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Reduced bone formation in UK Gulf War veterans: a bone histomorphometric study.

AIMS: Gulf War veterans report a high prevalence of musculoskeletal symptoms. The aim of this study was to establish whether there were abnormalities in bone turnover and remodelling in a group of symptomatic subjects who had served in the Gulf War. METHODS: Iliac crest bone biopsies were obtained from 17 Gulf War veterans who were seeking litigation and compared with those of 13 age and sex matched healthy controls. Bone histomorphometry was performed using image analysis. RESULTS: Cancellous bone area was significantly lower in Gulf War veterans than in control subjects (p = 0.027) and this was associated with a significantly reduced mineral apposition rate (p = 0.002), mean wall width (p < 0.0001), and bone formation rate at the tissue level (p < 0.0001). CONCLUSIONS: These results demonstrate that in this group of Gulf War veterans there was a significant reduction in bone formation at both the cellular and tissue level and this was associated with a reduction in cancellous bone area. The cause of these abnormalities is unknown but might be related to potentially harmful exposures during service in the Gulf War or to changes in life style as a result of chronic ill health. The clinical relevance of the observed reduction in bone formation remains to be established.

Adult↗

Cardiovascular abnormalities associated with human and rodent obesity.

Obesity is a major risk factor for cardiovascular disease. However, a direct link between these two states is difficult to establish, since obesity frequently occurs with other disease states such as diabetes, hypertension and atherosclerosis. Clinical studies have clearly shown that uncorrected obesity is associated with cardiac hypertrophy and compromised ventricular function. A number of rodent models of obesity have been studied in terms of cardiovascular adaptations. Cardiac function of the obese Zucker rat appears to be normal at a younger age. Only after several months is depression in cardiac function discernable. These animals are mildly hypertensive, but do not exhibit the characteristic increase in cardiac output associated with human obesity. A unique characteristic of JCR:LA-cp rat is that they develop atherosclerotic and myocardial lesions. Hearts from these animals will maintain normal function when perfused with physiological levels of calcium. At higher calcium concentrations, however, mechanical function becomes impaired. Dietary-induced obese rats exhibit many of the hemodynamic alterations associated with human obesity, but there is no evidence to-date that these animals will develop severe cardiac depression. Short-term weight reduction apparently has beneficial cardiovascular effects, but weight cycling may be harmful. Given the widespread occurrence of obesity, further studies are warranted to characterize the cardiac manifestations of this condition.

Animals↗

Statin-related adverse events: a meta-analysis.

BACKGROUND: The absolute frequencies of adverse events (AEs) between statins and placebo are very low in clinical trials, making clinical interpretation and application difficult. OBJECTIVES: This meta-analysis was intended to synthesize the collective AE data observed in prospective randomized clinical trials to facilitate clinical interpretation. METHODS: Using the search terms atorvastatin, simvastatin,pravastatin, rosuvastatin, fluvastatin, lovastatin, prospective trial, and randomized trial, the MEDLINE/EMBASE and the Cochrane Collaboration databases were reviewed for prospective randomized primary and secondary prevention trials of statin monotherapy. Nonrandomized uncontrolled studies and those missing AE data were excluded. The Mantel-Haenszel test for fixed and random effects was used to calculate odds ratios (ORs) and log ORs. RESULTS: Eighteen trials including 71,108 persons, and 301,374 person-years of follow-up were represented in this analysis. There were 36,062 persons receiving a statin and 35,046 receiving a placebo. Statin therapy increased the risk of any AE by 39% (OR = 1.4; 95% CI, 1.09-1.80; P = 0.008; NNH [number needed to harm] = 197) compared with placebo. Statins were associated with a 26% reduction in the risk of a clinical cardiovascular event (OR = 0.74; 95% CI, 0.69-0.80; P < 0.001; number needed to treat = 27). Treating 1000 patients with a statin would prevent 37 cardiovascular events, and 5 AEs would be observed. Serious events (creatine phosphokinase >10 times the upper limit of normal or rhabdomyolysis) are infrequent (NNH = 3400) and rhabdomyolysis, although serious, is rare (NNH = 7428). Atorvastatin was associated with the greatest risk of AEs and fluvastatin with the least risk. Simvastatin, pravastatin, and lovastatin had similar odds of AEs. Nonurgent AEs such as myalgia and liver function elevations were responsible for approximately two thirds of AEs reported in trials. CONCLUSIONS: Statin therapy was associated with greater odds of AEs compared with placebo but with substantial clinical benefit. Similar rates of serious AEs were observed between statin and placebo.

Humans↗

Some aspects of the pathophysiology of semicarbazide-sensitive amine oxidase enzymes.

The widespread distribution of enzymes classed as semicarbazide-sensitive amine oxidases (SSAO enzymes) throughout a very wide range of eukaryotic as well as prokaryotic organisms encourages the aspirations of those who wish to demonstrate physiological, pathological or pharmacological importance. Such enzymes are found in several tissues of mammals, both freely soluble, as in blood plasma, and membrane-bound, for example, in smooth muscle and adipose tissue. While they are capable of deaminating many amines with the production of an aldehyde and hydrogen peroxide, doubt still surrounds the identity of the most important endogenous substrates for these enzymes. At present, methylamine and aminoacetone appear to head the list of candidates. The possibility that SSAO enzymes can convert amine substrates to highly toxic metabolites is illustrated by the production of acrolein from the xenobiotic amine, allylamine and formaldehyde and methylglyoxal from methylamine and aminoacetone, respectively. Activities of SSAO enzymes may be influenced by physiological changes, such as pregnancy or pathologically by disease states, including diabetes, tumours and burns. Increased deamination of aminoacetone by tissue and plasma SSAO enzymes as a result of its increased production from L-threonine in conditions such as exhaustion, starvation and diabetes mellitus may be harmful. Such dangers could be mitigated either physiologically by a compensatory reduction in SSAO activity or pharmacologically by treatment with inhibitors of SSAO.

Amine Oxidase (Copper-Containing)↗

A survey of physician advice about caffeine.

Six hundred and ninety-seven medical specialists were surveyed to determine whether there is any consensus on the harmful effects of caffeine. More than 75% of the specialists recommended reduction in caffeine in patients with anxiety, arrhythmias, esophagitis/hiatal hernia, fibrocystic disease, insomnia, palpitations, and tachycardia.

Attitude of Health Personnel↗

Randomized clinical trial of intravenous magnesium sulfate as an adjunctive medication for emergency department treatment of migraine headache.

STUDY OBJECTIVE: We test the hypothesis that intravenous magnesium sulfate is an effective adjunctive medication for treatment of acute migraine. METHODS: In this randomized, double-blind, placebo-controlled trial, adults presenting to 2 urban emergency departments with headache meeting International Headache Society criteria for acute migraine received either 20 mg of intravenous metoclopramide plus 2 g of intravenous magnesium sulfate or 20 mg of intravenous metoclopramide plus a placebo of intravenous saline solution at 15-minute intervals for a maximum of 3 doses or until pain relief occurred. At 0, 15, 30, and 45 minutes, patients recorded pain intensity using a standard visual analog scale (VAS). The primary study end point was the between-group difference in pain improvement when initial and final VAS scores were compared. RESULTS: Of 44 patients enrolled (21 randomized to metoclopramide plus magnesium and 23 to metoclopramide plus placebo), 42 (95%) were women. Baseline features were comparable in both groups. Each group experienced a more than 50-mm improvement in VAS score during the study. However, this improvement was smaller in the magnesium group for the primary end point (16-mm difference favoring placebo [95% confidence interval (CI) -2 to 34 mm]), as was the proportion with normal functional status at their final rating (36% absolute difference also favoring placebo [95% CI 7% to 65%]). Using a 50% reduction in pain to dichotomize VAS scores, the number needed to harm with magnesium plus metoclopramide versus metoclopramide alone is 4 patients (95% CI 2 to 36). CONCLUSION: Although this result was unexpected, our data suggest that the addition of magnesium to metoclopramide may attenuate the effectiveness of metoclopramide in relieving migraine. Countertherapeutic cerebral vasodilatation caused by magnesium is a plausible, although unproven, explanation for this finding. Because of the preponderance of women in our trial, these data may not be generalizable to men.

Adult↗

The emergency care setting for screening and intervention for alcohol use problems among injured and high-risk drivers: a review.

Each year thousands of people are treated in emergency departments and trauma centers for alcohol-related injuries, including those sustained in drinking driving crashes. Emergency departments and trauma centers provide an opportunity to screen for alcohol use problems and intervene with injured or high-risk drivers to reduce future alcohol-related traffic and injury risk. Recently physicians have expressed interest in exploring screening and intervention for alcohol use problems in these venues as a means of improving clinical care. This article reviews the literature that has examined screening and brief interventions in acute care settings to reduce future alcohol consumption and alcohol-related injury. The methodological and practical issues inherent in conducting these studies as well as in actual practice are discussed. The chaotic environment of acute care, the large numbers of patients required to be screened to obtain an adequate study sample, and high attrition rates make study in these settings difficult at best and are methodological problems that should be addressed in future research. A basic question that has not been adequately answered by research to date is whether reduction in alcohol consumption will translate to reduced alcohol-related harm, such as driving while impaired, or injurious or fatal crashes. Long-term studies that assess records-based outcomes in addition to alcohol-consumption levels are needed.

Accidents, Traffic↗

17alpha-ethinylestradiol reduces the competitive reproductive fitness of the male guppy (Poecilia reticulata).

Whether endocrine disruption in an individual male is actually translated into reduced reproductive success in a natural competitive environment is extremely difficult to predict. Here, we have used paternity analysis to provide new information on the ability of an endocrine disruptor to deleteriously affect male guppy reproductive fitness by including the effect of intermale competition. Groups of male guppies were exposed to 10.5, 44.4, or 112 ng/L of the synthetic estrogen 17alpha-ethinylestradiol (EE2) from birth to adulthood. Subsequently, an exposed male competed against an unexposed male for the opportunity to fertilize a receptive female. The successful males siring the majority of the offspring in each brood were then identified using microsatellites in genetic paternity analysis. Only the highest dose of EE2 produced harmful effects with a significantly female-biased sex ratio, significant reductions in male sperm count, testis weight, body coloration and courtship behavior, and a significant increase in body size. These feminizing effects were translated into a highly significant reduction in fertility, where only 1 of the 17 exposed males sired offspring in competition with unexposed males. The evidence suggests that EE2-treated males have reduced reproductive fitness compared with untreated males, possibly the result of EE2 effects on multiple fitness traits. To our knowledge, this is the first study providing evidence of endocrine disruption at the population level that has included the ecologically highly relevant effect of sexual competition on male reproductive fitness.

Animals↗

Comparison of posterior and transforaminal approaches to lumbar interbody fusion.

STUDY DESIGN: A study of the transforaminal lumbar interbody fusion and the posterior lumbar interbody fusion techniques was performed. OBJECTIVES: To describe the transforaminal lumbar interbody fusion technique, and to compare operative data, including blood loss and operative time, with data from posterior lumbar interbody fusion technique. SUMMARY OF BACKGROUND DATA: The evolution of posterior lumbar fusion combined with anterior interbody fusion has resulted in increased fusion rates as well as improved reductions and stability. The transforaminal lumbar interbody fusion technique pioneered by Harms and Jeszensky offers potential advantages and provides a surgical alternative to more traditional methods. METHODS: In 13 consecutive months, two spinal surgeons performed 40 transforaminal lumbar interbody fusions and 34 posterior lumbar interbody fusion procedures. Data regarding blood loss, operative times, and length of hospital stay were recorded. These data were analyzed using analysis of variance to show any significant differences between the two techniques. To determine whether differences in measured variables were dependent on patient gender or number of levels fused, epsilon(chi2) analysis was used. RESULTS: No significant differences were found between transforaminal and posterior lumbar interbody fusions in terms of blood loss, operative time, or duration of hospital stay when a single-level fusion was performed. Significantly less blood loss occurred when a two-level fusion was performed using the transforaminal approach instead of the posterior approach (P < 0.01). Differences in measured variables for the two procedures were independent of patient age, gender, and the number of levels fused. There were no complications with the transforaminal approach, but the posterior approach resulted in multiple complications. CONCLUSIONS: In this comparison of patients receiving transforaminal lumbar interbody fusion versus posterior lumbar interbody fusion, no complications occurred with the transforaminal approach, whereas multiple complications were associated with the posterior approach. Similar operative times, blood loss, and duration of hospital stay were obtained in single-level fusions, but significantly less blood loss occurred with the transforaminal lumbar interbody approach in two-level fusions. The transforaminal procedure preserves the interspinous ligaments of the lumbar spine and preserves the contralateral laminar surface as an additional surface for bone graft. It may be performed at all lumbar levels because it avoids significant retraction of the dura and conus medullaris.

Adult↗

Therapeutic controversies in primary hyperparathyroidism.

There is little debate about the primacy of surgery in the management of classical PHPT. Rather, the question has been what to do about the many patients with nonclassical disease. A 1990 NIH consensus conference (55) clearly recommended surgery for patients with significant adverse effects of PHPT, for patients with complicating coexistent illnesses, for younger patients, and for those in whom consistent long-term follow-up could not be assured. It allowed that conscientious surveillance may be justified in patients with minimal hypercalcemia and no adverse effects, but it recognized that for many patients, the time and expense involved in rigorous follow-up would outweigh the burden of surgery. Nine years later, the demonstrated prevalence of nonclassical symptoms and their reversibility, the evidence of "asymptomatic" but harmful effects reversible by surgery, and the accumulating evidence for surgical reduction of increased long-term mortality risk substantially strengthen the argument for surgery in such patients. For these reasons, parathyroidectomy should generally be recommended for patients with a secure diagnosis of PHPT, even in the absence of classical symptoms.

Calcium↗

Alcohol and its relation to all-cause and cardiovascular mortality.

There exists a considerable body of evidence indicating that light-to-moderate alcohol consumption is associated with a reduced mortality from ischaemic heart disease (IHD). However, an L-shaped saturation curve has been observed in many prospective studies on alcohol consumption and IHD mortality. No further risk reduction is expected if more than 30 grams of ethanol per day is consumed. In ecological studies, particularly wine showed a strongly negative correlation with IHD mortality. This possible specific effect of wine has not yet been confirmed in observational prospective studies. The evidence found in the ecological studies may partly be explained by several healthy dietary habits associated with wine drinking. Although the results of the prospective studies are less consistent for stroke mortality, the largest risk reduction was observed among the drinkers with 10-20 grams of ethanol per day, and then the risk increased. However as an opposite effect of alcohol is expected to ischaemic and haemorrhagic stroke, further studies with consideration to the type of stroke are needed. Several prospective studies demonstrated a J-shaped curve between alcohol consumption and all-cause mortality both in men and women. It is usually explained by a risk reduction of mortality from IHD and stroke among light drinkers. Considering that the risk reduction for all-cause mortality is limited in light-to-moderate drinkers and the reduction is small and that heavy alcohol consumption has an apparently harmful effect, a general increase in alcohol consumption at the population level is not recommended.

Alcohol Drinking↗

Measures of association in clinical trials: definition and interpretation.

The choice of randomized controlled trials as the best evidence on therapeutic (or preventive) measures is based on the fact that this design is the only one that allows the establishment of causality, i.e. a relationship between an intervention and an outcome. For example, it is essential for the cardiologist treating patients with congestive heart failure (CHF) from systolic dysfunction of the left ventricle to know if the use of selective beta-blockers will reduce mortality. In order to find this out, he must have access to the published evidence on beta-blockers use in CHF, either through primary sources--RCTs--or secondary sources--systematic reviews. The results from clinical trials must be presented in a standardized way: in RCTs, authors usually present proportions (or rates, or percentages) of events (acute myocardial infarction, stroke, death) in each study group: experimental and control. These events are usually dichotomous, i.e. they are either present or not. In this paper, we will discuss the meaning as well as the interpretation of a number of measures of association in RCTs: absolute risk and absolute risk reduction, relative risk and relative risk reduction, odds ratios, number needed to treat and number needed to harm.

Coronary Disease↗

Causes of low birthweight in Hungary.

An analysis is offered of the factors contributing to the very high incidence of low birthweight infants in Hungary, based on data of the last three decades. The incidence increased by 30% from 1950 to 1974, and since 1974 there has been a reduction by 20%. The main factors of the high incidence are harmful habits (smoking, alcohol consumption, etc.) during pregnancy, the uneven level of antenatal care, the low level of education and health culture, and the frequency of induced abortion. Further improvement can only be expected from a planned influence on the above factors.

Female↗

Cigarette smoking in pregnancy and risk of pre-eclampsia.

The relationship between smoking in pregnancy and the development of pre-eclampsia has not been well studied. Smoking habits were prospectively evaluated in 117 patients with pre-eclampsia and 468 normotensive control pregnancies. Twenty cases (17.1%) and 120 controls (25.6%) reported smoking at any time during pregnancy. In stepwise multiple logistic regression analysis, smoking in pregnancy was a significant protective factor against the occurrence of pre-eclampsia (adjusted odds ratio = 0.50; 95% confidence interval 0.28-0.80, P = 0.018). On the other hand, a history of pre-eclampsia in previous pregnancies, low (< 6th grade) educational level, a body mass index > 24 and maternal blood group AB were factors independently associated with an increased risk of pre-eclampsia. In conclusion, this study confirms that smoking in pregnancy reduces the risk of pre-eclampsia. However, the harmful consequences of smoking on pregnancy outcome far outweigh this risk reduction.

Adolescent↗

Strategies for preventing suicide.

BACKGROUND: The Health of the Nation includes a target for reducing population suicide rates. We have examined and quantified various high-risk and population-based strategies for prevention based upon a number of stated assumptions and hypothetical interventions. METHOD: The published literature was used to estimate the population attributable fractions for both high-risk and population-based strategies. The number needed to treat for the high-risk strategies was calculated, assuming an intervention that reduced suicide rates by 25%. RESULTS: Interventions that would reduce rates of suicide by 25% would reduce population rates by about 2.6% for those recently discharged from hospital and by up to 5.8% for those presenting to general hospital with deliberate self-harm. The population attributable fraction for unemployment was 10.9%. CONCLUSIONS: High-risk strategies will have only a modest effect on population suicide rates, even if effective interventions are developed. Evaluating interventions for deliberate self-harm patients seems worthwhile. The UK Government's target for suicide reduction is more likely to be achieved using population-based strategies. Reducing the availability of methods commonly used for committing suicide is the most practicable current policy, although more radical approaches, for example reducing unemployment, may also substantially reduce suicide rates.

Analgesics↗

Effects of a vegetarian diet vs. a vegetarian diet enriched with avocado in hypercholesterolemic patients.

To determine the effects of a vegetarian diet with avocado as a source of monounsaturated fat on serum lipids, thirteen patients with phenotype II (twelve with IIa and one with IIb) dyslipidemia were included in a prospective, transversal and comparative study in which three four-week diets randomly assigned were assessed. One vegetarian diet (ALVD) was composed of 70% carbohydrates, 10% proteins and 20% lipids. Another was composed of 60% carbohydrates, 10% proteins and 30% lipids, 75% of which was supplied by avocado (AVD). A third diet was an avocado-added free diet (FDWA). Body weight, body mass index (BMI), and serum lipids (total cholesterol (TC), high (HDL) and low density lipoprotein (LDL) cholesterol and triglycerides (TG)) were evaluated. AVD produced a significant decrease in LDL. ALVD did not change TC and LDL, while FDWA increased them slightly. The three diets reduced TG levels, but only ALVD did so significantly. All three diets reduced HDL levels, particularly ALVD, which produced the greatest reduction. Low-fat, carbohydrate-rich vegetarian diets may be harmful to hypercholesterolemic patients. The avocado addition to a vegetarian diet does not correct these undesirable effects. To obtain beneficial effects on lipid profile with avocado, lower amounts of carbohydrates and polyunsaturated fatty acids are probably needed.

Adult↗

Health sector approach to vulnerability reduction and emergency preparedness.

Vulnerability is increasing year by year. Statistics show that not only are the human and economic costs of emergencies and disasters increasing, but that the cost of relief assistance has increased 10-fold in the last 11 years. Relief assistance alone can lead to increased vulnerability, by reducing development assistance and leading to further social crises The concept of vulnerability consist of two aspects, susceptibility and resilience; vulnerability reduction aims to reduce susceptibility to hazards and increase community resilience to emergencies. Vulnerability reduction involves vulnerability assessment, hazard prevention and mitigation, and emergency preparedness. Vulnerability reduction aims to decrease community susceptibility and increase community resilience, and can focus on emergencies thus preventing many disasters. Vulnerability reduction protects human development, and prepared communities can maintain and improve their level of development. Vulnerability reduction is the responsibility of all, including the health sector, and all sectors at all levels must assist communities to participate in reducing vulnerability. The health sector work in vulnerability reduction requires coordination at all levels within a country. WHO has been assisting in this work at the international, regional and country levels for many years. There is a need for statistical indicators of vulnerability and the harm caused by major emergencies. Data from these indicators will assist in monitoring and evaluating vulnerability reduction, and targeting communities at risk.

Disaster Planning↗

Light-to-moderate alcohol consumption and mortality in the Physicians' Health Study enrollment cohort.

OBJECTIVES: This study examined the relationship between light-to-moderate alcohol consumption and cause-specific mortality. BACKGROUND: Previous studies suggest a J-shaped relation between alcohol and total mortality in men. A decrease in cardiovascular disease (CVD) mortality without a significant increase in other causes of mortality may explain the overall risk reduction at light-to-moderate levels. METHODS: We conducted a prospective cohort study of 89,299 U.S. men from the Physicians' Health Study enrollment cohort who were 40 to 84 years old in 1982 and free of known myocardial infarction, stroke, cancer or liver disease at baseline. Usual alcohol consumption was estimated by a limited food frequency questionnaire. RESULTS: There were 3,216 deaths over 5.5 years of follow-up. We observed a U-shaped relationship between alcohol consumption and total mortality. Compared with rarely/never drinkers, consumers of 1, 2 to 4 and 5 to 6 drinks per week and 1 drink per day had significant reductions in risk of death (multivariate relative risks [RRs] of 0.74, 0.77, 0.78 and 0.82, respectively) with no overall benefit or harm detected at the > or =2 drinks per day level (RR = 0.95; 95% confidence interval (CI), 0.79 to 1.14). The relationship with CVD mortality was inverse or L-shaped with apparent risk reductions even in the highest category of > or =2 drinks per day (RR = 0.76; 95% CI, 0.57 to 1.01). We found no clear harm or benefit for total or common site-specific cancers. For remaining other cancers, there was a nonsignificant 28% increased risk for those consuming > or =2 drinks per day. CONCLUSIONS: These data support a U-shaped relation between alcohol and total mortality among light-to-moderate drinking men. The U-shaped curve may reflect an inverse association for CVD mortality, no association for common site-specific cancers and a possible positive association for less common cancers.

Adult↗