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Biomedical subjects

J Rubin

Publications and source records attributed to J Rubin.

At least 235 records · Page 13Linked to original sources
PubMed1985

Substitution of a starch polymer for glucose in peritoneal dialysis.

We compared a starch-derived polymer (molecular weight = 900) as the osmotically active agent in peritoneal dialysate (3 and 6% solutions) to results obtained with commercially available glucose dialysate (1.5 and 4.25%). 12 dogs were dialyzed with glucose for 7 days, and 9 received the polymer for 5 days. For dialysate exchanges with an intraperitoneal residence of 240 min the 1.5 and 3% solutions generated similar volumes of ultrafiltrate as did the 4.25 and 6% solutions. However, for exchanges of 960 min the 1.5% dialysate was significantly reabsorbed when compared to the other dialysate concentrations. The serum polymer concentration increased with continued dialysis. The rate of transfer from dialysate to serum in man must still be determined. The lower diffusivity of the polymer will certainly be evidenced. For certain clinical applications where diminished ultrafiltration occurs, the polymer may be of benefit to man.

Animals↗
PubMed1985

Demographic factors associated with dialysis technique failures among patients undergoing continuous ambulatory peritoneal dialysis.

We evaluated factors that would predict a successful outcome on continuous ambulatory peritoneal dialysis. We found that poverty, the need for a helper to carry out the dialysis, and physician allocation to therapy was associated with a poorer technique success. Neither age, education, marital status, sex, rural home, nor the presence of diabetes were important risk factors by themselves.

Adolescent↗
PubMed1984

Phase II study of recombinant leukocyte A interferon (rIFN-alpha A) in disseminated malignant melanoma.

Thirty-one patients with disseminated malignant melanoma received intramuscular recombinant leukocyte A interferon (rIFN-alpha A), 50 X 10(6) units/m2 three times weekly for a planned treatment duration of 3 months. Seven objective regressions (23%), which ranged in duration from 3 to 11.2+ months, were observed. Forty-two percent of 12 patients who were fully active (Eastern Cooperative Oncology Group [ECOG] performance score, 0) responded compared to 11% of 19 patients with impairment of performance status (ECOG, 1-3). Prior chemotherapy did not influence response rate. For all patients the median time to progression and of survival was 2 months and 6 months, respectively. Four patients had partial regressions in soft tissue (3, 4.6 months), pulmonary (7 months), and prostatic lesions (3 months). The latter was biopsy-proven and assessed by serial computerized tomography (CT) scans. Three had complete regressions of soft tissue disease (2 patients, 6.4 and 10+ months each), and liver involvement (11.2+ months). The major toxicities were moderate to severe fatigue (87%), anorexia (58%), and confusion (23%). Performance score deteriorated in 84% of patients during the time they were receiving rIFN-alpha A. Among the 13 patients whose tumors did not progress for at least 12 weeks, 7 required dose reductions or termination of treatment due to toxicities. Hematologic and hepatic toxicity was transient and of little clinical significance. The study indicates that rIFN-alpha A has some antitumor activity accompanied by difficult side effects in patients with disseminated malignant melanoma.

Adult↗
PubMed1984

Failure of bleomycin to improve the therapeutic effects of a combination of cyclophosphamide, doxorubicin, and cisplatin (CAP) in advanced sarcomas.

Fifty-eight adults with unresectable metastatic sarcomas received monthly courses of bleomycin, cylcophosphamide, doxorubicin, and cisplatin (BCAP) in combination. Following four courses of BCAP, alternating monthly courses of vincristine, cyclophosphamide, dactinomycin and vincristine, doxorubicin, and dacarbazine were begun. Treatment was continued until disease progression or the achievement of disease resectability, with elimination of doxorubicin after a total dose of 520 mg/m2 had been received. Ten patients electively stopped treatment prematurely. One other patient was removed from treatment because of significant pulmonary toxicity. Of the 58 patients 20 (34%) achieved partial regression of disease including 10 of 18 with leiomyosarcoma, 2 of 8 with malignant fibrous histiocytomas, 3 of 8 with osteosarcoma, 3 of 7 with fibrosarcoma, 1 of 2 with epithelioid sarcoma, and 1 of 1 with mesenchymal chondrosarcoma. Median time to disease progression was 174 days and median survival was 341 days. The percentage of patients achieving disease regression on this study was nearly the same as the percentage achieving disease regression on study of CAP in advanced sarcomas.

Adult↗
PubMed1984

Treatment of psoriasis with N-phosphonacetyl-L-aspartate.

Seven patients with severe psoriasis were treated with the aspartate carbamylase inhibitor N-phosphonacetyl-L-aspartate (PALA). Three patients showed a definite improvement lasting up to 3 months after each course of therapy. Three other patients showed more limited responses of shorter duration, and one patient experienced progressive worsening of his psoriasis while on the study. Psoriatic arthritis did not appear to be improved by the PALA therapy. Side effects were usually mild and limited to skin irritation and diarrhea. The development of alternate schedules of administration may lead to a more useful treatment response in patients with severe psoriasis.

Adult↗
PubMed1984

Dialysate flow rate and peritoneal clearance.

We evaluated the influence of dialysate flow rates upon peritoneal clearance of urea, creatine, protein losses into dialysate, glucose disappearance from dialysate, sodium removal from the patient during dialysis, and ultrafiltration rate in 64 patients undergoing intermittent peritoneal dialysis. We evaluated three dialysate flow rates: 2 L/h, 3 L/h, and 4 L/h. All dialysate contained 1.5% glucose. The clearance of urea in milliliters per minute (2-L series 14.0, 3-L series 15.1, 4-L series 17.6) and creatinine in milliliters per minute (2-L series 9.3, 3-L series 10.6, 4-L series 11.6) determined at a dialysate flow rate of 4 L/h was significantly greater than the clearances determined at 3 and 2 L/h of dialysate flow (P less than 0.05). The clearance of glucose from the peritoneal cavity in milliliters per minute (2-L series 6.9, 3-L series 7.9, 4-L series 8.9) was significantly greater for the 4-L series as compared with the 2-L series (P less than 0.05). There were no other significant differences. Neither sex, race, previous episodes of peritonitis, nor etiology of renal failure influenced the results. Given the high cost of dialysate, we recommend dialysate flows of 2 L/h if a patient has a residual renal clearance of 2.5 mL/min. Although increasing dialysate flow rate may compensate for renal clearances significantly less than this, we believe the patient should be offered hemodialysis, continuous cyclic peritoneal dialysis (CCPD), or continuous ambulatory peritoneal dialysis (CAPD).

Creatinine↗
PubMed1984

An unexpected major groove binding of netropsin and distamycin A to tRNA(phe).

Crystalline complexes of yeast tRNA(phe) and the oligopeptide antibiotics netropsin and distamycin A were prepared by diffusing drugs into crystals of tRNA. X-ray structure analyses of these complexes reveal a single common binding site for both drugs which is located in the major or deep groove of the tRNA T-stem. The netropsin-tRNA complex is stabilized by specific hydrogen bonds between the amide groups of the drug and the tRNA bases G51 O(6), U52 O(4) and G53 N(7) on one strand, and is further stabilized by electrostatic interactions between the positively charges guanidino side chain of the drug and the tRNA phosphate P53 on the same strand and the positively charged amidino propyl side chain and the phosphates P61, P62 and P63 on the opposite strand of the double helix. These results are in contrast to the implicated minor groove binding of these drugs to non-guanine sequences in DNA. The binding to the GUG sequence in tRNA implies that major groove binding to certain DNA sequences is possible.

Binding Sites↗
PubMed1984

A phase II study of chlorozotocin in advanced large bowel carcinoma. A cooperative study between two institutions.

Mayo clinic and georgetown university carried out a cooperative phase II study of chlorozotocin in measurable advanced large bowel carcinoma. Of 78 evaluable patients randomized, 39 received low-dose (120 mg/m2 if previously untreated, 100 mg/m2 if previously treated) and 39 high-dose (200 mg/m2 if previously untreated, 175 mg/m2 if previously treated) chlorozotocin intravenously at 6-week intervals. Both groups were comparable in regard to age, prior treatment, treating institution, site of metastases, and performance scores. Overall response rate was 8%, including 5% in low-dose patients and 10% in high-dose patients. Toxicity was mild to moderate, with gastrointestinal toxicity substantially, and hematologic toxicity somewhat less, than seen with other nitrosoureas. Time to progression and survival showed no significant difference between patients treated on the low- and high-dose schedules. As chlorozotocin produced less nausea and vomiting than other nitrosoureas, even in the high-dose regimen, it should be considered for evaluation in neoplasms where nitrosoureas have shown more activity than in colorectal carcinoma.

Adenocarcinoma↗
PubMed1984

A phase II study of the combination, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and N-(phosphonacetyl)-L-aspartate (PALA), in patients with advanced large bowel cancer.

A phase II study of BCNU and PALA was undertaken in advanced large bowel carcinoma. Thirty patients with advanced metastatic colorectal carcinoma were treated with the combination BCNU (200 mg/m2) every 6 weeks, and PALA (5.0 g/m2) every 3 weeks. Fifteen patients had received no prior chemotherapy and 15 had been previously treated with one or more cytotoxic agents. Only one patient met the criteria for a partial response, and this response was of only 3 months' duration. It would seem unlikely that the combination of BCNU and PALA holds the potential of response greater than BCNU alone and that further trials of this treatment regimen for this tumor type seem unwarranted.

Adenocarcinoma↗
PubMed1984

CT appearance of the inferior mesenteric vein.

The CT appearance of the inferior mesenteric vein (IMV) was studied. It can best be identified by its location behind or to the left of the duodenojejunal flexure. Superiorly, it drains into either the splenic vein, superior mesenteric vein, or the splenoportal junction. Inferiorly, it continues to the left of the fourth stage of the duodenum, lying in the left anterior pararenal space. Occasionally, the left colic vein is seen draining into the IMV. In 14 normal cases the diameter of the IMV, measured behind or to the left of the duodenojejunal flexure, was 3-6 mm with a mean of 3.9 mm and a standard deviation of 0.83 mm. In a case of portal hypertension it measured 9 mm. Thus, the IMV can be used to suggest portal hypertension.

Adult↗
PubMed1984

Osmotic control of vasopressin with chronically altered volume states in anephric dogs.

Continuous peritoneal dialysis has been used to maintain anephric dogs at chronically sustained low, normal, and high volume states in order to study the long-term interaction of volume and osmotic stimuli in the control of plasma vasopressin (PAVP). Bilaterally nephrectomized dogs were maintained for 1-3 mo with normal plasma sodium and potassium levels and blood urea nitrogen of 70.1 +/- 10.8 mg/dl. During the first month, the dogs were dialysized to each of the three volume states. After each volume state had been maintained for 7 days, an osmotic forcing with intravenous distilled H2O and hypertonic NaCl was performed in the conscious state to quantitate the relationship between plasma osmolality (Posm) and PAVP. During the osmotic forcings left atrial pressure (LAP) averaged -2.4 +/- 0.5, 2.6 +/- 0.8, and 11.9 +/- 1.1 cmH2O; mean arterial pressure averaged 113 +/- 11, 125 +/- 10, and 148 +/- 8 mmHg, both respective for the low, normal, and high volume states. The slope of the normovolemic Posm-PAVP relationship was determined to be 0.047 pg X ml-1 X mosmol-1 X kg-1, and neither the hypovolemic or hypervolemic relationships were significantly different. The results demonstrate two additional points that must be considered in the control of PAVP. First, the severely depressed sensitivity of osmotic PAVP control suggests that either the dialysis procedures or the absence of the kidneys suppressed or eliminated some factor normally important to the secretion of vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Clinical trial of sequential N-phosphonacetyl-L-aspartate, thymidine, and 5-fluorouracil in advanced colorectal carcinoma.

Preclinical studies have demonstrated enhanced cytotoxic effects of 5-fluorouracil (5-FU) when given in conjunction with N-phosphonacetyl-L-aspartate (PALA) or thymidine in several murine systems. Early clinical studies have demonstrated significant delayed depletion of pyrimidine nucleotides in tumor biopsy specimens following systemic PALA administration and prolonged serum levels of 5-FU after thymidine administration. Each of these biochemical effects would be anticipated to augment the cytotoxic activity of 5-FU. A phase II trial of a timed sequential administration schedule of PALA, thymidine, and 5-FU was conducted in 37 patients with advanced measurable colorectal cancer. Ten of 37 patients (27%) experienced objective tumor responses with a median response duration of 22 weeks, and 18 patients (49%) had stable disease for a median duration of 20 weeks. Six of 13 patients (46%) with anaplastic histology and/or rapidly progressive tumors experienced high-quality tumor responses. Leukopenia and neurologic side effects were the primary toxicities, including one death caused by sepsis. This regimen has demonstrated striking alteration in the 5-FU dose-effect relationship and definite antitumor activity in patients with advanced colorectal cancer. Further trials in patients with anaplastic carcinomas of the colon or other anatomic sites should be considered.

Adult↗
PubMed1984

Metabolic studies of delta-9-tetrahydrocannabinol in cancer patients.

The metabolism of oral delta-9-tetrahydrocannabinol (THC) was studied in nine patients with gastrointestinal neoplasms receiving chemotherapy regimens containing 5-FU and semustine. Plasma levels of THC and its metabolites 11-OH-delta-9-THC (11-OH-THC) and 11-nor-9-carboxy-delta-9-THC (C-THC) were measured. Plasma levels of THC and its metabolites were quite variable among the patients studied. Plasma levels of THC and 11-OH-THC tended to peak at the same time; the C-THC levels peaked later and lasted much longer than the others. Mean half-lives of THC, 11-OH-THC, and C-THC were estimated to be 1.5, 2.1, and 4.4 hours, respectively. Multiple doses of THC did not produce a significant additive effect on the plasma concentrations of the biologically active metabolites THC and 11-OH-THC. No correlation between antiemetic effect or cannabinoid toxicity and plasma levels of the three metabolites could be made in this small number of patients.

Adult↗
PubMed1984

Evaluation of combined cyclophosphamide and methotrexate therapy in the treatment of metastatic carcinoid tumor and the malignant carcinoid syndrome.

Sixteen patients with metastatic carcinoid tumor and the malignant carcinoid syndrome were treated with combined cyclophosphamide and methotrexate therapy in a regimen previously described as highly effective. Toxicity was relatively mild and consisted primarily of leukopenia. One patient experienced some symptomatic benefit and minor reduction in hepatomegaly and 5-hydroxyindoleacetic acid excretion. None met our criteria for an objective response. Combined cyclophosphamide and methotrexate therapy does not appear to offer significant benefit for this disease.

Adult↗
PubMed1984

Pharmacological characterization of teroxirone, a triepoxide antitumor agent, in rats, rabbits, and humans.

Teroxirone is an experimental triepoxide antitumor agent currently undergoing evaluation in clinical trials. We have developed an assay based on derivatization with diethyldithiocarbamate followed by normal-phase high-performance liquid chromatographic analysis. When 14C-labeled teroxirone is administered to rabbits by rapid i.v. infusion, plasma disappearance of parent drug is very rapid (t1/2 less than 5 min), while plasma 14C-labeled drug equivalents are eliminated at a much slower rate (t1/2 greater than 60 min). Twenty-four-hr urinary recovery of parent drug is less than 1%, while recovery of 14C total radioactivity is 60 to 70%. Rapid plasma elimination (t1/2 less than 5 min) and total body clearance (greater than 5 liters/min) are observed following rapid i.v. administration of teroxirone to humans. When teroxirone is administered to humans at constant rates of infusion, plateau concentrations are rapidly achieved and maintained during infusion. Plasma concentrations rapidly decrease upon cessation of infusion. Less than 1% parent drug is recovered in 24-hr urine. Teroxirone is relatively stable in fresh human plasma and whole blood. Teroxirone is metabolized by rat liver, but not lung, microsomal preparations by an NADPH-independent pathway. Epoxide hydrolysis metabolites are detected in microsomal incubations, and cyclohexene oxide inhibits teroxirone metabolism, suggesting that epoxide hydrase may be responsible for teroxirone biotransformation. Cytotoxicity of teroxirone against continuous human tumor cell lines is abolished in the presence of 9000 X g rat liver supernatant preparations but partially restored when cyclohexene oxide is added to incubation mixtures.

Animals↗
PubMed1983

Intravenous midazolam does not change lower oesophageal sphincter pressure.

The effect of intravenous midazolam 0.3 mg/kg on lower oesophageal sphincter (LOS) pressure was studied in 8 healthy volunteers. No effect on LOS pressure was noted. The importance of this finding in relation to the possible danger of gastro-oesophageal reflux and pulmonary aspiration of gastric acid content during induction of general anaesthesia is discussed.

Adult↗