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Biomedical subjects

C Jacobs

Publications and source records attributed to C Jacobs.

At least 235 records · Page 13Linked to original sources

Modification of cisplatin toxicity with diethyldithiocarbamate.

Diethyldithiocarbamate (DDTC), a heavy metal-chelating agent, has been shown to decrease cisplatin (CP) toxicity in preclinical studies. This phase I dose-escalation study was undertaken to investigate DDTC as a chemoprotector in patients with advanced cancer. Thirty-five courses of CP in doses ranging from 120 to 160 mg/m2 were given intravenous (IV) bolus to 19 patients. DDTC at 4 g/m2 was infused over 1 hour, starting 45 minutes after CP. There was minimal nephrotoxicity with a mean creatine clearance of 99 mL/min +/- 4 pretreatment and 86 mL/min +/- 4 on day 21. Two courses were associated with a WBC count less than 2,000/mm3 and one course with a platelet count of 15,000/mm3. Two patients had grade 2 neurotoxicity. Hearing loss occurred in 11 patients: five greater than or equal to 20 dB, five greater than or equal to 40 dB, and one greater than or equal to 60 dB. All patients who received cranial irradiation had ototoxicity compared with 43% of those without radiation (P less than .05). All patients experienced toxicity during the DDTC infusion, including hypertension, flushing, diaphoresis, agitation, and local burning. We conclude that DDTC can protect against CP nephrotoxicity at doses up to 160 mg/m2. Ototoxicity became the dose-limiting factor.

Adult↗

[Demographic development and methods of treatment for end stage chronic uremia in aged patients over 65 years in France during the 1980's. Committee of the EDTA Registry].

The data that constitute the basis for this analysis come from the files of all the French patients over 65 years registered on the EDTA-ERA Registry between 1980 and 1990. The percentage of these patients treated by regular dialysis, which was of 14% in 1980 has increased to 24% in 1989. Most of these patients are treated by centre hemodialysis. Survival has significantly improved: in 1984 the mortality reached 54.4% at three years in patients aged 65-75 and 44.4% in the over 75 years group.

Aged↗

Hemolytic uremic syndrome in patients with Behçet's disease treated with cyclosporin A: report of 2 cases.

Hemolytic uremic syndrome (HUS) has been reported in patients treated with cyclosporin A (CsA) following bone, hepatic and kidney transplantation. We report two patients with Behçet's disease (BD) under CsA treatment because of severe uveitis, who developed HUS several months after the initiation of treatment. Renal biopsies showed lesions consistent with the diagnosis of the arterial form of thrombotic microangiopathy: vascular thrombosis with extensive glomerular ischemia. Renal failure persisted after withdrawal of CsA: one patient is in chronic renal failure (CRF) with a 4-year follow-up; the other died after refusal of chronic hemodialysis. In our two patients, excessive doses of CsA with high trough levels are likely to have contributed to the development of HUS. A rapid adjustment of CsA doses and an early detection of signs of the microangiopathic process might have prevented this severe complication of CsA treatment.

Adult↗

[Continuous ambulatory peritoneal dialysis. Current concepts after 10 years' experience].

Designed, in contrast with hemodialysis (HD), as a permanent dialysis procedure, CAPD progressively established itself as an accepted mode of therapy of end stage renal disease. About 8 p 100 of the total population currently undergoing renal replacement therapy in France is being treated by CAPD. Important technical advances were made over the last decade. The recent disconnectable systems reduced the rate of peritonitis down to one episode every two to three years of treatment. Loss of ultrafiltration and sclerosing peritonitis can also be efficiently prevented. Maintenance of an adequate nutritional status in the patients remains however an often difficult problem. CAPD is now preferably recommended for young patients awaiting renal transplantation, diabetics, children and also elderly patients provided a satisfactory nutritional status can be maintained over time. Although a randomized study is not practically feasible, it can be stated that HD and CAPD yield similar overall results in comparable groups of patients with end stage renal disease. Long term studies do not show any substantial decrease over time of the permeability and clearance performances of the peritoneal membrane.

Adolescent↗

The effects of diltiazem on methotrexate-induced nephrotoxicity.

We have tested the effects of calcium channel blockade with diltiazem on methotrexate-induced nephrotoxicity in patients with biopsy-proven malignant disease. The patients were randomized in a cross-over fashion to receive MTX (4 g.m-2 body surface area) with or without Diltiazem (360 mg per day orally) during two consecutive periods separated by a 3-week interval. Methotrexate caused reversible acute renal failure, with an increase in serum creatinine from 89 (7)mumol.l-1 on day 0 to 150 (6)mumol.l-1 on Day 6. The patterns of beta 2-microglobulin and N-acetyl glucosaminidase urinary excretion were similar, with a sharp increase from Day 0 to Day 3. Urinary beta 2-microglobulin excretion increased from 161 (57) micrograms.l-1 on Day 0 to 1160 (840) micrograms.l-1 on Day 3 and fell to 918 (530) micrograms.l-1 on Day 10. Urinary N-acetyl glucosaminidase excretion increased from 250 (100) mmol.h-1 per mg of creatinine on Day 0 up to 655 (261) on Day 3 and fell to 285 (82) on Day 10. The evolution of renal function was not influenced by diltiazem. In patients receiving diltiazem, serum creatinine increased from 93 (0) mumol.l-1 on Day 0 to 151 (68) mumol.l-1 on Day 6 (p = NS when compared with control values). Urinary enzyme excretion also markedly increased from Day 0 to Day 3 to the same extent as in the group not receiving diltiazem. Our data indicate that acute deterioration in renal function caused by methotrexate is accompanied by tubular damage. Diltiazem was ineffective in preventing the acute renal failure induced by methotrexate.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Disopyramide-induced hypoglycemia: case report and review of the literature.

Disopyramide is a group I antiarrhythmic drug which is mainly used for the treatment of ventricular and supraventricular rhythm disturbances. Commonest side effects result from disopyramide's anticholinergic activity. Other side effects such as hypoglycemia have been reported less frequently. We report one observation of disopyramide induced hypoglycemia, and a review of the literature is presented. Including our observation, 14 cases (9 men and 5 women, aged from 41 to 88) have so far been reported. Doses of disopyramide ranged from 200 to 1,200 mg per day, administered from one day to one year. Symptomatology was mainly neurologic (12 patients) and two patients were clinically asymptomatic. The outcome was favorable in all but the 2 patients who died with persistent hypoglycemia after a single dose of 250 mg in one patient and after 400 mg daily during 4 days in the other (without stopping the drug). Renal function was markedly impaired in 9 patients, two of these patients being on a long term dialysis therapy. Blood levels of disopyramide were measured in 7 patients and ranged from 1 to 11.4 ng/ml. In five patients it was in the normal range (1-4 ng/ml). Three patients were rechallenged for disopyramide: hypoglycemia occurred in all, without clinical symptoms in two of them. The main risk factors of disopyramide induced hypoglycemia are a preexisting chronic renal failure, advanced age, and malnutrition. In these patients normally non toxic disopyramide blood levels, as defined in normal subjects, seem to be inappropriately high. We suggest that in patients at risk, disopyramide blood levels should be maintained at the lower range of therapeutic level.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Clinical aspects of continuous ambulatory and continuous cyclic peritoneal dialysis in diabetic patients.

The treatment of end-stage renal diabetic nephropathy remains a challenge. A large experience allows us to clearly outline the advantages and the drawbacks of continuous ambulatory peritoneal dialysis (CAPD) and continuous cyclic peritoneal dialysis (CCPD). Eighty-one patients, mean age 51.3 years, were treated over the last 9 years by CAPD-CCPD. Extrarenal complications, mainly vascular lesions, were present in this high-risk group of patients. The technique was modified in order to inject intraperitoneally, 4 times per day, insulin to control blood glucose level in CAPD patients. Actuarial survival was 92% at 1 year, 50% at 4 years mainly influenced by age: 85% survival at 2 years in 35 patients aged less than 50 years old and 62% at 2 years in 46 patients aged more than 50 years old. The main causes of death were of cardiovascular origin: myocardial infarction, stroke, atherosclerotic vasculopathy. The main causes of transfer to hemodialysis were due to technical complications. Peritonitis rate was one episode every 14 patient-months. Control of blood pressure, blood glucose levels, main biological parameters, and visual status were the clear advantages of the method. Peripheral vascular disease is not influenced by the technique. CAPD-CCPD is the technique of first choice in young diabetics and the preferential technique for home dialysis.

Actuarial Analysis↗

Will the "short dialysis" of the eighties be adequate?

Almost 30 years have elapsed since the first successful attempts by Scribner and his associates of the Seattle Group to sustain life for an unlimited period of time in patients with end-stage renal failure. More than 250,000 patients are currently treated worldwide with various methods of maintenance dialysis, with survival rates reaching 75% at 10 years and 65% at 15 years reported by experienced groups. Such results are all the more remarkable (and initially unexpected) both because maintenance hemodialysis can replace only partially the numerous sophisticated regulatory functions of the normal kidney and despite our persistent ignorance of many factors involved in uremic toxicity. Moreover, an entirely new, multifaceted pathology has developed in the population of patients submitted to long-term hemodialysis as a consequence of the permanently incomplete correction of the uremic syndrome together with the multiple disorders and complications induced by dialysis and its related therapeutic procedures. In this context, the key question concerning the optimal duration of hemodialysis required to provide patients with a life as close to normal as possible, and in the highest conditions of safety and comfort, remains a matter of ongoing debate. The advances made through the years in understanding the mechanisms of many of the complications occurring in hemodialyzed patients have generated the concept of "adequate" dialysis. According to this concept, the weekly amount of dialysis delivered to a patient is the basic factor that must be considered in terms of a prescription; the weekly duration of dialysis represents only one variable among many that must be taken into account to define a "dialysis strategy" for a given patient. The large body of knowledge accumulated over time concerning the multiple aspects of the pathology arising in hemodialysis patients has contributed to the development of many technical advances; these have allowed ever more efficacious and safe control of the clinical and biologic disturbances caused by long-lasting terminal uremia. The average weekly dialysis time of 24 to 40 hours 25 years ago was reduced to less than 12 hours in the '70s and currently may be as few as 6 hours. Will the criteria for "adequate" dialysis be met in the long run despite this dramatic reduction in weekly dialysis time? That is the question to which this paper attempts to suggest at least a partial answer. We shall limit the scope of this study to the theoretical and practical problems relevant to maintenance hemodialysis therapy. Those specific to hemofiltration will not be discussed here.

Humans↗

Recombinant interferon-gamma in the treatment of recurrent nasopharyngeal carcinoma.

The etiologic relationship of the Epstein-Barr virus (EBV) to nasopharyngeal carcinoma prompted this study of the efficacy of interferon-gamma (IFN-gamma), which possesses antiviral and antitumor activity, in the treatment of recurrent carcinoma. Fourteen patients received recombinant IFN-gamma in daily intramuscular doses of 5-10 X 10(6) U/m2. Of 13 patients evaluable for response, five had a minor response; disease was stable in two and had progressed in six. EBV serology for immunoglobin (Ig) G, IgA-VCA, and early antigen was measured in six patients. In four of these, titers rose consistently with disease progression and in one patient, titers decreased with minor response.

Adult↗

Recovery of renal function in patients treated by CAPD.

Recovery of renal function was observed in 10 out of 300 patients (3.3%) treated by CAPD. These 10 patients presented the following primary renal diseases: 4 nephroangiosclerosis, 4 interstitial nephropathies, 1 diabetic nephropathy, 1 unknown nephropathy, and were treated by CAPD for a mean period of 10.2 +/- 5.5 months. CAPD was discontinued when residual renal function reached 12 ml/min. After recovery 8 patients were still alive, including 1 patient who returned to dialysis. 2 patients died. When risk factors such as uncontrolled hypertension, cardiac failure, severe nephrotic syndrome, rapidly progressive renal failure, analgesics or non steroidal anti-inflammatory drug treatments or abuses, chronic urinary obstruction, cholesterol emboli were associated with end stage renal failure, CAPD should be the dialysis treatment of choice, expecting the preservation of the kidney capacities and further a recovery of renal function.

Aged↗

Idiopathic acute interstitial nephritis associated with anterior uveitis in adults.

Concomitant renal and ocular lesions have been described in a few systemic diseases. The association of acute interstitial nephritis (AIN) and anterior uveitis without determined cause was first described in children. Recently, the same clinical association has been reported in adults. We report 3 cases of this association and present a review of the literature. Including our 3 patients, 7 cases of this association have been reported in adults. All patients were females aged 27-74 years. Initial symptoms were either ocular, or pseudoviral (fever, myalgia and fatigue). Histological renal studies revealed acute interstitial nephritis with tubular lesions. Immunofluorescence and electron microscopy were not contributive. Ocular prognosis was always good. In 5 patients, the evolution of renal function was excellent with complete resolution of acute renal failure within a few weeks. Chronic renal failure developed in two of the four patients who did not receive systemic steroid therapy (with evolution towards terminal renal failure in one patient). Three of the patients received 60 mg per day of prednisone and none of them developed chronic renal failure. Despite the small number of patients reported and the possibility of spontaneous regression, these data suggest a beneficial effect of systemic steroid therapy to prevent or reduce interstitial inflammation and subsequent fibrosis.

Acute Disease↗