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Biomedical subjects

R Kaplan

Publications and source records attributed to R Kaplan.

At least 73 records · Page 4Linked to original sources
PubMed1994

High-dose dextromethorphan in amyotrophic lateral sclerosis: phase I safety and pharmacokinetic studies.

Much interest has focused on the role of glutamate-mediated excitotoxicity in the etiopathogenesis of amyotrophic lateral sclerosis (ALS). We therefore conducted a phase I study of high-dose dextromethorphan (DM) in ALS. DM is a selective, noncompetitive antagonist of the N-methyl-D-aspartate subtype of the glutamate receptor. Thirteen patients were given DM in an escalating dose fashion, to a target of 10 mg/kg/day or the maximum tolerable dose, and then maintained on this dose for up to 6 months. Total daily doses ranged from 4.8 to 10 mg/kg (median, 7 mg/kg). Side effects were dose limiting in most patients. The most common side effects were light-headedness, slurred speech, and fatigue. Detailed pharmacokinetic and neuropsychology studies were performed. This study demonstrates the feasibility of long-term administration of high-dose DM in ALS, as well as in other conditions associated with glutamate excitotoxicity.

Adult↗
PubMed1993

Phase II trial of etoposide and cisplatin in patients with refractory and relapsed non-Hodgkin's lymphoma: Cancer and Leukemia Group B study 8351.

A phase-II study was conducted by the Cancer and Leukemia Group B (CALGB) in patients with refractory and relapsed non-Hodgkin's lymphoma (NHL) to assess the activity of the combination of etoposide and cisplatin. Sixty-five patients were entered on study, and 51 patients were evaluated for this report. The treatment regimen consisted of etoposide, 80 mg/m2 IV daily times 5 and cisplatin 20 mg/m2 IV daily times 5, repeated every 21 days. All patients had failed 1-3 prior chemotherapeutic regimens, had measurable disease, and had a performance status of 0-2. In the 51 evaluable patients, there were 4 complete responses (8%) and 12 partial responses (23%), for an overall response rate of 31% (95% Cl: 19%, 46%). In addition, 15 patients (29%) had some improvement in disease and 6 (12%) had stable disease. Failure-free survival for the 51 eligible patients was 40% at 3 months, 23% at 6 months, and 15% at 1 year. Significant toxicity was observed with this regimen. Severe neutropenia occurred in 20 patients (39%), severe anemia in 8 patients (16%), and severe thrombocytopenia in 18 patients (35%). One patient died of infection. Severe neurotoxicity (1) and hemorrhage (3) were also seen. The etoposide, cisplatin combination is active in NHL; however, in this dose and schedule their combined activity is only minimally better than published reports of etoposide alone. Further studies of related combinations are under evaluation by the CALGB.

Adolescent↗
PubMed1993

Microalbuminuria in a normotensive insulin-treated diabetic population.

Thirty-five insulin-treated diabetics without overt proteinuria or hypertension, and taking no antihypertensive medications were screened at three clinical centers for the presence of microalbuminuria. In addition to the presence of albuminuria, patients were evaluated for duration and type of diabetes, retinopathy, blood pressure, and degree of diabetic control. In these patients, it was possible to examine the degree of microalbuminuria as a function of systolic and diastolic blood pressures, age and sex of the patient, site of recruitment, duration of diabetes, and glycemic control. On multivariate statistical analysis, systolic blood pressure was the only factor that contributed to microalbuminuria. An additional 37 patients had urinary albumin excretion measured, although biochemical and clinical characteristics were incompletely determined. Blood pressures were documented to be normal in 23 of these individuals, while the other fourteen were normal by history. The range of urinary albumin excretion was comparable in the patients with complete data bases and those without. Overall, 22.2% of the normotensive insulin-treated patients screened had microalbuminuria, 5.5% had gross albuminuria, while 72.2% had normal urinary albumin excretion. We agree with previous reports that microalbuminuria is relatively uncommon in the normotensive diabetic population, but further conclude that even in the context of "normal" blood pressure, systolic blood pressure should be carefully observed in diabetic patients. It is possible that these individuals should be considered for more aggressive monitoring programs, e.g., ambulatory blood pressure recording.

Adult↗
PubMed1992

Modern methods of searching the medical literature.

OBJECTIVE: To review the methods of electronic retrieval of biomedical journal articles; to demonstrate CD-ROM and online searching techniques; and to compare major biomedical databases. DESIGN: A CD-ROM MEDLINE search was made by a medical practitioner, with the assistance of an experienced librarian. An online MEDLINE/Excerpta Medica search was made by the same medical practitioner after completion of a two-day course in search techniques. The search example covered the period 1983 to 1992, and the topic was "whether steroid use for asthma/airways disease leads to osteoporosis". OUTCOMES: Search duration, article yield and search cost were assessed. RESULTS: The CD-ROM MEDLINE literature search took 60 minutes to find 31 articles (43% of the possible articles). This compared with an online search to the Bibliographic Retrieval Services database in Chicago, which produced the same articles when MEDLINE was searched (but took only 16 minutes) and which also found 47 articles (with an overlap of only seven) when Excerpta Medica was searched. We estimated that the combined MEDLINE and Excerpta Medica search detected 93% of all known relevant articles, based upon an assumed gold standard. CONCLUSIONS: Online searching is a fast and powerful alternative to CD-ROM searching. Formal training is necessary for quick and cheap reference finding. Other benefits such as direct transfer from online searching to your own computer bibliography database make online searching of biomedical databases essential to consider.

CD-ROM↗
PubMed1992

Reduced glomerular thromboxane receptor sites and vasoconstrictor responses in diabetic rats.

Glomerular thromboxane production and urinary thromboxane excretion are increased in early diabetes, but in spite of this renal blood flow and glomerular filtration rate are significantly higher than in control animals. To study the possibility of a defect in thromboxane actions in the kidney, we have measured glomerular thromboxane receptors and the renal hemodynamic response to the administration of a stable thromboxane analog in diabetic rats. Glomerular thromboxane receptors were studied in hyperglycemic diabetic rats 7 to 10 days after injection of streptozotocin (65 mg/kg, i.v.) and in normal controls. Scatchard analysis of equilibrium binding using the thromboxane antagonist, [3H]-SQ29548, demonstrated one class of high affinity thromboxane receptor sites in control (Kd = 19.9 +/- 2.6 nM, N = 16) and diabetic rats (Kd = 19.8 +/- 2.1 nM, N = 8, P = NS). The number of thromboxane receptors was reduced by 44% in diabetic rats (control, 374 +/- 20 vs. diabetic, 210 +/- 21 fmol/mg, P less than 0.01). Thromboxane binding in diabetic rats was not restored to normal levels by thromboxane synthetase inhibition with OKY046. Diabetic rats had higher renal blood flow (diabetic, 7.03 +/- 0.18 vs. control, 6.33 +/- 0.13 ml/min, P less than 0.05) and glomerular filtration rate (2.42 +/- 0.10 vs. 1.96 +/- 0.07 ml/min, P less than 0.05). Infusion of the stable thromboxane agonist, U46619 (0.1 micrograms/kg/min), reduced renal blood flow and glomerular filtration rate in all animals, but the constrictor responses were blunted by 50% in hyperglycemic diabetic rats compared with normal controls or euglycemic diabetic rats (P less than 0.05). Control of blood glucose with insulin normalized the number of glomerular thromboxane receptor sites, reversed hyperfiltration and restored glomerular responses to thromboxane agonist. The abnormalities of glomerular thromboxane receptors are similar to changes in angiotensin II receptors, and suggest a generalized defect in vasoconstrictor receptors in the diabetic kidney.

Animals↗