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Biomedical subjects

C Jacobs

Publications and source records attributed to C Jacobs.

At least 55 records · Page 3Linked to original sources
PubMed1993

Comparative nephrotoxicity of carboplatin and cisplatin in euvolemic and dehydrated rats.

The aim of this study was to compare the renal tolerance of cisplatin and carboplatin in euvolemic and dehydrated rats. A total of 79 euvolemic or dehydrated male rats were randomly assigned to receive cisplatin (5 mg/kg body weight, i.p.), carboplatin (40 mg/kg body weight, i.p.) or vehicle. Body weight, serum creatinine, creatinine clearance, fractional excretion of sodium and urinary NAG excretion were recorded on days 1 and 5. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and renal histology were determined on day 5. In the euvolemic and dehydrated control and carboplatin groups we observed no change in serum electrolytes, serum creatinine, creatinine clearance, GFR and ERPF. In the euvolemic and dehydrated control groups we observed no change in urinary NAG excretion. Carboplatin induced a slight but significant increase in urinary NAG excretion. In dehydrated rats carboplatin induced a significantly higher increase in urinary NAG excretion than in euvolemic rats. Cisplatin induced a marked and significant decrease in GFR and ERPF, and a significant increase in NAG. Dehydration markedly potentiated cisplatin nephrotoxicity. Euvolemic rats treated with cisplatin exhibited slight renal lesions with a mean score which was similar to the control group. The most extensive lesions were observed in euvolemic and dehydrated cisplatin treated rats with tubular necrosis in the outer stripe of the medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Definitive end-stage chronic kidney failure after cisplatin treatment].

Renal failure secondary to CDDP is due to acute tubular necrosis and is usually reversible. We report 4 cases of definitive renal failure secondary to administration of cisplatin (CDDP). Three women and one man, mean age 40 +/- 8 years (24 to 64 years), at onset of dialysis are reported. They had received 1 to 4 courses of CDDP for an endometrial carcinoma (n = 2), a breast carcinoma or a thymoma. The mean total dose of CDDP was 447 +/- 169 mg (160 to 900 mg). There was no additional nephrotoxic drug. Before treatment serum creatinine concentration was normal (77 +/- 7 mumol per liter) in all patients. In 2 cases dehydration (due to vomiting and use of mannitol) occurred during CDDP treatment. One patient was treated 30 days after a nephrectomy. At the onset of dialysis, renal ultrasound was normal. In 3 cases dialysis was necessary within 15 days following chemotherapy. In one case renal function deteriorated progressively to end stage renal failure 12 months after CDDP treatment. Dialysis was performed in 3 cases by hemodialysis and in one patient by peritoneal dialysis. All patients remained more than 6 months on dialysis. Three patients died from their cancer. One patient, being considered cured from his thymoma, is currently being evaluated for a kidney transplantation. Our observations outline the potential severity of CDDP nephrotoxicity. Systemic hydration with serial serum creatinine measurements are mandatory during and after CDDP administration these patients.

Adult↗
PubMed1993

[Renal effects of endothelins].

Since the discovery of endothelin in 1988, numerous studies have been undertaken to evaluate their physiopathologic role. There is three types of endothelin ET-1, ET-2 and ET-3, which probably play an essential role in renal and cardiovascular homeostasis. Their principal actions consist in an increase of the arterial pressure, a negative inotrope and chronotrope effect, a coronary vasoconstriction, a decrease in cardiac output and a fall in the renal blood flow and glomerular filtration rate. An elevation of endothelin level has been reported in numerous clinical conditions. However the interest of these descriptions remains unclear. Indeed the absence of pharmacological inhibitors of the synthesis or effect of endothelin prevent the understanding of the interest of these abnormalities. Furthermore the endothelins should not be considered as a hormone but as a paracrine substance.

Animals↗
PubMed1993

Chronic cisplatin nephropathy in rats.

The long-term renal effects of cisplatin have been very poorly studied. Therefore we investigated the chronic renal effects of various doses of cisplatin in three groups of male Sprague-Dawley rats. Group I received two injections of 5 mg/kg body weight (bw) at 4-week intervals, group II four injections of 2.5 mg/kg bw at 4-weeks intervals, and group III one injection of 5 mg/kg bw and four injections of 2.5 mg/kg bw at 4-weeks intervals. Controls received an equivalent amount of isotonic saline. Each group was evaluated 1, 3, or 6 months after the last injection of cisplatin. One, 3 and 6 months after the last injection, cisplatin induced a marked decrease in glomerular filtration rate (GFR) evaluated as clearance of [99mTc]DTPA and creatinine clearance in all treated rats. Urinary NAG excretion remained unaltered. At 3 months post-cisplatin treatment GFR was significantly less (P < 0.05) in group III (0.18 +/- 0.02 ml/min/100 g bw) when compared with group I (0.23 +/- 0.02 ml/min/100 g bw) or II (0.23 +/- 0.04 ml/min/100 g bw). In group I GFR was similar 1 month (0.24 +/- 0.02), 3 months (0.23 +/- 0.02) and 6 months (0.23 +/- 0.03 ml/min/100 g bw) after cisplatin treatment. Cisplatin induced atrophy and dilatation of tubules with mononuclear cell infiltration associated with cyst formation. The glomerular and tubulointerstitial lesions were significantly enhanced in group III when compared with groups I and II. This study indicates that repeated administration of cisplatin may induce a chronic tubulointerstitial nephropathy associated with a marked decrease in GFR, which is stable over time. The incidence and severity of chronic cisplatin toxicity is dose-related and is not modified by dividing the dose.

Animals↗
PubMed1992

[Amplification of a circulating CD4+CD7- T lymphocytes subset in kidney transplantation].

A minor subset of CD4+ T-cells (10 +/- 4 percent) that does not express the CD7 antigen is detectable in normal individuals. These CD4+CD7- T-cells have lower proliferative capacities than autologous CD4+CD7- T-cells. We observed an expansion of CD4+CD7- peripheral T-cells in 45 kidney transplant recipients. The CD4+CD7- TL expansion (23 +/- 20 percent was observed in both short term (< 6 months, n = 20) and long term transplanted patients (> 3 years, n = 25). These results significantly differed from those observed in patients on dialysis (10 +/- 4 percent, P < 0.002). The percentages of CD4+CD7- TL in kidney recipients are significantly correlated with the percentages of CD4+CD57+ and CD8+CD57+ T-cells subsets. A three-color immunofluorescence analysis indicated that 75 percent of the CD4+CD7- TL express the CD57 molecule contrasting with those in normal individuals (0.3 percent). Purified CD4+CD7- T-cells from kidney recipients have lower proliferative responses after PHA, CD2 and CD3 stimulations than autologous CD4+CD7+ TL. The proliferative response is partially restored by the addition of anti-CD28 moAb or IL2. We have highlighted, in kidney recipients with good graft function, an expansion of CD4+CD7- T lymphocytes which could be associated with CD4+ T-cell anergy and tolerance.

Antigens, CD↗
PubMed1992

Renal function and blood pressure in patients receiving long-term, low-dose cyclosporine therapy for idiopathic autoimmune uveitis.

OBJECTIVE: To determine the renal side effects of long-term, low-dose cyclosporine therapy (initial dose, 5 mg/kg body weight per day) in patients with autoimmune idiopathic uvetis. DESIGN: Cohort study with at least 2 years of follow-up. SETTING: A teaching hospital in Paris, France (Hôpital Pitié-Salpétrière). PATIENTS: Sixteen patients with idiopathic autoimmune uveitis who were normotensive and had normal renal function before treatment. Cyclosporine was administered orally for at least 2 years at an initial dosage of 5 mg/kg body weight per day. RESULTS: After 2 years of treatment, the serum creatinine level increased by 35 +/- 5 mumol/L (0.40 +/- 0.06 mg/dL) (95% CI, 25 to 46 mumol/L, [73 +/- 4 to 108 +/- 4 mumol/L]). Creatinine clearance decreased significantly from 120 +/- 5 mL/min to 75 +/- 4 mL/min. Glomerular filtration rate decreased from 116 +/- 8 mL/min to 75 +/- 3 mL/min, and effective renal plasma flow decreased from 455 +/- 24 mL/min to 338 +/- 30 mL/min (P less than 0.05). Cyclosporine induced a significant increase in serum uric acid, total cholesterol, and serum potassium levels. Blood pressure was normal in all patients before treatment; 81% (95% CI, 64% to 98%) of these patients developed hypertension after 24 months of treatment. Blood pressure was controlled with a single drug in all but two patients. CONCLUSIONS: In patients with healthy native kidneys, long-term cyclosporine therapy, even at a low dose (5 mg/kg per day), is nephrotoxic and is associated with a high incidence of hypertension.

Adult↗
PubMed1992

Mutation of serine residue 318 in the class C beta-lactamase of Enterobacter cloacae 908R.

The involvement of the serine residue 318 in the specificity of a class C beta-lactamase was investigated. Multiple site-directed mutants at this position were generated using a polymerase chain reaction technique. These mutants were then probed for their activity towards various beta-lactam compounds. One mutant, S318G was further purified and its physico-chemical and catalytic properties determined. It was shown that the observed minimal inhibitory concentration values of this mutant could be correlated to its kinetic properties using a 'diffusion-hydrolysis' model. However, the data showed that residue 318 has little influence on the specificity of class C beta-lactamases.

Base Sequence↗
PubMed1992

Enhanced release of cytokines, interleukin-2 receptors, and neopterin after long-distance running.

This study was designed to examine cytokine production in a group of 22 well-trained runners covering a distance of 20 km within 2 hr. After running, all participants displayed a marked granulocytosis for 7 hr. Plasma neopterin levels increased 1 hr after exercise for 24 hr. Except for interleukin-6 (IL-6), cytokines were not reliably detected in plasma but were present in urine. Already before exercise, cytokines were detected in the urine of runners when compared to sedentary controls. Directly after running, interferon-gamma and tumor necrosis factor-alpha were further elevated but rapidly declined to preexercise levels. Interleukin-1 beta and interleukin-6 increased at a slower rate after exercise but secretion into urine persisted longer until 12 and 7 hr, respectively. Interleukin-2 (IL-2) was not detected but soluble IL-2 receptors appeared in the urine directly after running. Enhanced cytokine levels were accompanied by an only low creatinin kinase increase, indicating little muscle damage. These data show that long-distance running elevates cytokine production which supports the concept that regular, but not excessive, physical exercise may be beneficial by maintaining a stimulated immune system.

Adult↗
PubMed1992

Gd-DOTA: evaluation of its renal tolerance in patients with chronic renal failure.

Gd-DOTA is an intravenous contrast medium used in MRI. The clinical and biological tolerance of Gd-DOTA was studied in patients with chronic renal failure (e.g., those having a glomerular filtration rate of less than 60 mL/min). Twenty patients were randomized into two groups. In the control group, spin-echo (SE) T1- and T2-weighted images of the kidneys were obtained without injection of Gd-DOTA. In the DOTA-group, patients received 0.1 mmol/kg of Gd-DOTA. SE T1-weighted images were obtained before and after injections; a T2-weighted sequence was performed before injection. Clinical data, serum creatinine, and laboratory parameters were estimated before, and 24 and 48 hr after MRI. No adverse reaction was reported after injection of Gd-DOTA. Mean serum creatinine and glomerular filtration rate remained unchanged in both groups. For five patients in the control group and three patients in the DOTA-group the serum creatinine levels increased more than 10% and less than 25%. No evidence of nephrotoxicity was observed with Gd-DOTA in patients with chronic renal failure.

Contrast Media↗
PubMed1992

Endothelin in chronic renal failure.

The aims of the present study were to determine plasma endothelin (ET) in chronically uraemic patients, the renal clearance of endogenous ET in normal dog and man, and the effect of acute volaemic expansion on ET. The mean plasma ET concentration in haemodialysis patients was 57.5 +/- 5 pg/ml before haemodialysis and remained unchanged at 52.5 +/- 5 pg/ml after haemodialysis. They were thus significantly elevated both before and after haemodialysis (P less than 0.01) compared with plasma ET in normal subjects of 20.8 +/- 0.8 pg/ml. There was no evidence of ET clearance across the cuprophane membrane of the dialyser. Resting plasma ET values in the 15 non-dialysed uraemic patients ranged between 20 and 52.5 pg/ml (mean 38.2 +/- 2.3 pg/ml), significantly greater than those observed in controls (P less than 0.01). In CAPD patients, plasma ET was also significantly (P less than 0.01), elevated (63 +/- 10 pg/ml) when compared to controls, and similar to those observed in patients before haemodialysis. In dogs, mean ET did not diminish between the aorta and the renal vein (28.1 +/- 1 versus 28.4 +/- 2 pg/ml). In man mean ET did not significantly decline between the renal artery and the renal vein (17 +/- 3 to 13 +/- 0.8 pg/ml). In the seven healthy subjects who received 2000 ml of isotonic saline intravenously ET remained unchanged (24 +/- 2; 23 +/- 1 and 23 +/- 2 pg/ml before and 1 and 2 h after starting hydration respectively). We have thus shown that plasma ET is elevated in patients with chronic renal failure especially those on dialysis and CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Avoidance of endotoxin-induced inflammation during studies of albumin clearance from caprine joints.

Intra-articular injection of radiolabelled, commercial goat serum albumin (GSA) produces acute arthritis in caprine joints. This inflammation distorts clearance values and vitiates studies of normal lymphatic function. Endotoxin, routinely found in commercial albumin preparations, appears to cause this local reaction. We describe a simple method for the preparation of low-endotoxin, radioiodinated serum albumin from aseptically collected serum. We have used this technique to prepare GSA for use as a tracer molecule in clearance studies of synovial joint lymphatic function. The isolated protein exhibits antigenic and chemical characteristics indistinguishable from those of commercial GSA but contains at least 1000-fold less endotoxin. In contrast to commercial GSA preparations, this albumin does not produce local inflammation when injected into synovial joints and is cleared from caprine joints in the normal monoexponential manner. Low levels of endotoxin seriously distort studies of articular albumin kinetics and may induce comparable artifacts when commercial protein preparations are used to study other physiological systems.

Animals↗
PubMed1992

Effects of cyclosporine on tubular acidification function in patients with idiopathic uveitis.

Renal tubular acidification function was studied in 12 patients treated with cyclosporine (Cy) for idiopathic uveitis (IU) and in 5 patients with IU not treated with Cy. After intravenous bicarbonate loading fractional bicarbonate excretion was similar in both groups indicating normal proximal tubular acidification function. Plasma renin activity, plasma aldosterone and transtubular potassium gradient were similar in both groups. Distal hydrogen ion secretion evaluated by the ability to increase urine-blood (U-B) pCO2 in a highly alkaline urine was impaired in Cy-treated patients (31.8 +/- 3.2 mm Hg) as compared to controls (47.9 +/- 0.5 mm Hg) (p < 0.005). We conclude that Cy therapy is associated with a distal acidification defect with a low U-B pCO2 gradient during sodium bicarbonate loading. Because none of our Cy-treated patients spontaneously developed over metabolic acidosis one could classify them as having an incomplete form of distal tubular acidosis.

Acidosis, Renal Tubular↗
PubMed1992

Reappraisal of long-term renal replacement therapy. Renal transplantation: medical versus statistical approach.

The validity of the numerous statistical methods used for the assessment of the results achieved with renal transplantation performed for terminally uremic patients may be challenged by a medicalized approach of the patient's post transplantation course and outcome. This assumption has been applied to a population of 700 patients who received a grafted kidney in our unit between November 1972 and December 1990. Among 77 patients who had been followed up for 10-15 years after grafting, 75% had not suffered any serious related complication during the first decade after transplantation. In contrast, among the whole transplant population, transplantation entailed either a rapidly fatal issue due to an unpredictable and irreversible complication in 45 patients (6.4%), or a state of chronic illness with severely disabling complications in 150 others (21.5%). At present, the main cause of concern remains, however, the persistent long-term graft loss due to chronic rejection. Nevertheless, the advances and results achieved in the field of organ transplantation in recent years justifies the policy which privileges renal transplantation as the first-choice method of renal replacement therapy for every terminally uremic patient aged less than 60-65 years in whom careful workup does not reveal any clinical/psychological contraindication.

Actuarial Analysis↗
PubMed1992

A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck.

PURPOSE: To determine whether combination chemotherapy is superior to single agents for recurrent/metastatic head and neck cancer, we compared the efficacy and toxicity of cisplatin (CP) and fluorouracil (5-FU), alone and in combination in a phase III trial. PATIENTS AND METHODS: Two hundred forty-nine patients with recurrent head and neck cancer were randomized to one of three treatments: CP (100 mg/m2) and 5-FU (1 g/m2 x 4), CP, or 5-FU every 3 weeks. RESULTS: The overall response rate to the combination (32%) was superior to that of CP (17%) or 5-FU (13%) (P = .035). Response was associated with good performance status (PS) but not with primary site, site of recurrence, histology, prior irradiation, or relative dose intensity. Median time to progression was less than 2.5 months, and there was no significant difference in median survival (5.7 months) among the groups. By multivariate analysis, patients with better PS and poorly differentiated tumors had superior survival. Hematologic toxicity and alopecia were worse in the combination arm. CONCLUSION: Although the response rate to the combination of CP plus 5-FU was superior to that achieved with single agents, survival did not improve.

Analysis of Variance↗
PubMed1992

In vivo effects of interleukin-1 beta on blood leukocytes in BB rats prone or resistant to diabetes.

Previous studies have determined that daily low dose injections of the potent cytokine interleukin-1 beta (IL-1 beta) decreased the frequency of insulin-dependent diabetes mellitus (IDDM) in diabetes-prone (DP) BB rats. In contrast, high dose injections induced an earlier than normal onset. In this study we tested whether the effects of daily human recombinant IL-1 beta injections on leukocyte subsets were associated with its modulation of IDDM onset in BB rats. Prior to the onset of IDDM in DP BB rats, high dose IL-1 beta induced leukocytosis (P less than 0.05), neutrophilia (P less than 0.01), and monocytosis (P less than 0.001). At the onset of IDDM, lymphocyte (P less than 0.01) and neutrophil (P less than 0.001) numbers were increased in high dose treated DP rats but not in rats given saline or low dose IL-1 beta. In 60-day-old diabetes-resistant (DR) BB rats, neurophilia was induced by both low (P less than 0.05) and high (P less than 0.001) dose IL-1 beta without the development of IDDM. At 130 days of age, when the rats were killed, it was discovered that 14/22 (64%) IL-1 beta injected DR rats developed neutralizing IL-1 beta antibodies. Significantly lower neutrophil numbers were observed in high dose DR rats which developed IL-1 beta antibodies compared with those which did not (P = 0.032). Thus, neutrophilia was dissociated from high IL-1 beta acceleration of IDDM onset.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗