The prognostic value of age and follicle-stimulating hormone levels in women over forty years of age undergoing in vitro fertilization.

PURPOSE: Basal follicle-stimulating hormone (FSH) and age are predictors of successful outcome in in vitro fertilization (IVF). More recently, the clomiphene citrate challenge test (CCCT) has been proposed as a better way to predict IVF outcome than FSH alone. The purpose of this study was to determine which indicator of ovarian reserve--basal (day 3) FSH or the CCCT--is the better predictor of IVF success in the critical age group of women over the age of 40. METHODS: In this retrospective study, basal FSH and clomiphene-stimulated FSH levels from 104 women who underwent 175 cycles of IVF were analyzed. RESULTS: Neither basal FSH level nor stimulated FSH level alone were statistically significant predictors of IVF success; however, no patient with a day 3 FSH level > 11.1 mIU/ml or a stimulated day 10 FSH level > 13.5 mIU/ml conceived and carried a pregnancy. All ongoing pregnancies occurred in the first two cycles of IVF. CONCLUSIONS: Clear prognostic cutoff values were found to predict IVF success in women over age 40. IVF programs should consider limiting the number of cycles of IVF in women above age 40.

Morbidity and prescribing patterns for the middle-aged population of Scotland.

BACKGROUND: As part of a large national survey of morbidity recording on general practice computers, morbidity and prescribing data were collected from three separate sources for more than 10,000 patients aged 45-64 years, randomly selected from 41 Scottish general practices. AIM: To amalgamate the three sources of data to provide estimates of prevalence rates for a range of common chronic diagnoses, and of medication rates for associated repeat prescription drugs. METHOD: Forty-one Scottish general practices were selected on a geographic basis in relation to the national population distribution. Within each practice, 250 patients aged 45-64 years were selected at random. Data relating to 19 diagnoses and 40 repeat prescription drugs were extracted from the computer records of these patients and compared with information held on patients' paper records and supplied by patients in response to a postal questionnaire. After assessing the completeness and accuracy of computer-held information, the three sources of data were amalgamated according to agreed protocols. RESULTS: Lifetime prevalence rates are presented for each diagnosis, broken down by sex and age group. Differences in rates between the sexes, and with change in age, were in the expected direction for all diagnoses, and were matched by corresponding differences in entitlements to repeat prescription drugs. Comparison of these lifetime rates with published prevalence rates indicates a latent pool of morbidity within the community, which ranges from 1.0 to 10.0 times the annual prevalence rate for different conditions. CONCLUSION: The amalgamated data provide an estimate of lifetime prevalence rates for the range of conditions examined. They complement conventional morbidity statistics and have potential value in allowing the underlying management costs of specific chronic conditions to be evaluated.

Completeness and accuracy of morbidity and repeat prescribing records held on general practice computers in Scotland.

BACKGROUND: A high proportion of Scottish general practices use a standard computer software package (GPASS, general practice administration system for Scotland), and thus, Scotland is uniquely placed to amalgamate primary care data on a national scale. Practices, however, vary widely in the nature and extent of data entered on computer and a major limitation on the use of the collected data is the absence of information on the completeness and accuracy of the computer database. AIM: This study set out to assess the quality of morbidity and repeat prescribing records held on computer by general practices in Scotland. METHOD: Forty-one practices, with above average levels of morbidity data recorded on computer, were selected on a geographic basis in relation to the national population distribution. Within each practice, 250 patients aged 45-64 years were selected at random. Data relating to 19 diagnoses, six surgical procedures and 40 repeat prescription drugs were extracted from the computer records of these patients and compared with information held on patients' paper records and supplied by patients in response to a postal questionnaire. The completeness and accuracy of computer entries were assessed in terms of sensitivity and positive predictive value, respectively. RESULTS: For the 5567 patients for whom all three sources of data (validated computer records, paper records and questionnaire responses) were available, sensitivity (completeness) of morbidity recording had median values of 0.67 for diagnoses, 0.93 for surgical procedures and 0.75 over all conditions examined. Practices varied both in the completeness of recording of each condition and in their overall performance. The predictive value (accuracy) of morbidity data was uniformly high for all conditions examined (median 1.00). For repeat prescription drugs, recording on GPASS was both complete and accurate. CONCLUSION: The recording of morbidity data on GPASS for 45-64-year-old patients in a selected group of 41 highly-computerized practices is about 75% complete and highly accurate. For national morbidity studies, it seems likely that amalgamated data from the best GPASS practices will be as complete and accurate as the morbidity statistics currently derived from hospital-based activities in Scotland.

Plasma adenosine concentrations during adenosine-induced respiratory stimulation in man.

Intravenous infusion of the nucleoside adenosine stimulates respiration, probably at least partly by an action in the carotid bodies, and also potentiates the ventilatory response to hypoxia, suggesting that it might be involved in the control of breathing. Whether the effects of adenosine occur at concentrations likely to be achieved in vivo is unknown and was investigated in 7 patients with arterial catheters inserted for diagnostic purposes. During intravenous infusion of adenosine (Maximum dose per min: mean 130 micrograms kg-1) mean minute ventilation increased from 5.5 to 10.9 l min-1 while mean plasma adenosine concentration in the aortic arch increased from 0.07 to 1.2 microM. In 3 patients ventilation first increased without a detectable increase in aortic adenosine concentration, suggesting a possible intra-pulmonary effect of adenosine, although increased concentrations were apparent at higher doses. Micromolar concentrations of adenosine are probably achieved in vivo in tissues during hypoxia. The present results show that at such concentrations adenosine stimulates respiration and are consistent with the suggestion that adenosine release may mediate or modulate the ventilatory response to hypoxia. A possible intra-pulmonary effect of adenosine merits further study.

Acute haemodynamic effects of intravenous infusion of adenosine in conscious man.

The acute haemodynamic effects of intravenous infusion of adenosine, a dilator of most vascular beds, were studied in 16 patients (seven with coronary artery disease, nine with normal coronary arteries) undergoing cardiac catheterization for investigation of chest pain. At the lowest dose used (4.3 mg min-1) adenosine increased minute ventilation by 44% (P less than 0.01, n = 11) and reduced pulmonary vascular resistance by 20% (P less than 0.05) without causing other significant haemodynamic changes. Symptoms, including chest discomfort in 14 patients and dyspnoea in 11, limited the maximum dose to 8.5 +/- 2.3 mg min-1 (mean +/- SD, 108 +/- 24 micrograms kg-1 min-1). At this dose, adenosine reduced pulmonary and systemic vascular resistance (by 38% and 34%, respectively) and increased heart rate (by 34%), stroke index (by 12%) and cardiac index (by 52%). Systemic blood pressure and right atrial pressure did not change. Unexpectedly, adenosine increased left ventricular end-diastolic pressure (LVEDP) (from 5 +/- 6 to 14 +/- 10 mmHg, n = 8), pulmonary capillary wedge pressure (from 3 +/- 2 to 10 +/- 5 mmHg, n = 16) and consequently mean pulmonary artery pressure (from 10 +/- 2 to 16 +/- 5 mmHg). Minute ventilation increased by 84% (n = 11), resulting in hypocapnia (PCO2: 31 +/- 3 mmHg, n = 8) and alkalosis (pH: 7.46 +/- 0.02, n = 8). Oxygen consumption was unchanged during the infusion, but increased by 21% 5 min post infusion. All effects were similar in patients with and without coronary artery disease. Adenosine therefore causes pulmonary and systemic vasodilation and respiratory stimulation. Symptoms and an increase in LVEDP of uncertain cause, which occur with high doses, may limit the use of adenosine as a systemic vasodilator in conscious subjects. However at lower doses adenosine causes selective pulmonary vasodilation which merits further study.

Medicines regulation in the United Kingdom.

Modern society seeks pharmaceutical products which are safe, effective and of good quality. Many health workers may be unfamiliar with the licensing system for human medicines which attempts to ensure that those goals are attained. In the United Kingdom the legislative framework to attain these objectives is the Medicines Act 1968, together with relevant European Community Directives. This paper briefly describes an outline of the licensing structure, explains the steps by which a new human medicine may reach the market and gives an indication of current licensing procedures by describing some considerations in the handling of an application for a product licence.

Adenosine-induced respiratory and heart rate changes in young and elderly adults.

The effects of intravenous boluses of adenosine on respiration and heart rate were compared in young and elderly individuals. Respiratory stimulation and biphasic changes in heart rate were confirmed. The dose-response relationship for the effects of adenosine on respiration and heart-rate did not differ significantly between 10 young (mean age 25.2 +/- 4.9 years) and 10 elderly (mean age 66 +/- 3.1 years) drug-free individuals, indicating that age is unlikely to be a major determinant of adenosine responsiveness.

Adenosine causes transient dilatation of coronary arteries in man.

We investigated the effects of i.v. adenosine on coronary blood flow in 10 normal subjects undergoing investigation for chest pain. Coronary flow transiently doubled after greater than or equal to 3.5 mg adenosine without increase in perfusion pressure, systolic load or inotropic state at a constant, paced heart rate. The data provide direct evidence that adenosine dilates coronary arteries in man. The transience of the effect suggests a possible role for adenosine in repeated estimations of coronary flow reserve.

A comparison of the effects of oral nadolol and topical timolol on intraocular pressure, blood pressure, and heart rate.

We compared the effects of oral nadolol 20 mg once daily and topical timolol 0.25% twice daily on the intraocular pressures of 22 glaucoma suspects, in a 12 week double-masked crossover study. Both nadolol and timolol reduced intraocular pressure (p less than 0.001). The reductions in intraocular pressure did not differ significantly after two weeks and four weeks of treatment. Nine of these subjects underwent treadmill exercise tests in order to compare the effects of nadolol and timolol on the cardiovascular system. The effects of the two treatments on blood pressure were comparable, but nadolol caused a significantly greater reduction in heart rate than timolol at rest (p less than 0.05). Nadolol reduces intraocular pressure effectively and may prove a useful alternative treatment for chronic simple glaucoma.

Left main coronary artery occlusion with preserved left ventricular function: a report of three cases.

Three patients with angina pectoris are reported in whom occlusion of the left main coronary artery was found at coronary arteriography. In these three patients left ventricular function was well preserved. In all three the right coronary artery was dominant and there were prominent epicardial and septal collateral vessels to the territories normally supplied by the left anterior descending and circumflex arteries. It seems reasonable to suggest that this coronary artery anatomy and collateral vessel formation accounted for the preservation of the left ventricular myocardium in these patients.

Adenosine-induced respiratory stimulation in man depends on site of infusion. Evidence for an action on the carotid body?

Adenosine is an endogenous nucleoside which stimulates respiration in man and other mammals. In animals adenosine appears to initiate respiratory stimulation within the carotid body, but whether this is the site of action in man is not known. We administered adenosine by intra-aortic infusion to 12 subjects undergoing cardiac catheterisation. When adenosine was infused at three sites proximal to the carotid circulation, minute ventilation was significantly higher than baseline values or those during adenosine infusion at a more distal site. These results support the hypothesis that adenosine-induced respiratory stimulation in man is mediated in the carotid body.