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Biomedical subjects

G T John

Publications and source records attributed to G T John.

At least 19 recordsLinked to original sources
PubMed2006

Acute graft pyelonephritis following renal transplantation.

BACKGROUND: Urinary tract infection is the most common form of bacterial infection encountered in a renal transplant recipient. Studies explaining the long-term consequences of acute graft pyelonephritis (AGPN) are few. METHODS: A total of 1022 consecutive renal allograft recipients were studied retrospectively over a period of 10 years for evidence of AGPN. These patients were classified into two groups according to the presence or absence of at least one AGPN episode. Only culture-proven infections were included in the study. RESULT: Of the 1022 renal transplant recipients, 169 patients (16.5%) developed AGPN. In the multivariate analysis with stepwise logistic regression, significant associations were observed between AGPN and placement of ureteric stent (odds ratio [OR]=4.6), urological malformations of native kidney (OR=2.1), cytomegalovirus (CMV) disease (OR=2.0), mycophenolate mofetil (MMF)-based regimen (OR=1.9), and acute rejection episodes (OR=1.5). However, age>40 years, female gender, induction therapy, anti-CD3 treatment, and hyperglycemia did not show such an association. In comparison with the non-AGPN group, these patients had a lower graft and patient survival (though it did not attain statistical significance). In the multivariate analysis using the Cox model for the entire study population, AGPN did not independently contribute to poor graft or patient survival. CONCLUSION: AGPN in the renal transplant setting is an ominous event, as these patients are also more prone to develop bacteremia, acute rejection, and CMV disease, which could then lead to poor graft and patient survival. Its association with MMF needs further clarification.

Acute Disease↗
PubMed2006

Leflunomide: a possible alternative for gangciclovir sensitive and resistant cytomegalovirus infections.

The search for newer more cost effective treatments for infectious diseases remains a challenge. Cytomegalovirus (CMV) infection, which is especially common in the immunosupressed, is an important challenge for treating physicians. Gangciclovir's cost is a major hurdle in developing countries. Leflunomide is cheaper and is easily given orally. It works by a novel mechanism inhibiting virion assembly. It also has immunosuppressive properties. It and has been shown to be effective in both gangciclovir sensitive as well as resistant cases of CMV infection. Given these considerations we believe that leflunomide is an exiting new drug for CMV infection. However, hepatotoxicity and teratogenicity are known side effects. The exact dose and duration of treatment for CMV infection, for secondary prophylaxis, and in situations of gangciclovir resistance need further study.

Animals↗
PubMed2005

Characterisation of operation conditions and online monitoring of physiological culture parameters in shaken 24-well microtiter plates.

A new online monitoring technique to measure the physiological parameters, dissolved oxygen (DO) and pH of microbial cultures in continuously shaken 24-well microtiter plates (MTP) is introduced. The new technology is based on immobilised fluorophores at the bottom of standard 24-well MTPs. The sensor MTP is installed in a sensor dish reader, which can be fixed on an orbital shaker. This approach allows real online measurements of physiological parameters during continuous shaking of cultures without interrupting mixing and mass transfer like currently available technologies do. The oxygen transfer conditions at one constant shaking frequency (250 1/min) and diameter (25 mm) was examined with the chemical sulphite oxidation method. Varied filling volumes (600-1,200 microL) of Escherichia coli cultures demonstrated the importance of sufficient oxygen transfer to the culture. Cultures with higher filling volumes were subjected to an oxygen limitation, which influenced the cell metabolism and prolongated the cultivation time. The effects could be clearly monitored by online DO and pH measurements. A further study of different media in an E. coli fermentation elucidated the different growth behaviour in response to the medium composition. The MTP fermentations correlated very well with parallel fermentations in shake flasks. The new technique gives valuable new insights into biological processes at a very small scale, thus enabling parallel experimentation and shorter development times in bioprocessing.

Cell Culture Techniques↗
PubMed2005

A prospective evaluation of leflunomide therapy for cytomegalovirus disease in renal transplant recipients.

AIM: A preliminary observation suggests leflunomide is effective in the treatment of cytomegalovirus (CMV) disease in renal transplant recipients. A prospective evaluation was conducted in renal transplant recipients to study the efficacy of leflunomide in the treatment of CMV disease. PATIENTS AND METHODS: With prior approval and informed consent for therapy and follow-up, 17 consecutive consenting renal transplant recipients with proven CMV disease were treated with leflunomide. CMV disease was defined as a clinical syndrome of fever and/or symptoms of organ involvement, leukopenia, and a positive nested CMV quantitative PCR test at 0.001 microg/5 microL template input, with or without histologic evidence of tissue invasion. Leflunomide metabolite concentrations (A77 1726) were monitored. RESULTS: Of the 17 patients, 14 patients were treated for 6 months for CMV disease the first time; the remaining 3 received leflunomide treatment for relapse after ganciclovir treatment, for a year. Seven patients had fever with viremia and no organ involvement, nine had viremia with involvement of gastrointestinal tract, and one had fever with CMV inclusions in the allograft, with no demonstrable viremia. The three patients with relapse treated with leflunomide responded. Overall, 15 patients (88%) clinically responded to leflunomide therapy and with viral clearance from blood and healing of involved organs. The cost of therapy with intravenous ganciclovir (Cymevene, Roche) for 2 weeks was US 721 dollars while that of leflunomide (Cleft, Cipla Ltd) for 6 months was US 64 dollars. CONCLUSION: Leflunomide treatment for CMV disease in renal transplant recipients is effective, simple, and economical.

Adult↗
PubMed2003

Pre- and postrenal transplantation pharmacokinetics of cyclosporine microemulsion.

UNLABELLED: The availability of a microemulsion formulation (ME) of cyclosporin (CyA) displays improved bioavailability and reduced inter and intra-patient variability, resulting in improved long-term outcomes. Recent developments in therapeutic drug monitoring stress the need to optimize peak drug levels during the early posttransplant period to obtain long-term benefit. METHODS: We studied early CyA-ME pharmacokinetics, comparing pre- versus immediate posttransplant values, to assess predictability of pre-transplant profiles in 22 patients including 3 diabetics. An 8 mg/kg per day amount in two divided doses was administered, for 5 days pretransplant and 10-14 days posttransplant before performing the pharmacokinetic studies. Drugs interacting with CyA metabolism/absorption were withdrawn and patients with liver disease were excluded the CyA level monitoring used a 5-point blood sampling (at 0 hours, 1 hours, 2 hours, 3 hours, and 4 hours post-dose). The study compared actual concentrations at each individual time and the limited 0-4 hour AUC. RESULTS: The paired values at each point pre- and posttransplant were: C0 = 171 +/- 63 and 215 +/- 112, C1 = 723.86 +/- 345 and 1239.95 +/- 415, C2 = 972 +/- 185 and 1249.95 +/- 336, C3 = 822 +/- 242 and 942.7 +/- 286, and C4 = 601.54 +/- 190 and 670.5 +/- 208 ng/mL respectively. The C1 and C2 values were significantly higher posttransplant (P =.008 and 0.0045 respectively), suggesting a steeper absorption phase, a conclusion consistent with the higher 0-4 hour AUC posttransplant (P =.0089). However, linear regression analysis of pre- versus posttransplant values showed poor correlations. CONCLUSIONS: CyA absorption is significantly lower among patients on maintenance hemodialysis and showed no predictive correlation with posttransplant levels. The possible role of uremia in retarding absorption which may have clinical significance for primary graft dysfunction, needs further evaluation.

Biological Availability↗
PubMed2002

Problems of classification of Henoch Schonlein purpura: an Indian perspective.

A 2-year prospective study was carried out in which 71 patients with primary cutaneous vasculitis were classified using the American College of Rheumatology (ACR) classification and the Chapel Hill Consensus Conference (CHCC) recommendations for Henoch Schonlein purpura (HSP). The sensitivity of the ACR criteria was 64.8% and that of the CHCC definition 31%. When the ACR criteria were combined with results of direct immunofluorescence (DIF) the sensitivity was 78.9%. The concordance between the two systems was low as only 12 patients fulfilled criteria for both classifications. Although the ACR criteria were found to be more useful in the classification of HSP our data suggest that they need to be modified to include adults with disease. The age at onset of disease was higher than that in the west. Seventy per cent of patients identified by either classification were > 20 years of age. The prevalence of gut involvement, microhaematuria and proteinuria was < 25% in both groups. The sensitivity of histopathology on the other hand was 80.4% and was not influenced by the duration of the lesion. The DIF test was a useful adjunct to histopathology if it was done within 48 h as the yield of a positive test was significantly higher in this group as compared to the patients who had the test done later.

Adolescent↗
PubMed2001

Quantitative screening method for hydrolases in microplates using pH indicators: determination of kinetic parameters by dynamic pH monitoring.

The presented pH-dyn assay serves as a versatile tool for screening enzymatically catalyzed reactions consuming or producing acids. The method is based on material balances of substrates and products. Ion balances relate concentrations of acids and bases to pH. pH-changes caused by the enzymatically catalyzed reaction in a well-defined buffer system are recorded by light-absorption measurements of a pH-indicator. Kinetic parameters are estimated by fitting the modeled pH changes to the experimentally observed ones. The enzymatically catalyzed hydrolysis of 4-nitrophenol is used as a model system. A pH indicator, bromothymol blue, is used to monitor the reaction progress. The reaction is monitored until the limiting substrate is completely consumed. This allows the estimation of the parameters of the Michaelis-Menten kinetics, K(M) and k(cat), in a single run. The results agree well with conventional spectrophotometric experiments and values reported in literature. Around pH 7, environmental CO(2) influences pH. Carbon dioxide influence was included in the model. Thus it was possible to estimate initial CO(2) concentrations as a model parameter, and therefore automatic correction for the CO(2) disturbances was achieved. This was important to detect low conversions at low buffer concentrations.

Calibration↗
PubMed2001

Risk factors for post-transplant tuberculosis.

BACKGROUND: Post-transplant tuberculosis (post-TxTB) occurs in 12 to 20% of patients in India and results in the death of 20 to 25% of those patients. Prospective studies on post-TxTB are few. METHODS: Renal allograft recipients were studied prospectively for 3.1 (0 to 13.9) median (range) years for incidence, manifestations, risk factors, and prognosis for post-TxTB. Kaplan-Meier analysis was used to study the survival rates. The extended Cox proportional model for time-dependent covariates was used to measure the risk factors when the hazard was nonuniform. RESULTS: Of the 1414 patients considered for inclusion, multiple-transplant subjects (N = 37) and patients who developed pre-transplant TB (pre-TxTB; N = 126) were excluded from the study. The prevalence of post-TxTB was 13.3% (N = 166). The risk of post-TxTB when on cyclosporine (CsA) therapy was 2.5 (P = 0.0311) and 1.9 (P = 0.0430) times at < or =6 and < or =12 months, respectively, compared with patients on prednisolone plus azathioprine (PRED + AZA). The risk of post-TxTB in the presence of diabetes mellitus, chronic liver disease, and other co-existing infections [including deep mycoses, cytomegalovirus (CMV), Pneumocystis carinii pneumonia (PCP), nocardia] was 2.2 (P = 0.0011), 1.7 (P = 0.0010) and 2.4 (P < 0.0001) times, respectively. Of the 166 patients with post-TxTB, 53 patients died, and of those deaths, 17 (32%) were due to post-TxTB; 11 (65%) of the 17 had co-existing infections. The factors associated with death were HLA mismatches, PRED + AZA immunosuppression, pre- and post-TxTB, diabetes mellitus, post-transplant diabetes (PTDM), and other co-existing infections. The extended Cox model for death as the outcome variable showed the following to be significant risk factors: post-TxTB> 2 years (P = 0.0036), chronic liver disease> 6 years (P = 0.0457), PTDM> 5 years (P = 0.0729), diabetes mellitus (P = 0.0091), human lymphocyte antigen match < or =1 antigen (P = 0.0134), two to three antigens (P = 0.0448), and the presence of other co-existing infections (P < 0.0001). CONCLUSIONS: Cyclosporine therapy is associated with early post-TxTB. Diabetes mellitus and chronic liver disease are risk factors for post-TxTB. The occurrence of both pre-TxTB and post-TxTB (>2 years) along with hyperglycemia, liver disease, and other co-existing infections are important risk factors for death.

Adult↗
PubMed2000

Role of molecular techniques in the detection of HBV DNA & HCV RNA among renal transplant recipients in India.

In this study we have investigated the occurrence of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) infections among 68 renal transplant recipients. Replicative HBV and replicative HCV infections were seen in 12 (17.6%) and 38 (55.9%) patients respectively, the difference was statistically significant (P < 0.001). Among the 38 HCV RNA+ individuals, anti-HCV was present only in 23. Anti-HCV in the absence of HCV RNA was detected in one patient. Anti-HDV antibody was seen in 2 (15.4%) of the 13 HBV infected individuals. Nine (13.2%) of the 68 individuals had replicative dual infection with HBV and HCV. Triple infection (HBV DNA+, HCV RNA+, anti-HDV+) was seen in 2 transplant recipients. There was significantly higher demonstration of replicative HCV (P < 0.001) in transplant recipients having elevated liver enzymes (n = 34) as compared to transplant recipients having normal liver enzyme levels (n = 34). Though not significant, a higher detection rate was also seen with replicative HBV infection and replicative dual infection among transplant recipients with elevated liver enzymes. The higher detection of HCV in renal transplant recipients by molecular techniques, emphasizes the need for HCV RNA testing. Further deliberate attempts to change practices to reduce this problem may also improve graft and patient survival in recipients.

Adolescent↗
PubMed1999

Prognostic factors in diffuse proliferative lupus nephritis.

BACKGROUND: Patients with diffuse proliferative lupus nephritis (DPLN) can have variable clinical course. Identification of the predictors of outcome would help to improve the management. We have studied the prognostic significance of clinical, laboratory and histological parameters in patients with DPLN. METHODS: Twenty nine patients diagnosed to be having DPLN seen between 1987 and 1991 were followed up for over 57 months. Parameters assessed for prognostic significance included serum creatinine, urine protein at the time of biopsy, blood pressure, type of immunosuppression, composite scores and individual components of activity index (AI) and chronicity index (CI). Kaplan-Meier survival curves were plotted and the results were compared using log rank test. Fishers' exact test was used to study the risk factors. RESULTS: End stage renal failure developed in 7/29 (24.1%) patients; 7/19 (36.8%) who had hypertension and 7/16 (43.8%) who had nephrotic proteinuria developed renal failure, while none who had normal blood pressure or nonnephrotic proteinuria, developed renal failure (p < 0.01). Three patients had high activity index (> 12) and all three developed renal failure. Other parameters such as age, gender, serum creatinine, type of immunosuppression, CI and individual components of AI failed to predict the outcome (p > 0.05). CONCLUSION: Hypertension, nephrotic proteinuria and high AI were predictive of progression to end stage renal failure in patients with diffuse proliferative lupus nephritis.

Adolescent↗
PubMed1998

Leprosy and renal transplantation.

Nine cases of leprosy in patients treated at a large renal transplant centre in South Asia are described. Three had leprosy diagnosed before transplantation and had either completed or were continuing chemotherapy at the time of transplantation. One showed exacerbation of undisclosed leprosy after transplantation. Five patients developed the disease for the first time 22 months to 12 years after transplantation. Immunosuppression did not adversely affect the treatment of leprosy in any of the patients though concurrent liver disease required cessation of rifampicin in one patient.

Adult↗
PubMed1996

Gastric aspiration for diagnosis of pulmonary tubercolosis in adult renal allograft recipients.

Of 213 renal allgraft recipients suspected to have had pulmonary tuberculosis, 132 had sputum examinations and 14 showed acid-fast bacilli. Of the remaining 118 patients, 25 had gastric aspirations, 18 had bronchoalveolar lavage, and 75 did not require further investigation because of spontaneous improvement or confirmation of an alternative diagnosis. While 9 of the 25 patients' gastric aspirate examination was positive, all the 18 who had bronchoalveolar lavage were negative for acid-fast bacilli. Eighty-one patients without expectoration had gastric aspiration directly and 14 showed acid-fast bacilli. Of the remaining 67 patients only 17 had bronchoalveolar lavage, of which three were positive for AFB and the rest did not require further testing for tuberculosis. A total of 106 patients had gastric aspiration. Acid-fast bacillus positivity was significantly more (P<.01) in patients with abnormal chest radiographs as compared with patients with normal chest radiographs as compared with patients with normal chest radiograph results. We suggest gastric aspiration for AFB in all renal transplant recipients who have fever, scanty expectoration, and abnormal chest radiograph with clinical suspicion of pulmonary tuberculosis.

Bacteriological Techniques↗
PubMed1996

Renal functional reserve in kidney donors assessed in different settings using scintigraphy.

Glomerular filtration rate (GFR) was measured in 9 voluntary male kidney donors by scintigraphy. In the basal state, the mean GFR was 96.1 +/- 22 ml/min/1.73 m2. Four weeks after donor nephrectomy, the GFR of the remaining kidney had increased by 22.8 +/- 20.7% (p < 0.05). A protein meal given at this time failed to significantly augment the GFR. The GFR of the grafted kidney increased by 59.7 +/- 24.4% after 6 months (p < 0.01). Renal functional reserve was thus demonstrated in the remaining kidney and the allograft, though a further reserve could not be elicited in the remaining kidney.

Adult↗
PubMed1995

Bilateral emphysematous pyelonephritis responding to nonsurgical management.

Bilateral emphysematous pyelonephritis is a rare condition, with only 14 cases reported in the English literature. It carries a bad prognosis, surgical management being the recommended mode of therapy. We report a case of bilateral emphysematous pyelonephritis in a 50-year-old diabetic lady which was successfully managed using antibiotics alone.

Cefuroxime↗