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Biomedical subjects

D Dubovsky

Publications and source records attributed to D Dubovsky.

At least 19 recordsLinked to original sources

Phase II evaluation of fluorouracil and recombinant alpha-2a-interferon in previously untreated patients with pancreatic adenocarcinoma.

BACKGROUND: Based on initial encouraging results of the combination of 5-fluorouracil (5-FU) with recombinant alpha-2a-interferon (r alpha-2a-IFN) in the treatment of advanced colorectal carcinomas, a clinical trial was conducted using 5-FU with r alpha-2a-IFN in 49 patients with advanced pancreatic adenocarcinoma. METHODS: Forty-nine patients who had bidimensionally measurable disease and had not been treated previously with chemotherapy were entered in the trial. Starting on day 1, 5-FU was administered as a continuous infusion at a dose of 750 mg/m2/day for 5 consecutive days. Starting on day 12, it was administered as an intravenous bolus of 750 mg/m2 a week for 7 weeks. The r alpha-2a-IFN was administered subcutaneously at a dose of 9 x 10(6) units three times a week during weeks 1-8. RESULTS: Of the 46 patients evaluable for response, none had a complete response, and two had partial responses that lasted 14 and 28 weeks. The overall response rate was 4% (95% confidence interval, 1-15%). Fourteen patients had minor responses (median duration of response, 12 weeks). The median length of survival of all patients enrolled in this trial was 22 weeks. Grade 3-4 toxicities included oral mucositis in 19 patients, granulocytopenia in 16, fatigue in 8, and diarrhea in 3. One patient had severe ataxia and leg weakness. Another died of neutropenic sepsis. CONCLUSIONS: This regimen had significant toxicity and little evidence of therapeutic activity against advanced pancreatic carcinoma.

Adult

Agnogenic myeloid metaplasia and spinal cord compression.

A 55-year-old White male with agnogenic myeloid metaplasia, proved on bone marrow trephine biopsy, underwent splenectomy for abdominal discomfort. Six months later he developed paraparesis and on myelography multiple extradural obstructions were seen. In the absence of other obvious diagnostic possibilities, these were attributed to areas of extramedullary haematopoiesis, and he was treated with local radiotherapy. However, the neurological deficit progressed and emergency laminectomy and decompression were undertaken. Tissue obtained at this time confirmed the diagnosis of agnogenic myeloid metaplasia. A repeat myelogram showed complete relief of the obstruction, but the patient developed fulminating septicaemia and died. These findings are reported in view of the great rarity of spinal cord compression due to multiple areas of extramedullary haematopoiesis.

Humans

Bone marrow culture in vitro. A technique for analysis and permanent recording of cellular composition.

The in vitro cloning of haematopoietic progenitor cells derived from blood or bone marrow is now an established technique for the study of normal and abnormal blood formation. In semi-solid agar the results are conventionally recorded as the number of clusters or colonies that grow on the plate under controlled culture conditions. However, the demonstration of detailed morphology within these cellular aggregates remains unsatisfactory. Aspiration techniques are cumbersome and invariably disturb cellular relationships within the supporting matrix while supravital staining is limited by variable uptake of dye by the agar. We describe a method in which the entire cell-containing layer is removed from the Petri dish, fixed, and after mounting on a glass-slide, is air-dried. This preparation stains well with a wide variety of biological dyes, is minimally influenced by background colouration of the culture medium and excellent demonstration of morphologic detail is possible. A permanent record of the cellular composition of the culture is easily obtained by mounting the stained agar disc.

Animals

The infective complications of aggressive induction of clinical remission in adult acute non-lymphoblastic leukaemia.

The infectious complications after induction of remission in 31 previously untreated adult patients with acute myeloid leukaemia are described. Clinically, most of the febrile episodes were associated with infection, and in 11 of the patients who died infection was the direct cause. In 6 out of these 11 the causal organism was diagnosed ante mortem. In 6 of the 15 patients who regenerated to clinical remission and who had fever the causal organism was isolated. The policy of management of fever in this group of patients is outlined.

Acute Disease

Acute of fulminating myelofibrosis.

Patients who run a fulminating course in association with histologically proven myelofibrosis are distinctly unusual, since the natural history of this entity is characteristically one of slow progression. Because of its rarity and proteam manifestations, acute myelofibrosis may easily go unrecognized. We report 2 such patients. In one, rapid clinical deterioration was dominated by spreading skin lesions, and in the other by refractory intravascular haemolysis. There was no splenomegaly in the first patient, and it was minimal in the second. Although it is seen in frequently, it should be emphasized that myelofibrosis may arise de novo as an acute illness in which the usual degree of splenomegaly is absent.

Acute Disease

Acute leukaemia.

Current concepts underlying the treatment of the acute leukaemias are presented. Improved drug regimens and ancillary services have been developed and their role in the management of acute leukaemia is reviewed.

Acute Disease

Acute leukaemia and allogeneic granulocyte support.

Infusion of functional allogeneic granulocytes is rational therapy in pyrexial patients with severe neutropenia when combined with appropriate antibiotic administration. On the basis of our first year's experience we endorse this approach, but emphasise the need for further critical evaluation of these cells, and present an approach to placing this procedure on a more scientific basis.

Acute Disease