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Biomedical subjects

M B Garnick

Publications and source records attributed to M B Garnick.

123 records · Page 7Linked to original sources
PubMed1979

Intralesional immune therapy: methanol extraction residue of BCG or purified protein derivative.

6 patients with cutaneous malignant melanoma and multiple secondary cutaneous lesions were treated with intralesional methanol extraction residue of bacillus Calmette Guerin (MER-BCG). Separate lesions were injected with purified protein derivatives (PPD) in 5 of the study patients. 5 of the 6 MER-BCG injection lesions developed marked inflammation clinically. Excisional biopsy 7-14 days later demonstrated complete dissolution of tumor in 2 patients and was accompanied by infiltration with acute and chronic inflammatory cells; 3 lesions revealed necrosis with residual tumor, and in 1 patient there was no apparent host response. Clinical tumor regression was not observed with PPD applied intralesionally, although histopathologic analysis revealed a granulomatous inflammatory response in 3 of 5 patients. No patient demonstrated regression of uninjected cutaneous lesions (4 evaluable patients) or visceral lesions (2 patients). The critical determinants of tumor regression are the size, site and depth of the lesion in relationship to the cutaneous surface. The mechanism of tumor eradication may be related to 'innocent bystander' necrosis secondary to nonspecific inflammation rather than immunologically mediated via host sensitization.

Adult↗
PubMed1979

Low density lipoprotein metabolism and lipoprotein cholesterol content in southwestern American Indians.

The prevalence of ischemic heart disease is significantly lower in southwestern American Indians than in Caucasians. To investigate this difference, the metabolism of low density lipoprotein apoprotein (apo-LDL) and plasma lipoprotein cholesterol composition were studied in 10 southwestern American Indians and 5 Caucasian controls. The plasma concentration of LDL cholesterol in American Indians was 88 +/- 5 mg/dl (mean +/- SEM) and 111 +/- 7 mg/dl in Caucasians. The corresponding values of apo-LDL concentrations were 53 +/- 3 mg/dl and 77 +/- 4 mg/dl, respectively. Conversely, high density lipoprotein cholesterol (HDL) concentrations were significantly higher in American Indians (56 +/- 4 mg/dl) than in Caucasians (37 +/- 3 mg/dl). There were no statistically significant differences in the biological half-life of apo-LDL, calculated from the second exponential of the plasma die-away curve (3.06 +/- 0.15 days vs. 3.45 +/- 0.11 days), the fractional catabolic rate of apo-LDL (0.432 +/- 0.01 vs. 0.411 +/- 0.01), or the fraction of total exchangeable apo-LDL in the intravascular space (70 +/- 1 vs. 67 +/- 3%). As derived from the absolute catabolic rate under steady-state conditions, the synthetic rate of apo-LDL in American Indians was, however, significantly lower than in Caucasians (334.6 +/- 7.8 mg/m(2) per day vs. 507.2 +/- 6.7 mg/m(2) per day; P < 0.001). These data indicate that the lower levels of plasma LDL cholesterol and apo-LDL in American Indians are due to a reduced rate of apo-LDL synthesis rather than to differences in fractional catabolic rates. These differences, in combination with higher HDL cholesterol levels, may contribute to the lower prevalence of ischemic heart disease in American Indians.

Adult↗
PubMed1979

Initial clinical evaluation of N-trifluoroacetyladriamycin-14-valerate (AD-32), an adriamycin analog.

N-Trifluoroacetyladriamycin-14-valerate (AD-32) is superior to Adriamycin in murine L1210 and P388 leukemias and in a number of solid tumor systems, including Ridgway osteogenic sarcoma and Lewis lung carcinoma. In preclinical toxicology studies, AD-32 was less toxic than Adriamycin in both tumor- and non-tumor-being mice and in rabbits. An initial clinical trial was carried out in 23 patients who received a total of 74 courses of AD-32 over a dose range of 100--700 mg/m2 administered at 21-day intervals. Hydrocortisone given during the period of infusion prevented all clinical manifestations of acute toxicity. The AD-32 dose-limiting toxicity, leukopenia, was comparable to that of Adriamycin at a dose of 10:1, but at these equivalently myelosuppressive doses, AD-32 induced less gastrointestinal toxicity and alopecia than Adriamycin and it did not cause local tissue damage following inadvertent paravenous extravasation. Although two responses are reported, the therapeutic activity of AD-32 cannot be assessed because of an inadequate number of patients in any given tumor type. A phase II study is being initiated at a dose of 600 mg/m2 given at 21-day intervals.

Doxorubicin↗
PubMed1978

Carcinoembryonic antigen (CEA) as a monitor of chemotherapy in disseminated colorectal cancer.

A rising CEA level is accepted as a sensitive indicator of recurrent colorectal carcinoma. In order to assess its efficacy in monitoring responses to chemotherapy in disseminated disease, 47 patients with documented metastatic colorectal cancer were studied. All had pretreatment CEA determinations and 40/47 (85%) patients had CEA levels greater than 4.0 ng/ml. Patients with hepatic metastases had the highest CEA values and none were found to have levels less than 4.0 ng/ml. Thirty patients received chemotherapy and had serial CEA determinations. 4/30 (13.3%) demonstrated probable tumor regression, 7/30 (23.3%) had stable disease, while 19/30 (63.3%) showed disease progression. CEA titers declined in all four responders, but in only one instance did the level fall to below 4.0 ng/ml and provide evidence of a tumor response not appreciated clinically. The only cytotoxic drugs effecting tumor regressions were 5-FU and 5-FUDR. CEA levels usually rose as disease progressed, but once elevated, absolute values did not correlate directly with tumor burden. The further usefulness of CEA assays in monitoring disseminated colorectal cancer awaits the development of improved chemotherapeutic agents.

Adult↗
PubMed1978

Sex differences in the size of bile acid pools.

In view of the excess prevalence of gallstones among women and the association of gallstones with diminished bile acid pool size, we measured bile acid pools in 27 male and 25 female healthy human volunteers. The average bile acid pool in the women was significantly smaller than in the men (2.25 +/- .12 g versus 2.88 +/- .16 g; p = 0.003). Chenodeoxycholic acid pool size, computed from bile acid composition data available in 43 of these subjects, was also smaller in women than men (0.94 +/- 0.06 versus 1.22 +/- 0.07 g; p = 0.004). Age, race, and body size bore no statistically significant relationship to bile acid pool size. Biliary cholesterol saturation was positively correlated with weight and obesity and showed a significant inverse correlation with chenodeoxycholic acid pool size, but not with total bile acid pool size. These findings suggest a possible mechanism for the higher prevalence of gallstones among women.

Adolescent↗
PubMed1977

Effect of phenobarbital on biliary lipid metabolism in normal man.

The efficacy of phenobarbital in altering biliary lipid composition in normal man was investigated by determining parameters of biliary lipid metabolism in 8 human subjects without biliary tract disease before and after oral phenobarbital administration at a dose of approximately 3 mg per kg per day for 25 to 54 days. In 8 subjects studied, phenobarbital did not produce any statistically significant changes in the following parameters: bile lipid composition, cholesterol saturation index, total bile acid pool size, daily fractional turnover rate of cholic acid, hepatic secretion rates of cholesterol, bile acids, or phospholipids, and the fraction of the total bile acid pool represented by individual bile acids. Therefore, phenobarbital is not an effective agent, at least when used alone, in inducing changes in bile lipid composition during a short term of administration in normal man. This would indicate that phenobarbital would not be a useful modality in the prevention of the development of cholesterol gallstones, but its prophylactic value in subjects with bile of higher lithogenicity cannot be predicted from these studies.

Administration, Oral↗
PubMedDate not supplied

Phase I trial of bruceantin.

Bruceantin was administered to 33 patients with advanced solid tumors or hematologic neoplasms. The schedule consisted of four weekly iv injections at one dose level followed by a 2-week "no-treatment" period; this program was repeated every 6 weeks. A total of 156 weekly injections were given over a dose range of 0.8-8.5 mg/m2. Systolic and diastolic hypotension was dose-related and dose-limiting at doses of greater than or equal to 6.0 mg/m2. Transient febrile reactions were dose-related. Gastrointestinal toxicity was commonly observed but was not dose-limiting. There was no hematologic or renal toxicity; hepatic toxicity was subclinical and reversible. Of 18 patients evaluable for antitumor response one patient with adenocarcinoma of the cervix experienced a less than 50% disease regression lasting 10 months and one patient with pleural mesothelioma experienced disease stabilization lasting 4 months. A phase II study of bruceantin is recommended at a starting dose of 5.5 mg/m2 weekly for 4 weeks as a 4-hour iv infusion repeated at 6-week intervals.

Adenocarcinoma↗
PubMedDate not supplied

Phase I--II trial of methyl-GAG in the treatment of patients with metastatic renal adenocarcinoma.

Methyl-GAG, a polyamine synthesis inhibitor, was prospectively evaluated in the treatment of advanced renal adenocarcinoma. Twenty-five patients with measurable disease received methyl-GAG weekly at a starting dose of 500 mg/m2 iv, with dose escalation by 50 mg/m2/week (maximum dose, 825). All 25 patients are evaluable for response. Four of these patients (16%) achieved responses including three partial responses and one complete response, with a median duration of 9 weeks (range, 4--15). Nine patients (36%) remained stable and 12 (48%) had progressive disease. In the four responders, regression of disease occurred within the first 4 weeks of therapy. Toxic effects were generally mild and included nausea or vomiting (68%), myalgia (44%), mucositis (40%), neuralgia (40%), weight loss (32%), diarrhea (24%), skin rash (8%), leukopenia (8%), and genital ulcers (4%). We conclude that methyl-GAG has clear, albeit limited, activity against renal adenocarcinoma.

Adenocarcinoma↗
PubMedDate not supplied

Sequential combination chemotherapy and surgery for disseminated testicular cancer: cis-dichlorodiammineplatinum(II), vinblastine, and bleomycin remission-induction therapy followed by cyclophosphamide and adriamycin.

A multimodality treatment program for disseminated testicular cancer using vinblastine/bleomycin/cis-dichlorodiammineplatinum(II) remission-induction therapy followed by surgery and cyclophosphamide/Adriamycin maintenance therapy has been used in 25 patients. The overall complete and partial response rate was 100%. Six of six patients (100%) with stage II (advanced abdominal) disease have remained in complete remission for a median followup period of 8 months. Seventeen of 19 patients (89%) with stage III metastatic disease have been in complete remission for a median duration of 20 months. No relapses have occurred in any patients who achieved a complete remission. Two of 19 patients (11%) with stage III disease achieved a partial response; one died at 4 months and the other died at 14 months. The toxicity was severe, especially during remission induction. However, there were no drug- or surgically related deaths.

Antineoplastic Agents↗