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Biomedical subjects

M A Friedman

Publications and source records attributed to M A Friedman.

At least 91 records · Page 5Linked to original sources
PubMed1989

A randomized trial of continuous intravenous versus hepatic intraarterial floxuridine in patients with colorectal cancer metastatic to the liver: the Northern California Oncology Group trial.

In 1983, the Northern California Oncology Group (NCOG) instituted a randomized trial of intravenous (IV) versus intraarterial (IA) floxuridine (FUDR) administered via an implantable pump for patients with colorectal cancer metastatic to the liver. The study objectives were to compare the hepatic response rate, time to hepatic progression, and toxicity for the two treatment arms. The study design, which allowed patients failing IV FUDR to crossover to the IA arm, prevents a meaningful comparative analysis of survival. Patients with liver-only metastases (N = 143) were randomized, 76 to the IV arm and 67 to the IA arm, and 115 patients (65 IV, 50 IA) were fully evaluable. Of the 65 patients in the IV arm, 28 crossed over to IA treatment after failing IV FUDR. The dose-limiting toxicity of IV FUDR was diarrhea, whereas biliary toxicity limited both the dose and duration of IA FUDR therapy. Of the first 25 patients treated with IA FUDR at a dose of .3 mg/kg/day, 10 developed radiographically evident biliary strictures, and three developed permanent jaundice. With reduction of the initial IA FUDR dose to .2 mg/kg/day, and adoption of a policy of early dosage reduction, treatment interruption, or termination of therapy for persistent elevations in alkaline phosphatase, only two further cases of serious biliary toxicity occurred. However, 26 of the 50 IA FUDR patients ultimately had therapy terminated because of drug toxicity rather than disease progression. When compared with systemic infusion, infusion into the hepatic artery greatly enhanced the antitumor activity of FUDR against colorectal liver metastases. Although biliary toxicity is the most serious limitation of this form of therapy, biliary stricture and jaundice usually can be averted through careful monitoring of liver enzymes and early dosage reduction.

Adult↗
PubMed1988

Three-generation reproduction study with caprolactam in rats.

In a three-generation reproduction study, rats were given caprolactam in the diet of 0, 1000, 5000 and 10,000 ppm. No treatment-related effects were observed in the parental animals with respect to mortality, clinical signs, reproductive performance or gross pathology findings. Consistently lower body weights were noted in the P2 and P3 mid- and high-dose males and females. Consistently lower mean food consumption values were noted in the P2 and P3 mid- and high-dose males and the high-dose females. These differences were generally significant (P less than or equal to 0.05) in the high-dose group of both sexes. Compound-related histopathologic findings noted in the high-dose P1 males consisted of a slight increase in the severity of spontaneous nephropathies, occasionally accompanied by granular casts. The offspring data revealed no treatment-related effect with respect to gross appearance, gross pathology, survival, number of pups, percentage of male pups or kidney weight. Analysis of the offspring body weights on Days 1, 7 and 21 of lactation revealed consistently and generally significant lower mean values in the high-dose male and female animals of all filial generations. The mean body weights of both sexes in the mid-dose group were generally lower than those of the controls. The effects on mean body weight, mean food consumption and the group increases in the severity of nephropathy, accompanied by the presence of granular casts in some animals, are considered to be related to the administration of caprolactam.

Animals↗
PubMed1988

Surgical oncology research. A disappointing status report.

The purpose of this paper is to evaluate certain aspects of the present status of surgical oncology research. We have attempted to define the magnitude of the problem, characterize features unique to the surgical community, and formulate potential solutions. Demographic data concerning grant applications submitted to and funded by the National Cancer Institute (NCI) over the time period from 1980 to 1985 were analyzed. Departments of surgery submitted and were awarded substantially fewer grants over the study period than departments of medicine. Additionally, the number of applications submitted from departments of medicine increased during this time period while those from departments of surgery declined. This record is particularly worrisome because it occurred during a period of time of unprecedented scientific and educational opportunities and support mechanisms provided by the NCI. Further conclusions and potential solutions are discussed in this paper.

Evaluation Studies as Topic↗
PubMed1988

Phase III trial of irradiation plus chemotherapy for patients with hepatic metastases and hepatoma: experience of the Northern California Oncology Group.

The effects of iv or intra-arterial chemotherapy added to hepatic irradiation were evaluated in a 3-arm randomized trial. Patients with predominantly hepatic metastases or with hepatoma were eligible. They were randomized to receive 2,100 cGy in seven fractions alone or with 5-fluorouracil given either intra-arterially or by iv infusion; doxorubicin and mitomycin were given by bolus simultaneously with the radiation in a single course. A total of 166 patients were entered in the study. Toxicity was acceptable, with no sign of enhanced radiation damage. Response was evaluated 4-6 weeks after treatment. No complete responses were seen, but partial responses greater than or equal to 50% were observed in the groups treated with radiation only (17%), radiation plus drug given iv (25%), and radiation plus drug given intra-arterially (20%) (P greater than .3). Disease progression occurred in a larger number of patients who received radiation only (29%) at 6 weeks than in the other 2 groups (7% and 18%, respectively; P less than .03). Thus, in terms of local response duration, the addition of chemotherapy enhanced the effect of the radiation. Survival was not different among the 3 groups.

Adult↗
PubMed1987

Behavioral and histological effects of acrylamide in rainbow trout.

A histological and behavioral study was used to assess whether acrylamide produced neurotoxic effects in rainbow trout. Swimming performance of trout exposed to 0, 12.5, or 25 mg/liter acrylamide for 15 days was unaffected. Swimming performance of animals exposed to 50 mg/liter acrylamide for a similar time period was compromised by morbidity and mortality of the animals in this treatment group. The absence of dose-related histological lesions in central neurons, peripheral neurons or muscle suggested that the observed deficit in swimming performance was due to a generalized toxic response. Acrylamide treatment produced dose-related lesions in the gill and liver of rainbow trout.

Acrylamide↗
PubMed1987

Combined radiotherapy and chemotherapy with bleomycin and methotrexate for advanced inoperable head and neck cancer: update of a Northern California Oncology Group randomized trial.

Between 1978 and 1984, the Northern California Oncology Group (NCOG) conducted a randomized trial to study the efficacy of combined radiotherapy (RT) and chemotherapy (CT) for stage III or IV inoperable head and neck cancer. One hundred four patients were randomized to receive: (1) RT alone, or (2) RT plus CT. RT consisted of 7,000 cGy to the involved areas and 5,000 cGy to uninvolved neck at 180 cGy/fraction, five fractions/wk. CT consisted of bleomycin, 5 U intravenously (IV), twice weekly during RT, followed by bleomycin, 15 U IV, and methotrexate, 25 mg/m2 IV weekly for 16 weeks after completion of RT. Fifty-one patients in the RT alone group and 45 in the combined treatment group were evaluable. The local-regional complete response (CR) rate was 45% v 67% (P = .056); the 2-year local-regional control rate, including salvage surgery, was 26% v 64% (P = .001); and the incidence of distant metastasis was 24% v 38% (P greater than .25), for the RT alone and RT plus CT groups, respectively. The relapse-free survival curves were significantly different (P = .041), favoring the combined treatment. However, the survival curves were not significantly different (P = .16). Patient compliance to maintenance CT was poor. Bleomycin significantly increased the acute radiation mucositis, although the difference in late normal tissue toxicity was not statistically significant. Thus, bleomycin and concurrent RT produced a more favorable CR rate, local-regional control rate, and relapse-free survival, but the difference in survival was not statistically significant.

Adult↗
PubMed1986

Chronic toxicity and oncogenicity study on acrylamide incorporated in the drinking water of Fischer 344 rats.

Male and female Fischer 344 rats were maintained on treated drinking water providing dosages of 0 (controls), 0.01, 0.1, 0.5, or 2.0 mg acrylamide/kg body wt/day for 2 years to assess the chronic toxicity and oncogenic potential of the chemical. The mean body weights of male and female rats receiving 2.0 mg/kg/day and of male rats receiving 0.5 mg/kg/day were minimally decreased when compared with controls. During the last 4 months of the study, there was an increase in mortality among male and female rats receiving 2.0 mg/kg/day. A target organ effect, characterized by degeneration of peripheral nerves, was observed in rats receiving 2.0 mg/kg/day. The incidence of several tumor types was increased in the rats receiving 2.0 mg/kg/day when compared with controls. In females, increased tumor incidences were observed in the mammary gland, central nervous system, thyroid gland-follicular epithelium, oral tissues, uterus, and clitoral gland. In males the incidence of tumors of the thyroid gland-follicular epithelium and scrotal mesothelium was increased. Male rats receiving 2.0 mg/kg/day also had increased incidence of central nervous system tumors when compared to historical controls but not when compared to concurrent controls. The only tumor incidence which was significantly increased at the 0.5 mg/kg/day level was scrotal mesothelioma. There was no statistically significant increase of any tumor type at the 0.1 or 0.01 mg/kg/day dose levels. However, the incidence of scrotal mesothelioma at the 0.1 mg/kg/day level was greater than that observed in the control group or historically reported in this laboratory.

Acrylamide↗
PubMed1986

The distribution of [14C]acrylamide in male and pregnant Swiss-Webster mice studied by whole-body autoradiography.

Male and 13.5- and 17.5-day pregnant Swiss-Webster mice were administered 120 mg/kg [2,3-14C]acrylamide orally. The male mice were frozen 0.33, 1, 3, 9, 24, 72, and 216 hr later, and the pregnant mice at each gestational period were frozen at 3 and 24 hr. Whole-body autoradiographs from the male mice at early time intervals revealed accumulation of radioactivity in the contents of the gastrointestinal tract, liver, pancreas, testis, brain and gallbladder, and epithelia of oral cavity, esophagus, and bronchi. The distribution appears to be similar in the male and pregnant mice. Absorption from the stomach was virtually complete by 3 hr; renal and hepatic elimination was essentially complete at 24 hr. Radioactivity in the male reproductive tract appeared in the parenchyma of the testis at 1 hr, moved to the seminiferous tubules and head of the epididymis at 9 hr, and by 9 days remained only in the tail of the epididymis and the crypts of the epithelium of the glans penis. This movement parallels that of spermatids. The 13.5-day fetuses were uniformly labeled except for a slightly increased uptake in fetal brain. The distribution of radioactivity in the 17.5-day fetal tissues resembled that in maternal tissues; the remarkable exception was an intense accumulation in fetal skin. This study indicates that acrylamide is efficiently absorbed from the stomach and eliminated by the liver, kidney, and possibly the pancreas. A previously unrecognized affinity of acrylamide or a metabolic product was demonstrated for fetal skin in late gestation and for adult epithelia of oral cavity, esophagus, forestomach, and bronchi. Also, acrylamide or a metabolite appears to bind to spermatids at a specific stage near maturation.

Acrylamide↗
PubMed1986

Subepidermal vesicular dermatosis and sensory peripheral neuropathy caused by pyridoxine abuse.

A woman who had ingested 2 gm of pyridoxine (vitamin B6) daily for 2 years for menstrual water retention developed a subepidermal vesicular eruption on the dorsa of the hands and toes, as well as a sensory peripheral neuropathy. The cutaneous and neurologic manifestations subsided about 2 months after discontinuation of the pyridoxine. The possible relationship of subepidermal vesicular eruptions caused by pyridoxine abuse to epidermolysis bullosa acquisita is discussed.

Female↗
PubMed1986

A critical appraisal of low-dose cytosine arabinoside in patients with acute non-lymphocytic leukemia and myelodysplastic syndromes.

We reviewed 53 publications reporting 751 patients with hematologic malignancies treated with low doses (5 to 20 mg/m2/d) of cytosine arabinoside (LoDAC). Of 507 patients evaluable for response, complete remission (CR) rates varied from 32% for patients with primary acute non-lymphoblastic leukemia (1 degree ANLL) to 16% for patients with hematologic malignancies secondary to previous chemotherapy or following a myelodysplastic syndrome (MDS) (2 degrees ANLL), and 16% for MDS. Median duration of CR was 9.5 months for 1 degree ANLL, and 10.5 months for both 2 degrees ANLL and MDS. Based on limited available survival data, overall median survival for these groups was 9 months, 3 months, and 15 months, respectively. Only three CRs were reported of 31 evaluable patients treated for a variety of other hematologic malignancies. CR rates for patients with 1 degree ANLL greater than or equal to 50 years old was 56%, compared with 29% less than 50 years old (P = .10). While prior chemotherapy was more common in 1 degree ANLL patients less than 50 years of age (86% v 21%; P less than .001), it did not influence response rates in those greater than 50 years of age, suggesting other biases. Hematologic toxicity was mentioned in only 33 of 53 publications, affecting 254 of 289 patients (88%), with at least 15% treatment-related deaths. LoDAC hypothetically acts as a differentiating agent; however, correlative laboratory studies were rarely performed. Cytogenetic data were available for only 15%, and in vitro studies for 10% of all patients with marked discrepancies in the interpretation of results. LoDAC is clearly cytotoxic for both malignant and normal hematopoietic cells. While large numbers of patients have been reported, the lack of well-designed clinical trials prohibits definitive conclusions as to its role as a differentiating agent. Future LoDAC studies should determine optimal dose and schedule, with clinical laboratory correlates to assess differentiation. Trials in ANLL comparing LoDAC with conventional chemotherapy, and in MDS with supportive care alone, may help identify the role of LoDAC. Until appropriate indications can be identified, LoDAC should not be routinely used in clinical practice.

Acute Disease↗
PubMed1986

Gonadotropin hormone-releasing hormone analogues: a new therapeutic approach for prostatic carcinoma.

The introduction of potent analogues of gonadotropin hormone-releasing hormone (GnRH) into clinical practice and their use in patients with metastatic prostatic carcinoma provides an effective alternative to the exogenous administration of pharmacologic doses of estrogens or surgical castration. Their advantages over estrogens are primarily related to a lower incidence of cardiovascular toxicity and gynecomastia. Their choice over orchiectomy is based on cosmetic and psychologic factors since their endocrine effects and clinical benefits are virtually the same. In this review, we describe the current experience with GnRH analogues in the treatment of prostatic carcinoma and discuss their use in the context of other endocrine manipulations. GnRH analogues act on the pituitary and indirectly affect gonadal function, and represent an opportunity for combination with other compounds capable of suppressing or interfering with the effects of circulating and androgens. The availability of several new compounds affecting different aspects of androgen metabolism provides promise for rational drug selection and testing.

Buserelin↗