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.     

The effects of cigarette smoking and alcohol consumption on blood haemoglobin,erythrocytes and leucocytes: a dose related study on male subjects

Summary The objective of this study was to quantify the combined dose related effects of cigarette smoking and alcohol consumption on blood haemoglobin concentration, erythrocytes and leucocytes. The subjects consisted of 17 670 males attending for routine health screening, with an average age of 43 years and a range of 16–91 years. The number of cigarettes smoked each day was divided into six categories, and declared alcohol consumption into seven. Of the 42 different combinations of smoking and drinking groups, five were not reported because they contained less than 30 subjects. Haemoglobin concentration was significantly increased in those smoking more than 10 cigarettes per day. Smoking also increased the PCV. Alcohol had no effect on Hb or PCV. The red cell count was reduced by alcohol consumption, with even the lowest consumption producing a significant decrease. Both smoking and drinking raised the MCV in a linear dose relationship. The marked increase in white cell count with smoking was seen even in subjects smoking 10 cigarettes per day or less. It is suggested that social habits such as smoking and drinking should be considered when interpreting blood haematology values. Changes in haematology results could be used to encourage a healthier lifestyle.     

A Phase I study of acivicin in refractory pediatric solid tumors

Forty-two patients with progressive solid tumors and brain tumors were entered in this Phase I study of the glutamine antagonist acivicin given intravenously over thirty minutes daily for five days. The major toxicities encountered were myelosuppression and central nervous system toxicity (nightmares and somnolence). The maximum tolerated dosage on this schedule was 26 mg/M² daily for five days. Six patients including three patients with brain tumor had stable disease.     

Management of the menopause.

The management of the peri- or postmenopausal patient, whether symptomatic or asymptomatic, involves a careful assessment of the problems and expectations of each patient and the matching of appropriate treatment to their needs. The effects of the menopause and its treatment on the patient's immediate and long-term health must be taken into account. This may involve consideration of aspects of medical topics as diverse as gynaecological endocrinology, bone metabolism, oncology and cardiology. Although the benefits of oestrogen therapy are well established the response to therapy must be carefully monitored. Vigilance in the monitoring and seeking out of adverse effects both in individuals and populations must continue to ensure that any problems with this form of therapy are detected at the earliest possible stage.     

HRT: developments in therapy.

Various forms of oestrogen have been available for use as Hormone Replacement Therapy (HRT) for approximately 50 years. However, there has been little change in the mode of administration until the last 10-15 years. Although the oral route has remained the mainstay of therapy, non-oral routes of administration have been developed. During the 1970s it became clear that use of unopposed oestrogens in women with an intact uterus resulted in an increase in risk of endometrial carcinoma and thus the current practice of adding a sequential progestogen each month, to prevent endometrial hyperplasia, was introduced. However, certain progestogens can cause side-effects and some of the metabolic changes which they induce are potentially undesirable. Thus the search continues for new oral progestogens which are more 'metabolically friendly' than those in current use. Additionally, non-oral delivery systems for progestogens have been studied, such as the transdermal route (patches) and local administration within the uterine cavity (progestogen-containing intra-uterine devices). Both these strategies may minimise their symptomatic, psychological and metabolic effects. Continuous (every day) administration of progestogens in combination with the oestrogen, or the use of new compounds (e.g. tibolone) may overcome the problem of regular withdrawal bleeding which some women find unacceptable. However, it remains to be determined whether such therapies are as efficacious as conventional oestrogen/sequential progesterone regimens.     

Prospective epidemiological studies involving paired organs

Standard methods for analysing survival data or case-control data normally concern factors affecting a subject as a whole. However, in a study of a condition that might develop in one or both of a pair of bodily organs information on response and on covariates may be available for each separately. This information can be used to investigate whether the presence of a factor on one side is associated with the condition on that same side, and thus leads to more direct evidence concerning aetiology. In this paper methods of analysing data on paired organs are described. The techniques are illustrated using data from a case-control study of breast cancer, in which the role of breast calcifications was of interest.     

The disposition of ketoprofen enantiomers in man.

1. The disposition of ketoprofen enantiomers was studied in 21 patients taking racemic ketoprofen (Orudis SR). 2. In each patient the plasma concentrations of the R- and S-enantiomers were similar at all times over a 24 h dosing interval. The mean (+/- s.e. mean) time-averaged plasma ketoprofen concentrations over the dosage interval were 0.76 (+/- 0.06) mg l-1 for R-ketoprofen and 0.78 (+/- 0.06) mg l-1 for S-ketoprofen. 3. Creatinine clearances for the 21 patients ranged from 6-162 ml min-1. There was no correlation between creatinine clearance and time-averaged plasma concentration for either R- or S-ketoprofen. 4. Approximately 30% of the dose was recovered in urine (unconjugated + glucuronide conjugate) and this was made up of 43% R-ketoprofen and 57% S-ketoprofen. Because of incomplete urine recoveries of ketoprofen it was not possible to determine whether inversion from the R- to the S-enantiomer takes place in man. 5. The data suggest that in terms of total (bound + unbound) ketoprofen, half the concentration value derived by a non-enantiospecific analysis would give a reasonable approximation of the pharmacologically active S-enantiomer concentration in plasma.     

Time and depth resolved visualisation of the diffusion of a lipophilic dye into the hair follicle of fresh unfixed human scalp skin.

Visualising the penetration pathway of a lipophilic model dye into the hair follicle of fresh unfixed human skin would facilitate optimisation of drug formulations for local delivery to the pilosebaceous unit. A block of fresh human scalp skin was mechanically fixed in a newly designed combination of cutting device/on-line diffusion cell, manual cross-sectioned perpendicular to the skin surface and sealed to create the donor and acceptor compartment. The donor phase consisted of a saturated solution of Bodipy FL C(5) in a citric acid buffer solution. Images were obtained on-line by confocal laser scanning microscopy (CLSM) every 30 min for 16 h. For each time point and each skin region relative intensity values were calculated. The on-line visualisation showed a fast diffusion of the label into the gap of the hair follicle followed by a fluorescent staining in the gap itself. The data strongly indicate that the fluorescence in the cuticle originates mainly from the dye of the gap and not from the surrounding epidermis. The on-line visualisation provides a new and excellent tool to monitor simultaneous changes in distribution profiles in the various skin layers including the hair follicle. This information can be used to determine penetration pathways in the skin.