[show abstract][hide abstract] ABSTRACT: Apophysomyces elegans was considered a rare but medically important zygomycete. We analyzed the clinical records of eight patients from a single center in whom zygomycosis due to A. elegans was diagnosed over a span of 25 months. We also attempted a DNA-based method for rapid identification of the fungi and looked for interstrain polymorphism using microsattelite primers. Three patients had cutaneous and subcutaneous infections, three had isolated renal involvement, one had rhino-orbital tissue infection, and the final patient had a disseminated infection involving the spleen and kidney. Underlying illnesses were found in two patients, one with diabetes mellitus and the other with chronic alcoholism. A history of traumatic implantation was available for three patients. All except two of the patients responded to surgical and/or medical therapy; the diagnosis for the two exceptions was made at the terminal stage of infection. Restriction enzyme (MboI, MspI, HinfI) digestion of the PCR-amplified internal transcribed spacer region helped with the rapid and specific identification of A. elegans. The strains could be divided into two groups according to their patterns, with clustering into one pattern obtained by using microsatellite [(GTG)(5) and (GAC)(5)] PCR fingerprinting. The study highlights the epidemiology, clinical spectrum, and diagnosis of emerging A. elegans infections.
Journal of Clinical Microbiology 03/2003; 41(2):783-8. · 4.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hypertension is a rare complication of acute intermittent porphyria (AIP) and is related to the sympathetic over-activity seen in this condition. We report a patient with AIP with malignant hypertension that recurred with a subsequent episode. Mechanisms of hypertension and renal damage are discussed.
The Journal of the Association of Physicians of India 03/2003; 51:225-6.
[show abstract][hide abstract] ABSTRACT: Despite the endemic distribution of visceral leishmaniasis in certain parts of our country, there are only a few reports of this infection in renal transplant recipients. We report one renal transplant recipient from non-endemic area with visceral leishmaniasis and graft dysfunction that responded to treatment with stibogluconate. The infection should be considered in the differential diagnosis of a febrile transplant recipient with pancytopenia and allograft dysfunction.
The Journal of the Association of Physicians of India 08/2002; 50:979-80.
[show abstract][hide abstract] ABSTRACT: To define the spectrum of zygomycosis due to mucorales in an Indian scenario.
One-hundred and twenty-nine patients with zygomycosis due to mucorales diagnosed at the Postgraduate Institute of Medical Education and Research, Chandigarh, India during 1990-99, were retrospectively analysed regarding the sites of involvement, underlying disease, species of fungi isolated and outcome of therapy.
Higher prevalence rate (19.4%) was observed in 1999. Rhino-orbito-cerebral type (44.2%) was the commonest presentation followed by cutaneous (15.5%) and renal (14.0%) involvement. Disseminated zygomycosis was seen in 11.6% patients. Pulmonary and gastrointestinal zygomycosis were diagnosed in 10.1% and 4.7% patients, respectively. Uncontrolled diabetes mellitus (in 50% of cases) was the significant risk factor in rhino-orbito-cerebral type [odds ratio (OR), 9.3; P<or=0.001) and breach of skin (in 40% cases) in cutaneous zygomycosis (OR, 6.9; P<or=0.01). However, a considerable number of 22 (22.9%) patients were apparently healthy hosts in this series. Forty-five patients (34.9%) of this series were diagnosed only at post-mortem. Among 47 patients where culture was attempted, mucorales were isolated from 25 patients with Rhizopus arrhizus (11 patients) and Apophysomyces elegans (eight patients) as the predominant isolates. Adequate therapy could be provided in 33 patients. A combination of aggressive surgical debridement of necrotic tissue and amphotericin-B was found to be the best treatment protocol as 81.3% patients treated with surgical debridement and amphotericin-B were cured, compared with 46.7% patients treated with amphotericin-B alone.
The study highlights the importance of increased awareness for early diagnosis of zygomycosis and aggressive management. The large number of cases in apparently healthy hosts and increased isolation of A. elegans in the present series are important characteristics of this disease in India and requires further evaluation.
Journal of Infection 05/2001; 42(4):261-6. · 4.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Nitric oxide (NO) plays a significant role in the inflammatory process and has been implicated in several autoimmune disorders. This study was carried out prospectively to estimate the levels of nitrite and citrulline in the serum and urine, as surrogate markers of NO production, among patients with systemic lupus erythematosus (SLE). Forty-seven patients and 44 age- and sex-matched, healthy volunteers were studied. Nitrite and citrulline were measured in serum and urine by spectrophotometry.Median serum nitrite and citrulline levels and urine citrulline levels were higher among patients as compared with controls (p < 0.05). Patients with skin involvement stood out and had higher median serum and urine citrulline levels (p < 0.05). Disease activity correlated with steroid dosage, serum nitrite levels, and serum and urine citrulline levels (p < 0.05). Steroid dosage correlated with serum citrulline level (p < 0.05). Serum and urine citrulline levels correlated with each other (p < 0.01). In the subset of 13 individuals with renal involvement, serum and urine citrulline levels correlated with each other (p < 0.01) as did urine nitrite and citrulline levels (p < 0.05).NO production is increased among patients with SLE, and this increase correlates with disease activity and dosage of steroids used. The addition of a urine test to measure NO production as a marker of disease activity using simple spectrophotometry can be a valuable adjunct to other tests, can obviate the need for drawing a blood sample for this purpose, and can be repeated as often as necessary.
[show abstract][hide abstract] ABSTRACT: Renal transplant recipients are at risk of developing various infectious and non-infectious complications affecting the central nervous system (CNS). There is paucity of data regarding the spectrum of CNS complications and the epidemiology of infective agents varies according to geographical location. We retrospectively studied the spectrum of CNS complications seen in 792 renal allograft recipients followed up at this tertiary care centre in north India over a 19-year period. Autopsy findings of 78 allograft recipients who died in the hospital were also reviewed and included. The brain was examined in 22 of these patients. Overall, 79 (10%) patients developed some form of CNS dysfunction with a mortality rate of 60.8%. CNS infections occurred in 31 renal allograft recipients (3.9% of total) and accounted for the largest group (39.2%). Fungi were the commonest etiological agents (21 patients) and were associated with a 70% mortality, with cryptococcal meningitis occurring in 12, mucormycosis in six, aspergillosis in one, and other unusual fungal infections in the remaining two patients. All patients with mucormycosis had a fatal outcome. The second largest group comprised of patients with non-uremic encephalopathies (23 patients, 29.1%) with metabolic encephalopathy occurring in 13, toxic encephalopathy in nine and hypertensive encephalopathy in one patient) and was associated with an overall mortality rate of 60.9%. Cerebrovascular accidents occurred in 12 patients (15.2%) and were associated with a mortality of 91.7%. Other CNS complications included treatment related complications in four (5.1%), primary CNS lymphomas in three (3.8%), and miscellaneous complications in six patients (7.6%). Patients with non-cryptococcal fungal infections of the CNS, hepatic and toxic encephalopathy and those with cerebrovascular accidents had the worst outcome. There was no relationship between the development of infection or stroke and the type of maintenance immunosuppression used. We conclude that complications involving the CNS occur in 10% of all renal transplant recipients and are associated a with high mortality, warranting early diagnosis and aggressive treatment.
Journal of the Neurological Sciences 02/2001; 183(1):89-93. · 2.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: High treatment costs force the discontinuation of cyclosporine (CSA) in a vast majority of renal transplant recipients in India. The impact of CSA withdrawal among 108 living related renal transplant recipients 12.54 +/- 4.2 months after transplantation was studied retrospectively. In 83 patients, CSA was withdrawn over a 12-week period (group I). Azathioprine dosage was increased to 2 to 2.5 mg/kg/d, and prednisolone, to 30 mg/d 2 weeks and 1 week before starting CSA withdrawal, respectively. In the other 25 patients, CSA had to be withdrawn faster (mean, 28.52 +/- 14.18 days; group II). Twenty-nine rejection episodes (26.9%) were noted in 22 patients (20.4%; 19% in group I and 52% in group II; P: = 0.008). Fifteen group-I patients (18%) and 11 group-II patients (44%) died or lost their grafts (P: = 0.017). There was no difference in age, donor source, HLA matches, pretransplantation cross-match positivity, delayed graft function, immunosuppressive drug doses, rejection episodes, or prewithdrawal serum creatinine levels between the patients who did or did not develop acute rejection after CSA withdrawal. On follow-up, 10 patients (50%) died or returned to dialysis among the rejection group compared with 16 patients (18%) in the nonrejection group (P: = 0.007). The mean creatinine level at last follow-up was greater in the rejection group (3.97 +/- 2.54 versus 1.65 +/- 1.1 mg/dL; P: < 0.001). CSA withdrawal because of economic constraints carries a significant risk for acute rejection and death and/or graft loss in Indian living donor renal transplant recipients, even after 12 months.
American Journal of Kidney Diseases 02/2001; 37(1):119-124. · 5.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: Transplant recipients are predisposed to develop opportunistic infections such as tuberculosis, and isoniazid (INH) is used in most antitubercular therapeutic and prophylactic protocols. Cyclosporine (CyA) bioavailability increases with the concomitant use of drugs that inhibit hepatic cytochrome P-450 enzymes. There are conflicting reports on a possible interaction between the two drugs. Seven renal transplant recipients on CyA (Sandimmun Neoral) with slow acetylation status and also requiring concomitant INH prophylaxis (300 mg/day) against tuberculosis were studied. There were no significant changes in CyA pharmacokinetic parameters including CyA trough levels, total CyA exposure and CyA clearance before and 2 weeks after instituting INH prophylaxis. There was also no statistically significant correlation between INH levels and changes in CyA pharmacokinetic parameters before and after administration of INH. Even after all post-INH pharmacokinetic parameters were adjusted for INH levels, the differences in the above pre- and post-INH parameters did not reach statistical significance. Renal function during the study period remained constant and there were no episodes of CyA toxicity or acute rejection during and up to 4 weeks of INH treatment. We conclude that concomitant administration of INH and CyA is safe and is not associated with any appreciable alterations in the bioavailability of CyA.
Methods and Findings in Experimental and Clinical Pharmacology 11/2000; 22(8):647-9. · 0.77 Impact Factor
[show abstract][hide abstract] ABSTRACT: With the increase in the number of patients of AIDS, the incidence of cryptococcosis is on the rise in India. It was therefore considered important to evaluate the predisposing factors, laboratory investigations and outcome of patients with cryptococcosis in this changed scenario.
We assessed 58 patients with cryptococcosis retrospectively over a five year period (January 1995-December 1999) at the Nehru Hospital, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh.
The annual incidence of cryptococcosis in PGIMER, Chandigarh has increased about 15 fold from 1970-1982 (pre AIDS era) to 1995-1999 (present series). Of the 47 patients studied for predisposing factors, 36 patients were identified with predisposing factors, HIV infection (57.4%) was the commonest followed by haematologic malignancies (6.3%) and renal transplant (4.2%). Forty one patients were diagnosed by isolation of the organism as well as antigen detection in cerebrospinal fluid/serum, 9 by isolation alone and 8 by antigen detection alone. Quantitative antigen titres were done in 38 patients and a significantly higher (P < 0.01) antigen titre (> 512) was observed in HIV positive patients as compared to HIV negative patients. All isolates tested were of Cryptococcous neoformans var neoformans biotype and no resistance to antifungal agents was noted. Twenty of 41 patients receiving treatment improved. The results were compared with other studies available from India.
The incidence of cryptococcosis is on the rise in this part of north India and this can be attributed to an increase in AIDS cases.
The Indian journal of medical research 08/2000; 112:56-60. · 2.06 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cardiac arrhythmias are noted in a significant proportion of chronic renal failure (CRF) patients on hemodialysis (HD), and may contribute to cardiovascular mortality. A number of factors have been implicated in the genesis of these arrhythmias. The role of silent myocardial ischemia (SMI), however, has not been evaluated systematically. We prospectively studied 38 unselected CRF patients on regular HD by continuous Holter monitoring starting 24 hours before HD, lasting through the dialysis session and continued for 20 hours thereafter. The recordings were analyzed for frequency, timing and severity of supraventricular and ventricular arrhythmias and SMI as identified by ST-segment depression. Ventricular arrhythmias during HD were noted in 11 (29%) patients (group I), and were potentially life-threatening (Lown Class III and IVa) in 13%. The remaining 27 patients (group II) had no ventricular arrhythmias during HD. There was no difference in the age, sex ratio, duration of HD, blood pressure, fluctuations in weight, hematocrit, predialysis creatinine, sodium, potassium, calcium or inorganic phosphate levels between patients in the two groups. The number of patients with clinical ischemic heart disease was significantly greater in group I. SMI was noted in 72% and 33% of group I and II patients respectively (p = 0.026). 46% of those with and 25% of those without ST changes during HD developed ventricular arrhythmias during HD. Both SMI and ventricular arrhythmias were noted most frequently during the last hour of dialysis. Hypertension, diabetes mellitus and ischemic heart disease were observed more frequently amongst patients with SMI. Ventricular arrhythmias are detected in a significant proportion of CRF patients on HD. These are probably related to coronary artery disease since silent myocardial ischemia is also noted more frequently during HD in these patients. Further studies incorporating coronary angiography are needed in a larger number of patients to establish a definite causal relationship.
[show abstract][hide abstract] ABSTRACT: We retrospectively reviewed the CT findings in 24 cases of autosomal dominant polycystic kidney disease (ADPKD) to assess the role of CT in the diagnostic work-up of patients with complicated ADPKD.
Twenty-four patients with ADPKD underwent unenhanced and contrast-enhanced CT for flank pain, haematuria, or fever. The images were retrospectively reviewed for presence of complicated cysts, their morphological features and associated findings in the perinephric space/retroperitoneum.
Cyst haemorrhage was present in all patients, seen as high-density cysts, which were mostly bilateral. Most of these cysts had sharply outlined contours, sharp interfaces with adjacent renal parenchyma, imperceptible walls, and homogeneous density, and did not enhance following i.v. contrast administration. However, a few haemorrhagic cysts (9 cysts in 6 patients) showed inhomogeneous density (n=7), dependent layering of high-density blood leading to fluid-fluid level (n=2), and contour irregularity (n=3). CT revealed presence of cyst infection in 6 cases; the involved cysts were larger (average size 4.2 cm) than adjacent cysts, had only a mildly increased or near water density, and showed wall thickening and enhancement. Other findings included air within the infected cyst (n=1), thickening and enhancement of peri- and paranephric fasciae (n=5), and abscesses in the posterior paranephric space and adjoining psoas muscle (n=2). In 2 other patients, although CT suggested cyst infection because of presence of wall enhancement, diagnostic needle aspiration revealed only sterile haemorrhagic fluid. In 1 case, CT revealed a soft tissue density enhancing mass in one of the cysts; this proved to be a renal cell carcinoma by fine-needle biopsy. Calculi were observed in 7 patients, and cyst wall calcification in 11 cases.
A combination of unenhanced and contrast-enhanced CT allows correct diagnosis and differentiation amongst the various complications affecting patients with ADPKD. However, in a small subgroup of patients, it may not be possible to differentiate between haemorrhage and infection; such cases require diagnostic needle aspiration for diagnosis.
[show abstract][hide abstract] ABSTRACT: Elderly individuals need a host of diagnostic procedures and therapeutic interventions to take care of ailments. This prospective study was carried out to determine the magnitude of treatment-related acute renal failure (ARF) in the elderly in a hospital setting, to know about pathogenetic factors and to study the factors that could predict an adverse outcome.
All elderly patients (>60 years) admitted over a 12-month period were screened prospectively throughout their hospital stay for the development of ARF.
Of 31860 patients admitted, 4176 (13%) were elderly. Of these 59 (1.4%) developed ARF in the hospital. Nephrotoxic drugs contributed towards development of ARF in 39 (66%), sepsis and hypoperfusion in 27 (45.7%) each, contrast medium in 10 (16.9%) and postoperative ARF occurred in 15 (25.4%) patients. These pathogenetic factors were responsible for ARF in different combinations. Amongst these combination of pathogenetic factors, radiocontrast administration (partial chi(2) 28.1, P<0.0001), surgery (partial chi(2) 14.89, P=0.001), and drugs (partial chi(2) 6. 22, P=0.0126) predicted ARF on their own. Nine patients (15.23%) needed dialytic support. Of 59 patients, 15 (25.4%) died, of those who survived, 38 (86.3%) recovered renal function completely and six (13.6%) partially. Mortality in the elderly with ARF was significantly higher than in those without ARF (25.4 vs 12.5%; chi(2) 8.3, P=0.03). Sepsis (odds ratio 43), oliguria (odds ratio 64), and hypotension (odds ratio 15) were independent predictors of poor patient outcome on logistic regression analysis.
Incidence of treatment-related ARF in the elderly was 1.4%, with more than one pathogenetic factor playing a role in the development of ARF in the majority. Sepsis, hypotension, and oliguria were the independent predictors of poor patient outcome.
[show abstract][hide abstract] ABSTRACT: Renal involvement in 204 cases with multiple myeloma admitted over a 10-year period to this tertiary care center in north India was retrospectively examined. Renal involvement occurred in 55 cases (27%); the vast majority of whom (94.5%) had presented with renal failure and 7.3% had nephrotic syndrome. The diagnosis of multiple myeloma was made after admission in 51 of the 55 (92.7%) cases. Oliguria was seen in 23.6% and two-third patients required dialysis. Factors precipitating renal failure were identified in 53% and included dehydration (33%), hypercalcemia (24%), nephrotoxic drugs (16%), sepsis (9%), recent surgery (5%) and contrast media (2%), Severe anemia, hypercalcemia, Bence Jones proteinuria and skeletal abnormalities were more frequent in those with renal involvement. Patients with renal involvement were more likely to have a high tumor burden. The myeloma was of light chain type in 68% of those with renal involvement whereas IgG myeloma was commonest (57%) in those without evidence of renal disease. Renal histology was studied in 27 cases with myeloma cast nephropathy seen in over 60%. Tubulointerstitial nephritis was seen in 14% cases, 11% had amyloidosis, 7% had acute tubular necrosis and 3.6% each had nodular glomerulosclerosis and plasma cell infiltration. In 8 cases (14.6%), renal biopsy provided the first clue to the diagnosis of myeloma. Renal function improved in 33% cases. Only 22% of patients on dialysis survived over 6 months. Median survival in those with renal involvement was only 4 months. Development of unexplained renal failure in an elderly individual with normal sized kidneys, in association with disproportionate anemia even in the absence of skeletal lesions should alert the physician to the diagnosis of multiple myeloma.
[show abstract][hide abstract] ABSTRACT: We describe a renal transplant recipient who presented with tropical myositis and acute allograft dysfunction 2(1/2) years after transplantation. Graft biopsy showed immune-complex crescentic glomerulonephritis. He was receiving only 7.5 mg/d of prednisolone for more than 2 months before presentation. Renal function did not improve despite treatment with antibiotics, methylprednisolone pulse therapy, and cyclophosphamide. He died of septicemia.
American Journal of Kidney Diseases 01/2000; 34(6):E25. · 5.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: Invasive zygomycosis (mucormycosis) occurs predominantly in immunocompromised patients in whom it carries a grave prognosis. While renal involvement is not so uncommon in disseminated infection, isolated renal zygomycosis is rare.
Forty-five patients with systemic zygomycosis were seen over a 12-year period from January 1986 to December 1997. Among these, 18 had renal involvement, nine with disseminated disease and nine with isolated renal zygomycosis. No underlying predisposing disease was identified in the majority of patients (72%). Renal involvement was confirmed at autopsy in 13 and by ante-mortem renal biopsy in five patients. The infection involved one kidney in five patients and was bilateral in the remaining. The manifestations included fever, flank pain, haematuria and pyuria with evidence of enlarged non-functioning kidneys on computerised tomography (CT). Of those with bilateral disease, 12 (92.3%) had anuric acute renal failure. Anti-fungal therapy was given to six patients (amphotericin B in mean total dose of 1.1 g) and of these only two with unilateral disease who also underwent nephrectomy survived while all the other 16 died.
This study shows that renal zygomycosis has emerged as a cause of acute renal failure in the last decade since no patient with renal involvement was identified at our centre prior to 1986 even though autopsies have been done regularly in patients dying of unknown causes. Bilateral renal zygomycosis should be suspected in any patient who presents with haematuria, flank pain and otherwise unexplained anuric renal failure. Characteristic CT findings and an early renal biopsy can confirm the diagnosis and help in effective management of this serious disease.
[show abstract][hide abstract] ABSTRACT: Pulmonary infections, especially tuberculosis, are responsible for significant mortality and morbidity among renal transplant recipients in developing countries. Conventional diagnostic modalities are associated with a low yield, delaying specific therapy.
All patients transplanted within a 1.5-year period were prospectively followed-up for one year. Patients were on a cyclosporine-based triple immunosuppressive regimen. None received isoniazid prophylaxis, and those transplanted in the last seven months of the study period received daily cotrimoxazole. Patients exhibiting unequivocal evidence of pulmonary infections underwent further evaluation. Search for offending organisms was made by sputum examination and bronchoalveolar lavage (BAL).
. Thirty-nine infection episodes were recorded in 34 patients. M. tuberculosis was isolated during 10 episodes, pyogenic bacteria and Pneumocystis carinii in 6 each, candida in 4, aspergillus in 3, cytomegalovirus (CMV) in 3, and nocardia and mucor in one episode each. More than one organism was isolated during five episodes. Bacterial pneumonia and tuberculosis were diagnosed in another seven and two patients, respectively, on the basis of a therapeutic response to specific chemotherapy. Over two thirds of the organisms were identified by examination of BAL fluid. BAL was useful in the diagnosis of tuberculosis and P. carinii pneumonia but was relatively insensitive for CMV and bacterial infections. An increased frequency of acute rejection and higher serum creatinine were factors that predisposed to infections. All patients with pulmonary tuberculosis made a full recovery.
Tuberculosis and P. carinii are the most common nonpyogenic infections in the first year after transplantation in developing countries. An aggressive search for tubercle bacilli should be made using bronchoscopy and examination of BAL fluid in patients not responding to a short trial of antibiotics. A four-drug regime without rifampicin given for 18 months is effective for pulmonary tuberculosis in patients on cyclosporine. We recommend routine prophylactic use of one single-strength tablet of cotrimoxazole daily for at least six months after transplantation.
Kidney International 12/1999; 56(5):1944-50. · 7.92 Impact Factor