, respectively. Thus, immunosuppressive treatments, particularly corticosteroids plus mycophenolate mofetil, can be beneficial in C3 glomerulonephritis.
Weening, Jan J; D'Agati, Vivette D; Schwartz, Melvin M; Seshan, Surya V; Alpers, Charles E; Appel, Gerald B; Balow, James E; Bruijn, Jan A; Cook, Terence; Ferrario, Franco; Fogo, Agnes B; Ginzler, Ellen M; Hebert, Lee; Hill, Gary; Hill, Prue; Jennette, J Charles; Kong, Norella C; Lesavre, Philippe; Lockshin, Michael; Looi, Lai-Meng; Makino, Hirofumi; Moura, Luiz A; Nagata, Michio
The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving <50% of total number of glomeruli) with subdivisions for active and sclerotic lesions; class IV for diffuse glomerulonephritis (involving > or = 50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions]. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.
Weening, Jan J; D'Agati, Vivette D; Schwartz, Melvin M; Seshan, Surya V; Alpers, Charles E; Appel, Gerald B; Balow, James E; Bruijn, Jan A; Cook, Terence; Ferrario, Franco; Fogo, Agnes B; Ginzler, Ellen M; Hebert, Lee; Hill, Gary; Hill, Prue; Jennette, J Charles; Kong, Norella C; Lesavre, Philippe; Lockshin, Michael; Looi, Lai-Meng; Makino, Hirofumi; Moura, Luiz A; Nagata, Michio
The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving <50% of total number of glomeruli) with subdivisions for active and sclerotic lesions; class IV for diffuse glomerulonephritis (involving > or =50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.
Tabata, Nobuko; Yoshizawa, Hideka
Generalized pustular lesions characterized by acute onset with fever occur in pustulosis acuta generalisata, acute generalized exanthematous pustulosis, and generalized pustular psoriasis. In the present report, we describe a pediatric case of generalized pustular eruption that was not completely consistent with clinical features. Our patient had no evidence of a post-streptococcal infection. We observed scattered symmetric eruption of discrete pustules with an inflammatory halo on normal skin. The eruption was absent on her palms and soles of the feet. To the best of our knowledge, there are no reports in the English literature of cases with clinical features similar to those of our patient. PMID:27462226
Sun, L; Yuan, Q; Feng, J; Yao, L; Fan, Q; Ma, J; Wang, L
Mycobacterium tuberculosis infection causing glomerulonephritis is a rare disorder. This retrospective study analyzed the clinical characteristics of patients diagnosed with tuberculosis-mediated glomerulonephritis (TB-GN) between 2002 and 2009, as well as the diagnostic tools used. These findings were then compared with those of patients with primary glomerulonephritis (P-GN). The records of all patients were reviewed. The diagnosis of TB-GN was based on renal hematuria and/or proteinuria and cure after antituberculosis therapy alone plus urine culture positive for M. tuberculosis, demonstration of typical tubercle granulomas on renal biopsy specimens, or the detection of M. tuberculosis DNA by polymerase chain reaction (PCR) on renal specimens. Forty-six patients with TB-GN and 49 patients with P-GN were included. Compared with patients in the P-GN group, most (76%) patients with TB-GN had a history of TB. Systemic symptoms were much more frequent in patients with TB-GN than local genitourinary symptoms. Serological testing showed a statistical difference between the two groups. Immunoglobulin A nephropathy was found in the majority (72%) of patients with TB-GN. M. tuberculosis DNA detection was positive in 39 (84.8%) patients, a much higher positive rate of diagnosis than that with urine culture for M. tuberculosis. The manifestation of TB-GN is atypical and nonspecific. It warrants a high index of suspicion when patients with renal hematuria and proteinuria fail to respond to standard treatments for P-GN. Clinicians should pay close attention to the medical history and results of special laboratory tests. M. tuberculosis DNA detection on renal biopsy specimens should be considered in order to confirm the diagnosis of TB-GN.
Kurosu, Akira; Oka, Noriko; Hamaguchi, Takeshi; Yoshikawa, Norishige; Joh, Kensuke
Immunoglobulin A nephropathy (IgAN) showing predominant IgA and complement 3 (C3) deposition on the mesangium is an immune complex-mediated glomerulonephritis. This renal disease is the most common primary glomerular disease worldwide. However, infantile onset of IgAN is rare. In the present patient, urinary protein and occult blood were detected in a girl aged 1 year and 8 months on urinalysis at a nursery school. Despite being young, a kidney biopsy was performed for diagnosis and the correct choice of therapy. Glomerular mesangial cell proliferation and a double contour of the glomerular basement membrane (GBM) resembling a railroad track were noted on light microscopy. Therefore, the patient was diagnosed morphologically with membranoproliferative glomerulonephritis (MPGN), because mesangial hypercellularity and thickening of the GBM were identified. However, on immunofluorescent staining, the deposition of immune complexes mainly consisting of IgA, IgG, and C3 was noted in the mesangial region and glomerular capillary loops. On electron microscopy, electron-dense deposits were recognized in the subendothelial and paramesangial regions associated with mesangial cell interposition into the subendothelial space. Autoimmune diseases and infection-associated secondary glomerulonephritis were clinically excluded, because there were no relevant signs or symptoms. Steroid treatment was initiated and findings of urinalysis were normalized within 8 months. This patient was finally diagnosed with IgA nephropathy showing the features of MPGN. The present patient was the youngest among reported cases of IgA nephropathy, suggesting that early onset of IgAN is associated with an MPGN-like lesion. The present report provides information for pathogenesis of IgA nephropathy.
Fujiwara, Takashi; Komatsuda, Atsushi; Ohtani, Hiroshi; Togashi, Masaru; Sawada, Ken-Ichi; Wakui, Hideki
A 25-year-old woman was admitted because of proteinuria. A renal biopsy showed mesangial/endocapillary proliferative glomerulonephritis with IgG2-κ deposits. Electron microscopy showed immune complex-type deposits. She also had Coombs-positive hemolytic anemia, anticardiolipin antibodies, and antinuclear antibodies. Middle-dose steroid therapy led to improvement of proteinuria and hemolytic anemia. Six years later, she developed crescentic glomerulonephritis with IgG2-κ deposits during pregnancy. Middle-dose steroid therapy improved renal dysfunction. This is an exceptional case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), a recently described rare dysproteinemia-related glomerulonephritis, associated with autoimmune disease. This case also suggests that crescentic glomerulonephritis can be superimposed on PGNMID.
Gowda, K K; Joshi, K; Ramachandran, R; Nada, R
A 40-year-old male presented with nephrotic syndrome. Light microscopic analysis of the renal biopsy showed thickening of the glomerular capillary wall. Immunofluorescence examination revealed granular deposition of monoclonal immunoglobulin (Ig) G3-kappa and complement C3 along the glomerular basement membrane. Electron microscopy showed subepithelial electron dense deposits, thus confirming membranous glomerulonephritis (MGN) with monoclonal gammopathy. MGN with monoclonal gammopathy is an extremely rare but distinctive entity. This patient was treated with a combination of bortezomib, thalidomide and dexamethasone and showed partial remission of his nephrotic state and dysproteinemia.
Cronin, Mary; Robin, Adam; Lorna, Campbell; Rosenthal, Ann K.
Pauci-immune crescentic glomerulonephritis is commonly seen in ANCA-associated vasculitis but it is rarely seen during the course of other connective tissue diseases like lupus or Sjogren's syndrome or MCTD. We report 3 cases of pauci-immune crescentic glomerulonephritis in patients with connective tissue disease other than vasculitis. We reviewed literature and made summary of previously reported cases of this rare entity. Clinical and laboratory features of these patients varied widely, but most of patients have met criteria for lupus. In this small population of patients there is no correlation with ANCAs. Most of the patients were treated with aggressive immunosuppression and did well if they were treated early in the course of their disease. One of our patients required renal transplant, but she presented late in the course of her disease, as evidenced by chronicity on her renal biopsy. Whether these patients are overlap of vasculitis and other connective tissue diseases or to be considered as a separate entity is yet to be described. Clinicians must be aware of these presentations because initial presentation can be severe. PMID:27504208
Glomerulonephritis (GN) encompasses a range of immune-mediated disorders that cause inflammation within the glomerulus of the kidney. The pathogenesis of GN is complex. Intricacy arises from factors such as autoimmunity, cancer and structural abnormalities within the kidney. Studies using animal models have highlighted crucial interaction between inflammatory cells and cells intrinsic to the kidney, both of which are fundamental to the pathogenesis of GN. This review aims to provide insight on a 'suitable' model for nephrotoxic nephritis and glomerulonephritis (NTN GN) and relate its experimental validity to humans. The BALB/c NTN murine model and Wistar Kyoto (WKY) rat have held experimental validity in the study of GN in humans. The chemokine receptor CXCR3 also mediates renal T-cell recruitment and subsequent tissue injury in NTN. It is noteworthy to consider CXCR3 blockade in Th1-mediated renal inflammation as future therapeutic options for patients with GN and subsets thereof. Currently used immunosuppressive therapies for GN are not always uniformly effective and are frequently associated with serious side-effects. Corticosteroids are effective in several types of GN owing to their ability to inhibit the pro-inflammatory effects of cytokines known to promote glomerular inflammation. Differences between experimental and human GN complicate translation of experimental therapies into practice. More research is required to translate animal model research into a better comprehension of human GN disease. However, the complexity of GN research makes findings a challenge to replicate.
Soto, K; Wu, YL; Ortiz, A; Aparício, SR; Yu, CY
Homozygous complement C4B deficiency is described in a Southern European young female patient with Membranoproliferative Glomerulonephritis (MPGN) type III characterized by renal biopsies with strong complement C4 and IgG deposits. Low C4 levels were independent of clinical evolution or type of immunosuppression and were found in three other family members without renal disease or infections. HLA typing revealed that the patient has homozygous A*02, Cw*06, B*50 at the class I region, and DRB1*08 and DQB1*03 at the class II region. Genotypic and phenotypic studies demonstrated that the patient has homozygous monomodular RCCX in the HLA class III region, with single long C4A genes coding for C4A3 and complete C4B deficiency. Her father, mother, son and niece have heterozygous C4B deficiency. The patient’s deceased brother had a history of Henoch-Schönlein Purpura (HSP), an immune complex-mediated proliferative glomerulonephritis. These findings challenge the putative pathophysiological roles of C4A and C4B and underscore the need to perform functional assays, C4 allotyping and genotyping on patients with persistently low serum levels of a classical pathway complement component and glomerulopathy associated with immune deposits. PMID:20580617
Soto, K; Wu, Y L; Ortiz, A; Aparício, S R; Yu, C Y
Homozygous complement C4B deficiency is described in a Southern European young female patient with Membranoproliferative Glomerulonephritis (MPGN) type III characterized by renal biopsies with strong complement C4 and IgG deposits. Low C4 levels were independent of clinical evolution or type of immunosuppression and were found in three other family members without renal disease or infections. HLA typing revealed that the patient has homozygous A*02, Cw*06, B*50 at the class I region, and DRB1*08 and DQB1*03 at the class II region. Genotypic and phenotypic studies demonstrated that the patient has homozygous monomodular RCCX in the HLA class III region, with single long C4A genes coding for C4A3 and complete C4B deficiency. Her father, mother, son and niece have heterozygous C4B deficiency. The patient's deceased brother had a history of Henoch-Schönlein Purpura (HSP), an immune complex-mediated proliferative glomerulonephritis. These findings challenge the putative pathophysiological roles of C4A and C4B and underscore the need to perform functional assays, C4 allotyping and genotyping on patients with persistently low serum levels of a classical pathway complement component and glomerulopathy associated with immune deposits.
... a strep infection and if you might have rheumatic fever or kidney problems ( glomerulonephritis ) due to that infection. ... Read More Antibody Antigen Post-streptococcal glomerulonephritis (GN) Rheumatic fever Review Date 5/1/2015 Updated by: Jatin ...
Liu, Chih-Hao; Du, Yong; Singh, Manmohan; Wu, Chen; Han, Zhaolong; Li, Jiasong; Mohammadzai, Qais; Raghunathan, Raksha; Hsu, Thomas; Noorani, Shezaan; Chang, Anthony; Mohan, Chandra; Larin, Kirill V.
Acute Glomerulonephritis caused by anti-glomerular basement membrane disease has a high mortality due to delayed diagnosis. Thus, an accurate and early diagnosis is critical for preserving renal function. Currently, blood, urine, and tissue-based diagnoses can be time consuming, while ultrasound and CT imaging have relatively low spatial resolution. Optical coherence tomography (OCT) is a noninvasive imaging technique that provides superior spatial resolution (micron scale) as compared to ultrasound and CT. Pathological changes in tissue properties can be detected based on the optical metrics analyzed from the OCT signal, such as optical attenuation and speckle variance. Moreover, OCT does not rely on ionizing radiation as with CT imaging. In addition to structural changes, the elasticity of the kidney can significantly change due to nephritis. In this work, we utilized OCT to detect the difference in tissue properties between healthy and nephritic murine kidneys. Although OCT imaging could identify the diseased tissue, classification accuracy using only optical metrics was clinically inadequate. By combining optical metrics with elasticity, the classification accuracy improved from 76% to 95%. These results show that OCT combined with OCE can be potentially useful for nephritis detection.
Zhou, Hui; Chen, Min; Zhu, Ying; Wang, Bing; Liu, Xiao-ning; Zuo, Zhi; Tang, Feng-Ying
End-stage renal disease (ESRD) was defined as start of renal replacement therapy or death due to kidney disease. However, death due to acute kidney injury was not included. It typically occurs when chronic renal failure progresses to a point where the kidneys are permanently functioning at less than 10% of their capacity. Oxidative stress (OS) plays a crucial role in ESRD. Nicotinamide adenine dinucleotide phosphate (NADPH) is one of the most important enzymes during oxidative stress. Cytochrome b light chain (CYBA), encoded by a polymorphic gene, which is a critical component of the nicotinamide adenine dinucleotide (NADH)/NADPH oxidase system and plays an important role in electron transport and superoxide anion production, is located on chromosome band 16q24 and has six exons spanning almost 7.76 kb of genomic DNA. CYBA gene polymorphisms can influence the activity of NADPH oxidase. To evaluate the association between CYBA gene polymorphisms and ESRD, we genotyped five CYBA polymorphisms using TaqMan allelic discrimination assay on DNA samples from 306 healthy controls and 332 patients with ESRD. Our results suggested that rs1049255 polymorphism of CYBA modified the risk of ESRD (p = 0.019; OR = 0.625; 95%CI = 0.424-0.921). GG genotype and G allele might be a protective factor against the risk of ESRD, especially in patients with chronic glomerulonephritis.
Nakada, Yasuyuki; Tsuboi, Nobuo; Takahashi, Yasuto; Yoshida, Hiraku; Hara, Yoriko; Okonogi, Hideo; Kawamura, Tetsuya; Arimura, Yoshihiro; Yokoo, Takashi
We report a case in which antineutrophil cytoplasmic antibody- (ANCA-) associated glomerulonephritis and membranous glomerulopathy (MGN) were detected concurrently. The patient showed rapidly progressive renal deterioration. A renal biopsy showed crescentic glomerulonephritis, together with marked thickening and spike and bubbling formations in the glomerular basement membranes. Indirect immunofluorescence examination of the patient's neutrophils showed a perinuclear pattern. Enzyme-linked immunosorbent assays revealed that the ANCA in this case did not target myeloperoxidase (MPO) or proteinase 3 (PR3) but bactericidal-/permeability-increasing protein, elastase, and lysosome. The relationship between these two etiologically distinct entities, MPO-/PR3-negative ANCA-associated glomerulonephritis and MGN, remains unclear. PMID:25648906
Sung, Woo Kyung; Jeong, Jin Uk; Bang, Ki Tae; Shin, Jong Ho; Yoo, Ji Hyung; Kim, Nak Min; Park, Jun Hyung; Kim, Joo Heon
A 58-yr-old man presented with leg edema and subacute weakness of his bilateral lower extremities. Urinary and serum immunoelectrophoresis revealed the presence of lambda-type Bence Jones proteins. He was ultimately diagnosed with monoclonal gammopathy of undetermined significance (MGUS). A renal biopsy specimen showed fibrillary glomerulonephritis (FGN), which was randomly arranged as 12–20 m nonbranching fibrils in the basement membranes. Immunofluorescence studies were negative for immunoglobulin (Ig)G, IgM, IgA, C3, and kappa light chains in the capillary walls and mesangial areas. A Congo red stain for amyloid was negative. Electromyography and nerve conduction velocity examinations results were compatible with the presence of demyelinating polyneuropathy. This case showed a rare combination of FGN, without Ig deposition, and MGUS combined with chronic inflammatory demyelinating polyneuropathy (CIDP). PMID:26484033
Baba, Hiroshi; Kudo, Tomoo; Makino, Yoshinori; Mochizuki, Yasumasa; Takagi, Takayo; Une, Yumi
Spontaneous crescentic glomerulonephritis (CrGN) in animals has only been reported in dog and sheep. We report the pathological features of CrGN in a 17-year-old male polar bear that died due to renal failure. Histologically, the lesions were characterized by fibrocellular crescents, adhesion between Bowman's capsule and the glomerular capillary tuft and an increase in the mesangial matrix in glomeruli. The proliferating cells in the crescent were partly immunopositive for cytokeratin and intensely positive for vimentin, WT-1 and α-smooth muscle actin, suggesting they originated from parietal epithelial cells. Ultrastructually, thickening of the glomerular basement membrane and loss of epithelial cell foot processes were observed with electron-dense deposits.
Ray, Susan; Rouse, Kelly; Appis, Andrew; Novak, Robert; Haller, Nairmeen Awad
Fibrillary glomerulonephritis (FGN) is a relatively rare cause of renal disease, found in only 0.6-1.5% of native renal biopsies. The pathogenesis of FGN is not well described, and very few associations with disease processes other than hepatitis C virus (HCV) have been made. We describe a case that provides evidence in support of the FGN-HCV association, as well as introduces the association of FGN-HCV and hypocomplementemia. The case is a 53-year-old African-American female demonstrating a classical presentation of FGN complicated by a concomitant HCV infection. Treating an HCV infection with alpha-interferon has been shown to result in subsequent improvement in the nephrotic syndrome and renal function. However, this patient is unique in that she is complicated with hypocomplementemia, creating a complex treatment situation.
Chaurasia, Jai Kumar; Soni, Mayank; Ahmed, Murad; Naim, Mohammed
A 5-month-old male infant presented with a 15 day history of distension of abdomen. On clinical examination, a soft lump was palpable in the left lumbar region. Radiological findings suggested an enlarged non-functional left kidney with ureteropelvic adhesive obstruction. The left renal mass was excised and submitted for histopathological examination. The excised renal mass was cystic with its wall partly white and partly blue. Gross and histopathological findings were diagnostic of a white-blue pyelocalyceal cyst with hydrotic glomerulonephritis. This entity needs to be differentiated from a large number of other cystic diseases of the kidney. Intrauterine screening and diagnosis may be significant for a possible early intrauterine uro-laparoscopic recanalisation of the pyeloureteral obstruction to save the affected kidney.
Van Haare Heijmeijer, Sophie; Wilmes, Dunja; Aydin, Selda; Clerckx, Caroline; Labriola, Laura
Infective endocarditis (IE) and small-vessel vasculitis may have similar clinical features, including glomerulonephritis. Furthermore the association between IE and ANCA positivity is well documented, making differential diagnosis between IE- and ANCA-associated vasculitis particularly difficult, especially in case of culture-negative IE. We report on one patient with glomerulonephritis secondary to culture-negative IE caused by Bartonella henselae which illustrates this diagnostic difficulty. PMID:26819786
Cybulsky, Andrey V; Walsh, Michael; Knoll, Greg; Hladunewich, Michelle; Bargman, Joanne; Reich, Heather; Humar, Atul; Samuel, Susan; Bitzan, Martin; Zappitelli, Michael; Dart, Allison; Mammen, Cherry; Pinsk, Maury; Muirhead, Norman
The KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for management of glomerulonephritis was recently released. The Canadian Society of Nephrology convened a working group to review the recommendations and comment on their relevancy and applicability to the Canadian context. A subgroup of adult nephrologists reviewed the guideline statements for management of glomerular disease in adults and agreed with most of the guideline statements developed by KDIGO. This commentary highlights areas for which there is lack of evidence and areas in need of translation of evidence into clinical practice. Areas of controversy or uncertainty, including the choice of second-line agents, are discussed in more detail. Existing practice variation also is addressed. The relevance of treatment recommendations to the Canadian practitioner is discussed.
Alexander, Jessy J; Chaves, Lee D; Chang, Anthony; Jacob, Alexander; Ritchie, Maria; Quigg, Richard J
In chronic serum sickness, glomerular immune complexes form, yet C57BL/6 mice do not develop glomerulonephritis unless complement factor H (CfH) is absent, indicating the relevance of complement regulation. Complement receptor 3 (CD11b) and Fcγ receptors on leukocytes, and CfH on platelets, can bind immune complexes. Here we induced immune complex-mediated glomerulonephritis in CfH(-/-) mice chimeric for wild-type, CfH(-/-), CD11b(-/-), or FcRγ(-/-) bone marrow stem cells. Glomerulonephritis was worse in CD11b(-/-) chimeras compared with all others, whereas disease in FcRγ(-/-) and wild-type chimeras was comparable. Disease tracked strongly with humoral immune responses, but not glomerular immune complex deposits. Interstitial inflammation with M1 macrophages strongly correlated with glomerulonephritis scores. CD11b(-/-) chimeras had significantly more M1 macrophages and CD4(+) T cells. The renal dendritic cell populations originating from bone marrow-derived CD11c(+) cells were similar in all experimental groups. CD11b(+) cells bearing colony-stimulating factor 1 receptor were present in kidneys, including CD11b(-/-) chimeras; these cells correlated negatively with glomerulonephritis scores. Thus, experimental immune complex-mediated glomerulonephritis is associated with accumulation of M1 macrophages and CD4(+) T cells in kidneys and functional renal insufficiency. Hence, CD11b on mononuclear cells is instrumental in generating an anti-inflammatory response in the inflamed kidney.
Kucherenko, A G; Markov, Kh M; Zokirov, N Z; Naumova, V I
A study was made of renin-angiotensin-aldosterone system activity and plasmic concentrations of atrial natriuretic peptide (NUP) as well as antidiuretic hormone in children with primary glomerulonephritis. A close relationship was established of these parameters in regulation of water-salt homeostasis. The above systems are involved in pathogenesis of childhood glomerulonephritis. This finding should be considered in development of pathogenetically validated therapy of glomerulonephritis, including introduction of synthetic NUP.
Kain, Renate; Exner, Markus; Brandes, Ricarda; Ziebermayr, Reinhard; Cunningham, Dawn; Alderson, Carol A; Davidovits, Agnes; Raab, Ingrid; Jahn, Renate; Ashour, Oliver; Spitzauer, Susanne; Sunder-Plassmann, Gere; Fukuda, Minoru; Klemm, Per; Rees, Andrew J; Kerjaschki, Dontscho
Pauci-immune focal necrotizing glomerulonephritis (FNGN) is a severe inflammatory disease associated with autoantibodies to neutrophil cytoplasmic antigens (ANCA). Here we characterize autoantibodies to lysosomal membrane protein-2 (LAMP-2) and show that they are a new ANCA subtype present in almost all individuals with FNGN. Consequently, its prevalence is nearly twice that of the classical ANCAs that recognize myeloperoxidase or proteinase-3. Furthermore, antibodies to LAMP-2 cause pauci-immune FNGN when injected into rats, and a monoclonal antibody to human LAMP-2 (H4B4) induces apoptosis of human microvascular endothelium in vitro. The autoantibodies in individuals with pauci-immune FNGN commonly recognize a human LAMP-2 epitope (designated P41–49) with 100% homology to the bacterial adhesin FimH, with which they cross-react. Rats immunized with FimH develop pauci-immune FNGN and also develop antibodies to rat and human LAMP-2. Finally, we show that infections with fimbriated pathogens are common before the onset of FNGN. Thus, FimH-triggered autoimmunity to LAMP-2 provides a previously undescribed clinically relevant molecular mechanism for the development of pauci-immune FNGN. PMID:18836458
Rubio, E; Acevedo, M
A 68-year-old male with macroscopic hematuria and constitutional symptoms as fever and weight loss. There was nothing interesting in the anamnesis or in the physical exploration. The laboratory test had an elevation of creatinine of 4 mg/dL and ten days before it had been 1.4 mg/dL. In the urine analysis: proteinuria of 1.5 G/24 h, and hematuria. On the second day we made a renal biopsy where we could seen segmental glomerular necrosis and crescent fromation in 80% of the glomeruli. In the immune study c-ANCA anti-PR3 was positive. In the complementary studies we didn't find other organs affected. With the diagnosis of pauci-immune glomerulonephritis limited to the kidney we began treatment with corticosteroids and cyclophosphamide. As the renal function was severely affected the patient needed one dialysis session. We began with 1 g intravenous methylprednisolone daily for 3 days followed by oral prednisone 60 mg daily tapering to 10 mg daily by 3 months. This was combined with 150 mg oral cyclophosphamide daily. Seven plasma exchanges were performed. At the beginning of treatment creatinine was 7 mg/dL, it was decreasing rapidly and three week after cretinine was 3 mg/Dl and he was asymptomatic. One year after treatment, creatinine is 1.4 mg/dL and the urine analysis is normal, C-ANCA are negative.
Yokoyama, Hitoshi; Okuyama, Hiroshi; Yamaya, Hideki
Lupus nephritis comprises a spectrum of glomerular, vascular, and tubulointerstitial lesions, which has significant racial variation in severity and manifestations. The current classification (ISN/RPS 2003) has been improved successfully for the categorization of lupus glomerulonephritis (LGN). On the basis of this classification, 480 Japanese cases revealed the following distribution: class I 3%, class II 16%, class III 13%, class IV-S 11%, class IV-G 41%, class V 16%, and class VI 1%. Class IV-G with chronicity tended to have the worst renal outcome. Nephrotic syndrome was a more frequent complication in class IV-S (50%), class IV-G (72%), and class V (56%), with poor renal and actuarial outcomes. With regard to therapy, treatment options including glucocorticoids alone or combined with antimetabolites (azathioprine, mizoribine, mycophenolate mofetil), calcineurin inhibitors (cyclosporine A, tacrolimus), or alkylating agents (intravenous cyclophosphamide injection) improved the outcome of LGN; however, there is no high-grade clinical evidence from Japan. Further studies are needed to resolve the clinicopathological problems of LGN, especially IV-S, IV-G, and pure membranous lupus nephritis in Japanese patients.
Huraib, Sameer O; Qureshi, Junaid I; Quadri, Khaja Hm; Al Flaiw, Ahmed; Al Ghamdi, Ghormullah; Jumani, Abdulqadir; Al Hejaili, Fayez; Raza, Hammad; Al Johani, Abdulaziz; Al-Katheri, Abdulmalik; Al-Khader, Abdullah A
Mycophenolate Mofetil MMF has been widely used in post-transplant immunosuppression. Its role is emerging in GN. MMF demonstrated promising results compared with cyclosphosphamide in stage IV lupus nephritis, in a recently published trial. It has been found to have a wide safety profile, with mostly gastroinetestinal side effects, which can be avoided through titration. Its action is through inhibition of the enzyme IMDPH (ionosine monophosphate dehydrogenase), leading to purine antagonism and inhibition of lymphocytes. We were aiming to demonstrate the efficacy of MMF in our GN population. In this study, we reviewed 17 patients who received MMF (dose - 1 gm po bid) for the past year. They were only included if it was given for the management of resistant primary glomerulonephritis. Complete remission has been defined as proteinuria of less than 0.5 g/day and partial remission as a reduction of proteinuria 50% of starting MMF therapy; all 17 MMF therapy patients uniformly achieved good BP ((29%) achieved complete remission and this group consisted of 1 membranous GN, 2 lupus GN (type IV and membranous), one FSGS and one with MPGN. Four of 17 (23%) were non-responders to therapy. This group articles.aspx? id=41 to side effects. We conclude that the MMF appears to be an effective alternate treatment modality in resistant membranous GN, lupus nephritis (type IV and V) and possibly MPGN, and to a lesser extent in resistant FSGS. Further prospective data may demonstrate the efficacy of MMF in GN.
van der Woude, F J; Hoedemaeker, P J; van der Giessen, M; de Graeff, P A; de Monchy, J; The, T H; van der Hem, G K
Circulating immune complexes after a test meal were measured with three methods (PEG precipitation, Clq-ELISA and the indirect granulocyte phagocytosis test) in 10 controls, two symptomless persons with selective IgA deficiency and 14 patients with various types of glomerulonephritis, of which two patients (with idiopathic membranous glomerulopathy and local focal glomerulonephritis) also had selective IgA deficiency. The PEG and Clq-ELISA test did not show significant differences between the groups. In the two symptomless persons with selective IgA deficiency and in the patient with local focal glomerulonephritis and selective IgA deficiency the indirect granulocyte phagocytosis test (IGFT) showed a reproducible increase in IgG, IgM and complement containing immune complexes. In the last patient multiple food antigens were probably responsible for this phenomenon, a rapid amelioration of kidney function could be induced three times by giving an antigen free diet. PMID:6851247
Jiménez, Angeles; Sánchez, Belén; Pérez Alenza, Dolores; García, Pilar; López, Jose Vicente; Rodriguez, Alejandro; Muñoz, Alvaro; Martínez, Fernando; Vargas, Astrid; Peña, Laura
The Iberian lynx is the most endangered felid species in the world, confined nowadays to two isolated metapopulations in the southwest of Spain, where less than 200 individuals survive. Little is known about the diseases that affect these animals in the wild or in captivity. Kidney samples from necropsies of 27 Iberian lynxes, wild and captive, were examined by histopathology, immunohistochemistry (IgG, IgM, IgA, laminin, type IV collagen, and fibronectin), electron microscopy (n=8) and immunogold labelling for IgM, IgG and IgA in one case, in order to characterize the glomerulopathy prevalent in this species. Urinalyses from records were available for 9 of the necropsied animals and blood and urine samples from 23 free ranging and captive Iberian lynxes were prospectively obtained in order to evaluate the renal function of the living population. A focal, diffuse membranous glomerulonephritis (MGN) that progressed with age was diagnosed in all but one of the animals in different stages not associated to concurrently known infectious diseases. Positive immunoexpression of IgM and IgG was observed in the glomerular capillary basement membranes and intramembranous electron-dense deposits, compatible with immune complexes (ICs) were seen with electron microscopy. The immunogold labelling was also positive for IgM and IgG in the electron-dense areas. The serum biochemistry and urinalyses also revealed signs of mild chronic kidney disease in 16 of the 23 animals evaluated. In conclusion, the membranous glomerulopathy affecting the Iberian lynx is a progressive disease of immune origin. We postulate a possible genetic predisposition towards the disease, enhanced by inbreeding and a possible connection to an immune-mediated systemic disease.
Hebert, L.A.; Cosio, F.G.; Birmingham, D.J.; Mahan, J.D.; Sharma, H.M.; Smead, W.L.; Goel, R. )
This study was undertaken to develop a model of immune complex (IC)-mediated glomerulonephritis (GN) in the nonhuman primate that could be used in subsequent studies to examine critically the role of the erythrocyte complement receptor (E-CR) in the pathogenesis of IC-mediated disease. Cynomolgus monkeys were chosen for study because they constitutively express E-CR levels that are either less than, equal to, or greater than that seen in normal man. After immunization with bovine gamma globulin (BGG), the GN induction protocol was begun in 10 cynomolgus by initiating daily i.v. administration of BGG in amounts sufficient to achieve or exceed antigen/antibody equivalence (assessed by the quantitative precipitin assay) for precipitating antibody present in the plasma volume. We found that within eight weeks of daily BGG administration of all the cynomolgus developed IC-mediated GN, irrespective of the initial E-CR level of the animals. However, the high E-CR cynomolgus tended to receive the higher BGG doses because of higher initial antibody levels to BGG. When the total number of glomerular deposits (determined by morphometric studies) per total BGG dose for each animal was plotted against the initial CR/E of that animal, there was a tendency for the animals with higher CR/E levels to have a lower number of glomerular deposits/BGG dose. Also, the total number of glomerular deposits correlated with the severity of the GN. During the early weeks of the GN induction protocol, the IC that formed in vivo (assessed by infusion of 125I-BGG) bound in large amounts to the circulating erythrocytes of the cynomolgus with medium or high E-CR levels. However, when tested after the onset of heavy proteinuria, which occurred between weeks 5 and 8 of daily BGG administration, the IC that formed in the circulation bound only poorly to circulating erythrocytes.
Göçeroğlu, Arda; Berden, Annelies E.; Fiocco, Marta; Floßmann, Oliver; Westman, Kerstin W.; Ferrario, Franco; Gaskin, Gill; Pusey, Charles D.; Hagen, E. Christiaan; Noël, Laure-Hélène; Rasmussen, Niels; Waldherr, Rüdiger; Walsh, Michael; Bruijn, Jan A.; Jayne, David R. W.; Bajema, Ingeborg M.
Relapse in ANCA-associated vasculitis (AAV) has been studied previously, but there are few studies on renal relapse in particular. Identifying patients at high risk of renal relapse may aid in optimizing clinical management. We investigated which clinical and histological parameters are risk factors for renal relapse in ANCA-associated glomerulonephritis (AAGN). Patients (n = 174) were newly diagnosed and had mild–moderate or severe renal involvement. Data were derived from two trials of the European Vasculitis Society: MEPEX and CYCAZAREM. The Cox regression model was used to identify parameters increasing the instantaneous risk (= rate) of renal relapse (useful for instant clinical decisions). For identifying predictors of renal relapse during follow-up, we used Fine & Gray’s regression model. Competing events were end-stage renal failure and death. The cumulative incidence of renal relapse at 5 years was 9.5% (95% CI: 4.8–14.3%). In the Cox model, sclerotic class AAGN increased the instantaneous risk of renal relapse. In Fine & Gray’s model, the absence of interstitial infiltrates at diagnosis was predictive for renal relapse. In this study we used two different models to identify possible relationships between clinical and histopathological parameters at time of diagnosis of AAV with the risk of experiencing renal relapse. Sclerotic class AAGN increased the instantaneous risk of renal relapse. This association is most likely due to the high proportion of sclerosed glomeruli reducing the compensatory capacity. The absence of interstitial infiltrates increased the risk of renal relapse which is a warning sign that patients with a relatively benign onset of disease may also be prone to renal relapse. Renal relapses occurring in patients with sclerotic class AAGN and renal relapses occurring in patients without interstitial infiltrates were mutually exclusive, which may indicate that they are essentially different. PMID:27973575
Alexander, Jessy J; Chaves, Lee D; Chang, Anthony; Jacob, Alexander; Ritchie, Maria; Quigg, Richard J
In chronic serum sickness, glomerular immune complexes form, yet C57BL/6 mice do not develop glomerulonephritis unless complement factor H (CfH) is absent, indicating the relevance of complement regulation. Complement receptor 3 (CD11b) and Fcγ receptors on leukocytes, and CfH on platelets, can bind immune complexes. Here we induced immune complex–mediated glomerulonephritis in CfH−/− mice chimeric for wild-type, CfH−/−, CD11b−/−, or FcRγ−/− bone marrow stem cells. Glomerulonephritis was worse in CD11b−/− chimeras compared with all others, whereas disease in FcRγ−/− and wild-type chimeras was comparable. Disease tracked strongly with humoral immune responses, but not glomerular immune complex deposits. Interstitial inflammation with M1 macrophages strongly correlated with glomerulonephritis scores. CD11b−/− chimeras had significantly more M1 macrophages and CD4+ T cells. The renal dendritic cell populations originating from bone marrow–derived CD11c+ cells were similar in all experimental groups. CD11b+ cells bearing colony-stimulating factor 1 receptor were present in kidneys, including CD11b−/− chimeras; these cells correlated negatively with glomerulonephritis scores. Thus, experimental immune complex–mediated glomerulonephritis is associated with accumulation of M1 macrophages and CD4+ T cells in kidneys and functional renal insufficiency. Hence, CD11b on mononuclear cells is instrumental in generating an anti-inflammatory response in the inflamed kidney. PMID:25565310
Shimizu, Maki; Sekiguchi, Takanori; Kishi, Natsuko; Goji, Aya; Takahashi, Tomoko; Kozan, Hiroko; Sakaguchi, Zenichi; Kinoshita, Yukiko; Matsuura, Sato; Suga, Kenichi; Urushihara, Maki; Kondo, Shuji; Kagami, Shoji; Ohara, Katsuaki
A 6-year-old girl was admitted to our hospital with proteinuria, hematuria, skin rash and joint pain of the lower limbs. Due to rapid progression of renal insufficiency, hemodialysis and peritoneal dialysis were performed. She was diagnosed with rapidly progressive glomerulonephritis. Kidney biopsy showed severe crescent formation (50% of glomeruli) and no deposition of any immunoglobulins or complements. Serologically, anti-neutrophil cytoplasmic autoantibody (ANCA) was negative not only by ELISA against proteinase-3 and myeloperoxidase-ANCA but also by indirect immunofluorescent assay against cytoplasmic and perinuclear ANCA. Anti-glomerular basement membrane antibody was also negative. In the acute phase, proinflammatory cytokines such as soluble tumor necrosis factor receptor 1 (sTNFR1), soluble interleukin (IL)-2 receptor (sIL2R), IL-6 and chemokine IL-8 were elevated. The patient was diagnosed with ANCA-negative pauci-immune crescentic glomerulonephritis (CrGN). Intensive treatment with methylprednisolone pulse therapy, plasma exchange, and multiple drug therapy including prednisolone and cyclophosphamide resulted in histopathological improvement and complete remission of proteinuria. There was a possibility that sTNFR1, sIL2R, IL-6 and IL-8 might be involved in the initiation and progression of ANCA-negative pauci-immune CrGN, and to remove and suppress these cytokines might be an effective way to treat ANCA-negative pauci-immune CrGN.
Lovett, D. H.; Johnson, R. J.; Marti, H. P.; Martin, J.; Davies, M.; Couser, W. G.
Secretion of glomerular cell-derived matrix metalloproteinases (MMPs) and their specific inhibitors, TIMP-1,2, may play an important role in the turnover of the glomerular extracellular matrix under basal and pathologic conditions. A 66-68 kd MMP secreted by cultured mesangial cells (MC) with activity against Type IV collagen and gelatin was purified and shown by amino-acid sequence analysis to be identical with a Type IV collagenase/gelatinase secreted by certain transformed tumor cell lines. The expression of the mesangial MMP in vivo was limited within the kidney to a small subset of the intrinsic glomerular mesangial cell population. After induction of acute anti-Thy 1.1 glomerulonephritis, there was a large increment in the number of Type IV collagenase-secreting MC, temporally coincident with the development of mesangial hypercellularity. The expression of the MMP inhibitor protein, TIMP-1, was not changed over this period. Ultrastructural studies localized the mesangial MMP to areas of evolving mesangiolysis and at sites of glomerular basement membrane disruption. Enhanced expression of the mesangial cell-derived Type IV collagenase may contribute to the evolution of glomerular injury in this model of immune complex-mediated glomerulonephritis or may be involved in the extensive matrix remodeling process that accompanies this form of glomerular injury. Images Figure 2 Figure 3 Figure 5 Figure 4 Figure 6 Figure 7 Figure 8 and Figure 9 Figure 10 Figure 11 Figure 12 PMID:1321565
Birmingham, D.J.; Hebert, L.A.; Cosio, F.G.; VanAman, M.E. )
Multiple lines of evidence indicate that the erythrocyte complement receptor (E-CR) system, which is unique to the primate, may play an important role in the clearing of immune complexes (ICs) from the circulation. However, all previous investigations of IC/E-CR interactions in vivo have involved the study of small amounts of preformed or passively formed ICs interacting with E-CR that were numerically in vast excess. The present study was undertaken to assess IC/E-CR interactions under conditions in which large amounts of ICs were formed in the circulation, amounts that when sustained for several weeks by daily intravenous administration of antigen resulted in the development of active glomerulonephritis. Twelve cynomolgus monkeys with E-CR levels ranging from 25 to 5000 mean CRs per erythrocyte (CR/E) were actively immunized to BGG, and 6 to 12 weeks later they were studied first at low levels of IC formation in vivo and then at high levels of IC formation in vivo (H-Protocol experiments, mean 125I-labeled BGG dose 4.9 mg/kg given over 10 minutes, a state approximating antigen-antibody equivalence). Cynomolgus monkeys with fewer than 100 CR/E showed no evidence of binding of ICs to erythrocytes with either low-dose or high-dose 125I-labeled BGG. However, cynomolgus monkeys with greater than 450 CR/E showed significant binding of ICs to erythrocytes: mean peak binding of 125I-labeled BGG to erythrocytes was 22.1% +/- 1.1% in the L-Protocol experiments and 33.4% +/- 8.0% in the H-Protocol experiments. During H-Protocol experiments, mean CR/E, measured by using a monoclonal anti-human CR1 antibody, decreased acutely, with recovery of E-CR levels within the next 24 to 72 hours. The acute decrease in E-CR levels could not be accounted for by occupancy of E-CR by ICs or by change in hematocrit.
Glomerulonephritis (GN) characterized by immune complex deposits typical of postinfectious GN but with a paucity or absence of overt clinical symptoms and/or urinary abnormalities may occur after a group A streptococcus infection. The overall incidence of this type of subclinical GN is not known. To address this question, electron microscopy findings in 1012 consecutive renal biopsy specimens (952 native kidney, 60 transplant) examined by a single renal pathologist from August 1999 to April 2002 were retrospectively reviewed for the presence of distinct subepithelial and intramembranous deposits indicative of postinfectious GN. Such deposits were noted in 83 biopsy specimens, including 26 with a primary diagnosis of postinfectious GN (acute, persistent, or latent) and 57 in which these deposits were an incidental finding. In each of the latter 57 cases, some or all of the deposits showed partial or extensive loss of electron density typical of partially or largely resorbed deposits. A diagnosis of incidental postinfectious GN was not made in any biopsy specimen exhibiting another immune complex-related glomerular disease that could possibly account for the deposits, composing 443 of the 1012 biopsy specimens examined. Thirty of the 57 biopsy specimens with incidental postinfectious GN showed mesangial hypercellularity, although this was focal and segmental in all but 3 cases and was not accompanied by the endocapillary hypercellularity typical of acute postinfectious lesions. Immunofluorescence microscopy revealed glomerular deposits of C3 in >90% of these biopsy specimens and IgM deposits in 66%, but only rare IgG, IgA, and Cq deposits. Twenty-three (40%) of these 57 biopsy specimens exhibited diabetic nephropathy, either alone or in combination with another lesion; for perspective, only 128 (13%) of the 1012 biopsy specimens examined showed evidence of diabetic nephropathy. In summary, incidental evidence of resolving or largely healed postinfectious GN was noted
Burke, Rebecca J; Chang, Christopher
Acute rheumatic fever is an inflammatory sequela of Group A Streptococcal pharyngitis that affects multiple organ systems. The incidence of acute rheumatic fever has been declining even before the use of antibiotics became widespread, however the disease remains a significant cause of morbidity and mortality in children, particularly in developing countries and has been estimated to affect 19 per 100,000 children worldwide. Acute rheumatic fever is a clinical diagnosis, and therefore subject to the judgment of the clinician. Because of the variable presentation, the Jones criteria were first developed in 1944 to aid clinicians in the diagnosis of acute rheumatic fever. The Jones criteria have been modified throughout the years, most recently in 1992 to aid clinicians in the diagnosis of initial attacks of acute rheumatic fever and to minimize overdiagnosis of the disease. Diagnosis of acute rheumatic fever is based on the presence of documented preceding Group A Streptococcal infection, in addition to the presence of two major manifestations or one major and two minor manifestations of the Jones criteria. Without documentation of antecedent Group A Streptococcal infection, the diagnosis is much less likely except in a few rare scenarios. Carditis, polyarthritis and Sydenham's chorea are the most common major manifestations of acute rheumatic fever. However, despite the predominance of these major manifestations of acute rheumatic fever, there can be significant overlap with other disorders such as Lyme disease, serum sickness, drug reactions, and post-Streptococcal reactive arthritis. This overlap between disease processes has led to continued investigation of the pathophysiology as well as development of new biomarkers and laboratory studies to aid in the diagnosis of acute rheumatic fever and distinction from other disease processes.
Cook, H. T.; Sullivan, R.
Nitrite (NO2-) is the major end product of nitric oxide (NO) production in cell culture. The authors have examined nitrite production by glomeruli in in situ immune complex glomerulonephritis in the rat. Glomerulonephritis was induced by unilateral renal perfusion of cationized human gamma G immunoglobulin (IgG) in preimmunized rats. NO2- was measured in culture supernatants of isolated glomeruli after 48 hours. NO2- was produced by nephritic glomeruli with a maximum 4 days after induction of glomerulonephritis (24.4 +/- 11.4 pmol/glomerulus/48 hours). Production was increased by lipopolysaccharide (LPS; 1 micrograms/ml) (54 +/- 4.9 pmol/glomerulus; P less than 0.001). NO2- production was inhibited by the nitric oxide synthase inhibitor NG-monomethyl-L-arginine demonstrating synthesis through NO. Dexamethasone (10(-7) mol/l [molar]) reduced LPS-stimulated production by peritoneal macrophages and nephritic glomeruli (P less than 0.01). Macrophages isolated from nephritic glomeruli produced NO2- (4.9 +/- 0.6 nmols/10(5) cells). The production of NO by nephritic glomeruli has implications for mechanisms of glomerular injury and glomerular hemodynamics. The effect of dexamethasone may explain in part the ameliorative effect of steroids in glomerulonephritis. Images Figure 4 PMID:1951626
Raybould, Jillian E; Raybould, Alison L; Morales, Megan K; Zaheer, Misbah; Lipkowitz, Michael S; Timpone, Joseph G; Kumar, Princy N
Among culture-negative endocarditis in the United States, Bartonella species are the most common cause, with Bartonella henselae and Bartonella quintana comprising the majority of cases. Kidney manifestations, particularly glomerulonephritis, are common sequelae of infectious endocarditis, with nearly half of all Bartonella patients demonstrating renal involvement. Although a pauci-immune pattern is a frequent finding in infectious endocarditis-associated glomerulonephritis, it is rarely reported in Bartonella endocarditis. Anti-neutrophil cytoplasmic antibody (ANCA) positivity can be seen with many pathogens causing endocarditis and has been previously reported with Bartonella species. In addition, ANCA-associated vasculitis can also present with renal and cardiac involvement, including noninfectious valvular vegetations and pauci-immune glomerulonephritis. Given the overlap in their clinical presentation, it is difficult to differentiate between Bartonella endocarditis and ANCA-associated vasculitis but imperative to do so to guide management decisions. We present a case of ANCA-positive Bartonella endocarditis with associated pauci-immune glomerulonephritis that was successfully treated with medical management alone.
McPhaul, J J; Mullins, J D
A prospective study was undertaken to establish the incidence of glomerular basement membrane (GBM) antibody-mediated glomerulonephritis and its histopathological characteristics in a clinical group of patients presenting with renal disease. Biopsies from 43 of 409 consecutive patients technically satisfactory for direct immunofluorescent (IF) examination had diffuse and generalized linear localization of host immunoglobulin (Ig); two other badly scarred kidneys tested negative to IF although GBM antibodies were eluted. Confirmatory evidence of GBM antibody-mediated disease in these patients came from whole kidney or biopsy elutions (15 patients), serologic assays for circulating GBM antibodies by indirect IF (9 of 38 patients), radioimmunoassay (26 of 34), and hemagglutination (31 of 32). Although sera were not tested from six patients, circulating antibodies were demonstrated by some test in 36 of 39 of the remainder. Histologically, half of the patients had minor and nonspecific glomerular abnormalities or mild focal proliferative glomerulonephritis. More severely involved kidneys had focal necrotizing (17%), rapidly progressive (7%), and chronic, usually sclerosing, glomerulonephritis (27%). Clinical courses of these patients comparably were quite variable, ranging from indolent microhematuria and/or gross hematuric bouts to progressive renal failure; nephrotic syndrome was observed in 11 patients. GBM antibody-mediated glomerulonephritis may be a relatively mild disease with apparently stable renal function, although 16 patients have experienced functional deterioration, and 11 have progressed to dialysis, renal transplantation, or death. Images PMID:56340
Zhang, Hongxia; Mao, Xing; Sun, Yu; Hu, Ruimin; Luo, Weili; Zhao, Zhonghua; Chen, Qi; Zhang, Zhigang
Podocyte injury is a pivotal factor during the progression of glomerular diseases. It has been demonstrated that the expression of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is increased in injured podocytes in a number of types of glomerulonephritis. However, its mechanism of regulation remains to be elucidated. A previous study by our group suggested that UCH-L1 is a downstream protein of nuclear factor (NF)-κB signaling. In the present study, the involvement of NF-κB in the regulation of the expression of UCH-L1 was investigated in diseased podocytes in vivo and in vitro. Increases in the expression of phosphorylated NF-κB at p65 and UCH-L1 were detected using immunohistochemical analysis of kidney biopsy tissues from 56 cases of nephritis, including immunoglobulin A nephropathy, membranous glomerulonephritis and lupus nephritis. The two indicators were also analyzed using western blot analysis in cultured murine podocytes stimulated by inflammatory factors. The results of the present study demonstrated that in human renal biopsies of several cases of immune complex-mediated glomerulonephritis, the increases of NF-κB and UCH-L1 were positively correlated with the number of diseased podocytes. By contrast, in non-immune complex-mediated glomerulonephritis, no clear activation of NF-κB and increase of UCH-L1 expression was observed. In vitro, immune stimulation also led to the upregulation of UCH-L1 through the NF-κB signaling pathway in mouse podocytes. In conclusion, the results of the present study suggested that the activation of NF-κB and upregulation of UCH-L1 in podocytes may be vital in podocyte injury associated with immune complex-mediated glomerulonephritis.
Couser, W G; Johnson, R J; Young, B A; Yeh, C G; Toth, C A; Rudolph, A R
Complement is a major mediator of tissue injury in several types of glomerulonephritis. However, no therapeutic agents that inhibit complement activation are available for human use. sCR1 (TP10, BRL 55736) is a recombinant, soluble human complement receptor 1 (CR1) molecule lacking transmembrane and cytoplasmic domains that inhibits C3 and C5 convertase activity by preferentially binding C4b and C3b. To test the efficacy of sCR1 on complement-mediated glomerulonephritis, rats were pretreated with sCR1 (60 mg/kg per day) before and during the induction of three models of complement-dependent glomerulonephritis (concanavalin A and antithymocyte serum models of proliferative glomerulonephritis, passive Heyman nephritis). Daily sCR1 and complement hemolytic activity levels were measured, and renal histology and urine protein excretion were examined. Mean serum sCR1 levels of 100 to 200 micrograms/mL were maintained with a reduction in complement hemolytic activity to less than 15% in most animals. In the antithymocyte serum model, sCR1-treated animals had significant reductions in mesangiolysis, glomerular platelet and macrophage infiltrates, and proteinuria at 48 h. In the concanavalin A model, sCR1 significantly reduced glomerular C3 and fibrin deposits, platelet infiltrates, and proteinuria at 48 h. In passive Heymann nephritis, proteinuria was also significantly reduced (199 +/- 8.5 versus 125 +/- 16 mg/day, P < 0.002) at 5 days. It was concluded that sCR1 significantly reduces both morphologic and functional consequences of several different types of complement-mediated glomerulonephritis and deserves evaluation as a potential therapeutic agent in complement-mediated immune glomerular disease in humans.
Haas, M; Jafri, J; Bartosh, S M; Karp, S L; Adler, S G; Meehan, S M
Antineutrophil cytoplasmic autoantibodies (ANCA) are commonly associated with a necrotizing and crescentic glomerulonephritis (GN) that is pauci-immune, with few or no glomerular immune complex deposits detectable by immunofluorescence (IF) or electron microscopy (EM). Immunoglobulin A (IgA) nephropathy may also be manifest as a crescentic GN, but it is characterized by mesangial immune complex deposits containing IgA and is rarely associated with myeloperoxidase (MPO)- or proteinase 3 (PR3)-specific ANCA when an enzyme immunoassay is used to detect these antibodies. This report describes six patients with severe crescentic GN with mesangial IgA deposits by IF and mesangial electron-dense deposits by EM in patients with positive ANCA serological test results (four patients, anti-PR3; one patient, anti-MPO; one patient, anti-PR3 and anti-MPO). Patients presented with acute or progressive renal insufficiency, hematuria, proteinuria (nephrotic range in two patients), and hypertension. Three patients had evidence of systemic vasculitis: two patients at initial presentation and one patient later in the clinical course. Renal biopsy specimens showed crescents in greater than 50% of glomeruli in all cases, but only mild, focal and segmental mesangial and endocapillary hypercellularity, more typical of ANCA-associated crescentic GN than of crescentic IgA nephropathy without associated ANCA. Semiquantitative analysis of mesangial and endocapillary cellularity performed on renal biopsy slides from these six patients and from eight ANCA-negative patients with IgA nephropathy and crescents in greater than 50% of glomeruli showed significantly greater hypercellularity in the ANCA-negative cases. Three of five ANCA-positive patients for whom follow-up clinical data were available showed improved renal function after treatment with cyclophosphamide and corticosteroids and have not developed end-stage renal disease 17, 20, and 25 months postbiopsy. The remaining two patients were
Luna, Mariana; Bocanegra, Victoria; Vallés, Patricia G
Granulomatosis with polyangiitis (GPA) is associated with a broad range of clinical manifestations including renal disease. It is a systemic vasculitis that is rarely encountered in children. We present a 14-year-old girl who suffered from pharyngitis 1 week before admittance to hospital. She was admitted for macroscopic hematuria and oliguria, under the possibility of nephritic syndrome. Renal failure with rapidly progressive glomerulonephritis occurred within 24 hours. Immunologic tests showed the presence of type-C anti-neutrophil cytoplasmic antibodies (c-ANCA with antiproteinase 3 specificity) and renal biopsy revealed pauci-immune crescentic focal necrotizing glomerulonephritis. Treatment including methylprednisolone and cyclophosphamide intravenous pulses allowed renal recovery after 3 weeks. The clinical, hematological, and biochemical parameters improved substantially, achieving remission. Granulomatosis with polyangiitis, although rare in children, should be considered in the above clinical scenario. This case underlines that knowledge of renal histology diagnosis and early aggressive immunosuppressive therapy are essential for the management of these patients. PMID:24790466
Diouf, B; Diao, M; Niang, A; Ka, E F; Moreira Diop, T
Berger's disease or IgA glomerulonephritis is the most common glomerular nephropathy in Europe and represent a rare event in blacks. Here, we describe the case of a 43 years old black Senegalese whose disease was discovered while investigating a persistent proteinuria with high blood pressure and chronic renal failure, but without hematuria. We point out the uncommon feature of this clinical presentation and the importance of bad prognostic factors presented by this patient. We obtained a good outcome by means of converting enzyme inhibitors and corticosteroid therapies: regression of renal failure and normalization of blood pressure. The generalization of renal biopsy practice would lead to a better knowledge of the incidence of this disease among Senegalese people. Indeed, renal biopsy is the main tool to diagnose glomerulonephritis and subsequently adapt the therapy aimed at preventing the possible evolution to end stage renal disease.
Wu, Jian-Guo; Wu, Jin-Zhong; Sun, Lian-Na; Han, Ting; Du, Jian; Ye, Qi; Zhang, Hong; Zhang, Yu-Guang
Membranous glomerulonephritis (MGN) remains the most common cause of adult-onset nephrotic syndrome in the world and up to 40% of untreated patients will progress to end-stage renal disease. Although the treatment of MGN with immunosuppressants or steroid hormones can attenuate the deterioration of renal function, numerous treatment-related complications have also been established. In this study, the ameliorative effects of arctiin, a natural compound isolated from the fruits of Arctium lappa, on rat glomerulonephritis induced by cationic bovine serum albumin (cBSA) were determined. After oral administration of arctiin (30, 60, 120 mg/kgd) for three weeks, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) and 24-h urine protein content markedly decreased, while endogenous creatinine clearance rate (ECcr) significantly increased. The parameters of renal lesion, hypercellularity, infiltration of polymorphonuclear leukocyte (PMN), fibrinoid necrosis, focal and segmental proliferation and interstitial infiltration, were reversed. In addition, we observed that arctiin evidently reduced the levels of malondialdehyde (MDA) and pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF-alpha), suppressed nuclear factor-kappaB p65 (NF-kappaB) DNA binding activity, and enhanced superoxide dismutase (SOD) activity. These findings suggest that the ameliorative effects of arctiin on glomerulonephritis is carried out mainly by suppression of NF-kappaB activation and nuclear translocation and the decreases in the levels of these pro-inflammatory cytokines, while SOD is involved in the inhibitory pathway of NF-kappaB activation. Arctiin has favorable potency for the development of an inhibitory agent of NF-kappaB and further application to clinical treatment of glomerulonephritis, though clinical studies are required.
Howell, David N
Kidney biopsy is a mainstay in the diagnosis and management of renal disease in patients with systemic lupus erythematosus. Though biopsies from patients with lupus typically show various forms of immune complex glomerulonephritis, other pathologies are occasionally encountered, including unusual lupus-related nephropathies, other forms of autoimmune disease, and occasional renal disorders without any direct connection with lupus or autoimmunity. Electron microscopy is a powerful tool for detecting and classifying these unusual conditions, which frequently have important therapeutic and prognostic implications.
Ma, Frank Y.; Han, Yingjie; Nikolic-Paterson, David J.; Kolkhof, Peter; Tesch, Greg H.
Background/Aim Steroidal mineralocorticoid receptor antagonists (MRAs) are effective in the treatment of kidney disease; however, the side effect of hyperkalaemia, particularly in the context of renal impairment, is a major limitation to their clinical use. Recently developed non-steroidal MRAs have distinct characteristics suggesting that they may be superior to steroidal MRAs. Therefore, we explored the benefits of a non-steroidal MRA in a model of rapidly progressive glomerulonephritis. Methods Accelerated anti-glomerular basement membrane (GBM) glomerulonephritis was induced in groups of C57BL/6J mice which received no treatment, vehicle or a non-steroidal MRA (BR-4628, 5mg/kg/bid) from day 0 until being killed on day 15 of disease. Mice were examined for renal injury. Results Mice with anti-GBM glomerulonephritis which received no treatment or vehicle developed similar disease with severe albuminuria, impaired renal function, glomerular tuft damage and crescents in 40% of glomeruli. In comparison, mice which received BR-4628 displayed similar albuminuria, but had improved renal function, reduced severity of glomerular tuft lesions and a 50% reduction in crescents. The protection seen in BR-4628 treated mice was associated with a marked reduction in glomerular macrophages and T-cells and reduced kidney gene expression of proinflammatory (CCL2, TNF-α, IFN-γ) and profibrotic molecules (collagen I, fibronectin). In addition, treatment with BR-4626 did not cause hyperkalaemia or increase urine Na+/K+ excretion (a marker of tubular dysfunction). Conclusions The non-steroidal MRA (BR-4628) provided substantial suppression of mouse crescentic glomerulonephritis without causing tubular dysfunction. This finding warrants further investigation of non-steroidal MRAs as a therapy for inflammatory kidney diseases. PMID:26700873
Schulze, M.; Pruchno, C. J.; Burns, M.; Baker, P. J.; Johnson, R. J.; Couser, W. G.
In antibody-mediated glomerular disease, deposits of C3 (C3b) are common and are degraded by factor I to C3c and C3d. However, the kinetics of C3b degradation in glomerulonephritis have not been defined. To do this, we studied three models of complement-dependent glomerulonephritis with established C3 deposits (passive Heymann nephritis, cationized immunoglobulin G membranous nephropathy, and concanavalin A-anticoncanavalin A glomerulonephritis). C3b deposition was halted by administration of cobra venom factor, and the disappearance of C3c and C3d from glomeruli was measured with specific antibodies and quantitative fluorescence densitometry. Results showed that C3c deposits were reduced by over 85% within 24 hours in all three models. C3c clearance was unaffected by site or mechanism of deposit formation. C3d deposits persisted despite lack of ongoing complement activation. In passive Heymann nephritis when disease activity was monitored by urinary C5b-9 excretion, C3c was cleared in parallel with return of urine C5b-9 excretion to normal values. We conclude that glomerular deposits of C3c are cleared within 24 hours of cessation of complement activation. Positive staining for C3 utilizing antibody specific for the C3c portion documents recent complement activation usually reflecting new immune deposit formation. Images Figure 1 Figure 2 Figure 3 PMID:7678717
Turner, Jan-Eric; Paust, Hans-Joachim; Steinmetz, Oliver M.; Peters, Anett; Riedel, Jan-Hendrik; Erhardt, Annette; Wegscheid, Claudia; Velden, Joachim; Fehr, Susanne; Mittrücker, Hans-Willi; Tiegs, Gisa; Stahl, Rolf A.K.
T cells recruited to the kidney contribute to tissue damage in crescentic and proliferative glomerulonephritides. Chemokines and their receptors regulate T cell trafficking, but the expression profile and functional importance of chemokine receptors for renal CD4+ T cell subsets are incompletely understood. In this study, we observed that renal FoxP3+CD4+ regulatory T cells (Tregs) and IL-17–producing CD4+ T (Th17) cells express the chemokine receptor CCR6, whereas IFNγ-producing Th1 cells are CCR6−. Induction of experimental glomerulonephritis (nephrotoxic nephritis) in mice resulted in upregulation of the only CCR6 ligand, CCL20, followed by T cell recruitment, renal tissue injury, albuminuria, and loss of renal function. CCR6 deficiency aggravated renal injury and increased mortality (from uremia) among nephritic mice. Compared with wild-type (WT) mice, CCR6 deficiency reduced infiltration of Tregs and Th17 cells but did not affect recruitment of Th1 cells in the setting of glomerulonephritis. Adoptive transfer of WT but not CCR6-deficient Tregs attenuated morphologic and functional renal injury in nephritic mice. Furthermore, reconstitution with WT Tregs protected CCR6−/− mice from aggravated nephritis. Taken together, these data suggest that CCR6 mediates renal recruitment of both Tregs and Th17 cells and that the reduction of anti-inflammatory Tregs in the presence of a fully functional Th1 response aggravates experimental glomerulonephritis. PMID:20299360
Aoki, Yoshihiro; Tanimoto, Izumi; Miyauchi, Yoshihiro; Suzuki, Yoshio; Shiojiri, Toshiaki
Patient: Female, 44 Final Diagnosis: Anti-glomerular basement membrane glomerulonephritis Symptoms: Fever Medication: — Clinical Procedure: — Specialty: Nephrology Objective: Rare co-existance of disease or pathology Background: Type 1 diabetes mellitus (DM) tends to complicate other autoimmune diseases. When considering renal dysfunction in patients with DM, diabetic nephropathy is a likely diagnosis. By contrast, anti-glomerular basement membrane (GBM) glomerulonephritis, an autoimmune disease, is one cause of rapidly progressive glomerulonephritis. Case Report: We report the case of a 44-year-old woman diagnosed with anti-glomerular basement membrane (GBM) glomerulonephritis. The diagnosis was made on the basis of serological test results and pathological findings of a renal biopsy. Five years before admission, she was diagnosed with type 1 DM. At admission, she presented with a fever, chills, nausea, low back pain, and malaise, which were followed by progressive renal dysfunction. The initial presentation mimicked a urinary tract infection, which delayed the correct diagnosis. Conclusions: Our patient’s course strongly suggests that rapidly progressive glomerulonephritis should be considered as an early differential diagnosis in cases of progressive renal dysfunction, especially when accompanied by fever, regardless of the underlying disease. PMID:28344312
Miyata, Naoko; Kobayashi, Tomoko; Matsukawa, Yoshihiro; Sawada, Shigemasa; Nishinarita, Susumu; Horie, Takashi
We report two patients with scleroderma, 73-year-old female and 67-year-old female, who developed anti neutrophil cytoplasmic autoantibody (ANCA) associated rapid progressive glomerulonephritis (RPGN). Both patients have had a long history of scleroderma (23 and 14 years, respectively) when ANCA-associated glomerulonephritis occurred. In the first patient, scleroderma was localized in both fingers. She has been followed-up as CREST syndrome rather than systemic sclerosis. The complaints on admission were leg edema and left chest pain in the first patient, and a pyrexia and dyspnea in the second patient. Both patients showed pulmonary manifestation (pleural effusion in the first patient, interstitial pneumonia and alveolar hemorrhage in the second patient, respectively) and rapid progressive glomerulonephritis. Both patients died in spite of corticosteroid therapy. Autopsy findings in the second patient demonstrated crescentic glomerulonephritis and alveolar hemorrhage. Our cases demonstrated that MPO-ANCA associated glomerulonephritis could be associated with limited scleroderma as well as systemic scleroderma. In these condition, the prognosis will be poor if scleroderma seemed to be stable.
Background Immune complex deposition is the accepted mechanism of pathogenesis of VL glomerulopathy however other immune elements may participate. Further in the present study, no difference was seen between immunoglobulin and C3b deposit intensity in glomeruli between infected and non-infected dogs thus T cells, adhesion molecules and parameters of proliferation and apoptosis were analysed in dogs with naturally acquired VL from an endemic area. The dog is the most important domestic reservoir of the protozoa Leishmania (L.) chagasi that causes visceral leishmaniasis (VL). The similarity of VL manifestation in humans and dogs renders the study of canine VL nephropathy of interest with regard to human pathology. Methods From 55 dogs with VL and 8 control non-infected dogs from an endemic area, kidney samples were analyzed by immunohistochemistry for immunoglobulin and C3b deposits, staining for CD4+ and CD8+ T cells, ICAM-1, P-selectin and quantified using morphometry. Besides proliferation marker Ki-67, apoptosis markers M30 and TUNEL staining, and related cytokines TNF-α, IL-1α were searched and quantified. Results We observed similar IgG, IgM and IgA and C3b deposit intensity in dogs with VL and non-infected control dogs. However we detected the Leishmania antigen in cells in glomeruli in 54, CD4+ T cells in the glomeruli of 44, and CD8+ T cells in 17 of a total of 55 dogs with VL. Leishmania antigen was absent and T cells were absent/scarse in eight non-infected control dogs. CD 4+ T cells predominate in proliferative patterns of glomerulonephritis, however the presence of CD4+ and CD8+ T cells were not different in intensity in different patterns of glomerulonephritis. The expression of ICAM-1 and P-selectin was significantly greater in the glomeruli of infected dogs than in control dogs. In all patterns of glomerulonephritis the expression of ICAM-1 ranged from minimum to moderately severe and P-selectin from absent to severe. In the control animals the
Luque, Yosu; Cathelin, Dominique; Vandermeersch, Sophie; Xu, Xiaoli; Sohier, Julie; Placier, Sandrine; Xu-Dubois, Yi-Chun; Louis, Kevin; Hertig, Alexandre; Bories, Jean-Christophe; Vasseur, Florence; Campagne, Fabien; Di Santo, James P; Vosshenrich, Christian; Rondeau, Eric; Mesnard, Laurent
Crescentic glomerulonephritis is a life-threatening renal disease that has been extensively studied by the experimental anti-glomerular basement membrane glomerulonephritis (anti-GBM-GN) model. Although T cells have a significant role in this model, athymic/nude mice and rats still develop severe renal disease. Here we further explored the contribution of intrinsic renal cells in the development of T-cell-independent GN lesions. Anti-GBM-GN was induced in three strains of immune-deficient mice (Rag2(-/-), Rag2(-/-)Il2rg(-/-), and Rag2(-/-)Il2rb(-/-)) that are devoid of either T/B cells or T/B/NK cells. The Rag2(-/-)Il2rg(-/-) or Rag2(-/-)Il2rb(-/-) mice harbor an additional deletion of either the common gamma chain (γC) or the interleukin-2 receptor β subunit (IL-2Rβ), respectively, impairing IL-15 signaling in particular. As expected, all these strains developed severe anti-GBM-GN. Additionally, bone marrow replenishment experiments allowed us to deduce a protective role for the glomerular-expressed γC during anti-GBM-GN. Given that IL-15 has been found highly expressed in nephritic kidneys despite the absence of lymphocytes, we then studied this cytokine in vitro on primary cultured podocytes from immune-deficient mice (Rag2(-/-)Il2rg(-/-) and Rag2(-/-)Il2rb(-/-)) compared to controls. IL-15 induced downstream activation of JAK1/3 and SYK in primary cultured podocytes. IL-15-dependent JAK/SYK induction was impaired in the absence of γC or IL-2Rβ. We found γC largely induced on podocytes during human glomerulonephritis. Thus, renal lesions are indeed modulated by intrinsic glomerular cells through the γC/IL-2Rβ receptor response, to date classically described only in immune cells.
Jacob, Alexander; Chaves, Lee; Eadon, Michael T; Chang, Anthony; Quigg, Richard J; Alexander, Jessy J
Complement factor H (Cfh) is a key regulator of the complement cascade and protects C57BL/6 mice from immune complex-mediated complement-dependent glomerulonephritis. In chronic serum sickness (CSS) there are increased deposits of immune complexes in the glomeruli with inflammation and a scarring phenotype. As cucurmin is an effective anti-inflammatory agent and reduces complement activation, we hypothesized that it should alleviate renal disease in this setting. To determine the effectiveness of curcumin, an apoferritin-induced CSS model in Cfh-deficient (Cfh−/−) mice was used. Curcumin treatment (30 mg/kg) given every day in parallel with apoferritin reduced glomerulonephritis and enhanced kidney function (blood urea nitrogen, 45·4 ± 7·5 versus 35·6 ± 5·1; albuminuria, 50·1 ± 7·1 versus 15·7 ± 7·1; glomerulonephritis, 2·62 + 0·25 versus 2 + 0·3, P < 0·05). In line with reduced IgG deposits in mice with CSS given curcumin, C9 deposits were reduced indicating reduced complement activation. Mice treated with curcumin had a significant reduction in the number of splenic CD19+ B cells and the ratio of CD19 : CD3 cells (P < 0·05) with no change in the T-cell population. Myeloperoxidase assay showed reduced macrophages in the kidney. However, a significant reduction in the M2 subset of splenic macrophages by apoferritin was prevented by curcumin, suggesting a protective function. Curcumin treatment reduced mRNA expression of inflammatory proteins monocyte chemoattractant protein-1 and transforming growth factor-β and matrix proteins, fibronectin, laminin and collagen. Our results clearly illustrate that curcumin reduces glomerulosclerosis, improves kidney function and could serve as a therapeutic agent during serum sickness. PMID:23347386
Jacob, Alexander; Chaves, Lee; Eadon, Michael T; Chang, Anthony; Quigg, Richard J; Alexander, Jessy J
Complement factor H (Cfh) is a key regulator of the complement cascade and protects C57BL/6 mice from immune complex-mediated complement-dependent glomerulonephritis. In chronic serum sickness (CSS) there are increased deposits of immune complexes in the glomeruli with inflammation and a scarring phenotype. As cucurmin is an effective anti-inflammatory agent and reduces complement activation, we hypothesized that it should alleviate renal disease in this setting. To determine the effectiveness of curcumin, an apoferritin-induced CSS model in Cfh-deficient (Cfh(-/-)) mice was used. Curcumin treatment (30 mg/kg) given every day in parallel with apoferritin reduced glomerulonephritis and enhanced kidney function (blood urea nitrogen, 45·4 ± 7·5 versus 35·6 ± 5·1; albuminuria, 50·1 ± 7·1 versus 15·7 ± 7·1; glomerulonephritis, 2·62 + 0·25 versus 2 + 0·3, P < 0·05). In line with reduced IgG deposits in mice with CSS given curcumin, C9 deposits were reduced indicating reduced complement activation. Mice treated with curcumin had a significant reduction in the number of splenic CD19(+) B cells and the ratio of CD19 : CD3 cells (P < 0·05) with no change in the T-cell population. Myeloperoxidase assay showed reduced macrophages in the kidney. However, a significant reduction in the M2 subset of splenic macrophages by apoferritin was prevented by curcumin, suggesting a protective function. Curcumin treatment reduced mRNA expression of inflammatory proteins monocyte chemoattractant protein-1 and transforming growth factor-β and matrix proteins, fibronectin, laminin and collagen. Our results clearly illustrate that curcumin reduces glomerulosclerosis, improves kidney function and could serve as a therapeutic agent during serum sickness.
Yamaguchi-Yamada, Misuzu; Akashi, Naotsugu; Goto, Yasufumi; Anan, Sayuri; Yamamoto, Yoshie; Ogura, Atsuo; Manabe, Noboru
The ICR-derived glomerulonephritis (ICGN) mouse is an appropriate model for anemia associated with chronic renal disorder (CRD). Insufficient renal production of erythropoietin (EPO) induces the anemia associated with CRD. EPO mRNA is expressed in both kidneys and liver of progressing-stage ICGN mice. Hypoxic stimulation induced the EPO mRNA expression in the liver as well as in the kidneys of ICGN mice. The localization of EPO-producing cells in the liver remains controversial. Present study using an amplified in situ hybridization technique identified that nonparenchymal cells were the source of hepatic EPO production in ICGN mice under both normoxia and hypoxia.
Rampelli, S K; Rajesh, N G; Srinivas, B H; Harichandra Kumar, K T; Swaminathan, R P; Priyamvada, P S
There is limited data on the etiology, clinical and histopathological spectrum and outcomes of crescentic glomerulonephritis (CrGN) in adult Indian population. This prospective study was done to evaluate the etiology, clinicohistological patterns and predictors of outcome of CrGN in South Indian population. All the patients received standard protocol based immunosuppression in addition to supportive care. Immune-complex glomerulonephritis (ICGN) was the most common etiology (n = 31; 77.5%) followed by pauci-immune glomerulonephritis (PauciGN; n = 8; 20%) and anti-glomerular basement membrane disease (n = 1; 2.5%). The most common etiology of ICGN was IgA nephropathy (n = 11; 27.5%) followed by lupus nephritis (n = 7; 17.5%) and post-infectious glomerulonephritis (PIGN) (n = 7; 17.5%). The patients with PauciGN were significantly older compared to those with ICGN (44.5 ± 15 years vs. 31.8 ± 11 years; P = 0.01). The patients with PauciGN presented with significantly higher serum creatinine (9.7 ± 4.4 vs. 6.6 ± 3.3 mg/dl; P = 0.03). The histopathologic parameters of ICGN and PauciGN were comparable except for a higher proportion of sclerosed glomeruli in ICGN. At the end of 3 months follow-up, only two patients went into complete remission (5.4%). Majority of the patients had end-stage renal failure (48.6%) and were dialysis dependent and seven patients (18.9%) expired. There was no signifi difference in the renal survival (10.9 ± 1.9 vs. 9.6 ± 3.3 months) or patient survival (17.5 ± 2.1 vs. 17.3 ± 4.3 months). The parameters associated with adverse outcomes at 3 months were hypertension (odds ratio [OR]: 0.58; confidence interval [CI]: 0.36-0.94), need for renal replacement therapy (OR: 0.19; CI: 0.04-0.9), serum creatinine at admission (P = 0.019), estimated glomerular filtration rate (P = 0.022) and percentage of fibrocellular crescents (P = 0.022).
Babar, Faizan; Posner, Jeffery N.; Obah, Eugene A.
Hydralazine has been used since the 1950s for the management of hypertension. Evidence for hydralazine-associated vasculitis dates to pre-ANCA (antineutrophil cytoplasmic antibodies) era. This abstract describes two cases of ANCA-positive pauci-immune glomerulonephritis (GN) in challenging scenarios where diagnosis was misconstrued. A comprehensive literature review was done to understand the pathogenesis of drug-induced pauci-immune GN. We have described key diagnostic features that are helpful in distinguishing idiopathic ANCA vasculitis from drug-induced vasculitis. Additionally, we have also described different treatments meant to provide therapy options with the least side effects. PMID:27124161
Babar, Faizan; Posner, Jeffery N; Obah, Eugene A
Hydralazine has been used since the 1950s for the management of hypertension. Evidence for hydralazine-associated vasculitis dates to pre-ANCA (antineutrophil cytoplasmic antibodies) era. This abstract describes two cases of ANCA-positive pauci-immune glomerulonephritis (GN) in challenging scenarios where diagnosis was misconstrued. A comprehensive literature review was done to understand the pathogenesis of drug-induced pauci-immune GN. We have described key diagnostic features that are helpful in distinguishing idiopathic ANCA vasculitis from drug-induced vasculitis. Additionally, we have also described different treatments meant to provide therapy options with the least side effects.
Moll-Guillen, Jose-Luis; Espí-Reig, Jordi; Blanes-Julia, Marino; García-Martínez, Ana-María; Pujol-Marco, Conrad; Hernández-Jaras, Julio
Levamisole is illicitly employed as a cocaine adulterant. The consumption of levamisole-adulterated cocaine can provoke anti-neutrophil cytoplasmic antibody (ANCA)-associated syndromes. Patients carrying an HLAB27 allele are known to be at higher risk of developing agranulocytosis when treated with levamisole. Likewise, patients with ANCA-associated vasculitis (AAV) and internal organ involvement have typically been exposed to offending agents for prolonged periods of time, often on the order of years. Here, we report an unusual case of a patient in which kidney biopsy showed membranous glomerulonephritis with cellular crescents associated with levamisole-contaminated cocaine use. PMID:26605317
Moscoso-Solorzano, Grace T.; Madureira-Silva, Marcus V.; Balda, Carlos; Franco, Marcello F.; Mastroianni-Kirsztajn, Gianna
Background There are few reports of glomerulonephritis (GN) with crescents and a rapidly progressive course that lead to a diagnosis of a previously unsuspected B-cell dyscrasia. Case Presentation: We report a case of rapidly progressive GN: the patient showed no evidence of etiology at the time of biopsy and was diagnosed as IgA multiple myeloma (MM) during investigation based on a renal biopsy. He presented diffuse proliferative and exudative GN and marked plasma cell infiltration of the kidney. Conclusion The present case raises the possibility that proliferative GN with crescents may be a rare mode of presentation of MM. PMID:22470380
Sánchez-Cordón, P J; Salguero, F J; Núnez, A; Gómez-Villamandos, J C; Carrasco, L
This article describes a case of glomerulonephritis and immunocomplex (IgM, IgG and C3c) deposition in the mesangium and basement membranes of a 2-year-old dog with canine viral hepatitis and dirofilariasis. The deposits observed in the mesangium were in the vicinity of cells with viral replication. However, no clear relationship was found between viral replication and the deposition of immunocomplexes in the glomerular capillary basement membranes, which may be the reason why these deposits have only been tentatively related to the concomitant infestation by Dirofilaria immitis.
Al-Brahim, Nabeel; Zaki, Ashraf H; El-Merhi, Khaled; Ahmad, Mahmoud S
Kaposi sarcoma is a malignant vascular neoplasm uncommonly seen in immunosuppressed patients. Herein we report an unusual case of tonsillar Kaposi sarcoma in a patient with membranous glomerulonephritis treated with prednisolone and cyclosporine. The patient presented after 10 months of starting the treatment with a tonsillar mass. Histological examination was typical of monomorphic spindle cell proliferation with slit-like vascular channels. The tumor cells expressed CD34, D2-40 and positive nuclear stain for HHV-8. Kaposi sarcoma is associated with immunosuppression and rarely occurs in the tonsil. Clinicians should be aware of this rare presentation of Kaposi sarcoma.
Motiram Kakalij, Rahul; Tejaswini, G; Patil, Madhoosudan A; Dinesh Kumar, B; Diwan, Prakash V
Preclinical Research Vanillic acid (VA) is a dihydroxybenzoic acid derivative widely used as a flavoring agent. It has chemopreventive effects on experimentally-induced carcinogenesis and in ulcerative colitis. The object of the present study was to investigate the effects of VA, alone and in combination with methylprednisolone (MP), on cationic bovine serum albumin (cBSA induced immune-complex glomerulonephritis in female BALB/c mice. Pre-immunization was carried out with cBSA in BALB/c mice and repeated (cBSA, 13 mg/kg, 3 times/week, i.v.) for 6 weeks to induce glomerulonephritis which was confirmed by the presence of severe proteinuria. The effect of VA (50, 100, and 200 mg/kg, p.o.) and its combination with MP (12.5 mg/kg, p.o.) was assessed in the nephrotic disease model. Treatment with VA decreased inflammatory nephrotic injury as evidenced by decreased proteinuria, serum creatinine, blood urea nitrogen, serum IgG1 and TNF-α levels. Co-administration of VA with MP showed an improvement in the immunohistochemistry of glomerular nephrin and podocin. The present results indicate that VA has a nephroprotective effect in the management of autoimmune nephritis. Drug Dev Res 77 : 171-179, 2016. © 2016 Wiley Periodicals, Inc.
Maratou, K; Behmoaras, J; Fewings, C; Srivastava, P; D'Souza, Z; Smith, J; Game, L; Cook, T; Aitman, T
Crescentic glomerulonephritis (CRGN) is a major cause of rapidly progressive renal failure for which the underlying genetic basis is unknown. Wistar-Kyoto (WKY) rats show marked susceptibility to CRGN, whereas Lewis rats are resistant. Glomerular injury and crescent formation are macrophage dependent and mainly explained by seven quantitative trait loci (Crgn1-7). Here, we used microarray analysis in basal and lipopolysaccharide (LPS)-stimulated macrophages to identify genes that reside on pathways predisposing WKY rats to CRGN. We detected 97 novel positional candidates for the uncharacterized Crgn3-7. We identified 10 additional secondary effector genes with profound differences in expression between the two strains (>5-fold change, <1% false discovery rate) for basal and LPS-stimulated macrophages. Moreover, we identified eight genes with differentially expressed alternatively spliced isoforms, by using an in-depth analysis at the probe level that allowed us to discard false positives owing to polymorphisms between the two rat strains. Pathway analysis identified several common linked pathways, enriched for differentially expressed genes, which affect macrophage activation. In summary, our results identify distinct macrophage transcriptome profiles between two rat strains that differ in susceptibility to glomerulonephritis, provide novel positional candidates for Crgn3-7 and define groups of genes that play a significant role in differential regulation of macrophage activity.
Villaro, J; Sánchez Ibarrola, A; Purroy, A
To study the participation of the Hageman factor-related contact system of plasma in the pathogenesis of glomerulonephritis (GN), an anti-BM GN was induced in a group of 10 normal Brown Norway rats and another of seven Brown Norway BN/Mai Pfd f rats. The latter strain is characterized by a congenital deficiency of plasma prekallikrein and of high-molecular weight kininogen, with lengthening of the activated partial thromboplastin time. In the deficient group, one animal developed crescents in less than 25% of glomeruli, five in 25-50% and one in 50-75%. In the group of normal rats, extracapillary proliferation was of greater severity: one animal showed crescents in less than 25% of glomeruli, two in 50-75% and five in more than 75% of glomeruli. Although in both groups intense glomerular fibrin deposition was documented, the intensity of these deposits was less severe in the deficient animals. These data suggest, in the first place, that functional integrity of the contact system is not a necessary requirement for glomerular fibrinogenesis, other mechanisms being implicated in this phenomenon. On the other hand, this functional deficit has exerted a protective effect on crescent formation, which suggests that the contact system can play a role as a mediator of injury in glomerulonephritis, perhaps through the release of contact system-dependent mediators of inflammation. PMID:3396222
Alexander, Mariam P; Fervenza, Fernando C; De Vriese, An S; Smith, Richard J H; Nasr, Samih H; Cornell, Lynn D; Herrera Hernandez, Loren P; Zhang, Yuzhou; Sethi, Sanjeev
C3 glomerulonephritis (C3GN) results from genetic or acquired dysregulation of the alternative complement pathway. A subset of patients may have clinical and biochemical characteristics compatible with an autoimmune disorder. We studied a cohort of 85 patients with confirmed C3GN (2007-2014), of which ten patients (3 male, 7 female; mean age 38.5 years) had an associated autoimmune disorder. All patients had abnormal ANA titers, 6 also had positive ds-DNA titers. At the time of presentation with C3GN, all 7 female patients had autoimmune-related presentations. Of the 3 male patients, only 1 patient had autoimmune-related presentations. Kidney biopsy showed predominantly mesangial proliferative or membranoproliferative glomerulonephritis. In 5 patients, the alternative pathway was evaluated. All had allele variants/polymorphisms associated with C3GN. One patient was also positive for C3Nefs. Treatment varied form conservative management to the use of prednisone alone or with cytotoxic therapy. Mean serum creatinine decreased from 2.0 to 1.4 mg/dL while proteinuria decreased from 2300 to 994 mg/24 h in 8 patients with follow-up. The study highlights the association between C3GN and autoimmune disorders, particularly in female patients. The study suggests that an autoimmune milieu may act as a trigger for the development of C3GN in genetically susceptible patients. Short-term prognosis of C3GN associated with autoimmune disorders appears excellent.
Kamenetskiĭ, M S; Pervak, M B; Tkachenko, G D; Vernikov, B L
To develop criteria for determining predisposition to pulmonary edema in patients with glomerulonephritis, clinical, laboratory and X-ray examinations were made in 697 patients with glomerulonephritis at different stages of its development. X-ray examination included chest tele X-ray and its densitometric analysis. Twenty two patients underwent computerized tomography with histographic analysis. In 106 patients, X-ray findings were compared with the volume of circulating blood, cardiac and stroke indices. Changes in the lungs and pleural cavities were found in 22.7%, pulmonary edema was revealed in 15.7% of the patients. The prognostically unfavourable criteria for the development of pulmonary edema were found to be Stage II pulmonary venous hypertension with hypervolemia and peripheral edemas. The densitometrically detected increase in the density of the lower lungs in patients with Stage II venous hypertension suggests early manifestations of interstitial edema of the lung and the narrowing of the histogram angle limited by its ascending and descending lines is indicative of the fact that interstitial edema progresses to alveolar one.
Nagai, Kei; Usui, Joichi; Noguchi, Kazuyuki; Unai, Kei; Hiwatashi, Akira; Arakawa, Yoh; Togashi, Amane; Morito, Naoki; Saito, Chie; Yoh, Keigyou; Tsuruoka, Syuichi; Kojima, Hiroshi; Aita, Kumi; Nagata, Michio; Yamagata, Kunihiro
Renal involvement is a significant complication of multicentric Castleman's disease (MCD) and various glomerular involvements have been reported. A 45-year-old Japanese man presented with persistent proteinuria, with lymphadenopathy and hypergammaglobulinemia. He had been diagnosed 4 years previously with MCD. As his renal impairment had progressed to renal failure, he underwent a renal biopsy. Histology revealed diffuse and global membranous lesions with large and heterogeneous epimembranous deposits. In addition, mesangial cell proliferation and focal extracapillary lesions were found. Under immunofluorescence, granular staining for anti-IgG, IgG1, IgG2 and IgA was strongly positive in the capillary loop, and weakly positive in the mesangium. As such, there was a diversity of histological features. Our perspective with regard to pathogenesis is that the formation of the immune-complex contributed to the membranoproliferative glomerulonephritis type 3-like lesion. This histological multiform with MCD is valuable for increasing our understanding of the mechanism for onset of immune-complex glomerular deposition and cellular proliferation of glomerulonephritis.
Background Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder that is characterized by the development of cysts in the kidneys and other organs. Urinary protein excretion is usually less than 1 g/day, and ADPKD is rarely associated with nephrotic syndrome or rapidly progressive glomerulonephritis (RPGN). To date, myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated crescentic glomerulonephritis (CrGN) has not been reported in a patient with ADPKD. Case presentations We report two cases of MPO-ANCA positive ADPKD. A 60-year-old Japanese woman (case 1) and a 54-year-old Japanese woman (case 2) presented with RPGN featuring severe proteinuria and microscopic hematuria. In both patients percutaneous needle biopsy of the kidney revealed MPO-ANCA-associated CrGN with a paucity of glomerular immunoglobulin staining. Each patient received intravenous methylprednisolone for 3 days, followed by oral prednisolone. Case 1 showed gradual improvement and has not progressed to end-stage renal disease (ESRD), but case 2 developed ESRD requiring hemodialysis within one month despite treatment. Conclusion These are the first two reported cases of MPO-ANCA-associated CrGN in patients with ADPKD. Our experience suggests that serial measurement of the ANCA titer and renal biopsy should be considered for accurate diagnosis and appropriate treatment of ADPKD patients who present with proteinuria, hematuria, and rapid decline of renal function. PMID:23617397
Campbell, G Adam; Hu, Daniel; Okusa, Mark D
Acute kidney injury (AKI) is a frequent and significant complication of cancer and cancer therapy. Cancer patients frequently encounter risk factors for AKI including older age, CKD, prerenal conditions, sepsis, exposure to nephrotoxins, and obstructive physiology. AKI can also be secondary to paraneoplastic conditions, including glomerulonephritis and microangiopathic processes. This complication can have significant consequences, including effects on patients' ability to continue to receive therapy for their malignancy. This review will serve to summarize potential etiologies of AKI that present in patients with cancer as well as to highlight specific patient populations, such as the critically ill cancer patient.
Fernández, J; Colomé, Jaime Fernández; Sanz-Gallén, P; Sanz-Gallén, Pere; Nogué, S; Xarau, Santiago Nogué
For several years we carried out a follow-up of two patients with IgA mesangial glomerulonephritis with antecedents of exposure to toxic substances (cadmium and organic solvents). The first case involved a 47 year old male who was diagnosed with mesangial IgA glomerulonephritis eight years ago; he had been working for twelve years as a solderer. He had used metal bars containing 25% cadmium as part of the soldering material. Very high levels of cadmium were detected in his blood and urine. The second case involved a 50 year male who was exposed to a wide number of organic dissolvents for 23 years. Three years ago he was diagnosed with a proliferative diffuse mesangial glomerulonephritis with IgA deposits; in spite of that, the patient continued working until one year ago, when was found to have a chronic stage 3 renal disease secondary to IgA nephropathy. Patients diagnosed with mesangial IgA glomerulonephritis should be kept apart from exposure to nephrotoxic substances.
Martínez-Odriozola, P; Gutiérrez-Macías, A; Moina Eguren, I; Arrieta Lezama, J
We report a case of idiopathic retroperitoneal fibrosis and rapidly progressive glomerulonephritis with serum antiproteinase 3 antineutrophil cytoplasmic antibodies (anti-PR3-ANCA), without clinical or histological signs of Wegener's granulomatosis, in a 46-year-old man. Our case and previously reported cases showing the same association support the hypothesis that the association is not fortuitous, but reflects a common immunological mechanism.
Smith, Andrew; L'Imperio, Vincenzo; De Sio, Gabriele; Ferrario, Franco; Scalia, Carla; Dell'Antonio, Giacomo; Pieruzzi, Federico; Pontillo, Claudia; Filip, Szymon; Markoska, Katerina; Granata, Antonio; Spasovski, Goce; Jankowski, Joachim; Capasso, Giovambattista; Pagni, Fabio; Magni, Fulvio
Idiopathic glomerulonephritis (GN), such as membranous glomerulonephritis, focal segmental glomerulosclerosis (FSGS), and IgA nephropathy (IgAN), represent the most frequent primary glomerular kidney diseases (GKDs) worldwide. Although the renal biopsy currently remains the gold standard for the routine diagnosis of idiopathic GN, the invasiveness and diagnostic difficulty related with this procedure highlight the strong need for new diagnostic and prognostic biomarkers to be translated into less invasive diagnostic tools. MALDI-MS imaging MALDI-MSI was applied to fresh-frozen bioptic renal tissue from patients with a histological diagnosis of FSGS (n = 6), IgAN, (n = 6) and membranous glomerulonephritis (n = 7), and from controls (n = 4) in order to detect specific molecular signatures of primary glomerulonephritis. MALDI-MSI was able to generate molecular signatures capable to distinguish between normal kidney and pathological GN, with specific signals (m/z 4025, 4048, and 4963) representing potential indicators of chronic kidney disease development. Moreover, specific disease-related signatures (m/z 4025 and 4048 for FSGS, m/z 4963 and 5072 for IgAN) were detected. Of these signals, m/z 4048 was identified as α-1-antitrypsin and was shown to be localized to the podocytes within sclerotic glomeruli by immunohistochemistry. α-1-Antitrypsin could be one of the markers of podocyte stress that is correlated with the development of FSGS due to both an excessive loss and a hypertrophy of podocytes.
... glomeruli. The glomeruli of the kidney help filter wastes and fluids from the blood to form urine. ... the glomerular basement membrane. This membrane helps filter wastes and extra fluids from the blood. Damage to ...
Petrin, J; Rozman, B; Dolenc, P; Logar, D; Bozic, B; Vizjak, A; Ferluga, D; Jezersek, P
In spite of several articles questioning the general opinion that arterial hypertension in patients with systemic lupus erythematosus (SLE) is only the consequence of lupus glomerulonephritis (LGN), this still remains the usual pathophysiologic explanation. The purpose of this study was to explore the correlations between hypertension and LGN and to assess the importance of hypertension control for the prognosis of patients. A retrospective analysis of 173 patients with SLE over a period of 14 years was performed. For most of the patients, data were available from regular follow-up visits over an average of 6 years. Our results show a dissociation of hypertension and LGN and an association of hypertension and renal dysfunction. Severe hypertensive renal vascular lesions correlated well with a decrease of renal function. Successful treatment of hypertension is therefore essential in order to prevent deterioration of renal function in patients with LGN.
Gupta, A.; Agrawal, V.; Kaul, A.; Verma, R.; Pandey, R.
Anti-glomerular basement membrane (anti-GBM) disease is an autoimmune disease that most commonly presents as rapidly progressive glomerulonephritis with or without pulmonary involvement. It is characterized by the presence of antibodies directed to antigenic targets within glomerular and alveolar basement membranes. This study was performed to evaluate the clinicopathological features and outcome in anti-GBM crescentic glomerulonephritis (CrGN) at a tertiary care center in North India over a period of 9 years (January 2004 to December 2012). A diagnosis of anti-GBM CrGN was made in the presence of >50% crescents, linear deposits of IgG along GBM, and raised serum anti-GBM antibody titer. Of 215 cases of CrGN diagnosed during this period, 11 had anti-GBM CrGN. Anti-GBM CrGN was found at all ages but was most common in the third to fifth decade with no gender predilection (mean age 48 +/- 15 years, 13–67 years). Patients presented with a mean serum creatinine of 10.2 +/- 5.3 mg/dl and sub-nephrotic proteinuria. Pulmonary involvement was present in two patients. Myeloperoxidase-antineutrophil cytoplasmic antibody was positive in two (2/11) elderly patients. Follow-up was available in four patients for a range of 30-270 (mean 99.5 ± 114.5) days, two remained dialysis dependent while two died due to uremia and sepsis. Our findings show that anti-GBM disease is a rare cause of CrGN in India, accounting for only 5% of patients. It usually presents as a renal-limited disease and is associated with a poor renal outcome. PMID:27795626
Walsh, Michael; Catapano, Fausta; Szpirt, Wladimir; Thorlund, Kristian; Bruchfeld, Annette; Guillevin, Loic; Haubitz, Marion; Merkel, Peter A.; Peh, Chen Au; Pusey, Charles; Jayne, David
Background Plasma exchange may be effective adjunctive treatment for renal vasculitis. We performed a systematic review and meta-analysis of randomized control trials of plasma exchange for renal vasculitis. Study Design Systematic review and meta-analysis of manuscripts identified from electronic databases, bibliographies, and studies identified by experts. Data was abstracted in parallel by two reviewers. Setting & Population Adults with idiopathic renal vasculitis or rapidly progressive glomerulonephritis Selection Criteria for Studies Randomized controlled trials that compared standard care with standard care plus adjuvant plasma exchange in adult patients with either renal vasculitis or idiopathic rapidly progressive glomerulonephritis. Intervention Adjuvant plasma exchange Outcome Composite of end-stage renal disease or death. Results We identified 9 trials including 387 patients. In a fixed-effects model the pooled relative risk of end-stage renal disease or death was 0.80 for patients treated with adjunctive plasma exchange compared to standard care alone (95% confidence interval 0.65 to 0.99; p=0.04). No significant heterogeneity was detected (p=0.5; I2=0%). The effect of plasma exchange did not differ significantly across the range of baseline serum creatinine values (p=0.7) or number of plasma exchange treatments (p=0.8). The relative risk for end-stage renal disease was 0.64 (95% confidence interval 0.47 to 0.88; p=0.006) while the relative risk for death alone was 1.01 (95% confidence interval 0.71 to 1.4; p=0.9). Limitations Although the primary result was statistically significant, there is insufficient statistical information to reliable determine if plasma exchange reduces the composite of end-stage renal disease or death. Conclusions Plasma exchange may reduce the composite endpoint of end-stage renal disease or death in renal vasculitis. Further trials are required given the limited data available. PMID:21194817
Hohenstein, Bernd; Daniel, Christoph; Johnson, Richard J; Amann, Kerstin U; Hugo, Christian P M
Although platelets are well-known effector cells of inflammatory renal disease, clinical studies were not able to establish platelet inhibition as an effective therapy. Our previous studies using Vasodilator stimulated Phosphoprotein- and P2Y1-deficient mice suggested some early, but no long-term effects of platelets in passive crescentic glomerulonephritis. To define the role of platelets for this disease model, passive crescentic glomerulonephritis was induced in 72 C57Bl/6 mice by intraperitoneal injection of sheep anti-rabbit glomerular basement membrane antibody on 2 consecutive days. Platelets were depleted using anti-glycoprotein Ibα antibodies (p0p3/p0p4) every 4th day. Mice treated with equal amounts of sterile Phosphate buffered solution or rat-IgG served as controls. Blood, urine, and tissues were harvested on days 3 and 28. Renal tissue sections were evaluated after immunostaining using (semi)quantitative and computer-assisted image analysis. Compared to controls, efficient depletion was achieved as indicated by a markedly prolonged bleeding time and a more than 90% reduction in platelet counts (800/nl vs. 42/nl; P < 0.001). Functional (creatinine-clearance and proteinuria) parameters demonstrated no significant differences between the groups. Neither parameters of renal injury (glomerulosclerosis and fibrosis) nor glomerular/tubulointerstitial matrix expansion (by collagen IV staining), glomerular capillary rarefaction (lectin staining), and the glomerular/tubulointerstitial proliferative response (proliferating cell nuclear antigen) demonstrated any differences between platelet-depleted mice and PBS- or rat-IgG-treated nephritic mice at any time point. Despite effective platelet inhibition/depletion, neither the short- nor long-term course of passive crescentic nephrotoxic nephritis was affected. These data indicate that platelets play a minor role during the time course of this disease model in the mouse.
Salvadori, Maurizio; Rosso, Giuseppina
This review revises the reclassification of the membranoproliferative glomerulonephritis (MPGN) after the consensus conference that by 2015 reclassified all the glomerulonephritis basing on etiology and pathogenesis, instead of the histomorphological aspects. After reclassification, two types of MPGN are to date recognized: The immunocomplexes mediated MPGN and the complement mediated MPGN. The latter type is more extensively described in the review either because several of these entities are completely new or because the improved knowledge of the complement cascade allowed for new diagnostic and therapeutic approaches. Overall the complement mediated MPGN are related to acquired or genetic cause. The presence of circulating auto antibodies is the principal acquired cause. Genetic wide association studies and family studies allowed to recognize genetic mutations of different types as causes of the complement dysregulation. The complement cascade is a complex phenomenon and activating factors and regulating factors should be distinguished. Genetic mutations causing abnormalities either in activating or in regulating factors have been described. The diagnosis of the complement mediated MPGN requires a complete study of all these different complement factors. As a consequence, new therapeutic approaches are becoming available. Indeed, in addition to a nonspecific treatment and to the immunosuppression that has the aim to block the auto antibodies production, the specific inhibition of complement activation is relatively new and may act either blocking the C5 convertase or the C3 convertase. The drugs acting on C3 convertase are still in different phases of clinical development and might represent drugs for the future. Overall the authors consider that one of the principal problems in finding new types of drugs are both the rarity of the disease and the consequent poor interest in the marketing and the lack of large international cooperative studies. PMID:27458560
L'Imperio, Vincenzo; Smith, Andrew; Chinello, Clizia; Pagni, Fabio; Magni, Fulvio
Glomerulonephritis (GN) is one of the most common origins of chronic kidney disease and its careful evaluation is crucial for prognostic and therapeutic purposes, with the renal biopsy still playing a central role for the diagnosis. However, due to its invasiveness, it is not devoid of complications and many investigations have focused on identifying biomarkers for chronic kidney diseases using less-invasive and easy-to-collect samples, such as urine and blood. In this context, proteomics has played a crucial role in determining the molecular changes related to disease progression and early pathological glomerular modifications. Here, we report a review of selected literature for each GN, based on selected works published in the last 10 years, showing how these approaches have generated clinically relevant findings in the study of glomerulonephritis. We also describe several proteomic strategies, highlighting their technical advantages and limitations, future perspectives for proteomic applications in the study of GNs, and their possible application in routine practice.
Fujita, Emiko; Shimizu, Akira; Masuda, Yukinari; Kuwahara, Naomi; Arai, Takashi; Nagasaka, Shinya; Aki, Kaoru; Mii, Akiko; Natori, Yasuhiro; Iino, Yasuhiko; Katayama, Yasuo; Fukuda, Yuh
Macrophages are heterogeneous and include classically activated M1 and alternatively activated M2 macrophages, characterized by pro- and anti-inflammatory functions, respectively. Macrophages that express heme oxygenase-1 also exhibit anti-inflammatory effects. We assessed the anti-inflammatory effects of statin in experimental anti-glomerular basement membrane glomerulonephritis and in vitro, focusing on the macrophage heterogeneity. Rats were induced anti-glomerular basement membrane glomerulonephritis and treated with atorvastatin (20 mg/kg/day) or vehicle (control). Control rats showed infiltration of macrophages in the glomeruli at day 3 and developed crescentic glomerulonephritis by day 7, together with increased mRNA levels of the M1 macrophage-associated cytokines, interferon-gamma, tumor necrosis factor-alpha, and interleukin-12. In contrast, statin reduced the level of proteinuria, reduced infiltration of macrophages in glomeruli with suppression of monocyte chemotactic protein-1 expression, and inhibited the formation of necrotizing and crescentic lesions. The number of glomerular ED3-positive macrophages decreased with down-regulation of M1 macrophage-associated cytokines. Furthermore, statin augmented ED2-positive M2 macrophages with up-regulation of the M2 macrophage-associated chemokines and cytokines, chemokine (C-C motif) Iigand-17 and interleukin-10. Statin also increased the glomerular interleukin-10-expressing heme oxygenase-1-positive macrophages. Statin inhibited macrophage development, and suppressed ED3-positive macrophages, but augmented ED2-positive macrophages in M2-associated cytokine environment in vitro. We conclude that the anti-inflammatory effects of statin in glomerulonephritis are mediated through inhibition of macrophage infiltration as well as augmentation of anti-inflammatory macrophages.
Reynolds, John; Preston, Gloria A.; Pressler, Barrak M.; Hewins, Peter; Brown, Michael; Roth, Aleeza; Alderman, Elizabeth; Bunch, Donna; Jennette, J. Charles; Cook, H. Terence; Falk, Ronald J.; Pusey, Charles D.
‘Autoantigen complementarity’ is a theory proposing that the initiator of an autoimmune response is not necessarily the autoantigen or its molecular mimic, but may instead be a peptide that is ‘antisense/complementary’ to the autoantigen. We investigated whether such complementary proteins play a role in the immunopathogenesis of autoimmune glomerulonephritis. Experimental autoimmune glomerulonephritis, a model of anti-glomerular basement membrane (GBM) disease, can be induced in Wistar Kyoto (WKY) rats by immunization with the α3 chain of type IV collagen. In this study, WKY rats were immunized with a complementary α3 peptide (c-α3-Gly) comprised of amino acids that ‘complement’ the well characterized epitope on α3(IV)NC1, pCol(24–38). Within 8 weeks post-immunization, these animals developed cresentic glomerulonephritis, similar to pCol(24–38)-immunized rats, while animals immunized with scrambled peptide were normal. Anti-idiotypic antibodies to epitopes from c-α3-Gly-immunized animals were shown to be specific for α3 protein, binding in a region containing sense pCol(24–38) sequence. Interestingly, anticomplementary α3 antibodies were identified in sera from patients with anti-GBM disease, suggesting a role for ‘autoantigen complementarity’ in immunopathogenesis of the human disease. This work supports the idea that autoimmune glomerulonephritis can be initiated through an immune response against a peptide that is anti-sense or complementary to the autoantigen. The implications of this discovery may be far reaching, and other autoimmune diseases could be due to responses to these once unsuspected ‘complementary’ antigens. PMID:25841937
Resch, M; Banas, B; Endemann, D; Mack, M; Riegger, G A J; Gröne, H J; Krämer, B K
A 15-year-old girl with a history of Kawasaki disease was admitted to our nephrological department due to acute renal failure. Despite antibiotic therapy because of fever and the symptoms of a pharyngitis in the last few days, the girl showed persisting fever and developed arthralgias, an exanthema and a rising serum creatinine as well as anuria. A wide variety of differential diagnoses has to be thought of because of the history of the Kawasaki disease (symptoms like fever, pharyngitis, exanthema and arthralgia), i.e. hemolytic-uremic syndrome, vasculitis, ascending infection, postinfection glomerulonephritis. In consideration of etiologically unclear "rapidly progressive renal failure" with anuria and thrombocytopenia an immediate renal biopsy was done and revealed a severe drug induced acute interstitial nephritis. Due to this diagnosis we treated the patient with corticosteroids. Within 4 weeks serum creatinine declined to 1.8 mg/dl but did not normalize.
Dewan, Deepak; Gulati, Sanjeev; Sharma, Raj K; Prasad, Narayan; Jain, Manoj; Gupta, Amit; Kumar, Alok
Crescentic glomerulonephritis (CsGN) is an uncommon entity in children. This prospective study was conducted to evaluate the aetiology, clinical spectrum and outcome in children with crescentic glomerulonephritis. The single-centre prospective study comprised of 22 children with biopsy proven CsGN who had been referred to our institute over the period January 2000 to December 2005. These patients were subjected to detailed clinical and biochemical examinations. The diagnosis of underlying renal disease was based on various criteria, including the clinical picture, serology and histopathology. The patients received intravenous methyl prednisolone, oral steroid treatment, and oral cyclophosphamide with or without plasmapheresis. All patients received supportive care, including control of hypertension and oedema and supportive management of renal insufficiency. During this 5-year period, CsGN accounted for 5.1% of all biopsies done in children. The mean age was 12.27 years (range 4 years to 18 years). There were eight girls and 14 boys. The mean duration of symptoms prior to referral was 2.47 months (range 5 days to 21 months). Aetiology was immune complex in 19 cases, anti-glomerular basement membrane (anti-GBM) antibody disease in two cases and pauci-immune (Wegener's granulomatosis) in one case. The percentage of crescents ranged from 50% to 100% (mean 70.6%). Twenty-one out of 22 (95.5%) children in our series had hypertension at presentation that required treatment with antihypertensive medications. The serum creatinine level at presentation ranged from 1.5 mg/dl to 11.4 mg/dl (mean 5.5 mg/dl). Of the 22 children, two were lost to follow-up, while the mean follow-up period of the rest of the 20 children was 8.13 months (range 1 month to 43 months). At the last follow-up of the 22 children, ten had stage 5 chronic kidney disease (CKD) and three had stage 4 CKD, while seven children had a calculated glomerular filtration rate (GFR) of >60 ml/min per 1.73 m(2) body
Stangou, M.; Bantis, C.; Skoularopoulou, M.; Korelidou, L.; Kouloukouriotou, D.; Scina, M.; Labropoulou, I. T.; Kouri, N. M.; Papagianni, A.; Efstratiadis, G.
IgA nephropathy (IgAN) and focal segmental necrotizing glomerulonephritis (FSNGN) are characterized by proliferation of native glomerular cells and infiltration by inflammatory cells. Several cytokines act as mediators of kidney damage in both diseases. The aim of the present study was to investigate the role of Th1, Th2 and Treg/T17 cytokines in these types of proliferative glomerulonephritis. Simultaneous measurement of Th1 interleukin (IL-2, IL-12, tumor necrosis factor-alpha [TNF-α], interferon-gamma [INF-γ]), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), Treg/T17 transforming growth factor-beta 1 (TGF-β1, granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-17) cytokines and C-C chemokines Monocyte chemoattractant protein-1 (MCP-1, macrophage inflammatory protein-1 [MIP-1] β) was performed in first-morning urine samples, at the day of renal biopsy, using a multiplex cytokine assay. Cytokine concentrations were correlated with histological findings and renal function outcome. Urinary excretion of Th1, Th2 and Treg/Th17 cytokines were significantly higher in FSNGN compared to IgAN patients. In IgAN patients (n = 50, M/F: 36/14, M age: 40.7 [17–67] years), Th1, Th2 and T17 cytokines correlated significantly with the presence of endocapillary proliferation, while in FSNGN patients (n = 40, M/F: 24/16, M age: 56.5 [25–80] years), MCP-1 and TGF-β1 had a positive correlation with severe extracapillary proliferation (P = 0.001 and P = 0.002, respectively). Urinary IL-17 was the only independent parameter associated with endocapillary proliferation in IgAN and with MCP-1 urinary excretion in FSNGN. Response to treatment was mainly predicted by IL-6 in IgAN, and by Th2 (IL-4, IL-6), Treg (GM-CSF) cytokines and MIP-1 β in FSNGN. Th1, Th2 and T17 cytokines were directly implicated in renal pathology in IgAN and possibly through MCP-1 production in FSNGN. IL-17 and IL-6 seem to have a central role in inflammation and progression of kidney injury. PMID:27194829
Barnes, J. L.; Torres, E. S.; Mitchell, R. J.; Peters, J. H.
Fibronectin (Fn) plays an important role in tissue remodeling during embryogenesis, wound repair, and vascular disease, and is thought to regulate cellular processes such as cell adhesion, migration, proliferation, and differentiation through specialized domains within the molecule. In addition, Fn can be alternatively spliced at three regions: extradomains EIIIA, EIIIB, and a variable segment V, potentially giving rise to functionally distinct variants of the molecule. We have previously shown a sequential expression of cellular Fn first by platelets, followed by macrophages, then mesangial cells in habu snake venom-induced proliferative glomerulonephritis (Am J Pathol 145: 585-597, 1994). These studies examined the cellular sources and glomerular localization of Fn in general but did not distinguish between the various alternatively spliced isoforms. In this study, we examine by in situ hybridization and immunohistochemistry the temporal expression and cellular sources of EIIIA, EIIIB, and V in a model of proliferation glomerulonephritis that has cell migration, proliferation, and extracellular matrix synthesis as features of tissue remodeling. Macrophages were the first cells to express Fn mRNA showing an EIIIA+, EIIIB-, and V95+ pattern beginning at 8 hours after habu snake venom injection. Migrating mesangial cells at the margins of early lesions (8 and 24 hours) did not overexpress mRNA encoding these Fn variants, but immunofluorescence microscopy revealed V95 and EIIIA protein at the margins of lesions. EIIIB was absent in lesions at this time. At 48 hours and peaking at 72 hours after habu snake venom injection, mesangial cells in central aspects of glomerular lesions expressed abundant mRNA and protein for V95 and EIIIA. EIIIB mRNA and protein was slight in the mesangium at these times. Parietal epithelial cells, particularly adjacent to glomerular lesions, also expressed abundant mRNA and protein for all three variants throughout the course of the disease
The role of the membrane attack complex (MAC) as a mediator of renal tissue injury was evaluated in rats affected by bovine serum albumin (BSA)-induced immune complex glomerulonephritis. Immunofluorescence studies revealed concurrent deposits of IgG, BSA, C3, and the MAC along glomerular capillary walls, although the MAC manifested a more restricted distribution than that observed for immune complexes. Immunoelectron microscopic techniques were utilized to demonstrate immune complexes, C3, and the MAC within dense deposits in the subepithelial aspect of the basement membrane. Visceral epithelial foot processes were fused in areas overlying large dense deposits and exhibited intense staining for the MAC, lesser reactivity for C3 but IgG was absent from the foot process membranes. Smaller granular deposits of immune complexes, C3, and the MAC were observed in the subendothelial region of the lamina rara interna and the lamina densa. Immune complexes may activate the classical complement pathway causing diffuse injury to the glomerular basement membrane (GBM), allowing subepithelial accumulation of complexes. These observations implicate the MAC as a mediator of GBM and juxtaposed podocyte membrane injury, thereby contributing to disruption of the glomerular filtration barrier. IgG and C3 were demonstrated within tubulointerstitial regions on the surface of collagen fibers in close proximity to the tubular basement membrane (TBM) of proximal convoluted tubules. Within the TBM, C3 localization was prominent with diminished reactivity for the MAC, but IgG was not detectable. The demonstration of C3 and scant MAC deposits in the TBM of nonimmunized control rats without evidence of interstitial IgG and C3 deposits suggests that both nonimmune and immune processes play a role in the pathogenesis of extraglomerular lesions. Evidence derived from these morphologic studies indicates that the MAC is associated with injury to the GBM, foot process membranes of visceral
Darouich, Sihem; Goucha, Rym; Jaafoura, Mohamed Habib; Zekri, Semy; Kheder, Adel; Ben Maiz, Hédi
Membranoproliferative glomerulonephritis with isolated C3 deposits (MPGNC3) is an uncommon condition characterized by overt glomerular C3 deposits in the absence of immunoglobulins and intramembranous dense deposits. Here the authors describe the clinical and morphological features of primary MPGNC3 in a 13-year-old boy and critically review the previously published cases. The patient presented with nephrotic syndrome and microscopic hematuria. Blood tests revealed very low circulating C3 levels. The renal biopsy exhibited subendothelial, subepithelial, and mesangial deposits, with C3 but not immunoglobulins seen on immunofluorescence. This case and the review of the literature indicate that the serum complement profile with decreased levels of C3 and normal levels of classical pathway components together with glomerular deposits containing exclusively complement C3 is highly suggestive of alternative pathway activation. The diagnosis of acquired and/or genetic complement abnormalities in some cases supports that complement dysregulation is implicated in the pathogenesis of MPGNC3. Such data show great promise to provide new therapy strategies based on modulation of the complement system activity.
Sugiura, Tokio; Yamada, Takuji; Kimpara, Yuri; Fujita, Naoya; Goto, Kenji; Koyama, Norihisa
Hepatitis C virus (HCV) infection leads to chronic liver disease, but it has also been associated with extrahepatic manifestations. Membranoproliferative glomerulonephritis (MPGN) is the most common renal disease associated with HCV. Although renal disease related to HCV in adults has been well studied, it has not been well studied in children because it is rare. A recent study found that antiviral therapy was effective for adult patients with HCV-associated MPGN. We report a 9-year-old girl with HCV-associated MPGN. Her HCV genotype was 1b, and her virus load was high. The first renal biopsy showed mesangial proliferation and partial double contours of the basement membrane on light microscopy and immunofluorescence staining with immunoglobulin (Ig) M, IgG, and C3. The patient was successfully treated with pegylated interferon (IFN) alpha-2a monotherapy. The antiviral therapy was generally well tolerated. After antiviral therapy, a sustained virological response-defined as negative HCV ribonucleic acid (RNA) at least 24 weeks after antiviral treatment-was achieved, the proteinuria disappeared, and the second renal biopsy showed improvement.
Trascasa, M L; Egido, J; Sancho, J; Hernando, L
Eleven out of 15 patients with IgA mesangial glomerulonephritis (Berger's disease) had an increased proportion of serum IgA in 9-21S fractions on 5-40% sucrose density-gradient ultracentrifugation; the heavier fractions decreased at acid pH. Serum IgA purified by starch electrophoresis was subjected to reduction-alkylation yielding fragments of lower molecular weight. J chain was detected on urea alkaline polyacrylamide electrophoresis and the high-molecular weight IgA bound the human secretory component. In six patients treated with phenytoin for 1 year there was a decrease in polymeric IgA and an increase in monomeric IgA adopting a pattern similar to that of the controls. Our results show the presence of a large amount of true IgA polymers, partially as immune complexes, in the serum of patients with Berger's disease. These data together with their normalization after phenytoin treatment may open a new pathogenic and therapeutic approach to this entity.
Roberts, J L; Schwartz, M M; Lewis, E J
Although an unusually high incidence of immunological diseases has been described in patients with hereditary C2 deficiency, the severity of these illnesses has been relatively mild, suggesting that blocking complement activation beyond C4 may protect against significant complement-mediated inflammation. This report describes studies in a C2-deficient patient with severe systemic lupus erythematosus (SLE) and diffuse proliferative glomerulonephritis. An immunopathological study of the kidney revealed the deposition of properdin, properdin factor B, C3 and C5 in a pattern similar to immunoglobulin G deposits. Serum properdin and properdin factor B levels were low at various times during the patient's course. In vitro complement fixation studies showed C3 fixation by glomerular deposits could occur via the alternative pathway. Studies of the immune deposits in the patients' skin revealed similar results. These studies suggest that inflammation may be effectively mediated via the alternative complement pathway in the C2 deficiency-lupus syndrome. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 PMID:348363
Tovbin, David; Shnaider, Alla; Kachko, Leonid; Basok, Anna; Vorobiov, Marina; Rogachev, Boris; Abramov, Dan; Zlotnik, Moshe
Rapidly progressive glomerulonephritis (RPGN) is a rare occurrence in IgA nephropathy (IgAN) in renal transplant patients on immunosuppressive therapy. RPGN post ischemia-reperfusion has not been previously reported. We report a 62 year old male patient on azathioprine therapy, 9 years after left cadaveric renal transplantation due to end stage renal disease of unknown etiology, who presented with progressive deterioration in renal function and hematuria. Renal biopsy was consistent with IgAN. Duplex and CT scan demonstrated a decreased renal graft perfusion, due to severe atherosclerosis and stenosis of iliac arteries. The patient underwent left axilo-femoral bypass graft surgery with improvement in kidney graft perfusion and function. However, few weeks later, patient presented with pulmonary edema and advanced renal failure and he was initiated on hemodialysis. Repeated renal biopsy demonstrated crescentic GN. To the best of our knowledge, this is the first report of RPGN following reversal of ischemia and reperfusion. There was no evidence for atherembolic disease which is not uncommon after vascular surgery and it has been reported to be rarely associated to crescentic GN. Theoretical explanations for exacerbation of IgAN to crescentic GN, following successful reperfusion, could be enhancement of capillary damage, inflammation and oxidative stress. Putative mechanisms for these phenomena may be interaction of reperfusion-induced hyperfiltration, high intraglomerular capillary pressure, oxidative stress, increased polymorphonucler cells infiltration and inflammation; the presence of IgA immune deposits and azathioprine metabolites, both can also be associated to enhancement of oxidative stress.
Jennette, J C; Tidwell, R R; Geratz, J D; Bing, D H; Falk, R J
Proteases are involved in the pathogenesis of inflammatory diseases by participating in the activation of mediator systems and by producing proteolytic tissue injury. Homeostatic control of inflammation is accomplished in part by physiologic protease inhibitors. The authors investigated the effectiveness of a number of synthetic protease inhibitors in ameliorating the glomerular injury induced by immune complex-mediated glomerulonephritis in mice. Two amidine-type protease inhibitors, bis (5-amidino-2-benzimidazolyl)methane and 1,2-bis (5-amidino-2-benzimidazolyl)ethane, had the greatest effects. They caused a marked reduction in glomerular necrosis (P less than 0.001) but did not affect the amount or site of immune complex localization or leukocyte influx. The inhibition constants of the protease inhibitors against nine purified physiologic proteases were determined. These results were discussed in relation to the effectiveness of the protease inhibitors in reducing glomerular injury. This investigation indicates that the administration of synthetic protease inhibitors can have a beneficial effect on immune-mediated inflammatory injury.
Bob, Flaviu Raul; Gluhovschi, Gheorghe; Herman, Diana; Potencz, Elena; Gluhovschi, Cristina; Trandafirescu, Virginia; Schiller, Adalbert; Petrica, Ligia; Velciov, Silvia; Bozdog, Gheorghe; Vernic, Corina
The aim of this study was to determine the relationship between histological, immunohistochemical (IHC) and biological data in the assessment of interstitial fibrosis in patients with glomerular diseases. A group of 41 patients with primary and secondary glomerulonephritis was studied. In order to quantify the histological changes and to assess the extent of active-inflammatory and chronic-sclerotic/fibrotic interstitial lesions, we adapted a scoring system, initially used for lupus nephritis, and ANCA-associated vasculitis. IHC labeling procedures with monoclonal antibodies anti-smooth muscle actin (SMA), anti-vimentin and anti-transforming growth factor beta (TGFbeta) were assessed using a semi-quantitative score, correlated with the histological and biological data. Our results showed that interstitial labeling of SMA correlated with scores for sclerotic/fibrotic lesions (chronicity index) and with active-inflammatory lesions (interstitial infiltrate, activity index). Interstitial vimentin correlated with the score for interstitial infiltrate. Both interstitial vimentin and TGFbeta immunopositivity correlated with sclerotic/fibrotic lesions (interstitial fibrosis, tubular atrophies, vascular hyalinosis/fibrosis, chronicity index), and negatively with glomerular filtration rate. An important correlation was found between the interstitial labeling of the two IHC markers of myofibroblasts (SMA and vimentin). We conclude that IHC studies related to clinico-biological and histological data can have an important role in the evaluation of the glomerular diseases, but the classical histological investigation assessed through quantification has still not lost its importance.
Donadio, J.V. Jr.; Anderson, C.F.; Mitchell, J.C.; Holley, K.E.; Ilstrup, D.M.; Fuster, V.; Chesebro, J.H.
Forty patients with Type I membranoproliferative glomerulonephritis were treated for one year with dipyridamole, 225 mg per day, and aspirin, 975 mg per day, in a prospective, randomized, double-blind, placebo-controlled study. At the base line, the half-life of /sup 51/Cr-labeled platelets was reduced in 12 of 17 patients. The platelet half-life became longer and renal function stabilized in the treated group, as compared with the placebo group, suggesting a relation between platelet consumption and the glomerulopathy. The glomerular filtration rate, determined by iothalamate clearance, was better maintained in the treated group (average decrease, 1.3 ml per minute per 1.73 m/sup 2/ of body-surface area per 12 months) than in the placebo group (average decrease, 19.6). Fewer patients in the treated group than in the placebo group had progression to end-stage renal disease (3 of 21 after 62 months as compared with 9 of 19 after 33 months). The data suggest that dipyridamole and aspirin slowed the deterioration of renal function and the development of end-stage renal disease.
Mori, Yutaro; Ihara, Katsuhito; Yamaguchi, Wakaba; Fujii, Tetsuro; Toda, Takayuki; Nagata, Michio; Matsui, Noriaki
A 26-year-old man diagnosed with nephrotic syndrome was administered steroid monotherapy. Urinary protein excretion was 2-3 g/day despite the therapy. Percutaneous renal biopsy revealed Type I idiopathic membranoproliferative glomerulonephritis (IMPGN). Although intravenous steroid therapy at the dose of 1,000 mg/day for 3 days was administered, proteinuria persisted at the level of 1 g/day. Renal dysfunction (cystatin C, 1.33 mg/L) was evident. Strong inflammation was suggested by occult blood (3+) and urinary (red blood cells: 30-50/high power field) sediment. We considered steroid monotherapy to be ineffective, and initiated combina-tion therapy with mycophenolate mofetil (MMF) and steroids. Consequently, urinary protein excretion moderately decreased to 0.34 g/day without adverse events or worsening of the renal function. The steroid quantity could be reduced without relapse. Subsequently, we were able to reduce the dose of MMF gradually, then terminated the medication. IMPGN is a rare disease with a poor renal prognosis. Recently, MMF therapies for IMPGN have been attempted, but there are few cases in Japan. Our case suggests that combination therapy with MMF and steroids is effective and safe for treating IMPGN.
Wang, Changsong; Feng, Yue; Wang, Mingao; Pi, Xin; Tong, Hongshuang; Wang, Yue; Zhu, Lin; Li, Enyou
Urinary volatile organic compounds (VOCs) analysis for kidney diseases has attracted a large amount of scientific interest recently, and urinary metabolite analysis has already been applied to many diseases. Urine was collected from 15 mesangial proliferative glomerulonephritis (MsPGN) patients, 21 IgA nephropathy (IgAN) patients and 15 healthy controls. Solid phase microextraction–chromatography– mass spectrometry (SPME-GC-MS) was used to analyse the urinary metabolites. The statistical methods principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLSDA) were performed to process the final data. Five metabolites were significantly greater in the group of MsPGN patients than in the normal control group (P < 0.05) while three metabolites were found at increased levels in the group of IgAN patients compared with the normal controls (P < 0.05). In addition, five metabolites were significantly increased in the group of IgAN patients compared with the MsPGN patients (P < 0.05). These five metabolites may be specific biomarkers for distinguishing between MsPGN and IgAN. The analysis of urinary VOCs appears to have potential clinical applications as a diagnostic tool. PMID:26443483
Truong, Luan D; Seshan, Surya V
Membranous glomerulonephritis (MGN) is a very significant kidney disease. It is one of the frequent causes of heavy protein excretion in urine. MGN is thought to be an immune-mediated disease caused by glomerular deposition of antigen-antibody complexes. The pathogenic antigen, however, has been an enigma until recently. It was discovered in 2009 that phospholipase A2 receptor (PLA2R), a normal transmembrane protein in podocyte plasma membrane, is the antigen causing MGN. Within 5 yr of its discovery, this seminal finding has leaded to novel insights into the treatment of this disease including diagnosis, therapy, and prediction of outcome. This finding also paves the way for fundamental studies on how and why autoimmunity against PLA2R develops. The discovery of PLA2A as the cause of "idiopathic" MGN after a half century of speculation, followed by further fundamental insights with such an expedient and successful application in patient care, embodies the elegance of science at its junction with society. This perspective traces the story of this remarkable discovery.
Wu, Di; Chen, Jin-Song; Cheng, Dong-Rui; Chen, Hao; Li, Xue; Ji, Shu-Ming; Xie, Ke-Nan; Ni, Xue-Feng; Liu, Zhi-Hong; Wen, Ji-Qiu
Proliferative glomerulonephritis with monoclonal IgG deposits manifesting as a nephrotic syndrome recently has been described as a renal disease with the pathological features of mesangial and subendothelial deposits of monoclonal IgG. Eight cases of recurrent proliferative glomerulonephritis with monoclonal IgG deposits after a renal transplant have been reported. Almost all of these patients had a certain remission of proteinuria by steroids alone or with cyclophosphamide, and had further remission through other special treatments (ie, rituximab and plasmapheresis). We present a case of recurrent proliferative glomerulonephritis with monoclonal IgG deposits of the IgG3? subtype after a renal transplant, which was insensitive to pulse intravenous methyl-prednisolone and cyclophosphamide remitted by double filtration plasmapheresis. This case report reveals that recurrent proliferative glomerulo-nephritis with monoclonal IgG deposits may be insensitive to intravenous pulse therapy of methylprednisolone and cyclophosphamide. We advocate double filtration plasmapheresis as an effective treatment of proliferative glomerulo-nephritis with monoclonal IgG deposits on remission of proteinuria.
Graham, D I; Behan, P O; More, I A
The neuropathological findings in six patients who developed neurological signs after the onset of "septic shock" caused by Gram-negative septicaemia are described. The changes in the brains were characteristic of acute haemorrhagic leucoencephalitis, and there was evidence, particularly in the kidneys, of disseminated intravascular coagulation with tubular necrosis and, in some, appearances indistinguishable from membrano-proliferative glomerulonephritis. It is agreed that acute haemorrhagic leucoencephalitis is another manifestation of a generalised Shwartzman reaction, and it is suggested that activation of complement is the final common pathway that produces tissue damage in the brain and kidney. Images PMID:762582
Esposito, Susanna; Bianchini, Sonia; Fastiggi, Michele; Fumagalli, Monica; Andreozzi, Laura; Rigante, Donato
Group A Streptococcus (GAS) strains are lately classified on the basis of sequence variations in the emm gene encoding the M protein, but despite the high number of distinct emm genotypes, the spectrum of phenotypes varying from invasive suppurative to non-suppurative GAS-related disorders has still to be defined. The relationship of GAS types with the uprising of acute rheumatic fever (ARF), a multisystemic disease caused by misdirected anti-GAS response in predisposed people, is also obscure. Studies published over the last 15 years were retrieved from PubMed using the keywords: "Streptococcus pyogenes" or "group A Streptococcus" and "acute rheumatic fever": the prevalence of peculiar emm types across different countries of the world is highly variable, depending on research designs, year of observation, country involved, patients' age, and gender. Most studies revealed that a relatively small number of specific emm/M protein types can be considered "rheumatogenic", as potentially characterized by the possibility of inducing ARF, with remarkable differences between developing and developed countries. The association between emm types and post-streptococcal manifestations is challenging, however surveillance of disease-causing variants in a specific community with high rate of ARF should be reinforced with the final goal of developing a potential primary prophylaxis against GAS infections.
Succar, Lena; Boadle, Ross A; Harris, David C; Rangan, Gopala K
Purpose In crescentic glomerulonephritis (CGN), the development of cellular bridges between podocytes and parietal epithelial cells (PECs) triggers glomerular crescent formation. However, the sequential changes in glomerular ultrastructure in CGN are not well defined. This study investigated the time course of glomerular ultrastructure in experimental CGN. Methods Transmission electron microscopy (TEM) was performed using kidney samples from rats with nephrotoxic serum nephritis (NSN) from day 1 to day 14. Morphometric analysis was conducted on randomly selected glomeruli captured on TEM digital images. Results On day 1 of NSN, there was widespread formation of focal contacts between the cell bodies of neighboring podocytes, and tight junctions were evident at the site of cell-to-cell contact. This was confirmed by the increased expression of the tight junction molecule, zonula occludens-1 (ZO-1), which localized to the points of podocyte cell–cell body contact. On day 2, the interpodocyte distance decreased and the glomerular basement membrane thickness increased. Foot process effacement (FPE) was segmental on day 3 and diffuse by day 5, accompanied by the formation of podocyte cellular bridges with Bowman’s capsule, as confirmed by a decrease in podocyte-to-PEC distance. Fibrinoid necrosis and cellular crescents were evident in all glomeruli by days 7 and 14. In vitro, the exposure of podocytes to macrophage-conditioned media altered cellular morphology and caused an intracellular redistribution of ZO-1. Conclusion The formation of tight junctions between podocytes is an early ultrastructural abnormality in CGN, preceding FPE and podocyte bridge formation and occurring in response to inflammatory injury. Podocyte-to-podocyte tight junction formation may be a compensatory mechanism to maintain the integrity of the glomerular filtration barrier following severe endocapillary injury. PMID:27920570
Baikunje, Shashidhar; Vankalakunti, Mahesha; Nikith, A.; Srivatsa, A.; Alva, Suhan; Kamath, Janardhan
Background Crescent formation generally reflects severe glomerular injury. There is sparse literature on post-infectious glomerulonephritis (PIGN) with crescents in adults. This retrospective study looked at nine such cases to see if there is a correlation between the severity of presentation, steroid treatment, histological severity and outcome. Methods Biopsy reports of all the adults who underwent kidney biopsy from February 2010 to June 2014 in a tertiary care hospital were screened and all the cases with the diagnosis of PIGN with crescents were selected. Clinical presentation, laboratory data, histology, treatment and outcome were analysed. Results Six patients had evidence of recent/current infection, but all except two were non-streptococcal. The mean creatinine was 360.67 μmol/L (range 70.72–770.85) and the mean estimated glomerular filtration rate (MDRD eGFR) was 30.28 mL/min/1.73 m2 (range 6.4–111.1) on presentation. All five patients who were treated with steroids had an excellent response. Among the four patients who did not receive steroids, two were left with significant renal impairment (mean MDRD eGFR 23.5 mL/min/1.73 m2) at a mean follow-up of 15.5 months (range 10–21). The mean percentage of glomeruli with crescents was 36.13% (range 11.76–100) and except in one, there was no tubular atrophy or interstitial fibrosis and none had glomerulosclerosis. None of the patients progressed to end-stage renal disease. Conclusion Non-streptococcal infections are more common precipitants. There was no correlation between histological and clinical severity. Patients treated with steroids had better renal outcomes. PMID:26985372
Aglan, Ahmed; Longen, Sebastian; Dehne, Nathalie; Köhler, Yvette; Hassan, Mohamed; Beck, Martina; Tredup, Claudia; Boosen, Meike; Hsieh, Tzung-Harn Louise; Schaefer, Liliana; Beck, Karl-Friedrich; Pfeilschifter, Josef
Renal mesangial cells are regarded as main players in glomerular inflammatory diseases. To investigate a possible crosstalk between inflammatory and hypoxia-driven signaling processes, we stimulated cultured mouse mesangial cells with different inflammatory agents and analyzed the expression of prolyl hydroxylase domain containing proteins (PHDs), the main regulators of hypoxia-inducible factor (HIF) stability. Administration of IL-1β (1 nM) and TNF-α (1 nM), a combination further referred to as cytokine mix (CM), resulted in a fivefold increase in PHD3 but not PHD1 and PHD2 mRNA expression compared to untreated controls. In contrast, a combination of IL-1β, TNF-α with lipopolysaccharide (10 μg/ml), and interferon-γ (20 ng/ml) designated as CM+ showed a high (60-fold) induction of PHD3 and a moderate (twofold) induction of PHD2 mRNA expression. Interestingly, CM+ but not CM induced the expression of inducible NO synthase and endogenously produced NO was responsible for the immense induction of PHD3 in mesangial cells treated with CM+. We found that CM+ affected PHD3 expression mainly via the NO/HIF axis, whereas PHD3 regulation by CM occurred in a NF-κB-dependent manner. In turn, silencing of PHD3 expression resulted in a decrease in the mRNA expression of ICAM-1, MIP-2, MCP-1, and CXCL-10, which are under control of NF-κB. In a rat model of mesangio-proliferative glomerulonephritis, PHD3 mRNA and protein expression was markedly induced and this effect was nearly abolished when rats were treated with the iNOS-specific inhibitor L-NIL, thus confirming our findings also in vivo.
Veronese, F.V.; Dode, R.S.O.; Friderichs, M.; Thomé, G.G.; da Silva, D.R.; Schaefer, P.G.; Sebben, V.C.; Nicolella, A.R.; Barros, E.J.G.
Levamisole has been increasingly used as an adulterant of cocaine in recent years, emerging as a public health challenge worldwide. Levamisole-associated toxicity manifests clinically as a systemic vasculitis, consisting of cutaneous, hematological, and renal lesions, among others. Purpura retiform, cutaneous necrosis, intravascular thrombosis, neutropenia, and less commonly crescentic nephritis have been described in association with anti-neutrophil cytoplasmic antibodies (ANCAs) and other autoantibodies. Here we report the case of a 49-year-old male who was a chronic cocaine user, and who presented spontaneous weight loss, arthralgia, and 3 weeks before admission purpuric skin lesions in the earlobes and in the anterior thighs. His laboratory tests on admission showed serum creatinine of 4.56 mg/dL, white blood count 3,800/μL, hemoglobin 7.3 g/dL, urinalysis with 51 white blood cells/μL and 960 red blood cells/μL, and urine protein-to-creatinine ratio 1.20. Serum ANCA testing was positive (>1:320), as well as serum anti-myeloperoxidase and anti-proteinase 3 antibodies. Urine toxicology screen was positive for cocaine and levamisole, with 62.8% of cocaine, 32.2% of levamisole, and 5% of an unidentified substance. Skin and renal biopsies were diagnostic for leukocytoclastic vasculitis and pauci-immune crescentic glomerulonephritis, respectively. The patient showed a good clinical response to cocaine abstinence, and use of corticosteroids and intravenous cyclophosphamide. Last serum creatinine was 1.97 mg/dL, white blood cell count 7,420/μL, and hemoglobin level 10.8 g/dL. In levamisole-induced systemic vasculitis, the early institution of cocaine abstinence, concomitant with the use of immunosuppressive drugs in severe cases, may prevent permanent end organ damage and associate with better clinical outcomes. PMID:27119429
Sawada, Anri; Kawanishi, Kunio; Horita, Shigeru; Koike, Junki; Honda, Kazuho; Ochi, Ayami; Komoda, Mizuki; Tanaka, Yoichiro; Unagami, Kohei; Okumi, Masayoshi; Shimizu, Tomokazu; Ishida, Hideki; Tanabe, Kazunari; Nagashima, Yoji; Nitta, Kosaku
Immunoglobulin (Ig) A nephropathy (IgAN) is a known autoimmune disease due to abnormal glycosylation of IgA1, and occasionally, IgG co-deposition occurs. The prognosis of IgG co-deposition with IgAN is adverse, as shown in the previous studies. However, in the clinical setting, monoclonality of IgG co-deposition with IgAN has not been observed. We describe a case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) combined with IgAN in a renal allograft. A-21-year-old man developed end-stage renal failure with unknown aetiology and underwent living-donor kidney transplantation from his mother 2 years after being diagnosed. One year after kidney transplantation, proteinuria 2+ and haematuria 2+ were detected; allograft biopsy revealed mesangial IgA and C3 deposits, indicating a diagnosis of IgAN. After tonsillectomy and steroid pulse therapy, proteinuria and haematuria resolved. However, 4 years after transplantation, pedal oedema, proteinuria (6.89 g/day) and allograft dysfunction (serum creatinine (sCr) 203.3 µmol/L) appeared. A second allograft biopsy showed mesangial expansion and focal segmental proliferative endocapillary lesions with IgA1λ and monoclonal IgG1κ depositions. Electron microscopic analysis revealed a massive amount of deposits, located in the mesangial and subendothelial lesions. A diagnosis of PGNMID complicated with IgAN was made, and rituximab and plasmapheresis were added to steroid pulse therapy. With this treatment, proteinuria was alleviated to 0.5 g/day, and the allograft dysfunction recovered to sCr 132.6 µmol/L. This case suggests a necessity for investigation of PGNMID and IgA nephropathy in renal allografts to detect monoclonal Ig deposition disease.
Barnes, J. L.; Hastings, R. R.; De la Garza, M. A.
Fibronectin (Fn) regulates cell migration, proliferation, and extracellular matrix formation during embryogenesis, angiogenesis, and wound healing. Fn also promotes mesangial cell migration and proliferation in vitro and contributes to extracellular matrix formation and tissue remodeling during glomerular disease. In this study, we examined, by immunohistochemistry and in situ hybridization, the temporal glomerular localization and cellular sources of Fn in Habu snake venom (HSV)-induced proliferative glomerulonephritis. Early HSV-induced glomerular lesions consisted of microaneurysms devoid of resident glomerular cells and filled with platelets, leukocytes, and erythrocytes. Over the course of the disease, mesangial cells migrated into the lesions, proliferated, and formed a confluent cellular mass. Fn was present in lesions beginning at 8 hours, with highest intensity at 72 hours and diminishing at 2 weeks after HSV. Staining for Fn at 8 and 24 hours after HSV was attributed to platelets and macrophages. In situ hybridization and phenotypic identification of cell types within lesions revealed macrophages as the predominant source of cellular Fn mRNA at these times. At 48 hours after HSV, Fn mRNA was expressed in proliferating mesangial cells in addition to macrophages. Most cells in lesions at 72 hours after HSV were mesangial, at a time when expression of Fn mRNA peaked. Cellular expression for Fn mRNA and translated protein declined at 2 weeks after HSV. These studies support the hypothesis that Fn, derived from platelets and macrophages, provides a provisional matrix involved with mesangial cell migration into glomerular lesions. Fn produced by mesangial cells might contribute to the formation of a stable extracellular matrix. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8080041
Bontscho, Julia; Manz, Rudolf A.; Schneider, Wolfgang; Luft, Friedrich C.; Kettritz, Ralph
Anti-neutrophil cytoplasmic autoantibodies (ANCA) cause vasculitis and necrotizing crescentic glomerulonephritis (NCGN). Steroids and cytotoxic drugs reduce mortality but can cause significant adverse events. The proteasome inhibitor bortezomib (BTZ) prevents glomerulonephritis in mouse models of lupus but its efficacy in ANCA-associated glomerulonephritis is unknown. We induced anti-MPO IgG-mediated NCGN by transplanting wild-type bone marrow (BM) into irradiated MPO-deficient mice immunized with MPO. Four weeks after BM transplantation, we treated mice with steroid/cyclophosphamide (S/CYC) or BTZ. Compared with untreated control mice, both S/CYC and BTZ significantly reduced urine abnormalities, NCGN, and infiltration of neutrophils and macrophages. Response to BTZ depended on timing of administration: BTZ abrogated NCGN if begun 3 weeks, but not 5 weeks, after BM transplantation. BTZ treatment significantly reduced total and MPO-specific plasma cells in both the spleen and bone marrow, resulting in significantly reduced anti-MPO titers. Furthermore, BTZ affected neither B cells nor total CD4 and CD8 T cells, including their naive and effector subsets. In contrast, S/CYC reduced the total number of cells in the spleen, including total and MPO-specific plasma cells and B cells. In contrast to BTZ, S/CYC did not affect total and MPO-specific plasma cells in the bone marrow. Three of 23 BTZ-treated mice died within 36 hours after BTZ administration. In summary, BTZ depletes MPO-specific plasma cells, reduces anti-MPO titers, and prevents NCGN in mice. PMID:21233415
Black, Leland L.; Srivastava, Roshni; Schoeb, Trenton R.; Moore, Ray D.; Barnes, Stephen; Kabarowski, Janusz H.
Apolipoprotein A-I (ApoA-I), the major lipid-binding protein of high-density lipoprotein (HDL), can prevent autoimmunity and suppress inflammation in hypercholesterolemic mice by attenuating lymphocyte cholesterol accumulation and removing tissue oxidized lipids. However, whether ApoA-I mediates immune suppressive or anti-inflammatory effects in normocholesterolemic conditions and the mechanisms involved remain unresolved. We transferred bone marrow from SLE-prone Sle123 mice into normal, ApoA-I knockout (ApoA-I−/−) and ApoA-I transgenic (ApoA-Itg) mice. Increased ApoA-I in ApoA-Itg mice suppressed CD4+ T and B cell activation without changing lymphocyte cholesterol levels or reducing major ApoA-I-binding oxidized fatty acids. Unexpectedly, oxidized fatty acid peroxisome proliferator-activated receptor gamma (PPARγ) ligands 13-hydroxyoctadecadienoic acid (HODE) and 9-HODE were increased in lymphocytes of autoimmune ApoA-Itg mice. ApoA-I reduced Th1 cells independently of changes in CD4+FoxP3+ regulatory T cells or CD11c+ dendritic cell activation and migration. Follicular helper T cells, germinal center B cells and autoantibodies were also lower in ApoA-Itg mice. Transgenic ApoA-I also improved SLE-mediated glomerulonephritis. However, ApoA-I deficiency did not have opposite effects on autoimmunity or glomerulonephritis, possibly due to compensatory increases of ApoE on HDL. We conclude that although compensatory mechanisms prevent pro-inflammatory effects of ApoA-I deficiency in normocholesterolemic mice, increasing ApoA-I can attenuate lymphocyte activation and autoimmunity in SLE independently of cholesterol transport, possibly through oxidized fatty acid PPARγ ligands, and can reduce renal inflammation in glomerulonephritis. PMID:26466956
Starczewska, Małgorzata H; Wawrzyńska, Liliana; Opoka, Lucyna; Małek, Grzegorz; Wieliczko, Monika; Amatuszkiewicz-Rowińska, Joanna; Szturmowicz, Monika
Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease that is characterized by its chronic course and the involvement of many organs and systems. The most common abnormality in the respiratory system of SLE patients is lupus pleuritis. Less common is parenchymal involvement, which may present as acute lupus pneumonitis (ALP) or chronic interstitial lung disease. Other possible pulmonary manifestations of SLE include pulmonary embolism, diffuse alveolar haemorrhage, acute reversible hypoxaemia, and shrinking lung syndrome. We present the case report of a young woman with previously diagnosed membranous glomerulonephritis with nephrotic syndrome and antiphospholipid syndrome, who was admitted with marked of shortness of breath. The diagnostic process, including imaging studies and laboratory tests, enabled us to confirm a diagnosis of ALP. After initiation of treatment with high doses of methyloprednisolone, nearly complete remission of pulmonary changes was observed. We also perform a literature review regarding acute lupus pneumonitis.
Konstantinov, Konstantin N; Harris, Alexis A; Barry, Marc; Murata, Glen H; Tzamaloukas, Antonios H
A woman diagnosed with mixed connective tissue disease (MCTD) developed an anti-myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA) and nephrotic syndrome with normal serum creatinine. Percutaneous kidney biopsy showed pauci-immune glomerulonephritis with superimposed immune complex deposition. After treatment with cyclophophamide and prednisone, proteinuria decreased progressively to a level of 0.4 g/g creatinine, ANCA became undetectable, while serum creatinine remained normal seven years after the beginning of treatment. Sustained remission of nephrotic proteinuria with preserved renal function may follow treatment of ANCA-mediated disease developing in patients with MCTD.
Cazzato, Massimiliano; Neri, Rossella; Possemato, Niccolo; Puccini, Rodolfo; Bombardieri, Stefano
PFAPA is an acronym for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis. This syndrome has been usually described in pediatric patients and it generally resolves spontaneously. The endocapillary proliferative glomerulonephritis (EPG) is a glomerular injury characterized by hypercellularity in glomerular lumen and is caused by post-infectious or autoimmune diseases. In this paper, we describe the case of a 35-year-old man affected by PFAPA and EPG. To our knowledge this association has never been reported in the literature before.
Stills, H. F.; Bullock, B. C.; Clarkson, T. B.
A study was conducted to compare the effects of experimental immune complex disease on the development of glomerulonephritis and aortic and coronary artery atherosclerosis. Fourteen adult male macaques (Macaca fascicularis) were fed a mildly atherogenic diet. Ten of these animals were given repeated intravenous injections of bovine serum albumin (BSA), and the remaining 4 were given similar injections of saline. Three of the monkeys given BSA responded with a high antibody titer, 4 with a moderate titer, and 3 with a low level titer to BSA. In all 4 monkeys with the moderate antibody response glomerulonephritis developed, characterized by increased glomerular cellularity, electron-dense deposits in the glomerular capillary basal lamina, and deposits of IgG, IgM, C3, C4, and BSA. Glomerulonephritis was not seen in the other 6 monkeys given BSA or the 4 control monkeys. Aortic lesions seen at necropsy consisted of a few fatty intimal streaks with no differences between test monkeys (given BSA) and control monkeys (given saline). There was no correlation between total serum cholesterol concentration, high-density lipoprotein cholesterol concentration, or BSA antibody levels and the degree of aortic atherosclerosis. Immunochemical stains for immunoglobulins and complement components revealed increased intimal staining when intimal thickness increased. Medial staining for immunoglobulin and complement components appeared to be slightly increased in monkeys with moderately high-level titers of BSA. The extent of atherosclerosis in the coronary arteries of monkeys given BSA was greater than in the control animals. Differences in the extent and severity of the atherosclerotic lesions were most pronounced in the proximal portions of the main coronary arteries, suggesting an increased susceptibility of this site to immune-complex-exacerbated atherosclerosis. In addition to the increased lesion severity in monkeys given BSA, there were numerous granulocytes seen within
Pepper, Ruth J.; Wang, Hsu-Han; Rajakaruna, Gayathri K.; Papakrivopoulou, Eugenia; Vogl, Thomas; Pusey, Charles D.; Cook, H. Terence; Salama, Alan D.
Glomerulonephritis is a common cause of end-stage renal disease. Infiltrating leukocytes interacting with renal cells play a critical role during the initiation and progression of glomerulonephritis, but the exact mechanisms are not clearly defined. By using the murine model of nephrotoxic nephritis, we investigated the role of S100A8/A9 [myeloid-related protein (MRP) 8/14, calprotectin] in promoting glomerulonephritis. In nephrotoxic nephritis, wild-type (WT) mice with glomerulonephritis have elevated serum levels of S100A8/A9, whereas mice deficient in MRP14 (S100a9−/−), and hence S100A8/A9, are significantly protected from disease. By using bone marrow transplants, we showed that MRP14 deficiency is required in both the hemopoietic and intrinsic cells for the protective effect. In vitro, both the WT bone marrow–derived macrophages and renal mesangial cells stimulated with S100A8/A9 secrete IL-6, CXCL1, and tumor necrosis factor α; however, Mrp14−/− cells exhibit significantly blunted proinflammatory responses. The interaction of WT bone marrow–derived macrophages with renal microvascular endothelial cells results in increased levels of monocyte chemotactic protein 1, IL-8, and IL-6 cytokines, which is attenuated in Mrp14−/− bone marrow–derived macrophages. Data shows that S100A8/A9 plays a critical role during glomerulonephritis, exerting and amplifying autocrine and paracrine proinflammatory effects on bone marrow–derived macrophages, renal endothelial cells, and mesangial cells. Therefore, complete S100A8/A9 blockade may be a new therapeutic target in glomerulonephritis. PMID:25759267
Pepper, Ruth J; Wang, Hsu-Han; Rajakaruna, Gayathri K; Papakrivopoulou, Eugenia; Vogl, Thomas; Pusey, Charles D; Cook, H Terence; Salama, Alan D
Glomerulonephritis is a common cause of end-stage renal disease. Infiltrating leukocytes interacting with renal cells play a critical role during the initiation and progression of glomerulonephritis, but the exact mechanisms are not clearly defined. By using the murine model of nephrotoxic nephritis, we investigated the role of S100A8/A9 [myeloid-related protein (MRP) 8/14, calprotectin] in promoting glomerulonephritis. In nephrotoxic nephritis, wild-type (WT) mice with glomerulonephritis have elevated serum levels of S100A8/A9, whereas mice deficient in MRP14 (S100a9(-/-)), and hence S100A8/A9, are significantly protected from disease. By using bone marrow transplants, we showed that MRP14 deficiency is required in both the hemopoietic and intrinsic cells for the protective effect. In vitro, both the WT bone marrow-derived macrophages and renal mesangial cells stimulated with S100A8/A9 secrete IL-6, CXCL1, and tumor necrosis factor α; however, Mrp14(-/-) cells exhibit significantly blunted proinflammatory responses. The interaction of WT bone marrow-derived macrophages with renal microvascular endothelial cells results in increased levels of monocyte chemotactic protein 1, IL-8, and IL-6 cytokines, which is attenuated in Mrp14(-/-) bone marrow-derived macrophages. Data shows that S100A8/A9 plays a critical role during glomerulonephritis, exerting and amplifying autocrine and paracrine proinflammatory effects on bone marrow-derived macrophages, renal endothelial cells, and mesangial cells. Therefore, complete S100A8/A9 blockade may be a new therapeutic target in glomerulonephritis.
Okpechi, Ikechi G.; Ameh, Oluwatoyin I.; Bello, Aminu K.; Ronco, Pierre; Swanepoel, Charles R.; Kengne, Andre P.
Background and aim Glomerulonephritis (GN) is a leading cause of end-stage renal disease (ESRD) in Africa. Data on epidemiology and outcomes of glomerular diseases from Africa is still limited. We conducted a systematic review on the epidemiology of histologically proven glomerular diseases in Africa between 1980 and 2014. Materials and methods We searched literature using PubMed, AfricaWide, the Cumulative Index to Nursing and Allied Health Literature on EBSCO Host, Scopus, African Journals online databases, and the African Index Medicus, for relevant studies. The review was conducted using standard methods and frameworks using only biopsy-confirmed data. Results Twenty four (24) studies comprising 12,093 reported biopsies from 13 countries were included in this analysis. The median number of biopsies per study was 127.0 (50–4436), most of the studies (70.0%) originated from North Africa and the number of performed kidney biopsies varied from 5.2 to 617 biopsies/year. Nephrotic syndrome was the commonest indication of renal biopsy. The frequency of reported primary pathologic patterns included, minimal change disease (MCD); 16.5% (95%CI: 11.2–22.6), focal segmental glomerulosclerosis (FSGS); 15.9% (11.3–21.1), mesangiocapillary GN (MCGN); 11.8% (9.2–14.6), crescentic GN; 2.0% (0.9–3.5) and IgA nephropathy 2.8% (1.3–4.9). Glomerular diseases related to hepatitis B and systemic lupus erythematosus had the highest prevalence among assessed secondary diseases: 8.4% (2.0–18.4) and 7.7% (4.5–11.7) respectively. There was no evidence of publication bias and regional differences were seen mostly for secondary GNs. Conclusions Glomerular diseases remain poorly characterized in sub-Saharan Africa due to declining renal biopsy rates and consequent paucity of data on pathologic patterns of key renal diseases. Development of renal biopsy registries in Africa is likely to enable adequate characterization of the prevalence and patterns of glomerular diseases
Idasiak-Piechocka, I; Oko, A; Łochyńska, K; Woźniak, A; Czekalski, S
Wegener's granulomatosis (WG) is characterized by granulomatous vasculitis of the respiratory tract and glomerulonephritis (GN). Prognosis of this disease is poor and about 20% of untreated patients die after one year from the onset. WG was recognized in 45-year-old patient on the basis of: 1) clinical symptoms (joint pain and swollen, purpura on the skin which appeared one week after respiratory tract infection, ulceration of the tonsils and lingula), 2) results of additional testing (X-chest-ray-infiltrates of both lungs), positive results of the cANCA (titre 1:640) and rapidly progressive renal failure [the increase of serum creatinine level (Pcr) from 123.7 to 707 mumol/l (1.4 to 8.0 mg/dl) during one week]. Renal biopsy revealed extracapillary GN (cellular crescents in 7 out of 8 glomeruli and scattered foci of fibrinoid necrosis of capillary walls in all). At the beginning of the treatment Pcr raised to 884 mumol/l (10 mg/dl) and the patient required hemodialysis. He was treated with methylprednisolone (M) at flash doses of 1000 mg/24 h by three days followed by 125 mg/24 h i.v.--because of peptic ulcer, with cyclophosphamide (C-150 mg/24 h p.p.), with trimetoprim/sulphametoxazole, with pentoxifylline and omeprazol. After six weeks of the treatment in the control kidney biopsy sclerotic changes in 10 out of 13 glomeruli and diffuse interstitial fibrosis were found. However, during the same time, we observed clinical remission of the disease and the decrease of Pcr to 176.8 mumol/l (2 mg/dl). The M dosis was reduced by 5 mg every weeks and the C dosis--to 50 mg (because of the increase of aminotransferase levels) After six months of the treatment Pcr was 132.6 mumol/l (1.5 mg/dl) and CANCA titer was 1:16. In this case of RPGN, despite off the progression of the morphological changes in the kidney, we obtained the clinical remission of the disease and significant decrease of Pcr level. These results suggest that aggressive treatment of WG is justified even in
Tang, W W; Feng, L; Vannice, J L; Wilson, C B
The contribution of IL-1 to leukocyte infiltration in anti-glomerular basement membrane (GBM) antibody (Ab) glomerulonephritis (GN) was examined by the administration of a specific IL-1 receptor antagonist (IL-1ra). Lewis rats received anti-GBM Ab or normal rabbit serum and were treated with either 0.9% saline or 6 mg IL-1ra over a 24-h time period. Plasma IL-1ra concentration was 2,659 +/- 51 ng/ml 4 h after anti-GBM Ab and IL-1ra administration. PMN and monocyte/macrophage infiltration declined 39% (9.8 +/- 1.9 to 6.0 +/- 1.5 PMN/glomerulus, P < 0.001) and 29% (4.9 +/- 0.8 to 3.5 +/- 0.8 ED-1 cells/glomerulus, P = 0.002) with IL-1ra treatment at 4 h, respectively. Similarly, the number of glomerular cells staining for lymphocyte function-associated molecule-1 beta (CD18) declined 39% from 16.7 +/- 1.9 to 10.7 +/- 1.6 cells/glomerulus at 4 h (P = 0.0001). This was associated with a decrease in glomerular intracellular adhesion molecule-1 expression. The mean glomerular intracellular adhesion molecule-1 score in anti-GBM Ab GN rats treated with IL-1ra was less than that of rats administered anti-GBM Ab and 0.9% saline at 4 (2.0 +/- 0.2 vs 2.5 +/- 0.2, P < 0.05) and 24 (2.5 +/- 0.1 vs 3.1 +/- 0.2, P = 0.0001) h. These immunopathologic changes correlated with a 50% reduction in proteinuria from 147 +/- 34 to 75 +/- 25 mg/d (P < 0.002). Treatment with IL-1ra did not affect the steady state mRNA expression of either IL-1 beta or TNF alpha. An increase in the IL-1ra dose to 30 mg given within the initial 4 h provided no additional benefit. The decline in PMN and monocyte/macrophage infiltration of the glomerulus at 4 h was similar to that found in the initial study. Furthermore, the protective benefit of IL-1ra was abrogated by doubling the dose of the anti-GBM Ab GN, despite administering high dose IL-1ra (30 mg). In these studies, detectable IL-1ra was found in the serum of untreated anti-GBM Ab GN controls. These data suggest a positive yet limited role for IL-1ra in
Ferluga, D; Jerse, M; Vizjak, A; Hvala, A; Rozman, B; Kos-Golja, M; Bren, A F
In addition to the conventional World Health Organization (WHO) classification of lupus glomerulonephritis (GN), various concomitant approaches have been introduced in the evaluation of renal biopsies of patients with systemic lupus erythematosus (SLE) in order to increase the impact of biopsies on the decision concerning the most appropriate therapy as well as for establishing the prognosis. Three hundred and seventy kidney tissue samples from 267 SLE patients were analysed using standardised light, electron and immunofluorescence microscopic techniques. In 155 patients, a comparative clinical follow-up study and statistical analysis were performed. The study highlighted the heterogeneity of WHO classes IV and III, which include 5 and 6 different conventional histomorphologic types of GN, respectively. Mixed membranous and proliferative GN associated with "full-house" mesangial-transmembranous immune deposits, demonstrated in more than one third of our SLE cases, appears to be diagnostically most characteristic. Immune deposits distributed in the glomeruli in five different patterns, obviously play a major role in the pathogenesis of various WHO classes and histomorphologic types of lupus GN. Additional mechanisms related to the occurrence of antiphospholipid antibodies and antineutrophil cytoplasmic antibodies are suggested to contribute to the histomorphologic heterogeneity of WHO class III and IV lupus GN, particularly to the development of thrombotic, necrotising and crescentic glomerular lesions. In the present study, a statistically significant association was demonstrated between increasing mean values of the activity index and glomerular deposit distribution patterns labeled by subendothelial deposits. Furthermore, a significant correlation was established between an increasing risk of developing renal failure and increasing mean values of the chronicity index. Differences in the increasing risk of developing renal failure between groups with different
Oliveira, A. V.; Roque-Barreira, M. C.; Sartori, A.; Campos-Neto, A.; Rossi, M. A.
likely that they are implicated in the pathogenesis of the mesangial proliferative glomerulonephritis in hamsters experimentally infected with L donovani. The glomerular changes may also explain the loss of immunoglobulins in the urine and the consequent lowering of serum immunoglobulin levels. Images Figure 2 Figure 3 Figure 4 PMID:4025511
Samuel, Susan; Bitzan, Martin; Zappitelli, Michael; Dart, Allison; Mammen, Cherry; Pinsk, Maury; Cybulsky, Andrey V; Walsh, Michael; Knoll, Greg; Hladunewich, Michelle; Bargman, Joanne; Reich, Heather; Humar, Atul; Muirhead, Norman
The KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for management of glomerulonephritis was recently released. The Canadian Society of Nephrology convened a working group to review the recommendations and comment on their relevancy and applicability to the Canadian context. A subgroup of pediatric nephrologists reviewed the guideline statements for management of childhood nephrotic syndrome and agreed with most of the guideline statements developed by KDIGO. This commentary highlights areas in which there is lack of evidence and areas in need of translation of evidence into clinical practice. Areas of controversy or uncertainty, including the length of corticosteroid therapy for the initial presentation and relapses, definitions of steroid resistance, and choice of second-line agents, are discussed in more detail. Existing practice variation is also addressed.
Peces, R; Rodríguez, M; Pobes, A; Seco, M
We report a case of rapidly progressive glomerulonephritis caused by anti-glomerular basement membrane (anti-GBM) antibodies that progressed to end-stage renal disease in a 67-year-old woman with diabetes. Intensive combined immunosuppressive therapy with methylprednisolone bolus, oral prednisone, and cyclophosphamide led to negativity of anti-GBM antibodies but was not able to restore renal function. After 28 months of hemodialysis, the patient suddenly presented with pulmonary hemorrhage. In this setting, high levels of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) and negative anti-GBM antibodies were found. Therapy with oral prednisone and cyclophosphamide led to resolution of pulmonary hemorrhage and negativity of MPO-ANCA.
Zeman, Marilyn; Campbell, Patricia; Bain, Vincent G
Postrenal transplant hepatitis C is increasing in frequency due to the high prevalence of hepatitis C among patients with renal failure. Despite this, there is still no standard hepatitis C treatment available for renal transplanted recipients. Combination antiviral hepatitis C therapy, the standard of care in the nontransplant population, is generally avoided because of documented renal graft rejection secondary to interferon treatment. A case of a male patient with postrenal transplant hepatitis C, which was associated with cryoglobulinemia and glomerulonephritis of the graft, is presented. He was treated with standard interferon with ribavirin. Sustained viral clearance was achieved despite ongoing evidence of cryoglobulinemia. Renal function, which had been deteriorating before treatment, improved as evidenced by the stabilization of serum creatinine and marked improvement of proteinuria. In conclusion, in selected patients, combination antiviral therapy may still be a viable option postrenal transplant. PMID:16779461
Shah, Shivani; Havill, John; Rahman, M Hafizur; Geetha, Duvuru
Anti-neutrophil cytoplasmic antibodies (ANCA) play an important role in the pathogenesis of ANCA-associated vasculitis. The lack of ANCA antibodies may indicate a variation in clinical presentation and outcomes of this disease. We identified 74 adult patients between 1995 and 2009 with the diagnosis of pauci-immune glomerulonephritis. Demographics, histological features, and treatment outcomes were compared between ANCA-positive and ANCA-negative patients. These factors were correlated with renal function at presentation and follow-up. Of the 74 patients, 57 were ANCA-positive, and 17 were ANCA-negative. Demographics and mean Birmingham Vasculitis Activity Score were similar between ANCA-negative and ANCA-positive patients at presentation. Renal function was significantly worse at presentation in the ANCA-negative patients (eGFR 16.59 vs. 31.89 ml/min/1.73 m(2), p = 0.03). Patients in the ANCA-negative group had a significantly higher interstitial fibrosis score compared to the ANCA-positive group (2.1 vs.1.6, p = 0.04). The median time to remission was shorter in the ANCA-negative patients (51 vs. 78 days, p = 0.01). Long-term renal function and 1-year patient and renal survival were similar between ANCA-negative and ANCA-positive patients. Baseline eGFR, percentage of normal glomeruli, glomerular sclerosis, and tubulointerstitial scarring predicted eGFR at 1 year in both groups similarly. This is the first historical review of American patients with pauci-immune glomerulonephritis, comparing patients with ANCA-negative and ANCA-positive serology. Although ANCA-negative patients present with lower eGFR and more interstitial fibrosis, 1-year and long-term outcomes in both groups are similar.
Higuchi, N; Maruyama, H; Kuroda, T; Kameda, S; Iino, N; Kawachi, H; Nishikawa, Y; Hanawa, H; Tahara, H; Miyazaki, J; Gejyo, F
Gene therapy is expected to revolutionize the treatment of kidney diseases. Viral interleukin (vIL)-10 has a variety of immunomodulatory properties. We examined the applicability of vIL-10 gene transfer to the treatment of rats with crescentic glomerulonephritis, a T helper 1 (Th 1) predominant disease. To produce the disease, Wistar-Kyoto rats were injected with a rabbit polyclonal anti-rat glomerular basement membrane antibody. After 3 h, a large volume of plasmid DNA expressing vIL-10 (pCAGGS-vIL-10) solution was rapidly injected into the tail vein. pCAGGS solution was similarly injected into control rats (pCAGGS rats). We confirmed the presence of vector-derived vIL-10 mainly in the liver and observed high serum vIL-10 levels in pCAGGS-vIL-10-injected rats. Compared with the pCAGGS rats, the pCAGGS-vIL-10 rats showed significant therapeutic effects: reduced frequency of crescent formation, decrease in the number of total cells, macrophages, and CD4+ T cells in the glomeruli, decrease in urine protein, and attenuation of kidney dysfunction. Using quantitative real-time polymerase chain reaction, we also observed that this model was Th1-predominant in the glomeruli and that the ratio of the transcripts of CD4, interferon-gamma, tumor necrosis factor-alpha, and monocyte chemotactic protein-1 to the transcripts of glucose-6-phosphate dehydrogenase in the glomeruli were all significantly lower in the pCAGGS-vIL-10 rats than in the pCAGGS rats. These results demonstrate that pCAGGS-vIL-10 gene transfer by hydrodynamics-based transfection suppresses crescentic glomerulonephritis.
Watanabe, S; Yamaguchi, Y; Suzuki, T; Ikezoe, M; Matsumoto, N; Chikamoto, H; Nagafuchi, H; Horita, S; Hattori, M; Shiraga, H; Tokumoto, T; Tanabe, K; Toma, H; Ito, K
A 38-yr-old man with factor H dysfunction and unknown glomerular disease received first and second renal transplantations (Tx) from living-related donors. His examination showed a low percentage activity of factor H (31%). Factor H dysfunction has been known to be associated with type II or III membranoproliferative glomerulonephritis (MPGN), haemolytic uraemic syndrome and IgA GN. The first graft from his mother showed diffuse mesangial deposit of IgA. His son has had IgA GN and his data also revealed a low percentage activity of factor H (33%). He and his son both showed a low activity of C3. Moreover, his father, who was the donor of the second Tx, had a low percentage activity of factor H (25%), and presented with mild glomerular deposit of C3 at operation, while he has been healthy through his entire 67 yr of life. Each of them had a low percentage activity of factor H. These findings through three generations suggested the inheritance of factor H dysfunction. The patient presented with proteinuria 3 months after the first Tx. At the first biopsy 30 months after the first Tx, light microscopy revealed minor glomerular abnormalities with electron dense deposits in subepithelial, intramembranous and mesangial regions, while immunofluorescence showed massive glomerular deposits of C3. In the second biopsy 51 months after the first Tx, the glomerulonephritis developed mesangial proliferation and crescent formation, accompanied by more massive C3 deposit and intramembranous, mesangial and subepithelial dense deposits. He then required redialysis. At the second and third biopsies within 2 months after the second Tx, the renal graft showed similar findings to the first biopsy after the first Tx. He perhaps presented with a recurrence of complement-associated GN, showing an atypical form of MPGN after Tx. These findings suggest that factor H dysfunction may play an important role of a certain pathogenesis of GN.
Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...
[Hypocomplementary membrano-proliferative glomerulonephritis in a Malagasy patient with schistosomiasis mansoni (detection of bilharzial antigen on glomerular basement membrane using monoclonal antibodies)].
Rajaonarivelo, P; Rajaona, H R; Alix, J L; Couderc, P; Daveau, C; Santoro, F; Nogueira-Quetroz, J A; Lovens, M; Capron, A; Cordonnier, D
Schistosomiasis due to Schistosoma mansoni affects more than 40 millions people all over the world. Renal involvement is observed mainly in endemic areas. We report a case of hypocomplementemic membrano-proliferative glomerulonephritis in a malagasy man who suffered also from hepatosplenic bilharziosis. The relation between Schistosoma mansoni and the nephropathy was proved by indirect immunofluorescence test using a monoclonal antibody directed against the caecum of adult Schistosoma mansoni.
Butler, Louise; Brockley, Tomos; Denning, David; Richardson, Malcolm; Chisholm, Roger; Sinha, Smeeta; O’Driscoll, Ronan
A non-immunocompromised man developed acute Aspergillus pneumonia after spreading mouldy tree bark mulch. Despite normal renal function at presentation, he developed rapidly progressive glomerulonephritis with acute kidney injury due to anti-glomerular basement membrane antibodies (anti-GBM) 4 weeks later. He remained dialysis dependent and died of sepsis 10 months later. We hypothesise that he contracted invasive pulmonary Aspergillosis from heavy exposure to fungal spores, leading to epitope exposure in the alveoli with subsequent development of GBM auto-antibodies. PMID:24432235
Mavani, Gaurang P; Pommier, Max; Win, Sandar; Michelis, Michael F; Rosenstock, Jordan
A 69-year-old male had initially presented with low-grade proteinuria, microhematuria, and a positive myeloperoxidase anti-neutrophilic antibody (ANCA). He subsequently developed deterioration of kidney function and developed uremic symptoms. Creatinine was 486.2 μmol/L (5.5 mg/dL). Anti-MPO was positive (titer >8 U, normal <0.4). He was clinically diagnosed with rapidly proliferative glomerulonephritis most likely due to ANCA vasculitis. He received three doses of pulse methylprednisolone therapy. Kidney biopsy showed pauci-immune glomerulonephritis. Immunofluorescence was positive for faint linear IgG staining of glomerular basement membrane (GBM). Anti-GBM antibody was positive 2.1 U (normal <1). He was started on high-dose oral steroids; monthly intravenous cyclophosphamide and plasmapheresis were also initiated. His symptoms improved and creatinine is 247.5 μmol/L (2.8 mg/dL). His repeat anti-GBM antibody was negative. This is a rare case of rapidly progressive glomerulonephritis due to dual MPO-ANCA antibodies and anti-GBM antibodies (DAV).
Mavani, Gaurang P.; Pommier, Max; Win, Sandar; Michelis, Michael F.; Rosenstock, Jordan
A 69-year-old male had initially presented with low-grade proteinuria, microhematuria, and a positive myeloperoxidase anti-neutrophilic antibody (ANCA). He subsequently developed deterioration of kidney function and developed uremic symptoms. Creatinine was 486.2 μmol/L (5.5 mg/dL). Anti-MPO was positive (titer >8 U, normal <0.4). He was clinically diagnosed with rapidly proliferative glomerulonephritis most likely due to ANCA vasculitis. He received three doses of pulse methylprednisolone therapy. Kidney biopsy showed pauci-immune glomerulonephritis. Immunofluorescence was positive for faint linear IgG staining of glomerular basement membrane (GBM). Anti-GBM antibody was positive 2.1 U (normal <1). He was started on high-dose oral steroids; monthly intravenous cyclophosphamide and plasmapheresis were also initiated. His symptoms improved and creatinine is 247.5 μmol/L (2.8 mg/dL). His repeat anti-GBM antibody was negative. This is a rare case of rapidly progressive glomerulonephritis due to dual MPO-ANCA antibodies and anti-GBM antibodies (DAV). PMID:26301224
Suzuki, Eiji; Karam, Eva; Williams, Sarah; Watson, Dennis K; Gilkeson, Gary; Zhang, Xian K
Expression of transcription factor Fli-1 is implicated in the development of glomerulonephritis. Fli-1 heterozygous knockout (Fli1(+/-)) NZM2410 mice, a murine model of lupus, had significantly improved survival and reduced glomerulonephritis. In this study, we found that infiltrated inflammatory cells were significantly decreased in the kidneys from Fli-1(+/-) NZM2410 mice. The expression of monocyte chemoattractant protein-1 (MCP-1) was significantly decreased in kidneys from Fli-1(+/-) NZM2410 mice. The primary endothelial cells isolated from the kidneys of Fli-1(+/-) NZM2410 mice produced significantly less MCP-1. In endothelial cells transfected with specific Fli-1 siRNA the production of MCP-1 was significantly reduced compared to cells transfected with negative control siRNA. By Chromatin Immunoprecipitation (ChIP) assay, we further demonstrated that Fli-1 directly binds to the promoter of the MCP-1 gene. Our data indicate that Fli-1 impacts glomerulonephritis development by regulating expression of inflammatory chemokine MCP-1 and inflammatory cell infiltration in the kidneys in the NZM2410 mice.
Jonsson, C A; Svensson, L; Carlsten, H
The aim of the present study was to evaluate the therapeutic effect of mycophenolate mofetil (MMF) on the course of disease in SLE-prone MRLlpr/lpr mice. Three-months-old mice displaying clinical symptoms of glomerulonephritis were given MMF (100 mg/kg per day) orally via the drinking water. Control mice received i.p. injections of cyclophosphamide (CYC) (1.8 mg/mouse per week) or saline. Survival, albuminuria and haematuria, immunoglobulin levels and anti-dsDNA antibodies in serum, frequencies of immunoglobulin-producing B lymphocytes and glomerular deposits of immunoglobulin and C3 were analysed. The results showed that MMF treatment significantly prolonged survival and reduced the occurrence of albuminuria and haematuria in MRLlpr/lpr mice. In addition, the number of immunoglobulin-producing B cells and serum levels of IgG and IgG anti-dsDNA antibodies were reduced after MMF and CYC treatment. MMF treatment significantly reduced the extent of deposition of C3 in glomeruli. We conclude that the reduced severity of glomerulonephritis following treatment of lupus-prone mice with MMF was as efficacious as that of CYC. These results warrant clinical trials of MMF in SLE patients with glomerulonephritis. PMID:10361247
Upadhaya, Bala Krishna; Sharma, Alok; Khaira, Ambar; Dinda, Amit K; Agarwal, Sanjay K; Tiwari, Suresh C
Dengue virus infection can clinically manifest as dengue fever, dengue shock syndrome and dengue hemorrhagic fever. Acute kidney injury as a result of dengue virus infection can occur due to various reasons including hypotension, rhabdomyolysis, sepsis and rarely immune complex mediated glomerular injury. However, glomerulonephritis associated with IgA Nephropathy in dengue virus infection has not been reported previously. We report a case of 15-year-old boy who was admitted with dengue fever and dialysis dependant acute kidney injury. Urine examination showed microscopic glomerular hematuria and proteinuria. Kidney biopsy showed mesangial proliferation with mesangial IgA dominant immune complex deposits and acute tubular necrosis. A repeated kidney biopsy 6 weeks after clinical recovery showed reversal of glomerular changes as well as resolution of mesangial IgA deposits.
Introduction Autosomal dominant polycystic kidney disease is an inherited disorder that is characterized by the development and growth of cysts in the kidneys and other organs. Urinary protein excretion is usually less than 1 g/24 hours in autosomal dominant polycystic kidney disease, and an association of nephrotic syndrome with this condition is considered rare. There are only anecdotal case reports of autosomal dominant polycystic kidney disease associated with nephrotic syndrome, with focal segmental glomerulosclerosis being the most commonly reported histopathological diagnosis. Nephrotic-range proteinuria in the presence of autosomal dominant polycystic kidney disease, with or without an accompanying decline in renal function, should be investigated by open renal biopsy to exclude coexisting glomerular disease. To the best of our knowledge, this is the first case of autosomal dominant polycystic kidney disease with histologically proven diffuse proliferative glomerulonephritis presenting with nephrotic-range proteinuria. No other reports of this could be found in a global electronic search of the literature. Case presentation We report the case of a 35-year-old Indo-Aryan man with autosomal dominant polycystic kidney disease associated with nephrotic syndrome and a concomitant decline in his glomerular filtration rate. Open renal biopsy revealed diffuse proliferative glomerulonephritis. An accurate diagnosis enabled us to manage him conservatively with a successful outcome, without the use of corticosteroid which is the standard treatment and the drug most commonly used to treat nephrotic syndrome empirically. Conclusion Despite the reluctance of physicians to carry out a renal biopsy on patients with autosomal dominant polycystic kidney disease, our case supports the idea that renal biopsy is needed in patients with polycystic kidney disease with nephrotic-range proteinuria to make an accurate diagnosis. It also illustrates the importance of open renal
Giannico, Giovanna A; Arnold, Shanna; Langone, Anthony; Schaefer, Heidi; Helderman, J Harold; Shaffer, David; Fogo, Agnes B
We have observed a predominantly mesangial non-immunoglobulin A immune complex mesangial glomerulopathy (MG) in renal transplants with mesangial deposits by immunofluorescence and electron microscopy. Clinicopathological features of 28 patients with MG were analyzed and compared with 28 transplant controls, matched for age, sex, ethnicity, donor type, estimated glomerular filtration rate, and interval from transplant to biopsy. Indications for biopsy in the MG group were allograft dysfunction in 64%, allograft dysfunction/proteinuria in 29%, and proteinuria in 7%. Biopsy indications in controls were allograft dysfunction (61%), allograft dysfunction/proteinuria (18%), proteinuria (14%), and delayed graft function (7%). Most MG cases had mild mesangial hypercellularity with endocapillary proliferation in 2 and crescents in 2 without fibrinoid necrosis. Immunoglobulin M-dominant deposits were present in 83%, and immunoglobulin G was dominant in 17% with mesangial deposits in 93% of cases by electron microscopy. Compared with controls, MG had higher Banff interstitial inflammation score (i) (P = .036) and was associated with concurrent acute T-cell-mediated rejection (P = .023), but not with acute or chronic antibody-mediated rejection. MG patients and controls had similar prevalence of polyomavirus nephropathy and Epstein-Barr virus infection. At follow-up, most MG patients had stable estimated glomerular filtration rate with no or stable proteinuria. Disease-specific graft survival was not different in MG versus controls. We conclude that, in view of the apparent self-limited nature of this lesion, additional treatment may not be required in these patients. Awareness of this lesion may thus spare patients unwarranted further intervention.
Hamano, Yoshitomo; Yoshizawa, Hiromichi; Sugase, Taro; Miki, Takuya; Ohtani, Naoko; Hanawa, Shiho; Takeshima, Eri; Morishita, Yoshiyuki; Saito, Osamu; Takemoto, Fumi; Muto, Shigeaki; Yumura, Wako; Kusano, Eiji
We report the case of a 36-year-old Japanese woman with nephrotic syndrome due to membranoproliferative glomerulonephritis (MPGN) Type I diagnosed after a 5-year history of periodic fever syndrome (PFS). Hypocomplementemia and elevation of anti-proteinase 3 anti-neutrophil cytoplasmic autoantibody (PR3-ANCA) were observed. HIV, and hepatitis B and C serology were negative. Nephrotic syndrome and periodic fever did not respond to oral steroid and intravenous steroid pulse therapies combined with cyclosporine, dipyridamole, warfarin and losartan. We tried immunotherapy using rituximab, a human-mouse chimeric monoclonal antibody directed against the CD20 antigen on mature B cells. This therapeutic approach led to improvement of renal function and remission of nephrotic syndrome and hypocomplementemia. However, it did not have a beneficial effect on periodic fever. Suspecting adult-onset hereditary PFS, we analyzed her genetic alteration of MEFV and TNFRSF1A genes. A rare genotype in intron 6 of TNFRSF1A was revealed. The etiological relationship between periodic fever and MPGN is discussed. Rituximab is a hopeful choice of induction therapy for refractory MPGN. PMID:23197963
Sui, Weiguo; Li, Huan; Ou, Minglin; Tang, Dong'e; Dai, Yong
Mesangial proliferative glomerulonephritis (MsPGN) is one of the most common immune-mediated renal diseases. The mesangium is expanded and hypercellular, immuno-globulin deposits can be found in the mesangium, but the mechanism underlying its cause remains largely unclear. There is a large amount of evidence suggesting that long ﹥200 nucleotide) non-coding RNAs (lncRNA) have important regulatory functions in the epigenetic control of gene expression. Multiple lines of evidence increasingly link mutations and dysregulations of lncRNAs to a diverse number of human diseases. Through microarray expression analysis, tests show that thousands of lncRNAs and protein-coding genes are significantly differentially expressed in IgA-negative MsPGN. Some lncRNAs and their neighboring protein-coding genes are closely related and are cooperatively expressed. This may be part of a potential regulatory mechanism. The malfunction of regulation in the network of lncRNAs may be a possible mechanism for the development of IgA-negative MsPGN. Our observations suggest that some lncRNAs are closely related to IgA-negative MsPGN and may be playing an important role in this disease.
Yamaguchi-Yamada, Misuzu; Manabe, Noboru; Uchio-Yamada, Kozue; Akashi, Naotsugu; Goto, Yasufumi; Miyamoto, Youhei; Nagao, Masaya; Yamamoto, Yoshie; Ogura, Atsuo; Miyamoto, Hajime
The ICR-derived glomerulonephritis (ICGN) mouse, a new inbred mouse strain with a hereditary nephrotic syndrome, is considered to be a good model of human idiopathic nephrotic syndrome and notably exhibits proteinuria and hypoproteinemia from the neonatal stage. In chronic renal disorder (CRD), anemia is a major subsequent symptom (renal anemia). The precise cause of renal anemia remains unclear, primarily owing to the lack of appropriate spontaneous animal models for CRD. To establish adequate animal models for anemia with CRD, we examined the hematological-biochemical properties and histopathological characteristics. With the deterioration of renal function, ICGN mice developed a normochromic and normocytic anemia, and exhibited normochromic and microcytic at the terminal stage. The expression of erythropoietin (EPO) mRNA both in the kidneys and liver and the EPO leak into the urine were observed in ICGN mice, indicating a disrupted metabolism of EPO in ICGN mice. In addition, a lack of iron induced by the hemolysis in the spleen and the leak of transferrin into urine as proteinuria aggravated the anemic condition. In conclusion, the ICGN mouse is a good model for anemia with CRD.
Reynolds, John; Abbott, Danielle S.; Karegli, Julieta; Evans, David J.; Pusey, Charles D.
Experimental autoimmune glomerulonephritis (EAG), an animal model of Goodpasture’s disease, can be induced in Wistar Kyoto (WKY) rats by immunization with the noncollagenous domain of the α 3 chain of type IV collagen, α3(IV)NC1. Recent studies have identified an immunodominant peptide, pCol (24-38), from the N-terminus of rat α3(IV)NC1; this peptide contains the major B- and T-cell epitopes in EAG and can induce crescentic nephritis. In this study, we investigated the mechanisms of mucosal tolerance in EAG by examining the effects of the nasal administration of this peptide after the onset of disease. A dose-dependent effect was observed: a dose of 300 μg had no effect, a dose of 1000 μg resulted in a moderate reduction in EAG severity, and a dose of 3000 μg produced a marked reduction in EAG severity accompanied by diminished antigen-specific, T-cell proliferative responses. These results demonstrate that mucosal tolerance in EAG can be induced by nasal administration of an immunodominant peptide from the N-terminus of α3(IV)NC1 and should be of value in designing new therapeutic strategies for patients with Goodpasture’s disease and other autoimmune disorders. PMID:19406992
Gupta, Ruchika; Sharma, Alok; Agarwal, Sanjay K; Dinda, Amit K
C1q nephropathy is a recently described clinico-pathologic entity with a variable clinical presentation and pathology. Crescentic glomerulonephritis (GN) has been reported in only two patients in the available literature. CD59 deficiency, along with lack of CD55, is responsible for paroxysmal nocturnal hemoglobinuria (PNH). Few cases of isolated CD59 deficiency have been described with PNH-like features. A middle-aged adult male presented with rapidly progressive renal failure. Serological investigations were negative. A renal biopsy revealed necrotizing crescentic GN with rupture of Bowman's capsule. Immunofluorescence on the frozen sections showed dominant mesangial deposits of C1q along with IgM. Hematological work-up of the patient revealed isolated CD59 deficiency. Hence, a final diagnosis of C1q nephropathy and CD59 deficiency manifesting as crescentic GN and hemolytic anemia was made. The co-existence of two rare disorders, C1q nephropathy and CD59 deficiency, in a patient with necrotizing crescentic GN is described for the first time to the best of our knowledge. The pathogenetic link of these two entities with the clinical manifestation requires further study.
Müller, G A; Gebhardt, M; Kömpf, J; Baldwin, W M; Ziegenhagen, D; Bohle, A
Frequencies of the HLA antigens ABC, DR and MT, as well as of the properdin factor alleles were determined in 24 unrelated patients presenting with immune complex mediated idiopathic rapidly progressive glomerulonephritis (RPGN) type II. As in Goodpasture syndrome (RPGN type I with pulmonary hemorrhage), a significant association with the B-cell alloantigen HLA-DR 2 was demonstrated (relative risk for HLA-DR 2 positive individuals was 3.54; P less than 0.01). In addition a marked increase of the HLA specificity MT 3 was shown, which is supposed to belong to an antigen system of a second HLA-D region locus. The highest relative risk of 14.67 (P less than 0.00001), however, was calculated for all patients carrying the BfF phenotype. Increased numbers of patients positive for HLA-DR 2 and -MT 3, as well as BfF suggested immune response genes or disease-related mutations on different haplotypes responsible for a MHC (major histocompatibility complex) associated predisposition of RPGN type II.
Multiple studies have identified CD4+ T cells as central players of glomerulonephritis (GN). Cells of the Th1 and Th17 responses cause renal tissue damage, while Tregs mediate protection. Recently, a high degree of plasticity among these T cell lineages was proposed. During inflammation, Th17 cells were shown to have the potential of transdifferentiation into Th1, Th2, or alternatively anti-inflammatory Tr1 cells. Currently available data from studies in GN, however, do not indicate relevant Th17 to Th1 or Th2 conversion, leaving the Th17 cell fate enigmatic. Tregs, on the other hand, were speculated to transdifferentiate into Th17 cells. Again, data from GN do not support this concept. Rather, it seems that previously unrecognized subspecialized effector Treg lineages exist. These include Th1 specific Treg1 as well as Th17 directed Treg17 cells. Furthermore, a bifunctional Treg subpopulation was recently identified in GN, which secrets IL-17 and coexpresses Foxp3 together with the Th17 characteristic transcription factor RORγt. Similarities between these different and highly specialized effector Treg subpopulations with the corresponding T helper effector cell lineages might have resulted in previous misinterpretation as Treg transdifferentiation. In summary, Th17 cells have a relatively stable phenotype during GN, while, in the case of Tregs, currently available data suggest lineage heterogeneity rather than plasticity. PMID:27974866
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Mandal, A K; Baig, M; Koutoubi, Z
urine output and urinary sodium excretion, and a rapid decrease in blood urea nitrogen, constitutes strong evidence for prerenal ARF. However, these indices are unreliable when prerenal ARF has progressed to ATN or when ARF has an obstructive pattern to begin with. In all cases of ARF, especially in elderly men, urinary tract obstruction should be suspected unless the history is otherwise clear cut. Ultrasound of the kidneys and bladder is a simple, non-invasive and meaningful test that can be used to rule out obstructive causes of ARF. If obstruction is the cause of ARF, ultrasound will be positive; in contrast, urinary obstruction is very unlikely if ultrasound findings are normal in a patient who has been oliguric or anuric for 48 hours or more. Similarly, acute glomerulonephritis, including rapidly progressive glomerulonephritis, should be suspected when ARF is associated with heavy proteinuria. In such instances, percutaneous renal biopsy is essential to document the diagnosis. It is of utmost importance to establish whether ARF is of prerenal or postrenal type, both of which are potentially fully reversible. In contrast, patients with ATN or rapidly progressive glomerulonephritis may not recover, or may only partially recover, their renal function. Haemodialysis and nutritional support are common measures for patients with severe ATN and a highly catabolic state. Corticosteroids and immunosuppressive therapy should be instituted for rapidly progressive glomerulonephritis, in addition to haemodialysis. haemodiafiltration instead of haemodialysis is recommended for patients who are haemodynamically unstable [i.e., with a persistently low blood pressure (systolic < or = 100 mm Hg)]. Haemodiafiltration has been shown to improve acid-base balance and uraemia better than standard haemodialysis. However, despite dialysis, mortality in patients with ARF associated with ischaemic ATN remains high.
Wu, Chien-Te; Fu, Lin-Shien; Wen, Mei-Chin; Hung, Shein-Chung; Chi, Ching-Shiang
Several risk factors have been associated with the prognosis of lupus nephritis. However, few studies have focused on renal vascular lesions (such as thrombi due to immune complexes) as a prognostic factor in this disease. Here we present a case of systemic lupus erythematosus (SLE) in a 12-year-old girl who exhibited acute renal failure and severe hypertension on admission. Renal pathology findings included diffuse proliferative glomerulonephritis (class IVb) and lupus vasculopathy (LV) with immune complex deposition within glomerular capillaries and the preglomerular arteriolar lumen. Her clinical condition deteriorated rapidly, even after cyclophosphamide and methylprednisolone pulse therapy. It improved after 5 days of plasmapheresis and remained stable for up to 6 months under regular treatment. We suggest that renal biopsy performed early in SLE patients with renal involvement should be studied carefully for the presence of vascular lesions. Additionally, plasmapheresis can be considered in patients with LV refractory to other modalities of therapy.
Ramírez Ponferrada, R; Gallardo Avilla, A; Solís García, E; Castilla, J M; Martínez, R; Rodríguez, B
A relation between kidney and inner ear disease, specifically neurosensorial hearing loss, has been established. Likewise, the role of tonsillitis in certain glomerulonephritides is well known. A case of post-streptococcal mesangial glomerulonephritis with IgA deposit (Berger's disease) and neurosensorial hearing loss is reported. The absence of any relevant family or personal history suggests an immunological origin for both disorders.
Jarrot, Pierre-Andre; Chiche, Laurent; Hervier, Baptiste; Daniel, Laurent; Vuiblet, Vincent; Bardin, Nathalie; Bertin, Daniel; Terrier, Benjamin; Amoura, Zahir; Andrés, Emmanuel; Rondeau, Eric; Hamidou, Mohamed; Pennaforte, Jean-Loup; Halfon, Philippe; Daugas, Eric; Dussol, Bertrand; Puéchal, Xavier; Kaplanski, Gilles; Jourde-Chiche, Noemie
Abstract The aim of the study was to report the clinical, biological, and pathological characteristics of patients with glomerulonephritis (GN) secondary to systemic lupus erythematosus (SLE)/antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) overlap syndrome. A nationwide survey was conducted to identify cases of SLE/AAV overlap syndrome. Data were collected from SLE and AAV French research groups. Inclusion criteria were diagnosis of both SLE and AAV according to international classification criteria and biopsy-proven GN between 1995 and 2014. Additional cases were identified through a systematic literature review. A cohort of consecutive biopsy-proven GN was used to study the prevalence of overlapping antibodies and/or overlap syndrome. The national survey identified 8 cases of SLE/AAV overlap syndrome. All patients were female; median age was 40 years. AAV occurred before SLE (n = 3), after (n = 3), or concomitantly (n = 2). Six patients had rapidly progressive GN and 3/8 had alveolar hemorrhage. All patients had antinuclear antibodies (ANA); 7/8 had p-ANCA antimyeloperoxidase (MPO) antibodies. Renal biopsies showed lupus nephritis (LN) or pauci-immune GN. Remission was obtained in 4/8 patients. A literature review identified 31 additional cases with a similarly severe presentation. In the GN cohort, ANCA positivity was found in 30% of LN, ANA positivity in 52% of pauci-immune GN, with no correlation with pathological findings. The estimated prevalence for SLE/AAV overlap syndrome was 2/101 (2%). In patients with GN, SLE/AAV overlap syndrome may occur but with a low prevalence. Most patients have an aggressive renal presentation, with usually both ANA and anti-MPO antibodies. Further studies are needed to assess shared pathogenesis and therapeutic options. PMID:27258503
Rollino, Cristiana; Coppo, Rosanna; Giacchino, Franca; Savoldi, Silvana; Manganaro, Marco; Amore, Alessandro; Colla, Loredana; Ferro, Michela; Demicheli, Giovanni; Berutti, Silvia; Burdese, Manuel; Paternoster, Giuseppe; Cravero, Raffaella; Benozzi, Luisa; Vagelli, Giuseppe; Messuerotti, Alessandra; Licata, Carolina; Bainotti, Serena; Patti, Rosaria Rita; Quaglia, Marco; Costantini, Luigia; Stratta, Piero; Segoloni, Giuseppe
The treatment of membranous glomerulonephritis (MGN) is controversial, especially in cases of no response to first-line treatment or multiple relapses. The Clinical Nephrology Group of Piedmont carried out a multicenter analysis of the treatment of patients affected by MGN in 15 nephrology units in Piedmont. The first treatment is usually started after a waiting period of 3-6 months in case of proteinuria in the nephrotic range but normal or slightly impaired renal function. A history of cancer, the presence of infectious disease, and secondary forms of MGN are criteria for exclusion from treatment. As first-line treatment, Piedmont nephrologists prescribe corticosteroids alternated with immunosuppressive drugs, generally preferring cyclophosphamide to chlorambucil. Only one nephrology unit uses cyclosporin A (CyA) as the first choice. In case of no response to treatment, a second therapeutic approach is undertaken after 2-12 months. Second-line treatment consists of CyA if immunosuppressive drugs were given before, and corticosteroids/ immunosuppressive drugs if CyA was the first treatment. A further choice may be ACTH or rituximab. In case of multiple relapses the treatment options are the same but previous immunosuppressive treatment, patient age, and the duration of kidney disease with a greater probability of renal failure and progression towards sclerosis require careful attention. Concern has been expressed regarding the potentially severe side effects of ACTH including myopathy, cataract and diabetes. In conclusion, the applied therapeutic approaches in Piedmont reflect the difficulty reported in the literature in identifying simple recommendations. ACTH and rituximab are increasingly preferred for the treatment of MGN and there is a need for prospective studies to determine the best protocol for rituximab and the safety profile of ACTH.
Scandiuzzi, Lisa; Beghdadi, Walid; Daugas, Eric; Åbrink, Magnus; Tiwari, Neeraj; Brochetta, Cristiana; Claver, Julien; Arouche, Nassim; Zang, Xingxing; Pretolani, Marina; Monteiro, Renato C.; Pejler, Gunnar; Blank, Ulrich
Mast cells exert protective effects in experimental antiglomerular basement membrane-induced glomerulonephritis (GN), yet the responsible mediators have not been identified. In this study, we investigated the role of mouse mast cell protease (mMCP)-4, the functional homolog of human chymase, using mMCP-4–deficient mice. Compared with wild type animals, mMCP-4–deficient mice exhibited lower proteinuria, blood creatinine, and blood urea nitrogen levels, indicating an aggravating role of mMCP-4. Kidney histology confirmed less severe renal damage in mMCP-4–deficient mice with reduced deposits, glomerular and interstitial cellularity, and fibrosis scores. High amounts of mMCP-4 were detected in renal capsules, but not in the whole kidney, from wild type mice. Its expression in renal capsules was markedly decreased after GN induction, suggesting that locally released enzyme by degranulated mast cells could contribute to the functional and physiopathological hallmarks of GN. Supporting a proinflammatory role, glomerular and interstitial macrophage and T cell infiltration, levels of proinflammatory TNF and MCP-1 mRNA, and the expression of the profibrotic peptide angiotensin II together with type I collagen were markedly down-regulated in kidneys of mMCP-4–deficient mice. We conclude that mMCP-4 chymase, contrary to the global anti-inflammatory action of mast cells, aggravates GN by promoting kidney inflammation. These results highlight the complexity of mast cell-mediated inflammatory actions and suggest that chymase inhibition may represent a novel therapeutic target in GN. PMID:20530261
Background Renal biopsies provide important diagnostic and prognostic information in ANCA associated glomerulonephritis. A new classification for prognostication of pauci-immune glomerulonephritis (GN) based on four categories (Mixed, Crescentic, Sclerotic and Focal) was proposed by an international working group of renal pathologists (IWGRP). The goal of our study was to apply the proposed classification system to a United States cohort of vasculitis patients and determine the association of IWGRP class with estimated glomerular filtration rate (eGFR) at one year. Methods Seventy-six cases of pauci-immune glomerulonephritis diagnosed from 1995 to 2011 from a single center were identified for this retrospective study. Clinical data were collected by abstraction from medical records. Histology was reviewed by a pathologist and classified according to the new classification. MDRD formula was used to calculate eGFR. We correlated IWGRP class to renal function at presentation and at one year. ×2, ANOVA, and linear regression analysis were performed as appropriate. Results Renal biopsies were categorized as focal: n = 20, crescentic: n = 18, mixed: n = 27, sclerotic: n = 11. The baseline e-GFR was lowest in the crescentic class and highest in the focal class. In linear regression analysis investigating e-GFR at 1 year; age and baseline e-GFR were independent predictors of e-GFR at 1 year. Conclusions The e-GFR at diagnosis and age were predictors of e-GFR at 1 year. Pathologic class at diagnosis may also be a helpful tool in risk stratification at diagnosis. PMID:24093336
Okuda, S; Languino, L R; Ruoslahti, E; Border, W A
Glomerular accumulation of extracellular matrix is a prominent feature of progressive glomerulonephritis. Previously, we have shown that transforming growth factor-beta (TGF-beta) is unique among growth factors in regulating the production of the proteoglycans biglycan and decorin by glomerular mesangial cells in vitro. We now provide evidence of an elevated expression of TGF-beta, proteoglycans, and fibronectin in glomerulonephritis induced in rats by injection of anti-thymocyte serum (ATS). Glomeruli were cultured from rat kidneys at 1, 4, 7, 14, and 28 d after ATS administration. Increased proteoglycan synthesis was detected beginning on day 4, which peaked at a 4,900% increase compared with control on day 7, and returned toward control levels by day 28. The increased proteoglycan synthesis by cultured nephritic glomeruli, as well as that of fibronectin, were greatly reduced by addition of antiserum raised against a synthetic peptide from TGF-beta. Conditioned media from ATS glomerular cultures, when added to normal cultured mesangial cells, induced elevated proteoglycan synthesis that also peaked on day 7 and that mimicked the response to added exogenous TGF-beta. The stimulatory activity of the conditioned media was blocked by addition of TGF-beta antiserum. Prior addition of the immunizing peptide to the antiserum abolished the blocking effect. The main induced proteoglycans were identified as biglycan and decorin by immunoprecipitation with antiserum made against synthetic peptides from the proteoglycan core proteins. Glomerular histology showed mesangial matrix expansion in a time course that roughly paralleled both the elevated proteoglycan synthesis by the ATS glomeruli and the ability of the conditioned media from these glomeruli to induce proteoglycan synthesis. At the same time there was an increased expression of TGF-beta mRNA and TGF-beta protein in the glomeruli. These results suggest a central role for TGF-beta in the accumulation of pathological
Sumida, Keiichi; Ubara, Yoshifumi; Marui, Yuji; Nakamura, Michio; Takaichi, Kenmei; Tomikawa, Shinji; Fujii, Takeshi; Ohashi, Kenichi
Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMID) is a recently described disease entity. In the kidney transplantation literature, only 6 recurrent and 2 de novo PGNMID cases, including 7 of the IgG3 subclass (6 with κ light chain and 1 with λ light chain) and 1 of the IgG1 subclass (λ light chain), have been described to date. We describe a 52-year-old man with end-stage renal disease whose primary glomerular disease had been suggested to be membranoproliferative glomerulonephritis. The patient underwent living related donor kidney transplantation and presented with proteinuria, hematuria, and decreased kidney function at 4 months posttransplantation. Biopsy of the transplanted kidney showed diffuse endocapillary proliferative glomerulonephritis. Immunofluorescence microscopy showed prominent granular glomerular staining for IgG, C3, and λ light chain, with IgM, IgA, and κ light chain undetectable. Immunofluorescence staining for IgG subclass showed signal for IgG2 only. Retrospective analysis of the native kidney biopsy specimen also showed the same monoclonal glomerular staining for the IgG2λ subtype. These findings led us to the diagnosis of PGNMID of the IgG2λ subtype as both the primary glomerular disease and recurrent disease in the transplanted kidney. Recurrence was treated with high-dose prednisolone, which decreased proteinuria, hematuria, and serum creatinine level. The case demonstrates that PGNMID of the IgG2λ subtype also can recur in the transplanted kidney.
Song, Jingjing; Wang, Yingwu; Liu, Chungang; Huang, Yan; He, Liying; Cai, Xueying; Lu, Jiahui; Liu, Yan; Wang, Di
Membranous glomerulonephritis (MGN) is a common pathogenesis of nephritic syndrome in adult patients. Nuclear factor kappa B (NF-κB) serves as the main transcription factor for the inflammatory response mediated nephropathy. Cordyceps militaris, containing various pharmacological components, has been used as a kind of crude drug and folk tonic food for improving immunity and reducing inflammation. The current study aims to investigate the renoprotective activity of Cordyceps militaris aqueous extract (CM) in the cationic bovine serum albumin (C-BSA)-induced rat model of membranous glomerulonephritis. Significant renal dysfunction was observed in MGN rats; comparatively, 4-week CM administration strongly decreased the levels of 24 h urine protein, total cholesterol, triglyceride, blood urea nitrogen and serum creatinine, and increased the levels of serum albumin and total serum protein. Strikingly, recovery of the kidney histological architecture was noted in CM-treated MGN rats. A significant improvement in the glutathione peroxidase and superoxide dismutase levels, and a reduced malondialdehyde concentration were observed in the serum and kidney of CM-treated rats. Altered levels of inflammatory cytokines including interleukins, monocyte chemoattractant protein-1, intercellular adhesion molecule 1, vascular adhesion molecule 1, tumor necrosis factor-α, 6-keto-prostaglandin F1α, and nuclear transcriptional factor subunit NF-κB p65 reverted to normal levels upon treatment with CM. The present data suggest that CM protects rats against membranous glomerulonephritis via the normalization of NF-κB activity, thereby inhibiting oxidative damage and reducing inflammatory cytokine levels, which further provide experimental evidence in support of the clinical use of CM as an effective renoprotective agent.
Kato, Akihiko; Sugiura, Takeshi; Yamamoto, Tatsuo; Misaki, Taro; Tsuji, Takayuki; Sakao, Yukitoshi; Sakakima, Masaaki; Yasuda, Hideo; Fujigaki, Yoshihide; Hishida, Akira
We reported the case of a 70-year-old woman with moderate renal failure due to anti-neutrophil cytoplasmic antibody-related glomerulonephritis who developed symptomatic water intoxication (serum Na: 108 mEq/L) following treatment with oral low-dose cyclophosphamide (CY) (50mg/day). Estimated glomerular filtration rate was 29.5 mL/min/1.73 m(2). She had drunk >2 L of fluid in 12 h prior to the development of cerebral oedema. This rare case suggests that oral low-dose CY could be an occult cause of water intoxication in patients with chronic kidney disease taking large fluid volumes.
Toda, Naohiro; Mori, Kiyoshi; Kasahara, Masato; Ishii, Akira; Koga, Kenichi; Ohno, Shoko; Mori, Keita P.; Kato, Yukiko; Osaki, Keisuke; Kuwabara, Takashige; Kojima, Katsutoshi; Taura, Daisuke; Sone, Masakatsu; Matsusaka, Taiji; Nakao, Kazuwa; Mukoyama, Masashi; Yanagita, Motoko; Yokoi, Hideki
Connective tissue growth factor (CTGF) coordinates the signaling of growth factors and promotes fibrosis. Neonatal death of systemic CTGF knockout (KO) mice has hampered analysis of CTGF in adult renal diseases. We established 3 types of CTGF conditional KO (cKO) mice to investigate a role and source of CTGF in anti-glomerular basement membrane (GBM) glomerulonephritis. Tamoxifen-inducible systemic CTGF (Rosa-CTGF) cKO mice exhibited reduced proteinuria with ameliorated crescent formation and mesangial expansion in anti-GBM nephritis after induction. Although CTGF is expressed by podocytes at basal levels, podocyte-specific CTGF (pod-CTGF) cKO mice showed no improvement in renal injury. In contrast, PDGFRα promoter-driven CTGF (Pdgfra-CTGF) cKO mice, which predominantly lack CTGF expression by mesangial cells, exhibited reduced proteinuria with ameliorated histological changes. Glomerular macrophage accumulation, expression of Adgre1 and Ccl2, and ratio of M1/M2 macrophages were all reduced both in Rosa-CTGF cKO and Pdgfra-CTGF cKO mice, but not in pod-CTGF cKO mice. TGF-β1-stimulated Ccl2 upregulation in mesangial cells and macrophage adhesion to activated mesangial cells were decreased by reduction of CTGF. These results reveal a novel mechanism of macrophage migration into glomeruli with nephritis mediated by CTGF derived from mesangial cells, implicating the therapeutic potential of CTGF inhibition in glomerulonephritis. PMID:28191821
Sun, Jian-Yong; Sun, Yu; Wu, Hui-Juan; Zhang, Hong-Xia; Zhao, Zhong-Hua; Chen, Qi; Zhang, Zhi-Gang
Polyethylenimine (PEI), a cationic polymer, is one of the most efficient non-viral vectors for transgene therapy. Decorin (DCN), a leucine-rich proteoglycan secreted by glomerular mesangial cells (MC), is a promising anti-fibrotic agent for the treatment of glomerulonephritis. In this study, we used PEI-DCN nanocomplexes with different N/P ratios to transfect MC in vitro and deliver the MC vector with PEI-DCN expressing into rat anti-Thy1.1 nephritis kidney tissue via injection into the left renal artery in vivo. The PEI-plasmid DNA complex at N/P 20 had the highest level of transfection efficiency and the lowest level of cytotoxicity in cultured MC. Following injection, the ex vivo gene was transferred successfully into the glomeruli of the rat anti-Thy1.1 nephritis model by the MC vector with the PEI-DCN complex. The exogenous MC with DCN expression was located mainly in the mesangium and the glomerular capillary. Over-expression of DCN in diseased glomeruli could result in the inhibition of collagen IV deposition and MC proliferation. The pathological changes of rat nephritis were alleviated following injection of the vector. These findings demonstrate that the DCN gene delivered by the PEI-DNA nanocomplex with the MC vector is a promising therapeutic method for the treatment of glomerulonephritis.
Subramaniam, S. Ravih; Cader, Rizna Abdul; Mohd, Rozita; Yen, Kong Wei; Ghafor, Halim Abdul
Patient: Male, 48 Final Diagnosis: Low dose cyclophosphamide-induced acute hepatotoxicity Symptoms: Epigastric pain Medication: Withdrawal of cyclophosphamide Clinical Procedure: — Specialty: Nephrology • Hepatology • Gastroenterology • Toxicology Objective: Unexpected drug reaction Background: Cyclophosphamide is commonly used to treat cancers, systemic vasculitides, and kidney diseases (e.g., lupus nephritis and focal segmental glomerulosclerosis). Acute adverse effects include bone marrow suppression, hemorrhagic cystitis, nausea, vomiting, and hair loss. Hepatotoxicity with high dose cyclophosphamide is well recognized but hepatitis due to low dose cyclophosphamide has rarely been described. Case Report: We report the case of a 48-year-old Chinese man with a rapidly progressive glomerulonephritis secondary to granulomatosis with polyangiitis who developed severe acute hepatic failure within 24 hours of receiving low-dose intravenous cyclophosphamide. The diagnosis of granulomatosis with polyangiitis was supported with a positive c-ANCA serology. The patient was treated with high dose methylprednisolone, plasmapheresis, intermittent hemodialysis, and low-dose intravenous cyclophosphamide. Conclusions: Hepatotoxicity may occur even after low-dose intravenous cyclophosphamide treatment. To the best of our knowledge, this is the first report of severe, non-viral, liver inflammation developing within 24 hours of administration of low-dose intravenous cyclophosphamide (200 mg). Physicians should be aware of this serious adverse reaction and should not repeat the cyclophosphamide dose when there is hepatotoxicity caused by the first dose. Initial and follow-up liver function tests should be monitored in all patients receiving cyclophosphamide treatment. PMID:24023976
Singri, Naveen; Gleason, Briana; Flamm, Steve L; Kanwar, Yashpal S; Ghossein, Cybele
Patients with end-stage liver disease are prone to hemodynamic and immunologic renal injury, the latter at times manifesting as glomerulonephritis. Elevated serum immunoglobulin A (IgA) levels and mesangial IgG-IgA deposits are common in these patients, but are often clinically silent. We report a patient with autoimmune hepatitis and secondary IgA nephropathy (IgAN) who presented with nephrotic syndrome, acute renal failure (ARF), with 30% of the renal glomeruli having undergone crescentic change, and with IgA2 deposits in the glomerular mesangium. This article discusses secondary IgAN pathogenesis and its therapeutic management.
... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...
Hecker, M; Mayer, K; Askevold, I; Collet, P; Weigand, M A; Krombach, G A; Padberg, W; Hecker, A
Acute pancreatitis is a potentially fatal disease with individually differing expression of systemic involvement. For this reason early diagnosis with subsequent risk stratification is essential in the clinical management of this frequent gastroenterological disorder. Severe forms of acute pancreatitis occur in approximately 20 % of cases often requiring intensive care monitoring and interdisciplinary therapeutic approaches. In the acute phase adequate fluid replacement and sufficient analgesic therapy is of major therapeutic importance. Concerning the administration of antibiotics and the nutritional support of patients with acute pancreatitis a change in paradigms could be observed in recent years. Furthermore, endoscopic, radiological or surgical interventions can be necessary depending on the severity of the disease and potential complications.
... to breathe. Other symptoms of bronchitis are a cough and coughing up mucus. Acute means the symptoms ... diagnosed with chronic bronchitis, you must have a cough with mucus on most days for at least ...
... bronchitis? Acute bronchitis is inflammation of your bronchial tree. The bronchial tree consists of tubes that carry air into your ... weeks or months. This happens because the bronchial tree takes a while to heal. A lasting cough ...
... Chronic Kidney Disease Kidneys and Urinary Tract Kidney Stones Ultrasound: Renal (Kidneys, Ureters, Bladder) When Your Child ... Blood in the Urine (Hematuria) Kidney Disease Kidney Stones Kidney Transplant Kidneys and Urinary Tract Dialysis Lupus ...
Kato, Akihiko; Sugiura, Takeshi; Yamamoto, Tatsuo; Misaki, Taro; Tsuji, Takayuki; Sakao, Yukitoshi; Sakakima, Masaaki; Yasuda, Hideo; Fujigaki, Yoshihide; Hishida, Akira
We reported the case of a 70-year-old woman with moderate renal failure due to anti-neutrophil cytoplasmic antibody-related glomerulonephritis who developed symptomatic water intoxication (serum Na: 108 mEq/L) following treatment with oral low-dose cyclophosphamide (CY) (50mg/day). Estimated glomerular filtration rate was 29.5 mL/min/1.73 m2. She had drunk >2 L of fluid in 12 h prior to the development of cerebral oedema. This rare case suggests that oral low-dose CY could be an occult cause of water intoxication in patients with chronic kidney disease taking large fluid volumes. PMID:18795141
Bates, Melissa A.; Brandenberger, Christina; Langohr, Ingeborg; Kumagai, Kazuyoshi; Harkema, Jack R.; Holian, Andrij; Pestka, James J.
Genetic predisposition and environmental factors influence the development of human autoimmune disease. Occupational exposure to crystalline silica (cSiO2) has been etiologically linked to increased incidence of autoimmunity, including systemic lupus erythematosus (SLE), but the underlying mechanisms are poorly understood. The purpose of this study was to test the hypothesis that early repeated short-term cSiO2 exposure will modulate both latency and severity of autoimmunity in the lupus-prone female NZBWF1 mouse. Weekly intranasal exposure to cSiO2 (0.25 and 1.0 mg) for 4 wk beginning at 9 wk of age both reduced latency and increased intensity of glomerulonephritis. cSiO2 elicited robust inflammatory responses in the lungs as evidenced by extensive perivascular and peribronchial lymphoplasmacytic infiltration consisting of IgG-producing plasma cells, and CD45R+ and CD3+ lymphocytes that were highly suggestive of ectopic lymphoid tissue (ELT). In addition, there were elevated concentrations of immunoglobulins and the cytokines MCP-1, TNF-α and IL-6 in bronchoalveolar lavage fluid. cSiO2-associated kidney and lung effects paralleled dose-dependent elevations of autoantibodies and proinflammatory cytokines in plasma. Taken together, cSiO2-induced pulmonary inflammation and ectopic lymphoid neogenesis in the NZBWF1 mouse corresponded closely to systemic inflammatory and autoimmune responses as well as the early initiation of pathological outcomes in the kidney. These findings suggest that following airway exposure to crystalline silica, in mice genetically prone to SLE, the lung serves as a platform for triggering systemic autoimmunity and glomerulonephritis. PMID:25978333
Kim, Eun Jung; Shin, Dong Ho; Jeon, Hee Jung; Rhee, So Yon; Nam, Eun Sook; Park, Ji Young
POEMS syndrome is a rare paraneoplastic syndrome and there are few reports of polyneuropathy and monoclonal gammopathy associated with kidney dysfunction. Here, we report a case of POEMS syndrome with recurrent acute kidney injury (AKI). A 52-year-old man presented with bilateral aggravating paresthesia and latermotor weakness of the lower extremities accompanied by repeated elevation of serum creatinine. The patient was finally diagnosed with POEMS syndrome on the basis of fulfilling the two mandatory major criteria (polyneuropathy and monoclonal gammopathy), one other major criterion (sclerotic bone lesion), and several minor criteria. A renal biopsy was performed to clarify the cause of AKI and showed membranoproliferative glomerulonephritis-like lesions with mesangiolysis and endothelial cell injury. This case illustrates that renal manifestations, not included in the diagnostic criteria for POEMS, can be apparent before various other systemic symptoms. PMID:27453713
Geokas, Michael C.
For many decades two types of acute pancreatitis have been recognized: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary α-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess. PMID:4559467
Activation of Autophagy and Nucleotide-Binding Domain Leucine-Rich Repeat–Containing-Like Receptor Family, Pyrin Domain–Containing 3 Inflammasome during Leishmania infantum–Associated Glomerulonephritis
Esch, Kevin J.; Schaut, Robert G.; Lamb, Ian M.; Clay, Gwendolyn; Morais Lima, Ádila L.; do Nascimento, Paulo R.P.; Whitley, Elizabeth M.; Jeronimo, Selma M.B.; Sutterwala, Fayyaz S.; Haynes, Joseph S.; Petersen, Christine A.
Chronic kidney disease is a major contributor to human and companion animal morbidity and mortality. Renal complications are sequelae of canine and human visceral leishmaniasis (VL). Despite the high incidence of infection-mediated glomerulonephritis, little is known about pathogenesis of VL-associated renal disease. Leishmania infantum–infected dogs are a naturally occurring model of VL-associated glomerulonephritis. Membranoproliferative glomerulonephritis type I [24 of 25 (96%)], with interstitial lymphoplasmacytic nephritis [23 of 25 (92%)], and glomerular and interstitial fibrosis [12 of 25 (48%)] were predominant lesions. An ultrastructural evaluation of glomeruli from animals with VL identified mesangial cell proliferation and interposition. Immunohistochemistry demonstrated significant Leishmania antigen, IgG, and C3b deposition in VL dog glomeruli. Asymptomatic and symptomatic dogs had increased glomerular nucleotide-binding domain leucine-rich repeat–containing-like receptor family, pyrin domain containing 3 and autophagosome-associated microtubule-associated protein 1 light chain 3 associated with glomerular lesion severity. Transcriptional analyses from symptomatic dogs confirmed induction of autophagy and inflammasome genes within glomeruli and tubules. On the basis of temporal VL staging, glomerulonephritis was initiated by IgG and complement deposition. This deposition preceded presence of nucleotide-binding domain leucine-rich repeat–containing-like receptor family, pyrin domain containing 3–associated inflammasomes and increased light chain 3 puncta indicative of autophagosomes in glomeruli from dogs with clinical VL and renal failure. These findings indicate potential roles for inflammasome complexes in glomerular damage during VL and autophagy in ensuing cellular responses. PMID:26079813
Dassan, Pooja; Clarke, Charles; Sharp, David J
High antistreptococcal antibody titer (ASOT) was measured in a 31-year-old Caucasian lady presenting with opsoclonus and myoclonus. She was treated with oral steroids and 8 weeks after the onset of symptoms she had a normal ASOT and only mild residual symptoms. This is one of the first cases of opsoclonus-myoclonus syndrome developing, following a streptococcal infection in adults.
The presentation of acute vertigo may represent both a common benign disorder or a life threatening but rare one. Familiarity with the common peripheral vestibular disorders will allow the clinician to rapidly “rule-in” a benign disorder and recognize when further testing is required. Key features of vertigo required to make an accurate diagnosis are duration, chronicity, associated symptoms, and triggers. Bedside tests that are critical to the diagnosis of acute vertigo include the Dix-Hallpike maneuver and canalith repositioning manuever, occlusive ophthalmoscopy, and the head impulse test. The goal of this review is to provide the clinician with the clinical and pathophysiologic background of the most common disorders that present with vertigo to develop a logical differential diagnosis and management plan. PMID:23983835
Meekins, Jessica M
Sudden loss of vision is an ophthalmic emergency with numerous possible causes. Abnormalities may occur at any point within the complex vision pathway, from retina to optic nerve to the visual center in the occipital lobe. This article reviews specific prechiasm (retina and optic nerve) and cerebral cortical diseases that lead to acute blindness. Information regarding specific etiologies, pathophysiology, diagnosis, treatment, and prognosis for vision is discussed.
Ersdal, C; Jørgensen, H J; Lie, K-I
Polyarthritis caused by Erysipelothrix rhusiopathiae is a relatively common infection in lambs characterized by low mortality and high morbidity. E. rhusiopathiae is a ubiquitous Gram-positive bacterium that is both a commensal and a pathogen of vertebrates. The disease was studied during an outbreak in a Norwegian Spæl sheep flock. In the acute phase, 48 of 230 (20%) lambs developed clinical signs and 4 died (1.7%). One acute case was necropsied and E. rhusiopathiae was cultured from all major organs investigated and from joints. There was a fibrinous polyarthritis, increased presence of monocytes in vessels, and necrosis of Purkinje cells. Sixteen of the diseased animals (33%) developed a chronic polyarthritis. Eight of these lambs were necropsied; all had lesions in major limb joints, and 3 of 8 also had lesions in the atlanto-occipital joint. At this stage, E. rhusiopathiae was cultured only from the joints in 7 of 8 (87.5%) lambs, but by real-time polymerase chain reaction, we showed persistence of the bacterium in several organs. Pulsed-field gel electrophoresis typing of the bacterial isolates indicated that the same strain caused the acute and chronic disease. Five of 6 (83%) chronically affected animals had amyloidosis of the spleen, and 6 of 8 (75%) had amyloidosis of the liver. All chronically affected animals had a glomerulonephritis, and 6 of 8 (75%) had sparse degeneration in the brain. Ceruloplasmin and haptoglobin were significantly increased in the chronically diseased lambs. These results show that chronic ovine erysipelas is not restricted to joints but is a multisystemic disease.
Sartori, A; Roque-Barreira, M C; Coe, J; Campos-Neto, A
In a previous report analysing kidney sections by immunofluorescence we showed that hamsters infected with L. donovani develop a glomerulonephritis (GN) associated with deposition of hamster immunoglobulins and parasite antigens in the glomeruli. In this study we characterize these immune components eluted from the kidneys. The eluted immunoglobulins showed specificity for L. donovani antigens and hamster immunoglobulins (rheumatoid factor-like activity). The four isotypes IgG1, IgG2, IgA and IgM were detected. Several L. donovani antigens were detected in the renal eluates by Western blot and immunoprecipitation using 125I-labelled eluates. Proteins with mol. wt of 134, 82, 52, 31, and 26 kD were detected by Western blot and proteins with 134, 110, 93, 89 and 48 kD were detected by immunoprecipitation. With the exception of the 134 kD protein which was recognized by both rabbit anti-promastigote and rabbit anti-amastigote sera all the others were recognized only by the anti-amastigote serum. The 134 kD protein was the only one isolated from the kidneys of infected hamster immunocomplexed with IgG and was the only one detected in a promastigote lysate using IgG from L. donovani-infected hamsters. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:1544224
Emeksiz, Serhat; Kutlu, Nurettin Onur; Çaksen, Hüseyin; Alkan, Gülsüm; Yıkmaz, Hülya Şeker; Tokgöz, Hüseyin
Posterior reversible encephalopathy syndrome is characterized by hypertension, seizure, headache, clouding of consciousness, and visual disturbance, and is diagnosed in the presence of typical lesions on magnetic resonance imaging. We retrospectively evaluated five patients who were diagnosed as having posterior reversible encephalopathy syndrome and followed up in Meram Medical Faculty, Pediatric Intensive Care and Hematology wards, between January 2010 and January 2014. We reviewed the demographic and clinical data, and neuroimaging findings. The primary diseases of the subjects included acute lymphocytic leukemia (n=2), Henoch-Schönlein purpura (n=1), systemic lupus erythematous (n=1), and acute poststreptococcal glomerulonephritis (n=1). The mean age was 10±4.58 years (range, 5–14 years). Acute elevation of blood pressure was found in all patients (n=5). Initial neurologic manifestations included seizure, clouding of consciousness, headache, and visual disturbance. After the diagnosis was made through clinical evaluations and magnetic resonance imaging, complete clinical recovery was obtained in all patients with the appropriate therapeutic approach. In conclusion, posterior reversible encephalopathy syndrome should be considered in the differential diagnosis of patients who present with encephalopathy and underlying diseases such as nephritis, vasculitis, malignancy accompanied by hypertension, and a history of use of medication. PMID:28123335
Baxter, G M
Laminitis is an inflammation of the sensitive laminae along the dorsal aspect of the digit and is considered to be a secondary complication of several predisposing or primary factors. Affected horses are usually very lame, have increased digital pulses, are painful to hoof testers along the toe of the foot, and have evidence of downward rotation or distal displacement of the distal phalanx present on radiographs. Treatments for acute laminitis include anti-inflammatory drugs, anti-endotoxin therapy, vasodilators, antithrombotic therapy, corrective trimming and shoeing, and surgical procedures. Treatment regimens are very controversial and the true efficacy of these treatments is unknown. The quality of laminae damage that occurs with laminitis, however, probably has greater influence on the success of treatment and outcome of the horse than the treatment regimen itself.
Hachmo, Yafit; Kalechman, Yona; Skornick, Itai; Gafter, Uzi; Caspi, Rachel R.; Sredni, Benjamin
Crescentic glomerulonephritis (CGN) is the most aggressive form of GN and, if untreated, patients can progress to end-stage renal failure within weeks of presentation. The α4β1 integrin very late antigen-4 (VLA-4) is an adhesion molecule of fundamental importance to the recruitment of leukocytes in inflammation. We addressed the role of VLA-4 in mediating progressive renal injury in a rat model of CGN using a small tellurium compound. AS101 [ammonium trichloro(dioxoethylene-o,o′)tellurate]. This compound has been previously shown to uniquely inhibit VLA-4 activity by redox inactivation of adjacent thiols in the exofacial domain of VLA-4. The study shows that administration of AS101 either before or after glomerular basement membrane anti-serum injection ameliorates crescent formation or preserves renal function. This was associated with profound inhibition of critical inflammatory mediators, accompanied by decreased glomerular infiltration of macrophages. Mechanistic studies demonstrated vla-4 inactivation on glomerular macrophages both in vitro and in vivo as well as inhibition of caspase-1 activity. Importantly, this cysteine protease activity modification was dependent on VLA-4 inactivation and was associated with the anti-inflammatory activity of AS101. We propose that inactivation of macrophage VLA-4 by AS101 in vivo results in a decrease of inflammatory cytokines and chemokines produced in the glomeruli of diseased rats, resulting in decreased further macrophage recruitment and decreased extracellular matrix expansion. Thus, AS101, which is currently in clinical trials for other indications, might be beneficial for treatment of CGN. PMID:28326083
Repeated subcutaneous (SC) injections of mercuric chloride (MC) in Brown Norway (BN) rats induce an autoimmune glomerulonephritis (GN) due to antiglomerular basement membrane (BM) antibody deposition in the glomeruli. The aim of this study was to investigate the effects on MC-induced autoimmune GN of OKY-046, a selective TXA-synthetase inhibitor herring oil (HO), which is rich in eicosapentaenoic acid (EPA) (5.6%) precursor of the three series of prostaglandins (PGs) and of (inactive) thromboxane (TXA3), and evening primrose oil (EPO), which is rich in linoleic acid (LA) (72%) and gamma-linolenic acid (GLNA) (9%), precursors of the one series of PGs, mainly PGE1, and of (inactive) TXA1. The administration of OKY-046 significantly inhibited proteinuria, partially prevented fibrin thrombi (FT) formation in the glomeruli, decreased urinary TXB, enhanced 6ketoPGF excretion and, increased survival rate of the animals from 60% (group receiving only MC) to 86%. However, OKY-046 did not prevent body weight (BW) loss or the development and deposition of IgG in the glomeruli. Increased intake of HO (80 days prior and throughout the experiment) and avoidance of arachidonic acid (AA) intake produced an effect comparable to that of OKY-046 in the rats. Furthermore, HO significantly inhibited the deposition of IgG in the glomeruli, increased the survival rate of the animals to 100% and further enhanced the increased urinary PGE excretion induced by MC. However, HO did not prevent BW loss in the animals. Increased intake of EPO and avoidance of AA intake produced an effect comparable to that of HO. Additionally, EPO completely prevented BW loss induced by MC in these animals. These findings suggest that the metabolites of AA, EPA and GLNA play an important role either in the development or in the modulation of this model of MC induced GN.
Barnett, Timothy C.; McArthur, Jason D.; Cole, Jason N.; Gillen, Christine M.; Henningham, Anna; Sriprakash, K. S.; Sanderson-Smith, Martina L.; Nizet, Victor
SUMMARY Streptococcus pyogenes, also known as group A Streptococcus (GAS), causes mild human infections such as pharyngitis and impetigo and serious infections such as necrotizing fasciitis and streptococcal toxic shock syndrome. Furthermore, repeated GAS infections may trigger autoimmune diseases, including acute poststreptococcal glomerulonephritis, acute rheumatic fever, and rheumatic heart disease. Combined, these diseases account for over half a million deaths per year globally. Genomic and molecular analyses have now characterized a large number of GAS virulence determinants, many of which exhibit overlap and redundancy in the processes of adhesion and colonization, innate immune resistance, and the capacity to facilitate tissue barrier degradation and spread within the human host. This improved understanding of the contribution of individual virulence determinants to the disease process has led to the formulation of models of GAS disease progression, which may lead to better treatment and intervention strategies. While GAS remains sensitive to all penicillins and cephalosporins, rising resistance to other antibiotics used in disease treatment is an increasing worldwide concern. Several GAS vaccine formulations that elicit protective immunity in animal models have shown promise in nonhuman primate and early-stage human trials. The development of a safe and efficacious commercial human vaccine for the prophylaxis of GAS disease remains a high priority. PMID:24696436
Group A Streptococcus (GAS) infections cause substantial worldwide morbidity and mortality, mostly associated with suppurative complications such as pharyngitis, impetigo, and non-suppurative immune syndromes such as acute rheumatic fever, rheumatic heart disease, and acute post-streptococcal glomerulonephritis. Deaths occur mostly in children, adolescents, and young adults in particular pregnant women in low- and middle-income countries. GAS strains are highly variable, and a GAS vaccine would need to overcome the issue of multiple strains. Several approaches have been used multivalent vaccines using N-terminal polypeptides of different M protein; conserved M protein vaccines with antigens from the conserved C-repeat portion of the M protein; incorporation selected T- and B-cell epitopes from the C-repeat region in a synthetic polypeptide or shorter single minimal B-cell epitopes from this same region; and non-M protein approaches utilizing highly conserved motives of streptococcal C5a peptidase, GAS carbohydrate and streptococcal fibronectin-binding proteins. A GAS vaccine represents urgent need for this neglected disease and should therefore deserve the greatest attention of international organizations, donors, and vaccine manufacturers. PMID:27489799
Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)
A comparison of the effect of ramipril, felodipine and placebo on glomerular filtration rate, albuminuria, blood pressure and vasoactive hormones in chronic glomerulonephritis. A randomized, prospective, double-blind, placebo-controlled study over two years.
Pedersen, E B; Bech, J N; Nielsen, C B; Kornerup, H J; Hansen, H E; Spencer, E S; Sølling, J; Jensen, K T
The effects of an ACE-inhibitor (ramipril), a calcium antagonist (felodipine) and placebo on glomerular filtration rate (GFR), urinary albumin/creatinine ratio, blood pressure (BP) and vasoactive hormones were investigated in a randomized, prospective, double-blind, placebo-controlled study of patients with chronic glomerulonephritis and hypertension, with measurements at entrance and after 12 and 24 months. In total, 33 patients were included: 21 completed the study with 7 patients in each group. GFR was measured as 51Cr-EDTA clearance and the vasoactive hormones with radioimmunoassays. The reduction in GFR was significantly more pronounced in the felodipine group (-7 ml/min) than in the ramipril group (0 ml/min) but the same as in the placebo group (-6 ml/min). The urinary albumin/creatinine ratio was significantly more reduced in the ramipril group (-74 mg/mmol) than in the placebo group (-11 mg/mmol), which did not deviate from the felodipine group (-10 mg/mmol). BP was significantly reduced by ramipril and felodipine, but not by placebo. Angiotensin II and aldosterone in plasma increased or tended to increase in the felodipine and placebo groups, but were unchanged in the ramipril group. Endothelin increased only in the placebo group, and vasopressin, atrial natriuretic peptide, and brain natriuretic peptide were not significantly changed in any of the groups. It is concluded that ramipril seems to be superior to felodipine in chronic glomerulonephritis owing to better preservation of GFR.
[An experience of treatment of double positive myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA) and anti-glomerular basement membrane antibodies in Goodpasture's syndrome onset of crescentic glomerulonephritis].
Takeda, T; Takeda, T; Naiki, Y; Yonekawa, S; Sakaguchi, M; Iwamoto, I; Tanaka, H; Hasegawa, H; Imada, A; Kanamaru, A; Hiruma, S; Maekura, S; Hashimoto, S; Yamazumi, T
A 68-year-old woman was admitted to Kinki University Hospital because of progressive renal failure. She had been well until two months before admission. Laboratory data were as follows: serum creatinine 4.1 mg/dl, BUN 69 mg/dl, MPO-ANCA 33 EU, anti-glomerular basement membrane antibodies (AGBMA) 118 U. Histological findings showed cellular and fibrocellular crescents in many glomeruli. Therefore, we diagnosed rapidly progressive glomerulonephritis (RPGN) due to MPO-ANCA and anti-GBM associated renal disease. The patient was started on prednisolone and double filtration plasmapheresis (DFPP) therapy. Subsequently, the values of MPO-ANCA and AGBMA decreased. However, the patient's condition suddenly worsened and she died of interstitial pneumonia. Autopsy examination revealed crescentic glomerulonephritis and alveolar hemorrhage with linear deposition of IgG along the glomerular and alveolar capillary walls by immunofluorescence studies. We considered this to be a rare case of Goodpasture's syndrome associated with not only anti-GBM antibodies, but also MPO-ANCA.
Adike, Abimbola; Cherry, Mariyam; Awar, Melina
IgM nephropathy is a relatively rare cause of idiopathic nephrotic syndrome.1 It was initially described by van de Putte,2 then by Cohen and Bhasin in 1978, as a distinctive feature of mesangial proliferative glomerulonephritis.2 It is typically characterized by diffuse IgM deposits on the glomeruli and diffuse mesangial hypercellularity. Little is known about the pathogenesis and treatment of this disease.1,3 We describe a patient who presented with nonspecific symptoms of epigastric pain, nausea, and early satiety. Abdominal imaging and endoscopies were unremarkable. She was found to have significant proteinuria (6.4 g/24 hours), hyperlipidemia, and edema consistent with a diagnosis of nephrotic syndrome. Kidney biopsy was performed and confirmed an IgM nephropathy. Less than 2 weeks after her diagnosis of IgM nephropathy, she presented with an acute cerebellar stroke. Thrombophilia is a well-known complication of nephrotic syndrome, but a review of the literature failed to show an association between IgM nephropathy and acute central nervous system thrombosis. PMID:27057296
Lee, V K; Kimbrough, D J; Jarquin-Valdivia, A A
Acute bacterial parotitis (ABP) is a relatively uncommon condition that tends to occur in debilitated older patients. We report a case of an older woman that presented with an acute intracerebral hemorrhage who developed ABP. This morbidity led to endotracheal intubation, mechanical ventilation, tracheostomy and gastrostomy, all of which were not initially needed. We discuss the proposed physiopathology and etiopathogenesis of ABP in adults.
... hard for blood to do its work. In acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia, there are too ... of white blood cells called lymphocytes or lymphoblasts. ALL is the most common type of cancer in ...
Acute renal arterial thrombosis; Renal artery embolism; Acute renal artery occlusion; Embolism - renal artery ... kidneys need a good blood supply. The main artery to the kidney is called the renal artery. ...
Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... There are many possible causes of kidney damage. They include: ... cholesterol (cholesterol emboli) Decreased blood flow due to very ...
Monfared, Ali; Habibzadeh, Seyed Mahmoud; Mesbah, Seyed Alireza
We present acute phosphate nephropathy in a 28-year-old man, which was developed after a car accident due to rhabdomyolysis. Treatment of acute kidney injury was done with administration of sodium bicarbonate.
... and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as the sudden inflammation ... the incidence of recurrent attacks minimized. Timothy Gardner, MD is Director of Pancreatic Disorders at Dartmouth-Hitchcock ...
Kim, Ki Up; Kim, Jin Kyeung; Won, Jong Ho; Hong, Dae Sik; Park, Hee Sook; Park, Kyeung Kyu
The decision to operate for abdominal pain in patients with leukopenia can be exceedingly difficult. Surgical exploration may be the only effective way to differentiate acute appendicitis from other causes, but it involves considerable risk of infectious complications due to immunesuppression. Leukemic patients, who presented significant RLQ pain, had been indicated for operation, despite having advanced disease or having had received chemotherapy or steroids. Four adult leukemia patients, complicated by acute appendictis, were reviewed. Two patients were in induction chemotherapy, one receiving salvage chemotheapy due to relapse and the other was in conservative treatment. Two patients were acute myelocytic leukemia (AML), one had acute lymphocytic leukemia (ALL), and the other had aleukemic leukemia. All patients underwent appendectomy and recovered without complication. Our experience supports the theory that the surgical management of appendicitis in acute leukemia is the most effective way, in spite of leukopenia. PMID:8268146
Tristán, Bekinschtein; Gleichgerrcht, Ezequiel; Manes, Facundo
Acute loss of consciousness poses a fascinating scenario for theoretical and clinical research. This chapter introduces a simple yet powerful framework to investigate altered states of consciousness. We then explore the different disorders of consciousness that result from acute brain injury, and techniques used in the acute phase to predict clinical outcome in different patient populations in light of models of acute loss of consciousness. We further delve into post-traumatic amnesia as a model for predicting cognitive sequels following acute loss of consciousness. We approach the study of acute loss of consciousness from a theoretical and clinical perspective to conclude that clinicians in acute care centers must incorporate new measurements and techniques besides the classic coma scales in order to assess their patients with loss of consciousness.
Malbora, Baris; Bilaloglu, Eris
The presence of lupus anticoagulants (LAs) is an important cause of activated partial thromboplastin time (aPTT) prolongation found in children after an infection or during screening tests before surgical intervention. The authors retrospectively reviewed the charts of 68 patients who have been consulted from surgery departments with prolonged aPTT. These patients were reevaluated with aPTT analysis after 1 week. Thirteen patients had normal aPTTs. Therefore, 55 patients remained with prolonged aPTTs. LA positivity was detected in 39 patients. Sixteen of these had prolonged aPTT prior to surgery (41%). Others with LA positivity had systemic lupus erythematosus (SLE; n = 6), infection (n = 5), leukemia (n = 3), hemolytic uremic syndrome (n = 2), epistaxis (n = 2), antiphospholipid syndrome (APS; n = 1), chronic immune thrombocytopenic purpura (n = 1), acute poststreptococcal glomerulonephritis (n = 1), central nervous system (CNS) thrombosis (n = 1), and congenital heart disease (n = 1). None of the patients had bleeding history. LA positivity rarely leads to bleeding and/or thrombosis. Specific therapy is usually not needed. Further prospective multicenter studies are required to understand clinical outcomes and laboratory correlation in children with positive LA.
Heukelbach, Jörg; Feldmeier, Hermann
Scabies is a neglected parasitic disease that is a major public health problem in many resource-poor regions. It causes substantial morbidity from secondary infections and post-infective complications such as acute post-streptococcal glomerulonephritis. Disease control requires treatment of the affected individual and all people they have been in contact with, but is often hampered by inappropriate or delayed diagnosis, poor treatment compliance, and improper use of topical compounds such as permethrin, lindane, or benzyl benzoate. In addition to concerns over toxicity with such compounds, parasite resistance seems to be increasing. Oral ivermectin is an alternative that has been used successfully in community control programmes. Plant derivatives such as turmeric, neem, and tea tree oil are also promising future treatments. The disease is strongly associated with poverty and overcrowding, and the associated stigma can ostracise affected individuals. Treatment of scabies in poor countries needs to integrate drug treatment programmes with efforts to improve the socioeconomic conditions and education programmes to reduce stigma. We expect the future to bring more sensitive and specific clinical and laboratory-based diagnostic methods, as well as new therapeutic strategies.
Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia
Wald, Ellen R
Acute otitis media and acute bacterial sinusitis are 2 of the most common indications for antimicrobial agents in children. Together, they are responsible for billions of dollars of health care expenditures. The pathogenesis of the 2 conditions is identical. In the majority of children with each condition, a preceding viral upper respiratory tract infection predisposes to the development of the acute bacterial complication. It has been shown that viral upper respiratory tract infection predisposes to the development of acute otitis media in 37% of cases. Currently, precise microbiologic diagnosis of acute otitis media and acute bacterial sinusitis requires performance of tympanocentesis in the former and sinus aspiration in the latter. The identification of a virus from the nasopharynx in either case does not obviate the need for antimicrobial therapy. Furthermore, nasal and nasopharyngeal swabs are not useful in predicting the results of culture of the middle ear or paranasal sinus. However, it is possible that a combination of information regarding nasopharyngeal colonization with bacteria and infection with specific viruses may inform treatment decisions in the future.
Maier, Alexander; Kommer, Vera
We report on a young women with acute rheumatic fever. Acute rheumatic fever has become a rare disease in Germany, especially in adults. This carries the risk that it can be missed in the differential diagnostic considerations of acute rheumatic disorders and febrile status. If rheumatic fever is not diagnosed and treated correctly, there is a considerable risk for rheumatic valvular heart disease. In this article diagnosis, differential diagnosis and therapy of rheumatic fever are discussed extensively.
Naqvi, Rubina; Mubarak, Muhammed; Ahmed, Ejaz; Akhtar, Fazal; Bhatti, Sajid; Naqvi, Anwar; Rizvi, Adib
Introduction: Acute kidney injury (AKI) is common in nephro-urological practice. Its incidence, prevalence and etiology vary widely, mainly due to variations in the definitions of AKI. Objectives: We aim to report the spectrum of glomerular diseases presenting as AKI at a kidney referral center in Pakistan. Patients and Methods: An observational cohort of patients identified as having AKI which was defined according to RIFLE criteria, with normal size, non-obstructed kidneys on ultrasonography, along with active urine sediment, edema and new onset hypertension. Results: From 1990 to 2014, 236 cases of AKI secondary to acute glomerulonephritis (AGN) registered at this institution. Mean age of patients was 27.94± 12.79 years and M:F ratio was 0.77:1. Thirty percent patients revealed crescents on renal biopsy. AGN without crescents was seen in 33.05% of cases. Postinfectious GN was found in 14.4%, lupus nephritis in 8.5% and mesangiocapillary GN in 3.4% cases. Renal replacement therapy (RRT) required in 75.84% patients. Pulse steroids were given in 45.33% cases followed by oral steroids. Pulse cyclophoshphamide was given in 23.7% cases and plasmapheresis was used in 3.38% cases. Complete recovery was seen in 44%, while 11.44% died during acute phase of illness. About 19.49 % developed chronic kidney disease (CKD) and 25.84% were lost to long- term follow-up. Conclusion: Although glomerular diseases contribute only 4.19 % of total AKI at this center, morbidity associated with illness and its treatment is more marked than other AKI groups. Another notable factor is late referral of these patients to specialized centers resulting in undesirable outcome. PMID:26693497
Matsuo, Nanae; Yamamoto, Hiroyasu; Kobayashi, Akimitsu; Yamamoto, Izumi; Mitome, Jun; Maruyama, Yukio; Hayakawa, Hiroshi; Miyazaki, Yoichi; Utsunomiya, Yasunori; Hosoya, Tatsuo; Yamaguchi, Yutaka
A 59-yr-old Japanese woman with chronic renal failure caused by IgA nephropathy and antineutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis underwent kidney transplantation from a living unrelated spousal donor. The blood type was compatible, while the human leukocyte antigen (HLA) typing showed a 5/6 locus mismatch. She had become pregnant twice by her donor and had never received blood transfusions. Complement-dependent cytotoxicity cross-match, flow cytometry cross-match (FCXM), and flow panel reactive antibody (PRA) were negative. She initially underwent one week of immunosuppression with mycophenolate mofetil (MMF) and double filtration plasmapheresis (DFPP) immediately before transplantation to reduce the risk of antibody-mediated rejection. Induction therapy consisted of MMF, tacrolimus (TAC), methylprednisolone (MP), and basiliximab. The allograft function was excellent immediately after the operation. However, the urine output and platelet count declined rapidly on post-operative day (POD) 3, while the serum creatinine (sCr) and lactate dehydrogenase levels rose gradually. Subsequently, we could not detect the diastolic arterial flow on Doppler sonography. We diagnosed accelerated acute rejection and treated her with plasma exchange (PEX), intravenous MP pulse therapy, and rituximab. The first episode biopsy on POD 7 revealed acute vascular rejection and acute antibody-mediated rejection (Banff score AMR II). Her urinary excretion increased beginning on POD 13, while the sCr level decreased gradually and reached 0.9 mg/dL on POD 22. In our retrospective analysis, the LAB screen detected donor-specific antibody (DSA). This case suggested that, for successful kidney transplantation in highly sensitized recipients, such as husband-to-wife spousal kidney transplantation with a history of pregnancy, we should keep the risk of AMR in mind, even if the sensitive antibody detection tests are negative.
Gruys, E.; Toussaint, M.J.M.; Niewold, T.A.; Koopmans, S.J.
A review of the systemic acute phase reaction with major cytokines involved, and the hepatic metabolic changes, negative and positive acute phase proteins (APPs) with function and associated pathology is given. It appears that APPs represent appropriate analytes for assessment of animal health. Whereas they represent non-specific markers as biological effect reactants, they can be used for assessing nutritional deficits and reactive processes, especially when positive and negative acute phase variables are combined in an index. When such acute phase index is applied to separate healthy animals from animals with some disease, much better results are obtained than with single analytes and statistically acceptable results for culling individual animals may be reached. Unfortunately at present no cheap, comprehensive and easy to use system is available for assessing various acute phase proteins in serum or blood samples at the same time. Protein microarray or fluid phase microchip technology may satisfy this need; and permit simultaneous analysis of numerous analytes in the same small volume sample and enable integration of information derived from systemic reactivity and nutrition with disease specific variables. Applying such technology may help to solve health problems in various countries not only in animal husbandry but also in human populations. PMID:16252337
Tilouche, Samia; Masmoudi, Tasnim; Sahnoun, Maha; Chkirbène, Youssef; Mestiri, Sarra; Boughamoura, Lamia; Ben Dhiab, Mohamed; Souguir, Mohamed Kamel
Myocarditis is an inflammatory disease of the myocardium with heterogeneous clinical manifestations and progression. In clinical practice, although there are many methods of diagnosis of acute myocarditis, the diagnosis remains an embarrassing dilemma for clinicians. The authors report the case of 9-month-old infant who was brought to the Pediatric Emergency Department with sudden onset dyspnea. Examination disclosed heart failure and resuscitation was undertaken. The electrocardiogram showed an ST segment elevation in the anterolateral leads with a mirror image. Cardiac enzyme tests revealed a significant elevation of troponin and creatine phosphokinase levels. A diagnosis of acute myocardial infarction was made, and heparin therapy was prescribed. The infant died on the third day after admission with cardiogenic shock. The autopsy showed dilatation of the ventricles and massive edema of the lungs. Histological examinations of myocardium samples revealed the presence of a marked lymphocytic infiltrate dissociating myocardiocytes. Death was attributed to acute myocarditis. The authors call attention to the difficulties of differential diagnosis between acute myocarditis and acute myocardial infarction especially in children, and to the important therapeutic implications of a correct diagnosis. PMID:28210569
Atkinson, K.; Wells, D. G.; Clink, H. McD.; Kay, H. E. M.; Powles, R.; McElwain, T. J.
Seventy-eight adult patients with acute leukaemia were classified cytologically into 3 categories: acute lymphoblastic leukaemia (ALL), acute myelogenous leukaemia (AML) or acute undifferentiated leukaemia (AUL). The periodic acid-Schiff stain was of little value in differentiating the 3 groups. The treatment response in each group was different: 94% of patients with ALL (16/17) achieved complete remission with prednisone, vincristine and other drugs in standard use in childhood ALL; 59% of patients with AML (27/46) achieved complete remission with cytosine arabinoside and daunorubicin (22 patients), or 6-thioguanine and cyclophosphamide (2 patients), 6-thioguanine, cyclophosphamide and Adriamycin (1 patient), and cytosine and Adriamycin (1 patient); only 2 out of 14 patients (14%) with acute undifferentiated leukaemia achieved complete remission using cytosine and daunorubicin after an initial trial of prednisone and vincristine had failed. Prednisone and vincristine would seem to be of no value in acute undifferentiated leukaemia. It would seem also that no benefit is obtained by classifying all patients with acute leukaemia over 20 years of age as “adult acute leukaemia” and treating them with the same polypharmaceutical regimen. The problems posed by each disease are different and such a policy serves only to obscure them. ImagesFig. 1Fig. 2Fig. 3 PMID:4141625
Gray, Matthew Philip; Gorelick, Marc H
Acute disseminated encephalomyelitis is a primarily pediatric, immune-mediated disease characterized by demyelination and polyfocal neurologic symptoms that typically occur after a preceding viral infection or recent immunization. This article presents the pathophysiology, diagnostic criteria, and magnetic resonance imaging characteristics of acute disseminated encephalomyelitis. We also present evaluation and management strategies.
Van Hook, James W
Acute kidney injury complicates the care of a relatively small number of pregnant and postpartum women. Several pregnancy-related disorders such as preeclampsia and thrombotic microangiopathies may produce acute kidney injury. Prerenal azotemia is another common cause of acute kidney injury in pregnancy. This manuscript will review pregnancy-associated acute kidney injury from a renal functional perspective. Pathophysiology of acute kidney injury will be reviewed. Specific conditions causing acute kidney injury and treatments will be compared.
Mabuchi, T; Katada, N; Nishimura, D; Hoshino, H; Shimizu, F; Suzuki, R; Sano, H; Kato, K
MRCP has been recognized as a safe and noninvasive diagnostic method. In the present study we evaluated the usefulness of MRCP in diagnosis of chronic and acute pancreatitis. Two-dimensional fast asymmetric spin-echo (FASE) MRCP was performed in 40 patients with chronic pancreatitis and 13 with acute pancreatitis. In 29 patients (72.5%) with chronic pancreatitis and 9 (66.7%) with acute pancreatitis, main pancreatic duct (MPD) was visualized entirely. MRCP could demonstrate the characteristic findings of chronic pancreatitis such as dilatation and irregularity of MPD in most cases. In acute pancreatitis, MRCP indicated that MPD was normal in diameter, but irregular in configuration compared with that of the control group. MRCP may facilitate the diagnosis of chronic and acute pancreatitis.
Acute disseminated encephalomyelitis is an immune-mediated inflammatory and demyelinating disorder of the central nervous system, commonly preceded by an infection. It principally involves the white matter tracts of the cerebral hemispheres, brainstem, optic nerves, and spinal cord. Acute disseminated encephalomyelitis mainly affects children. Clinically, patients present with multifocal neurologic abnormalities reflecting the widespread involvement in central nervous system. Cerebrospinal fluid may be normal or may show a mild pleocytosis with or without elevated protein levels. Magnetic resonance image (MRI) shows multiple demyelinating lesions. The diagnosis of acute disseminated encephalomyelitis requires both multifocal involvement and encephalopathy by consensus criteria. Acute disseminated encephalomyelitis typically has a monophasic course with a favorable prognosis. Multiphasic forms have been reported, resulting in diagnostic difficulties in distinguishing these cases from multiple sclerosis. In addition, many inflammatory disorders may have a similar presentation with frequent occurrence of encephalopathy and should be considered in the differential diagnosis of acute disseminated encephalomyelitis.
... Adults About Acute Lymphocytic Leukemia (ALL) What Is Acute Lymphocytic Leukemia? Cancer starts when cells in the body begin ... Acute Lymphocytic Leukemia Research and Treatment? More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...
... Adults Treating Acute Lymphocytic Leukemia Targeted Therapy for Acute Lymphocytic Leukemia In recent years, new drugs that target specific ... Typical Treatment of Acute Lymphocytic Leukemia More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...
... Acute Myeloid Leukemia Treatment of Acute Promyelocytic (M3) Leukemia Early diagnosis and treatment of acute promyelocytic leukemia ( ... Comes Back After Treatment? More In Acute Myeloid Leukemia About Acute Myeloid Leukemia Causes, Risk Factors, and ...
Bissell, D. Montgomery; Wang, Bruce
The porphyrias comprise a set of diseases, each representing an individual defect in one of the eight enzymes mediating the pathway of heme synthesis. The diseases are genetically distinct but have in common the overproduction of heme precursors. In the case of the acute (neurologic) porphyrias, the cause of symptoms appears to be overproduction of a neurotoxic precursor. For the cutaneous porphyrias, it is photosensitizing porphyrins. Some types have both acute and cutaneous manifestations. The clinical presentation of acute porphyria consists of abdominal pain, nausea, and occasionally seizures. Only a small minority of those who carry a mutation for acute porphyria have pain attacks. The triggers for an acute attack encompass certain medications and severely decreased caloric intake. The propensity of females to acute attacks has been linked to internal changes in ovarian physiology. Symptoms are accompanied by large increases in delta-aminolevulinic acid and porphobilinogen in plasma and urine. Treatment of an acute attack centers initially on pain relief and elimination of inducing factors such as medications; glucose is administered to reverse the fasting state. The only specific treatment is administration of intravenous hemin. An important goal of treatment is preventing progression of the symptoms to a neurological crisis. Patients who progress despite hemin administration have undergone liver transplantation with complete resolution of symptoms. A current issue is the unavailability of a rapid test for urine porphobilinogen in the urgent-care setting. PMID:26357631
Acute renal failure (now acute kidney injury) is a common complication of critical illness affecting between 30 and 60% of critically ill patients. The development of a consensus definition (RIFLE--risk, injury, failure, loss, end-stage system) has allowed standardization of reporting and epidemiological work. Multicenter multinational epidemiological studies indicate that sepsis is now the most common cause of acute renal failure in the intensive care unit (ICU) followed by cardiac surgery-associated acute kidney injury. Unfortunately, our understanding of the pathogenesis of acute renal failure in these settings remains limited. Because of such limited understanding, no reproducibly effective therapies have been developed. In addition the diagnosis of acute renal failure still rests upon the detection of changes in serum creatinine, which only occur if more than 50% of glomerular filtration is lost and are often delayed by more than 24 hours. Such diagnostic delays make the implementation of early therapy nearly impossible. In response to these difficulties, there has been a concerted effort to use proteomics to identify novel early biomarkers of acute renal failure. The identification and study of neutrophil gelatinase- associated lipocalin has been an important step in this field. Another area of active interest and investigation relates to the role of intravenous fluid resuscitation and fluid balance. Data from large observational studies and randomized, controlled trials consistently indicate that a positive fluid balance in patients with acute renal failure represents a major independent risk factor for mortality and provides no protection of renal function. The pendulum is clearly swinging away from a fluid-liberal approach to a fluid-conservative approach in these patients. Finally, there is a growing appreciation that acute renal failure may identify patients who are at increased risk of subsequent chronic renal dysfunction and mortality, opening the way
Powell, Jessica; Graham, David; O'Reilly, Sarah; Punton, Gillian
Acute pulmonary oedema is a distressing and life-threatening illness that is associated with a sudden onset of symptoms. For the best possible patient outcomes, it is essential that nurses in all clinical areas are equipped to accurately recognise, assess and manage patients with acute pulmonary oedema. This article outlines the pathophysiology of acute cardiogenic and non-cardiogenic pulmonary oedema, and suggests a systematic approach to the recognition and management of its most serious manifestations. Long-term care and symptom recognition are discussed and suggestions for ongoing patient self-management are provided.
Moore, A W; Coke, J M
Acute porphyrias are classified into 3 distinct groups of rare genetic disorders of metabolic enzyme biosynthesis. Acute porphyrias can significantly impact multiple organ systems, which often provides a challenge to the dentist presented with such a patient. A case of hereditary coproporphyria is reported in a patient with many of the classical signs and symptoms. The patient also had complex dental needs that required special medical and pharmacotherapeutic modifications. The acute porphyrias are reviewed by the authors with presentation of this challenging case. Recommendations for other dental health care professionals encountering these patients are then presented.
... 2017 Apr 05, 2017 National Porphyria Awareness Week! Mar 23, 2017 National Porphyria Awareness Week is ONE ... 2017 National Porphyria Awareness Week (NPAW) 2017 date: Mar 1, 2017 FDA Meeting for Acute Porphyrias is ...
Cell death due to DNA damage by ionizing radiation causes acute radiation injury of tissues and organs. Frequency and severity of the injuries increase according to dose increase, when the dose becomes more than threshold dose. The threshold dose of acute human radiation death is 1 Gy and LD50 of human is 4 Gy. Human dies due to the cerebrovascular syndrome, the gastrointestinal syndrome or the hematopoetic syndrome, when he received more than 20 Gy, 10-20 Gy or 3-8 Gy to his total body, respectively. Any tissue or organ, including embryo and fetus, does not show the acute injury, when it received less than 100 mSv. Acute injuries are usually reversible, and late injuries are sometimes irreversible.
... angina? This content was last reviewed July 2015. Heart Attack • Home • About Heart Attacks Acute Coronary Syndrome (ACS) ... Recovery FAQs • Heart Attack Tools & Resources • Support Network Heart Attack Tools & Resources What Is a Heart Attack? How ...
Delgado-García, Silvia; Palacios-Marqués, Ana; Martínez-Escoriza, Juan Carlos; Martín-Bayón, Tina-Aurora
Acute genital ulcers, also known as acute vulvar ulcers, ulcus vulvae acutum or Lipschütz ulcers, refer to an ulceration of the vulva or lower vagina of non-venereal origin that usually presents in young women, predominantly virgins. Although its incidence is unknown, it seems a rare entity, with few cases reported in the literature. Their aetiology and pathogenesis are still unknown. The disease is characterised by an acute onset of flu-like symptoms with single or multiple painful ulcers on the vulva. Diagnosis is mainly clinical, after exclusion of other causes of vulvar ulcers. The treatment is mainly symptomatic, with spontaneous resolution in 2 weeks and without recurrences in most cases. We present a case report of a 13-year-old girl with two episodes of acute ulcers that fit the clinical criteria for Lipschütz ulcers. PMID:24473429
Brix, Silke; Stahl, Rolf
Acute kidney injury (AKI) is an important part of renal diseases and a common clinical problem. AKI is an acute decline in renal function. Due to a lack of therapeutic options, prevention and optimal management of patients with AKI are the most important strategies. Although seldom the sole cause of patients' death, AKI is associated with a significant increase in mortality. Our objective is to draw the attention towards the prevention of AKI of non-renal causes.
Bhatia, Madhav; Wong, Fei Ling; Cao, Yang; Lau, Hon Yen; Huang, Jiali; Puneet, Padmam; Chevali, Lakshmi
Acute pancreatitis is a common clinical condition. It is a disease of variable severity in which some patients experience mild, self-limited attacks while others manifest a severe, highly morbid, and frequently lethal attack. The exact mechanisms by which diverse etiological factors induce an attack are still unclear. It is generally believed that the earliest events in acute pancreatitis occur within acinar cells. Acinar cell injury early in acute pancreatitis leads to a local inflammatory reaction. If this inflammatory reaction is marked, it leads to a systemic inflammatory response syndrome (SIRS). An excessive SIRS leads to distant organ damage and multiple organ dysfunction syndrome (MODS). MODS associated with acute pancreatitis is the primary cause of morbidity and mortality in this condition. Recent studies have established the role played by inflammatory mediators in the pathogenesis of acute pancreatitis and the resultant MODS. At the same time, recent research has demonstrated the importance of acinar cell death in the form of apoptosis and necrosis as a determinant of pancreatitis severity. In this review, we will discuss about our current understanding of the pathophysiology of acute pancreatitis.
Bitar, Anas; Altaf, Muhammad; Sferra, Thomas J.
Summary Background: Pancreatitis in the pediatric age group is not as common as in adults. Etiologies are various and differ from those in adults. Although infectious etiology accounts for a significant number of cases of pancreatitis, acute infection with Human Immunodeficiency Virus (HIV) was rarely reported as a possible etiology for acute pancreatitis in adults. Acute pancreatitis has never been reported as a presenting manifestation of acute HIV infection in children. Case Report: We describe a pediatric patient who presented with acute pancreatitis that revealed acute HIV infection. Conclusions: Acute pancreatitis as a primary manifestation of HIV infection is very rare. It may represent an uncommon aspect of primary HIV infection. We suggest that acute HIV infection should be considered in the differential diagnosis of acute pancreatitis at all ages. PMID:23569476
Desai, Jay; Mitchell, Wendy G
Acute cerebellar ataxia and acute cerebellitis represent a process characterized by parainfectious, postinfectious, or postvaccination cerebellar inflammation. There is considerable overlap between these entities. The mildest cases of acute cerebellar ataxia represent a benign condition that is characterized by acute truncal and gait ataxia, variably with appendicular ataxia, nystagmus, dysarthria, and hypotonia. It occurs mostly in young children, presents abruptly, and recovers over weeks. Neuroimaging is normal. Severe cases of cerebellitis represent the other end of the spectrum, presenting with acute cerebellar signs often overshadowed by alteration of consciousness, focal neurological deficits, raised intracranial pressure, hydrocephalus, and even herniation. Neuroimaging is abnormal and the prognosis is less favorable than in acute cerebellar ataxia. Acute disseminated encephalomyelitis may be confused with acute cerebellitis when the clinical findings are predominantly cerebellar, but lesions on neuroimaging are usually widespread. Paraneoplastic opsoclonus-myoclonus syndrome is often initially misdiagnosed as acute cerebellar ataxia, but has very specific features, course, and etiopathogensis.
Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia
Deposition of alpha 1-antitrypsin and loss of glycoconjugate carrying Ulex europaeus agglutinin-I binding sites in the glomerular sclerotic process. Phenomena common to chronic pyelonephritis and chronic diffuse proliferative glomerulonephritis.
Yonezawa, S; Irisa, S; Nakamura, T; Uemura, S; Otsuji, Y; Ohi, Y; Sato, E
Sclerotic processes of glomeruli in chronic pyelonephritis (CPN) and chronic diffuse proliferative glomerulonephritis (CDPGN) were investigated in a lectin binding study in connection with an immunofluorescent examination of protease inhibitor deposition. Ulex europaeus agglutinin-I (UEA-I), which is specific to a certain terminal alpha-L-fucosyl residue of glycoconjugates, specifically labelled intact endothelia of glomerular capillaries, peritubular capillaries and blood vessels in human kidneys. Segmental or global loss of the UEA-I binding with glomerular capillaries was observed in the sclerotic areas where alpha 1-antitrypsin (alpha 1AT) deposits were always detected in the glomeruli with segmental or global sclerosis of CPN. This high correlation between loss of UEA-I binding and alpha 1AT deposition was also observed in the affected glomeruli of CDPGN. In considering glomerular sclerosis, it is significant that loss of UEA-I binding and alpha 1AT deposition are common to both CPN and CDPGN, although their original etiologies are quite different.
Rodriguez, Eduardo A.; Lopez, Marvin A.; Valluri, Kartik; Wang, Danlu; Fischer, Andrew; Perdomo, Tatiana
Patient: Female, 43 Final Diagnosis: Myeloid sarcoma appendicitis Symptoms: Abdominal pain • chills • fever Medication: — Clinical Procedure: Laparoscopic appendectomy, bone marrow biopsy Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: The gastrointestinal tract is a rare site for extramedullary involvement in acute promyelocytic leukemia (APL). Case Report: A 43-year-old female with no past medical history presented complaining of mild abdominal pain, fever, and chills for the past day. On examination, she was tachycardic and febrile, with mild tenderness of her right lower quadrant and without signs of peritoneal irritation. Laboratory examination revealed pancytopenia and DIC, with a fibrinogen level of 290 mg/dL. CT of the abdomen showed a thickened and hyperemic appendix without perforation or abscess, compatible with acute appendicitis. The patient was given IV broad-spectrum antibiotics and was transfused with packed red blood cells and platelets. She underwent uncomplicated laparoscopic appendectomy and bone marrow biopsy, which revealed neo-plastic cells of 90% of the total bone marrow cellularity. Flow cytometry indicated presence of 92.4% of immature myeloid cells with t (15: 17) and q (22: 12) mutations, and FISH analysis for PML-RARA demonstrated a long-form fusion transcript, positive for APL. Appendix pathology described leukemic infiltration with co-expression of myeloperoxidase and CD68, consistent with myeloid sarcoma of the appendix. The patient completed a course of daunorubicin, cytarabine, and all trans-retinoic acid. Repeat bone marrow biopsy demonstrated complete remission. She will follow up with her primary care physician and hematologist/oncologist. Conclusions: Myeloid sarcoma of the appendix in the setting of APL is very rare and it might play a role in the development of acute appendicitis. Urgent management, including bone marrow biopsy for definitive diagnosis and urgent surgical intervention
Dennert, Robert; Crijns, Harry J.; Heymans, Stephane
Acute myocarditis is one of the most challenging diagnosis in cardiology. At present, no diagnostic gold standard is generally accepted, due to the insensitivity of traditional diagnostic tests. This leads to the need for new diagnostic approaches, which resulted in the emergence of new molecular tests and a more detailed immunohistochemical analysis of endomyocardial biopsies. Recent findings using these new diagnostic tests resulted in increased interest in inflammatory cardiomyopathies and a better understanding of its pathophysiology, the recognition in overlap of virus-mediated damage, inflammation, and autoimmune dysregulation. Novel results also pointed towards a broader spectrum of viral genomes responsible for acute myocarditis, indicating a shift of enterovirus and adenovirus to parvovirus B19 and human herpes virus 6. The present review proposes a general diagnostic approach, focuses on the viral aetiology and associated autoimmune processes, and reviews treatment options for patients with acute viral myocarditis. PMID:18617482
Joseph, Susan M.; Cedars, Ari M.; Ewald, Gregory A.; Geltman, Edward M.; Mann, Douglas L.
Hospitalizations for acute decompensated heart failure are increasing in the United States. Moreover, the prevalence of heart failure is increasing consequent to an increased number of older individuals, as well as to improvement in therapies for coronary artery disease and sudden cardiac death that have enabled patients to live longer with cardiovascular disease. The main treatment goals in the hospitalized patient with heart failure are to restore euvolemia and to minimize adverse events. Common in-hospital treatments include intravenous diuretics, vasodilators, and inotropic agents. Novel pharmaceutical agents have shown promise in the treatment of acute decompensated heart failure and may simplify the treatment and reduce the morbidity associated with the disease. This review summarizes the contemporary management of patients with acute decompensated heart failure. PMID:20069075
Migraine is one of the most frequent disabling neurological conditions with a major impact on the patient’s quality of life. Migraine has been described as a chronic disorder that characterized with attacks. Attacks are characterized by moderate–severe, often unilateral, pulsating headache attacks, typically lasting 4 to 72 hours. Migraine remains underdiagnosed and undertreated despite advances in the understanding of its pathophysiology. This article reviews management of migraine acute pharmacological treatment. Currently, for the acute treatment of migraine attacks, non-steroidal anti-inflammatory drugs (NSAIDs) and triptans (serotonin 5HT1B/1D receptor agonists) are recommended. Before intake of NSAID and triptans, metoclopramide or domperidone is useful. In very severe attacks, subcutaneous sumatriptan is first choice. The patient should be treated early in the attack, use an adequate dose and formulation of a medication. Ideally, acute therapy should be restricted to no more than 2 to 3 days per week to avoid medication overuse.
Abdominal pain is among the most frequent ailments reported in the office setting and can account for up to 40% of ailments in the ambulatory practice. Also, it is in the top three symptoms of patients presenting to emergency departments (ED) and accounts for 5-10% of all ED primary presenting ailments. There are several common sources for acute abdominal pain and many for subacute and chronic abdominal pain. This article explores the history-taking, initial evaluation, and examination of the patient presenting with acute abdominal pain. The goal of this article is to help differentiate one source of pain from another. Discussion of acute cholecystitis, pancreatitis, appendicitis, ectopic pregnancy, diverticulitis, gastritis, and gastroenteritis are undertaken. Additionally, there is discussion of common laboratory studies, diagnostic studies, and treatment of the patient with the above entities.
Introduction Low back pain affects about 70% of people in resource-rich countries at some point in their lives. Acute low back pain can be self-limiting; however, 1 year after an initial episode, as many as 33% of people still have moderate-intensity pain and 15% have severe pain. Acute low back pain has a high recurrence rate; 75% of those with a first episode have a recurrence. Although acute episodes may resolve completely, they may increase in severity and duration over time. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of oral drug treatments for acute low back pain? What are the effects of local injections for acute low back pain? What are the effects of non-drug treatments for acute low back pain? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 49 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, advice to stay active, analgesics (paracetamol, opioids), back exercises, back schools, bed rest, behavioural therapy, electromyographic biofeedback, epidural corticosteroid injections, lumbar supports, massage, multidisciplinary treatment programmes, muscle relaxants, non-steroidal anti-inflammatory drugs (NSAIDs), spinal manipulation, temperature treatments (short-wave diathermy, ultrasound, ice, heat), traction, and transcutaneous electrical nerve stimulation
Ceranowicz, Piotr; Cieszkowski, Jakub; Warzecha, Zygmunt; Dembiński, Artur
Acute pancreatitis is a severe disease with high mortality. Clinical studies can bring some data about etiology, pathogenesis and the course of acute pancreatitis. However, studies concerning early events of this disease and the new concepts of treatment cannot be performed on humans, due to ethical reasons. Animal models of acute pancreatitis have been developed to solve this problem. This review presents currently used experimental models of acute pancreatitis, their properties and clinical relevance. Experimental models of acute pancreatitis can be divided into in vivo (non-invasive and invasive) and ex vivo models. The onset, development, severity and extent of acute pancreatitis, as well as the mortality, vary considerably between these different models. Animal models reproducibly produce mild, moderate or severe acute pancreatitis. One of the most commonly used models of acute pancreatitis is created by administration of supramaximal doses of cerulein, an analog of cholecystokinin. This model produces acute mild edematous pancreatitis in rats, whereas administration of cerulein in mice leads to the development of acute necrotizing pancreatitis. Acute pancreatitis evoked by retrograde administration of sodium taurocholate into the pancreatic duct is the most often used model of acute severe necrotizing pancreatitis in rats. Ex vivo models allow to eliminate the influence of hormonal and nervous factors on the development of acute pancreatitis.
Birewar, Sonali; Oppenheimer, Mark; Zawada, Edward T
Muscular disorders and even hypothyroid myopathy with elevated muscle enzymes are commonly seen in hypothyroidism. In this paper, we report a case of acute renal failure in a 35-year old male patient with myalgia. His serum creatinine reached a level of 2.4 mg/dl. Later, his myalgia was found to be due to hypothyroidism with TSH of over 500 uiv/ml. With thyroid replacement therapy, myalgia and his serum creatinine stabilized and subsequently improved. Hypothyroidism, although rare, has been reported as a definite and authentic cause of rhabdomyolysis. As a result, hypothyroidism must be considered in patients presenting with acute renal failure and elevated muscle enzymes.
Acute rhinosinusitis is a common illness in children. Viral upper respiratory tract infection is the most common presentation of rhinosinusitis. Most children resolve the infection spontaneously and only a small proportion develops a secondary bacterial infection. The proper choice of antibiotic therapy depends on the likely infecting pathogens, bacterial antibiotic resistance, and pharmacologic profiles of antibiotics. Amoxicillin-clavulanate is currently recommended as the empiric treatment in those requiring antimicrobial therapy. Isolation of the causative agents should be considered in those who failed the initial treatment. In addition to antibiotics, adjuvant therapies and surgery may be used in the management of acute bacterial rhinosinusitis.
Khurana, Vishal; Ganguly, Ishita
Recurrent acute pancreatitis (RAP) is commonly encountered, but less commonly understood clinical entity, especially idiopathic RAP, with propensity to lead to repeated attacks and may be chronic pancreatitis if attacks continue to recur. A great number of studies have been published on acute pancreatitis, but few have focused on RAP. Analysing the results of clinical studies focusing specifically on RAP is problematic in view due to lack of standard definitions, randomised clinical trials, standard evaluation protocol used and less post intervention follow-up duration. With the availability of newer investigation modalities less number of etiologies will remains undiagnosed. This review particularly is focused on the present knowledge in understanding of RAP.
Nason, Katie S
Acute intraoperative aspiration is a potentially fatal complication with significant associated morbidity. Patients undergoing thoracic surgery are at increased risk for anesthesia-related aspiration, largely due to the predisposing conditions associated with this complication. Awareness of the risk factors, predisposing conditions, maneuvers to decrease risk, and immediate management options by the thoracic surgeon and the anesthesia team is imperative to reducing risk and optimizing patient outcomes associated with acute intraoperative pulmonary aspiration. Based on the root-cause analyses that many of the aspiration events can be traced back to provider factors, having an experienced anesthesiologist present for high-risk cases is also critical.
Hani, Mohamed Aziz; Guesmi, Fethi; Ben Achour, Jamel; Zribi, Riadh; Bouasker, Ibtissem; Zoghlami, Ayoub; Najah, Nabil
Among digestive clinical presentations of systemic lupus erythematosus, acute pancreatitis remains a serious affection with very poor prognosis. To date, pathogenesis is still unclear. We report two cases of fatal acute pancreatitis related to systemic lupus erythematosus.
... Acute Myeloid Leukemia (AML) What Is Acute Myeloid Leukemia? Cancer starts when cells in a part of ... the body from doing their jobs. Types of leukemia Not all leukemias are the same. There are ...
Acute pancreatitis is acute inflammatory disease of the pancreas. Nutrition has a number of anti-inflammatory effects that could affect outcomes of patients with pancreatitis. Further, it is the most promising nonspecific treatment modality in acute pancreatitis to date. This paper summarizes the best available evidence regarding the use of nutrition with a view of optimising clinical management of patients with acute pancreatitis. PMID:24490104
Backache; Low back pain; Lumbar pain; Pain - back; Acute back pain; Back pain - new; Back pain - short-term; Back strain - new ... lower back supports most of your body's weight. Low back pain is the number two reason that Americans see ...
Shirtliff, Mark E; Mader, Jon T
Acute septic arthritis may develop as a result of hematogenous seeding, direct introduction, or extension from a contiguous focus of infection. The pathogenesis of acute septic arthritis is multifactorial and depends on the interaction of the host immune response and the adherence factors, toxins, and immunoavoidance strategies of the invading pathogen. Neisseria gonorrhoeae and Staphylococcus aureus are used in discussing the host-pathogen interaction in the pathogenesis of acute septic arthritis. While diagnosis rests on isolation of the bacterial species from synovial fluid samples, patient history, clinical presentation, laboratory findings, and imaging studies are also important. Acute nongonococcal septic arthritis is a medical emergency that can lead to significant morbidity and mortality. Therefore, prompt recognition, rapid and aggressive antimicrobial therapy, and surgical treatment are critical to ensuring a good prognosis. Even with prompt diagnosis and treatment, high mortality and morbidity rates still occur. In contrast, gonococcal arthritis is often successfully treated with antimicrobial therapy alone and demonstrates a very low rate of complications and an excellent prognosis for full return of normal joint function. In the case of prosthetic joint infections, the hardware must be eventually removed by a two-stage revision in order to cure the infection.
Califf, R.M.; Wagner, G.S.
This book contains 22 chapters. Some of the titles are: The measurement of acute myocardial infarct size by CT; Magnetic resonance imaging for evaluation of myocardial ischemia and infarction; Poistron imaging in the evaluation of ischemia and myocardial infarction; and New inotropic agents.
Monsalbe, V; Domíngues, C; Roa, I; Busel, D; González, S
Plasma Cell Leukemia is a very rare form of plasmocytic dyscrasia, whose clinical and pathological characteristics warrant its recognition as a distinct subentity. We report the case of a 60 years old man who presented a rapidly fatal acute plasma cell leukemia, with multiple osteolytic lesions, hipercalcemia, renal and cardiac failure.
Biologically motivated mathematical models, which describe the dynamics of the major hematopoietic lineages (the thrombocytopoietic, lymphocytopoietic, granulocytopoietic, and erythropoietic systems) in acutely/chronically irradiated humans are developed. These models are implemented as systems of nonlinear differential equations, which variables and constant parameters have clear biological meaning. It is shown that the developed models are capable of reproducing clinical data on the dynamics of these systems in humans exposed to acute radiation in the result of incidents and accidents, as well as in humans exposed to low-level chronic radiation. Moreover, the averaged value of the "lethal" dose rates of chronic irradiation evaluated within models of these four major hematopoietic lineages coincides with the real minimal dose rate of lethal chronic irradiation. The demonstrated ability of the models of the human thrombocytopoietic, lymphocytopoietic, granulocytopoietic, and erythropoietic systems to predict the dynamical response of these systems to acute/chronic irradiation in wide ranges of doses and dose rates implies that these mathematical models form an universal tool for the investigation and prediction of the dynamics of the major human hematopoietic lineages for a vast pattern of irradiation scenarios. In particular, these models could be applied for the radiation risk assessment for health of astronauts exposed to space radiation during long-term space missions, such as voyages to Mars or Lunar colonies, as well as for health of people exposed to acute/chronic irradiation due to environmental radiological events.
Roth, Sean M; Keyser, Gabrielle; Winfield, Michelle; McNeil, Julie; Simko, Leslie; Price, Karen; Moffa, Donald; Hussain, Muhammad Shazam; Peacock, W Frank; Katzan, Irene L
The Acute Care Team Educational Initiative (ACTEI) was developed as a quality improvement initiative for the recognition and initial management of time-sensitive medical conditions. For our first time-sensitive disease process, we focused on acute stroke [acute stroke initiative (ASI)]. As part of the larger ACTEI, the ASI included creating an ACT that responds to all suspected emergency department stroke patients. In this article, we describe the planning, process, and development of the ACTEI/ASI as well as how we created an acute response team for the diagnosis and management of suspected acute stroke.
Rolink, A.G.; Gleichmann, E.
Previous work from this laboratory has led to the hypothesis that the stimulatory pathological symptoms of chronic graft-vs.-host disease (GVHD) are caused by alloreactive donor T helper (TH) cells, whereas the suppressive pathological symptoms of acute GVHD are caused by alloreactive T suppressor (TS) cells of the donor. We analyzed the Lyt phenotypes of B10 donor T cells required for the induction of either acute or chronic GVHD in H-2-different (B10 X DBA/2)F1 recipients. When nonirradiated F1 mice were used as the recipients, we found unseparated B10 T cells induced only a moderate formation of systemic lupus erythematosus (SLE)-like autoantibodies, but a high percentage of lethal GVHD (LGVHD). In contrast, Lyt-1+2- donor T cells were unable to induce LGVHD in these recipients but were capable of inducing a vigorous formation of SLE-like autoantibodies and severe immune-complex glomerulonephritis. Lyt-1-2+ T cells were incapable of inducing either acute or chronic GVHD. The sensitivity and accuracy of the GVH system were increased by using irradiated F1 mice as recipients and then comparing donor-cell inocula that contained similar numbers of T lymphocytes. Donor-cell inocula were used that had been tested for their allohelper and allosuppressor effects on F1 B cells in vitro. In the irradiated F1 recipients unseparated donor T cells were superior to T cell subsets in inducing LGVHD. In contrast Lyt-1+2- T cells, but neither unseparated T cells nor Lyt-1-2+ T cells, were capable of inducing a vigorous formation of SLE-like auto-antibodies. We conclude that the stimulatory pathological symptoms of chronic GVHD are caused by Lyt-1+2- allohelper T cells. In contrast, the development of the suppressive pathological symptoms of acute GVHD appears to involve alloreactive Lyt-1+2+ T suppressor cells.
McLean, Florence E
Scabies prevalence remains unacceptably high in many regions throughout the world. Infestation with scabies significantly impacts quality of life and is linked to pyoderma and consequently to severe long-term sequelae such as post-streptococcal glomerulonephritis. In the past, control programs using topical treatments have met with poor compliance; however, the highly effective oral agent ivermectin may offer a new paradigm in scabies management. Problems still exist with insensitive diagnostic tests, questions concerning mite reservoirs, and restrictions on who can receive ivermectin. Despite these difficulties, the elimination of scabies in communities worst affected may soon be possible.
Chowdhary, Sheemona; Bhattacharyya, Rajasri; Banerjee, Dibyajyoti
Acute organophosphorus poisoning continues to be a detrimental problem and a potential cause of mortality especially in developing countries. Inhibition of acetylcholinesterase enzyme is the main mechanism of toxicity of such pesticides and measurement of acetylcholinesterase activity is the commonly used laboratory diagnosis approved for the purpose. It is now proved beyond any doubt that early intervention is beneficial for cases of acute organophosphorus poisoning and, therefore, considerable current interest has been generated for development of point of care testing tool for screening of the same. However, to the best of our knowledge so far the matter is not reviewed from the view of point of care testing tool development. In this paper, this subject is reviewed highlighting the methodological aspects and point of care testing tool development in the context of organophosphorus poisoning.
Hecker, M; Weigand, M A; Mayer, K
Acute respiratory distress syndrome (ARDS) is the clinical manifestation of an acute lung injury caused by a variety of direct and indirect injuries to the lung. The cardinal clinical feature of ARDS, refractory arterial hypoxemia, is the result of protein-rich alveolar edema with impaired surfactant function, due to vascular leakage and dysfunction with consequently impaired matching of ventilation to perfusion. Better understanding of the pathophysiology of ARDS has led to the development of novel therapies, pharmacological strategies, and advances in mechanical ventilation. However, protective ventilation is the only confirmed option in ARDS management improving survival, and few other therapies have translated into improved oxygenation or reduced ventilation time. The development of innovative therapy options, such as extracorporeal membrane oxygenation, have the potential to further improve survival of this devastating disease.
Figueiredo, Jacinta; Santos, Ângela; Clemente, Horácio; Lourenço, Augusto; Costa, Sandra; Grácio, Maria Amélia; Belo, Silvana
Acute appendicitis associated to Schistosoma haematobium and S. mansoni infection has been found in patients submitted to urgent appendectomy at the Hospital Américo Boavida in Luanda. Due to the high prevalence and morbidity caused by schistosomiasis (or bilharziasis) in the country, we suspect that the involvement of Schistosoma infection on appendicular pathology could be very frequent, in particular for those individuals more exposed to the parasite transmission. We report two clinical cases of acute appendicitis whose surgical specimens of the appendix revealed S. haematobium and S. mansoni eggs in histological samples. The reported patients live in endemic areas and have been exposed to schistosome during childhood, which may explain the infection's chronicity. Information of these clinical cases could be relevant, particularly for surgery specialists and clinical pathologists, due to the possibility of finding more patients with concurrent appendicitis and schistosomiasis.
Duvic, C; Nedelec, G; Debord, T; Herody, M; Didelot, F
Renal involvement in parasitic infections are polymorphic. Plasmodium malariae often leads to membranoproliferative glomerulonephritis whereas acute tubular necrosis or post-infectious acute glomerulonephritis are observed with Plasmodium falciparum. Urogenital taxis of Schistosoma haematobium is responsible for frequency of chronic tubular and interstitial nephritis. Without specific treatment, the renal function progressively deteriorates and urological complications appear. Schistosoma mansoni mainly leads to mesangial and membranoproliferative glomerulonephritis. Membranoproliferative and membranous glomerulonephritis are reported with loasis. Onchocerca volvulus also leads to membranoproliferative glomerulonephritis and lipoid nephrosis. Renal involvement with Wuchereria bancrofti is rare. With leishmaniosis, it is often mild but more serious observations are described: acute glomerulonephritis, nephrotic syndrome or acute interstitial nephritis. Renal hydatic cysts are diagnosed in two or three per cent of cases. Surgery is the only treatment. Immunosuppressive or antimalarial treatments seem to be ineffective in the outcome of chronic glomerulonephritis.
Introduction An estimated 4.6 billion cases of diarrhoea occurred worldwide in 2004, resulting in 2.2 million deaths. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for acute diarrhoea in adults living in resource-rich countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults from resource-rich countries travelling to resource-poor countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults living in resource-poor countries? What are the effects of treatments for acute severe diarrhoea in adults living in resource-poor countries? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 72 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, antimotility agents, antisecretory agents, bismuth subsalicylate, diet, intravenous rehydration, nasogastric tube rehydration, oral rehydration solutions (amino acid oral rehydration solution, bicarbonate oral rehydration solution, reduced osmolarity oral rehydration solution, rice-based oral rehydration solution, standard oral rehydration solution), vitamin A supplementation, and zinc supplementation. PMID:21718555
Kung, A. W.; Ma, J. T.; Yu, Y. L.; Wang, C. C.; Woo, E. K.; Lam, K. S.; Huang, C. Y.; Yeung, R. T.
Hypothyroid myopathy has so far been reported in long standing cases of hypothyroidism. We describe two adult patients with myopathy associated with acute transient hypothyroidism. Both presented with severe muscle aches and cramps, stiffness and spasms. Muscle enzymes were markedly elevated and electromyography in one patient showed myopathic features. Histological changes were absent in muscle biopsy, probably because of the short duration of metabolic disturbance. The myopathy subsided promptly when the hypothyroid state was reversed. PMID:3422868
Introduction Acute atrial fibrillation is rapid, irregular, and chaotic atrial activity of recent onset. Various definitions of acute atrial fibrillation have been used in the literature, but for the purposes of this review we have included studies where atrial fibrillation may have occurred up to 7 days previously. Risk factors for acute atrial fibrillation include increasing age, cardiovascular disease, alcohol, diabetes, and lung disease. Acute atrial fibrillation increases the risk of stroke and heart failure. The condition resolves spontaneously within 24 to 48 hours in more than 50% of people; however, many people will require interventions to control heart rate or restore sinus rhythm. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent embolism, for conversion to sinus rhythm, and to control heart rate in people with recent-onset atrial fibrillation (within 7 days) who are haemodynamically stable? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 26 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: amiodarone, antithrombotic treatment before cardioversion, atenolol, bisoprolol, carvedilol, digoxin, diltiazem, direct current cardioversion, flecainide, metoprolol, nebivolol, propafenone, sotalol, timolol, and verapamil. PMID:25430048
Cheng, Ke; Wang, Xue; Guo, Menghu; Wieland, L. Susan; Shen, Xueyong; Lao, Lixing
This is the protocol for a review and there is no abstract. The objectives are as follows: The objective of this review is to determine the effects and, when possible, the safety of acupuncture for the treatment of acute hordeola, in comparison to no specific treatment (e.g., observation), sham acupuncture, or other active treatments. Acupuncture as an adjuvant to another treatment also will be compared to that treatment alone. PMID:25214814
Kaise, T.; Watanabe, S.; Itoh, K.
The acute toxicity of arsenobetaine was studied in male mice. No deaths were observed with oral administration of 10 g/kg of arsenobetaine. Therefore the LD/sub 50/ value was higher than 10 g/kg. This compound was found in urine in the non-metabolized form. No particular toxic symptoms were observed following administration. These suggest that arsenobetaine has low toxicity and is not metabolized in mice.
Recent advances in immunotherapy of cancer may represent a successful example in translational research, in which progress in knowledge and technology in immunology has lead to new strategies of immunotherapy, and even past failure in many clinical trials have led to a better understanding of basic cancer immunobiology. This article reviews the latest concepts in antitumor immunology and its application in the treatment of cancer, with particular focus on acute leukemia. PMID:19100371
Background The incidence of AKI appears to have increasing trend. Up to now, prospective, multi-center, large-sample epidemiological study done on pediatric AKI on aspects of epidemiological characteristics, causes and outcomes have not reported. It is necessary to develop prospective, multi-center, large-sample epidemiological study in our country on pediatric AKI. The aim of this study was to determine the clinical features, etiology, and outcomes of acute kidney injury (AKI) in Chinese children. Method Paediatric patients (≤18 years old) admitted to 27 hospitals (14 children’s hospitals and 13 general hospitals) affiliated with the Medical University were investigated. AKI was defined using the 2005 Acute Kidney Injury Network criteria. Results During the study period, 388,736 paediatric patients were admitted. From this total, AKI was diagnosed in 1,257 patients, 43 of whom died. The incidence and mortality of AKI was 0.32% and 3.4% respectively. The mean (± SD) age of patients was 48.4 ± 50.4 months. Among the 1,257 AKI paediatric patients, 632 were less than one year old. Among the AKI paediatric patients, 615 (48.9%) were in stage 1, 277 (22.0%) in stage 2, and 365 (29.0%) in stage 3. The most common causes of AKI were renal causes (57.52%), whereas postrenal (25.69%) and prerenal (14.96%) causes were the least common. The three most common causes of AKI according to individual etiological disease were urolithiasis (22.35%), of which exposure to melamine-contaminated milk accounted for the highest incidence (63.7%); acute glomerulonephritis (10.10%); and severe dehydration (7.48%). A total of 43 AKI patients (3.4%) died during their hospital stay; 15 (34.9%) of the 43 died as a result of sepsis. Conclusion Primary renal diseases are a major risk factor for paediatric AKI in China. In terms of specific etiological disease, urolithiasis (postrenal disease) was the leading cause of paediatric AKI in 2008, when the disease was linked to exposure to
Lee, Yang Deok; Lee, Soo Teik
Doxylamine succinate is an antihistaminic drugwith additional hypnotic, anticholinergic and local anesthetic effects first described in 1948. In Korea and many other countries, it is a common-over-the counter medication frequently involved in overdoses. Clinical symtomatology of doxylamine succinate overdose includes somnolence, coma, seizures, mydriasis, tachycardia, psychosis, and rhabdomyolysis. A serious complication may be rhabdomyolysis with subsequent impairment of renal function and acute renal failure. We report a case of acute renal failure and acute pancreatitis complicating a doxylamine succinate intoxication.
Sánchez-Ortega, J L; Carpintero-Moreno, F; Olivares-López, A; Borrás-Rubio, E; Alvarez-López, M J; García-Izquierdo, A
We report a 72 years old woman with mild arterial hypertension and no other pathological history who presented an acute pulmonary edema due to acute obstruction of the upper airway secondary to vocal chord paralysis developing during the immediate postoperative phase of thyroidectomy. The acute pulmonary edema resolved after application of tracheal reintubation, mechanical ventilation controlled with end expiratory positive pressure, diuretics, morphine, and liquid restriction. We discuss the possible etiopathogenic possibilities of this infrequent clinical picture and we suggest that all patients who suffered and acute obstruction of the upper airways require a careful clinical surveillance in order to prevent the development of the pulmonary syndrome.
Singh, S K; Agrawal, J K; Srivastava, A S; Bhardwaj, V K; Bose, B S
A variable array of neuroglycopenic symptoms are frequently encountered in the hypoglycemic stage, but acute psychotic disorders are quite rare. A fifty five year old female presented with an acute psychosis following oral sulfonylurea induced hypoglycemia without preceding features of adrenomedullary stimulation. This case report suggests that an acute and transient psychotic disorder may be an important neuroglycopenic feature and its early recognition protects the patient from severe hypoglycemic brain damage in a state of hypoglycemia unawareness.
Ko, Fanny W; Chan, Ka Pang; Hui, David S; Goddard, John R; Shaw, Janet G; Reid, David W; Yang, Ian A
The literature of acute exacerbation of chronic obstructive pulmonary disease (COPD) is fast expanding. This review focuses on several aspects of acute exacerbation of COPD (AECOPD) including epidemiology, diagnosis and management. COPD poses a major health and economic burden in the Asia-Pacific region, as it does worldwide. Triggering factors of AECOPD include infectious (bacteria and viruses) and environmental (air pollution and meteorological effect) factors. Disruption in the dynamic balance between the 'pathogens' (viral and bacterial) and the normal bacterial communities that constitute the lung microbiome likely contributes to the risk of exacerbations. The diagnostic approach to AECOPD varies based on the clinical setting and severity of the exacerbation. After history and examination, a number of investigations may be useful, including oximetry, sputum culture, chest X-ray and blood tests for inflammatory markers. Arterial blood gases should be considered in severe exacerbations, to characterize respiratory failure. Depending on the severity, the acute management of AECOPD involves use of bronchodilators, steroids, antibiotics, oxygen and noninvasive ventilation. Hospitalization may be required, for severe exacerbations. Nonpharmacological interventions including disease-specific self-management, pulmonary rehabilitation, early medical follow-up, home visits by respiratory health workers, integrated programmes and telehealth-assisted hospital at home have been studied during hospitalization and shortly after discharge in patients who have had a recent AECOPD. Pharmacological approaches to reducing risk of future exacerbations include long-acting bronchodilators, inhaled steroids, mucolytics, vaccinations and long-term macrolides. Further studies are needed to assess the cost-effectiveness of these interventions in preventing COPD exacerbations.
In the 20th century, the complications of head injuries were controlled but not eliminated. The wars of the 21st century turned attention to blast, the instant of impact and the primary injury of concussion. Computer calculations have established that in the first 5 milliseconds after the impact, four independent injuries on the brain are inflicted: 1) impact and its shockwave, 2) deceleration, 3) rotation and 4) skull deformity with vibration (or resonance). The recovery, pathology and symptoms after acute brain trauma have always been something of a puzzle. The variability of these four modes of injury, along with a variable reserve of neurones, explains some of this problem. PMID:26688392
Martin, G T
In the 20th century, the complications of head injuries were controlled but not eliminated. The wars of the 21st century turned attention to blast, the instant of impact and the primary injury of concussion. Computer calculations have established that in the first 5 milliseconds after the impact, four independent injuries on the brain are inflicted: 1) impact and its shockwave, 2) deceleration, 3) rotation and 4) skull deformity with vibration (or resonance). The recovery, pathology and symptoms after acute brain trauma have always been something of a puzzle. The variability of these four modes of injury, along with a variable reserve of neurones, explains some of this problem.
One in 4 children will have at least 1 episode of acute otitis media (AOM) by age 10 years. AOM results from infection of fluid that has become trapped in the middle ear. The bacteria that most often cause AOM are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Differentiating AOM from otitis media with effusion (OME) is a critical skill for physicians, as accurate diagnosis will guide appropriate treatment of these conditions. Although fluid is present in the middle ear in both conditions, the fluid is not infected in OME as is seen in AOM patients.
Acute respiratory distress syndrome (ARDS) is a life-threatening condition with multiple causes and a high mortality rate. Approximately 150,000 cases are reported in the United States annually, making ARDS a public health concern. Management of the condition is complex because of its severity, and medical imaging is essential for both the diagnosis and management of ARDS. This article introduces common signs, symptoms, risk factors, and causes of ARDS. Diagnostic criteria, histopathology, treatment strategies, and prognostic information also are discussed. The article explains the value of medical imaging studies of ARDS, especially radiography, computed tomography, and ultrasonography.
Baldwin, Kathleen; Orr, Sean; Briand, Mary; Piazza, Carolyn; Veydt, Annita; McCoy, Stacey
Stroke is the third most common cause of death in the United States and is the number one cause of long-term disability. Legislative mandates, largely the result of the American Heart Association, American Stroke Association, and Brain Attack Coalition working cooperatively, have resulted in nationwide standardization of care for patients who experience a stroke. Transport to a skilled facility that can provide optimal care, including immediate treatment to halt or reverse the damage caused by stroke, must occur swiftly. Admission to a certified stroke center is recommended for improving outcomes. Most strokes are ischemic in nature. Acute ischemic stroke is a heterogeneous group of vascular diseases, which makes targeted treatment challenging. To provide a thorough review of the literature since the 2007 acute ischemic stroke guidelines were developed, we performed a search of the MEDLINE database (January 1, 2004-July 1, 2009) for relevant English-language studies. Results (through July 1, 2009) from clinical trials included in the Internet Stroke Center registry were also accessed. Results from several pivotal studies have contributed to our knowledge of stroke. Additional data support the efficacy and safety of intravenous alteplase, the standard of care for acute ischemic stroke since 1995. Due to these study results, the American Stroke Association changed its recommendation to extend the time window for administration of intravenous alteplase from within 3 hours to 4.5 hours of symptom onset; this recommendation enables many more patients to receive the drug. Other findings included clinically useful biomarkers, the role of inflammation and infection, an expanded role for placement of intracranial stents, a reduced role for urgent carotid endarterectomy, alternative treatments for large-vessel disease, identification of nontraditional risk factors, including risk factors for women, and newly published pediatric stroke guidelines. In addition, new devices for
Gross, R; Gerecke, D
The effective treatment of acute (myeloblastic and lymphoblastic) leukaemias depends on the induction of remissions as well as on the maintenance of these remissions. Whereas the use of anthracyclines and of cytosine arabinoside in different combinations notably increased the rate of induction of remissions, their maintenance was less successful until now. We present a scheme using, beside MTX and 6-MP, modified COAP regimes periodically every 3 months. The follow-up of 26 patients treated in this way is encouraging since nearly one third remained in full haematological remission after 3 years of observation.
Madonna, M B; Boswell, W C; Arensman, R M
The outcome for children with common surgical conditions that cause an acute abdomen is discussed. These conditions include appendicitis, intussusception, malrotation, inflammatory bowel disease, intestinal obstructions, and nonorganic pain. Emphasis is placed on surgical intervention and disease processes that significantly affect outcome. The outcome of many of the diseases discussed is strongly influenced by the timing of diagnosis and treatment. These children should have prompt care and intervention to prevent morbidity and mortality. In addition, many children who present with common pediatric surgical emergencies have other medical conditions and are best treated in an environment that has a multidisciplinary team to handle their care and decrease the long-term complications.
Abengowe, C U; McManamon, P J
Acute emphysematous cholecystitis is an uncommon condition caused by gas-forming organisms and characterized by the presence of gas in the wall and lumen of the gallbladder. Its incidence is higher among male diabetics. AEC in an elderly North American diabetic man with Indian ancestry is reported with a brief review of the world literature. The diagnosis was made preoperatively with the aid of plain radiographic films of the abdomen. A gangrenous distended gallbladder was removed at operation. Clostridium perfringens was cultured from the gallbladder contents and wall. If AEC is suspected, intensive antimicrobial therapy and fluid and electrolyte replacement should be given prior to early surgical intervention.
Aksoy, Ayse; Tanir, Gonul; Ozkan, Mehpare; Oguz, Melek; Yıldız, Yasemin Tasci
Acute disseminated encephalomyelitis is an acute demyelinating disorder of the central nervous system, which principally affects the brain and spinal cord. It usually follows a benign infection or vaccination in children. Although a number of infectious agents have been implicated in acute disseminated encephalomyelitis, Toxoplasma gondii infection has not been described previously in children. Acquired T. gondii infection presents with lymphadenopathy and fever and usually spontaneously resolves in immunocompetent patients. We describe a previously healthy 10-year-old boy with acute disseminated encephalomyelitis associated with acute acquired Toxoplasma gondii infection, the symptoms of which initially began with nuchal stiffness, difficulty in walking, and urinary and stool incontinence; he later had development of motor and sensory impairment in both lower extremities and classical magnetic resonance imaging lesions suggestive of the disease. The patient recovered completely after the specific therapy for acquired T. gondii infection and pulse prednisolone. Although acute acquired Toxoplasma gondii infection has not been reported previously in association with acute disseminated encephalomyelitis, clinicians should keep in mind this uncommon cause of a common disease when evaluating a patient with acute disseminated encephalomyelitis.
A novel class of autoantigens of anti-neutrophil cytoplasmic antibodies in necrotizing and crescentic glomerulonephritis: the lysosomal membrane glycoprotein h-lamp-2 in neutrophil granulocytes and a related membrane protein in glomerular endothelial cells
Necrotizing and crescentic glomerulonephritis (NCGN) is frequently associated with circulating antineutrophil cytoplasmic autoantibodies (ANCA). It is established that ANCA are specific for soluble enzymes of granules of polymorphonuclear neutrophil granulocytes (PMN), such as myeloperoxidase (MPO) or protease 3 (PR3). The purpose of this study was to identify membrane proteins of PMNs, and/or glomerular cells, as additional autoantigenic ANCA targets. When membrane protein fractions were prepared from PMNs and isolated human glomeruli, and immunoblotted with ANCA sera of NCGN patients, two bands with apparent molecular masses of 170 and 80-110 kD (gp170/80-110) were labeled in PMNs, and a 130-kD glycoprotein (gp130) in glomeruli. Gp130 was purified, and monoclonal and rabbit antibodies (Abs) were produced which showed the same double specificity as the patient's ANCA. Using these probes, evidence was provided that gp170/80-110 is identical with human lysosomal-associated membrane protein 2 (h-lamp-2), because both proteins were immunologically cross-reactive and screening of a cDNA expression library from human promyelocytic leukemia cells with anti- gp130 Ab yielded a clone derived from h-lamp-2. Gp170/80-110 was localized primarily in granule membranes of resting PMNs, and was translocated to the cell surfaces by activation with FMLP. By contrast, gp130 was localized in the surface membranes of endothelial cells of human glomerular and renal interstitial capillaries, rather than in lysosomes, as found for h-lamp-2. Potential clinical relevance of autoantibodies to gp170/80-110 and gp130 was assessed in a preliminary trial, in which ANCA sera of patients (n = 16) with NCGN were probed with purified or recombinant antigens. Specific reactivity was detected in approximately 90% of cases with active phases of NCGN, and frequently also in combination with autoantibodies specific for PR3 or MPO. Collectively, these data provide evidence that h-lamp-2 in PMNs and a
Matĕjovic, M; Novák, I; Srámek, V; Rokyta, R; Hora, P; Nalos, M
Acute respiratory distress syndrome (ARDS) is the general term used for severe acute respiratory failure of diverse aetiology. It is associated with a high morbidity, mortality (50-70%), and financial costs. Regardless of aetiology, the basic pathogenesis of ARDS is a systemic inflammatory response leading to a diffuse inflammatory process that involves both lungs, thus causing diffuse alveolar and endothelial damage with increased pulmonary capillary permeability and excessive extravascular lung water accumulation. ARDS is commonly associated with sepsis and multiple organ failure. The clinical picture involves progressive hypoxaemia, radiographic evidence of pulmonary oedema, decreased lung compliance and pulmonary hypertension. Despite the scientific and technological progress in critical care medicine, there is no specific ARDS therapy available at the moment and its management remains supportive. Therapeutic goals include resolution of underlying conditions, maintenance of acceptable gas exchange and tissue oxygenation and prevention of iatrogenic lung injury. Many new specific therapeutic strategies have been developed, however, most of them require further scientific evaluation. The paper reviews definition, basic pathogenesis and pathophysiology of ARDS and discusses current concepts of therapeutic possibilities of ARDS.
Becker, Dávid; Merkely, Béla
The acute coronary syndrome is the most severe form of coronary artery disease. It is an immediate threat of life and the mortality rate can be high without proper therapy and patient management. Based on the first ECG, two different forms can be distinguished: acute coronary syndrome with and without ST elevation. Besides adequate medication, management of these patients is an essential part of treatment. In case of ST elevation, coronarography and percutaneous coronary intervention is needed in general, within 24 hours from the onset of symptoms. When ST elevation is not detected on the ECG, individual ischemic risk factors and predictable mortality of the patient may define the necessity and the date of the invasive examination. The Hungarian hemodynamic laboratory network covers almost the whole country and, therefore, practically each patient may receive a state-of-the-art therapy. Although indicators of cardiovascular diseases are still prominent, the mortality rate of myocardial Infarction is decreasing in Hungary due to the well-organized invasive care.
Court, Jennifer Helen; Janicek, David
A 64-year-old man presented with a 2-day history of acute onset painless left ptosis. He had no other symptoms; importantly pupils were equal and reactive and eye movements were full. There was no palpable mass or swelling. He was systemically well with no headache, other focal neurological signs, or symptoms of fatigue. CT imaging showed swelling of the levator palpebrae superioris suggestive of myositis. After showing no improvement over 5 days the patient started oral prednisolone 30 mg reducing over 12 weeks. The ptosis resolved quickly and the patient remains symptom free at 6 months follow-up. Acute ptosis may indicate serious pathology. Differential diagnoses include a posterior communicating artery aneurysm causing a partial or complete third nerve palsy, Horner’s syndrome, and myasthenia gravis. A careful history and examination must be taken. Orbital myositis typically involves the extraocular muscles causing pain and diplopia. Isolated levator myositis is rare. PMID:25564592
Presle, Alexandra; Bertocchio, Jean-Philippe; Schneider, Nathalie; Maquart, François-Xavier; Ramont, Laurent; Oudart, Jean-Baptiste
Serum protein electrophoresis is commonly used in case of acute or chronic renal failure. It can lead to the etiologic diagnosis by detecting monoclonal gammopathies which are frequently complicated by renal failure, such as cast nephropathy, Randall's disease or amyloidosis, or to explore an associated inflammatory syndrome. We report the occurrence of two monoclonal components in a patient without any monoclonal component 10 days earlier. The sudden appearance of these two monoclonal components associated to the context of sepsis of urinary origin suggested the diagnosis of transient monoclonal gammopathy. This hypothesis was confirmed by monitoring serum protein electrophoresis that showed a gradual decrease of these two monoclonal components few weeks after the resolution of the infectious disease. The main etiological factors of transient monoclonal gammopathies are infectious or autoimmune diseases. In this context, it is important to delay the achievement of serum protein electrophoresis after the acute episode, in order to avoid to falsely conclude to hematologic malignancy diagnosis. This can prevent costly biological examinations of these transient monoclonal gammopathies and invasive procedures like bone marrow examination.
Zuk, Anna; Bonventre, Joseph V.
Acute kidney injury (AKI) is a global public health concern associated with high morbidity, mortality, and healthcare costs. Other than dialysis, no therapeutic interventions reliably improve survival, limit injury, or speed recovery. Despite recognized shortcomings of in vivo animal models, the underlying pathophysiology of AKI and its consequence, chronic kidney disease (CKD), is rich with biological targets. We review recent findings relating to the renal vasculature and cellular stress responses, primarily the intersection of the unfolded protein response, mitochondrial dysfunction, autophagy, and the innate immune response. Maladaptive repair mechanisms that persist following the acute phase promote inflammation and fibrosis in the chronic phase. Here macrophages, growth-arrested tubular epithelial cells, the endothelium, and surrounding pericytes are key players in the progression to chronic disease. Better understanding of these complex interacting pathophysiological mechanisms, their relative importance in humans, and the utility of biomarkers will lead to therapeutic strategies to prevent and treat AKI or impede progression to CKD or end-stage renal disease (ESRD). PMID:26768243
Zegers, Richard H C; Weigl, Andreas; Steptoe, Andrew
The early death of the composer Wolfgang Amadeus Mozart on 5 December 1791 has fascinated the world for more than 2 centuries. It has been suggested that his final illness was caused by poisoning, renal failure, Henoch-Schönlein purpura, trichinosis, and many other conditions. The official daily register of deaths in Mozart's Vienna was evaluated to provide an epidemiologic framework into which the observations of contemporary witnesses of his death can be integrated. All recorded deaths in Vienna during November and December 1791 and January 1792 were analyzed, together with the corresponding periods in 1790 to 1791 and 1792 to 1793. The deaths of 5011 adults (3442 men, 1569 women) were recorded over these periods. The mean ages of death were 45.5 years (SD, 18.5) for men and 54.5 years (SD, 19.9) for women. Tuberculosis and related conditions accounted for the highest number of deaths; cachexia and malnutrition ranked second, and edema was the third most common cause. According to eyewitness accounts, the hallmark of Mozart's final disease was severe edema. Deaths from edema were markedly increased among younger men in the weeks surrounding Mozart's death compared with the previous and following years. This minor epidemic may have originated in the military hospital. Our analysis is consistent with Mozart's last illness and death being due to a streptococcal infection leading to an acute nephritic syndrome caused by poststreptococcal glomerulonephritis. Scarlet fever, which represents the same underlying disease from an etiologic perspective, is a less likely possibility.
... Causes, Risk Factors, and Prevention Can Acute Myeloid Leukemia Be Prevented? It’s not clear what causes most ... Myeloid Leukemia Be Prevented? More In Acute Myeloid Leukemia About Acute Myeloid Leukemia Causes, Risk Factors, and ...
Canagliflozin is a new drug in class of sodium-glucose cotransporter 2 inhibitors used for treatment of type 2 diabetes mellitus. We describe a patient who developed moderately severe acute pancreatitis as an untoward consequence after being initiated on this drug. To the best of our knowledge, this is the first reported case of canagliflozin-associated acute pancreatitis in clinical literature.
Davis, Kimberly A; Rozycki, Grace S
At the center of the development of acute care surgery is the growing difficulty in caring for patients with acute surgical conditions. Care demands continue to grow in the face of an escalating crisis in emergency care access and the decreasing availability of surgeons to cover emergency calls. To compound this problem, there is an ever-growing shortage of general surgeons as technological advances have encouraged subspecialization. Developed by the leadership of the American Association for the Surgery of Trauma, the specialty of acute care surgery offers a training model that would produce a new breed of specialist with expertise in trauma surgery, surgical critical care, and elective and emergency general surgery. This article highlights the evolution of the specialty in hope that these acute care surgeons, along with practicing general surgeons, will bring us closer to providing superb and timely care for patients with acute surgical conditions.
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia
Tabbane, K; Charfi, F; Dellagi, L; Guizani, L; Boukadida, L
The post-partum is a high risk period for the development of acute psychotic disorders. The frequence of post-partum psychoses is evaluated at 1 to 2 per 1,000 births. Post-partum psychosis include major affective disorders which is the most frequent diagnosis. The clinical pictures have specific characteristics: rapid change of symptomatology, liability of mood, and frequent confusional signs. The short-term prognosis is generally good but the risk of recurrence of the mental disorder, in or outside puerperal context, is high. At clinical, evolutive and genetic levels, the studies do not provide arguments for nosological autonomy of post-partum psychosis. At therapeutic level, the ECT is particularly efficient in this indication.
Atkinson, Helen; Wallis, Sebastian; Coatesworth, Andrew P
Acute otitis media (AOM) is a common problem facing general practitioners, paediatricians and otolaryngologists. This article reviews the aetiopathogenesis, epidemiology, presentation, natural history, complications and management of AOM. The literature was reviewed by using the PubMed search engine and entering a combination of terms including 'AOM', 'epidemiology' and 'management'. Relevant articles were identified and examined for content. What is the take-home message? AOM is a very common problem affecting the majority of children at least once and places a large burden on health care systems throughout the world. Although symptomatic relief is often enough for most children, more severe and protracted cases require treatment with antibiotics, especially in younger children.
Gorguner, Metin; Akgun, Metin
Inhaled substances may cause injury in pulmonary epithelium at various levels of respiratory tract, leading from simple symptoms to severe disease. Acute inhalation injury (AII) is not uncommon condition. There are certain high risk groups but AII may occur at various places including home or workplace. Environmental exposure is also possible. In addition to individual susceptibility, the characteristics of inhaled substances such as water solubility, size of substances and chemical properties may affect disease severity as well as its location. Although AII cases may recover in a few days but AII may cause long-term complications, even death. We aimed to discuss the effects of short-term exposures (minutes to hours) to toxic substances on the lungs. PMID:25610115
Inaba, Hiroto; Greaves, Mel; Mullighan, Charles G.
Summary Acute lymphoblastic leukaemia (ALL) is seen in both children and adults, but its incidence peaks between ages 2 and 5 years. The causation of ALL is considered to be multi-factorial, including exogenous or endogenous exposures, genetic susceptibility, and chance. The survival rate of paediatric ALL has improved to approximately 90% in recent trials with risk stratification by biologic features of leukaemic cells and response to therapy, therapy modification based on patient pharmacodynamics and pharmacogenomics, and improved supportive care. However, innovative approaches are needed to further improve survival while reducing adverse effects. While most children can be cured, the prognosis of infants and adults with ALL remains poor. Recent genome-wide profiling of germline and leukaemic cell DNA has identified novel submicroscopic structural genetic alterations and sequence mutations that contribute to leukaemogenesis, define new ALL subtypes, influence responsiveness to treatment, and may provide novel prognostic markers and therapeutic targets for personalized medicine. PMID:23523389
Hassan, Ali; Ahmad, Bakhtiar; Ahmed, Zahoor; Al-Quliti, Khalid W.
Ruptured cerebral aneurysm is the most common cause of spontaneous subarachnoid hemorrhage (SAH). Rarely cerebral venous sinus thrombosis (CVST) may present initially as acute SAH, and clinically mimics aneurysmal bleed. We report 2 cases of CVST who presented with severe headache associated with neck pain and focal seizures. Non-contrast brain CT showed SAH, involving the sulci of the convexity of hemisphere (cSAH) without involving the basal cisterns. Both patients received treatment with anticoagulants and improved. Awareness of this unusual presentation of CVST is important for early diagnosis and treatment. The purpose of this paper is to emphasize the inclusion of vascular neuroimaging like MRI with venography or CT venography in the diagnostic workup of SAH, especially in a patient with strong clinical suspicion of CVST or in a patient where neuroimaging showed cSAH. PMID:25630784
Kumar, Andreas; Bagur, Rodrigo; Béliveau, Patrick; Potvin, Jean-Michel; Levesque, Pierre; Fillion, Nancy; Tremblay, Benoit; Larose, Éric; Gaudreault, Valérie
A 24-year-old healthy man consulted to our center because of typical on-and-off chest-pain and an electrocardiogram showing ST-segment elevation in inferior leads. An urgent coronary angiography showed angiographically normal coronary arteries. Cardiovascular magnetic resonance imaging confirmed acute myocarditis. Although acute myocarditis triggering coronary spasm is an uncommon association, it is important to recognize it, particularly for the management for those patients presenting with ST-segment elevation and suspect myocardial infarction and angiographically normal coronary arteries. The present report highlights the role of cardiovascular magnetic resonance imaging to identify acute myocarditis as the underlying cause. PMID:25276306
Kumar, Andreas; Bagur, Rodrigo; Béliveau, Patrick; Potvin, Jean-Michel; Levesque, Pierre; Fillion, Nancy; Tremblay, Benoit; Larose, Eric; Gaudreault, Valérie
A 24-year-old healthy man consulted to our center because of typical on-and-off chest-pain and an electrocardiogram showing ST-segment elevation in inferior leads. An urgent coronary angiography showed angiographically normal coronary arteries. Cardiovascular magnetic resonance imaging confirmed acute myocarditis. Although acute myocarditis triggering coronary spasm is an uncommon association, it is important to recognize it, particularly for the management for those patients presenting with ST-segment elevation and suspect myocardial infarction and angiographically normal coronary arteries. The present report highlights the role of cardiovascular magnetic resonance imaging to identify acute myocarditis as the underlying cause.
... Leukemia (ALL) What Are the Key Statistics About Acute Lymphocytic Leukemia? The American Cancer Society’s estimates for acute lymphocytic ... Acute Lymphocytic Leukemia Research and Treatment? More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...
The present article analyses the main presentations on acute pancreatitis at Digestive Disease Week 2015. Arterial pseudoaneurysm is an uncommon complication of acute pancreatitis (incidence 0.7%) and mortality from this cause is currently anecdotal. Diabetes mellitus has little impact on the clinical course of acute pancreatitis, unlike cirrhosis, which doubles the risk of mortality. Intake of unsaturated fat could be associated with an increased severity of acute pancreatitis and is a confounding factor in studies evaluating the relationship between obesity and morbidity and mortality. PET-CT (positron emission tomography-computed tomography) could be a non-invasive tool to detect infection of collections in acute pancreatitis. Peripancreatic fat necrosis is less frequent than pancreatic fat necrosis and is associated with a better clinical course. If the clinical course is poor, increasing the calibre of the percutaneous drains used in the treatment of infected necrosis can avoid surgery in 20% of patients. The use of low molecular-weight heparin in moderate or severe pancreatitis could be associated with a better clinical course, specifically with a lower incidence of necrosis. In acute recurrent pancreatitis, simvastatin is a promising drug for prophylaxis of new episodes of acute pancreatitis. Nutritional support through a nasogastric tube does not improve clinical course compared with oral nutrition.
Nakatani, Hajime; Hamada, Shinichi; Okanoue, Toyotake; Kawamura, Akihiro; Inoue, Yuichiro; Yamamoto, Shinya; Chikai, Takashi; Hiroi, Makoto; Hanazaki, Kazuhiro
Acute appendicitis often presents as right lower quadrant (RLQ) pain, severe tenderness at the point of McBurny or Lanz, and Blumberg's sign. Scrotal events with appendicitis are very rare. In our case, a 63-year-old Japanese man presented with severe RLQ pain and high fever. Physical examination revealed severe tenderness (including both points of McBurny and Lanz) and Blumberg's sign. The scrotum was slightly swollen and showed local heat with severe testicular pain. Abdominal computed tomography revealed ascites in a pelvic space and the right side of the spermatic cord was swollen. Emergency operation was performed and the final diagnosis was catarrhal appendicitis and acute epididymitis. This is the first report of acute appendicitis concomitant with acute epididymitis.
iganshina, L E; Abakumova, T R
The review discusses existing evidence of benefits and risks of cerebrolysin--a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue with proposed neuroprotective and neurotrophic properties, for acute ischemic stroke. The review presents results of systematic search and analysis of randomised clinical trials comparing cerebrolysin with placebo in patients with acute ischemic stroke. Only one trial was selected as meeting quality criteria. No difference in death and adverse events between cerebrolysin and placebo was established. The authors conclude about insufficiency of evidence to evaluate the effect of cerebrolysin on survival and dependency in people with acute ischemic stroke.
Neufeld, D; Sivak, G; Jessel, J; Freund, U
We performed 417 laparoscopic cholecystectomies, including 58 for acute cholecystitis, between September 1991 and April 1995,. All operations were successful, with no mortality or complications. In about 10%, the laparoscopic approach failed and we converted to open cholecystectomy. Average post-operative hospitalization was 24 hours. We also performed primary open cholecystectomies in 55 patients with acute cholecystitis, because of limitations of operating room and staff availability for unscheduled laparoscopic surgery. In these patients, hospital stay was longer and rate of complications higher. In our opinion laparoscopic cholecystectomy is safe and the preferred approach in acute cholecystitis.
Sánchez Marteles, Marta; Urrutia, Agustín
Acute cardiogenic pulmonary edema and cardiogenic shock are two of the main forms of presentation of acute heart failure. Both entities are serious, with high mortality, and require early diagnosis and prompt and aggressive management. Acute pulmonary edema is due to the passage of fluid through the alveolarcapillary membrane and is usually the result of an acute cardiac episode. Correct evaluation and clinical identification of the process is essential in the management of acute pulmonary edema. The initial aim of treatment is to ensure hemodynamic stability and to correct hypoxemia. Other measures that can be used are vasodilators such as nitroglycerin, loop diuretics and, in specific instances, opioids. Cardiogenic shock is characterized by sustained hypoperfusion, pulmonary wedge pressure > 18 mmHg and a cardiac index < 2.2l/min/m(2). The process typically presents with hypotension (systolic blood pressure < 90 mmHg or a decrease in mean arterial pressure > 30 mmHg) and absent or reduced diuresis (< 0.5 ml/kg/h). The most common cause is left ventricular failure due to acute myocardial infarction. Treatment consists of general measures to reverse acidosis and hypoxemia, as well as the use of vasopressors and inotropic drugs. Early coronary revascularization has been demonstrated to improve survival in shock associated with ischaemic heart disease.
Mokra, Daniela; Kosutova, Petra
Acute respiratory distress syndrome (ARDS) and its milder form acute lung injury (ALI) may result from various diseases and situations including sepsis, pneumonia, trauma, acute pancreatitis, aspiration of gastric contents, near-drowning etc. ALI/ARDS is characterized by diffuse alveolar injury, lung edema formation, neutrophil-derived inflammation, and surfactant dysfunction. Clinically, ALI/ARDS is manifested by decreased lung compliance, severe hypoxemia, and bilateral pulmonary infiltrates. Severity and further characteristics of ALI/ARDS may be detected by biomarkers in the plasma and bronchoalveolar lavage fluid (or tracheal aspirate) of patients. Changed concentrations of individual markers may suggest injury or activation of the specific types of lung cells-epithelial or endothelial cells, neutrophils, macrophages, etc.), and thereby help in diagnostics and in evaluation of the patient's clinical status and the treatment efficacy. This chapter reviews various biomarkers of acute lung injury and evaluates their usefulness in diagnostics and prognostication of ALI/ARDS.
... of the bronchial tubes, the part of the respiratory system that leads into the lungs. Acute bronchitis has a sudden onset and usually appears after a respiratory infection, such as a cold, and can be ...
Antoniuk, Sérgio A
Acute muscle weakness, a common disorder in pediatrics, can occur from impairment of any part of the motor unit, including the upper motor neuron, lower motor neuron, peripheral nerve, neuromuscular junction or muscle. It usually manifests itself as an acute or hyperacute motor disorder of progressive or rapidly progressive course. Acute muscle weakness is a neuromuscular emergency, especially if it affects the respiratory or oropharyngeal musculature. The location of the motor weakness and associated neurological signs and symptoms usually indicate the location of the lesion. The onset, speed and clinical evolution, as well as other data from the patient's history, suggest the pathophysiological differential diagnosis. Successful treatment depends on the immediate and correct differential diagnosis. This paper presents the main differential diagnosis of main neuromuscular diseases that cause acute muscle weakness in children.
Tabakovic, Mithat; Salkic, Nermin N.; Bosnjic, Jasmina; Alibegovic, Ervin
Acute pancreatitis is a rare but life-threatening complication in patients with transplanted kidney. The incidence of acute pancreatitis after kidney transplantation ranges from 2% to 7%, with mortality rate between 50 and 100%. We report a case of a female patient aged 46 years, developing an interstitial acute pancreatitis 8 years following a renal transplantation. The specific aethiological factor was not clearly established, although possibility of biliary pancreatitis with spontaneous stone elimination and/or medication-induced pancreatitis remains the strongest. Every patient after renal transplantation with an acute onset of abdominal pain should be promptly evaluated for presence of pancreatitis with a careful application of the most appropriate diagnostic procedure for each individual patient. PMID:23259142
Voiculescu, Mihai; Ionescu, Camelia; Ismail, Gener; Mandache, Eugen; Hortopan, Monica; Constantinescu, Ileana; Iliescu, Olguta
Renal transplantation is often associated with severe complications. Except for acute rejection, infections and toxicity of immunosuppressive treatment are the most frequent problems observed after transplantation. Infections with hepatic viruses (HBV, HDV, HCV, HGV) and cytomegalic virus (CMV) are the main infectious complications after renal transplantation. Cyclosporine toxicity is not unusual for a patient with renal transplantation and is even more frequent for patients with hepatic impairment due to viral infections. The subjects of this report are two renal transplant recipients with acute pancreatitis, severe hepatitis and acute renal failure on graft, receiving immunosuppressive therapy for maintaining renal graft function
Villela, Luis; Bolaños-Meade, Javier
The current treatment of patients with acute myeloid leukaemia yields poor results, with expected cure rates in the order of 30–40% depending on the biological characteristics of the leukaemic clone. Therefore, new agents and schemas are intensively studied in order to improve patients’ outcomes. This review summarizes some of these new paradigms, including new questions such as which anthracycline is most effective and at what dose. High doses of daunorubicin have shown better responses in young patients and are well tolerated in elderly patients. Monoclonal antibodies are promising agents in good risk patients. Drugs blocking signalling pathways could be used in combination with chemotherapy or in maintenance with promising results. Epigenetic therapies, particularly after stem cell transplantation, are also discussed. New drugs such as clofarabine and flavopiridol are reviewed and the results of their use discussed. It is clear that many new approaches are under study and hopefully will be able to improve on the outcomes of the commonly used ‘7+3’ regimen of an anthracycline plus cytarabine with daunorubicin, which is clearly an ineffective therapy in the majority of patients. PMID:21861539
Selewski, David T; Charlton, Jennifer R; Jetton, Jennifer G; Guillet, Ronnie; Mhanna, Maroun J; Askenazi, David J; Kent, Alison L
In recent years, there have been significant advancements in our understanding of acute kidney injury (AKI) and its impact on outcomes across medicine. Research based on single-center cohorts suggests that neonatal AKI is very common and associated with poor outcomes. In this state-of-the-art review on neonatal AKI, we highlight the unique aspects of neonatal renal physiology, definition, risk factors, epidemiology, outcomes, evaluation, and management of AKI in neonates. The changes in renal function with gestational and chronologic age are described. We put forth and describe the neonatal modified Kidney Diseases: Improving Global Outcomes AKI criteria and provide the rationale for its use as the standardized definition of neonatal AKI. We discuss risk factors for neonatal AKI and suggest which patient populations may warrant closer surveillance, including neonates <1500 g, infants who experience perinatal asphyxia, near term/ term infants with low Apgar scores, those treated with extracorporeal membrane oxygenation, and those requiring cardiac surgery. We provide recommendations for the evaluation and treatment of these patients, including medications and renal replacement therapies. We discuss the need for long-term follow-up of neonates with AKI to identify those children who will go on to develop chronic kidney disease. This review highlights the deficits in our understanding of neonatal AKI that require further investigation. In an effort to begin to address these needs, the Neonatal Kidney Collaborative was formed in 2014 with the goal of better understanding neonatal AKI, beginning to answer critical questions, and improving outcomes in these vulnerable populations.
The burden of asthma (death, disability, and an increasing prevalence) makes it a major public health problem worldwide. In an effort to decrease this burden, investigators are studying many aspects of this disease. The role of race, ethnicity, infections, and pollutants as triggers, as well as the risk factors are now being defined. Research into methods to decrease acute exacerbations and improve emergency and in-hospital management, using standardized protocols and incentives for follow-up care, has yielded valuable information but has met with limited success. Adherence to the national guidelines has been poor and to some extent can be attributed to the lack of a practical method of measuring the degree of lung inflammation and cumbersome treatment protocols. Exhaled nitric oxide is a noninvasive marker of inflammation and may provide a rational method to titrate corticosteroid and leukotriene receptor antagonist therapy. The best route and dosing regimen for corticosteroid administration (oral vs intramuscular vs nebulized) are the subject of several studies, with no clear-cut winner. The burden of asthma in developing countries with limited financial resources has also triggered a search for simpler, cheaper, and practical methods for beta-agonist delivery using indigenous spacers. Recent research in asthma has unveiled our incomplete knowledge of the disease but has also provided a sense of where efforts should be expended. Research into the genetics and pharmacogenetics of asthma and into the societal factors limiting the delivery of optimal care is likely to yield useful and practical information.
Kamenczak, A; Pokorska, M; Wołek, E; Kobyłecka, K
Zinc vapour poisoning by inhalation in the form of zinc fever is more frequent than oral zinc product poisoning, the product used in therapy. The main aim of the study was the evaluation of clinical manifestation present after Zincteral ingestion as well as attempt to find the relationship between the presence and aggravation of the clinical manifestation and zinc level in the blood. The course of acute clinical suicidal poisoning by ingestion of Zincteral 50 tablets (10.0 g) and 100 tablets (20.0 g) is presented. The clinical picture revealed the following symptoms and signs: tachycardia, changes of arterial BP, vascular shock; dyspeptic nausea, vomiting cramps in abdominal region, diarrhoea. Damage of the parenchymatous organs, mainly liver was evident. In pregnant woman (9-week-pregnancy) on the 12-th day of her stay in the Clinic complete miscarriage took place accompanied by haemorrhage from reproductive organs. The kind and exacerbation of the clinical manifestations in relation to the zinc level in body fluid were analysed.
Blackmore, Laura; Bernal, William
Acute liver failure (ALF) is a rare critical illness with high mortality whose successful management requires early recognition and effective initial management. Though it may result from a wide variety of causes, in the UK and much of the developed world most cases result from paracetamol-induced hepatotoxicity, and administration of antidotal N-acetyl cysteine at first recognition is key. Involvement of local critical care services should occur at an early stage for stabilisation, monitoring and supportive care with parallel discussion with specialist liver centres to identify those patients who may benefit from transfer. Prognostic criteria are applied to identify patients for emergency liver transplantation, and candidates for surgery are prioritised on waitlisting schemes. Outcomes now approach that of elective surgery. However, the majority of cases, and particularly those with paracetamol-induced disease, recover with supportive medical care alone. Overall outcomes for patients with ALF have improved dramatically over the last three decades, but mortality remains unacceptable and further advances in care are required.
Fernando, Suran L
Acute generalised exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction and is caused by drugs in >90% of cases. It is rare, with an incidence of 1-5 patients per million per year. The clinical manifestations are characterised by fever and the rapid appearance of disseminated sterile pustules 3-5 days after the commencement of treatment. It is accompanied by marked neutrophilia. Mucous membranes are not typically involved. The drugs conferring the highest risk of AGEP according to the EuroSCAR study are aminopenicillins, pristinamycin, hydroxychloroquine, antibacterial sulphonamides, terbinafine and diltiazem. The pathogenesis of AGEP involves the initial influx of CD8 cytotoxic T-cells resulting in the apoptosis of keratinocytes and formation of vesicles. Then CXCL-8-producing and granulocyte macrophage-colony stimulating factor-producing CD4 cells enter the epidermis, resulting in neutrophil mediated inflammation and the formation of pustules. As a result, the histology reveals intraepidermal, usually subcorneal, pustules and an accompanying neutrophilic and lymphocytic infiltrate. Epicutaneous patch testing may also support the diagnosis by causing a localised pustular reaction 48-96 h after the offending drug is applied. The condition usually resolves by 15 days after the causative drug is withdrawn but oral corticosteroid therapy may be necessary in some individuals. The mortality rate is up to 5% and mostly occurs in elderly people who have significant comorbidities.
Livingston, Man J.; Dong, Zheng
Acute kidney injury is a major kidney disease associated with poor clinical outcomes. The pathogenesis of acute kidney injury is multifactorial and is characterized by tubular cell injury and death. Recent studies have demonstrated autophagy induction in proximal tubular cells during acute kidney injury. The regulatory mechanisms of tubular cell autophagy are poorly understood; however, some recent findings have set up a foundation for further investigation. Although autophagy may promote cell death under certain experimental conditions, pharmacological and autophagy-related gene knockout studies have established a renoprotective role for autophagy in acute kidney injury. The mechanisms by which autophagy protects cells from injury and how, possibly, its pro-survival role switches to pro-death under certain conditions are discussed. Further research is expected to help us understand the regulatory network of tubular cell autophagy, define its precise roles in specific context of acute kidney injury, and identify autophagy-targeting strategies for the prevention and treatment of acute kidney injury. PMID:24485026
Monaco, R; Durante, E; Pampolini, M; Tioli, P
It is often difficult to differentiate acute pancreatitis (A.P.) from some other acute abdominal diseases, when there is an elevated serum amylase. In contrast, the renal clearance of amylase, expressed as a percentage of creatinine clearance, can separate patients with A.P. from patients with acute colecistitis, common duct stone without pancreatitis, hyperamylasemia after biliary surgery, acute peptic ulcer and acute salivary diseases.
Kujala, U M; Nylund, T; Taimela, S
The aim of this study was to characterize the type and severeity of acute injuries occurring in Finnish orienteerers in 1987 to 1991. The study is based on the orienteering license insurance records accounting for 2189 orienteering injuries during 69268 person-years of exposure in active orienteerers. Of these orienteerers, 73.0% were male; 73.5% (N = 1608) of all injuries occurred in males, so the injury rate was similar in males and females. The rate was highest in orienteerers 20 to 24 years of age and lowest in children. Injuries occurred most commonly during May to September (78.9% or all injuries), the months which include the orienteering competition season, and were more common during competitions (59.8%) than during training. A high number of the injuries occurred during weekends (58.9% of injuries) including 68.1% of all competition injuries and 44.9% of all training injuries. The lower limbs were involved in 1611 (73.6%) of cases, the ankle (28.7%) and the knee (23.2%) being the two most common injury locations. Sprains, strains and contusions were the most common injuries. Wounds were proportionally more common in males than in females while ankle sprains were more common in females. Fractures, seven open and 94 closed, accounted for 4.6% of injuries; they were most common in the hand/wrist/forearm (N = 44) and ankle (N = 16), and were more frequent during competition (62.3%) than during training. The most important areas for preventive measures seem to be the ankle and the knee.
Kam, H.J.; Choi, S.; Cho, J.P.; Min, Y.G.; Park, R.W.
Objective In an effort to identify and characterize the environmental factors that affect the number of patients with acute diarrheal (AD) syndrome, we developed and tested two regional surveillance models including holiday and weather information in addition to visitor records, at emergency medical facilities in the Seoul metropolitan area of Korea. Methods With 1,328,686 emergency department visitor records from the National Emergency Department Information system (NEDIS) and the holiday and weather information, two seasonal ARIMA models were constructed: (1) The simple model (only with total patient number), (2) the environmental factor-added model. The stationary R-squared was utilized as an in-sample model goodness-of-fit statistic for the constructed models, and the cumulative mean of the Mean Absolute Percentage Error (MAPE) was used to measure post-sample forecast accuracy over the next 1 month. Results The (1,0,1)(0,1,1)7 ARIMA model resulted in an adequate model fit for the daily number of AD patient visits over 12 months for both cases. Among various features, the total number of patient visits was selected as a commonly influential independent variable. Additionally, for the environmental factor-added model, holidays and daily precipitation were selected as features that statistically significantly affected model fitting. Stationary R-squared values were changed in a range of 0.651-0.828 (simple), and 0.805-0.844 (environmental factor-added) with p<0.05. In terms of prediction, the MAPE values changed within 0.090-0.120 and 0.089-0.114, respectively. Conclusion The environmental factor-added model yielded better MAPE values. Holiday and weather information appear to be crucial for the construction of an accurate syndromic surveillance model for AD, in addition to the visitor and assessment records. PMID:23616829
Kallet, Richard H; Matthay, Michael A
Prolonged breathing of very high FIO2 (FIO2 ≥ 0.9) uniformly causes severe hyperoxic acute lung injury (HALI) and, without a reduction of FIO2, is usually fatal. The severity of HALI is directly proportional to PO2 (particularly above 450 mm Hg, or an FIO2 of 0.6) and exposure duration. Hyperoxia produces extraordinary amounts of reactive O2 species that overwhelms natural antioxidant defenses and destroys cellular structures through several pathways. Genetic predisposition has been shown to play an important role in HALI among animals, and some genetics-based epidemiologic research suggests that this may be true for humans as well. Clinically, the risk of HALI likely occurs when FIO2exceeds 0.7, and may become problematic when FIO2 exceeds 0.8 for an extended period of time. Both high-stretch mechanical ventilation and hyperoxia potentiate lung injury and may promote pulmonary infection. During the 1960s, confusion regarding the incidence and relevance of HALI largely reflected such issues as the primitive control of FIO2, the absence of PEEP, and the fact that at the time both ALI and ventilator-induced lung injury were unknown. The advent of PEEP and precise control over FIO2, as well as lung-protective ventilation, and other adjunctive therapies for severe hypoxemia, has greatly reduced the risk of HALI for the vast majority of patients requiring mechanical ventilation in the 21st century. However, a subset of patients with very severe ARDS requiring hyperoxic therapy is at substantial risk for developing HALI, therefore justifying the use of such adjunctive therapies. PMID:23271823
Kawabe, Ken; Ito, Tetsuhide; Arita, Yoshiyuki; Sadamoto, Yojiro; Harada, Naohiko; Yamaguchi, Koji; Tanaka, Masao; Nakano, Itsuro; Nawata, Hajime; Takayanagi, Ryoichi
Acute organophosphate poisoning (OP) shows several severe clinical symptoms due to its strong blocking effect on cholinesterase. Acute pancreatitis is one of the complications associated with acute OP, but this association still may not be widely recognized. We report here the case of a 73-year-old man who had repeated abdominal pain during and after the treatment of acute OP. Hyperamylasemia and a 7-cm pseudocyst in the pancreatic tail were noted on investigations. We diagnosed pancreatic pseudocyst that likely was secondary to an episode of acute pancreatitis following acute OP. He was initially treated with a long-term intravenous hyperalimentation, protease inhibitors and octerotide, but eventually required surgical intervention, a cystgastrostomy. Acute pancreatitis and hyperamylasemia are known to be possible complications of acute OP. It is necessary to examine and assess pancreatic damage in patients with acute OP.
Binker, Marcelo G; Cosen-Binker, Laura I
Acute pancreatitis is an inflammatory disorder of the pancreas that may cause life-threatening complications. Etiologies of pancreatitis vary, with gallstones accounting for the majority of all cases, followed by alcohol. Other causes of pancreatitis include trauma, ischemia, mechanical obstruction, infections, autoimmune, hereditary, and drugs. The main events occurring in the pancreatic acinar cell that initiate and propagate acute pancreatitis include inhibition of secretion, intracellular activation of proteases, and generation of inflammatory mediators. Small cytokines known as chemokines are released from damaged pancreatic cells and attract inflammatory cells, whose systemic action ultimately determined the severity of the disease. Indeed, severe forms of pancreatitis may result in systemic inflammatory response syndrome and multiorgan dysfunction syndrome, characterized by a progressive physiologic failure of several interdependent organ systems. Stress occurs when homeostasis is threatened, and stressors can include physical or mental forces, or combinations of both. Depending on the timing and duration, stress can result in beneficial or harmful consequences. While it is well established that a previous acute-short-term stress decreases the severity of experimentally-induced pancreatitis, the worsening effects of chronic stress on the exocrine pancreas have received relatively little attention. This review will focus on the influence of both prior acute-short-term and chronic stress in acute pancreatitis. PMID:24914340
Wand, S; Waeschle, R M; Von Ahsen, N; Hawighorst, T; Bräuer, A; Quintel, M
Acute fatty liver of pregnancy (AFLP) is a rare but serious liver disease and typically occurs during the third trimester. It carries the risk for significant perinatal and maternal mortality. Therefore an early diagnosis and delivery, followed by close monitoring and optimized management of the impaired liver function with all associated problems are necessary to prevent maternal and foetal death. This case report focuses on the management of acute liver failure due to AFLP in a 31 year old women treated in our intensive care unit (ICU) after an emergency C-section.
Wintermark, Max; Albers, Gregory W.; Alexandrov, Andrei V.; Alger, Jeffry R.; Bammer, Roland; Baron, Jean-Claude; Davis, Stephen; Demaerschalk, Bart M.; Derdeyn, Colin P.; Donnan, Geoffrey A.; Eastwood, James D.; Fiebach, Jochen B.; Fisher, Marc; Furie, Karen L.; Goldmakher, Gregory V.; Hacke, Werner; Kidwell, Chelsea S.; Kloska, Stephan P.; Köhrmann, Martin; Koroshetz, Walter; Lee, Ting-Yim; Lees, Kennedy R.; Lev, Michael H.; Liebeskind, David S.; Ostergaard, Leif; Powers, William J.; Provenzale, James; Schellinger, Peter; Silbergleit, Robert; Sorensen, Alma Gregory; Wardlaw, Joanna; Wu, Ona; Warach, Steven
The recent “Advanced Neuroimaging for Acute Stroke Treatment” meeting on September 7 and 8, 2007 in Washington DC, brought together stroke neurologists, neuroradiologists, emergency physicians, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Biomedical Imaging and Bioengineering (NIBIB), industry representatives, and members of the US Food and Drug Administration (FDA) to discuss the role of advanced neuroimaging in acute stroke treatment. The goals of the meeting were to assess state-of-the-art practice in terms of acute stroke imaging research and to propose specific recommendations regarding: (1) the standardization of perfusion and penumbral imaging techniques, (2) the validation of the accuracy and clinical utility of imaging markers of the ischemic penumbra, (3) the validation of imaging biomarkers relevant to clinical outcomes, and (4) the creation of a central repository to achieve these goals. The present article summarizes these recommendations and examines practical steps to achieve them. PMID:18477656
Fonseca, Paulo; Dias, Adelaide; Gonçalves, Helena; Albuquerque, Aníbal; Gama, Vasco
Acute hepatitis is a very rare, but potentially fatal, adverse effect of intravenous amiodarone. We present a case of an 88-year-old man with history of ischemic dilated cardiomyopathy and severely depressed left ventricular function that was admitted to our coronary care unit with diagnosis of decompensated heart failure and non-sustained ventricular tachycardia. A few hours after the beginning of intravenous amiodarone he developed an acute hepatitis. There was a completely recovery within the next days after amiodarone withdrawn and other causes of acute hepatitis have been ruled out. This case highlights the need for close monitoring of hepatic function during amiodarone infusion in order to identify any potential hepatotoxicity and prevent a fatal outcome. Oral amiodarone is, apparently, a safe option in these patients.
Kawaguchi, Tatsushi; Spencer, Doran B; Mochizuki, Manabu
Acute retinal necrosis is a progressive necrotizing retinopathy caused by herpes simplex virus (HSV) or varicella zoster virus (VZV). The mainstay of its treatment is antiviral therapy against these pathogenic organisms, such as intravenous acyclovir or oral valacyclovir. Systemic and topical corticosteroids together with antiviral therapy are used as an anti-inflammatory treatment to minimize damages to the optic nerve and retinal blood vessels. Because the majority of severe cases of the disease show occlusive retinal vasculitis, a low dosage of aspirin is used as anti-thrombotic treatment. Vitreo-retinal surgery is useful to repair rhegmatogenous retinal detachment, one of the main late-stage complications. Moreover, recent articles have reported some encouraging results of prophylactic vitrectomy before rhegmatogenous retinal detachment occurs. The efficacy of laser photocoagulation to prevent the development or extension of rhegmatogenous retinal detachment is controversial. Despite these treatments, the visual prognosis of acute retinal necrosis is still poor, in particular VZV-induced acute retinal necrosis.
Hunjan, Tia; Chaudery, Muzzafer; Zaidi, Ahsan; Beggs, Andrew D
Appendicular sarcoidosis is a very rare cause of acute abdominal pain, with only seven cases reported previously in the literature. A 45-year-old woman, known to have sarcoidosis, presented to the emergency department with a 1-week history of epigastric and right iliac fossa abdominal pain. At diagnostic laparoscopy, an acutely inflamed appendix was found and removed as well as an omental mass which was biopsied. Subsequent histopathological examination of the appendix demonstrated appendicular sarcoidosis without acute appendicitis and chronic inflammatory changes in the omental biopsy. The patients’ symptoms completely resolved postoperatively. It is important to undertake urgent operative intervention in patients with sarcoidosis who present with right iliac fossa pain, owing to the high risk of perforation. PMID:23162022
Acute otitis media is the most common bacterial infection in the child under 5 years of age and the leading reason for antibiotic prescriptions in Western countries. The choice of optimal antibiotic treatment is based essentially on microbiologic epidemiologic studies. The bacteria most often responsible for otitis belong to the commensal flora of the nasopharynx. French studies using paracentesis show that the main bacteria responsible for acute otitis media are H. influenzae, S. pneumoniae and M. catarrhalis. The epidemiology of resistance to antibiotics has recently changed, with the appearance of pneumococcal strains having reduced sensitivity to penicillin, and which have played a major role in treatment failures.
Agrawal, Naman; Kumar, Akshay; Aggarwal, Praveen; Jamshed, Nayer
Sympathetic crashing acute pulmonary edema (SCAPE) is the extreme end of the spectrum of acute pulmonary edema. It is important to understand this disease as it is relatively common in the emergency department (ED) and has better outcomes when managed appropriately. The patients have an abrupt redistribution of fluid in the lungs, and when treated promptly and effectively, these patients will rapidly recover. Noninvasive ventilation and intravenous nitrates are the mainstay of treatment which should be started within minutes of the patient's arrival to the ED. Use of morphine and intravenous loop diuretics, although popular, has poor scientific evidence. PMID:28149030
Agrawal, Naman; Kumar, Akshay; Aggarwal, Praveen; Jamshed, Nayer
Sympathetic crashing acute pulmonary edema (SCAPE) is the extreme end of the spectrum of acute pulmonary edema. It is important to understand this disease as it is relatively common in the emergency department (ED) and has better outcomes when managed appropriately. The patients have an abrupt redistribution of fluid in the lungs, and when treated promptly and effectively, these patients will rapidly recover. Noninvasive ventilation and intravenous nitrates are the mainstay of treatment which should be started within minutes of the patient's arrival to the ED. Use of morphine and intravenous loop diuretics, although popular, has poor scientific evidence.
Bruun, Marie; Højgaard, Joan L Sunnleyg; Kondziella, Daniel
Acute vertigo of neurological origin may be caused by haemorrhages and tumours in the posterior fossa and, most frequently, by ischaemic infarction in the vertebrobasilar circulation. Urgent diagnosis is necessary to avoid further ischaemic episodes, herniation due to cerebellar oedema and/or fatal brainstem infarction. The history should focus on accompanying neurological symptoms. However, vertigo with cerebellar lesions may be monosymptomatic and then bedside evaluation of oculomotor function is the key to correct diagnosis. This paper discusses the pathophysiology, symptomatology and clinical evaluation of acute vertigo of neurological origin.
Kröber, S M
A 65-year old man presented with acute abdominal pain and fever. The initial diagnosis was small bowel gangrene. Pathology revealed small to large abdominal vessels obliterated by cells of intravascular B-cell-lymphoma (IVL). Visceral IVL involvement is common at autopsy but rarely reported in patients with acute abdomen. The subtype of diffuse large B-cell lymphoma is a rare and aggressive malignancy, which in typical cases is characterized by cephalic or cutaneous manifestation. Few cases showed involvement of large vessels which in combination to fibrin thrombi may lead to infarction of the organ involved. Thus IVL should be considered in cases of ischemic diseases with fever of unknown origin.
Srivastava, G N; Prasad, Rajniti; Meena, Manoj; Hussain, Moosa
We present a case of acute silicosis with bilateral pneumothorax of a 28-year-old man working at a stone crusher factory for 1 year. He presented to the emergency department with cough, respiratory distress and diffuse chest pain. The patient was managed with bilateral intercostal tube drainage under water seal, oxygen inhalation and conservative therapy. On follow-up he showed improvement of resting dyspnoea and was doing well. This case is being reported because of the rare complications of acute silicosis as bilateral pneumothorax.
Ichikawa, Hitoshi; Imai, Jin; Mizukami, Hajime; Uda, Shuji; Yamamoto, Soichiro; Nomura, Eiji; Tajiri, Takuma; Watanabe, Norihito; Makuuchi, Hiroyasu
We report a case of amoebic appendicitis without colitis symptoms. Acute appendicitis is commonly encountered by gastroenterologists in their daily practice. The number of cases of amoebiasis increases annually in Japan, and is thought to be associated with an increase in sexually transmitted disease or travel to endemic areas. However, acute amoebic appendicitis is rare and the prognosis is very poor compared to nonamoebic appendicitis. In our case, appendectomy was performed immediately after onset, and the patient was discharged without complications. It is difficult to differentiate between amoebic and nonamoebic appendicitis preoperatively, and the possibility of amoebic appendicitis should be kept in mind.
Galtés, Ignasi; Gallego, María Ángeles; Esgueva, Raquel; Martin-Fumadó, Carles
A 54-year-old man was admitted to hospital after being found unconscious in his home. He had a history of alcoholism, multiple drug addictions, and type I diabetes mellitus. At admission, he had hyperglycaemia (550 mg/dL) with glucosuria and ketone bodies in the urine, along with septic shock refractory to bilateral alveolar infiltrates and severe respiratory failure. The patient died 24 hours post admission due to multiple organ failure, with diabetic ketoacidosis decompensated by possible respiratory infection in a patient with polytoxicomania. The autopsy confirmed the presence of acute bilateral bronchopneumonia, chronic pancreatitis, severe hepatic steatosis, and generalized congestive changes. At the oesophagus, acute oesophageal necrosis was evident.
... Detection, Diagnosis, and Types How Is Acute Myeloid Leukemia Diagnosed? Certain signs and symptoms might suggest that ... of samples used to test for acute myeloid leukemia If signs and symptoms and/or the results ...
... Your 1- to 2-Year-Old Acute Myeloid Leukemia (AML) KidsHealth > For Parents > Acute Myeloid Leukemia (AML) ... Treatment Coping en español Leucemia mieloide aguda About Leukemia Leukemia is a type of cancer that affects ...
Singh, Sarvesh Pal
Acute kidney injury is a common complication after pediatric cardiac surgery. The definition, staging, risk factors, biomarkers and management of acute kidney injury in children is detailed in the following review article. PMID:27052074
... acute myeloid leukemia, a cancer of the blood-forming tissue ( bone marrow ). In normal bone marrow, hematopoietic ... 7186-203. Review. Citation on PubMed de Thé H, Chen Z. Acute promyelocytic leukaemia: novel insights into ...
... Types What Should You Ask Your Doctor About Acute Lymphocytic Leukemia? It is important to have frank, honest discussions ... Your Doctor About Acute Lymphocytic Leukemia? More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...
Shadgan, Babak; Macnab, Andrew; Stothers, Lynn; Nigro, Mark; Afshar, Kourosh; Kajbafzadeh, A. M.
Acute scrotum is a urologic condition defined by scrotal pain, swelling, and redness of acute onset. Prompt diagnosis and treatment are necessary to preserve testicular viability. The history and clinical symptoms reported are key to diagnosis and proper treatment, but are not always readily obtained in children, in whom common causes of acute scrotum include testicular torsion, torsion of the appendix testis, and epididymitis. These acute conditions have different causal pathology that mandate specific treatment, hence the importance of early and accurate diagnosis.
Hydronephrosis is a rare complication of acute appendicitis. We present a case of missed appendicitis in a 52-year-old female which presented as a right-sided hydronephrosis. 2 days after admission to the Department of Urology CT revealed acute appendicitis for what open appendectomy was performed. Acute appendicitis can lead to obstructive uropathy by periappendiceal inflammation due to adjacency. Urologists, surgeons, and emergency physicians should be aware of this rare complication of atypical acute appendicitis. PMID:27818827
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia
Bertozzi, Mirko; Rinaldi, Victoria Elisa; Prestipino, Marco; Giovenali, Paolo; Appignani, Antonino
Human infections caused by Dirofilaria repens have been reported in many areas of the world. We describe a case of a 3-year-old child with an intrascrotal mass caused by D repens mimicking an acute scrotum. This represents the first case of scrotal dirofilariasis described in pediatric age with such an unusual presentation.
Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan
Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF–VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis. PMID:25778551
Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan
Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF-VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis.
Horwitz, Rany J.; And Others
The University of Illinois' medical school has a third-year program of weekly role-playing exercises focusing on management of acute medical problems. Students are responsible for creating the cases, complete with scenarios and treatment teams, simulating them, and successfully treating or reaching an impasse. Little teacher preparation time is…
Rosen, Thomas; Furman, Janet
Acute calcium pyrophosphate deposition (CPPD) arthropathy, also called pseudogout, is common, and becomes more prevalent as patients age. The presenting symptoms are similar to both gout and septic arthritis but may be treated differently. This article describes a typical patient presentation and management from an emergency medicine and orthopedic surgery standpoint.
... 1- to 2-Year-Old Acute Lymphoblastic Leukemia (ALL) KidsHealth > For Parents > Acute Lymphoblastic Leukemia (ALL) Print A A A What's in this article? ... child will develop acute lymphoblastic, or lymphoid, leukemia (ALL). This is the most common type of childhood ...
... 1- to 2-Year-Old Acute Lymphoblastic Leukemia (ALL) KidsHealth > For Parents > Acute Lymphoblastic Leukemia (ALL) A A A What's in this article? About ... child will develop acute lymphoblastic, or lymphoid, leukemia (ALL). This is the most common type of childhood ...
Califf, R.M.; Wagner, G.S.
This book contains 58 chapters. Some of the chapter titles are: Radionuclide Techniques for Diagnosing and Sizing of Myocardial Infarction; The Use of Serial Radionuclide Angiography for Monitoring Function during Acute Myocardial Infarction; Hemodynamic Monitoring in Acute Myocardial Infarction; and The Valve of Radionuclide Angiography for Risk Assessment of Patients following Acute Myocardial Infarction.
Cesarani, A; Alpini, D; Monti, B; Raponi, G
Vertigo and dizziness are very common symptoms in the general population. The aim of this paper is to describe the physical and pharmacological treatment of symptoms characterized by sudden onset of rotatory vertigo. Acute vertigo can be subdivided into two main groups: (1) spontaneous vertigo and (2) provoked vertigo, usually by postural changes, generally called paroxysmal positional vertigo (PPV). Sudden onset of acute vertigo is usually due to acute spontaneous unilateral vestibular failure. It can be also fluctuant as, e.g., in recurrent attacks of Ménière's disease. Pharmacotherapy of acute spontaneous vertigo includes Levo-sulpiride i.v., 50 mg in 250 physiologic solution, once or twice a day, methoclopramide i.m., 10 mg once or twice a day, or triethilperazine rectally, once or twice a day, to reduce neurovegetative symptoms; diazepam i.m., 10 mg once or twice a day, to decrease internuclear inhibition, sulfate magnesium i.v., two ampoules in 500 cc physiological solution, twice a day, or piracetam i.v., one ampoule in 500 cc physiological solution, twice a day, to decrease vestibular damage. At the onset of the acute symptoms, patients must lie on their healthy side with the head and trunk raised 20 degrees. The room must be quiet but not darkened. If the patient is able to swallow without vomiting, it is important to reduce nystagmus and stabilize the visual field with gabapentine, per os, 300 mg twice or three times a day. The first step of the physical therapy of acute vertigo is vestibular electrical stimulation, that is to say, a superficial paravertebral electrical stimulation of neck muscles, aimed to reduce antigravitary failure and to increase proprioceptive cervical sensory substitution. PPV is a common complaint and represents one of the most common entities in peripheral vestibular pathology. While the clinical picture is well known and widely described, the etiopathogenesis of PPV is still a matter of debate. Despite the different
Whitford, Gary Milton
This chapter discusses the characteristics and treatment of acute fluoride toxicity as well as the most common sources of overexposure, the doses that cause acute toxicity, and factors that can influence the clinical outcome. Cases of serious systemic toxicity and fatalities due to acute exposures are now rare, but overexposures causing toxic signs and symptoms are not. The clinical course of systemic toxicity from ingested fluoride begins with gastric signs and symptoms, and can develop with alarming rapidity. Treatment involves minimizing absorption by administering a solution containing calcium, monitoring and managing plasma calcium and potassium concentrations, acid-base status, and supporting vital functions. Approximately 30,000 calls to US poison control centers concerning acute exposures in children are made each year, most of which involve temporary gastrointestinal effects, but others require medical treatment. The most common sources of acute overexposures today are dental products - particularly dentifrices because of their relatively high fluoride concentrations, pleasant flavors, and their presence in non-secure locations in most homes. For example, ingestion of only 1.8 ounces of a standard fluoridated dentifrice (900-1,100 mg/kg) by a 10-kg child delivers enough fluoride to reach the 'probably toxic dose' (5 mg/kg body weight). Factors that may influence the clinical course of an overexposure include the chemical compound (e.g. NaF, MFP, etc.), the age and acid-base status of the individual, and the elapsed time between exposure and the initiation of treatment. While fluoride has well-established beneficial dental effects and cases of serious toxicity are now rare, the potential for toxicity requires that fluoride-containing materials be handled and stored with the respect they deserve.
Ahmed, A.; Thongprayoon, C.; Pickering, B.W.; Akhoundi, A.; Wilson, G.; Pieczkiewicz, D.; Herasevich, V.
Summary Background Identifying patients at risk for acute respiratory distress syndrome (ARDS) before their admission to intensive care is crucial to prevention and treatment. The objective of this study is to determine the performance of an automated algorithm for identifying selected ARDS predisposing conditions at the time of hospital admission. Methods This secondary analysis of a prospective cohort study included 3,005 patients admitted to hospital between January 1 and December 31, 2010. The automated algorithm for five ARDS predisposing conditions (sepsis, pneumonia, aspiration, acute pancreatitis, and shock) was developed through a series of queries applied to institutional electronic medical record databases. The automated algorithm was derived and refined in a derivation cohort of 1,562 patients and subsequently validated in an independent cohort of 1,443 patients. The sensitivity, specificity, and positive and negative predictive values of an automated algorithm to identify ARDS risk factors were compared with another two independent data extraction strategies, including manual data extraction and ICD-9 code search. The reference standard was defined as the agreement between the ICD-9 code, automated and manual data extraction. Results Compared to the reference standard, the automated algorithm had higher sensitivity than manual data extraction for identifying a case of sepsis (95% vs. 56%), aspiration (63% vs. 42%), acute pancreatitis (100% vs. 70%), pneumonia (93% vs. 62%) and shock (77% vs. 41%) with similar specificity except for sepsis and pneumonia (90% vs. 98% for sepsis and 95% vs. 99% for pneumonia). The PPV for identifying these five acute conditions using the automated algorithm ranged from 65% for pneumonia to 91 % for acute pancreatitis, whereas the NPV for the automated algorithm ranged from 99% to 100%. Conclusion A rule-based electronic data extraction can reliably and accurately identify patients at risk of ARDS at the time of hospital
Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia
Ring, Johannes; Grosber, Martine; Möhrenschlager, Matthias; Brockow, Knut
Anaphylaxis is the maximal variant of an acute life-threatening immediate-type allergy. Due to its often dramatic onset and clinical course, practical knowledge in the management of these reactions is mandatory both for physicians and patients. It has to be distinguished between acute treatment modalities and general recommendations for management of patients who have suffered from an anaphylactic reaction. Acute treatment comprises general procedures like positioning, applying an intravenous catheter, call for help, comfort of the patient as well as the application of medication. The acute treatment modalities are selected depending upon the intensity of the clinical symptomatology as they are categorized in 'severity grades'. First of all it is important to diagnose anaphylaxis early and consider several differential diagnoses. This diagnosis is purely clinical and laboratory tests are of no help in the acute situation. Epinephrine is the essential antianaphylactic drug in the pharmacologic treatment. It should be first applied intramuscularly, only in very severe cases or under conditions of surgical interventions intravenous application can be tried. Furthermore, glucocorticosteroids are given in order to prevent protracted or biphasic courses of anaphylaxis; they are of little help in the acute treatment. Epinephrine autoinjectors can be used by the patient him/herself. Histamine H(1)-antagonists are valuable in mild anaphylactic reactions; they should be given intravenously if possible. The replacement of volume is crucial in antianaphylactic treatment. Crystalloids can be used in the beginning, in severe shock colloid volume substitutes have to be applied. Patients suffering from an anaphylactic episode should be observed over a period of 4-10 h according to the severity of the symptomatology. It is crucial to be aware or recognize risk patients as for example patients with severe uncontrolled asthma, or under beta-adrenergic blockade. When bronchial
Douma, Joeri A J; Smulders, Yvo M
Many physicians are resistant to the idea of prescribing loperamide for acute infectious traveller's diarrhoea and community-acquired diarrhoea because of the fear of possible adverse effects. Large randomized trials with loperamide, either alone or as an adjunct to antibiotic treatment, have in fact revealed positive rather than negative effects. International guidelines now often support the use of loperamide for the treatment of infectious diarrhoea without dysentery. There seems to be no reason to systematically avoid loperamide in patients with dysentery, but caution is advised. Loperamide can be used as monotherapy or as an adjunct to antibiotic treatment in immunocompetent adults with acute infectious traveller's diarrhoea or community-acquired diarrhoea without severe comorbidities. This can reduce both the frequency of diarrhoea and the time until the diarrhoea stops without the risk of severe complications.
Aggarwal, Aakash; Manrai, Manish; Kochhar, Rakesh
Acute pancreatitis remains a clinical challenge, despite an exponential increase in our knowledge of its complex pathophysiological changes. Early fluid therapy is the cornerstone of treatment and is universally recommended; however, there is a lack of consensus regarding the type, rate, amount and end points of fluid replacement. Further confusion is added with the newer studies reporting better results with controlled fluid therapy. This review focuses on the pathophysiology of fluid depletion in acute pancreatitis, as well as the rationale for fluid replacement, the type, optimal amount, rate of infusion and monitoring of such patients. The basic goal of fluid epletion should be to prevent or minimize the systemic response to inflammatory markers. For this review, various studies and reviews were critically evaluated, along with authors’ recommendations, for predicted severe or severe pancreatitis based on the available evidence. PMID:25561779
Dunn, E K; Macchia, R J; Chauhan, P S; Laungani, G B; Solomon, N A
The efficacy and merit of testicular imaging, utilizing Tc-99m pertechnetate, were studied prospectively in a group of patients who presented with acute onset of scrotal pain. Consecutive admissions were studied. All were managed according to the likelihood of the problem being testicular torsion, which was determined from the clinical history, physical examination and the routine laboratory data. The final diagnostic outcome, whether by surgical exploration or clinical progress with conservative treatment, is collated with the preoperative scintigraphic interpretations, made with respect to predefined criteria. Analysis of the pretreatment images obtained in 57 patients shows that the radionuclide study is highly reliable in cases of testicular torsion and epididymo-orchitis. It appears to be much less dependable, however, in the other acute scrotal conditions. Torsions that are intermittent in nature or corrected manually apparently can have variable presentations. Certain difficulties and potential pitfalls encountered in interpreting the scintigraphic studies are discussed.
Rao, K. Santosh Mohan; Balasubramaniam, Chidambaram; Subramaniam, K.
Syringohydromyelia is a frequent finding in cases of tethered cord syndrome. The classical teaching is that the development and progression of a syrinx is a chronic process. We present a case report of an acute onset syringomyelia in an infant, who underwent an excision of a lumbosacral transitional lipoma and detethering of the cord. Immediately after recovery, the infant was found to have flaccid paraplegia. An emergency magnetic resonance imaging revealed a large acute onset syringomyelia for which he underwent an emergency midline myelotomy and release of fluid from the syrinx. Though the eventual recovery was good, this made us re-visit our understanding of the concept of syringohydromyelia. The case details and a plausible hypothesis for the rapid development of the syrinx are presented. PMID:26557165
Serra E Moura Garcia, C; Sokolova, A; Torre, M L; Amaro, C
Acute Hemorrhagic Edema of Infancy is a small vessel leucocytoclastic vasculitis affecting young infants. It is characterized by large, target-like, macular to purpuric plaques predominantly affecting the face, ear lobes and extremities. Non-pitting edema of the distal extremities and low-grade fever may also be present. Extra-cutaneous involvement is very rare. Although the lesions have a dramatic onset in a twenty-four to forty-eight hour period, usually the child has a non-toxic appearance. In most cases there are no changes in laboratory parameters. The cutaneous biopsy reveals an inflammatory perivascular infiltrate. It is a benign and auto-limited disease, with complete resolution within two to three weeks leaving no sequelae in the majority of cases. No recurrences are described. We report a case of a 42-day old girl admitted at our hospital with Acute Hemorrhagic Edema of Infancy.
Díaz-Rubio, José Luis; Torre-Delgadillo, Aldo; Robles-Díaz, Guillermo
Exocrine and endocrine components of pancreas are interrelated anatomically and functionally. Exocrine pancreatic dysfunction often accompanies endocrine pancreatic impairment and vice versa. Diabetes mellitus resulting from alterations of exocrine pancreas, such as acute or chronic pancreatitis, is known as pancreatic diabetes. Hyperglycemia during acute pancreatitis (AP) can be due to abnormalities in insulin secretion, increase in counterregulatory hormones release, or decrease in glucose utilization by peripheral tissues. Causal association is suggested between diabetic ketoacidosis and AP and is attributed to alternation in metabolism of triglycerides. High blood glucose levels are associated with severe AP and constitute factor of worst prognosis. Some patients are discharged with diabetes after AP episode, while others develop diabetes during first year of follow-up. Origin and frequency of glycemic abnormalities associated with AP have not been settled yet accurately. Also, predictive factors for diabetes development and persistence after AP have not been recognized to date.
McLean, K H; Bett, J N; Saltups, A
In 1505 patients with acute myocardial infarction (MI) serious ventricular arrhythmias were commoner in those with transmural ECG changes, and were associated with an increase in mortality and in the incidence of left ventricular failure (LVF) as well as higher peak serum lactic dehydrogenase (LDH) levels. Atrial fibrillation (AF) occurred more often in older patients and in those with LVF and clinical evidence of pericarditis.
Kadia, Tapan M.; Ravandi, Farhad; O’Brien, Susan; Cortes, Jorge; Kantarjian, Hagop M.
Significant progress has been made in the treatment of acute myeloid leukemia (AML). Steady gains in clinical research and a renaissance of genomics in leukemia have led to improved outcomes. The recognition of tremendous heterogeneity in AML has allowed individualized treatments of specific disease entities within the context of patient age, cytogenetics, and mutational analysis. The following is a comprehensive review of the current state of AML therapy and a roadmap of our approach to these distinct disease entities. PMID:25441110
Rosenbaum, Yoseph A; Awan, Hisham M
Hand and wrist injuries in athletes are common, representing between 3 and 25% of all sports injuries. As many as a quarter of all sports injuries involve the hand or wrist. We review the recent literature regarding acute hand injuries in athletes based on the structures involved - bone, muscle/tendon, ligament, and neurovascular - including diagnosis and pathophysiology of these injuries, focusing on athlete-specific facets of treatment, and when available, opinions on return to play.
Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia
Kijowski, R; Roemer, F; Englund, M; Tiderius, C J; Swärd, P; Frobell, R B
Joint injury has been recognized as a potent risk factor for the onset of osteoarthritis. The vast majority of studies using imaging technology for longitudinal assessment of patients following joint injury have focused on the injured knee joint, specifically in patients with anterior cruciate ligament injury and meniscus tears where a high risk for rapid onset of post-traumatic osteoarthritis is well known. Although there are many imaging modalities under constant development, magnetic resonance (MR) imaging is the most important instrument for longitudinal monitoring after joint injury. MR imaging is sensitive for detecting early cartilage degeneration and can evaluate other joint structures including the menisci, bone marrow, tendons, and ligaments which can be sources of pain following acute injury. In this review, focusing on imaging following acute knee trauma, several studies were identified with promising short-term results of osseous and soft tissue changes after joint injury. However, studies connecting these promising short-term results to the development of osteoarthritis were limited which is likely due to the long follow-up periods needed to document the radiographic and clinical onset of the disease. Thus, it is recommended that additional high quality longitudinal studies with extended follow-up periods be performed to further investigate the long-term consequences of the early osseous and soft tissue changes identified on MR imaging after acute knee trauma.
Lees, K R
1. Potential therapies for ischaemic stroke include agents to reduce oedema, to improve cerebral perfusion, to reduce excitotoxic damage, to minimise free-radical induced injury and to reduce complications such as deep venous thrombosis. 2. Of the anti-oedema drugs, steroids are ineffective and possibly dangerous; intravenous glycerol is unproven. 3. Haemodilution to reduce whole blood viscosity and improve perfusion is ineffective. Thrombolytic drugs have not been adequately tested but several randomised multicentre trials are now commencing. Early treatment and CT scanning are essential. 4. Anticoagulants and antiplatelet drugs may have wide applicability but have not been tested in the acute phase of stroke. A multi-centre trial will address this issue. 5. Neuronal cytoprotection offers exciting prospects for acute stroke treatment. Antagonists of glutamate at the NMDA receptor, calcium and sodium channel blocking agents and free radical scavenging drugs have potent effects experimentally. Several agents are now reaching clinical trials. The calcium antagonist nimodipine has been disappointing in large scale trials but some studies were flawed by late treatment. 6. Successful treatment of acute stroke is likely to combine several approaches. 7. Therapeutic trials in stroke must include CT scanning, early treatment and a multicentre approach to achieve large numbers of patients. PMID:1493080
Danys, Donatas; Poskus, Tomas; Mikalauskas, Saulius; Poskus, Eligijus; Jotautas, Valdemaras; Beisa, Virgilijus; Strupas, Kestutis
Abstract Objective The optimal diagnostics and treatment of acute appendicitis continues to be a challenge. A false positive diagnosis of appendicitis may lead to an unnecessary operation, which has been appropriately termed negative appendectomy. The aim of our study was to identify the effectiveness of preoperative investigations in preventing negative appendectomy. Methods A retrospective study was performed on adult patients who underwent operation for suspected acute appendicitis from 2008 to 2013 at Vilnius University Hospital Santariskiu Klinikos. Patients were divided into two groups: group A underwent an operation, where appendix was found to be normal (non-inflamed); group B underwent an appendectomy for inflamed appendix. Groups were compared for preoperative data, investigations, treatment results and pathology findings. Results 554 patients were included in the study. Preoperative laboratory tests results of hemoglobin, hematocrit concentrations and white blood cell count were significantly higher in group B (p<0.001). Ultrasonography was performed for 78 % of patients in group A and 74 % in group B and did not provide any statistically significant results. Comparing Alvarado score results, there were more patients with Alvarado score less than 7 in group A than in group B. In our large series we could find only four independent risk factors, and they could only account for 24 % of cases. Conclusions In summary, acute appendicitis is still often misdiagnosed and the ratio of negative appendectomies remains rather high. Additional investigations such as observation and computed tomography should be used to prevent this.
Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia
Berber, Ilhami; Erkurt, Mehmet Ali; Yetkin, Funda; Unlu, Serkan; Yilmaz, Sami; Bentli, Recep; Bazna, Sezai
Some infectious organisms may give rise to acute pancreatitis; brucellosis, however, extremely rarely leads to acute pancreatitis. A 40-year-old man was diagnosed with acute pancreatitis, the etiology of which was determined to be acute brucellosis. The patient was discharged without complications approximately 15 days after the initiation of trimethoprim-sulfamethoxazole and doxycycline treatment. Brucella infections may rarely be complicated by acute pancreatitis. Thus, brucellosis should be remembered in the etiology of acute pancreatitis in regions such as Turkey, where Brucella infections are endemic.
Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Recurrent Childhood Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies
Kim, Dong Han; Park, Hyeuk; Moon, Seung Won; Jeong, Jong Hyuk; Yang, Hyuk Seung; Kim, Do Hyun; Kim, Ho Dong
Acute hepatitis E is an endemic disease, commonly reported in Indian subcontinent, China, Africa, Central America, and so forth. It is a self-limiting disease like other acute hepatitis except in pregnant patient. Although sporadic hepatitis E is noted all over the world, most of them are associated with travel history to HEV-endemic area. In Korea, Hepatitis E is rarely reported. Moreover, sporadic acute hepatitis E without travel history to HEV-endemic area is very rare. We experienced three sporadic cases of acute hepatitis E, without travel history. All of them presented acute hepatitis symptoms, elevated aminotransferase, and positive IgM HEV Ab. Symptoms and aminotransferase levels were normalized during hospitalization and IgM HEV Ab converted negative after 4-8 months. We report three sporadic cases of onset-acute hepatitis E without travel history to HEV-endemic area.
Acute pancreatitis is a common clinical condition. Excessive systemic inflammatory response syndrome (SIRS) in acute pancreatitis leads to distant organ damage and multiple organ dysfunction syndrome (MODS), which is the primary cause of morbidity and mortality in this condition. Development of in vivo experimental models of acute pancreatitis and associated systemic organ damage has enabled us to study the role played by inflammatory mediators in the pathogenesis of acute pancreatitis and associated systemic organ damage. Using these models, recent studies by us and other investigators have established the critical role played by inflammatory mediators such as TNF-a, IL-1b, IL-6, PAF, IL-10, CD40L, C5a, ICAM-1, chemokines, substance P and hydrogen sulfide in acute pancreatitis and the resultant MODS. This chapter intends to present an overview of different experimental animal models of acute pancreatitis and associated MODS and the role of inflammatory mediators in the pathogenesis of this condition.
Collard, Harold R.; Moore, Bethany B.; Flaherty, Kevin R.; Brown, Kevin K.; Kaner, Robert J.; King, Talmadge E.; Lasky, Joseph A.; Loyd, James E.; Noth, Imre; Olman, Mitchell A.; Raghu, Ganesh; Roman, Jesse; Ryu, Jay H.; Zisman, David A.; Hunninghake, Gary W.; Colby, Thomas V.; Egan, Jim J.; Hansell, David M.; Johkoh, Takeshi; Kaminski, Naftali; Kim, Dong Soon; Kondoh, Yasuhiro; Lynch, David A.; Müller-Quernheim, Joachim; Myers, Jeffrey L.; Nicholson, Andrew G.; Selman, Moisés; Toews, Galen B.; Wells, Athol U.; Martinez, Fernando J.
The natural history of idiopathic pulmonary fibrosis (IPF) has been characterized as a steady, predictable decline in lung function over time. Recent evidence suggests that some patients may experience a more precipitous course, with periods of relative stability followed by acute deteriorations in respiratory status. Many of these acute deteriorations are of unknown etiology and have been termed acute exacerbations of IPF. This perspective is the result of an international effort to summarize the current state of knowledge regarding acute exacerbations of IPF. Acute exacerbations of IPF are defined as acute, clinically significant deteriorations of unidentifiable cause in patients with underlying IPF. Proposed diagnostic criteria include subjective worsening over 30 days or less, new bilateral radiographic opacities, and the absence of infection or another identifiable etiology. The potential pathobiological roles of infection, disordered cell biology, coagulation, and genetics are discussed, and future research directions are proposed. PMID:17585107
Recurrent Adult Acute Myeloid Leukemia; Relapsed Adult Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia Arising From Previous Myeloproliferative Disorder
... Acute kidney failure Acute tubular necrosis Amino acids Ammonia blood test Gastrointestinal bleeding Glomerulonephritis Heart attack Heart failure - overview Hypovolemic shock Metabolism Renal Shock Review Date 4/30/2015 Updated ...
Raja, Jowad; Munneke, Graham; Morgan, Robert; Belli, Anna-Maria
Management of critical limb ischemia of acute onset includes surgical embolectomy, bypass grafting, aspiration thrombectomy, thrombolysis, and mechanical thrombectomy followed by treatment of the underlying cause. We present our experience with the use of stents to treat acute embolic/thrombotic occlusions in one iliac and three femoropopliteal arteries. Although this is a small case series, excellent immediate and midterm results suggest that stenting of acute occlusions of the iliac, superficial femoral, and popliteal arteries is a safe and effective treatment option.
Queen, J S; Clegg, H W; Council, J C; Morton, D
Eikenella corrodens is a slow-growing facultative anaerobe present in the normal oral flora. Two children have been described with acute suppurative thyroiditis with E corrodens as the major pathogen. Staphylococci are the most frequently identified pathogens in acute suppurative thyroiditis. Penicillin or ampicillin are the drugs of choice for infections caused by E corrodens. Anatomic defects should be searched for in children with acute suppurative thyroiditis.
Pavlov, A Iu; Nechaeva, T N; Shchedrov, D N
Differentiated surgical policy was applied in the treatment of 147 children aged under 18 years with acute epididymitis. Basing on laboratory, clinical and ultrasound characteristics, three treatment methods were used: conservative treatment, puncture of the scrotum, revision of the scrotum. Puncture treatment of acute epididymitis appeared effective in accurate diagnosis of indications for this therapy and due performance. Ultrasound potential is shown in differential diagnosis in acute scrotum syndrome.
Kundavaram, Abhilash Pp; Das, Sohini; George, Varghese M
Scrub typhus is a mite-borne infectious disease caused by Orientia tsutsugamushi, which presents as an acute febrile illness with headache, myalgia, breathlessness, and an eschar, a pathognomonic sign, in a varying proportion of patients. However, this illness can present unusually with fever and severe abdominal pain mimicking acute abdomen. A careful search for an eschar in all patients with an acute febrile illness would provide a valuable diagnostic clue and avoid unnecessary investigations and surgical exploration.
Sawyer, E. K.; Anderson, J. R.
Occupational medicine physicians frequently are presented with requests by employers to determine the work-relatedness of medical illnesses or injuries. Occasionally, this involves a sudden onset of acute epididymitis in the male employee after strenuous activity in the workplace. Because the vast majority of acute epididymitis cases have an underlying sexually transmitted disease component, this poses a real dilemma for the consulting physician. This article discusses the etiology and pathogenesis of acute epididymitis along with its epidemiologic significance and reviews workers' compensation and its possible legal interpretation when acute epididymitis occurs at the worksite. PMID:8691501
Chandak, Rakhi; Degwekar, Shirish; Chandak, Manoj; Rawlani, Shivlal
Many conditions affect the salivary glands. Acute sialadenitis is infectious or inflammatory disorders of the salivary glands. The exact frequency of submandibular sialadenitis is unclear. The acute conditions more typically involve the parotid and submandibular glands. During an acute inflammatory process, there is swelling of the affected gland, overlying pain, gland tenderness, fever, and on occasion difficulty in opening the mouth. Initial treatment should include rehydration oral antistaphylococcal antibiotic should be started while awaiting culture results. Hygiene and repeated massaging of the gland when tenderness had subsided. The present report describes a case of acute submandibular sialadenitis in a 70-year-old female. PMID:22888457
Taniguchi, Hiroyuki; Kondoh, Yasuhiro
Idiopathic interstitial pneumonias (IIPs) may have an acute or subacute presentation, or acute exacerbation may occur in a previously subclinical or unrecognized chronic IIP. Acute or subacute IIPs include acute interstitial pneumonia (AIP), cryptogenic organizing pneumonia (COP), nonspecific interstitial pneumonia (NSIP), acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) and AE-NSIP. Interstitial lung diseases (ILDs) including connective tissue disease (CTD) associated ILD, hypersensitivity pneumonitis, acute eosinophilic pneumonia, drug-induced lung disease and diffuse alveolar haemorrhage need to be differentiated from acute and subacute IIPs. Despite the severe lack of randomized controlled trials for the treatment of acute and subacute IIPs, the mainstream treatment remains corticosteroid therapy. Other potential therapies reported in the literature include corticosteroids and immunosuppression, antibiotics, anticoagulants, neutrophil elastase inhibitor, autoantibody-targeted treatment, antifibrotics and hemoperfusion therapy. With regard to mechanical ventilation, patients in recent studies with acute and subacute IIPs have shown better survival than those in previous studies. Therefore, a careful value-laden decision about the indications for endotracheal intubation should be made for each patient. Noninvasive ventilation may be beneficial to reduce ventilator associated pneumonia.
Ramzisham, A R M; Arief, H; Ngoo, K S; Zamrin, D M; Joanna, O S M
Acute aortic dissection is a life-threatening condition, warranting prompt diagnosis and treatment. Management of which incorporates multidisciplinary expertise from the medical, surgical and intensive care. If left untreated, the mortality rate of acute aortic disease exceeds 50% within 48 hours and 80% within two weeks, with a 5-year survival rate of 19%. The most common cause of death in untreated acute aortic dissection, regardless of aetiology, is aortic rupture. We would like to share our successful experience of cases at the two extreme ages of acute aortic dissection. Literature review with their pathogenesis are discussed.
Lai, Shih-Wei; Lai, Hsueh-Chou; Lin, Cheng-Li; Liao, Kuan-Fu
The aim of this study was to examine whether there is an association between finasteride use and the risk of acute pancreatitis. This population-based case-control study used the database of the Taiwan National Health Insurance Program. There were 2,530 male subjects aged 40-84 years with a first-attack of acute pancreatitis during the period of 1998-2011 as the case group and 10,119 randomly selected subjects without acute pancreatitis as the control group. Both groups were matched by age and index year of diagnosing acute pancreatitis. Subjects who never had finasteride prescription were defined as "never use." Subjects who at least received 1 prescription for finasteride before the date of diagnosing acute pancreatitis were defined as "ever use." The association of acute pancreatitis with finasteride use was examined by the odds ratio (OR) and 95% confidence interval (CI) using the multivariable unconditional logistic regression model. The crude OR of acute pancreatitis was 1.78 (95%CI 1.33, 2.39) for subjects with ever use of finasteride, when compared with subjects with never use of finasteride. After adjusting for potential confounders, the adjusted OR of acute pancreatitis decreased to 1.25 (95%CI 0.90, 1.73) for subjects with ever use of finasteride, but no statistical significance was seen. No association can be detected between finasteride use and the risk of acute pancreatitis.
Skipworth, James R A; Shankar, Arjun; Pereira, Stephen P
Pancreatitis may be acute or chronic. Although both can be caused by similar aetiologies, they tend to follow distinct natural histories. Around 80% of acute pancreatitis (AP) diagnoses occur secondary to gallstone disease and alcohol misuse. AP is commonly associated with sudden onset of upper abdominal pain radiating to the back that is usually severe enough to warrant the patient seeking urgent medical attention. Onset of pain may be related to a recent alcohol binge or rich, fatty meal. The patient may appear unwell, be tachycardic and have exquisite tenderness in the upper abdomen. Overall, 10-25% of AP episodes are classified as severe, leading to an associated mortality rate of 7.5%. Disease severity is best predicted from a number of clinical scoring systems which can be applied at diagnosis in association with repeated clinical assessment, measurement of acute inflammatory markers, and CT. All patients with suspected AP should be referred urgently. Chronic pancreatitis (CP) follows continued, repetitive or sustained injury to the pancreas and 70% of diagnoses occur secondary to alcohol abuse. The characteristic presenting feature of CP is insidious progression of chronic, severe, upper abdominal pain, radiating to the back, caused by a combination of progressive pancreatic destruction, inflammation and duct obstruction. Signs and symptoms include weight loss and steatorrhoea and later on diabetes. CP patients may also present with recurrent episodes mimicking AP, both symptomatically and metabolically. Diagnosis of CP should be based on symptom profile, imaging and assessment of exocrine and endocrine pancreatic function. CT should be the first-line imaging investigation.
Fulmer, T; Ashley, J; Reilly, C
In conclusion, it is important to reiterate the interdependent nature of the functional health patterns as they relate to the geriatric patient in the acute care setting. Further, the combination of the primary nursing model with the functional health pattern approach that leads to subsequent nursing diagnoses provides a comprehensive care approach, which is so important for the elderly patient. As elders live longer, become frailer, and are subject to increasingly frequent hospitalizations, it will become more and more important to provide care in a manner that decreases fragmentation, increases individualization, and makes provisions for comprehensive and wholistic continuing care.
Almost two thirds of acute trusts rate the quality of commissioning from their PCTs at three out of 10 or less, according to the latest HSJ Barometer survey. This is the lowest score since we began the survey a year ago. Confidence in their performance against the 98 per cent four-hour A&E target fell sharply from a December high to an average of 6.87. The survey also found that fewer than one in seven trusts were confident of winning foundation status by the end of 2006-07.
External abdominal hernia occurs when abdominal organs or tissues leave their normal anatomic site and protrude outside the skin through the congenital or acquired weakness, defects or holes on the abdominal wall, including inguinal hernia, umbilical hernia, femoral hernia and so on. Acute incarcerated hernia is a common surgical emergency. With advances in minimally invasive devices and techniques, the diagnosis and treatment have witnessed major changes, such as the use of laparoscopic surgery in some cases to achieve minimally invasive treatment. However, strict adherence to the indications and contraindications is still required. PMID:25489584
Kawedia, Jitesh D; Rytting, Michael E
Cure rates in pediatric acute lymphoblastic leukemia have significantly improved over the past decades. Now, almost 90% of children will survive the disease. The cure rates in adolescents, young adults, and adults have not kept pace with the improvements in younger patients, even though almost an equal proportion of adult patients achieve complete remission as their pediatric counterparts. Differences in treatment regimens might be important. Intensive use of asparaginase has been a key component of successful pediatric therapy. In this review, we focus on the use of asparaginase and the potential of optimizing asparaginase use via monitoring to minimize adverse drug events and improve efficacy of the drug.
Chang, Timothy S; Jensen, Matthew B
Background Ischaemic stroke interrupts the flow of blood to part of the brain. Haemodilution is thought to improve the flow of blood to the affected areas of the brain and thus reduce infarct size. Objectives To assess the effects of haemodilution in acute ischaemic stroke. Search methods We searched the Cochrane Stroke Group Trials Register (February 2014), the Cochrane Central Register of Controlled Trials (Issue 1, 2014), MEDLINE (January 2008 to October 2013) and EMBASE (January 2008 to October 2013). We also searched trials registers, scanned reference lists and contacted authors. For the previous version of the review, the authors contacted manufacturers and investigators in the field. Selection criteria Randomised trials of haemodilution treatment in people with acute ischaemic stroke. We included only trials in which treatment was started within 72 hours of stroke onset. Data collection and analysis Two review authors assessed trial quality and one review author extracted the data. Main results We included 21 trials involving 4174 participants. Nine trials used a combination of venesection and plasma volume expander. Twelve trials used plasma volume expander alone. The plasma volume expander was plasma alone in one trial, dextran 40 in 12 trials, hydroxyethyl starch (HES) in five trials and albumin in three trials. Two trials tested haemodilution in combination with another therapy. Evaluation was blinded in 14 trials. Five trials probably included some participants with intracerebral haemorrhage. Haemodilution did not significantly reduce deaths within the first four weeks (risk ratio (RR) 1.10; 95% confidence interval (CI) 0.90 to 1.34). Similarly, haemodilution did not influence deaths within three to six months (RR 1.05; 95% CI 0.93 to 1.20), or death and dependency or institutionalisation (RR 0.96; 95% CI 0.85 to 1.07). The results were similar in confounded and unconfounded trials, and in trials of isovolaemic and hypervolaemic haemodilution. No
Karasick, S.; Karasick, D.; Schilling, J.
Acute megakaryoblastic leukemia or acute 'malignant' myelosclerosis is an acute and rapidly progressive myeloproliferative syndrome characterized by minimal or absent splenomegaly, pancytopenia, diffuse marrow fibrosis, and circulating blasts of megakaryocytic origin. The disease must be differentiated from other hematologic malignancies especially myelofibrosis with myeloid metaplasia. The radiographic changes of osteosclerosis in our patient have not been previously reported in the literature.
Acute Leukemia of Ambiguous Lineage; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia
Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myelomonocytic Leukemia (M4); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia
Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies
The present article analyzes the main presentations on acute pancreatitis (AP) in Digestive Disease Week 2013. Perfusion computed tomography allows early diagnosis of pancreatic necrosis. Neutrophil gelatinase-associated lipocalin predicts the development of acute renal failure, severe AP and death. Factors associated with greater fluid sequestration in AP are alcoholic etiology, an elevated hematocrit, and the presence of criteria of systemic inflammatory response syndrome; fluid sequestration is associated with a worse outcome. True pseudocysts (fluid collections without necrosis for more than 4 weeks) are a highly infrequent complication in AP. Patients with necrotic collections have a poor prognosis, especially if associated with infection. A meta-analysis on fluid therapy suggests that early aggressive fluid administration is associated with higher mortality and more frequent respiratory complications. According to a meta-analysis, enteral nutrition initiated within 24 hours of admission improves the outcome of AP compared with later initiation of enteral nutrition. Pentoxifylline could be a promising alternative in AP; a double-blind randomized study showed that this drug reduced the length of hospital and intensive care unit stay, as well as the need for intensive care unit admission. The association of octreotide and celecoxib seems to reduce the frequency of organ damage compared with octreotide alone. Mild AP can be managed in the ambulatory setting through hospital-at-home units after a short, 24-hour admission.
Dubus, J C; Bodiou, A C; Buttin, C; Jouglet, T; Stremler, N; Mély, L
Acute asthma attack in children is an attack responsible for life-threatening acute respiratory distress with partial or no response to bronchodilator drugs. The severity of the episode needs to be quickly evaluated. This presupposes a perfect knowledge of the clinical signs of severity. Treatment is urgent and first based on the administration of high doses of inhaled short-acting beta 2-agonists. In the more obstructed children, anti-cholinergic drugs can be added to nebulized beta 2-agonists. Because of their delayed effect, systemic steroids require an early prescription. Symptomatic treatments are: urgent hospitalization, oxygen if needed, proper hydratation. Continuous nebulization or intravenous perfusion of beta 2-agonists are prescribed with cardiac monitoring when no objective improvement is noted. Admission into the pediatric intensive care unit when bronchial obstruction continues will permit the association of bronchodilator drugs and the proposal of mechanical ventilation if needed. When the episode is resolved, a prophylactic treatment using inhaled corticosteroids must be prescribed. Clinical and spirometric follow-up has to be organized, and the patient and his/her family have to be educated.
Arsenic toxicity is a global health problem affecting many millions of people. Contamination is caused by arsenic from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Arsenic is present as a contaminant in many traditional remedies. Arsenic trioxide is now used to treat acute promyelocytic leukaemia. Absorption occurs predominantly from ingestion from the small intestine, though minimal absorption occurs from skin contact and inhalation. Arsenic exerts its toxicity by inactivating up to 200 enzymes, especially those involved in cellular energy pathways and DNA synthesis and repair. Acute arsenic poisoning is associated initially with nausea, vomiting, abdominal pain, and severe diarrhoea. Encephalopathy and peripheral neuropathy are reported. Chronic arsenic toxicity results in multisystem disease. Arsenic is a well documented human carcinogen affecting numerous organs. There are no evidence based treatment regimens to treat chronic arsenic poisoning but antioxidants have been advocated, though benefit is not proven. The focus of management is to reduce arsenic ingestion from drinking water and there is increasing emphasis on using alternative supplies of water. PMID:12897217
Mihalik, Zoltán; Arányi, Zsuzsanna; Siska, Eva; Nyulasi, Tibor; Pénzes, István
A 36-year-old female was admitted to the intensive care unit after resuscitation diagnosed with diabetic ketoacidotic coma, which was the first manifestation of her diabetes mellitus. It may have been provoked by pulmonary or gastrointestinal coinfection. Five days following admission the patient regained consciousness and homeostasis returned to normal. One week after the stabilization of her cardiopulmonary state, weaning from the respirator turned out to be unsuccessful: flaccid tetraparesis developed with rapid muscle atrophy and absence of deep tendon reflexes. The sensory system and cranial nerves remained intact. Electrophysiological studies and muscle biopsy showed serious acute illness myopathy with mild demyelination owing probably to the latent diabetes. The course of acute quadriplegia was fluctuating and correlated mainly with the activity of the systemic inflammatory response syndrome mechanisms. Myopathy might have been aggravated by using high-dose glucocorticoid therapy. The patient's general condition improved quickly as a result of full recovery from sepsis, discontinuation of glucocorticoids and normoglicaemia maintained by subcutan insulin substitution. Eight months after admission almost full neuromuscular restitution was achieved showing the reversibility of this grave illness.
Verghese, Susan T; Hannallah, Raafat S
The greatest advance in pediatric pain medicine is the recognition that untreated pain is a significant cause of morbidity and even mortality after surgical trauma. Accurate assessment of pain in different age groups and the effective treatment of postoperative pain is constantly being refined; with newer drugs being used alone or in combination with other drugs continues to be explored. Several advances in developmental neurobiology and pharmacology, knowledge of new analgesics and newer applications of old analgesics in the last two decades have helped the pediatric anesthesiologist in managing pain in children more efficiently. The latter include administering opioids via the skin and nasal mucosa and their addition into the neuraxial local anesthetics. Systemic opioids, nonsteroidal anti-inflammatory agents and regional analgesics alone or combined with additives are currently used to provide effective postoperative analgesia. These modalities are best utilized when combined as a multimodal approach to treat acute pain in the perioperative setting. The development of receptor specific drugs that can produce pain relief without the untoward side effects of respiratory depression will hasten the recovery and discharge of children after surgery. This review focuses on the overview of acute pain management in children, with an emphasis on pharmacological and regional anesthesia in achieving this goal. PMID:21197314
Verghese, Susan T; Hannallah, Raafat S
The greatest advance in pediatric pain medicine is the recognition that untreated pain is a significant cause of morbidity and even mortality after surgical trauma. Accurate assessment of pain in different age groups and the effective treatment of postoperative pain is constantly being refined; with newer drugs being used alone or in combination with other drugs continues to be explored. Several advances in developmental neurobiology and pharmacology, knowledge of new analgesics and newer applications of old analgesics in the last two decades have helped the pediatric anesthesiologist in managing pain in children more efficiently. The latter include administering opioids via the skin and nasal mucosa and their addition into the neuraxial local anesthetics. Systemic opioids, nonsteroidal anti-inflammatory agents and regional analgesics alone or combined with additives are currently used to provide effective postoperative analgesia. These modalities are best utilized when combined as a multimodal approach to treat acute pain in the perioperative setting. The development of receptor specific drugs that can produce pain relief without the untoward side effects of respiratory depression will hasten the recovery and discharge of children after surgery. This review focuses on the overview of acute pain management in children, with an emphasis on pharmacological and regional anesthesia in achieving this goal.
Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail
Acute kindney injury (AKI) is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate, causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid base disorders. In intensive care unit sepsis and septic shock are leading causes of AKI. Sepsis-induced AKI literally acts as a biologic indicator of clinical deterioration. AKI triggers variety of immune, inflammatory, metabolic and humoral patways; ultimately leading distant organ dysfunction and increases morbidity and mortality. Serial mesurements of creatinine and urine volume do not make it possible to diagnose AKI at early stages. Serum creatinine influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reason we need new markers, and many biomarkers in the diagnosis of early AKI activity is assessed. Historically "Risk-Injury-Failure-Loss-Endstage" (RIFLE), "Acute Kidney Injury Netwok" (AKIN) and "The Kidney Disease/ Improving Global Outcomes" (KDIGO) classification systems are used for diagnosing easily in clinical practice and research and grading disease. Classifications including diagnostic criteria are formed for the identification of AKI. Neutrophil gelatinase associated lipocalin (NGAL), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and also "cell cycle arrest" molecules has been concerned for clinical use. In this review the pathophysiology of AKI, with the relationship of sepsis and the importance of early diagnosis of AKI is evaluated.
Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail
Acute kindney injury (AKI) is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate, causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid base disorders. In intensive care unit sepsis and septic shock are leading causes of AKI. Sepsis-induced AKI literally acts as a biologic indicator of clinical deterioration. AKI triggers variety of immune, inflammatory, metabolic and humoral patways; ultimately leading distant organ dysfunction and increases morbidity and mortality. Serial mesurements of creatinine and urine volume do not make it possible to diagnose AKI at early stages. Serum creatinine influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reason we need new markers, and many biomarkers in the diagnosis of early AKI activity is assessed. Historically “Risk-Injury-Failure-Loss-Endstage” (RIFLE), “Acute Kidney Injury Netwok” (AKIN) and “The Kidney Disease/ Improving Global Outcomes” (KDIGO) classification systems are used for diagnosing easily in clinical practice and research and grading disease. Classifications including diagnostic criteria are formed for the identification of AKI. Neutrophil gelatinase associated lipocalin (NGAL), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and also “cell cycle arrest” molecules has been concerned for clinical use. In this review the pathophysiology of AKI, with the relationship of sepsis and the importance of early diagnosis of AKI is evaluated. PMID:27366441
Papafragkakis, Haris; Singhal, Shashideep; Anand, Sury
Acute fatty liver of pregnancy is a rare but serious and potentially fatal complication of pregnancy. It typically presents in the third trimester with microvesicular fatty infiltration of the liver and can lead to multiorgan failure and death. Differentiation from hemolysis-elevated liver enzymes-low platelets syndrome can guide management. A high index of suspicion is necessary in the appropriate clinical setting to identify clinical manifestations and complications and manage them appropriately. In severe cases, prompt delivery can be lifesaving for the mother and fetus. Liver transplantation remains controversial and must be considered individually. Defects in fatty acid oxidation secondary to various enzymatic deficiencies have been associated with acute fatty liver of pregnancy. Women or couples with known defects in fatty acid oxidation and women with a history of previous liver disease during pregnancy or sudden death of a child within the first 2 years of life should be assessed for a defect in fatty acid oxidation and monitored carefully. Our review summarizes the current knowledge in pathophysiology, diagnostic approach and management of this disorder.
Dorman, D.C.; Dye, J.A.; Nassise, M.P.; Ekuta, J.; Bolon, B.
The pig has been proposed as a potential animal model for methanol-induced neuro-ocular toxicosis in humans because of its low liver tetrahydrofolate levels and slower rate of formate metabolism compared to those of humans. To examine the validity of this animal model, 12 4-month-old female minipigs (minipig YU) were given a single oral dose of water or methanol at 1.0, 2.5, or 5.0 g/kg body wt by gavage (n = 3 pigs/dose). Dose-dependent signs of acute methanol intoxication, which included mild CNS depression, tremors, ataxia, and recumbency, developed within 0.5 to 2.0 hr, and resolved by 52 hr. Methanol- and formate-dosed pigs did not develop optic nerve lesions, toxicologically significant formate accumulation, or metabolic acidosis. Based on results following a single dose, female minipigs do not appear to be overtly sensitive to methanol and thus may not be a suitable animal model for acute methanol-induced neuroocular toxicosis.
Becker, Jonathan A; Daily, Jennifer P; Pohlgeers, Katherine M
Acute monoarthritis can be the initial manifestation of many joint disorders. The most common diagnoses in the primary care setting are osteoarthritis, gout, and trauma. It is important to understand the prevalence of specific etiologies and to use the appropriate diagnostic modalities. A delay in diagnosis and treatment, particularly in septic arthritis, can have catastrophic results including sepsis, bacteremia, joint destruction, or death. The history and physical examination can help guide the use of laboratory and imaging studies. The presence of focal bone pain or recent trauma requires radiography of the affected joint to rule out metabolic bone disease, tumor, or fracture. If there is a joint effusion in the absence of trauma or recent surgery, and signs of infection (e.g., fever, erythema, warmth) are present, subsequent arthrocentesis should be performed. Inflammatory synovial fluid containing monosodium urate crystals indicates a high probability of gout. Noninflammatory synovial fluid suggests osteoarthritis or internal derangement. Pitfalls in the diagnosis and early treatment of acute monoarthritis include failure to perform arthrocentesis, administering antibiotics before aspirating the joint when septic arthritis is suspected (or failing to start antibiotics after aspiration), and starting treatment based solely on laboratory data, such as an elevated uric acid level.
Although the etiology of acute leukemia is largely unknown, some facets of the puzzle are becoming clarified. Recognition of important patterns in age-specific mortality rates has suggested that events early in life, perhaps even prenatally, may have an influence on developing leukemia in childhood. The racial differences evident in mortality, incidence, and immunologic subtype of ALL suggest either differences in exposures to certain factors or differences in responses to those factors by white children. Hereditary factors appear to play a role. Familial and hereditary conditions exist that have high incidences of acute leukemia. Chromosomal anomalies are common in these conditions. Viral infections may play a role by contributing to alteration in genetic material through incorporation of the viral genome. How that virus is dealt with after primary infection seems important. The presence of immunodeficiency may allow wider dissemination or enhanced replication of such viruses, thereby increasing the likelihood of cellular transformation to an abnormal cell. Proliferation of that malignant cell to a clone may depend on other cofactors. Perhaps prolonged exposure to substances like benzene or alkylating agents may enhance these interactions between virus and genetic material. Does this change DNA repair mechanisms. Are viral infections handled differently. Is viral genomic information more easily integrated into host cells. Ionizing radiation has multiple effects. Alteration in genetic material occurs both at the molecular and chromosomal levels. DNA may be altered, lost, or added in the cell's attempt to recover from the injury.
... What Are the Key Statistics About Acute Myeloid Leukemia? The American Cancer Society’s estimates for leukemia in ... Leukemia Research and Treatment? More In Acute Myeloid Leukemia About Acute Myeloid Leukemia Causes, Risk Factors, and ...
Suzuki, Mitsuyoshi; Sai, Jin Kan; Shimizu, Toshiaki
In this Topic Highlight, the causes, diagnosis, and treatment of acute pancreatitis in children are discussed. Acute pancreatitis should be considered during the differential diagnosis of abdominal pain in children and requires prompt treatment because it may become life-threatening. The etiology, clinical manifestations, and course of acute pancreatitis in children are often different than in adults. Therefore, the specific features of acute pancreatitis in children must be considered. The etiology of acute pancreatitis in children is often drugs, infections, trauma, or anatomic abnormalities. Diagnosis is based on clinical symptoms (such as abdominal pain and vomiting), serum pancreatic enzyme levels, and imaging studies. Several scoring systems have been proposed for the assessment of severity, which is useful for selecting treatments and predicting prognosis. The basic pathogenesis of acute pancreatitis does not greatly differ between adults and children, and the treatments for adults and children are similar. In large part, our understanding of the pathology, optimal treatment, assessment of severity, and outcome of acute pancreatitis in children is taken from the adult literature. However, we often find that the common management of adult pancreatitis is difficult to apply to children. With advances in diagnostic techniques and treatment methods, severe acute pancreatitis in children is becoming better understood and more controllable. PMID:25400985
Lankisch, P G; Koop, H; Winckler, K; Fölsch, U R; Creutzfeldt, W
Because somatostatin (SRIF) reduces exocrine pancreatic secretion, its effect on acute pancreatitis was investigated in rats. Linear SRIF reduced serum amylase and lipase but had no effect on pancreatic necrosis, oedema, leucocyte infiltration, and enzyme content. The mortality rate was not reduced. These results do not recommend the use of SRIF in the treatment of acute pancreatitis. PMID:604191
Leşe, Mihaela; Pop, C; Naghi, Ildiko; Mureşan, Lavinia
The necrosectomy, celiostomy and pancreatic drainage represent the surgical treatment of choice in necrotizing pancreatitis. We present the clinical observation of a patient 59 years old operated in surgical service of Baia Mare for acute necrotizing pancreatitis, discussing the moment of operation, tips of operations, postoperative complications as well as our experience in acute grave pancreatitis treatment.
Chronic No-Observed Effect Concentrations (NOEC) are commonly determined by either using acute-to-chronic ratios or by performing an ANOVA on chronic test data; both require lengthy and expensive chronic test results. Acute-to-Chronic Estimation (ACE) software was developed to p...
Alexandrescu, D T; Dasanu, C A; Kauffman, C L
The association of vitamin C deficiency with nutritional factors is commonly recognized. However, an acute form of scurvy can occur in patients with an acute systemic inflammatory response, which is produced by sepsis, medications, cancer or acute inflammation. The frequency of acute hypovitaminosis C in hospitalized patients is higher than previously recognized. We report the occurrence of acute signs and symptoms of scurvy (perifollicular petechiae, erythema, gingivitis and bleeding) in a patient hospitalized for treatment of metastatic renal-cell carcinoma with high-dose interleukin-2. Concomitantly, serum vitamin C levels decreased to below normal. Better diets and longer lifespan may result a lower frequency of acute scurvy and a higher frequency of scurvy associated with systemic inflammatory responses. Therefore, increased awareness of this condition can lead to early recognition of the cutaneous signs of acute scurvy in hospitalized patients with acute illnesses or in receipt of biological agents, and prevent subsequent morbidity such as bleeding, anaemia, impaired immune defences, oedema or neurological symptoms.
Pezzilli, Raffaele; Morselli-Labate, Antonio Maria; Corinaldesi, Roberto
The resulting pain is the main symptom of acute pancreatitis and it should be alleviated as soon as possible. NSAIDs are the first line therapy for pain and they are generally administered to acute pancreatitis patients upon admission to the hospital. In addition, these drugs have also been used to prevent post-endoscopic cholangiopancreatography (ERCP) acute pancreatitis. On the other hand, there are several reports indicating that NSAIDs may be the actual cause of acute pancreatitis. We carried out a literature search on PubMed/MEDLINE; all full text papers published in from January 1966 to November 2009 on the use of NSAIDs in acute pancreatitis were collected; the literature search was also supplemented by a review of the bibliographies of the papers evaluated. Thus, in this article, we will systematically review the current literature in order to better illustrate the role of NSAIDs in acute pancreatitis, in particular: i) NSAIDs as a cause of acute pancreatitis; ii) their use to prevent post-retrograde ERCP pancreatitis and iii) their efficacy for pain relief in the acute illness of the pancreas. PMID:27713268
McNamee, H B; Mendelson, J H; Korn, J
Forty healthy adult male volunteers were studied to determine the efficacy of fenmetozole to antagonize the effects of acute alcholol intoxication. Twenty subjects receive placebo and 20 fenmetozole in dosage of 100 mg and 200 mg in a double-blind paradigm. Pretreatment with fenmetozole failed to antogonize or attenuate cognitive, perceptual, motor and affective changes associated with acute alchol intoxication.
Cahalane, Alexis M.; Smith, Myles J.; Ryan, James; Maguire, Donal
Gestational hypertriglyceridaemia is a rare cause of acute pancreatitis. Its pathophysiology is incompletely understood. Severity scoring and effective management remain challenging. We report a case of acute pancreatitis secondary to gestational hypertriglyceridaemia. We describe the use of computed tomography to provide an alternative determination of severity, as well as plasmapheresis as a means of treating the condition. PMID:22844296
Perticoni, G F; Bondi, L
Trichloroethylene (TCE), a solvent widely used in the chemical industry, in dry cleaning because of its degreasing action and as a household grease remover, is known to have a toxic action, especially on the nervous system. Cases of intoxication, acute and chronic, due to inhalation, are reported. We report a case, certainly an unusual one, of acute oral intoxication.
Miani, S; Boneschi, M; La Penna, A; Erba, M; De Monti, M; Giordanengo, F
Acute vascular abdomen is a severe and life-threatening pathology due to arterial degeneration, leading to hemorrhage or arterial occlusion leading to ischemia. Differential diagnosis of patients with severe abdominal pain and/or shock include several vascular and traumatic diseases, the most common being rupture of abdominal aortic aneurysm (AAA), or less frequently rupture of visceral artery aneurysm. Also acute aortic dissection, iatrogenic injury and acute mesenteric ischemia may lead to acute vascular abdomen. Clinical evaluation of the haemodynamic status of the patient may be very difficult, and may require airway maintenance and ventilation with a rapid treatment of hemorrhagic shock. In the stable patient with an uncertain diagnosis, CT scan, NMR and selective angiography may be helpful in diagnosis before vascular repair. On the contrary, the unstable patient, after hemodynamic resuscitation, must be operated on expeditiously. We present our vascular algorithms, to assess timing of diagnosis and treatment of this severe acute disease.
Hallstrand, Teal S; Fahy, John V
All asthma patients are at risk for acute asthma exacerbations. Moderate to severe exacerbations account for many emergency department visits and subsequent hospitalizations each year. Recent studies have advanced our understanding of the pathogenesis and treatment of acute asthma. The purpose of this review is to provide practical guidance in the assessment and treatment of adults with acute asthma in the hospital setting. Managing patients with acute asthma involves assessing the severity of the exacerbation, implementing measures to rapidly reverse airflow limitation, and instituting therapies that limit the progression of airway inflammation. Some patients may benefit from other supportive measures such as heliox and noninvasive ventilation. If the patient continues to deteriorate and requires mechanical ventilation, then ventilator settings that minimize the risk of hyperinflation should be chosen. After an episode of acute asthma, long-term preventive medications, especially inhaled corticosteroids, should be prescribed and education should be provided to prevent future episodes.
Anyaegbu, Elizabeth; Goodman, Michael; Ahn, Sun-Young; Thangarajh, Mathula; Wong, Michael; Shinawi, Marwan
Acute intermittent porphyria is a metabolic disorder rarely seen in prepubertal children. A delay in diagnosis of acute intermittent porphyria is common because of variable and nonspecific symptoms. We report an 8-year-old boy with right hemimegalencephaly and intractable seizures, who presented with dark-colored urine, hypertension, increasing lethargy, fluctuating seizures, and poor oral intake. He subsequently developed hyponatremia secondary to syndrome of inappropriate antidiuretic hormone secretion. His urinalysis was negative for red blood cells, and a random urine porphobilinogen level was elevated. Further biochemical and molecular testing confirmed the diagnosis of acute intermittent porphyria. His antiepileptic medications were discontinued and hemin administered, with dramatic clinical improvement. The diagnosis of acute intermittent porphyria was challenging because of his underlying neurologic condition. This case highlights the variable presentation of acute intermittent porphyria and emphasizes the importance of considering the diagnosis even in young patients with underlying neurologic conditions when they present with nonspecific neurovisceral symptoms or with unexplained neurologic deterioration.
Buitrago, Juliana; Santa, Sandra Viviana
The porphyrias are inherited disorders of the heme biosynthetic pathway. They are relatively rare and often misdiagnosed; however, acute episodes can be curtailed by early administration of heme arginate. Acute intermittent porphyria is the commonest of acute forms of porphyria. Here, a case is presented of a 23-year-old male with acute intermittent porphyria who came to the emergency clinic with an unexplained abdominal pain. In addition, he exhibited spontaneous hemothorax (two liters of blood accumulated in the chest) as an unusual manifestation of the disease. The most relevant aspects of acute intermittent porphyria are discussed, along with its epidemiology, diagnosis, clinical presentation and treatment. Complexities and diagnostic requirements in making a diagnosis of porphyria are described.
Akhavan, Reza; Zandi, Behrouz; Pezeshki-Rad, Masoud; Farrokh, Donya
Colloid cysts are benign slow-growing cystic lesions located on the roof of the third ventricle that usually present with symptoms related to gradual rise of intracranial pressure. They mostly remain asymptomatic and sometimes grow progressively and cause diverse symptoms associated with increased intracranial pressure such as headache, diplopia, and sixth cranial nerve palsy. Here we report a 47-year-old female who presented to the emergency department with acute severe headache and nausea/vomiting. On MRI examination acute hydrocephaly due to hemorrhagic colloid cyst was detected. Acute hemorrhage in colloid cysts is extremely rare and may present with symptoms of acute increase in the intracranial pressure. Intracystic hemorrhage is very rarely reported as a complication of colloid cyst presenting with paroxysmal symptoms of acute hydrocephaly. PMID:28210514
Pääkkönen, Markus; Peltola, Heikki
Acute septic arthritis is a rare, but potentially devastating disease. The treatment is initiated intravenously, but can be safely switched to oral after 2-4 days providing large doses of a well-absorbing antibiotic and, for time-dependent antibiotics, 4 times-a-day administration are used. Empiric treatment should always cover Staphylococcus aureus and common respiratory pathogens, whereas Kingella kingae and Salmonella are important only regionally. Studies conducted by our group have shown that a total course of 10 days may suffice for previously healthy children in a Western setting. Treatment of neonates, patients with immunodeficiency or cases caused by methicillin-resistant S. aureus, may deserve a different approach.
Seitz, Rüdiger J.; Donnan, Geoffrey A.
In acute stroke, the major factor for recovery is the early use of thrombolysis aimed at arterial recanalization and reperfusion of ischemic brain tissue. Subsequently, neurorehabilitative training critically improves clinical recovery due to augmention of postlesional plasticity. Neuroimaging and electrophysiology studies have revealed that the location and volume of the stroke lesion, the affection of nerve fiber tracts, as well as functional and structural changes in the perilesional tissue and in large-scale bihemispheric networks are relevant biomarkers of post-stroke recovery. However, associated disorders, such as mood disorders, epilepsy, and neurodegenerative diseases, may induce secondary cerebral changes or aggravate the functional deficits and, thereby, compromise the potential for recovery. PMID:26617568
Swanson, Allison M; Hughey, Lauren C
Scurvy is a well-known disease of vitamin C deficiency that still occurs in industrialized countries. The clinical manifestations of follicular hyperkeratosis, perifollicular petechiae, corkscrew hairs, and easy bruising are due to defective collagen synthesis and can be mistaken for small vessel vasculitis. Populations at risk for development of scurvy include elderly patients, alcohol and drug users, individuals who follow restrictive diets or have eating disorders, patients with malabsorption, and individuals with mental illness. We report an acute case of scurvy presenting in the inpatient/hospital setting with clinical findings initially thought to represent vasculitis. A high index of suspicion for scurvy must be kept in the appropriate clinical context, and a thorough medical history and physical examination are vital to make the diagnosis.
Laxdal, Oliver E.; Robertson, H. E.; Braaten, Virgil; Walker, W. Alan
During a seven-month period from November 1960 to May 1961, 181 infants and children, hospitalized because of acute respiratory infections, were studied intensively to determine the responsible etiologic agents. Forty-two per cent of the illnesses in this group appeared to be caused by bacterial agents, either primary or secondary to virus. Parainfluenza viruses were identified as causes of laryngotracheobronchitis in nearly 50% of the cases. Adenoviruses were also found to be important pathogens, particularly as causes of pneumonia in infants. The over-all infection rate attributed to adenoviruses was 11.6%. An epidemic due to Influenza B virus affected approximately 40% of children in this city just following the hospital study. This study was conducted as the first step in a long-term project undertaken at the Regina General Hospital to determine the effectiveness of vaccines in the prevention and treatment of respiratory infections in children. PMID:20327546
Jones, Kelsey D J; Berkley, James A
Severe acute malnutrition (SAM) is associated with increased severity of common infectious diseases, and death amongst children with SAM is almost always as a result of infection. The diagnosis and management of infection are often different in malnourished versus well-nourished children. The objectives of this brief are to outline the evidence underpinning important practical questions relating to the management of infectious diseases in children with SAM and to highlight research gaps. Overall, the evidence base for many aspects covered in this brief is very poor. The brief addresses antimicrobials; antipyretics; tuberculosis; HIV; malaria; pneumonia; diarrhoea; sepsis; measles; urinary tract infection; nosocomial Infections; soil transmitted helminths; skin infections and pharmacology in the context of SAM. The brief is structured into sets of clinical questions, which we hope will maximise the relevance to contemporary practice. PMID:25475887
Jones, Kelsey D J; Berkley, James A
Severe acute malnutrition (SAM) is associated with increased severity of common infectious diseases, and death amongst children with SAM is almost always as a result of infection. The diagnosis and management of infection are often different in malnourished versus well-nourished children. The objectives of this brief are to outline the evidence underpinning important practical questions relating to the management of infectious diseases in children with SAM and to highlight research gaps. Overall, the evidence base for many aspects covered in this brief is very poor. The brief addresses antimicrobials; antipyretics; tuberculosis; HIV; malaria; pneumonia; diarrhoea; sepsis; measles; urinary tract infection; nosocomial Infections; soil transmitted helminths; skin infections and pharmacology in the context of SAM. The brief is structured into sets of clinical questions, which we hope will maximise the relevance to contemporary practice.
Mehrotra, T N; Mital, H S; Gupta, S K
This article reports a case of acute pancreatitis in a patient taking the oral contraceptive pill. A 32 year old mother had been on combined contraceptive pills since 1975. In 1978 she started having upper abdominal and retrosternal pain. She became critically ill with peripheral circulatory collapse, dyspnoea and cyanosis. A superficial thrombophlebitis was noted on the medial aspect of the right thigh. The diagnosis of pancreatitis was considered with history of recurrent abdominal pain. After several tests and supportive therapy (intravenous fluids, antibiotics, steriods), the woman started showing improvements in 48 hours and recovered in 10 days. This case differs from previously described cases in that the cholesterol and triglyceride levels were normal. The hypoglycemia has not been described previously.
Shao, Emily Ximin; Wilson, Gregory John; Ranganathan, Dwarakanathan
Acute interstitial nephritis (AIN) has a number of medication-related aetiologies. Antibiotics, proton pump inhibitors and non-steroidal anti-inflammatory drugs are common causes; however, any medication has the potential to cause drug-induced AIN. We report the first case of phentermine-induced AIN. A Caucasian woman aged 43 years presented with a 5-week history of lethargy, left-sided lower abdominal pain, nausea and vomiting. She had been taking phentermine for weight loss for 9 months and had recently ceased the medication. The patient underwent a renal biopsy that showed a predominantly lymphohistiocytic interstitial infiltrate with a moderate number of eosinophils consistent with AIN. Phentermine is increasingly used for weight loss in obese patients. This is the first case implicating phentermine as the causative agent for drug-induced AIN. While rare, phentermine-induced AIN is a possible adverse reaction of phentermine. Physicians and patients need to be aware of this risk.