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Biomedical subjects

A N Stark

Publications and source records attributed to A N Stark.

24 records · Page 2Linked to original sources

Prolymphocytoid transformation of CLL: a clinical and immunological study of 22 cases.

The clinical, morphological and immunological features of 22 cases of chronic lymphocytic leukaemia in 'prolymphocytoid' transformation (CLL-Pro) are reported. Immunophenotypic patterns in CLL-Pro differ from CLL by the appearance of significant (greater than 15%) FMC7-positive components and/or increased SIg densities in most cases. Membrane TU1 and MRBC receptor expression was similar to that found in typical CLL. Morphologically, all cases showed a mixture of small lymphocytes and larger nucleolated 'prolymphocytes' although the degree of prolymphocytoid change was unrelated to immunological patterns. Clinically, the cases behaved in a very heterogeneous fashion, with some patients dying rapidly following transformation despite treatment, while others even if untreated had a long, stable and relatively benign course. It was not possible to predict which patients would do badly from immunological or morphological features but the presence of more than one involved lymph node site and the occurrence of B-symptoms appeared to identify a group that did badly. Immunological assessments were however important in therapeutic terms, drawing distinction between CLL-Pro variants and prolymphocytic leukaemia (PLL).

Humans↗

Myelodysplastic syndrome coexisting with acute lymphoblastic leukaemia.

A 55 year old woman developed chronic myelomonocytic leukaemia (CMML) one year after she had been successfully treated for acute lymphoblastic leukaemia (ALL). When the ALL relapsed the CMML remitted only to return with further remission of the ALL. A consistent chromosomal abnormality, t(4;11), was present during both CMML and ALL phases.

Chromosome Aberrations↗

Trilostane and the normal hypothalamic-pituitary-adrenocortical axis.

Trilostane has been used to treat Cushing's syndrome and other adrenocortical disorders. To investigate its effect on the normal adrenal gland, trilostane (initially 240 mg/day) was given to ten healthy men, the dose increasing at weekly intervals by 240 mg/day up to a final dose of 960 mg/day. The drug was well tolerated although one subject withdrew after the first week because of gastrointestinal side effects. Trilostane had no significant effect on aldosterone levels or blood pressure. The mean 24-h urinary free cortisol excretion rose from 14.2 to 22.0 mumol/mol creatinine (P less than 0.01) before and after trilostane 240 mg/day but did not rise thereafter. Early morning serum cortisol and plasma ACTH levels did not change on trilostane. The mean increment in serum cortisol after the i.v. injection of 0.25 mg of ACTH was reduced from 398 nmol/l before trilostane to 287 nmol/l on 240 mg/day and to 291 nmol/l on 960 mg/day (P less than 0.01). Insulin-induced hypoglycaemia while on 960 mg/day produced a maximum increment in serum cortisol of 361 +/- 118 nmol/l (mean +/- SD) although one subject had a subnormal increment of 180 nmol/l (normal greater than 200 nmol/l). Plasma ACTH rose with hypoglycaemia in all cases. We conclude that trilostane has only a minor effect on the normal hypothalamic-pituitary-adrenocortical axis.

Adrenocorticotropic Hormone↗

Diagnostic features and survival in typical and prolymphocytoid variants of chronic lymphocytic leukemia.

Diagnostic features were evaluated with regards to survival in 203 cases of typical and prolymphocytoid chronic lymphocytic leukemia. Excluding 27 (13 per cent) patients with second malignancies, survival analyses indicated that the prognostic factors with greatest significance were age at presentation (less than 65 years and 65 years or more: p = 0.0004), proportions of prolymphocytoid cells (less than 10 per cent and 10 per cent or more: p less than 0.0001 age corrected) and surface immunoglobulin (SIg) density (weak and more than weak: p = 0.001 age corrected). In contrast, sex, absolute numbers of prolymphocytoid cells, SIg light chain type and FMC7 expression were not prognostically significant. These observations suggest that the recognition and delineation of prolymphocytoid CLL variants by morphological and immunophenotypic criteria, although important in diagnostic terms, may have less relevance with respect to prognosis and patient management.

Adult↗