Effects of tibolone on lipoprotein(a) and HDL subfractions

Objective: To determine the effects of tibolone, a synthetic steroid used to alleviate climacteric symptoms and prevent osteoporosis, on lipoprotein metabolism, with particular reference to lipoprotein(a) levels and HDL subfraction profiles.Design: Thirty nine postmenopausal women were treated with tibolone (Livial) 2.5 mg/day for 6 months and fasting serum lipoprotein levels were estimated at 0, 2, 4 and 6 months. Results: Lipoprotein(a) levels were reduced significantly over the 6 months from a median level of 245 (range <60–780) mg/I to 152 (range <60–530) mg/l, a reduction of 39% in the median level. A decrease was observed in approximately two thirds of the women. Reductions were noted in all 6 subjects whose pretreatment levels were high, although concentrations remained at a level associated with increased risk in all but one. There were significant decreases in triglycerides and VLDL cholesterol and no significant change in LDL cholesterol. There was a significant reduction of 18% in HDL cholesterol and a 26% reduction in the HDL₂:HDL₃ ratio. Conclusion: The reduction in lipoprotein(a) levels may have a beneficial effect on cardiovascular risk, which could go some way towards balancing the potentially adverse effect on the cardiovascular system caused by the reduction in HDL cholesterol.     

Social Security disability determinations. Knowledge and attitudes of consultative physicians

Social Security spends $135 million yearly, contracting with physicians to provide consultative examinations for disability applicants. However, little is known about who these physicians are or how they view the determination of impairment. We surveyed a random sample of 153 physicians from North Carolina who performed consultative examinations for the North Carolina Disability Determinations Agency in 1983 (the consultative group), and a randomly selected group of 165 physicians of similar medical specialties (the comparison group). Response rates were 75% for the consultative group and 66% for the comparison group. Most consultative physicians (63%) performed fewer than 6 examinations per month. Characteristics of the consultative physicians were similar to the comparison group. Both groups were skeptical of the claims of disability applicants; 48% of the consultative and 55% of the comparison group thought that a majority of applicants could be employed. Of the consultative physicians, 53% indicated that they had learned little about disability programs from any source. Most consultative physicians (58%) judged it "almost impossible" to determine impairment on the basis of a single office examination. However, consultative physicians were less likely than the comparison group to view Social Security as difficult to work with (25% vs. 54%; P less than 0.01). Agencies that determine disability ask physicians to perform a task for which they feel ill prepared and have little special knowledge.     

Validation and application of single breath cardiac output determinations in man

Cardiac outputs by single breath (Qsb) and Fick (Qf) procedures were compared in five healthy males during supine rest and exercise with Qf ranging from 6-19 L X min-1. The prolonged exhalation (SB) was not controlled. The Qsb calculations incorporated an equation of the CO2 dissociation curve and a "moving spline" sequential curve-fitting technique to calculate the instantaneous R from points on the original expirogram. The resulting linear regression equation for all 38 comparisons obtained (r = +0.76, p less than 0.001, mean difference +/- S.D. = 2.93 +/- 2.72 L X min-1) indicated a 24% underestimation of Qf. A substantial portion of the variability during exercise (n = 28) was due to a difference in alveolar ventilation between the time of the mixed expired (E) gas collection and the SB maneuver. When Qsb was corrected (Qsb) by a linear regression based on the difference between Re and Rsb during exercise and by adding 2.44 L X min-1 at rest (the mean difference), the relationship was greatly improved (Qsb = 0.14 + 0.99 Qf, r = +0.93, mean difference +/- S.D. = 0 +/- 1.47 L X min-1). A subsequent study during upright rest and exercise to 80% of VO2max in 6 subjects indicated a close linear relationship between Q'sb and VO2 for all 95 values obtained (r = +0.94), with slope and intercept close to published studies utilizing invasive cardiac output measurements. Considerations of measured blood gases in relation to estimated values suggested that underestimates of Qf arose, at least in part, from arterial desaturation during the SB maneuver. Detailed computational procedures are provided for implementing this improved Qsb procedure.     

The complications of extracorporeal shockwave lithotripsy: management and prevention

Extracorporeal shockwave lithotripsy has been shown to be a safe and effective method of treating most upper urinary tract stones. Major complications, although few, include haemorrhage, septicaemia, "Steinstrasse" formation and cardiac arrhythmias. The experience from 600 consecutive cases is reviewed and methods of prevention are discussed.     

Effects of 8-OH-DPAT, 5-CT and muscimol on behaviour maintained by a DRL20 schedule of reinforcement, following microinjection into the dorsal or median raphe nuclei

Experiments were performed to investigate the effects of microinjections of the 5-HT(1A) agonist 8- hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), the non-selective 5-HT(1) agonist 5-carboxamidotryptamine (5-CT) and the GABA(A) agonist muscimol into the midbrain raphe nuclei, on behaviour maintained by a differential reinforcement of low rate (DRL) 20 schedule of food reinforcement. Following acquisition of responding under the DRL20 schedule, in which responses were reinforced only if they occurred at least 20s after the previous response, two groups of rats were prepared with a stainless steel guide cannula aimed at either the dorsal raphe nucleus or the median raphe nucleus. Injections of 8-OH-DPAT and 5-CT into the median raphe dose-dependently increased responding and reduced the number of reinforcers earned, leading to a net reduction in response efficiency from 45% to approximately 27% (5μg 8-OH-DPAT) and 22% (375ng 5-CT). Both drugs appeared to shift the frequency distribution of inter-response times (IRTs) towards shorter IRTs, and lowered the mean IRT. These effects were not observed after dorsal raphe injections of either drug. This pattern of results, together with results obtained in other paradigms measuring response inhibition, suggests that suppression of the activity of median raphe 5-HT neurones induces deficits in the ability to withhold responding. Muscimol increased responding, decreased the number of reinforcers earned and reduced response efficiency after both dorsal raphe and median raphe injections. These effects were more pronounced following median raphe injections, and were of considerably greater magnitude than those observed following treatment with the 5-HT agonists. Muscimol injected into the median raphe lowered the mean IRT, and increased the frequency of short duration IRTs. Thus, stimulation of GABA(A) receptors within the median raphe induces a pattern of behavioural disruption in the DRL task, that is more severe than that resulting from selective inhibition of 5-HT neural activity. The effects of muscimol probably arise from a general behavioural activation, rather than a specific deficit in the ability to withhold responding.