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Biomedical subjects

C Jacobs

Publications and source records attributed to C Jacobs.

At least 199 records · Page 11Linked to original sources
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↗
PubMed1992

Exogenous administration of IL-1 alpha inhibits active and adoptive transfer autoimmune diabetes in NOD mice.

Diabetes susceptibility in non-obese diabetic (NOD) mice may involve immune dysregulation resulting from cytokine deficiencies. The cytokine IL-1 plays a role in various immune as well as endocrine responses and may be hypoexpressed in NOD mice. Treatment with low levels of exogenous IL-1 alpha for 22 weeks prevented the naturally occurring insulitis and diabetogenic process in NOD mice during and at least 33 weeks after cessation of IL-1 alpha treatment. Treatment with IL-1 alpha also inhibited insulitis and hyperglycemia induced by adoptive transfer of pathogenic, polyclonal CD4+8- T cells. Even after islet-cell destruction, IL-1 alpha injections in diabetic NOD mice normalized plasma glucose levels when administered in combination with insulin, whereas equivalent levels of IL-1 alpha alone did not. Our studies support the hypothesis that IL-1 alpha suppresses autoimmune diabetes and hyperglycemia in NOD mice by pleiotropic effects on both immune and metabolic systems. Thus, IL-1 treatment could clinically be an effective immunotherapeutic modality for autoimmune diabetes mellitus by suppressing early disease progression or normalize plasma glucose levels when insulin is present.

Animals↗
PubMed1992

Pharmacokinetic parameters of recombinant mast cell growth factor (rMGF).

The gene product of the murine Steel (Sl) locus encodes an early-acting hematopoietic growth factor that is a ligand for the c-kit protooncogene. Several cDNAs for the Sl gene product, known as mast cell growth factor (MGF), stem cell factor (SCF), or kit ligand (KL), have recently been isolated, and both soluble and membrane-associated versions have been shown to be biologically active. The potential for therapeutic usage of recombinant MGF (rMGF) indicated a need for determining the biodistribution and elimination parameters of this cytokine. Pharmacokinetic studies demonstrated that radiolabeled rMGF had a distribution half-life of 2 min and an elimination half-life of 2.1 h in wild-type mice following iv injection, during which a striking localization of labeled rMGF in the lungs was noted. When administered by subcutaneous injection the elimination half-life was prolonged to 8.4 h. The primary sites of rMGF elimination appeared to be the kidneys and the liver. Pharmacokinetic analysis of labeled rMGF in mutant Sl/Sld mice, which are mast cell deficient, demonstrated similar distribution and elimination half-lives compared to wild-type mice (1.4 min and 1.8 h, respectively). In addition, the biodistribution pattern of the labeled rMGF in Sl/Sld mice was similar to that observed in wild-type mice, including the striking localization to the lungs. Binding of radiolabeled rMGF to lungs in vivo subsequent to iv injection was completely inhibited by excess unlabeled rMGF. Interestingly, mice that received an iv injection of the higher doses of rMGF (15 micrograms) demonstrated profound respiratory distress and hypotension within minutes of administration. Histologic analysis of lungs from such mice revealed extensive mast cell degranulation, which was associated with vasodilatation and pronounced hyperemia of virtually all pulmonary vessels. The respiratory distress in normal mice was probably a consequence of mast cell degranulation induced by rMGF since similar findings were not observed in Sl/Sld mice injected with identical concentrations of rMGF.

Animals↗
PubMed1992

[Value of tomodensitometry with injection and late images for the diagnosis of urinary leaks in kidney transplants].

Between May 1985 and May 1990, 263 renal transplantations were performed in 254 patients, with 4 kidney-pancreas double grafts. 12 urinomas were observed, i.e. 4.56%. In one half of cases, clinical examination alone was able to establish the diagnosis of urinoma, but in the other 6 cases, complementary investigations were required. Post-contrast computed tomography with late images (between 6 and 24 hours after the injection) would appear to be the most useful investigation. Performed in 6 cases, this examination established the diagnosis of urinoma in 5 cases and also suggested the mechanism of the leak, which was always confirmed at operation. The positive diagnosis is based on extravasation of contrast agent which is clearly visible, even in the presence of low concentrations due to impaired renal function. This extravasation occurred early in 3 cases, but was delayed in 2 cases, emphasising the importance of late images. Other investigations appear to be less useful either because of a lack of sensitivity or because of imprecise anatomical information. The severity of urine leaks and the need for rapid treatment justify post-contrast computed tomography with late images in any case of suspected urinoma.

Adult↗
PubMed1992

Inappropriate secretion of antidiuretic hormone (SIADH) in a patient with systemic lupus erythematosus (SLE): a case report.

The Syndrome of Inappropriate Secretion of Antidiuretic Hormone (ADH) or SIADH has been reported in a great variety of diseases and disorders of the central nervous system. However, to our knowledge only three cases [Kaplan et al., Decaux et al. 1981, Agus et al. 1983] of SIADH associated with systemic lupus erythematosus (SLE) have been described in the literature. We report here a new case of SIADH in association with SLE.

Adult↗
PubMed1992

[Which index to choose for quantification of the adequacy of filtration method in the hemodialysis patient?].

On the basis of a retrospective re-analysis of the data from the National Cooperative Dialysis Study, Sargent and Gotch have proposed the normalized index KT/V as an index of the level of dialytic therapy. However the current methods of calculating KT/V are complex for routine clinical use and require great care in order to avoid major inaccuracies on the estimation of dialyzer urea clearance and the subsequent calculation of the volume of distribution of urea. As the pre to post-dialytic plasma urea ratio C0/CF is a function of dialyzer urea clearance, duration of dialysis and urea distribution volume of the patient, it might well correlate with KT/V. The simplified index I = 1.2 x ln (C0/CF) is well correlating (r = 0.9; n = 15) and well approximating (3%) with KT/V and with other indexes derived from various formulas. Consequently the use of this index is electively proposed for routine determination of the quantification of dialysis.

Humans↗
PubMed1991

The use of probenecid as a chemoprotector against cisplatin nephrotoxicity.

Probenecid inhibits cisplatin (CP) secretion in humans and protects against CP-induced nephrotoxicity in rats. The authors conducted a Phase I trial of escalating doses of CP using probenecid as a chemoprotector. Fifty-four courses of CP at doses ranging from 100 to 160 mg/m2 were given by 24-hour infusion to 36 patients. There was no renal impairment at any dose. Ototoxicity, however, became the dose-limiting toxicity; 14 patients experienced a 20 or greater decibel (dB) loss. Seven percent of courses were associated with a leukocyte count of less than 1.5 x 10/microliters, and 19% with a platelet count of less than 50 x 10(3)/microliters. Only three patients developed neurotoxicity. Correlating pharmacokinetic data and toxicity, the authors found that high cumulative dose, area under the curve (AUC) for unbound platinum, and cumulative AUC were associated with ototoxicity and peripheral neuropathy. It was concluded that probenecid may protect against CP nephrotoxicity and warrants further investigation. Its unique mechanism of action and lack of toxicity make it ideal to combine with other chemoprotectors.

Adult↗
PubMed1991

Interleukin-1 beta regulation of islet and thyroid autoimmunity in the BB rat.

Daily injections of high dose human recombinant interleukin-1 beta (IL-1 beta) accelerated the onset of both insulin-dependent diabetes mellitus and lymphocytic thyroiditis in genetically prone BB rats. In diabetes-resistant BB rats, high dose IL-1 beta failed to induce diabetes. Additionally, the presence of neutralizing IL-1 beta antibodies in these rats strongly correlated with inhibition of lymphocytic thyroiditis. Since low dose IL-1 beta protects diabetes-prone rats from IDDM, we conclude that IL-1 beta is a potent modulator of autoimmune diabetes and thyroid disease in genetically susceptible rats.

Adrenal Glands↗
PubMed1991

Renal tolerance for ioxaglate in patients with chronic renal failure.

The authors sought to evaluate renal tolerance for ioxaglate sodium meglumine used as a contrast agent in patients with chronic renal failure. Eight male patients (mean age, 55 years +/- 5) with chronic renal insufficiency (glomerular filtration rate less than 60 mL/min) who underwent diagnostic cardiac catheterization were enrolled. Renal clearance of inulin and rho-aminohippuric acid and urinary enzyme excretion were studied 1 day before and 1 day after administration of 167 mL +/- 43 of ioxaglate. None of the patients experienced any adverse reactions. All the patients had markedly depressed renal clearance values before angiography. Mean serum creatinine level, glomerular filtration rate, effective renal plasma flow, and urinary beta 2-microglobulin excretion were unaltered by angiography. After the procedure, only one patient had an increase in serum creatinine level of more than 10% (from 115 to 159 mumol/L [1.3 to 1.8 mg/dL]), with a decrease in glomerular filtration rate from 34 to 27 mL/min. In this patient, serum creatinine level and glomerular filtration rate normalized within 72 hours. Using accurate and sensitive renal function tests, the authors have shown that ioxaglate may be used safely in patients with chronic renal failure.

Adult↗
PubMed1991

Nephrotoxicity of contrast media in high-risk patients with renal insufficiency: comparison of low- and high-osmolar contrast agents.

We have compared the renal effects of ioxitalamate, ioxaglate, and iopamidol in patients with chronic renal failure. Sixty consecutive patients with an estimated creatinine clearance (ECRCl) less than 60 ml/min were randomly assigned to receive either ioxitalamate, iopamidol, or ioxaglate. All patients received 500 cm3 isotonic saline before the procedure. Serum creatinine and ECRCl were estimated before, 1 and 2 or 3 days after the procedure. There was no statistical difference between the three groups with respect to age, sex, weight, renal function, amount of iodine, and type of procedure. Mean serum creatinine and ECRCl remained unchanged after administration of contrast media. No patient had nephrotoxicity or acute oliguria requiring dialysis as a result of the administration of contrast material. The number of patients with an increase in the serum creatinine level greater than 10% from the basal value did not differ in the treatment groups. The maximal increases in serum creatinine were 52 mumol/l (29%) in the ioxitalamate group, 56 mumol/l (18%) in the ioxaglate group, and 57 mumol/l (23%) in the iopamidol group (p = NS). Using a population carefully randomized and matched for renal insufficiency, we could not show any differences in nephrotoxicity between these three contrast agents. Clinically serious renal impairment was uncommon in our study, regardless of the contrast agent used. However, the interpretation of these favorable findings requires a cautionary note. All patients in this study were well hydrated before and after uro-/angiography, and none had a recent renal injury or a treatment with a nephrotoxic agent that would predispose to injury from contrast material.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

[Combined kidney-pancreas transplantation. Experience at the Urologic Clinic of the La Pitié Hospital].

The first attempts of pancreas transplantation were made in the middle of the 1960s and were further developed in the early 1980s with the coming of Cyclosporine. Various surgical techniques were used to carry out pancreas grafts; a total pancreatic transplantation with duodenovesical anastomosis was selected for 7 combined kidney-pancreas transplantations carried out during the past 18 months in our group. After a time lapse ranging from 18 months to 30 days, all patients were alive with functional kidney grafts. One patient only, who had lost his pancreatic graft, showed biological and histological signe of chronic rejection of his kidney graft. Five pancreas grafts are functioning, as is proved by the normal blood glucose and the normality of the markers. An immunosuppressant treatment was used in all similar cases, comprising, after an initial bolus of one gram of Methyl-Prednisolone, an initial four-drug treatment on 1/3 mg/kg/day of Prednisone, 7 mg/kg/day of Cyclosporine, 1 mg/kg/day of Imurel and, during the first fifteen days, the use of rabbit antithymocytic globulins. Ana analysis of the postoperative period revealed frequent local infectious complications, probably due to pancreatitis of the graft; however, in our experience so far, no pancreas graft was lost. The credit for this specific feature of our short series may be due to an exclusively subperitoneal approach for both the pancreas and the kidney transplantation, thus limiting the seriousness of postoperative infectious complications to a large extent.

Anastomosis, Surgical↗