Blood glutathione levels in head and neck malignancies.

Blood glutathione was estimated in fifty patients of head and neck cancer in the age group of 18-76 years and the results were compared with a group of normal healthy controls. Mean blood glutathione level was found to be significantly lowered in patients than the controls. Irrespective of the site, TNM classification, histopathology, and character of lesion, fall in blood glutathione was nearly same in all the patients. The mean level was significantly increased after radiotherapy when compared with the levels before radiotherapy. The decreased levels of GSH in-patients with head and neck cancer, observed in the present study, may be due to its increased utilization by the cells. The results suggest that patients with head and neck cancer have increased oxidative stress.

Myoglobinuria and renal failure after status epilepticus.

Acute renal failure developed in a 28-year-old man after status epilepticus. Myoglobinuria was contributed to by convulsions, trauma and coma during status epilepticus, the three mechanisms responsible for this condition.

Cyclophosphamide in renal transplantation.

Success in renal transplantation is now largely dependent on safe and effective immunosuppression. Nonspecific immunosuppression by chemical agents continues to be the mainstay of clinical immunosuppression. Azathioprine and prednisolone have remained the two main drugs used in combination in standard immunosuppressive therapy in renal transplantation for many years. Although cyclophosphamide (CP) was tried in the early years of transplantation, enthusiasm for its use was dampened by the advent of newer agents. We have analyzed our experience with 29 recipients of living-related donor (LRD) renal allotransplantation on cyclophosphamide therapy. Cyclophosphamide is a safe and effective alternative to azathioprine in clinical renal allotransplantation. Due to its easy availability and the fact that it is a cheaper alternative to azathioprine and cyclosporine, it is more significant for developing countries.

The high incidence of tuberculosis among renal transplant recipients in India.

Tuberculosis is an important infection encountered after renal transplantation in third-world countries. Over an 8-year period, 36 cases of tuberculosis were encountered in 305 renal transplant recipients (11.8%) with grafts functioning for more than 3 months followed up at our center. The infection was limited to the thoracic cavity in 41.7% and a single extrapulmonary site in 11.1%, and it was disseminated in 27.8% cases. In 19.4% of cases, the disease appeared as pyrexia of unknown etiology and the diagnosis was confirmed by a good therapeutic response to antitubercular therapy. Tuberculosis was diagnosed within 1 year of transplantation in 58.3% of cases. There was no significant difference in the incidence of tuberculosis in patients on different immunosuppressive regimens. The Mantoux test was positive in 33.3% patients. A total of 23 patients were treated with isoniazid and rifampicin, with the addition of a third drug for the first 2 months. Treatment was continued for 9 months in 11 cases with isolated pleuropulmonary disease and for 12-15 months in the other 12 patients. The other 13 were on cyclosporine and were given isoniazid, pyrazinamide, and ethambutol for 18 months. Two patients died of fulminant disease and five more died from unrelated causes. No recurrence of disease has been noted in any of the patients after a mean follow-up of 14.6 months. We conclude that the incidence of tuberculosis in renal allograft recipients in third world countries is much higher than that seen in the western world. Most of the cases are encountered in the first posttransplant year. Tuberculosis must be considered seriously in all patients who have prolonged fever of undetermined etiology. Treatment with isoniazid and rifampicin for 9 months is adequate for patients with localized pleuropulmonary disease. In patients on cyclosporine to whom rifampicin cannot be given because of economic considerations, treatment with isoniazid, pyrazinamide, and ethambutol should be given for 18 months.

Rhabdomyolysis and renal failure following status asthmaticus.

Acute renal failure developed in a 25-year-old man following status asthmaticus. He was found to have myoglobinuria. Vigorous contraction of the respiratory muscles and hypoxia were considered to be responsible for the development of myoglobinuria. Associated dehydration, in the presence of myoglobinuria, also contributed to the development of acute renal failure.

Acute renal failure of obstetric origin.

Acute renal failure of obstetric origin is common among North Indian patients and comprised 72 (22.1%) of 325 patients undergoing dialysis over an 11-year period. Of these, 46 gravidas had developed renal failure following abortion, and 29 cases were due to complications of late pregnancy. The most striking feature of this study was a high incidence of irreversible renal lesions of bilateral diffuse cortical necrosis in early (18.6%) as well as late pregnancy (37.8%). Overall incidence of diffuse cortical necrosis was 25%. In the remainder, acute tubular necrosis was seen in 52 (72.2%), patchy cortical necrosis in 1 (1.4%), and tubular necrosis along with glomerular involvement in 1 patient (1.4%). Pathogenetic factors which contributed to the development of renal failure, either singly or in combination, were loss of blood failure, either singly or in combination, were loss of blood (79.1%), septicemia (31.9%), hypotension due th hemorrhagic and septicemic shock (51.4%), eclamptic toxemia (11.1%), and disseminated intravascular coagulation in 12.5% patients. Infrequent occurrence of disseminated intravascular coagulation in the septic anc eclamptic patients who developed diffuse cortical necrosis was an interesting finding, as was the fact that coagulopathy was more frequently observed in acute tubular necrosis. Late referral, frequent sepsis, and high incidence of bilateral diffuse cortical necrosis contributed significantly to a high mortality (55.3%).

Differences in the care of ESRD patients worldwide: required resources and future outlook.

RRT has crossed the threshold of clinical applications, and its value as an effective modality for management of ESRD is fully established. However, RRT has emphasized the wide gap between developed and developing countries. Most of the developed nations are able to provide sufficient funds, directly or indirectly, for RRT and have organized cadaver donor networks. However, providing RRT is particulary difficult in the developing countries where national incomes are not sufficient to cover even the basic requirements of their citizens. Although some developing countries are making active efforts to establish cadaver donor transplant programs, these are virtually nonexistent in the majority at this time. The abject poverty in the developing world and the increasing success rate of transplantation following the discovery of cyclosporine have led to the commercialization and sale of kidneys for transplantation, an unethical practice which must be curbed. There is a near unanimity of opinion that renal transplantation is far cheaper than prolonged dialysis, and the benefit to the recipient is enormous in terms of the years of life saved and the quality of life. Until such time as cadaveric donor programs become a reality in the developing countries, short periods of dialysis followed by transplants with living-related donor kidneys appear to be the most cost-effective treatments of ESRD.

Complement depletion following envenomation by Russell's viper and Echis carinatus (saw-scaled viper) in the rhesus monkey.

Significant depletion of C3 was observed following administration of lethal and sublethal doses of Russell's viper and Echis carinatus venom to rhesus monkeys. A sequential study carried out over a period of 3 weeks following sublethal envenomation showed a steady rise in the C3 level from 48 hours onwards. By the 20th day the C3 values had attained the pre-envenomation levels. The extent of depletion of C3 was similar in both Russell's viper and E. carinatus envenomation. Because of the close immunological similarity of monkey and man, the rise in C3 which corresponded with recovery of the animals in this experimental model could serve as a useful parameter of recovery in clinical cases of snake poisoning.

Coagulation abnormalities induced by Russell's viper venom in the rhesus monkey.

Coagulation studies were carried out in a group of non-human primates (rhesus monkeys) following envenomation with lethal and sublethal doses of Russell's viper venom. The envenomated animals showed significant fibrinogenopenia in association with or without disseminated intravascular coagulation. The findings offer a rational explanation for the bleeding manifestations seen in clinical cases of Russell's viper bite.

Hemostatic abnormalities following Echis carinatus (saw-scaled viper) envenomation in the rhesus monkey.

Hemostatic abnormalities following lethal and sublethal doses of Echis carinatus venom were studied in a subhuman primate model. The observations suggest the occurrence of disseminated intravascular coagulation of varying magnitude within a few hours of envenomation. A procoagulant effect of the venom of Echis carinatus is likely to be the major cause of the disturbance in the hemostatic mechanism.

Acute renal failure following snakebite.

Eight patients with acute renal failure following snakebite were studied. Intravascular hemolysis and disseminated intravascular coagulation contributed to the development of acute renal failure in 6 patients. Direct nephrotoxicity causing acute renal failure is postulated in 2 patients, 1 of whom also revealed evidence of mild, disseminated intravascular coagulation. Three patients had histopathological lesions of acute symmetrical cortical necrosis and 3 had acute tubular necrosis. In 1 patient with acute tubular necrosis, in whom direct nephrotoxicity seemed to be responsible for renal failure, the striking histological feature was a uniform debasement and disappearance of tubular epithelium. In 2 patients with a clinical course of acute tubular necrosis, histological lesions could not be documented. All the 5 patients with acute tubular necrosis regained full recovery of renal function, 3 of them with the help of dialysis and 2 with conservative management. None of the 3 patients with acute cortical necrosis survived in spite of intermittent dialysis therapy.

Fatal complication of intravesical formalin during control of intractable hemorrhage from radiation cystitis.

Fatal acute tubular necrosis occurred in 1 patient in whom intravesical formalin was used to control massive persistent hemorrhage from radiation cystitis. A suggestion is made to monitor blood formic acid levels and institute prompt dialysis whenever these exceed 80 mg. per 100 ml. to avert such a catastrophe. Intravenous sodium bicarbonate appears to be indicated prophylactically in combating the associated metabolic acidosis due to absorbed formic acid.

Determination of erythrocyte superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, reduced glutathione and malonyldialdehyde in uremia.

Erythrocyte superoxide dismutase (SOD: EC 1.15.1.1), catalase (EC 1.15.1.6), glucose-6-phosphate dehydrogenase (G-6-PD: EC 1.1.1.49), reduced glutathione (GSH) and malonyldialdehyde (MDA) were studied in 27 patients with chronic and 11 patients with acute renal failure. A comparison with 15 age- and sex-matched healthy subjects showed that patients with both acute and chronic renal failure had significantly low G-6-PD (p less than 0.05) values whereas SOD, catalase and MDA showed significantly elevated levels (p less than 0.05). After adequate dialysis or renal transplantation the SOD, G-6-PD, catalase and MDA values returned to normal. The findings suggest that the erythrocyte SOD, catalase, and G-6-PD can undergo an adaptive alteration which however appears reversible.

Acute renal failure due to intravascular hemolysis in the North Indian patients.

Acute renal failure due to intravascular hemolysis is a common clinical problem in North Indian patients. It constituted 21.5 percent of 325 patients dialyzed for acute renal failure over an 11-year period at Chandigarh. Thirty patients had developed acute intravascular hemolysis in association with erythrocyte glucose-6 phosphate dehydrogenase (G-6PD) deficiency, 17 due to copper sulphate intoxication and 8 due to envenomation by snakes. Less frequent causes were insect stings, incompatible blood transfusion, intake of anti-leprosy drug--dapsone in non-G-6PD-deficient patients, and mercuric chloride toxicity in two patients each; naphthalene poisoning in one; and uncertain causes in six patients. Renal histology was available in 55 patients. Acute tubular necrosis was seen in 54 and bilateral diffuse cortical necrosis in one patient. Fifty patients (71.43 percent) survived and 20(28.6 percent) diet. G-6PD erythrocyte deficiency, which is present in 4.5 percent of the North Indian population, was the most frequent cause of acute renal failure in this group.

Spectrum of acute cortical necrosis in Indian patients.

Forty-nine out of 662 patients (7.4%) dialysed for acute renal failure were found to have bilateral renal cortical necrosis. Amongst 6061 autopsies carried out in our centre during the same period, the incidence of cortical necrosis was 0.7%. Obstetric causes were responsible for the renal lesion in 35 (71%) and non-obstetrical causes in 14 patients. In the obstetric group, cortical necrosis was observed in association with spontaneous or induced abortion in 39% and as a complication of late pregnancy in 33%. The non-obstetric causes included snake bite in 26 (12%), acute gastro-enteritis in 5 (10%), haemolytic uremic syndrome in 2 (4%) and G6PD deficiency with intravascular haemolysis in one patient (2%). Thirty-nine (80%) patients were anuric or severely oliguric throughout their illness but a steady rise in urinary output following a protracted phase of oligo-anuria was observed in ten patients. Forty-two (86%) patients died and seven survived. None of the survivors, however, achieved a normal renal function (Ccr 8 ml to 28 ml/min). The diagnosis of renal lesion was confirmed during life in 8 and after death in 41 patients. Morphological lesions were consistent with bilateral diffuse cortical necrosis in 39 (80%) and patchy lesions in 10 patients. Factors responsible for the high incidence of cortical necrosis amongst Indian patients have been high-lighted.

Does Convit vaccine (BCG + Mycobacterium leprae) afford protection against biochemical changes in renal brush border membrane in experimental leprosy?

Renal functional status in Mycobacterium leprae infected mice can be best studied by examining the enzymatic status of brush border membrane vesicles from proximal convoluted tubule. The role of vaccination in modulation of the renal status brought by the disease has been studied using this technique. The characteristic marker enzymes of renal brush border membrane--namely alkaline phosphatase, leucine aminopeptidase and gamma-glutamyl transpeptidase decreased significantly (p less than 0.01) in due course in M. leprae infection over a period of 9 months. The combined vaccine (BCG + M. leprae) may have a protective effect on renal abnormalities only in the initial stages of infection as indicated by a significant rise in enzymatic levels. However, no significant (p greater than 0.05) protective effect of vaccine was found in a more advanced disease state after 9 months in infected mice.

Transport of amino-acids across renal brush border membrane vesicles in Mycobacterium leprae infected Swiss albino mice--effect of Convit vaccine.

Brush border membrane vesicles prepared from kidneys of Mycobacterium leprae infected (non-vaccinated) and vaccinated-infected Swiss albino mice were used to assess the effect of Convit's combined vaccine (BCG + M. leprae) on amino acid transport activity across the tubular basement membrane. The protective effect of Convit's vaccine was more pronounced with respect to the uptake of L-alanine than L-aspartate. Uptake of L-lysine showed no significant difference in the different groups. Footpad counts followed characteristic growth curves in the non-vaccinated infected group but showed a lag in the development of peak levels in the vaccinated group. Further Convit's vaccine appeared to have a protective effect on renal impairment in the mouse model of leprosy in the initial stages of infection only, as indicated by the transient reversal of amino acid uptake and a diminution in the footpad counts induced by M. leprae infection. No significant (P > 0.05) protective effect of the vaccine was found in the advanced disease state.

Role of reactive oxygen species in renal damage in experimental leprosy.

Renal involvement is known to occur in leprosy. In the present study the possible role of reactive oxygen species (ROS) in causation of renal damage in mice infected with Mycobacterium leprae has been investigated. At least six animals from each group (control and infected) were killed at 0 day, 3, 6 and 9 months postinfection. The results showed a significant increase in the chemiluminescence (CL) response of peritoneal macrophages which was maximum between 3 and 6 months. No significant increase was observed in CL response of blood neutrophils. A significant increase in lipid peroxidation was observed at 3 and 6 months as evident by an increase in malondialdehyde levels. The increased ROS production might be the cause of lipid peroxidation. The renal damage is alos evident by decrease in the activity of renal brush border membrane enzymes, namely, alkaline phosphatase, leucine aminopeptidase and r-glutamyl transpeptidase. Thus ROS might play a role during early stages of M. leprae infection but in the later stages other immunological mechanisms may overpower the effect of ROS.

Free radical scavengers & lipid peroxidation in acute aluminium phosphide poisoning.

Free radicals scavengers superoxide dismuatase (SOD) and catalase and lipid peroxidation were studied in 45 patients of aluminium phosphide poisoning irrespective of age and sex admitted to a hospital in north India during the January 1992 to December 1993. Serial serum superoxide dismutase (SOD), catalase and MDA (malonyldialdehyde) were estimated on days 1, 2 and 5 post-admission depending on the survival of the patients. Serum SOD levels were significantly higher (P < 0.001) but serum catalase was significantly lower (P < 0.001) in patients than controls (patients of peripheral circulatory failure and normals) on days 1 and 2 which suggested stimulation of SOD and inhibition of catalase by phosphine resulting in excessive hydrogen peroxide (H2O2) load. Significantly higher levels of MDA (P < 0.001) in patients than controls on days 1 and 2 indicated enhanced lipid peroxidation in this poisoning. Twenty four patients died constituting a mortality rate of 53.3 per cent. The significantly high levels of SOD and MDA in non-survivors suggested their direct relation to mortality while catalase levels had an inverse relationship. Return of SOD and catalase and MDA to normal or near normal levels in survivors by day 5 suggested abolition of an oxidative stress due to elimination of phosphine.

Class specific antinuclear antibodies in systemic lupus erythematosus.

The incidence and significance of class specific antinuclear antibodies (ANA), specially with relevance to clinical manifestations of arthritis, renal disease and serositis was studied in 40 patients of systemic lupus erythematosus by the indirect immunofluorescent method. Clinical activity was scored by Morimoto's scoring system. A significant correlation was obtained between IgD ANA and clinical activity of the disease and IgG ANA exhibiting lupus pattern of immunofluorescence and serositis.