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Biomedical subjects

R B Weiss

Publications and source records attributed to R B Weiss.

At least 145 records · Page 8Linked to original sources
PubMed1985

Nephrotoxicity of lomustine. A case report and literature review.

A patient is presented who developed nephrotoxicity after therapy with lomustine (CCNU) for astrocytoma of the brain. Only three other cases of lomustine nephrotoxicity have been reported, and all cases have been associated with cumulative drug doses of greater than 1,500 mg/m2. The clinical and pathologic features of lomustine nephrotoxicity are reviewed. It is recommended that cumulative doses of more than 1,200-1,4000 mg/m2 lomustine be avoided because of the risk of nephrotoxicity.

Adult↗
PubMed1985

Non-Hodgkin's lymphoma after successful therapy of small cell lung carcinoma.

A patient is presented who developed a diffuse mixed lymphoma after successful treatment of small cell undifferentiated carcinoma of the lung. The patient was treated with cytotoxic chemotherapy and irradiation for the lung cancer, and had no recurrence during 6 years with no treatment. He then developed stage IV lymphoma. The relationship between these two cancers and the occurrence of treatment-induced second malignancies in small cell carcinoma are discussed.

Aged↗
PubMed1985

Mitomycin: ten years after approval for marketing.

Mitomycin was approved for marketing by the Food and Drug Administration in 1974 for use in gastric and pancreatic carcinomas when combined with other chemotherapeutic agents. Since then, mitomycin has been used extensively in combination chemotherapy for a variety of tumors, particularly in the past seven years. However, the contribution of this agent to the various drug regimens has not been adequately defined. Clear evidence of the drug's activity as a single agent has been seen in the intravesical treatment of superficial bladder carcinoma. Common toxicities include anorexia, vomiting, and myelosuppression. Less common, but potentially lethal, toxicities in the form of fibrosing alveolitis and microangiopathic hemolytic anemia with renal failure are being reported with increasing frequency. These potentially severe adverse effects, coupled with the still undefined role of mitomycin in systemic cancer chemotherapy, suggest that selection of this drug for other than investigational use should be made with care.

Antineoplastic Agents↗
PubMed1985

Neoplasia and the erythron.

Neoplasms may affect the erythroid system in a variety of ways. By far the most common abnormality associated with neoplastic disorders is anemia. It is important to recognize that there are multiple causes of anemia associated with neoplasms, because therapy of the anemia varies according to the causative mechanism. Less commonly, the paraneoplastic syndrome of erythrocytosis may occur in some patients with neoplasia. More subtle abnormalities of the erythrocytes associated with malignant disease include modification of the RBC membrane, changes in erythrocyte enzymes, and abnormalities in hemoglobin production. Clinical awareness of the multiple effects of neoplasms on the erythron will lead to better patient management and may also improve our understanding of erythropoiesis.

Anemia↗
PubMed1985

Hypersensitivity reactions to amsacrine.

Five cases of hypersensitivity reactions to amsacrine are reported. These five cases are compared to the three cases previously published. Sixty-two reports on the clinical use of amsacrine in a variety of solid tumors and hematological malignancy were reviewed. Nine cases of hypersensitivity were described in the 2095 patients reported in these clinical trials. The approximate incidence of hypersensitivity to amsacrine is 0.4%.

Adolescent↗
PubMed1984

Medulloblastoma metastatic to the marrow. Report of four cases and review of the literature.

Medulloblastoma is a malignant cerebellar tumor seen primarily in the pediatric age group that has a known ability to metastasize extraneurally. The skeleton is the most common site of extraneural metastases, but metastases to the bone marrow can also occur. Four cases of medulloblastoma metastatic to the marrow are reported. In addition, 31 cases from the medical literature are reviewed. Clinical features include bone tenderness, cytopenias and elevated serum alkaline phosphatase and lactic dehydrogenase levels. Skeletal involvement, especially of the pelvic bones, is frequently seen radiographically. Weight loss, soft tissue masses and a requirement for blood transfusion are also associated features. Marrow biopsy specimens are characterized by the presence of a small cell tumor often with fibrosis, necrosis and osteoblastic activity. The symptomatic response to chemotherapy is rapid, but chemotherapy resistance appears quickly. Only 1 in 4 cases diagnosed antemortem in this review lived for more than a year. We conclude that marrow aspiration and biopsy are indicated in the evaluation of patients with medulloblastoma and may serve to diagnose the cause of cytopenias, to verify extraneural spread and to provide prognostic information.

Adult↗
PubMed1984

Molecular model of ribosome frameshifting.

Normal tRNAs can cause two- and four-base translocation errors by mistranslating certain noncognate codons. Several cases have been reported that reveal the identities of the frameshift-provoking tRNAs--i.e., the shifty tRNAs--and the mRNA sequence encompassing the site of frameshifting--i.e., the shifty codons. Here, a striking uniformity between the anticodon loops of the shifty tRNAs and their shifty codons is described. Stable "offset" anti-codon X codon pairs are postulated for each of the shifty tRNA-shifty codon combinations. This offset anticodon X codon pair leads to two- and four-base translocations when viewed in terms of the reciprocating ratchet mechanism of translocation.

Codon↗
PubMed1984

A comparison of intermittent vs. continuous and of adriamycin vs. methotrexate 5-drug chemotherapy for advanced breast cancer. A Cancer and Leukemia Group B study.

The therapeutic effectiveness of intermittent vs. continuous combination chemotherapy and of the substitution of adriamycin for methotrexate in a 5-drug regimen was evaluated in women with metastatic breast carcinoma. Patients were randomly allocated to receive continuous therapy with cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisone ( CMFVP -C, 86 patients), intermittent CMFVP ( CMFVP -I, 109 patients), or intermittent CAFVP (107 patients). The CR + PR rate with CAFVP (71%) was superior to CMFVP -C (50%, p = 0.003) and to CMFVP -I (50%, p = 0.002). The remission duration with CAFVP (14 months, median) was superior to CMFVP -I (7 months) (p less than 0.01), and tended to be superior to CMFVP -C (9 months) (p = 0.07). There was a survival advantage of CAFVP (19 months, median) over CMFVP -I (13 months) (p = 0.01), but not over CMFVP -C (16 months) (p = 0.24). Among CR + PR patients, the survival with CAFVP (29 months, median) was superior (p = 0.02) to both CMFVP -I (18 months) and CMFVP -C (21 months). The CMFVP -C regimen was associated with the highest incidence of leukopenia and neurologic toxicity, but the lowest incidence of GI toxicity. The results indicate that the CAFVP regimen is well tolerated and is superior to the CMFVP regimens.

Age Factors↗
PubMed1984

Genetic screen for cloned release factor genes.

Nonsense suppression reflects competition between a nonsense suppressor tRNA and a translational release factor. This provides a simple way to screen for release factor genes cloned into a multicopy plasmid. We have confirmed that the expected competition occurs with the gene for release factor 2, cloned by C.T. Caskey et al. (C.T. Caskey, W.C. Forrester, W. Tate, and C.D. Ward, J. Bacteriol. 158:365-368, 1984), and used it to clone the gene for release factor 1.

Cloning, Molecular↗
PubMed1983

Enzymic detection of uracil in a cloned and sequenced deoxyribonucleic acid segment.

Uracil can occur in DNA either as a result of utilization of dUTP by DNA polymerases or from in situ deamination of cytosine. The latter results in transition mutations following the next round of replication. We describe a technique for the detection of uracil in DNA by a modification of the Maxam-Gilbert sequencing procedure. Reaction of end-labeled DNA with uracil-DNA glycosylase followed by 1 M piperidine results in scission products corresponding to locations of uracils. These are detected by autoradiography following electrophoresis through a sequencing gel. Comparison of these scission products with the DNA sequences elucidates the mechanism of origin of the DNA uracils. The technique was tested with a cloned human DNA sequence grown in a dut-,ung-strain of Escherichia coli, which incorporates uracil in place of thymine in its DNA, and by chemical deamination of cytosines in that sequence. The technique was expanded by use of alkaline and enzymic probes to investigate possible accumulation of uracil, base losses, and other modifications in human liver and brain DNA. No damaged DNA moieties were detected. This method is applicable to the study of any recoverable reiterated sequence by any enzyme preparation that can recognize modifications in DNA.

Adolescent↗
PubMed1983

Combination chemotherapy pneumonitis: a case report of possible synergistic toxicity.

A woman with pancreatic cancer developed acute interstitial infiltrates while receiving modest doses of two potential pulmonary toxins, mitomycin-C and chlorozotocin. Chemotherapy pneumonitis, confirmed by lung biopsy, responded dramatically to prednisone with negligible sequelae. Comparison with the doses in other reported cases suggested additive or synergistic toxicity between these two alkylating agents.

Adenocarcinoma↗
PubMed1983

A randomized trial of five and three drug chemotherapy and chemoimmunotherapy in women with operable node positive breast cancer.

Women with breast carcinoma and four or more involved ipsilateral axillary lymph nodes were randomly assigned to receive an induction course and 2 yr of maintenance chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF, 150 patients), CMF plus vincristine and prednisone (CMFVP, 166 patients), or chemoimmunotherapy with CMF plus the methanol extraction residue of BCG (CMF-MER, 85 patients). After 5 yr of accrual and a median follow-up of 34 mo, CMFVP is superior to CMF (p less than 0.01) with disease-free survival estimates at 4 yr of 60% for CMFVP compared to 45% for CMF. The disease-free survival advantage of CMFVP over CMF was greater in postmenopausal (p = 0.02) than in premenopausal patients (p = 0.09). CMF-MER was similar to CMF alone. CMF related side effects were similar in each regimen (see text), except for a greater incidence of leukopenia during induction with CMF than with CMFVP (p less than 0.01).

Adult↗
PubMed1983

A phase I and pharmacokinetic study of diamminecyclobutane-dicarboxylatoplatinum (NSC 241240).

Carboplatin (CBDCA; NSC 241240) is a second-generation platinum coordination compound which in preclinical testing was found to be less nephrotoxic and emetogenic than cis-diamminedichloroplatinum (CDDP), while retaining a broad spectrum of antitumor activity. We have conducted a Phase I trial of CBDCA in 38 patients with advanced carcinoma. The drug was given without hydration as a 24-hr constant i.v. infusion on Day 1 of a 28-day cycle. Seventy-five cycles of CBDCA were administered in eight dose levels ranging from 20 to 320 mg/sq m. Dose-limiting toxicity was myelosuppression, primarily thrombocytopenia, occurring between Days 14 and 28 of the cycle. Myelosuppression was first observed at a dose of 240 mg/sq m and became dose-limiting at 320 mg/sq m, which is the recommended dose for Phase II trial. Other toxicities included nausea and vomiting and reversible renal failure seen in two patients with low normal pretreatment creatinine clearances. No consistent changes were seen on serial audiograms. Plasma concentrations of total and ultrafilterable platinum were measured by flameless atomic absorption spectrophotometry. Following cessation of the infusion, a half-life of 170 +/- 34 min (S.D.) was found for CBDCA-derived ultrafilterable platinum. In vitro clonogenic assay of a CDDP-sensitive human ovarian cancer cell line using clinically achievable drug concentrations suggests that prolonged infusions of CBDCA may be more cytotoxic than bolus administration. In this study, minimal responses were seen in two patients with ovarian carcinoma who had failed previous combination chemotherapy including CDDP. In addition, three patients with refractory metastatic breast cancer responded to CBDCA (two minimal responses and one partial response) with remission durations averaging 3 months. CBDCA behaves as predicted by preclinical studies with different toxicities from CDDP and apparent activity in breast cancer.

Adult↗
PubMed1983

Nephrotoxicity of semustine.

Semustine is an investigational cancer chemotherapeutic agent in widespread use. This agent has now been documented to produce nephrotoxicity and renal failure with long-term administration. We collected 29 cases of semustine nephrotoxicity from the literature and six unpublished cases brought to the attention of the National Cancer Institute. Using these 35 cases as a data base, we have analyzed the incidence, dose and treatment duration relationships, clinical and histologic manifestations, and clinical course of semustine nephrotoxicity. In addition, we discuss the possible mechanisms of this nephrotoxicity based upon ongoing laboratory work. We conclude that there is a high risk of severe nephrotoxicity from semustine when the cumulative dose exceeds 1200 mg/m2 and that there may be considerable delay in onset of the renal dysfunction.

Animals↗
PubMed1983

Phase II trial of mitoguazone in patients with advanced squamous cell carcinoma of the head and neck.

We used mitoguazone (500 mg/m2 iv weekly, with 50-mg/m2 escalations weekly as tolerated) to treat 22 patients with squamous cell carcinoma of the head and neck which recurred after initial therapy. Nine of 22 (11%) patients responded: two had complete responses and seven had partial responses. Gastrointestinal toxicity and anemia were commonly seen. We conclude that mitoguazone is active in squamous cell carcinoma of the head and neck and should be incorporated into phase III trials.

Adult↗