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Biomedical subjects

R Chapman

Publications and source records attributed to R Chapman.

At least 127 records · Page 7Linked to original sources

Cisplatin, vindesine, and bleomycin chemotherapy of local-regional and advanced esophageal carcinoma.

Seventy-one patients with epidermoid carcinoma of the esophagus were treated with a three-drug combination of cisplatin, vindesine, and bleomycin. Forty-five patients had local-regional tumor and received chemotherapy prior to surgery or radiation therapy. Twenty-six patients with extensive disease were treated primarily with chemotherapy alone. The overall major objective response rate to cisplatin-vindesine-bleomycin was 53 percent (36 of 68 evaluable patients). Patients with local-regional disease had a higher response rate than those with extensive disease (63 and 33 percent, respectively). Following preoperative chemotherapy, 34 patients with local-regional disease underwent exploration. Resectable disease was present in 82 percent. There was no increase in operative morbidity or mortality (5.6 percent), when compared with historical control groups. The median survival for the preoperative chemotherapy group was 16.2 months, which is superior to that of a historical control group (p = 0.023). For patients with extensive disease, treated primarily with chemotherapy alone, the median duration of response was seven months. Toxicities of cisplatin-vindesine-bleomycin were in general well-tolerated, and included nausea and vomiting (seen less frequently because of extensive use of metoclopramide), alopecia, nephrotoxicity, and peripheral neuropathy. The dose-limiting toxicity was myelosuppression. Although conventional chemotherapeutic agents have little activity, these results indicate that the investigational combination of cisplatin, vindesine, and bleomycin can induce major regressions in a substantial proportion of patients with esophageal cancer. When this drug combination is used preoperatively, high resection rates and possibly improved survival are seen.

Adult↗

Combination chemotherapy of esophageal carcinoma using cisplatin, vindesine, and bleomycin.

Sixty-one patients with epidermoid carcinoma of the esophagus have been treated with a three drug combination of cisplatin, vindesine, and bleomycin. Of 53 patients currently evaluable for response, 29 (55%) have had partial remissions: 7/16 with metastatic, and 22/37 with local-regional disease. The median duration of response in metastatic patients is eight months. Of 28 patients treated preoperatively, 23 (82%) had resectable disease. The major toxicities seen were nephrotoxicity and myelosuppression. Cisplatin, vindesine and bleomycin is an effective combination in the treatment of esophageal carcinoma. Effects on long-term survival cannot yet be evaluated.

Acute Kidney Injury↗

Phase II trial of VP16-213 in non-small cell lung cancer (NSCLC).

Fifty-one patients with non-small cell lung cancer (NSCLC) were treated, during a phase II trial, with 4'demethylepipodophyllotoxin-beta-D-ethylidene glucoside (VP16-213). Forty-nine were evaluable for response, and of these two (4%) had partial responses lasting 5 and 6 months. Prior treatment with chemotherapy may have adversely affected response rate; none of the 24 previously treated patients had a major response. Myelosuppression was the dose limiting toxicity. Anorexia, nausea and vomiting, partial alopecia, and chills plus hypotension during drug infusion were the other toxic effects. We conclude that VP16-213 has only minimal activity as a single agent in NSCLC.

Adult↗

Action of iron and iron-complexes on Klebsiella pneumoniae (Klebsiella aerogenes).

Iron In the Fe(III) oxidation state had a negligible effect on the growth of Klebsiella pneumoniae even at the highest concentration (0.45 mM) obtainable without precipitation in a minimal medium containing glucose and inorganic salts together with Tris as the buffer and glycerol 2-phosphate as the phosphorus source. Nevertheless in its presence the toxic action of Cd2+, Zn2+ and Cu2+ was antagonized while that of Co2+ and Ni2+ was potentiated. Higher iron levels were obtained by supplementing the minimal medium with fructose, glycine, gluconate, tartrate and citrate at a range of concentrations. With fructose and glycine all of the resulting solutions were red-brown and non-toxic. This was also found with the other complexing agents when the ligand:iron were low, but at higher ligand:iron ratios the solutions were green and toxic. Iron-citrate systems were especially toxic but resistance developed and was of the graded type. The results are discussed with particular reference to earlier physico-chemical studies by other workers and it is concluded that the red-brown colour is characteristic of the presence of polymers of high molar mass and that the green colour signifies the formation of low molar mass species.

Drug Interactions↗

Phase II trials of methylglyoxal-bis (guanylhydrazone).

Broad phase II trial of methylglyoxal-bi (guanylhydrazone) (MGBG) is under way at the Memorial Sloan-Kettering Cancer Center. Studies in renal cell carcinoma, lymphomas, and non-small-cell lung cancer are completed, and substantial numbers of patients with esophageal and head and neck cancer have been treated. Small numbers of patients with other solid tumors have also been entered into the study. MGBG has significant antineoplastic activity against lymphomas, with 16/40 heavily pretreated patients (40%) having partial remissions (PR) lasting 1 to 8+ months. MGBG has also demonstrated more modest activity in non-small-cell lung cancer, esophageal, and head and neck carcinoma; it appears to have little or no therapeutic value in renal cell cancer. Toxicities have been manageable, and included mild nausea and vomiting, diarrhea, mucositis, and myelosuppression. The dose-limiting toxicity, seen most frequently in those patients with impaired renal function, was lethargy and fatigue. MGBG has demonstrated activity in lymphomas, lung, esophageal, and head and neck cancer. Further trials of this agent are indicated, both alone and in combination.

Adenocarcinoma↗

Phase II study of methyl-GAG in the treatment of esophageal carcinoma.

Twenty-four patients with epidermoid carcinoma of the esophagus have been treated, in a phase II trial, with methyl-GAG using a weekly schedule. Eighteen patients had received prior chemotherapy with cisplatin-containing combinations. Of 23 evaluable patients, four (17%) had partial remissions, each lasting 2 months. All patients had received prior chemotherapy. Toxic effects were manageable and included mild nausea and vomiting, mucositis, and fatigue. Using this schedule, methyl-GAG had modest activity in esophageal cancer, with acceptable toxicity. Its role in combination chemotherapy remains to be defined.

Aged↗

Lymphangiosarcoma.

Forty-four cases of lymphangiosarcoma treated at Memorial Sloan-Kettering Cancer Center were reviewed. With the exception of four patients with primary lymphangiosarcoma of the scalp, all patients had had chronic lymphedema of the involved limb for many years, usually following mastectomy for breast carcinoma, but occasionally due to other cases. Although chronic lymphedema could be implicated in the etiology of lymphangiosarcoma in all patients with neoplasms of an extremity, a significant number of patients did not have a history of radiation therapy at the site where their tumor developed. Histologically, although there were no differences in the lymphangiosarcomas between any of the groups of patients, the morphology of the tumors was influenced in the individual patient by the size and anatomic site of the sarcoma. Early amputation seemed to give the best chance of long-term survival, with responses to wide resection, chemotherapy, and radiation therapy generally only of short duration. Amputation after local recurrence was ineffective in preventing pulmonary metastases and death. At present, early amputation appears to be the treatment of choice for patients with lymphangiosarcoma.

Adult↗

Cyclical combination chemotherapy and thyroid function in patients with advanced Hodgkin's disease.

Clinical and biochemical assessment of thyroid function was undertaken in patients with Hodgkin's disease at designated points following diagnosis. At diagnosis, two of 20 patients had either abnormally low routine thyroid indices, or elevated thyroid stimulating hormone (TSH) levels that were not due to iodine-based investigations. Following lymphography, 76.5% of patients had TSH levels that remained elevated for a median period of 3 months. No detectable thyroid dysfunction was induced during chemotherapy. Fifty-four patients were studied at a median time of 35 months after chemotherapy. One euthyroid patient had a nodular goitre, and one had abnormal thyroid indices. Tsh levels were elevated in 44% of patients, although the median TSH level for the group was normal. Half the patients had abnormal TRH stimulation tests. Sixty patients were studied after irradiation and chemotherapy. Four patients had clinical thyroid dysfunction, and 10% of routine thyroid indices were abnormal. TSH levels were abnormal in 80%, with a markedly elevated median level. All thyroid releasing hormone stimulation tests were abnormal.

Antineoplastic Agents↗

Problems in attracting and retaining psychiatrists in rural areas.

Efforts to eliminate the shortage of psychiatrists in rural areas have been relatively unsuccessful due to the special personal and professional problems facing the rural psychiatrist. The rural psychiatrist may feel personally isolated, encountering a somewhat foreign culture and living in uncomfortable proximity to patients and their families. He may feel professionally frustrated, for his physician colleagues are usually conservative and hold dear the medical model of care. He may suffer the typical frustrations of the psychiatrist working out of a community mental health center, and has little opportunity for professional growth. Academic training centers that train psychiatrists in region where they will work can more adequately prepare trainees for rural practice and can offer continuing education courses to professionals already practicing in the area. These centers should collaborate with mental health facilities to define and respond to manpower problems. Finally, opportunities for rural practitioners to make shifts in career emphasis over time should be created.

Attitude↗

Phase II trial of methylglyoxal-bis-(guanylhydrazone) in non-small-cell lung cancer.

Fifty-two patients with metastatic or recurrent non-small-cell lung cancer (NSCLC) were treated, during a phase II trial, with methylglyoxal-bis-(guanylhydrazone) (MGBG). Of the 44 patients who had adequate trials, 4 had partial responses (PR), for an overall 9% PR rate. Response durations ranged from 3 to 5+ months. Prior treatment with chemotherapy may have adversely affected response rate; 15% of previously untreated patients responded, compared to only 4% of previously treated patients. A syndrome of weakness and fatigue was the most serious side effect. Anorexia and weight loss, stomatitis, nausea and vomiting, diarrhea, and peripheral neuropathy were the other toxic effects. We conclude that MGBG has activity in NSCLC, especially in previously untreated patients, and further studies are indicated in that population.

Adenocarcinoma↗

Primary tumors of the heart: a rewarding challenge.

During a 10-year period 21 patients were treated for tumors of the heart, including 19 myxomas, one fibroma, and one sarcoma. The latter two cases are presented separately, and the 19 myxomas are analyzed together. An unusual association of left-sided myxoma with mitral valve abnormalities was found. In the surgical group (18 patients) there were no deaths and one case of postoperative cerebrovascular accident (CVA) with residual sequelae during a mean follow-up of 55 months. The results show the good prognosis of patients operated upon for myxomas of the heart and that there is no need for routine full-thickness excision of the septum in its treatment.

Adolescent↗

Ulcerative colitis in association with Takayasu's disease.

A case of total ulcerative colitis associated with large-vessel disease consistent with a diagnosis of Takayasu's disease is described in a 21-year-old Pakistani female. The possible relationship between the two disorders is discussed.

Adult↗