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Biomedical subjects

M Whitehead

Publications and source records attributed to M Whitehead.

At least 91 records · Page 5Linked to original sources

Presence of an oestradiol receptor-related protein in the skin: changes during the normal menstrual cycle.

OBJECTIVE: To investigate the presence of an oestradiol receptor-related protein (P29) in skin and skin organelles, and to assess changes in its content during the normal menstrual cycle. DESIGN: An observational study. SETTING: King's College School of Medicine and Dentistry, London. SUBJECTS: Twenty-one premenopausal women with regular menstrual cycles undergoing gynaecological surgery. They were allocated to proliferative or secretory phases of the menstrual cycle on the basis of menstrual dating and histological examination of an endometrial sample. INTERVENTIONS: Small full thickness sections of skin (about 5 mm in depth) taken from the anterior abdominal wall at hysterectomy or laparoscopic sterilization. MAIN OUTCOME MEASURES: The concentration of the oestradiol receptor-related protein in skin and its organelles was assessed semi-quantitatively, using a monoclonal antibody technique. The intensity of staining was compared between the proliferative and secretory phases of the cycle. RESULTS: The receptor-related protein was consistently observed in epidermis, sebaceous glands, hair follicles and sweat ducts; there was no significant difference in its concentration between the proliferative and secretory phases of the menstrual cycle. The protein was not present in dermis and sweat ducts. CONCLUSIONS: Epidermis and some skin organelles contain an oestradiol receptor-related protein and must be considered as oestrogen target tissues. However, the content of this protein does not appear to change significantly during the normal menstrual cycle.

Adult↗

Rapid onset of blindness due to meningeal carcinomatosis from an oesophageal adenocarcinoma.

We report a 49 year old man who presented with left leg weakness, frontal headache, impaired concentration and dysphagia. He was thought to have a benign oesophageal stricture on barium swallow and oesophagoscopy though this was not initially biopsied. During admission his vision deteriorated so that he could only recognize bright light. Repeat oesophagoscopy demonstrated an oesophageal adenocarcinoma. The diagnosis of meningeal carcinomatosis was confirmed at post-mortem. Sudden bilateral blindness is a common feature of meningeal carcinomatosis but, as this is rare, it is not commonly considered in the differential diagnosis of visual loss. The visual loss can be explained by vascular insufficiency in association with tumour cuffing of the subarachnoid space of the optic nerve sheath, by neuronal toxins, or other, as yet unknown, mechanisms.

Adenocarcinoma↗

Poor prognosis of children with pre-B acute lymphoblastic leukemia is associated with the t(1;19)(q23;p13): a Pediatric Oncology Group study.

The prognostic significance of chromosomal translocations, particularly t(1;19) (q23;p13), was evaluated in children with pre-B and early pre-B acute lymphoblastic leukemia (ALL). Patients were treated on a risk-based protocol of the Pediatric Oncology Group (POG) between February 1986 and May 1989. An abnormal clone was detected in 46% (130 of 285) of pre-B cases and 56% (380 of 679) of early pre-B cases. Translocation of any type was associated with a worse treatment outcome than other karyotypic abnormalities: 15 of 66 versus 3 of 64 failed therapy in the pre-B group (P = .001), and 37 of 141 versus 23 of 239 failed in the early pre-B group (P less than .001). The t(1;19) (q23;p13) occurred significantly more often in cases of pre-B ALL with a clonal abnormality than in early pre-B ALL cases (29 of 130 v 5 of 380, P less than .001). Among the 285 pre-B cases in which bone marrow was studied cytogenetically, those with t(1;19) had a significantly worse treatment outcome than all others (11 of 29 v 27 of 256 have failed therapy, P less than .001). This difference is significant (P less than .001) after adjustment for leukocyte count, age, and other relevant features. Cases with the t(1;19) also had a worse prognosis than pre-B patients with other translocations (4 of 37 have failed, P less than .01) or with any other karyotypic abnormality (7 of 101 have failed, P less than .001). We conclude that chromosomal translocations confer a worse prognosis for non-T, non-B-cell childhood ALL, and that the t(1;19) is largely responsible for the poor prognosis of the pre-B subgroup.

B-Lymphocytes↗

Influence of superovulation on endometrial and embryonic development.

The authors have studied the temporal relationship between follicular rupture and endometrial development in 13 women during a natural ovarian cycle (length 25 to 35 days), and subsequently after standard treatment with clomiphene citrate, human menopausal gonadotropin and human chorionic gonadotropin (hCG) to induce multiple folliculogenesis for oocyte recovery, in vitro fertilization, and embryo freezing (cycle length 23 to 27 days). An endometrial biopsy was taken during both cycles 1.5 to 2.0 days after the oocytes had been released or removed. The samples were examined by light and transmission electron microscopy. Samples of peripheral blood were taken at defined times for hormone analysis. After treatment 11 subjects (85%) had advanced morphological development of the endometrium (8 women by 3 to 4 days, 3 women by 1 to 2 days). The concentrations of plasma estradiol (E2) and progesterone (P) on the days of follicular rupture and endometrial biopsy were significantly raised in the treatment cycles. The concentration of total urinary estrogens on the day of hCG administration and the mean change in the concentration of plasma E2 (treatment/control) on the days of endometrial biopsy were positively correlated with the extent of endometrial advancement. In addition, the mean change in the concentration of plasma P (treatment/control) was markedly increased on the days of follicular rupture and endometrial biopsy in those subjects with an advanced endometrium. Embryonic development was not so obviously related to the extent of superovulation. Asynchronous endometrial and embryonic development may therefore contribute to the low pregnancy rate in these patients.

Adult↗

Successful pregnancy following bone marrow transplantation for leukaemia.

We report three pregnancies with successful outcomes in two women following allogeneic bone marrow transplantation (BMT) for acute leukaemia using high dose melphalan alone as conditioning therapy. The increasing application and success of BMT together with the instigation of conditioning regimens that do not include total body irradiation should increase such cases. These and previous cases document that a normal outcome of pregnancy is likely in these patients.

Adult↗

Studies on folliculogenesis and in vitro fertilization outcome after the administration of follicle-stimulating hormone at different times during the menstrual cycle.

The authors have undertaken a prospective, randomized clinical trial of six treatments to optimize folliculogenesis in patients prior to oocyte collection, in vitro fertilization, and embryo transfer. All treatments involved the administration of the same daily dose of follicle-stimulating hormone (FSH), but at different times during the antecedent and/or current menstrual cycle. There was a significant difference (P less than 0.01, chi-square test) between treatments in the clinical pregnancy rate/patient (19 clinical pregnancies, 67 patients). No advantages were observed for regimens that involved starting treatment during the antecedent cycle. The study was continued with the three treatments that started during the current cycle (24 clinical pregnancies, 58 patients). The most cost-effective regimen was clomiphene citrate, 100 mg/day for days 2 to 6 inclusive; FSH, 150 units/day for days 1 to 4 inclusive; and human menopausal gonadotropin, 150 units/day from day 5 until the day of human chorionic gonadotropin administration.

Adult↗

The sequential use of a luteinizing hormone-releasing hormone (LH-RH) agonist and human menopausal gonadotropins to stimulate folliculogenesis in patients with resistant ovaries.

The diagnostic response toward the administration of a luteinizing hormone-releasing hormone (LH-RH) analogue in the early follicular phase has been used sequentially with conventional human menopausal gonadotropin (hMG) treatment in patients who had previously failed to develop multiple follicles in response to a combination of hMG and clomiphene citrate. Nine of fourteen patients (64%) showed an increase in the number of preovulatory follicles and five subjects reached oocyte recovery for the first time. Two patients (22%) became pregnant after in vitro fertilization and embryo transfer during the treatment cycle and had healthy babies. It is suggested that this treatment regimen may be advantageous in some patients with resistant ovaries.

Adult↗

The effect of hysterectomy on the age at ovarian failure: identification of a subgroup of women with premature loss of ovarian function and literature review.

The age at ovarian failure was determined in 90 women who had previously undergone abdominal hysterectomy with bilateral ovarian conservation and in 226 women who had undergone a spontaneous menopause. The mean age of ovarian failure in the hysterectomized group was 45.4 +/- 4.0 years (standard deviation), and this was significantly lower than the mean age of 49.5 +/- 4.04 years in the nonhysterectomized control group (P less than 0.001). There was a significant correlation between the age at hysterectomy and the age of ovarian failure in the women who were 44 years or less at the time of ovarian failure (r = 0.62, P less than 0.001), implying a causal relationship. The indication for hysterectomy did not influence the time of ovarian failure. Two explanations are proposed as to how conventional surgery for hysterectomy may adversely affect ovarian function.

Adult↗

Studies on the measurement and pharmacodynamics of human follicle-stimulating hormone.

The levels of immunoreactive follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), cortisol, and estradiol (E2) have been determined in serial samples of peripheral plasma from four subjects during the continuous, subcutaneous administration of Buserelin (Hoechst [UK] Ltd., Hounslow, UK) (250 micrograms/day) and after the intramuscular injection of purified, urinary FSH (Metrodin, Serono Laboratories [UK] Ltd., Welwyn Garden City, UK) (150 IU). During Buserelin administration the geometric mean levels of FSH and LH as measured by immunoradiometric assay were reduced by 87% and 37%, respectively, when compared with the corresponding values for days 1 and 2 of the menstrual cycle. After the intramuscular injection of FSH, peak levels (from 3.4 to 6.2 IU/l) occurred in peripheral plasma between 6 and 18 hours later. The levels were significantly elevated after 72 hours (P less than 0.01, Student's paired t-test). There was no obvious effect of the drugs on the circadian rhythms of plasma PRL or cortisol, and no significant effect on the circulatory levels of LH or E2.

Adult↗

A comparison of treatments with exogenous FSH to promote folliculogenesis in patients with quiescent ovaries due to the continued administration of an LH-RH agonist.

The circulating levels of plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH) and oestradiol (E2) have been determined in three groups of three subjects during the continuous, subcutaneous administration of an LH-RH agonist (250 micrograms/day) and after the intramuscular injection of urinary FSH (group I, 150 IU daily for 8 days, total 1200 IU; group II, 300 IU on alternate days for four injections, total 1200 IU; and group III, 150 IU on alternate days for four injections, total 600 IU). The level of circulating FSH in group I rose steadily from a geometric mean of 1.11 (pre-injection) to 8.76 U/l (at day 8), while the corresponding levels in groups II and III fluctuated according to the time and dose of the injected material. Twenty-four hours after the injection the mean level of FSH in group II was significantly higher (7.31 U/l) than the corresponding value for group I (2.79 U/l) or group III (3.48 U/l). Only those subjects in group II showed a resumption of folliculogenesis (leading, mean maximum follicular diameters of 16, 13 and 14 mm, respectively) and a corresponding increase in the concentration of plasma E2 (from 22, 43 and 103 to 906, 1477 and 2362 pmol/l, respectively).

Adult↗

Relationships between psychological symptoms, somatic complaints and menopausal status.

The importance of distinguishing climacteric symptoms from other psychological and somatic complaints has been repeatedly stressed, but as yet no detailed guidelines are available to assist the clinician in the day-to-day management of patients. Previous epidemiological surveys of climacteric symptoms have been criticised because of inadequate methodology. We have attempted to overcome most of these problems and to provide a more detailed analysis of the relationships between menopausal status and psychological and somatic symptoms. Eight hundred and fifty pre-, peri- and post-menopausal women, aged 45-65 yr, took part in a cross-sectional survey of general health, psychosocial factors and current symptomatology. They were a non-menopause clinic sample and were blind to the purpose of the study. Using a principal components analysis, the relationships between symptoms were examined. Certain psychological and somatic symptoms occurred together in specific clusters. Some of these symptom clusters, e.g., vasomotor symptoms and sexual difficulties, were best predicted solely by menopausal status, while others, such as psychological and somatic symptoms, were more clearly associated with psychosocial factors. On the basis of these results, guidelines for the assessment of climacteric and post-menopausal women can be suggested.

Aged↗

The hand-foot-uterus syndrome: a case study.

An autosomal dominant syndrome is described in 26 members of six generations in a single family. Distal extremity malformations are characteristic and superficially resemble those of arthrogryposis, chondroectodermal dysplasia, Cornelia de Lange syndrome, Faconi's anemia or Holt-Oram syndrome. There is an absence of spinal deformity, and females of the disorder have duplication of the genital tract.

Abnormalities, Multiple↗