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Biomedical subjects

B M Dale

Publications and source records attributed to B M Dale.

27 records · Page 2Linked to original sources

Effect of L-leucine on oral melphalan kinetics in patients.

Melphalan uptake in the intestine has recently been shown to be an energy-dependent process which is affected by metabolic inhibitors. It is therefore theoretically possible that amino acids in food could reduce melphalan absorption by competing for uptake at the sites of absorption in the intestine. Since L-leucine has been shown to be the most potent inhibitor of melphalan transport into cells in vitro, this amino acid was chosen for the present study in patients. Oral melphalan (4.5 +/- 0.5 mg/m2) was given to ten fasting patients with and without a 2-g oral dose of L-leucine on separate randomized occasions at least 1 week apart. Melphalan plasma levels were measured by high-performance liquid chromatography (HPLC) for 5-h after dosing. L-Leucine plasma levels were measured by HPLC before and at 1 h after dosing. The area under the curve for melphalan was lower in seven of the patients after L-leucine. Plasma L-leucine levels 1 h after melphalan administration were 15.4 +/- 3.7 micrograms/ml fasting and 35.4 +/- 5.2 micrograms/ml after L-leucine. The results indicate that L-leucine can reduce plasma melphalan levels in some patients, probably through a reduction in absorption of the drug from the gastrointestinal tract. However, the effect, like that of food, is highly variable.

Administration, Oral↗

The effect of food on oral melphalan absorption.

Fifteen patients receiving oral melphalan (4.2-5.3 mg/m2) for a variety of neoplastic disorders were studied. Ten patients received the drug on separate occasions, with and without a standardized breakfast. Eight of these patients also received an IV bolus dose (5 mg/m2) to determine bioavailability. Serial melphalan plasma samples were taken over 5 h after administration and assayed by high-performance liquid chromatography. The median area under the curve (AUC) when taken fasting was 179 (range 95-336) ng X h X ml-1, and when taken with food, 122 (47-227) ng X h X ml-1, the median reduction being 39% (P less than 0.01). In one patient, who died before completing the study, the drug was not detectable at all after being taken with food. In the eight patients who were also given IV melphalan, the median terminal melphalan half-life (57 min, range 38-71) was no different from its oral half-life [55 (27-104) min fasting; 55 (30-72) min with food] (P greater than 0.1). In these patients bioavailability was 85% (26-96)% when the drug was taken fasting and 58% (7-99)% when taken with food (P less than 0.025). Median clearance following IV administration was 362 ml/min/m2 (range 104-694). It was found that the melphalan level in a single plasma sample drawn 1.5 h after administration was highly predictive of oral melphalan AUC (rs = 0.915, P less than 0.1). This study suggests that to ensure optimum absorption of the drug, melphalan should not be taken with food.

Absorption↗

A complex translocation in acute promyelocytic leukemia.

The breakpoints of a complex three-way translocation involving chromosomes X, #15, and #17 were resolved in a case of acute promyelocytic leukemia (APL). It is now apparent that similar cases of variant chromosome translocations are found in both chronic granulocytic leukemia (CGL) and APL. The morphological and clinical findings in this case emphasize the variability found in some cases of APL.

Chromosomes, Human, 13-15↗

Congenital anti-thrombin III deficiency with mesenteric venous thrombosis--functional and immunological estimations.

Familial antithrombin III (AT III) deficiency, with mesenteric venous thrombosis, is reported in an Australian family. Antithrombin III was assayed chromogenically, fluorometrically, and immunologically. The deficiency was further analysed using crossed-immunoelectrophoresis. It is suggested that when AT III deficiency is suspected, both a functional and an immunological assay should be performed.

Adolescent↗

Hypertrophic osteoarthropathy complicating primary bone marrow lymphoma--association with invasive phycomycosis and aspergillus infections.

The development of hypertrophic osteoarthropathy in patients with leukaemia or lymphoma presents important diagnostic and therapeutic implications. Patients with these disorders are also predisposed to the development of invasive phycomycosis and aspergillus infections. We report a case of primary bone marrow lymphoma complicated by hypertrophic osteoarthropathy. At postmortem examination there was evidence of disseminated phycomycosis and aspergillus infections. We believe this relationship has not previously been reported.

Adult↗

Collection and cryopreservation of peripheral blood progenitor cells in chronic granulocytic leukaemia--a comparison of treated and untreated patients.

Buffy coat cells were collected by leukapheresis from 14 patients with C.G.L. and one patient with M.M.M. Six of the C.G.L. patients had received busulphan at intervals varying between 401 and 38 d before leukapheresis. Significantly more CFUc's could be collected per leukapheresis in untreated patients and in those patients not treated within 105 d prior to leukapheresis. Survival of CFUc's following freezing was significantly less in the 3 most recently treated patients. These results suggest that in C.G.L. patients recently treated with busulphan, both the number of CFUc's in the peripheral blood and the ability of these cells to survive the freeze thaw process are reduced. However, sufficient CFUc's could theoretically be collected, stored and recovered post-thaw from one leukapheresis to allow complete haematopoietic restoration in all but 2 patients.

Adult↗

Node-based T cell lymphoma. The clinical, immunological and morphological spectrum.

Four cases of node-based T cell lymphoma are presented. The tumours had 2 distinct morphologic patterns. Two cases showed a polymorphous proliferation of pleomorphic lymphoid cells, small lymphocytes, epithelioid cells and arborizing small vessels while the others displayed a monomorphous infiltrate of large atypical lymphoid cells characterized by granular nuclei with numerous tortuous folds to produce a 'squiggly' appearance. One case showed a progression from one histological pattern to the other. Confirmation of the T cell nature of these lymphomas was based on the demonstration of E-rosette formation by morphologically atypical lymphoid cells which also stained positive for acid alpha-naphthyl acetate esterase activity. The patients had an average age of 52 yr and presented with a variable distribution of lymphadenopathy and a predominance of extranodal involvement. Two cases disclosed hypergammaglobulinaemia, one of whom had a paraproteinaemia of IgM-k type. All patients responded poorly to standard combination chemotherapy, 2 expiring 48 and 53 mth after onset of symptoms.

Adult↗