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Biomedical subjects

M C Perry

Publications and source records attributed to M C Perry.

At least 91 records · Page 5Linked to original sources

Non-Hodgkin's lymphoma of the synovium simulating rheumatoid arthritis.

Skeletal involvement in patients with non-Hodgkin's lymphoma (NHL) is common, although direct involvement of the joints is unusual. We describe 2 adults who presented with features suggestive of a diagnosis of rheumatoid arthritis, but who were found to have diffuse NHL of the synovium. Results of a review of the literature, and assessment of the few similar cases in which NHL presented in the joint, suggest that the lymphoma may mimic either a monarticular or polyarticular synovitis, without lymphadenopathy or hepatosplenomegaly. Radiographic demonstration of associated bone destruction is the best evidence for non-Hodgkin's lymphomatous arthropathy in patients with rheumatic symptoms.

Aged↗

Chemohormonal therapy in advanced carcinoma of the breast: Cancer and Leukemia Group B protocol 8081.

In a prospective, randomized trial Cancer and Leukemia Group B (CALGB) evaluated CAF chemotherapy (cyclophosphamide + doxorubicin + 5-fluorouracil [5-FU]) v CAF plus tamoxifen (TCAF) in advanced breast cancer. Patients were stratified by estrogen receptor (ER) status, dominant site of metastatic disease, menopausal status, and prior adjuvant therapy. Regardless of ER status or menopausal status, the addition of tamoxifen conferred no significant advantage in response rate, response duration, time to treatment failure (TTF) or survival over CAF alone. A secondary objective was to compare the response to CAF of ER positive (ER+) and ER negative (ER-) patients to determine if there was a differential response to cytotoxic chemotherapy. Response rates of ER+ and ER- patients to CAF were identical (56%), but the response duration, time to treatment failure, and survival of ER+ patients were significantly longer than ER- patients. This lack of differential response implies that chemotherapy and hormonal therapy may compete for the same pool of ER+ cells. It also suggests that chemotherapy kills breast cancer cells indiscriminately, regardless of ER status.

Adult↗

Requirement for bivalent cations in the actions of insulin and sodium nitroprusside on metabolism in rat adipocytes.

The requirement for Ca2+ and Mg2+ in the actions of insulin and sodium nitroprusside on rat adipocyte metabolism was investigated: sodium nitroprusside, but not insulin, increased cGMP levels in cells incubated in the absence of Ca2+ and/or Mg2+; sodium nitroprusside and insulin are unable to increase the incorporation of [14C]glucose into triglycerides and [14C]leucine into proteins in the absence of Ca2+ and Mg2+; sodium nitroprusside and insulin showed antilipolytic actions in Ca2+- and Mg2+-free medium. We conclude that in the absence of Ca2+ and Mg2+, sodium nitroprusside and insulin have very similar regulatory properties on triglyceride, protein synthesis and adrenaline-stimulated lipolysis, but not on cGMP levels in rat adipocytes. This could provide evidence that omission of bivalent cations was inhibitory at more than one site, or that sodium nitroprusside mimics insulin's actions by another mechanism that does not involve cGMP.

Adipose Tissue↗

Chemotherapy for advanced pancreatic cancer. A comparison of 5-fluorouracil, adriamycin, and mitomycin (FAM) with 5-fluorouracil, streptozotocin, and mitomycin (FSM).

One hundred ninety-six patients with advanced pancreatic cancer were randomized to receive one of two combination chemotherapy programs: FAM (5-fluorouracil, Adriamycin [doxorubicin], mitomycin) or FSM (5-fluorouracil, streptozotocin, mitomycin). Patient characteristics were comparable in both groups. Overall response rates for those with measurable disease (14% on FAM, 4% on FSM) were not significantly different (P = 0.07). There was no significant difference in overall survival between patients treated with FAM and FSM (median survivals of 26 and 18 weeks, respectively). Survival benefits of FAM were significant only for patients with measurable disease. Toxicity of both regimens was acceptable and comparable, aside from greater renal toxicity and more nausea and vomiting with FSM. The results failed to confirm the 35% to 40% response rates previously reported for FAM and FSM in advanced pancreatic cancer.

Adenocarcinoma↗

Tumors of unknown origin in the bone marrow.

Tumors of unknown origin represent a common presentation of malignancy. However, tumors of unknown origin presenting as bone marrow metastases are infrequently reported. The records of 11,820 bone marrow biopsy procedures over a 15-year period at a university hospital and a veteran's hospital were reviewed, disclosing 25 cases of tumor of unknown primary site. Most of the patients were elderly and presented with bone pain or abdominal pain. Anemia, thrombocytopenia, and a leukoerythroblastic blood picture were common hematologic findings. Examination for detection of the primary site was usually unrewarding. The median survival of patients was very short (18 days) and therapy seldom altered survival.

Adenocarcinoma↗

Chemotherapy with cyclophosphamide, adriamycin, and 5-fluorouracil compared to chemotherapy plus hormonal therapy with tamoxifen in the treatment of advanced breast cancer: an interim analysis.

Between February 1980 and August 1982, the Cancer and Leukemia Group B (CALGB) performed a randomized study aimed to compare chemotherapy with CAF (Cyclophosphamide, Adriamycin, 5-Fluorouracil) versus the same chemotherapeutic regimen plus tamoxifen (T-CAF) in stage IV breast cancer patients. Patients were stratified on the basis of menopausal status, estrogen receptors (ER) status, dominant site of metastasis and prior adjuvant treatment. Overall 474 patients were entered into the study of whom 433 were assessable for response. 314 patients were postmenopausal, 85 premenopausal and 34 patients were unknown as far menopausal status was concerned. No difference was evident among postmenopausal patients in overall response rate and duration of responses between T-CAF and CAF (52% vs 50% respectively). Similarly no difference was shown among premenopausal patients, response rates being 63% with T-CAF and 60% with CAF. Lack of benefit from adding T to chemotherapy was seen also according to the different strata, including patients with ER positive tumors. The failure for this combination to be synergistic might reflect an effect of T on tumor kinetics interfering with the activity of chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

A comparison of the effects of sodium nitroprusside and insulin on the control of metabolism in rat isolated adipocytes.

Sodium nitroprusside, a known activator of guanylate cyclase within cells, was used as a probe to investigate the possible role of cyclic GMP in the control of metabolism within rat isolated white adipocytes. Over the concentration range 0-0.1 mM, it increased intracellular cyclic GMP concentrations up to 6-fold within 2 min. Over the same concentration range, it increased the incorporation of 14C from D-[U-14C]glucose into triacylglycerol and of L-[14C]leucine into protein. It also inhibited adrenalin -stimulated lipolysis in the cells, but had no effect on the transport of glucose into the cells. The effects of sodium nitroprusside were compared with those elicited by insulin under identical conditions, as this hormone was shown to cause a similar, but transient, rise in intracellular cyclic GMP concentrations within these cells. Nor insulin, neither sodium nitroprusside were able to increase cyclic AMP levels in adipocytes, whereas adrenalin (0.3 microM) stimulated this production. It is suggested that cyclic GMP may have a role in the control of some part of metabolism 'glucose or amino acids' in adipocytes, and that sodium nitroprusside is a useful probe to investigate this. The limitation of its use are discussed.

Adipose Tissue↗

Bisantrene (NSC 337766) (CL 216,942) in advanced breast cancer. A cancer and leukemia group B study.

Bisantrene (NSC 337766) is an anthracenedicarboxaldehyde hydrazone demonstrating a wide spectrum of activity in animal tumor model systems with no evidence of cardiotoxicity or alopecia, in contrast to doxorubicin. Thirty-three women with advanced adenocarcinoma of the breast were treated with 260 mg/m2 IV every 3 weeks. All patients had received at least one prior combination chemotherapy regimen for metastatic disease and 32/33 were refractory to doxorubicin. Of 28 patients evaluable for response one had a partial response lasting 10 weeks and three patients had stable disease for 22, 22, and 9 weeks. The most significant toxicities were nonhematologic: nausea and vomiting (41%), phlebitic reactions (38%), hypotension, one fatal anaphylactic reaction, and the development of a 7th cranial nerve palsy during drug infusion. Hematologic toxicity, leukopenia, was dose-limiting but manageable without associated infections or bleeding. These results indicate that bisantrene in this dose and schedule is not a useful drug in heavily pretreated breast cancer patients. The incidence and severity of phlebitic reactions limited venous access and adversely affected patient compliance. Preliminary results of other phase II breast cancer trials indicate a similar spectrum of toxicity but suggest more significant antitumor activity even in patients previously treated with doxorubicin. Trials conducted in patients with minimal prior treatment and with bisantrene administered via central line appear warranted for definitive assessment of the activity of this agent in breast cancer.

Adenocarcinoma↗

Phase I clinical evaluation of cytarabine and cisplatin in patients with advanced cancer.

Studies in cell culture systems and tumor-bearing animals have demonstrated synergistic cytotoxicity of cytarabine (ara-C) and cisplatin. We have conducted a phase I trial to assess the toxic effects and tolerable doses of these drugs in patients with advanced cancer. Forty-five such patients were treated with varying dosages of ara-C infused continuously during Days 1-3 of a 28-day cycle. Cisplatin at a dose of 100 mg/m2 was administered on Day 2 of the cycle. Using this schedule, the maximally tolerated dose of ara-C in previously untreated patients was 60 mg/m2/day (180 mg/m2). Hematologic toxicity was dose-limiting with median wbc and granulocyte count nadirs of 1800 and 168/mm3, respectively. Reduction of the cisplatin dose while maintaining the ara-C dose at 60 mg/m2/day resulted in less myelosuppression, suggesting that these drugs may have synergistic effects on the bone marrow. Objective responses were seen in six of 41 evaluable patients, including five of 12 patients with non-small cell lung cancer. The severe bone marrow toxicity observed at relatively low drug doses and the 42% response rate in patients with non-small cell lung cancer suggest that the combination of ara-C and cisplatin has substantial clinical activity. Phase II trials are warranted in non-small cell lung cancer and other tumors.

Adult↗

Survival, bodyweight and food consumption data obtained from life span rodent studies in isolated animal units.

A previous poster presentation proposed the use of isolated units for life span studies in rodents. This novel concept of design was considered to be the best available housing system for these studies. To further support our claim that these units provide good quality reproduceable results control data obtained from initial life span studies in the rat and mouse are reported.

Animals↗

Chemoendocrine therapy vs chemotherapy alone for advanced breast cancer in postmenopausal women: preliminary report of a randomized study.

From January 1980 to August 1982 the Cancer and Leukemia Group B conducted a prospective randomized trial comparing chemoendocrine therapy with T-CAF (cyclophosphamide, adriamycin, and 5-fluorouracil plus tamoxifen) to CAF alone in postmenopausal women with advanced breast cancer. The patients were stratified by estrogen receptor (ER) status into three groups: ER-negative, ER-positive, ER-unknown. They were also stratified by dominant site of metastatic disease: visceral and other (osseous and/or soft tissue). A total of 246 eligible patients were enrolled in the study; 232 were evaluable and constitute the basis for this report. The study revealed that there was no difference in overall response frequency or response duration between T-CAF and CAF; there was no difference in response between T-CAF and CAF in ER-positive or in ER-negative patients; and there was no difference in response between T-CAF and CAF by dominant site of metastatic disease. The expected advantage of T-CAF over CAF, especially for ER-positive patients, was not observed.

Antineoplastic Combined Chemotherapy Protocols↗

Hypokalemia in acute myelogenous leukemia.

Forty-two patients with acute myelogenous leukemia or one of its variants were studied at diagnosis to determine the incidence and cause(s) of hypokalemia. Forty-three percent of patients were hypokalemic, and an inappropriate renal loss of potassium was noted. This potassium wastage could not be explained by antibiotic-induced renal tubular dysfunction, lysozymuria, or alterations in renin-aldosterone secretion.

Aldosterone↗