Search PubMed⌕ Search

Biomedical subjects

D White

Publications and source records attributed to D White.

At least 145 records · Page 8Linked to original sources
PubMed1995

C-myc amplification, double minutes and homogenous staining regions in a case of AML.

c-myc amplification is usually associated with lymphoid malignancies and Burkitt's lymphoma in particular. We present a case of AML with c-myc amplification which was associated with homogenous staining regions (hsr) and double minutes (dmin). The administration of GCSF following induction chemotherapy resulted in a marked increase in blast numbers. The GCSF was stopped and further courses of chemotherapy given, which resulted in complete remission. The patient relapsed 7 months after diagnosis and failed to go into a second remission with reinduction therapy. We conclude that c-myc amplification is a rare event in AML, but may be associated with chemotherapy resistance and a poor prognosis, are as dmins and hsr. Growth factors should be used with caution in these patients.

Aged↗
PubMed1995

Refractory anaemia with preleukaemic polyclonal haemopoiesis and the emergence of monoclonal erythropoiesis on disease progression.

We describe a young woman with a myelodysplastic syndrome (MDS) of the type refractory anaemia (RA) which remained stable for 11 years and then underwent rapid progression manifested by bone marrow failure with the emergence of a complex clonal cytogenetic abnormality. Peripheral blood granulocytes, mononuclear cells and bone marrow erythroblasts were all polyclonal by X-inactivation analysis detected by the probe M27B during the preleukaemic phase. On disease progression, bone marrow erythroblasts developed an extremely skewed monoclonal pattern of X-inactivation. In some cases of MDS, therefore, polyclonal haemopoiesis can be detected for a considerable time during the preleukaemic phase and we report the demonstration of bone marrow erythroblasts changing from a polyclonal to a monoclonal pattern on disease progression.

Adult↗
PubMed1995

A novel CSF-1 binding factor in a patient in complete remission following cytotoxic therapy for lymphoma.

A novel colony stimulating factor-1 (CSF-1) binding factor present in the serum from a patient in remission from lymphoma is described. Radioimmunoassay (RIA) repeatedly failed to detect circulating levels of CSF-1 in the peripheral blood system of this patient. Molecular analysis showed a normal CSF-1 gene structure by Southern blot analysis and a 46,XX karyotype by cytogenetic analysis. CSF-1 mRNA expression in peripheral blood leucocytes was confirmed using reverse transcriptase polymerase chain reaction analysis. Morphological analysis of bone marrow cells was normal and peripheral blood progenitor cell colony assays showed a pattern of growth within the normal range in response to CSF-1 alone and in combination with other cytokines. Analysis of the patient's plasma and conditioned media prepared from peripheral blood mononuclear and granulocytic cell fractions for their ability to bind 125Iodine-labelled CSF-1 revealed the presence of a plasma CSF-1 binding factor. This binding factor was not present in the patient's urine, because CSF-1 was detected by RIA and production of the binding factor by the patients peripheral blood white cells could not be demonstrated in vitro. To our knowledge, this is the first reported case of a soluble CSF-1 binding factor.

Antineoplastic Agents↗
PubMed1995

Diurnal variation of sex hormone binding globulin and insulin-like growth factor binding protein-1 in women with polycystic ovary syndrome.

OBJECTIVES: The aim of this study was to examine (1) the diurnal variation in SHBG and (2) the inter-relationships of insulin, IGF-I, SHBG and IGFBP-1 over 24 hours in 10 women with anovulatory PCOS and compare them with weight-matched ovulatory controls. PATIENTS AND METHODS: The two groups comprised 10 anovulatory women with PCOS (as defined by clinical, ultrasound and biochemical criteria) and 10 weight matched controls. Serum samples were taken at two-hourly intervals for 24 hours and stored for measurement of SHBG, IGFBP-1, insulin and IGF-I. Differences between the groups were compared using the Wilcoxon ranked paired tests of the individual peak and trough concentrations in each group. The variation in insulin, IGFBP-1 and SHBG concentrations over 24 hours was tested using two-way analysis of variance with the factors time and subject. Spearman's correlation coefficient was calculated from the subjects' median value over 24 hours. RESULTS: The median (interquartile range) body mass index (BMI) was 25.2 (22.2-29.3) in the PCOS group and 24.3 (23.2-25.7) kg/m2 in the control group. Serum testosterone (T) and LH levels were significantly raised in the PCOS group compared to the control group; T 3.8 (2.9-5.6) vs 1.9 (1.9-2.5) nmol/l (P < 0.007) and LH 12 (10-15) vs 4.1 (3.6-4.5) IU/I (P < 0.005) respectively. There was no diurnal variation in SHBG. The median (interquartile ranges) of the peak SHBG concentrations was lower in the PCOS group: 29.4 (14.9-39.4) vs 52.1 (39.4-61) nmol/l in the control group (P < 0.01). The fasting levels of insulin at 0600 h (median (interquartile ranges)) were not significantly different between the groups; 6.6 (5.4-9.8) and 6.2 (1.9-7.6) mU/l, respectively, although the peak median concentrations were significantly different; PCOS 66.1 (50.9-129.2) vs 40 (36.1-74.2) mU/l (P < 0.05). Two-way analysis of variance showed a diurnal variation in insulin concentrations in the control group (P = 0.001) but not in the PCOS group (P = 0.1). The diurnal variation in IGFBP-1 was similar in the two groups but the peak median levels were lower in the women with PCOS 54.9 (22.3-79.2) vs 71.5 (60.5-99.3) micrograms/l (P < 0.03). The decline in IGFBP-1 concentrations correlated with the increase in insulin concentrations. The IGF-I concentrations were similar in the two groups. There was a significant negative correlation between SHBG and insulin (P < 0.05) and between insulin and IGFBP-1 (P < 0.01). CONCLUSION: This study demonstrates that there is no diurnal variation in SHBG concentrations and confirms the finding of a marked diurnal variation in the concentration of IGFBP-1. Women with PCOS who are anovulatory have an abnormal pattern of insulin secretion with an absence of diurnal variation compared to weight matched controls. This provides further evidence of the relative insulin resistance which is independent of weight found in women with anovulatory PCOS. The inverse correlations of insulin concentrations with SHBG and IGFBP-1 support the role of insulin as a possible regulator of the circulating levels of these binding proteins although the difference in the time course of their response makes it unlikely that they are co-regulated.

Circadian Rhythm↗
PubMed1995

Gonadotrophin and gonadal steroid response to a single dose of a long-acting agonist of gonadotrophin-releasing hormone in ovulatory and anovulatory women with polycystic ovary syndrome.

OBJECTIVE: A previously published study has identified that anovulatory women with PCOS have an increased response of 17 alpha-hydroxyprogesterone (17OHP) and androstenedione to a GnRH analogue suggesting dysregulation of cytochrome P450c17 alpha. The object of this study was to compare the responses of the pituitary-ovarian axis to a single dose of a long-acting GnRH agonist (GnRHa) in both ovulatory and anovulatory women with PCOS with those in normal subjects. DESIGN: Comparative study of responses of LH, FSH and ovarian steroids to buserelin and the adrenal steroid response to synthetic ACTH in two groups of women with hyperandrogenaemia and polycystic ovaries: those with anovulatory menses or amenorrhoea and those with equally elevated serum testosterone concentrations but regular menses. Results in both groups of women with PCO were compared with those in normal subjects. SUBJECTS AND METHODS: Twenty-four women with hyperandrogenism and PCO (14 had oligo or amenorrhoea, 10 regular cycles) and 12 weight matched controls with normal ovaries, regular cycles and neither clinical nor biochemical evidence of hyperandrogenism. Subjects were given synthetic ACTH (Synacthen) 250 micrograms i.v. on day 1 of the study and blood collected at 30 and 60 minutes thereafter. On the evening of day 1, dexamethasone treatment was commenced to suppress adrenal androgens. GnRHa 100 micrograms s.c. was given on day 2 and blood samples collected at 30-minute intervals for 4 hours and once more at 24 hours after the injection. RESULTS: The acute responses of both immunoactive and bioactive LH to GnRHa were significantly greater in the ovulatory PCO group (ovPCO) than controls but the response was greater in anovulatory women with polycystic ovaries (anovPCO) than in either ovPCO or controls, throughout the 24-hour study period. Despite the discrepancy in LH concentrations, basal serum concentrations of androstenedione were equally elevated in anovulatory and ovulatory women with PCO, compared with controls. There was a small but significant increase in androstenedione following GnRHa in both PCO groups at 24 hours but not in controls. A similar pattern was observed in the response of 17OHP to GnRHa although the response was significantly higher than controls in anovPCO women only. By contrast, the responses of both androstenedione and 17OHP to 250 micrograms synthetic ACTH were similar in PCO women to those in controls. CONCLUSIONS: These data provide evidence for ovarian hypersecretion of androgens in ovulatory, as well as anovulatory women with PCO, supporting the concept of abnormal regulation of 17-hydroxylase and (17,20-lyase activity in the ovary. The finding of an equal degree of hyperandrogenaemia in ovPCO and anovPCO groups, even though LH levels were much higher in the latter, suggests that hypersecretion of LH is not the primary cause of ovarian hyperandrogenism. Hyperandrogenism in PCOs may therefore represent an intrinsic abnormality of ovarian theca-interstitial cell function.

17-alpha-Hydroxyprogesterone↗
PubMed1995

Chronic alcoholism and male sexual function.

OBJECTIVE: The relation between chronic alcohol abuse and male sexuality remains uncertain. This study assessed the effect of chronic alcoholism on sexual function, marital adjustment, sleep-related erections, sleep disorders, and hormone levels during abstinence from alcohol. METHOD: Twenty chronically alcoholic men, aged 28-59 years, without evidence of severe hepatic disease and free from unrelated medical illnesses, were assessed 2-36 months after achieving sobriety and compared to a group of 20 nonalcoholic volunteers. Each subject and his sexual partner underwent semistructured interviews and completed several questionnaires; the men had medical and psychiatric evaluations and polygraphic assessment of sleep parameters and nocturnal penile tumescence during 4 nights, with the last night devoted to sequential blood sampling for evaluation of hormone levels. RESULTS: The alcoholic men did not differ from the comparison group in any sexual dimension or in the prevalence of sexual problems despite the significant marital dissatisfaction reported by their sexual partners. In addition, there were no differences between groups in sleep and nocturnal penile tumescence measures. The alcoholic group had a greater prevalence of periodic leg movement disorders but no respiratory abnormalities during sleep. Except for a significant overnight increase in plasma luteinizing hormone in the alcoholic men, there were no differences between groups in total and bioavailable testosterone, dihydrotestosterone, and prolactin or in the nocturnal circadian changes in testosterone and prolactin levels. CONCLUSIONS: These findings suggest that prolonged and severe alcohol abuse in men is compatible with normal sexual function during sobriety in the absence of substantial hepatic or gonadal failure.

Adult↗
PubMed1995

[Mental health policies and the transfer of services to the community].

In this article, the mental health policy is viewed as a pivotal element of the "psychiatric services" reform which began in Québec in the seventies. The authors advance the hypothesis that the community approach has played a fundamental role in developing the reform and that it has itself undergone deep changes. As a result, the policy's and the reform's effects are discussed from two angles, namely that of the communitization of services and that of the direction taken by the community approach during the reform process.

Community Mental Health Services↗
PubMed1995

Encouraging drinking at safe limits on single occasions: the potential contribution of protection motivation theory.

Protection Motivation Theory (PMT) is considered as a possible framework for understanding and moderating higher-risk drinking. To this end questionnaire data were collected from 196 participants about levels of their current drinking and, after they have been alerted to the dangers of excess drinking on single occasions, their cognitions relating to drinking and their intentions for future single occasion drinking. Comparisons of higher and lower risk drinkers among the sample provided support for the applicability of PMT, revealing differences in their cognitions and in their adaptive and maladaptive coping. A supplementary path analysis revealed that health beliefs and coping strategies associated with PMT, together with demographics, account for 42% of the variance in behavioural intentions. These results suggest that PMT could prove a valuable tool for those working in alcohol research and education. Implications for the design of effective interventions are discussed.

Adult↗
PubMed1995

Karyotypic evolution in CLL: identification of a new sub-group of patients with deletions of 11q and advanced or progressive disease.

Chronic lymphatic leukaemia (CLL) is the most common leukaemia and is characterized by long-term survival. Previous studies have shown that karyotypic abnormalities are relatively stable and that certain abnormalities may be associated with a poor prognosis. In a prospective 5-year study of 45 patients with typical CLL, sequential karyotypic studies were undertaken every 6-12 months. Clonal karyotypic abnormalities were identified in 62% of patients, either at diagnosis or during the study period with 38% (17/45) exhibiting clonal evolution. In patients with no clinical disease progression, 13q abnormalities were most commonly detected compared with 11q deletions in patients with progressive disease. Karyotypic evolution was significantly associated with progressive disease (12/16, 75% vs 5/29, 17%; P < 0.001, chi2). Thus, karyotypic evolution is not uncommon in CLL, is usually associated with disease progression and deletions of 11q are the commonest detected abnormalities.

Adult↗