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Biomedical subjects

J Rubin

Publications and source records attributed to J Rubin.

At least 145 records · Page 8Linked to original sources
PubMed1991

Phase I-II study of pibenzimol hydrochloride (NSC 322921) in advanced pancreatic carcinoma.

Pibenzimol is a fluorescent molecule known to bind to double stranded DNA. It also induces prolongation of the G2 phase of the cell cycle, inhibition of DNA replication and cessation of the growth of some cells in late S phase after DNA content has been doubled. It has been shown to increase the life span of mice bearing intraperitoneally implanted L1210 and P388 leukemia. These factors coupled with the affinity of pibenzimol for pancreatic tissue led us to conduct a phase I-II trial of pibenzimol hydrochloride in patients with advanced pancreatic cancer. Twenty-six patients were treated with a five day continuous infusion of pibenzimol at a dose ranging from 6-28 mg/m2/d. There were no treatment related deaths. Major toxicity was hyperglycemia which was self-limited. No objective responses were noted.

Adult↗
PubMed1991

Comparison of local signs and symptoms after the insertion of Norplant implants with and without a scalpel.

The study compares NORPLANT subdermal implants acceptors enrolled randomly for two different insertion procedures. One group (420 women) received the implants with the use of a scalpel according to the manufacturer's instructions. The other group (423 women) received the implant without an incision, directly through a sharpened trocar. The local signs and symptoms were observed at 7 and 30 days after insertion. Pain, tenderness, edema/swelling, ecchymosis and defective scar were considered. Complication rates were low and no significant differences were found between the two procedures. Based on the data of this study, we recommend inserting NORPLANT implants without the use of a scalpel.

Drug Administration Routes↗
PubMed1991

The right to refuse treatment: an application of the economic principles of decision-making under uncertainty.

When courts do not defer to professional judgment, alternative ways must be used to make treatment decisions for persons who are deemed incompetent. Rather than impose the preferences of society on the mentally ill individual, courts have favored alternative procedures. The two most common approaches are substituted judgment and best interests. In using both the substituted judgment standard and the best interest standard the guardian of a patient who is judged incompetent to make a treatment decision tries to make the decision the patient would have made, had he been competent. The guardian must consider the individual's attitude toward risk in making this assessment. Substituted judgment can be used when clear and convincing evidence of the patient's preferences exists. The evidence would come from a study of the patient's expressed attitudes towards medical treatment and behavior before he or she became incompetent. This approach is effective only if the patient has revealed his or her preferences toward relevant medical treatment in the past. The best interest standard is used when no clear and convincing evidence of the patient's treatment preferences exists. The treatment decisions of competent patients whose characteristics are similar to the incompetent patient's, and who have faced a similar situation, can be used as a proxy for the decision the incompetent patient would have made. Using the choice function of similar people may make it possible to develop a reasonably objective basis for determining what course of action is in the patient's best interest.

Antipsychotic Agents↗
PubMed1991

An autopsy study of the peritoneal cavity from patients on continuous ambulatory peritoneal dialysis.

Sixteen autopsies were performed on patients aged 56 +/- 15 (SD) years who were on continuous ambulatory peritoneal dialysis (CAPD) for 834 +/- 766 (SD) days. Lactate-buffered dialysate and povidone-iodine antiseptic were used in all cases. Multiple peritoneal sections were taken to evaluate peritoneal membrane thickening, inflammation, neovascularization, fibrosis, and adhesions. Peritoneal thickening, inflammation, or adhesions were not related to sex, race, or etiology of renal failure. Time on dialysis was also not a direct determinant of peritoneal adhesions or neovascularization. Peritonitis episodes correlated with chronic peritoneal serosal changes. This study supports the hypothesis that peritoneal alterations in patients on CAPD are related to episodes of peritonitis.

Adult↗
PubMed1991

Continuous ambulatory peritoneal dialysis: ten years at one facility.

A review of continuous ambulatory peritoneal dialysis (CAPD) performed at one facility over a period of 10 years showed that age and type II diabetes mellitus were associated with the worst technique survival. The median survival of patients entering CAPD was not significantly different when the etiology of renal failure was chronic glomerulonephritis (CGN; 27 months), chronic interstitial nephritis (CIN; 21 months), diabetes mellitus type I (21 months), or hypertension (16 months). Patients with diabetes mellitus type II had significantly (P less than 0.05) worse survival (11 months). A patient remaining on CAPD 6 months had a 55% to 60% chance of remaining on therapy at 2 years and a 47% chance at the end of 3 years, whereas a patient with diabetes mellitus type II had a 34% conditional probability of remaining on dialysis at 2 years and 18% at 3 years. Sex, race, and educational achievement were not important determinants of dialysis technique survival. Studies are indicated to identify predictors of a poor dialysis experience.

Aged↗
PubMed1991

A randomized trial of cyclophosphamide, doxorubicin, and prednisone versus cyclophosphamide, 5-fluorouracil, and prednisone in patients with metastatic breast cancer.

Ninety-four patients were entered in a clinical trial assessing the clinical activity of cyclophosphamide, doxorubicin, and prednisone (CAP) versus a combination of cyclophosphamide. 5-Fluorouracil, and prednisone (CFP) in patients with advanced breast cancer. Objective response rates were comparable, 49% for CFP and 46% for CAP. There was no statistical difference between the duration of response of the two regimens or in time to progression. Most importantly, survival differences were not apparent. Both regimens were clinically tolerable and toxicities, for the most part, were comparable. Thus, no therapeutic advantage existed for either of these polychemotherapy regimens in patients with advanced breast cancer.

Adult↗
PubMed1991

Tumor necrosis factor-alpha inhibits 1,25-dihydroxyvitamin D3-stimulated bone Gla protein synthesis in rat osteosarcoma cells (ROS 17/2.8) by a pretranslational mechanism.

Tumor necrosis factor-alpha (TNF alpha), a 17,000 mol wt protein, mediates a variety of immunological and inflammatory events. TNF alpha is a potent inhibitor of bone collagen synthesis and stimulator of osteoclastic bone resorption, the net effect of which is to cause bone loss. We have previously reported that TNF alpha inhibits the synthesis of collagen by osteoblastic cells in culture out of proportion to effects on total protein synthesis, suggesting that inhibition of bone formation by TNF alpha may be due to selective inhibition of matrix protein synthesis. To further test this hypothesis and to evaluate the mechanism of TNF alpha action, we studied the effect of TNF alpha on synthesis of the osteoblast-specific bone Gla protein (BGP) by ROS 17/2.8 cells, which have the osteoblast phenotype. Cells were cultured with 10 nM 1,25-dihydroxyvitamin D3 to stimulate BGP secretion, followed by the addition of TNF alpha (1-100 ng/ml) in 1,25-dihydroxyvitamin D3-containing medium. TNF alpha (10 ng/ml) inhibited BGP secretion to 42 +/- 5%, 19 +/- 10%, and 15 +/- 3% of control values after 24, 48, and 72 h of treatment. After 48 h, inhibition of BGP secretion was observed with 2 ng/ml TNF alpha and was maximum with 100 ng/ml. To determine the effect of TNF alpha on total protein synthesis, cells were pulse labeled with [14C]leucine during the last 4 h of TNF alpha treatment, and incorporation of radioactivity into trichloroacetic acid-precipitable protein in cell layer and medium was determined. The TNF alpha inhibition of BGP secretion was independent of changes in [14C]leucine incorporation, suggesting that TNF alpha did not have a general inhibitory effect on total protein synthesis. Cell number was not affected by TNF alpha. Northern analysis of steady state BGP mRNA revealed a dose-dependent decrease in the BGP/cyclophilin mRNA hybridization signal intensity after 24 h of treatment. The maximum inhibitory effect was 41 +/- 5% of the control value with 100 ng/ml TNF alpha. The effect of TNF alpha on steady state BGP mRNA levels was not prevented by treatment of cells with cycloheximide, suggesting that TNF-induced new protein synthesis was not required for TNF alpha action. These results suggest that the mechanism of TNF alpha inhibition of BGP synthesis includes a pretranslational site and support the hypothesis that TNF alpha inhibits bone formation by a selective inhibition of matrix protein production.

Animals↗
PubMed1990

A clinical trial of biochemical modulation of 5-fluorouracil with N-phosphonoacetyl-L-aspartate and thymidine in advanced gastric and anaplastic colorectal cancer.

A novel sequential administration schedule of PALA (N-phosphonoacetyl-L-aspartate) and thymidine to enhance the cytotoxic effect of 5-fluorouracil (5FU) was tested in 36 patients with advanced gastric cancer and 21 patients with advanced poorly differentiated (anaplastic) colorectal cancer. The potency of 5FU was dramatically increased as indicated by the observation of dose-limiting leukopenia at less than one tenth the maximum tolerated dose of 5FU when given as a single agent by intravenous bolus technique. Twenty-five percent of gastric cancer patients and 33% of colorectal cancer patients experienced an objective tumor response, including three patients with complete response. However, response duration was brief (median, 6 months), and there were four treatment-related fatalities due to severe and unpredictable leukopenia leading to sepsis. Survival was short with a median of 6 months for gastric cancer patients and 3 1/2 months for colorectal cancer patients. We conclude that therapeutic index of 5FU was not improved by the addition of PALA and thymidine in this patient population based on considerations of objective tumor response rate, patient survival, and toxicity.

Adult↗
PubMed1990

Phase I and clinical pharmacological evaluation of pirozantrone hydrochloride (oxantrazole).

Pirozantrone hydrochloride, an anthrapyrazole analogue, was selected for clinical evaluation based on broad antitumor activity against murine tumor systems and on potentially less cardiotoxicity when compared to anthracyclines. This anthrapyrazole analogue is currently under clinical evaluation, and we now report results on a Phase I clinical trial incorporating a pharmacologically guided dose-escalation scheme. Dose escalation was designed to proceed by factors of 2 until the patient drug exposure (concentration x time) was 40% of the murine exposure at the LD10 dose (90 mg/m2). Thereafter, more moderate dose escalations were employed. The target concentration x time value (59 micrograms-min/ml) derived from preclinical pharmacology data was exceeded in all three patients at a dose of 90 mg/m2. A dose of 160 mg/m2 was found to reproducibly result in appropriate myelosuppression. This dose is recommended for further testing in Phase II studies. Nonhematological toxicities encountered in this trial were mild, the most notable being phlebitis at the infusion site. Objective responses were observed in two patients, one with metastatic breast cancer and another with metastatic melanoma. Following a 60-min infusion, pirozantrone hydrochloride plasma elimination was monoexponential, with a half-life of approximately 30 min, mean total body clearance of 1.29 liters/min/m2, and mean steady state volume of distribution of 29 liters/m2.

Adult↗
PubMed1990

Extramedullary plasmacytoma of the thyroid associated with a serum monoclonal gammopathy.

Extramedullary plasmacytoma is a malignant plasma cell dyscrasia that is most commonly found in the head and neck. Progression to disseminated disease in the form of multiple myeloma occurs in 17% to 32% of cases. Herein, we describe a patient with extramedullary plasmacytoma of the thyroid gland in whom a serum monoclonal gammopathy resolved with surgery and irradiation of the primary. Although rare, this diagnosis should be considered in patients presenting with obstructive thyromegaly and autoimmune thyroiditis.

Aged↗
PubMed1990

Intra-arterial floxuridine vs systemic fluorouracil for hepatic metastases from colorectal cancer. A randomized trial.

Seventy-four patients with liver metastasis from proved colorectal primary adenocarcinoma were entered into a prospective, randomized clinical trial to evaluate treatment with intra-arterial floxuridine compared with standard outpatient therapy with fluorouracil delivered by intravenous bolus injection. Eligible patients were randomized to hepatic arterial chemotherapy with an implanted infusion pump or systemic chemotherapy. No crossover between treatment arms was permitted, and patients were followed up to progression and death. Objective tumor response was observed in 48% of patients receiving intra-arterial floxuridine and in 21% of patients receiving intravenous fluorouracil. Time to hepatic progression was significantly longer in the group given intra-arterial therapy: 15.7 vs 6.0 months. However, time to overall progression (6.0 vs 5.0 months) and survival (12.6 vs 10.5 months) were not statistically different. Based on these data, we cannot recommend treatment with intra-arterial floxuridine as given in this study for metastatic colorectal cancer to the liver.

Adenocarcinoma↗
PubMed1990

Human keratinocyte growth factor activity on proliferation and differentiation of human keratinocytes: differentiation response distinguishes KGF from EGF family.

Human keratinocyte growth factor (KGF) is an epithelial cell specific mitogen which is secreted by normal stromal fibroblasts. In the present studies, we demonstrate that KGF is as potent as EGF in stimulating proliferation of primary or secondary human keratinocytes in tissue culture. Exposure of KGF- or EGF-stimulated keratinocytes to 1.0 mM calcium, an inducer of differentiation, led to cessation of cell growth. However, immunologic analysis of early and late markers of terminal differentiation, K1 and filaggrin, respectively, revealed striking differences in keratinocytes propagated in the presence of these growth factors. With KGF, the differentiation response was associated with expression of both markers whereas their appearance was retarded or blocked by EGF. TGF alpha, which also interacts with the EGF receptor, gave a similar response to that observed with EGF. These findings functionally distinguish KGF from the EGF family and support the role of KGF in the normal proliferation and differentiation of human epithelial cells.

Biomarkers↗
PubMed1990

Pharmacodynamics of enoximone during intravenous infusion.

Twenty-one patients with heart failure (NYHA class II-IV) received a 24-hour infusion of enoximone, followed by a 12-hour washout period. Patients were randomly assigned to one of four treatment groups. Groups I-III received a 0.5 mg/kg bolus, followed by a maintenance infusion of 2.5, 5.0 or 10.0 micrograms/kg/minute. Group IV patients received a maintenance infusion of 5.0 micrograms/kg/minute without the bolus. Serial assessments of haemodynamics, plasma levels of enoximone and enoximone sulphoxide, and ventricular ectopy were performed. Enoximone produced a significant increase in cardiac index (28.1-46.7%) and a decrease in mean pulmonary artery wedge pressure (6.4-35.7%) and systemic vascular resistance (34.7-78.9%). Enoximone had minimal effect on heart rate and blood pressure. In patients who did not receive an initial bolus of 0.5 mg/kg, haemodynamic changes were delayed by approximately 1 hour. Significant haemodynamic improvement was noted at even the lowest infusion rate and did not increase in linear fashion at higher infusion rates. During infusion of enoximone at 10.0 micrograms/kg/minute, both enoximone and its sulphoxide accumulated non-linearly and did not achieve a steady state. No significant adverse effects were noted in these patients. Enoximone infusion at rates greater than 5.0 micrograms/kg/minute may confer minimal additional haemodynamic benefit, while resulting in significant accumulation of enoximone and enoximone sulphoxide. Ventricular ectopy did not increase significantly in most patients.

Cardiotonic Agents↗
PubMed1990

Nutritional support during peritoneal dialysis-related peritonitis.

Early intravenous (IV) hyperalimentation was used in seven patients who had peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD). Results were compared with those in a control group of seven nonperitonitis CAPD patients. Nitrogen balance was measured to determine whether this therapy was effective in nutritional maintenance during an episode of peritonitis. IV nutrition accounted for 70% to 80% of nitrogen intake. Caloric intake was similar in both groups (34 and 32 calories/d/kg). The control group received 22 g/d of nitrogen and the peritonitis group 17 g/d (P less than 0.05). Nitrogen losses in dialysate were 12.6 g/d in the control group and 13.6 g/d in the peritonitis group. The mean nitrogen balance (intake - output) was 9.5 g/d in controls and 3.7 g/d in the peritonitis group.

Adult↗
PubMed1990

Malignant external otitis: utility of CT in diagnosis and follow-up.

Malignant external otitis is a severe bacterial infection of the bone and soft tissues of the base of the skull that is frequently difficult to diagnose. The effectiveness of antibiotic therapy is likewise difficult to assess. Serial computed tomographic (CT) scans were obtained in 11 consecutive patients with malignant external otitis at time of diagnosis and periodically after conclusion of antibiotic therapy. All patients demonstrated abnormalities of the external auditory canal, with or without bone destruction. Soft tissue or fluid in the middle ear and mastoid, around the eustachian tube, and in the parapharyngeal space (both pre- and poststyloid) was seen in greater than 50% of the cases. While remineralization of bone was not seen, soft-tissue disease improved dramatically, and recurrence or persistence could be corroborated by detection of more extensive soft-tissue changes. By delineating the extra- and intracranial extent of disease, serial CT scans enable one to make the diagnosis, determine the extent of infection, document recurrence, exclude progression, and confirm resolution of malignant external otitis.

Blood Sedimentation↗