Significance of fingernail and toenail mercury concentrations as biomarkers for prenatal methylmercury exposure in relation to segmental hair mercury concentrations.

OBJECTIVE: To investigate the appropriateness of mercury (Hg) concentrations in fingernails and toenails at parturition for detecting prenatal exposure to methylmercury (MeHg). METHODS: Total Hg concentrations were measured in 54 paired samples of fingernails, toenails, maternal blood, and maternal hair (1cm incremental segments from the scalp toward the tip) collected at 4th weeks of (early) pregnancy, and the same specimens and cord blood collected at parturition. RESULTS: Strong correlations were observed between Hg concentrations in fingernails and toenails at early pregnancy (r=0.923, p<0.01) and at parturition (r=0.895, p<0.01). At early pregnancy, Hg concentrations in fingernails and toenails showed the strongest correlations with those in hair 3-4 cm from the scalp (r=0.818 and r=0.747, p<0.01, respectively) among the 1cm incremental hair segments. Mercury concentrations in fingernails and toenails at parturition represented strong correlations with those in cord blood (r=0.803, p<0.01 for fingernails and r=0.792, p<0.01 for toenails, respectively). At parturition, Hg concentrations in fingernails had the highest correlation with those in hair 0-1cm from the scalp (r=0.918, p<0.01), and Hg concentrations in toenails showed the highest correlation with those in hair at 2-3 cm from the scalp (r=0.872, p<0.01). In addition, Hg concentrations in both finger and toe nails at parturition had equally high (p<0.01) correlation coefficients with hair segments at 0-1, 1-2, and 2-3 cm from the scalp. CONCLUSIONS: Mercury in fingernails and toenails at early pregnancy reflected the maternal Hg body burden level approximately 5 months retroactively. At parturition, Hg levels in fingernails and toenails also showed strong correlations with those in cord blood. In addition, Hg levels in fingernails and toenails at parturition reflected more recent MeHg exposure, compared with those at early pregnancy. These results suggest that fingernails and toenails at parturition are useful biomarkers for prenatal MeHg exposure for mothers and fetuses, especially during the third-trimester of gestation.

New insights regarding tissue Se and Hg interactions on oxidative stress from plasma IsoP and IsoF measures in the Canadian Inuit population.

Despite animal and in vitro studies demonstrating pro-oxidative effects of Hg, previous human work showed no relationship between tissue Hg and plasma levels of F2-isoprostanes (IsoPs), a whole-body oxidative stress marker. We hypothesized that another IsoP species, isofurans (IsoFs), was a more sensitive indicator of Hg-mediated oxidative stress, which can be modified by tissue Se status. A cross-sectional study was carried out involving individuals from a random subset (n = 233) of Inuit adults from a population-based survey (n = 2,595) of 36 Canadian Arctic Inuit communities to assess the relationships of plasma IsoPs to Se and Hg status indicators. F2-IsoPs were inversely correlated with blood Se (r = -0.186, P = 0.005) and toenail Se (r = -0.146, P = 0.044), but not correlated with Hg. IsoFs were inversely correlated with blood Se (r = -0.164, P = 0.014) and positively correlated with Hg (r = 0.228, P < 0.001) and Hg:Se (r = 0.340, P < 0.001). The strength of the correlations remained unchanged after multivariate adjustments. Multivariate analysis showed that F2-IsoPs were not positively associated with Hg but with Hg:Se (ß = 0.148, P = 0.021). We conclude that Se and Hg status and their interactions are important factors modulating F2-IsoP and IsoF levels such that the Inuit may be protected from Hg-induced oxidative stress because of their high Se status.

Observations of environmental changes and potential dietary impacts in two communities in Nunavut, Canada.

INTRODUCTION: Inuit from communities across the Arctic are still existing in subsistence living. Hunting, fishing and gathering is an important part of the culture and the harvested 'country food' provides sources of nutrients invaluable to maintaining the health of the populations. However, Inuit are voicing their concerns on how observed climate change is impacting on their traditional life. The objective of this study was to report on observed climate changes and how they affect the country food harvest in two communities in the Canadian Arctic. The nutritional implications of these changes are discussed and also how the communities need to plan for adaptations. METHODS: A total of 17 adult participants from Repulse Bay and Kugaaruk, Nunavut were invited to participate. Participants were selected using purposeful sampling methods selecting the most knowledgeable community members for the study. Inuit Elders, hunters, processors of the animals, and other community members above the age of 18 years were selected for their knowledge of harvesting and the environment. Two-day bilingual focus groups using semi-directed, unstructured questions were held in each community to discuss perceived climate changes related to the access and availability of key species. Key topics of focus included ice, snow, weather, marine mammals, land mammals, fish, species ranges, migration patterns, and quality and quantity of animal populations. Maps were used to pinpoint harvesting locations. A qualitative analysis categorizing strategy was used for analysis of data. This strategy involves coding data in order to form themes and to allow for cross-comparison analysis between communities. Each major animal represented a category; other categories included land, sea, and weather. Results were verified by the participants and community leaders. RESULTS: Three themes emerged from the observations: (1) ice/snow/water; (2) weather; and (3) changes in species. Climate change can affect the accessibility and availability of the key species of country foods including caribou, marine mammals, fish, birds and plants. Various observations on relationship between weather and population health and distributions of the animal/plant species were reported. While many of the observations were common between the two communities, many were community specific and inconsistent. Participants from both communities found that climate change was affecting the country food harvest in both positive and negative ways. Key nutrients that could be affected are protein, iron, zinc, n-3 fatty acids, selenium and vitamins D and A. CONCLUSION: Community members from Repulse Bay and Kugaaruk have confirmed that climate change is affecting their traditional food system. Local and regional efforts are needed to plan for food security and health promotion in the region, and global actions are needed to slow down the process of climate change.

Development of Human Hair Reference Material Supporting the Biomonitoring of Methylmercury.

A certified reference material, NIMD-01, was developed for the analysis of mercury speciation in human hair. We collected the hair of Vietnamese males from a barbershop in Hanoi in 2016 and prepared 1200 bottles containing 3 g of sieved and blended hair powder. The certified value was given on a dry-mass basis, with the moisture content obtained by drying at 85°C for 4 h. Certified values with the expanded uncertainties (coverage factor, k = 2) were as follows: methylmercury, 0.634 ± 0.071 mg kg-1 as mercury; total mercury, 0.794 ± 0.050 mg kg-1; copper, 12.8 ± 1.4 mg kg-1; zinc, 234 ± 29 mg kg-1; selenium, 1.52 ± 0.29 mg kg-1. An indicative arsenic concentration of 0.17 ± 0.03 mg kg-1 was measured. Extended uncertainties were estimated by sample homogeneity, long- and short-term stabilities, and a characterization from measurements made by collaborating laboratories.

Effects of preparation on nutrient and environmental contaminant levels in Arctic beluga whale (Delphinapterus leucas) traditional foods.

For Canadian Arctic indigenous populations, marine mammal (MM) traditional foods (TFs) represent sources of both important nutrients and hazardous environmental contaminants. Food preparation is known to impact the nutrient and environmental contaminant content of processed items, yet the impacts of preparation on indigenous Arctic MM TFs remain poorly characterized. In order to determine how the various processes involved in preparing beluga blubber TFs affect their levels of nutrients and environmental contaminants, we collected blubber samples from 2 male beluga whales, aged 24 and 37 years, captured during the 2014 summer hunting season in Tuktoyaktuk, Northwest Territories, and processed them according to local TF preparation methods. We measured the levels of select nutrients [selenium (Se), polyunsaturated fatty acids (PUFAs)] and contaminants [organochlorine pesticides, perfluoroalkyl and polyfluoroalkyl substances (PFASs), polybrominated diphenyl ethers, polychlorinated biphenyls, polycyclic aromatic hydrocarbons (PAHs), mercury (Hg)] in raw and prepared (boiled, roasted, aged) beluga blubber TFs. The impacts of beluga blubber TF preparation methods on nutrient and environmental contaminant levels were inconsistent, as the majority of processes either did not appear to influence concentrations or affected the two belugas differently. However, roasting and ageing beluga blubber consistently impacted certain compounds: roasting blubber increased concentrations of hydrophilic substances (Se and certain PFASs) through solvent depletion and deposited PAHs from cookfire smoke. The solid-liquid phase separation involved in ageing blubber depleted hydrophilic elements (Se, Hg) and some ionogenic PFASs from the lipid-rich liquid oil phase, while PUFA levels appeared to increase, and hydrophobic persistent organic pollutants were retained. Ageing blubber adjacent to in-use smokehouses also resulted in considerable PAH deposition to processed samples. Our findings demonstrated that contaminant concentration differences were greater between the two sets of whale samples, based on age differences, than they were within each set of whale samples, due to variable preparation methods. When considering means to minimize human contaminant exposure while maximizing nutrient intake, consumption of aged liquid from younger male whales would be preferred, based on possible PUFA enhancement and selective depletion of hydrophilic environmental contaminants in this food item.

High hydrostatic pressure enhances whey protein digestibility to generate whey peptides that improve glutathione status in CFTR-deficient lung epithelial cells.

Whey protein isolates (WPI) may provide anti-inflammatory benefits to cystic fibrosis (CF), which could be mediated via peptides, as proteolytic digests of WPI enhance intracellular glutathione (GSH) concentrations. The objectives of this study were to investigate whether high hydrostatic pressure can (i) improve the in vitro digestibility of WPI; and (ii) generate low molecular weight (< 1 kDa) peptides from WPI hydrolysates that exert GSH-enhancing and anti-inflammatory properties in wild type and mutant CF transmembrane conductance regulator (CFTR) tracheal epithelial cells. Hydrostatic pressure processing enhanced the in vitro digestibility of WPI to proteolytic enzymes resulting in altered peptide profiles as assessed by CZE and GC-MS. The exposure of mutant CFTR cells to low molecular weight (< 1 kDa) peptides isolated from WPI hydrolysates exposed to pressure processing (pressurized WPI hydrolysates, pWPH), showed increased intracellular levels of reduced GSH and total GSH relative to treatment with peptides obtained from native WPI hydrolysates (nWPH). A tendency for decreased interleukin-8 secretion was associated with the pWPH and nWPH treatments in mutant CFTR cells, which was not observed in wild type cells. Hydrostatic pressure processing of whey proteins appears to enhance their impact on cellular GSH status in cells with the mutant CFTR condition.

Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls.

OBJECTIVE: To determine whether the risk of falling (with a possible increased chance of subdural hematoma) should influence the choice of antithrombotic therapy in elderly patients with atrial fibrillation. DESIGN: A Markov decision analytic model was used to determine the preferred treatment strategy (no antithrombotic therapy, long-term aspirin use, or long-term warfarin use) for patients with atrial fibrillation who are 65 years of age and older, are at risk for falling, and have no other contraindications to antithrombotic therapy. Input data were obtained by systematic review of MEDLINE. Outcomes were expressed as quality-adjusted life-years. RESULTS: For patients with average risks of stroke and falling, warfarin therapy was associated with 12.90 quality-adjusted life-years per patient; aspirin therapy, 11.17 quality-adjusted life-years; and no antithrombotic therapy, 10.15 quality-adjusted life-years. Sensitivity analysis demonstrated that, regardless of the patients' age or baseline risk of stroke, the risk of falling was not an important factor in determining their optimal antithrombotic therapy. CONCLUSIONS: For elderly patients with atrial fibrillation, the choice of optimal therapy to prevent stroke depends on many clinical factors, especially their baseline risk of stroke. However, patients' propensity to fall is not an important factor in this decision.

Warfarin for atrial fibrillation. The patient's perspective.

OBJECTIVE: To determine the minimal clinically important difference (MCID) of warfarin therapy for the treatment of nonvalvular atrial fibrillation from the perspective of patients using 2 different elicitation methods. DESIGN: All patients completed 2 face-to-face interviews, which were 2 weeks apart. For each interview, they were randomized to receive 1 of 2 elicitation methods: ping-ponging or starting at the known efficacy. SETTING: The practices of 2 university-affiliated family medicine centers (8 physicians each), 14 community-based family physicians, and 2 cardiologists. PATIENTS: Sixty-four patients with nonvalvular atrial fibrillation who were initiated with warfarin therapy at least 3 months before the study. INTERVENTION: During each interview, the patients' MCIDs were determined by using (1) a pictorial flip chart to describe atrial fibrillation; the consequences of a minor stroke, a major stroke, and a major bleeding episode; the chance of stroke if not taking warfarin; the chance of a major bleeding episode if taking warfarin; examples of the inconvenience, minor side effects, and costs of warfarin therapy; and then (2) 1 of the 2 elicitation methods to determine their MCIDs (the smallest reduction in stroke risk at which the patients were willing to take warfarin). Patients' knowledge of their stroke risk, acceptability of the interview process, and factors determining their preferences were also assessed. MAIN RESULTS: Given a baseline risk of having a stroke in the next 2 years, if not taking warfarin, of 10 of 100, the mean MCID was 2.01 of 100 (95% confidence interval, 1.60-2.42). Fifty-two percent of the patients would take warfarin for an absolute decrease in stroke risk of 1% over 2 years. Before eliciting their MCIDs, patients showed poor knowledge of their stroke risk, which improved afterward. The interview process was well accepted by the patients. The MCID using the ping-ponging elicitation method was 1.015 of 100 smaller compared with use of the starting at the known efficacy method (P = .01). CONCLUSIONS: We were able to determine the MCID of warfarin therapy for the prevention of stroke from the perspective of patients with nonvalvular atrial fibrillation. Their MCIDs were much smaller than those that have been implied by some experts and clinicians. The interview process, using the flip chart approach, appeared to improve the patients' knowledge of their disease and its consequences and treatment. The method used to elicit the patients' MCIDs can have a clinically important effect on patient responses. The method used in our study can be generalized to other conditions and, thus, could be helpful in 3 ways: (1) from a clinical decision-making perspective, it could facilitate patient-physician communication; (2) it could clarify the patient perspective when interpreting the results of previously completed trials; and (3) it could be used to derive more clinically relevant sample sizes for randomized treatment trials.

Severe clinical manifestations of primary HIV infection.

Three cases of oesophageal candidiasis in association with primary HIV infection are described. In each case the candidiasis was associated with a decreased number of circulating CD4+ cells and responded well to treatment with ketoconazole. Clinicians should be aware that severe opportunistic infections may develop during this stage of infection, presumably as a result of transient immunodeficiency. We argue that the definition of primary HIV infection should be extended to include severe opportunistic infections and neurologic presentations.

Aspirin for the primary prevention of stroke and other major vascular events: meta-analysis and hypotheses.

BACKGROUND: Aspirin therapy reduces stroke by about 25% for persons with atherosclerotic vascular disease, but the effect in those without clinically apparent vascular disease is distinctly different. OBJECTIVE: To define the effect of aspirin use on stroke and other major vascular events when given for primary prevention to persons without clinically recognized vascular disease. DATA SOURCES AND EXTRACTION: Systematic review of randomized clinical trials and large prospective observational cohort studies examining the relation between aspirin use and stroke in persons at low intrinsic risk. Studies were identified by a computerized search of the English-language literature. DATA SYNTHESIS: Five randomized trials of primary prevention included 52 251 participants randomized to aspirin doses ranging from 75 to 650 mg/d; the mean overall stroke rate was 0.3% per year during an average follow-up of 4.6 years. Meta-analysis revealed no significant effect on stroke (relative risk = 1.08; 95% confidence interval, 0.95-1.24) contrasting with a decrease in myocardial infarction (relative risk = 0.74; 95% confidence interval, 0.68-0.82). The lack of reduction of stroke by aspirin for primary prevention was incompatible with its protective effect against stroke in patients with manifest vascular disease (P = .001). Intracranial hemorrhage was increased by the regular use of aspirin (relative risk = 1.35; P = .03), similarly for both primary and secondary prevention. In 4 large observational studies, self-selected use of aspirin was consistently associated with higher rates of stroke. CONCLUSIONS: The effect of aspirin therapy on stroke differs between individuals based on the presence or absence of overt vascular disease, in contrast with the consistent reduction in myocardial infarction by aspirin therapy observed in all populations. We hypothesize that the effect of aspirin therapy on stroke for persons with major risk factors for vascular disease may be intermediate between a substantial decrease for those with manifest vascular disease and a possible small increase for healthy persons due to accentuated intracranial hemorrhage. When aspirin is given for primary prevention of vascular events, available data support using 75 to 81 mg/d.

The hierarchy of functional loss associated with cognitive decline in older persons.

OBJECTIVES: We studied a representative cohort of community-dwelling elderly persons to (i) examine the relationship between the loss of specific functional activities and cognitive status at the time of these losses, (ii) compare the cognitive status of participants who have and have not lost independence in these functional activities, and (iii) determine whether a hierarchical scale of functional loss is associated with declining cognitive status. METHODS: A cohort of 5874 community-dwelling persons aged 65 years and older from the Canadian Study of Health and Aging I and II were analyzed. At baseline and 5 years later, cognitive status with the Modified Mini-Mental State Examination (3MS) and functional status with 14 Older American Resources and Services (OARS) items were measured. For each OARS functional item, the mean 3MS scores for persons who lost independence during the 5-year period versus those who did not were compared. RESULTS: For each functional item, the 5-year decline in 3MS scores of persons who lost independence were significantly greater than those who remained independent (e.g., ability to do finances), with an 18-point decline for those who lost independence and a 2-point decline for those who retained independence. A hierarchy of functional items existed, with instrumental activities of daily living (ADLs) (e.g., shopping, banking, and cooking) being lost at higher cognitive scores than basic ADL items (e.g., eating, dressing, and walking), although there was some overlap. CONCLUSIONS: This is the first prospective study using a large representative cohort of elderly persons to demonstrate that progressive cognitive decline is associated with a specific pattern of loss of functional tasks. Clear cognitive thresholds at which development of dependency in OARS functional items occurred. By providing estimates of the cognitive status of persons at the time at which they developed dependency in specific functional items, a natural hierarchy of functional loss associated with cognitive decline emerged. For caregivers, clinicians, and health policy makers, this information can help anticipate the pattern of functional decline and the subsequent care needs of persons with declining cognition, potentially improving the quality of life of these persons and their caregivers and playing an important part in health care planning.

Patient preference-based treatment thresholds and recommendations: a comparison of decision-analytic modeling with the probability-tradeoff technique.

BACKGROUND: Decision analysis (DA) and the probability-tradeoff technique (PTOT) are patient preference-based methods of determining optimal therapy for individuals. Using aspirin therapy for the primary prevention of stroke and myocardial infarction (MI) in elderly persons as an example, the objective of this study was to determine whether group-level treatment thresholds and individual-level treatment recommendations derived using PTOT are identical to those of DA incorporating the patients' own values. METHODS: Persons in a pilot study of the efficacy of aspirin in the prevention of stroke and MI were asked to participate. Participant values and utilities for pertinent health states (e.g., minor and major stroke, MI, major bleeding episode) were determined. Then, in three hypothetical clinical situations in which the chance of stroke or MI was varied, PTOT was used to directly determine treatment thresholds for aspirin therapy (i.e., the smallest reduction in MI or stroke risk for which participants would be willing to take aspirin). Using DA modeling, with the same probabilities of events as in the PTOT exercise and incorporating participants' own values, treatment thresholds for the three clinical situations were determined. The thresholds determined by the two approaches were compared. Finally, based on these treatment thresholds, using the best estimates of the efficacy of aspirin to prevent first-time stroke and MI, PTOT and DA treatment recommendations for individual participants were compared. RESULTS: The 42 participants reported that a major stroke was the least desirable health state, followed by MI, minor stroke, and major bleeding. The minimum risk reduction required to take aspirin was greater for MI prevention compared with stroke prevention. For the two clinical situations in which the hypothetical efficacy of aspirin to prevent stroke was varied, treatment thresholds for the PTOT versus DA approaches differed (p < 0.04), but this difference was not significant (p = 0.19) for the MI-based clinical situation. Using the best estimate of the efficacy of aspirin to prevent first-time stroke and MI, PTOT and DA treatment recommendations whether or not to take aspirin were discordant for 38% of participants (16 of 42) (p < 0.001). CONCLUSIONS: Patient preference-based group-level treatment thresholds and individual-level treatment recommendations can differ significantly depending on whether PTOT or DA is used, apparently because the two emphasize different aspects of the decision-making process. DA theory assumes that effective therapeutic decision making should maximize both quality and quantity of life; with PTOT, the emphasis for effective clinical decision making allows patients to be fully engaged in the process, thus hopefully leading to fully informed decisions that may result in satisfaction and compliance.

Subcortical vascular dementia: survey of treatment patterns and research considerations.

BACKGROUND: Since few studies have examined the effectiveness of therapies for subcortical vascular dementia, treatment guidelines are not available. Current patterns in the treatment of such dementias have not been studied. OBJECTIVE: To determine the practice patterns of Canadian specialists for the treatment of subcortical vascular dementia, and to survey their opinions regarding issues which are important in the design of a randomized controlled trial (RCT) in this field. DESIGN: National survey of all specialists certified in Neurology or Geriatric Medicine. RESULTS: Of responding physicians (78%) prescribed antithrombotic therapy for patients with vascular dementia. Most begin treatment with aspirin 325 mg daily (64%). The next three most common initial treatments were; no pharmacotherapy (12%), aspirin 650 mg daily (11%), and aspirin 1300 mg daily (11%). If the dementia continued to progress despite initial therapy, the treatment options were more varied. Most specialists (69%) believed that an RCT to assess the efficacy of aspirin in vascular dementia is warranted. The majority (69%) also felt that serial neuroimaging would be required for participants in such a trial, with magnetic resonance imaging being cited most frequently (41%). The majority of specialists considered three years as the minimum duration for such a trial. CONCLUSIONS: Specialist physician practice patterns vary significantly for the treatment of patients with subcortical vascular dementia. Most physicians believe that an RCT testing the efficacy of aspirin in this condition is required. However, before such a trial can be conducted, many methodological difficulties need to be addressed.

Systematic assessment of the quality of osteoporosis guidelines.

BACKGROUND: Numerous agencies have developed clinical practice guidelines for the management of postmenopausal osteoporosis. The study objective was to conduct a systematic assessment of the quality of osteoporosis guidelines produced since 1998. METHODS: Guidelines were identified by searching MEDLINE (1998+), the world wide web, known guideline developer websites, bibliographies of retrieved guidelines, and through consultation with content experts. Each guideline was then assessed by three independent appraisers using the 'Appraisal Instrument for Clinical Guidelines' (version 1) by Cluzeau. RESULTS: We identified 26 unique guidelines from 1998-2001 and 21 met our inclusion criteria. Of the 21 guidelines reviewed, 8 were developed by medical societies, 6 by national groups, 6 by government agencies, and 1 by an international group. Twelve of the guidelines were published, 7 were organizational reports, and 2 were accessible only from the web. Half or more of the 20 items assessing the rigor of guideline development were met by 15% (median quality score 23%, range 5-80%, (95% CI 16.5, 34.7)), 81% met at least half of the 12 items assessing guideline content and context (median score 58%, range 17-83%, (95% CI 50.8, 65.5)), and none met half or more of the items assessing guideline application (median score 0%, range 0-47%, (95% CI -0.5 to 12.6)). Eight guidelines described the method used to assess the strength of evidence, and in 6 there was an explicit link between recommendations and the supporting evidence. Ten guidelines were judged not suitable for use in practice, 10 were acceptable with modification, and one was acceptable for use without modification. CONCLUSION: The methodological quality of current osteoporosis guidelines is low, although their scores for clinical content were higher. Virtually no guidelines covered dissemination issues. Few guidelines were judged as acceptable for use in their current format.

The Warthin-Starry stain in the diagnosis of small intestinal microsporidiosis in HIV-infected patients.

A protocol for the handling of small intestinal biopsies from HIV-infected patients is presented. This protocol includes the Warthin-Starry stain for the detection of microsporidia. This stain has proved a reliable and sensitive diagnostic technique for microsporidial infections as it stains both Enterocytozoon bieneusi and Septata intestinalis in duodenal enterocytes. Because the stain demonstrates Septata intestinalis in lamina propria macrophages as well as enterocytes, it allows for the practical differentiation of these two microsporidial infections. The Warthin-Starry stain has also demonstrated Septata intestinalis in nasal and colonic biopsies in some of these patients. Since the completion of an earlier study, a further 40 cases of Enterocytozoon bieneusi and three cases of Septata intestinalis have been diagnosed in just over 240 consecutive duodenal biopsies from HIV positive patients presenting with diarrhoea and other gastrointestinal complaints. Other opportunistic infections include cytomegalovirus in four cases, mycobacteria in eight cases, cryptosporidia in nine cases, giardia in four cases and Isospora belli in one case. Since the ratio of these opportunistic infections has remained much the same as in the previous study of 180 consecutive duodenal biopsies, we suggest that these rates may reflect the actual prevalence of microsporidial infections in AIDS patients in Sydney, Australia.

Meta-analysis of efficacy of quinine for treatment of nocturnal leg cramps in elderly people.

OBJECTIVE: To assess quantitatively the efficacy of quinine (as quinine sulphate) compared with placebo in the treatment of nocturnal leg cramps. DESIGN: A meta-analysis of six randomised, double blind, crossover trials. SETTING: Randomised trials that were available as of April 1994. SUBJECTS: A total of 107 general ambulatory patients who suffered from regular nocturnal leg cramps from six clinical trials. RESULTS: Data from individual patients were used to calculate point estimates and 95% confidence intervals for each of the outcome measures reported by these studies. Treatment with quinine resulted in a significant reduction in the number of cramps for a four week period compared with placebo (8.83 fewer cramps; 95% confidence interval 4.16 to 13.49). Treatment with quinine reduced the number of nights with cramps by 27.4% (24.0% to 30.8%) compared with placebo. Treatment did not produce a significant change in the severity or duration of individual nocturnal leg cramps. Side effects were uncommon. CONCLUSIONS: The results indicate that quinine can prevent nocturnal leg cramps in general ambulatory populations. Given the possible serious side effects of treatment with quinine, the benefits and risks in patients taking this drug should be closely monitored.

Diagnosis of human granulocytic anaplasmosis in Belgium by combining molecular and serological methods.

We report here one new, hospitalized case of Anaplasma phagocytophilum in Belgium. The clinical presentation of anaplasmosis, its treatment and the molecular and serological relevant laboratory methods are briefly developed.

What are the toxicological effects of mercury in Arctic biota?

This review critically evaluates the available mercury (Hg) data in Arctic marine biota and the Inuit population against toxicity threshold values. In particular marine top predators exhibit concentrations of mercury in their tissues and organs that are believed to exceed thresholds for biological effects. Species whose concentrations exceed threshold values include the polar bears (Ursus maritimus), beluga whale (Delphinapterus leucas), pilot whale (Globicephala melas), hooded seal (Cystophora cristata), a few seabird species, and landlocked Arctic char (Salvelinus alpinus). Toothed whales appear to be one of the most vulnerable groups, with high concentrations of mercury recorded in brain tissue with associated signs of neurochemical effects. Evidence of increasing concentrations in mercury in some biota in Arctic Canada and Greenland is therefore a concern with respect to ecosystem health.