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Biomedical subjects

F Richards

Publications and source records attributed to F Richards.

At least 145 records · Page 8Linked to original sources

Actinomycin D in the treatment of advanced breast cancer.

Actinomycin D is generally administered by serial low-dose injection over 5-10 days. Recent recognition of prolonged serum and tissue half-lives suggests that high-dose intermittent injecton should be equally effective and less toxic. An intermitten single dose schedule was selected for this phase II trial of actinomycin D in 23 patients with advanced breast cancer refractory to standard combination chemotherapy. The drug was given in doses of 0.75-1.5 mg/m2 at 2-week intervals or on days 1 and 8 of 28-day treatment cycles. One patient obtained a partial response with a duration of 5.7 months. Four patients experienced stabilization of advanced disease, with a mean duration of response of 6.4 months. Gastrointestinal toxicity occurred in 47% of patients and mild to moderate myelosuppression in 39%. We conclude that actinomycin D in this dosage and schedule has limited activity in advanced breast cancer. Higher doses might result in increased response rates but would be associated with greater toxicity.

Breast Neoplasms↗

Chemotherapy versus chemoimmunotherapy in advanced adenocarcinoma of the colon and rectum: a prospective randomized study.

The combination of vincristine, methyl-CCNU, and methotrexate with or without MER-BCG achieved a 2% complete response (CR) and a 11% partial response (PR) with a median duration of 25-29 weeks in 124 evaluable patients with advanced adenocarcinoma of the colon and rectum. Responses were seen in previously untreated patients and in patients refractory to 5-fluorouracil. The median survival of these objective responders (CR + PR) was 57 weeks. The addition of MER-BCG did not appear to influence response rate or duration of survival and was accompanied by significant toxicity. Response was significantly correlated with performance status, sex, and disease free interval and survival with alkaline phosphatase and performance status. Patients with advanced colorectal carcinoma should be stratified according to these variables.

Adenocarcinoma↗

Written informed consent in patients with breast cancer.

One hundred breast cancer patients, 35 adjuvant and 65 advanced, were interviewed 0-24 months after the start of chemotherapy to assess their knowledge and perceptions of the purposes, risks and benefits of treatment. Prior to therapy, all had been given verbal explanations and had signed informed consent forms explicitly detailing drugs, objectives and possible adverse effects of therapy. Seventeen percent of adjuvant and 29% of advanced patients were unable to name any of their drugs. While most patients recognized distressing side effects such as nausea and hair loss, less than 50% were aware of the potentially lethal complications of infection and bleeding. While the purpose of adjuvant therapy was cure, only 29% of the adjuvant patients were aware of this. In contrast, 35% of the advanced patients incorrectly stated that they were told their therapy was potentially curative. Explanations given by a nurse in addition to a physician were better understood than those given by a physician alone. We conclude that, in spite of intensive efforts at improving informed consent procedures, current results are unsatisfactory.

Adult↗

Monocyte and granulocyte defect in chronic lymphocytic leukemia.

Enzymatically homogeneous populations of lymphocytes, monocytes, and neutrophils were isolated by zonal centrifugation from 5 untreated patients with chronic lymphocytic leukemia (CLL) and 2 patients with CLL in full remission. The cells were then quantitatively analyzed for six leukocytic enzymes and compared with cells from normal subjects. CLL monocytes were deficient in beta-glucuronidase (0.06 units; normal, 0.16), myeloperoxidase (0.07 mg; normal, 0.5 mg), and lysozyme (0.7 mg; normal, 3.3 mg). In 2 cases, CLL neutrophils were severely deficient in lysozyme (1 to 2 mg; normal, 7 mg) and myeloperoxidase (2 to 3 mg; normal, 7 mg). Neutrophil alkaline phosphatase and neutral protease were unaffected. CLL lymphocytes shared with the monocytes the deficiency of beta-glucuronidase (0.03 units; normal, 0.09 units). The 2 CLL patients in full remission carried normal enzyme levels in leukocytes of all three cell lines. The CLL lymphocytes of untreated patients were unresponsive to mitogens but became responsive in remission. The CLL monocytes from both untreated and treated patients transformed into macrophages. The pattern of shared enzyme deficiency among lymphocytes, monocytes, and neutrophils of CLL patients and its normalization in all three cell types under remission suggest that the differentiation of the three leukocytic cell lines may be an enzymatically interlinked process and that the deficiency of these enzymes in leukemia may reflect an interrelated aberrant differentiation of the leukemic cells.

Acid Phosphatase↗

Absence of neutral protease and alkaline phosphatase in neutrophils of a case of hairy cell leukemia.

Enzymaticaly homogeneous fractions of lymphocytes, monocytes, and neutrophils were isolated by zonal centrifugation from peripheral blood of a patient with hairy cell leukemia, or leukemic reticuloendotheliosis, LRE,(with leukopenia, neutropenia, lymphocytosis, and massive splenomegaly). To detect enzymatic deficiencies, the cells were analyzed quantitatively for six leukocytic enzymes on three occasions: 1) before splenectomy, 2) 5 days after splenectomy, and 3) 6 weeks after splenectomy. Before splenectomy, the patient's cells showed moderate deficiency of beta-glucuronidase in lymphocytes and monocytes; server to modorate deficiency of lysozyme and myeloperoxidase in monocytes and granulocytes; and complete absence of neutral protease and alkaline phosphates in neutrophils. Full restoration of neutral protease and a three-fold rise in alkaline phosphatase activities occurred in the patient's neutrophils 5 days after splenectomy. Lysozyme and myeloperoxidase returned to normal in both monocytes and neutrophils of the patient. Six weeks following splenectomy, the alkaline phosphatase activity again disappeared from patient's neutrophils, although neutral protease remained normal. The patient's lymphocytes were unresponsive to PHA and PW mitogen before splenectomy but became responsive 6 weeks postoperatively. Monocytic transfomation into macrophges was supressed before and after splenectomy. The findings indicate that developmenally, in lymphocytic leukemia, a biochemical defect involves the patient's monocytes and neutrophils much more severely than it affects the leukemic lymphocytes. Functionally, the results partly explain the susceptibility of LRE patients to microbial infections.

Alkaline Phosphatase↗

Radionuclide scanning in patients with advanced malignant melanoma.

The results of liver, bone, and brain scans in 84 patients with recurrent or metastatic malignant melanoma were reviewed. The liver scan was initially positive in 18% (14/78) and ultimately in 32% (25/78). Serum alkaline phosphatase and lactic dehydrogenase were elevated in 92%. These patients ultimately developed positive liver scans, while convincing hepatomegaly was noted in only 44%. Bone scans were eventually positive in 33% (16/49), all of whom had pain. Brain scans were positive in 15% (10/65), all of whom had CNS symptoms. In asymptomatic patients, bone and brain scans only rarely disclosed occult lesions.

Bone Neoplasms↗

Gamma heavy chain disease seen initially as gastric neoplasm.

A patient with abdominal pain, weight loss, and a gastric mass was found to have a pleomorphic infiltrate of lymphocytes and plasma cells. Analysis of serum proteins revealed gamma heavy chains, which were detected in the urine as well. This case is unusual because of the extralymphatic involvement and the possibly unique character of the heavy chain, an insertion in added polypeptides.

Aged↗

Adriamycin versus methotrexate in five-drug combination chemotherapy for advanced breast cancer: a randomized trial.

Adriamycin is of noteworthy efficacy in the treatment of metastatic breast cancer. Its role in combination regimens is under investigation. One hundred seventy-five women with advanced breast cancer were entered into a prospectively randomized trial comparing two five-drug regimens. Regimen CMFVP consisted of cyclophosphamide (C), methotrexate (M), 5-fluorouracil (F), vincristine (V), and prednisone (P). Regimen CAFVP was identical but substituted Adriamycin (A) for methotrexate. Twenty-seven patients were disqualified; 148 were evaluable. With CMFVP the complete response rate (CR) was 11%, and the partial response rate (PR) was 46%; with CAFVP, CR was 13% and PR was 45%. Duration of response tended to be slightly longer for patients on the Adriamycin arm. The median survival for CR and PR patients with CMFVP was 20.2 months, which was shorter (p = .07) than the 33 month median survival with CAFVP. Although statistical significance was not reached at the 5% level, the increased survival of responders on the Adriamycin regimen supports the data of other studies which suggest that first line combination chemotherapy in advanced breast cancer should include Adriamycin.

Antineoplastic Agents↗

The control of chronic lymphocytic leukemia with mediastinal irradiation.

Forty patients with chronic lymphocytic leukemia have been treated with mediastinal irradiation. A full remission was achieved in 18 (45 per cent) patients, a partial response in eight (20 per cent), "WBC control" in eight (20 per cent) and no response in 6 (15 per cent). Although mediastinal irradiation benefited all stages of disease, earlier stages of disease correlated with more complete and longer response to mediastinal irradiation. Toxicity was mild and transient and included leukopenia in five patients (12 per cent), thrombocytopenia in eight patients (20 per cent), mild esophagitis in 12 patients (30 per cent) and pneumonitis in four patients (10 per cent). There were no toxic deaths and mediastinal irradiation did not adversely effect survival. Treatment was readily given on an ambulatory basis and completed within four weeks. In five of 11 patients, abnormal immunoglobulins became normal. Eleven patients had abnormal lymphocyte transformation with PHA, five had marked improvement and three had partial improvements following mediastinal irradiation. This improvement appeared to correlate with response and survival but further study is necessary to confirm this relationship. Although most patients required additional therapy within two years, eight patients have required no further therapy for periods of twenty-eight months to thirteen years.

Chlorambucil↗

Antibody to Tamm-Horsfall protein in patients with urinary tract obstruction and vesicoureteral reflux.

Urinary tract obstruction and vesicoureteral reflux, which are often associated with urinary tract infections, may lead to progressive renal damage. Relatively little is known about the pathophysiology of this process, and a need exists for noninvasive methods of its detection in its early stages. Because urine is refluxed into the venous and lymphatic drainage of the kidney in severe vesicoureteral reflux and urinary tract obstruction, an immune response to urinary tract components might play a role in the pathophysiology of progressive renal damage and serve as a serologic marker for its presence. A solid-phase radioimmunoassay for a protein found only in the urine (Tamm-Horsfall protein [THP]) was developed and used to measure antibody to THP in the serum of 60 subjects. Significant elevations of antibody to THP were observed in five of 15 patients with obstruction and infection of the urinary tract and in one of 10 patients with infection alone, when these patients were compared with 12 healthy control subjects. Similar elevations of antibody to THP were not seen in uninfected patients with urinary tract obstruction or in patients with low-grade vesicoureteral reflux or sepsis of nonrenal origin. These results suggest that the measurement of antibody to THP might be useful in the identification of patients with obstruction and infection of the urinary tract.

Adolescent↗

Chemoimmunotherapy for disseminated malignant melanoma: a prospective randomized study.

Twenty-eight patients with disseminated malignant melanoma were treated with DTIC (250 mg/m2 iv, Days 1--5) and actinomycin D (0.5 mg/day iv, Days 1--5) at 5-week intervals. Patients were randomly allocated to receive no immunotherapy or immunotherapy consisting of methanol extracted residue of bacillus Calmette-Guérin (0.5 mg intradermally; 100 microgram in five separate sites) every 5 weeks, concomitant with chemotherapy. Of these 28 evaluable patients, 13 received chemoimmunotherapy with one complete response (CR) and 15 received chemotherapy alone with one CR. Both responses occurred in lymph node metastases. No partial responses were seen.

BCG Vaccine↗