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Biomedical subjects

A Moudgil

Publications and source records attributed to A Moudgil.

At least 19 recordsLinked to original sources
PubMed2002

Hepatitis C therapy with long term remission after renal transplantation.

Hepatitis C virus infection (HCV) is common in patients with end-stage renal disease (ESRD) and long observation periods have shown the detrimental effect of HCV infection on patient and graft survival after renal transplantation. At present, interferon is the most important agent for the treatment of hepatitis C in ESRD; however, limited information exists concerning the long-term response of patients who undergo renal transplantation after successful antiviral therapy. We describe the evolution of HCV infection in a dialysis patient with hepatitis C who was successfully treated with interferon alpha and then underwent renal transplantation. He received aggressive immunosuppression during the induction phase and for allograft rejection; however, regular screening showed complete absence of biochemical and virological relapse of HCV over a 6-year post-transplantation period. We conclude that interferon can offer excellent response in selected dialysis patients with hepatitis C. Alternative strategies with newer antiviral agents are currently under active investigation.

Adult↗
PubMed2001

Cyclosporine microemulsion- and mycophenolate mofetil-related lymphoid aggregates are not associated with acute rejection.

BACKGROUND: Microemulsion cyclosporine, mycophenolate mofetil, and prednisone have become a common immunosuppressive protocol in renal transplantation. We identified lymphocytic infiltrates in transplant fine-needle aspirates and core biopsies from patients on this regimen without acute rejection clinically or by standardized morphological criteria and investigated this inflammatory response. METHODS: Twenty-eight aspirates from 21 patients were included and assessed in the standard fashion. Nine core biopsies showing interstitial lymphocytic infiltration were evaluated with antibodies against CD3, CD4, CD8, CD20, CD30, CD56, KP1, and epithelial membrane antigen (EMA). Aspirates and biopsies were assessed for tubular cell major histocompatibility complex (MHC) class II antigen and for gamma-interferon (gamma-IFN), interleukin-4 (IL-4), and IL-10 mRNAs by reverse transcription-polymerase chain reaction. RESULTS: Fifteen aspirates showed immune activation solely due to mature lymphocytes and monocytes; 13 had no immune activation. All aspirates were negative for MHC class II antigens. Of 6 activated aspirates assessed for gamma-IFN mRNA, 5 were negative. All 21 patients had similar clinical characteristics and recovered renal function without rejection treatment. The core biopsies had lymphocytes in 5-30% of the interstitium. The cells were 70-85% CD3+, with 50-85% CD4+, 3-10% KP1+, and rare cells CD56+. No T-cell activation was present (EMA- and CD30-). Seven biopsies were assessed and were negative for gamma-IFN mRNA; only one biopsy had weakly positive MHC class II staining. Two activated aspirates were negative for IL-4 and IL-10 mRNA, while three biopsies each contained IL-4 and IL-10 mRNAs. CONCLUSIONS: Inactive interstitial lymphoid infiltrates are frequent in patients on this drug regimen and should not be interpreted as acute rejection, particularly in aspirate samples. These lymphocytes may play a role in long-term allograft acceptance.

Antigens, CD↗
PubMed2001

Association of parvovirus B19 infection with idiopathic collapsing glomerulopathy.

BACKGROUND: Collapsing glomerulopathy (CG), a disorder with severe glomerular and tubular involvement, occurs either as an idiopathic lesion or in some patients with human immunodeficiency virus (HIV) infection known as HIV-associated nephropathy (HIVAN). We previously reported a renal transplant recipient with de novo CG and red cell aplasia in association with persistent parvovirus B19 (PVB19) infection. This prompted us to look for an association between PVB19 infection and CG. METHODS: DNA from archived biopsies of patients with CG was analyzed for PVB19 by polymerase chain reaction (PCR). Results were compared with HIVAN, idiopathic focal segmental glomerulosclerosis (FSGS), and controls. In situ hybridization (ISH) was done to localize PVB19 in renal biopsies. Peripheral blood specimens of patients with CG, HIV infection, healthy controls, and randomly selected hospitalized patients (sick controls) were also analyzed for PVB19. RESULTS: PVB19 DNA was detected in renal biopsies of 18 out of 23 (78.3%) patients with CG, 3 out of 19 (15.8%) with HIVAN, 6 out of 27 (22.2%) with FSGS, and 7 out of 27 (25.9%) controls (P < 0.01, CG vs. HIVAN, FSGS, and controls). PVB19 was detected in peripheral blood of 7 out of 8 (87.5%) CG patients, 3 out of 22 (13.6%) with HIV infection, 4 out of 133 (3%) healthy controls, and 2 out of 50 (4%) sick controls (P < 0.001, CG vs. HIV infected, healthy, and sick controls). PVB19 was identified in glomerular parietal and visceral epithelial and tubular cells by ISH. CONCLUSIONS: The significantly higher prevalence of PVB19 DNA in renal biopsies and peripheral blood of CG patients suggests a specific association between PVB19 infection and CG. In susceptible individuals, renal epithelial cell infection with PVB19 may induce CG.

Biopsy↗
PubMed2000

Nephrocalcinosis and renal cysts associated with apparent mineralocorticoid excess syndrome.

Apparent mineralocorticoid excess (AME) syndrome is a rare inherited disorder caused by 11beta-hydroxysteroid dehydrogenase (11-HSD 2) isozyme deficiency in the kidney. This enzyme is responsible for oxidizing cortisol to its inactive metabolite cortisone. An elevated tetrahydrocortisol (THF) and allotetrahydrocortisol (aTHF) to tetrahydrocortisone (THE) ratio in the urine is pathognomonic of AME syndrome. Clinical features include hypertension, hypokalemia, alkalosis, reduced plasma renin activity (PRA), low aldosterone levels, and occasionally nephrocalcinosis. Here we describe a 13-year-old boy who presented with severe hypertension, hypokalemia, low PRA and aldosterone levels, and elevated THF plus aTHF/THE ratio in the urine consistent with a diagnosis of AME syndrome. On ultrasound examination, he had severe nephrocalcinosis, and bilateral renal cysts. Renal cysts have not been previously reported in AME syndrome. The development of nephrocalcinosis and renal cysts may be associated with chronic long-standing hypokalemia. An early diagnosis and treatment of AME syndrome could help to prevent these sequelae, and to preserve renal function.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

Lung allograft dysfunction correlates with gamma-interferon gene expression in bronchoalveolar lavage.

BACKGROUND: Preceding episodes of acute cellular rejection (ACR) may predispose lung allografts to the subsequent development of irreversible dysfunction or bronchiolitis obliterans syndrome (BOS). Other histologic patterns such as bronchiolitis obliterans with organizing pneumonia (BOOP), organizing pneumonia, lymphocytic bronchiolitis and diffuse alveolar damage (DAD) may also adversely affect allograft function. We have previously reported the predominant expression of Th1 cytokines (IL-2 and interferon gamma) in rejecting and Th2 (IL-10) in a tolerant model of rat lung transplantation. Here we correlate the "Th1/Th2 paradigm" in clinical lung transplantation with histologic findings and assess the effect on serial spirometric function. METHODS: We examined the mRNA expression of IL-2, interferon gamma, IL-10 and ICAM-1 in 53 bronchoalveolar lavage (BAL) specimens from 23 lung transplant (LT) recipients utilizing qualitative "nested" reverse transcriptase polymerase chain reaction (RT-PCR). We also measured IgG1 and IgG2 levels in 44 BAL specimens by ELISA. The mRNA expression for cytokines, ICAM-1 and the IgG2/IgG1 ratios were correlated with the presence or absence of ACR and alternate "histologic patterns". Serial spirometry were analyzed for the 2-3 month interval before bronchoscopic (FOB) assessment to derive "baseline" forced expiratory volume-one second (FEV1) values. The change in FEV1 coincident with (deltaFEV1 pre) and for the 2-3 month interval subsequent to (deltaFEV1 post) FOB were expressed relative to "baseline" spirometric indexes. RESULTS: Detection of mRNA for interferon gamma and ICAM-1 correlated significantly with ACR, whereas IL-2 and IL-10 expression did not correlate. IL-10 was virtually "ubiquitous" in most BAL samples irrespective of the presence or absence of ACR. The highest correlation was observed with interferon gamma for acute cellular rejection whereupon the sensitivity was 77.7%, specificity 87.7%, positive predictive value 73.6% and negative predictive value 88.2%, although for ICAM-1 these values were 75%, 65.7%, 50.0% and 85.0%, respectively. Nevertheless, 4 of 5 episodes of respiratory tract infection (bacterial, CMV, Aspergillus spp.) were similarly associated with cytokine mRNA. The ratios of IgG2 to IgG1, a reflection of Th1/Th2 influence, were not statistically different when analyzed for the presence or absence of ACR (0.91+/-0.53 vs. 1.02+/-0.70, respectively; p = NS). By analysis of FEV1 trends, expression of interferon gamma was associated with a greater and persistent decrement (deltaFEV1 pre: -0.265+/-0.78 liters, and post: -0.236+/-0.1161; mean +/- SE) than ACR in the absence of interferon gamma expression (+0.158 +/- +0.065 and +0.236+/-0.007 liters, respectively) (Student-Newman-Keuls, p<.05). CONCLUSION: Our findings suggest that interferon gamma mRNA expression and ICAM-1 may be valuable in both the diagnosis and prognosis for lung allograft ACR. IL-10, a Th2 cytokine, was locally expressed both in the presence and absence of ACR. Expression of mRNA for interferon y in BAL and, to a lesser extent ICAM-1, were associated with increased lung allograft dysfunction. Whether BAL cytokine "immunosurveillance" would complement or possibly supplant a specific "histologic pattern" and thereby direct different therapies after lung transplantation, may be potentially rewarding areas of further investigation.

Acute Disease↗
PubMed1999

Expression of gamma-IFN mRNA in bronchoalveolar lavage fluid correlates with early acute allograft rejection in lung transplant recipients.

Various cytokines are upregulated in acute allograft rejection (AR). Local production of Th-1 cytokines is suggested to play a pathogenic role in AR, and Th-2 cytokines in the development of allograft tolerance. The purpose of this study was to correlate the expression of Th-1 [interleukin-2 (IL-2) and gamma-interferon (gamma-IFN)], and Th-2 [interleukin-10 (IL-10)] cytokines in bronchoalveolar lavage (BAL) fluid with AR in lung transplant (LT) recipients. The role of Th-1 dominance expressed as IgG2/IgG1 ratio in BAL in AR was also examined. The mRNA expression for IL-2, gamma-IFN and IL-10 was examined in 64 BAL specimens from 23 LT recipients using reverse transcriptase-polymerase chain reaction (RT-PCR). IgG1 and IgG2 levels were measured in 55 BAL specimens by enzyme-linked immunosorbent assay (ELISA). The expression on mRNA for these cytokines, and the ratio of IgG2/IgG1 was correlated with AR (early AR occurring within 3 months of transplant and late AR occurring after 3 months). Ten patients had 17 episodes of biopsy proven AR. Twelve episodes of AR (6 patients) occurred within the first 3 months of transplantation. In 5 patients, AR was diagnosed 4, 5, 6, 9 and 24 months post-transplantation. Detection of gamma-IFN mRNA correlated significantly with early AR (p < 0.001), whereas it lacked correlation with late AR. Expression of IL-2 and IL-10 mRNA did not correlate with AR. IL-10 was present in most samples irrespective of the presence or absence of AR. The ratio of IgG2/IgG1 was similar in patients with or without AR. Our findings suggest that the detection of gamma-IFN mRNA in BAL by RT-PCR is useful for immune monitoring of early AR in LT recipients. Absence of elevated IgG2/IgG1 ratio, and presence of IL-10 in BAL during AR suggests that Th-1 cytokines may not be the sole mediator of rejection in LT recipients.

Acute Disease↗
PubMed1999

Mutants of 11beta-hydroxysteroid dehydrogenase (11-HSD2) with partial activity: improved correlations between genotype and biochemical phenotype in apparent mineralocorticoid excess.

Mutations in the kidney isozyme of human 11-hydroxysteroid dehydrogenase (11-HSD2) cause apparent mineralocorticoid excess, an autosomal recessive form of familial hypertension. We studied 4 patients with AME, identifying 4 novel and 3 previously reported mutations in the HSD11B2 (HSD11K) gene. Point mutations causing amino acid substitutions were introduced into a pCMV5/11HSD2 expression construct and expressed in mammalian CHOP cells. Mutations L179R and R208H abolished activity in whole cells. Mutants S180F, A237V, and A328V had 19%, 72%, and 25%, respectively, of the activity of the wild-type enzyme in whole cells when cortisol was used as the substrate and 80%, 140%, and 55%, respectively, of wild-type activity when corticosterone was used as the substrate. However, these mutant proteins were only 0.6% to 5.7% as active as the wild-type enzyme in cell lysates, suggesting that these mutations alter stability of the enzyme. In regression analyses of all AME patients with published genotypes, several biochemical and clinical parameters were highly correlated with mutant enzymatic activity, demonstrated in whole cells, when cortisol was used as the substrate. These included the ratio of urinary cortisone to cortisol metabolites (R(2)=0.648, P<0.0001), age at presentation (R(2)=0.614, P<0.0001), and birth weight (R(2)=0.576, P=0.0004). Approximately 5% conversion of cortisol to cortisone is predicted in subjects with mutations that completely inactivate HSD11B2, suggesting that a low level of enzymatic activity is mediated by another enzyme, possibly 11-HSD1.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1998

Nephronophthisis associated with Ellis-van Creveld syndrome.

Ellis-van Creveld (EvC) and Jeune's asphyxiating thoracic dystrophy (ATD) are related disorders characterized by narrow thoracic cage and short-limbed dwarfism. Some patients have overlapping features of both ATD and EvC, indicating that these syndromes may be a part of a disease spectrum. Nephronophthisis has been occasionally reported in patients with ATD, but not with EvC syndrome. We report a patient who was diagnosed with EvC syndrome at birth. He developed hypertension at 5 months of age and gradually progressive renal failure, requiring renal transplantation at 8 years. Histopathological findings in the nephrectomy specimen were indicative of nephronophthisis. The association of nephronophthisis in a patient with EvC syndrome has not been reported previously. This association further supports the hypothesis that ATD and EvC syndromes are related and represent a spectrum of disorders.

Ellis-Van Creveld Syndrome↗
PubMed1997

Parvovirus B19 infection-related complications in renal transplant recipients: treatment with intravenous immunoglobulin.

BACKGROUND: Chronic red cell aplasia can develop in immunocompromised patients including transplant recipients infected with parvovirus B19 (PV B19). Renal involvement with PV B19 infection is not well-recognized. METHODS: We diagnosed erythroid hypoplasia associated with PV B19 infection in three renal transplant recipients; one of them developed de novo collapsing glomerulopathy. These patients were treated with intravenous immunoglobulin (IVIG). RESULTS: In two patients, anemia responded promptly to IVIG therapy. One of them had recurrence of anemia that responded to a second course of IVIG. Despite IVIG treatment, persistent infection with PV B19, recurrent anemia, and de novo collapsing glomerulopathy leading to allograft failure developed in the third patient, who had received the most intense immunosuppression. CONCLUSIONS: These findings indicate that PV B19 infection in transplant recipients can cause chronic red cell aplasia that generally responds to IVIG therapy. In some patients, particularly those who are heavily immunosuppressed, infection may persist despite treatment. As the cellular receptor for PV B19 is expressed in the kidney, persistent infection may result in development of glomerulopathies in these patients.

Adult↗
PubMed1997

Long-term allograft acceptance in a patient with posttransplant lymphoproliferative disorder: correlation with intragraft viral interleukin-10.

BACKGROUND: Viral (v) interleukin (IL)-10 is expressed by Epstein-Barr virus (EBV) and has pro- and anti-inflammatory actions similar to human IL-10. EBV is also a known factor in the development of posttransplant lymphoproliferative disorder (PTLPD) in allograft recipients. We observed a patient with widespread PTLPD 9 months after renal transplantation, who subsequently maintained renal function despite minimal immunosuppression, and we investigated a possible link between these factors. METHODS: The patient's chart was reviewed for relevant history. EBV DNA in blood and tissues was assessed by polymerase chain reaction. Human and vIL-10 and gamma-interferon mRNA were evaluated with reverse transcription-polymerase chain reaction using nested primers. RESULTS: After the diagnosis of PTLPD, the patient was maintained on prednisone (8 mg/day) as the only immunosuppression with preserved renal function for 17 months until death as a result of pulmonary failure. She had continuously high blood levels of EBV DNA, although only mild persistent intrarenal atypical lymphocytic infiltrates. Human IL-10 mRNA was never present; in contrast, intragraft vIL-10 mRNA was identified and associated with resolution of an intervening episode of severe acute transplant rejection. CONCLUSIONS: We suggest that the preserved renal function resulted from the anti-inflammatory actions of vIL-10 inhibiting acute rejection in the renal allograft.

Adult↗
PubMed1997

Ureteritis and cholecystitis: two unusual manifestations of cytomegalovirus disease in renal transplant recipients.

BACKGROUND: Common clinical manifestations of cytomegalovirus (CMV) infection include flu-like symptoms with fever, diarrhea, leukopenia, and elevated liver enzymes. Diagnosis is made by detection of the virus by buffy-coat blood culture or by polymerase chain reaction (PCR) analysis. METHODS: Here we describe two renal transplant recipients who presented with unusual manifestations of CMV disease (cholecystitis and ureteritis). In both patients, no symptoms or signs of systemic CMV infection were present, and they were thought to have other common causes for cholecystitis and ureteral obstruction. RESULTS: Retrospective analysis of peripheral blood by PCR analysis was positive for CMV DNA. Histologic examination of the resected gall bladder and stenotic ureteric segment showed CMV inclusions, confirmed subsequently by in situ hybridization. Thus, we report that CMV infection may present with acute cholecystitis or ureteral obstruction without its classical clinical symptoms. CONCLUSIONS: Because CMV infection is common in transplant patients, the atypical manifestations of CMV should be considered in the differential diagnosis of posttransplant complications. Detection of CMV DNA in the peripheral blood by PCR analysis may help identify these patients.

Adult↗
PubMed1997

Selective expression of the interleukin-2 gene discriminates between the auto- and allo-mixed lymphocyte reaction.

The in vitro mixed lymphocyte reaction (MLR) is a useful model to study alloresponsiveness to histocompatibility antigens. Secretion of different cytokine proteins in the supernatant of allo-MLR cultures has been reported in a few studies with no reference to results in auto-MLR. Since most cytokines are autocrine factors, their levels in the supernatant may not reflect the actual intracellular production. Therefore, we studied cytokine gene expression in auto- and allo-MLR by Northern dot blotting and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. mRNA for IL-beta and IL-8 was detected in both auto- and allo-MLR by Northern dot blotting. mRNA for IL-2, gamma-IFN, TNF-alpha, IL-4, IL-10 and IL-2 receptor (IL-2R) was not found by Northern dot blotting and could only be detected by RT-PCR. Expression of mRNA for IL-4, IL-10, TNF-alpha, gamma-IFN and IL-2R by RT-PCR analysis was seen in both auto- and allo-MLR. There was slightly increased expression of gamma-IFN, IL-2R and TNF-alpha in allo-MLR in comparison to auto-MLR. However, IL-2 was exclusively expressed in allo-MLR and was detected as early as 5 h of initiation of culture. These results indicate that mRNA expression for a number of cytokines can be seen in both auto- and allo-MLR using RT-PCR analysis. However, the consistent expression of IL-2 in the allo-MLR indicates that it is an important cytokine which discriminates an allo- from an autoresponse. These findings suggest that detection of IL-2 gene expression by RT-PCR may be useful for immune monitoring of allograft rejection.

Blotting, Northern↗
PubMed1997

Role of fibronectin in diagnosis of malignant ascites.

The aim of the study was to evaluate the role of ascitic fluid fibronectin in the diagnosis of malignant ascites. Fibronectin is a glycoprotein which plays an important role in regulating the organisation of the cell cytoskeleton and cell morphology. Ascitic fluid samples from 35 patients, 20 with portal hypertension (Group-I) and 15 with malignant ascites (Group-II) were analysed for proteins, cell counts, fibronectin levels and malignant cell cytology. Mean ascitic fluid fibronectin level was found to be significantly higher in malignant ascites as compared to portal hypertension (p < 0.001). At a cut off value of 94.67 microg/ml, the sensitivity, specificity, positive accuracy, negative accuracy and overall diagnostic accuracy was found to be 100%, 95%, 93.8%, 100% and 97.1% respectively.

Adult↗
PubMed1996

Protracted, gross hematuria in sickle cell trait: response to multiple doses of 1-desamino-8-D-arginine vasopressin.

Gross and microscopic hematuria are well-known complications in patients with sickle cell hemoglobinopathy. Most of these episodes of gross hematuria are self limiting, but rarely may be severe and persistent requiring definitive intervention. Before subjecting these patients to surgical management such as partial or total nephrectomy, several medical therapies of variable benefit have been suggested. We report a patient with sickle cell trait who experienced severe, intractable gross hematuria for 5 months and showed a dramatic response to multiple doses of 1-desamino-8-D-arginine vasopressin (DDAVP) infusion. The remarkable response observed in this patient suggests that treatment with DDAVP infusion may be considered in patients with unremitting gross hematuria associated with sickle cell trait.

Child↗
PubMed1996

Peripheral blood lymphocyte subsets in idiopathic nephrotic syndrome of childhood.

Lymphocyte subsets in the peripheral blood were examined in 34 patients with nephrotic syndrome [27 with minimal change nephrotic syndrome (MCNS), 7 with significant lesions] and 10 normal children. The investigations were done at the onset of disease before administering corticosteroids (n = 34), during the subsequent remission (n = 27), and the first relapse (n = 12). The proportions of T cell subsets (CD3, CD4 and CD8) were determined by immuno-alkaline phosphatase staining; interleukin-2 receptor (IL-2 R) positive cells, natural killer (NK) cells and B cells were studied by indirect immunofluorescence. No significant differences were found in the proportion of CD3, CD4, CD8 and IL-2 R positive cells in patients with MCNS as compared to controls. An increased proportion of NK and B cells was not specific to MCNS and was detected even in those with significant renal lesions. Our findings suggest that T lymphocyte subsets in MCNS are similar to those in normal children.

Adolescent↗