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Biomedical subjects

J M Bennett

Publications and source records attributed to J M Bennett.

At least 199 records · Page 11Linked to original sources

Evaluation of CCNU and misonidazole in the treatment of advanced colorectal cancer.

Eighteen adult colorectal cancer patients, previously untreated with systemic chemotherapy, were given CCNU and MISO. One patient had an excellent partial response of pulmonary metastases, but the overall response rate was only 6%. Gastrointestinal toxicity was modest, hematologic toxicity was similar to what would have been predicted for CCNU alone, and there was no neurotoxicity detected. This Phase II study demonstrates that these two agents can be administered safely, but have no advantage over CCNU alone.

Adult↗

Acute myeloid leukemia and other myelopathic disorders following treatment with alkylating agents.

Several large cohorts of patients treated with alkylating agents served as a means to review the clinical and pathologic features of 55 cases of myelopathic disorders that resulted. The incidence was 1.8% overall and consisted of five patients (9.9%) who developed bone marrow hypoplasia or aplasia, 15 (27.2%) who developed a myelodysplastic syndrome, and 35 cases of acute myeloid leukemia (62.9%). The median time to recognition of MPD was 14 months, following cessation of chemotherapy. The distribution of the treatment-related MDS cases was different than "de novo" MDS with a high percentage of RAEB-T, and with the treatment related AMLs, there were a higher percentage of patients with FAB M6 (erythroleukemia), and no cases of FAB M3 (hypergranular promyelocytic). The median survival of all patients was very brief.

Adolescent↗

Prolonged unmaintained remission after intensive consolidation therapy in adult acute nonlymphocytic leukemia.

Thirty-five adults with acute nonlymphocytic leukemia who were in complete remission after initial induction therapy received a single course of high-dose cytarabine and amsacrine as consolidation therapy. No further therapy was administered. Despite substantial toxicity, the median duration of disease-free survival was 12 months, and 30% of patients are projected to be alive in continuous complete remission at 3 years. A single course of intensive postremission chemotherapy provides long-term disease-free survival in the absence of any further treatment.

Acute Disease↗

The morphologic classification of acute lymphoblastic leukemia in childhood. Observations on concordance using a simple scoring system.

The French-American-British (FAB) cooperative group proposed a simple scoring system in 1981 to improve concordance among researchers and clinicians for the subclassification of acute lymphoblastic leukemia (ALL) into subtypes L1 and L2. The authors subtyped 50 consecutively admitted patients with common ALL of childhood according to the FAB scoring system to assess concordance among a member of the FAB group (J.B.) and two pathologists (S.S. and C.C.) who are not FAB members. The initial agreement of 66% was unsatisfactory to the authors prompting the critical evaluation of the major sources of disagreement. Concordance was improved greatly by the use of two technics that are logical extensions of the scoring system: performing 100-200 differential cell counts to determine the correct percentages in borderline cases, and using reference drawings that illustrate blasts with cytoplasmic contents of 15%, 20%, and 25% in determining the cell's nuclear cytoplasmic ratio. The authors believe that the criteria explicitly given greater weight by the FAB scoring system (nuclear cytoplasmic ratio and nucleoli) are the most subjective. By following the criteria carefully and resolving differences together at a multiheaded microscope, a concordance of 92% was achieved.

Bone Marrow↗

Comparison of allogeneic bone marrow transplantation and chemotherapy in adult acute nonlymphocytic leukemia. An Eastern Cooperative Oncology Group Study.

To compare the value of ABMT (allogeneic bone marrow transplantation) in first or second remission vs. conventional chemotherapy in adults with acute nonlymphocytic leukemia, we examined retrospectively the outcome of a recently completed chemotherapy trial. We evaluated the survival of patients, with and without histocompatible siblings, who were less than or equal to 45 years old and who had achieved initial complete remission. Of 20 patients who were referred by their physicians for ABMT in first remission, seven relapsed (median duration of remission, 4 months) prior to ABMT, three refused, and 10 underwent ABMT. Nine patients received ABMT in second remission. In comparison to the results of chemotherapy in patients who lacked histocompatible siblings (median duration of survival, 18.5 months), the survival of patients transplanted in first remission was worse (median, 8 months), whereas the survival of patients transplanted in second remission was substantially better (median greater than 22 months). Although ABMT in second remission clearly offers the potential for long-term survival not available by means of conventional chemotherapy, the value of ABMT in first remission remains uncertain.

Acute Disease↗

The significance of bone marrow involvement in non-Hodgkin's lymphoma: the Eastern Cooperative Oncology Group experience.

Data from four clinical trials conducted by the Eastern Cooperative Oncology Group (ECOG) were used to investigate the importance of bone marrow involvement as a prognostic factor in patients with non-Hodgkin's lymphoma (NHL). A total of 502 patients, 275 with nodular, poorly differentiated lymphocytic lymphoma (NLPD) and 227 with diffuse histiocytic lymphoma (DHL) or diffuse mixed-cell lymphoma (DML), were included in this analysis. Patients were separated into four categories: stage III, stage IV with bone marrow involvement (stage IV-M), stage IV without marrow involvement (stage IV-O), and stage IV with bone marrow and other organ involvement (stage IV-OM). Among the DHL and DML patients, the incidence of marrow involvement was 23%. However, stage IV-M patients had a prognosis that is similar to stage IV-O and stage IV-OM and worse than stage III patients. In contrast, the incidence of involvement with NLPD was 59% and patients with stage IV-M had a survival not different than stage III and not worse than stage IV-O and stage IV-OM. The results suggest that the current emphasis on bone marrow biopsy(s) as a routine diagnostic staging procedure for patients with NHL should be reevaluated. The necessity for this procedure in stage III patients with NLPD is not apparent from our data. One can still justify a bone marrow biopsy in stage I and II patients and can confirm the complete clinical response when all nodes have regressed in more advanced disease.

Antineoplastic Combined Chemotherapy Protocols↗

Melphalan may be a more potent leukemogen than cyclophosphamide.

We have evaluated the relation between alkylating agents and leukemic disorders in 3363 1-year survivors of ovarian cancer who were treated in five randomized clinical trials and at two large medical centers. Overall, 28 patients developed acute nonlymphocytic leukemia (expected, 1.2) and 7 developed preleukemia. A 93-fold increased risk for acute nonlymphocytic leukemia was seen in 1794 women treated with chemotherapy; the incidence of leukemic disorders was 7.7/1000 women per year. Risk was highest 5 to 6 years after the first treatment and appeared to decrease thereafter. The use of radiation therapy did not affect risk. The 10-year cumulative risk (mean +/- SE) of acquiring a leukemic disorder was 8.5% +/- 1.6% after treatment with any alkylating agent, 11.2% +/- 2.6% after treatment with melphalan, and 5.4% +/- 3.2% after cyclophosphamide treatment. A dose-response relationship was apparent in 605 women receiving melphalan and suggested in 333 women receiving cyclophosphamide. Women receiving melphalan were two to three times as likely to develop leukemic disorders than were women receiving cyclophosphamide. These data indicate that choice of chemotherapeutic agent and drug dosage may influence significantly the risk for long-term adverse effects of cancer therapy.

Acute Disease↗

Leukemia in Rochester (NY). A 17-year experience with an analysis of the role of cooperative group (ECOG) participation.

Every adult acute nonlymphocytic leukemia patient in Rochester, New York seen from January 1975 to January 1982 was studied. Fifty percent of the patients did not receive combination chemotherapy. Among those who did, there was a significant selection bias toward placing patients with better prognostic features on protocol. Protocol patients were also treated with higher doses of chemotherapy than nonprotocol patients. However, these factors did not completely explain the significantly better complete response (CR) rate and survival among protocol patients. Eastern Cooperative Oncology Group (ECOG) participation remained an independent variable associated with a better outcome. An improvement in CR rate was seen during the 7-year period studied as compared to that seen between 1965 and 1974. The study provided evidence that the availability and use of ECOG protocols was a positive factor in the improvement of leukemia treatment in Rochester.

Acute Disease↗

Torsade de pointes induced by sotalol and hypokalaemia.

The problem of a sotalol-induced ventricular arrhythmia (torsade de pointes) is presented and the contributory role of hypokalaemia is emphasized. It is concluded that sotalol may not be a suitable beta-blocker to use with a diuretic.

Drug Combinations↗

Chemotherapy for metastatic Merkel cell carcinoma.

Merkel cell carcinomas (also known as trabecular carcinomas) are primary cutaneous small cell neuroendocrine neoplasms with the potential to metastasize. Control of disseminated disease is therefore important. A case of metastatic Merkel cell carcinoma with an excellent response to chemotherapy is presented. The regimen chosen for this case is similar to that used for bronchogenic small cell anaplastic carcinoma. The reason for selecting this regimen was the common neuroendocrine differentiation and the similar histopathologic features of these two tumors. Only a few reports have described chemotherapy for Merkel cell carcinoma and similar agents were used. These cases are reviewed and critically analyzed.

Adenocarcinoma↗

Endobronchial metastases from carcinoma of the breast.

We report the case histories of four patients with endobronchial metastases from breast cancer, two of whom died of resultant respiratory insufficiency. To aid in earlier diagnosis and thus permit more rapid application of specific therapy, we characterized the epidemiology and presenting symptoms of these patients and 38 additional patients with endobronchial metastases from breast carcinoma that have been reported in the literature. The average age at presentation with endobronchial metastases was 55, and the average time from diagnosis of the breast primary lesion to the endobronchial metastasis was 77 months. Cough occurred in 71% of patients; wheezing and hemoptysis occurred in 25%. Segmental atelectasis occurred in 57% on chest roentgenogram. Average survival of patients from the time of diagnosis of endobronchial metastasis was 21 months; median survival was 19 months.

Adenocarcinoma↗

A randomized multicenter trial of cyclophosphamide, Novantrone and 5-fluorouracil (CNF) versus cyclophosphamide, Adriamycin and 5-fluorouracil (CAF) in patients with metastatic breast cancer.

As of August 1984, 115 women with advanced breast cancer have been randomized to receive a combination of either cyclophosphamide, Novantrone (mitoxantrone) and 5-fluorouracil (CNF) or cyclophosphamide, Adriamycin (doxorubicin) and 5-fluorouracil (CAF). Seventy-one percent of all patients were post-menopausal and 44% of CNF patients and 57% of CAF patients were estrogen receptor (ER) negative. Slightly over 30% of all patients had received hormonal therapy or chemotherapy in an adjuvant setting. Hematologic toxicity was similar in regard to platelet counts but slightly lower nadirs were experienced with CNF therapy than with CAF. However, there were fewer dosage decreases with CNF. Significantly less nausea and vomiting were observed with the CNF regimen compared to CAF. Moreover, alopecia was reduced appreciably in patients who received CNF. The response rate to CNF for the first 38 eligible and evaluable patients was 42%, and for 53 eligible and evaluable patients who received CAF the response rate was 45%, a non-significant difference. Median response durations were similar also, 140 days for CNF and 168 days for the CAF regimen. Time to treatment failure was similar for both regimens. CNF is an effective regimen for patients with advanced breast cancer, with less toxicity than CAF.

Adult↗

Radiosynthesis of [18F]3-acetylcyclofoxy: a high affinity opiate antagonist.

A convenient method for the preparation of high specific activity [18F]3-acetylcyclofoxy (3-acetyl-6-deoxy-6-beta-18F-fluoronaltrexone) was developed. The method utilizes reactor-produced [18F]-fluoride as its tetraethylammonium (TEA X F) salt in a SN2 displacement on a secondary triflate precursor. Typically, 45% of the 18F activity can be converted to the reactive TEAF in a 70 min preparation. From this, 35% yield (decay corrected) of the [18F]3-acetylcyclofoxy was obtained after HPLC purification with a specific activity of 25 Ci/mmol in a total synthesis time of 60 min.

Animals↗

Errors in measuring water potentials of small samples resulting from water adsorption by thermocouple psychrometer chambers.

The adsorption of water by thermocouple psychrometer assemblies is known to cause errors in the determination of water potential. Experiments were conducted to evaluate the effect of sample size and psychrometer chamber volume on measured water potentials of leaf discs, leaf segments, and sodium chloride solutions. Reasonable agreement was found between soybean (Glycine max L. Merr.) leaf water potentials measured on 5-millimeter radius leaf discs and large leaf segments. Results indicated that while errors due to adsorption may be significant when using small volumes of tissue, if sufficient tissue is used the errors are negligible. Because of the relationship between water potential and volume in plant tissue, the errors due to adsorption were larger with turgid tissue. Large psychrometers which were sealed into the sample chamber with latex tubing appeared to adsorb more water than those sealed with flexible plastic tubing. Estimates are provided of the amounts of water adsorbed by two different psychrometer assemblies and the amount of tissue sufficient for accurate measurements of leaf water potential with these assemblies. It is also demonstrated that water adsorption problems may have generated low water potential values which in prior studies have been attributed to large cut surface area to volume ratios.

Journal Article↗