Trends in analgesic self-poisoning in West-Fife, 1971-1985

All admissions for analgesic self-poisoning to a district poisons unit over a 15-year period have been reviewed. During this time overdose with analgesic drugs increased to represent almost half of all admissions for self-poisoning. The types of analgesics taken in overdose also changed significantly during the period of this review. Aspirin and Distalgesic poisoning declined in incidence and more cases of self-poisoning by paracetamol and non-steroidal anti-inflammatory agents were seen. The impact of these changes on the medical management and outcome of deliberate self-poisoning is analysed. The reasons behind the trends described in this paper are assessed and their implications for future prevention and treatment are discussed.     

Treatment of heart failure in the elderly

Heart failure is a syndrome of breathlessness, fatigue and oedema. The effects of ageing on myocardial function and the prevalence of often multiple cardiac pathologies makes heart failure a disease of the elderly, usually characterized by primary or secondary myocardial systolic dysfunction. Appropriate treatment, which requires precise diagnosis, involves correction of precipitating or aggravating factors and the rational use of drug therapy. Diuretics and ACE inhibitors offer a combination of both symptom control and improvement in prognosis. Other agents such as digoxin, xamoterol and nitrates may be particularly useful in the treatment of patients with associated problems such as atrial fibrillation and angina. Because both ageing and heart failure may alter pharmacokinetics and pharmacodynamics, safe and effective treatment of heart failure in the elderly requires understanding of the clinical pharmacology of the drugs used.     

Identified motoneurons and their innervation of axial muscles in the zebrafish

The organization of spinal cord motoneurons and their innervation of axial (white) muscles in the zebrafish were studied. Motoneurons can be divided into 2 classes, primary and secondary, on the basis of their cell-body sizes and positions. Each side of each spinal segment contains 3 primary motoneurons that are uniquely identifiable as individuals by their stereotyped cell-body positions and peripheral branching patterns. Moreover, these motoneurons precisely innervate cell-specific subsets of contiguous muscle fibers in mutually exclusive regions of their own body segment. Individual muscle fibers receive inputs from a single primary motoneuron and, in addition, from up to 3 secondary motoneurons. The results demonstrate that the precision of innervation previously described in invertebrates is also present in some vertebrates.     

Cardiovascular responses of pregnant women during aerobic exercise in water: a longitudinal study

To determine the effects of pregnancy on the cardiovascular responses to immersion and exercise in water, 12 women completed 20 min of immersion and 20 min of bicycle ergometry at 60% predicted VO2max in 30 degrees C water during their 15th, 25th, and 35th week of pregnancy as well as 8-10 weeks post partum. Immersion lowered the resting heart rate approximately 8 bts/min (P less than 0.05). Exercise in water also resulted in a lower heart rate as compared with the same level of exercise on land (132 +/- 4 vs 149 +/- 6 bts/min; P less than 0.05). Both the rest and exercise heart rate responses were independent of duration of pregnancy or pregnancy status. Post partum exercise cardiac output averaged 9.9 +/- 0.4 l/min, significantly lower (P less than 0.05) than the 15th (12.7 +/- 0.5), 25th (14.7 +/- 0.5), or 35th week (15.1 +/- 0.7 l/min). Total peripheral resistance was greatest (P less than 0.05) post partum (657 +/- 29 dyn.s/cm5) compared with either the 15th (515 +/- 27), 25th (407 +/- 18), or 35th week (450 +/- 23). The results indicate that exercise in water lowers the heart rate compared with land exercise at the same metabolic rate. The combined effect of exercise, water, and pregnancy may elevate the cardiac output more than expected on land, but the same general pattern of exercise response will be evident throughout the duration of pregnancy. The results further suggest that water alters the heart rate and blood pressure responses such that land-derived exercise target heart rates should not be used to prescribe exercise intensity in water.     

Treatment of chronic heart failure: a comparison between the major guidelines.

Because of rapid advances in the treatment of chronic heart failure, four important guidelines, including those from the European Society of Cardiology, have recently been updated. This review compares and contrasts the levels of evidence and classes of recommendation given to each of the key pharmacological and device therapies advocated by these guidelines. Possible explanations for discrepancies between the guidelines are discussed. Future approaches that might clarify the grade of evidence allocated and class of recommendation made are also described.     

Effects of the antimigraine compound zolmitriptan ('Zomig') on psychomotor performance alone and in combination with diazepam in healthy volunteers

Zolmitriptan (Zomig^TM) is a 5HT_1B/1D agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous system side effects, this randomized, double-blind, placebo-controlled, 6-period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following "treatments" as single doses: zolmitriptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg+diazepam 10 mg, zolmitriptan 5 mg+diazepam 10 mg and placebo. Pre-dose and at 1, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination.     

Indapamide inhibits endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat

Summary— Experiments were designed to determine whether or not indapamide, an antihypertensive agent with vasodilator properties, inhibits endothelium-dependent contractions. Rings of aortae with and without endothelium from spontaneously hypertensive rats (SHR) were suspended in conventional organ chambers for the measurement of isometric force. Acetylcholine and adenosine diphosphate-β-S in the presence of a nitric oxide synthase inhibitor, caused endothelium-dependent contractions, which were inhibited by indapamide. The compound (10⁻⁴M) also slightly reduced the contractions of rings without endothelium evoked by U-46,619, which activates thromboxane-endoperoxide receptors. These results demonstrate that indapamide inhibits endothelium-dependent contractions in the SHR aorta, and suggest that the inhibition is due, at least in part, to the action of the drug on the hypertensive vascular smooth muscle.     

Protein malnutrition alters the distribution of Fc gamma R+ (T gamma) and Fc mu R+ (T mu) T lymphocytes in experimental pulmonary tuberculosis.

Inbred, strain 2 guinea pigs were given isocaloric diets containing either 30% (control diet) or 10% (low-protein diet) ovalbumin and infected 4 weeks later by the respiratory route with virulent Mycobacterium tuberculosis. By using an Fc receptor rosette assay, the proportions of T lymphocytes bearing Fc receptors for immunoglobulin G (T gamma cells) or immunoglobulin M (T mu cells) were quantified in blood and lymphoid tissues taken postinfection. A significant elevation in the proportion of the putative suppressor T subset (T gamma) in the blood of protein-deprived guinea pigs was observed at all intervals postinfection. Conversely, the levels of the putative helper T subset (T mu) in the bronchotracheal lymph nodes draining the site of virulent infection in malnourished animals were significantly reduced. Diet did not influence T gamma or T mu cells in the spleens. Diet-induced loss of purified protein derivative-specific T-cell functions in tuberculosis may be associated with alterations in the proportions of or the balances between T gamma and T mu subsets.     

The effect of protein malnutrition on the IgA immune response in mice.

The influence of protein malnutrition on the IgA immune response was determined in BALB/c mice fed isocaloric diets containing 20% (control), 4%, or 2% protein. We describe here a severely protein-deficient state (6 weeks on a 2% protein diet) and a moderately malnourished state (6-8 weeks on a 4% protein diet). The total IgA concentration in intestinal washes, as determined by radial immunodiffusion, was reduced at 6 and 8 weeks in the 4% diet group and at 6 weeks in the 2% diet group, compared to the controls. Serum IgA levels were significantly elevated in both the 2% and 4% diet-fed groups at all time intervals. The IgA anti-sheep red blood cell (SRBC) plaque-forming cell (PFC) response generated after oral immunization with SRBC did not differ between the control and the 4% diet group at any time interval, yet the IgA PFC/spleen response was significantly reduced in the 2% diet group at all time intervals studied. However, the IgA PFC/10(6) spleen cells was reduced only with the 2% protein diet group at 6 weeks. Severely protein-deficient mice replenished with the control diet for 3 weeks showed a recovery to values similar to the 8-week control group of both the IgA PFC response and the total IgA concentration in intestinal washes. These results suggest that protein deprivation leads to a reversible reduction in the IgA response to antigens encountered at the intestinal mucosa.