The link between medical conditions and fatal drownings in Canada: a 10-year cross-sectional analysis

Background:Drowning accounts for hundreds of preventable deaths in Canada every year, but the impact of preexisting medical conditions on the likelihood of death from drowning is not known. We aimed to describe the prevalence of pre-existing medical conditions among people who fatally drowned in Canada and evaluate the risk of fatal drowning among people with common pre-existing medical conditions.Methods:We reviewed all Canadian unintentional fatal drownings (2007–2016) in the Drowning Prevention Research Centre Canada’s database. For each fatal drowning we established whether the person had pre-existing medical conditions and whether those conditions contributed to the drowning. We calculated relative risk (RR) of fatal drowning stratified by age and sex for each pre-existing medical condition using data from the Canadian Chronic Disease Surveillance System.Results:During 2007–2016, 4288 people fatally drowned unintentially in Canada, of whom one-third had a pre-existing medical condition. A pre-existing medical condition contributed to drowning in 43.6% (n = 616) of cases. Fatal drowning occurred more frequently in people with ischemic heart disease (RR 2.7, 95% confidence interval [CI] 2.5–3.0) and seizure disorders (RR 6.3, 95% CI 5.4–7.3) but less frequently in people with respiratory disease (RR 0.12, 95% CI 0.10–0.15). Females aged 20–34 years with a seizure disorder had a 23 times greater risk than their age- and sex-matched cohort (RR 23, 95% CI 14–39). In general, fatal drowning occurred more often while people were bathing (RR 5.9, 95% CI 4.8–7.0) or alone (RR 1.99, 95% CI 1.32–2.97) and less often in males (RR 0.92, 95% CI 0.88–0.95) or in those who had used alcohol (RR 0.72, 95% CI 0.65–0.80), among those with pre-existing medical conditions.Interpretation:The risk of fatal drowning is increased in the presence of some preexisting medical conditions. Tailored interventions aimed at preventing drowning based on pre-existing medical conditions and age are needed. Initial prevention strategies should focus on seizure disorders and bathtub drownings.

Drowning is an important cause of death in Canada and some aspects of its epidemiology have been characterized.^1,2 Identifying and addressing risk factors for fatal drowning can save lives. For example, after research showed a considerable proportion of child drownings occurred in unsecured household pools and the effectiveness of pool fencing at reducing these deaths, legislative changes were introduced in Quebec.^3–5Although studies evaluating risk factors frequently focus on modifiable environmental or behavioural factors (e.g., infant bath seats, supervision status or alcohol and drug use),^6–11 limited research has evaluated the relation between pre-existing medical conditions and the risk of drowning.Studies that have evaluated the association between pre-existing medical conditions and drowning are limited by small sample sizes and narrow focus on certain conditions (e.g., autism spectrum disorder, epilepsy), or are age-specific (e.g., children).^12–17 The association between various pre-existing medical conditions and drowning in different age groups is not well understood. This information could assist with the development of targeted drowning prevention strategies and prioritizing of resources spent on prevention.Forty-four percent of Canadian adults have at least 1 chronic disease, which suggests that millions of Canadians with conditions that potentially impair their heart, lungs or brain participate in water activities.¹⁸ Furthermore, swimming and aquatic fitness is often encouraged for those with chronic illness to promote health.^19,20 However, the public and physicians should be aware of pre-existing medical conditions that might place people at a higher risk of drowning, so that appropriate precautions can be taken to ensure safety while participating in aquatic activities.We sought to describe pre-existing medical conditions by age group among people who fatally drowned in Canada and to evaluate the risk of fatal drowning among people with common conditions to inform future public health interventions.     

Evaluation of the Anticonvulsant Effect of Brilliant Blue G,a Selective P2X7 Receptor Antagonist,in the <Emphasis Type="Italic">iv</Emphasis> PTZ-, Maximal Electroshock-, and 6 Hz-Induced Seizure Tests in Mice

Epilepsy is one of the most common neurological disorders which is diagnosed in around 65 million people worldwide. Clinically available antiepileptic drugs fail to control epileptic activity in about 30% of patients and they are merely symptomatic treatments and cannot cure or prevent epilepsy. There remains a need for searching new therapeutic strategies for epileptic disorders. The P2X7 receptor has been recently investigated as a new target in epilepsy treatment. Preclinical studies revealed that P2X7 receptor antagonists have anticonvulsant properties in some models of epilepsy. We aimed to investigate whether P2X7 receptor antagonist—brilliant blue G (BBG)—is able to change seizure threshold in three acute seizure models in mice, i.e., in the intravenous pentylenetetrazole seizure threshold, maximal electroshock seizure threshold and 6 Hz psychomotor seizure threshold tests. BBG was administered acutely (50–200 mg/kg, 30 min before the tests) and sub-chronically (25–100 mg/kg, once daily for seven consecutive days). Moreover, the chimney and grip strength tests were used to estimate the influence of BBG on the motor coordination and muscular strength in mice, respectively. Our results revealed only a week anticonvulsant potential of the studied P2X7 receptor antagonist because it showed anticonvulsant action only in the 6 Hz seizure test, both after acute and sub-chronic administration. BBG did not significantly influence seizure thresholds in the remaining tests. Motor coordination and muscular strength were not affected by the studied P2X7 receptor antagonist. In summary, BBG does not possess any remarkable anticonvulsant potential in acute seizure models in mice.     

Interacting Factors Associated with Adult Male Drowning in New Zealand

Objectives

i) to identify factors that contribute to the global trend of the higher incidence of male drowning relative to females, and; ii) to explore relationships between such factors from mortality data in New Zealand.

Methods

Drownings from 1983 to 2012 were examined for: Age, Ethnicity, Site, Activity, Buoyancy and Alcohol. Conditional frequency tables presented as mosaic plots were used to assess the interactions of these factors.

Results

Alcohol was involved in a high proportion of Accidental Immersion drownings (61%) and was highest for males aged 20-24 years. When alcohol was involved there were proportionally more incidences where a life jacket was Available But Not Worn and less incidences where a life jacket was Worn. Many 30-39 year old males drowned during underwater activities (e.g., snorkeling, diving). Older men (aged +55 years old) had a high incidence of drowning while boating. Different ethnicities were over-represented in different age groups (Asian men aged 25-29, and European men aged 65-74) and when involved in different activities.

Conclusions

Numerous interacting factors are responsible for male drownings. In New Zealand, drowning locations and activities differ by age and ethnicity which require targeted intervention strategies.     

Deaths During Skin and Scuba Diving in California in 1970

An investigation of 30 recorded deaths in sport diving in California in 1970 gave evidence of equipment failure in two, a failure of the victims'' judgment or training in 13, and a failure of rescue attempts in four instances. In three histories no cause could be found. Factors associated with the deaths are reported. In the same period there were recorded in the state 171 drownings in home pools out of a total of 712 drownings in water sports.     

Anticonvulsant Activity of B2, an Adenosine Analog,on Chemical Convulsant-Induced Seizures

Epilepsy is a chronic neurological disorder characterized by recurrent seizures. However, approximately one-third of epilepsy patients still suffer from uncontrolled seizures. Effective treatments for epilepsy are yet to be developed. N ⁶-(3-methoxyl-4-hydroxybenzyl) adenine riboside (B2) is a N⁶-substitued adenosine analog. Here we describe an investigation of the effects and mechanisms of B2 on chemical convulsant-induced seizures. Seizures were induced in mice by administration of 4-aminopyridine (4-AP), pentylenetetrazol (PTZ), picrotoxin, kainite acid (KA), or strychnine. B2 has a dose-related anticonvulsant effect in these chemical-induced seizure models. The protective effects of B2 include increased latency of seizure onset, decreased seizure occurrence, shorter seizure duration and reduced mortality rate. Radioligand binding and cAMP accumulation assays indicated that B2 might be a functional ligand for both adenosine A₁ and A_2A receptors. Furthermore, DPCPX, a selective A₁ receptor antagonist, but not {"type":"entrez-protein","attrs":{"text":"SCH58261","term_id":"1052882304"}}SCH58261, a selective A_2A receptor antagonist, blocked the anticonvulsant effect of B2 on PTZ-induced seizure. c-Fos is a cellular marker for neuronal activity. Immunohistochemical and western blot analyses indicated that B2 significantly reversed PTZ-induced c-Fos expression in the hippocampus. Together, these results indicate that B2 has significant anticonvulsant effects. The anticonvulsant effects of B2 may be attributed to adenosine A₁ receptor activation and reduced neuronal excitability in the hippocampus. These observations also support that the use of adenosine receptor agonist may be a promising approach for the treatment of epilepsy.     

Career and practice profiles of Alberta medical graduates (1973-85) practising in Alberta.

This collaborative study examined the career choices and practice locations of the 940 (58%) of the Alberta medical students graduating between 1973 and 1985 who remained in Alberta. Of the 686 practising graduates slightly less than two-thirds were in family/general practice; the remainder were in a specialty. More women (76%) than men (60%) had chosen family/general medicine. The women graduates spent about 10 hours less a week on patient care than their male colleagues. Personal and professional factors were cited most often as determinants of practice location. Approximately 20% of the practising graduates chose to locate in small towns or rural areas. Accessibility to consultants and opportunities for continuing medical education were reported as vital prerequisites for more physicians to move to smaller Alberta centres. These findings provide a starting point for studies designed to determine how Alberta medical school graduates are contributing to patient care within the province.     

The genetically epilepsy-prone rat: an overview of seizure-prone characteristics and responsiveness to anticonvulsant drugs

The Genetically Epilepsy-Prone Rat (GEPR) is rapidly gaining support as a model of epilepsy. In addition to a marked sensitivity to both sound-induced and hyperthermic seizures, GEPRs exhibit unusual sensitivity to a number of seizure-provoking modalities, including various forms of electrical and chemical stimulation. The existence of a moderate seizure colony (GEPR-3) and a severe seizure colony (GEPR-9) allows pathophysiological studies of seizure susceptibility and severity. The consistency of seizures within each colony allows for comparisons in seizure naive GEPRs and seizure experienced GEPRs. The consistent seizure responses of the GEPR are also ideal for the testing of anticonvulsant drugs. Further, the relative potencies of anticonvulsant drugs between the two colonies of GEPRs predict the clinical efficacies of traditional antiepileptic drugs and may be able to predict novel anticonvulsants.     

13例SCN2A 基因突变相关儿童神经系统疾病表型分析

摘要 目的：总结并分析SCN2A基因突变引起的儿童神经系统疾病相关表型谱特点。方法：采用回顾性研究,收集2018年6月至2021年6月在上海交通大学医学院附属上海儿童医学中心神经内科诊治的患儿,并经二代基因测序检测,纳入SCN2A基因突变者,研究并总结患儿神经系统临床表型特点。结果：共纳入13例SCN2A突变患儿,包括新生突变9例和遗传性突变4例。其中11例患儿伴有癫痫发作,发作年龄为1日龄~1岁11月龄,4例在新生儿期起病 （36%）,1~3 月龄起病2例（18%）,4~12月龄起病2例（18%）,1岁后起病3例（27%）;发作类型中强直阵挛发作、痉挛发作、局灶性发作均各有4例（36%）,阵挛发作1例（9%）。另有2例无癫痫发作的患儿,1例表现为全面性发育迟缓,另一例表现为发育迟缓合并孤独症谱系疾病。11例癫痫患儿中,丛集性发作患儿10例。遗传性突变4例患儿中2例智力、运动发育正常;9例新生突变的患儿中8例伴有运动、智力发育落后,1例发育正常。11例癫痫患儿表型中良性家族性新生儿癫痫1例,新生儿惊厥2例,婴儿痉挛症2例,不能分类的早发性癫痫性脑病3例,儿童期起病的癫痫性脑病2例,热厥附加症1例。结论：SCN2A基因突变引起的儿童神经系统疾病以癫痫表现居多、癫痫表型谱广,少数表现为不伴癫痫发作的发育迟缓和孤独症谱系疾病。     

Competitive NMDA receptor antagonists raise electrically kindled generalized seizure thresholds

A sensitive method of estimation of generalized seizure thresholds (GSTs) was used to estimate the relative anticonvulsant potencies of four competitive NMDA antagonists against fully amygdala-kindled seizures. All of the antagonists tested showed potent, dose-dependent anticonvulsant activity following focal administration at doses causing no, or only minimal, overt behavioural abnormalities. These doses were similar to those which have previously been shown to inhibit the development of the kindling process i.e. which show antiepileptogenic activity. Two novel, competitive NMDA antagonists, CGP 37849 and CGP 39551, both unsaturated analogues of the NMDA antagonist AP5, showed by far the greatest anticonvulsant potencies (211-fold and 33-fold greater activity than the parent molecule, respectively). Recent reports of oral anticonvulsant activity of these two compounds in both rodent and primate models of epilepsy (12, 13) make them leading candidates for clinical testing as novel antiepileptic agents in man. Previous reports of weak or non-existent anticonvulsant activity of competitive NMDA antagonists in the kindling model of epilepsy most likely result from the use of experimental protocols which are inherently insensitive in detecting drug-induced changes in seizure thresholds.Special issue dedicated to Dr. Morris H. Aprison.     

L-Type Calcium Channel Mediates Anticonvulsant Effect of Cannabinoids in Acute and Chronic Murine Models of Seizure

The anticonvulsant activities of cannabinoid compounds have been shown in various models of seizure and epilepsy. At least, part of antiseizure effects of cannabinoid compounds is mediated through calcium (Ca²⁺) channels. The L-type Ca²⁺ channels have been shown to be important in various epilepsy models. However, there is no data regarding the role of L-type Ca²⁺ channels in protective action of cannabinoids on acute and chronic models of seizure. In this study, the effects of cannabinoid compounds and L-type Ca²⁺ channels blockers, either alone or in combination were investigated using acute model of pentylenetetrazole (PTZ)-induced seizure in mice and chronic model electrical kindling of amygdala in rats. Pretreatment of mice with both cannabinoid CB1 receptor agonist arachidonyl-2′-chloroethylamide (ACEA) and endocannabinoid degradating enzyme inhibitor cyclohexylcarbamic acid 3′-carbamoyl-biphenyl-3-yl ester (URB597) produced a protective effect against PTZ-induced seizure. Administration of various doses of the two L-type Ca²⁺ channel blockers verapamil and diltiazem did not alter PTZ-induced seizure threshold. However, co-administration of verapamil and either ACEA or URB597 attenuated the protective effect of cannabinoid compounds against PTZ-induced seizure. Also, pretreatment of mice with diltiazem blocked the anticonvulsant activity of both ACEA and URB597. Moreover, (R)-(+)-[2,3-dihydro-5-methyl-3[(4-morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate (WIN55,212-2), the non-selective cannabinoid CB1 and CB2 receptor agonist showed anticonvulsant effect in amygdala-kindled rats. However, co-administration of WIN55,212-2 and verapamil attenuated the protective properties of WIN55,212-2. Our results showed that the anticonvulsant activity of cannabinoid compounds is mediated, at least in part, by L-type Ca²⁺ channels in these two models of convulsion and epilepsy.     

Alberta euthanasia survey: 2. Physicians' opinions about the acceptance of active euthanasia as a medical act and the reporting of such practice.

OBJECTIVE: To ascertain the opinions of Alberta physicians about the acceptance of active euthanasia as a medical act (the "medicalization" of active euthanasia) and the reporting of colleagues practising active euthanasia, as well as the sociodemographic correlates. DESIGN: Cross-sectional survey of a random sample of Alberta physicians, grouped by site and type of practice. SETTING: Alberta. PARTICIPANTS: A total of 2002 (46%) of the licensed physicians in Alberta were mailed a 38-item questionnaire in May through July 1991; usable responses were returned by 1391 (69%). RESULTS: Although only 44% of the respondents considered active euthanasia morally "right" at least 70% opted to medicalize the practice if it were legal by restricting it to be performed by physicians and to be taught at medical sites. Even though active euthanasia is criminal homicide in Canada, 33% of the physicians stated that they would not report a colleague participating in the act of anyone, and 40% and 60% stated that they would not report a colleague to medical or legal authorities respectively. Acceptance or rejection of active euthanasia as a medical act was strongly related to religious affiliation and activity (p < 0.01). CONCLUSIONS: This survey about active euthanasia revealed profound incongruities in the opinions of the sample of Alberta physicians concerning their ethical and social duties in the practice of medicine. These data highlight the need for relevant modifications of health education policies concerning biomedical ethics and physicians'' obligations to society.     

Anticonvulsant Activity of Pterostilbene in Zebrafish and Mouse Acute Seizure Tests

Pterostilbene (PTE), a natural dimethylated analog of resveratrol, possesses numerous health-beneficial properties. The ability of PTE to cross the blood–brain barrier raised the possibility that this compound may modulate central nervous system functions, including seizure activity. The aim of our study was to investigate the activity of PTE in the larval zebrafish pentylenetetrazole (PTZ) seizure assay and three acute seizure tests in mice, i.e., in the maximal electroshock seizure threshold (MEST), 6 Hz-induced psychomotor seizure threshold and intravenous (iv) PTZ tests. Additionally, potential antidepressant activity of PTE was estimated in the forced swim test in mice. The chimney test was used to determine the influence of PTE on motor coordination in mice, while its influence on neuromuscular strength was assessed in the grip strength test in mice. Locomotor activity was determined to verify the results from the forced swim test. PTE revealed an evident anticonvulsant effect both in zebrafish larvae (10 µM; 2 h-incubation) and mice (at doses of 100 and 200 mg/kg, intraperitoneally) but it did not exhibit antidepressant potential in the forced swim test. Furthermore, it did not cause any statistically significant changes in motor coordination, neuromuscular strength and locomotor activity in mice. In conclusion, our present findings demonstrate for the first time the anticonvulsant potential of PTE. The aforementioned results suggest that it might be employed in epilepsy treatment, however, further precise studies are required to verify its activity in other experimental seizure and epilepsy models and its precise mechanism of action should be determined.

     

Factors associated with physician agreement on verbal autopsy of over 11,500 injury deaths in India

INTRODUCTION: Worldwide, injuries account for 9.8% of all deaths. The majority of these deaths occur in low- and middle-income countries where vital registration systems are often inadequate. Verbal autopsy (VA) is a tool used to ascertain cause of death in such settings. Validation studies for VA using hospital diagnosed causes of death as comparisons have shown that injury deaths can be reliably diagnosed by VA. However, no study has assessed the factors that may affect physicians' abilities to code specific causes of injury death using VA. METHOD/PRINCIPAL FINDINGS: This study used data from over 11,500 verbal autopsies of injury deaths from the Million Death Study (MDS) in which 6.3 million people in India were monitored from 2001-2003 for vital events. Deaths that occurred in the MDS were coded by two independent physicians. This study focused on whether physician agreement on the classification of injury deaths was affected by characteristics of the deceased and respondent. Agreement was analyzed using three primary methods: 1) kappa statistic; 2) sensitivity and specificity analysis using the final VA diagnosed category of injury death as gold standard; and 3) multivariate logistic regression using a conceptual hierarchical model. The overall agreement for all injury deaths was 77.9% with a kappa of 0.74 (99% CI 0.74-0.75). Deaths in the injury categories of "transport", "falls", "drowning" and "other unintentional injury" occurring outside the home were associated with greater physician agreement than those occurring at home. In contrast, self-inflicted injury deaths that occurred outside the home were associated with lower physician agreement. CONCLUSIONS/SIGNIFICANCE: With few exceptions, most characteristics of the deceased and the respondent did not influence physician agreement on the classification of injury deaths. Physician training and continued adaptation of the VA tool should focus on the reasons these factors influenced physician agreement.     

Protective effects of long-term probiotic mixture supplementation against pentylenetetrazole-induced seizures,inflammation and oxidative stress in rats

Emerging evidence indicates that dysbiosis of gut microbiota plays an important role in epilepsy, although the underlying mechanisms remain unclear due to the complex nature of both microbial composition and pathophysiology of epilepsy. We investigated effects of long-term probiotics supplementation on epileptic seizures, and inflammatory and oxidant/antioxidant biomarkers in a pentylenetetrazole(PTZ)-induced seizure model in rats.Male Wistar weaner-rats were divided into four groups. The first two groups received 1 ml/day saline solution, while the other groups received 0.05 mg/1ml/day vehicle or 109cfu/1ml/day probiotic-mixture, respectively, for 60 days by gavage. Seizure was induced by a single convulsive dose of PTZ. Seizures were evaluated using Racine's scale. Concentrations of pro-inflammatory cytokines in plasma and brain tissue were determined using ELISA, while oxidant/antioxidant biomarkers were measured using an automated-colorimetric method.Probiotics supplementation exhibited anticonvulsant effects against PTZ-induced seizures by retarding onset-times of both myoclonic-jerk and generalized tonic–clonic seizure, and by shortening duration of generalized tonic–clonic seizure. Additionally, it alleviated PTZ-induced increases in levels of pro-inflammatory cytokines IL-1β, IL-6, and IL-17A, but not of IFNγ, in plasma and brain tissue. Moreover, it restored PTZinduced fluctuations in levels of oxidants TOS and disulfide, and of antioxidants native thiol and total thiol.Our findings suggest that long-term probiotics supplementation exhibits protective effects against epileptic seizures, and alleviates (neuro)inflammation and oxidative stress related to pathophysiology of epilepsy. A probiotic-rich diet provided from childhood may provide prophylaxis against epileptic seizures, especially in susceptible individuals, as the neonate diet represents a fundamental extrinsic factor in establishing gut microbiota.     

Photomyoclonic seizures in the baboon, Papio papio.

The inborn seizure response of Papio papio to intermittent light stimulation has been reviewed as a model of human epilepsy. The electrographic and clinical features have been described and useful methodology has been outlined. A diurnal cyclicity in seizure responsiveness has been described with greatest seizure severity at 8 AM in parallel with a rise in urinary output of cortisol. Hormonal influences on the seizure response have been described for ethinyl estradiol, thyroxin, and triiodothyronine. Evidence regarding neurotransmitter involvement has been reviewed. Data regarding use of the animal for anticonvulsant testing in single and chronic doses has been discussed. Particular advantages of the model for study of age-related drug effects and the assessment of the effects of chronically administered anticonvulsant agents on learning and memory have been described.     

Study of Uridine Effect on the Development of Audiogenic Tonic Seizures in Krushinsky–Molodkina Strain Rats

The latency of tonic seizure in response to loud sound (in rats of the Krushinsky–Molodkina strain with audiogenic epilepsy) had been slightly (although statistically significantly) longer after chronic uridine injections (100 mg/kg, i.p., three times a day during 9 or 12 days). The recovery time from the tonic seizure was shorter after 12 days of injections in comparison to the 9-day injection period. At the same time, the intensity of tonic seizures provoked by loud sound did not change after chronic uridine injections. The lack of uridine anticonvulsive effect demonstrated in the audiogenic epilepsy model contradicts the anticonvulsant effects of uridine in experiments with other seizure models, in which the epileptic foci were localized in the forebrain structures.     

Anticonvulsive properties of peptide ACTH4-7 pro-gly-pro detected in amygdaloid kindling and audiogenic epilepsy in rats

Effects of the ACTH4-7 pro-gly-pro, calcium valproate ("Germed", DDR) and nembutal on kindling preparation and audiogenic epilepsy were investigated. Development of after-discharges in response to repeated amygdaloid electrical stimulation was assessed in normal rats and in rats susceptible to audiogenic epilepsy (KM line of rats). ACTH4-7 pro-gly-pro had an anticonvulsant profile. ACTH4-7 pro-gly-pro decreased seizure threshold in the audiogenic epilepsy test, but did not prevent the motor convulsions.     

Mortality associated with HIV-1 infection over five years in a rural Ugandan population: cohort study.

OBJECTIVE: To assess the impact of HIV-1 infection on mortality over five years in a rural Ugandan population. DESIGN: Longitudinal cohort study followed up annually by a house to house census and medical survey. SETTING: Rural population in south west Uganda. SUBJECTS: About 10,000 people from 15 villages who were enrolled in 1989-90 or later. MAIN OUTCOME MEASURES: Number of deaths from all causes, death rates, mortality fraction attributable to HIV-1 infection. RESULTS: Of 9777 people resident in the study area in 1989-90, 8833 (90%) had an unambiguous result on testing for HIV-1 antibody; throughout the period of follow up adult seroprevalence was about 8%. During 35,083 person years of follow up, 459 deaths occurred, 273 in seronegative subjects and 186 in seropositive subjects, corresponding to standardised death rates of 8.1 and 129.3 per 1000 person years. Standardised death rates for adults were 10.4 (95% confidence interval 9.0 to 11.8) and 114.0 (93.2 to 134.8) per 1000 person years respectively. The mortality fraction attributable to HIV-1 infection was 41% for adults and was in excess of 70% for men aged 25-44 and women aged 20-44 years. Median survival from time of enrollment was less than three years in subjects aged 55 years or more who were infected with HIV-1. Life expectancy from birth in the total population resident at any time was estimated to be 42.5 years (41.4 years in men; 43.5 years in women), which compares with 58.3 years (56.5 years in men; 60.5 years in women) in people known to be seronegative. CONCLUSIONS: These data confirm that in a rural African population HIV-1 infection is associated with high death rates and a substantial reduction in life expectancy.     

Anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, in mice.

The anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, were investigated using pentylenetetrazole (PTZ)- and maximal electroshock (MES)-induced seizure models. We also studied the effect of thymoquinone on pentobarbital-induced hypnosis, locomotor activity, and motor coordination. In PTZ-induced seizure, the intraperitoneally injection of thymoquinone with doses of 40 and 80 mg/kg, prolonged the onset of seizures and reduced the duration of myoclonic seizures. The protective effect of thymoquinone against mortality was 71.4% and 100% in the mentioned doses, respectively. In MES model, thymoquinone failed to reduce the duration of seizure, whereas exhibited a complete protection against mortality. In PTZ model, flumazenil (10 mg/kg, i.p.), an antagonist of benzodiazepine (BZD) site in the GABAA-BZD receptor complex, inhibited the prolongation of seizure latency, but did not show any effect on the duration of myoclonic seizures. Also, pretreatment with naloxone (0.1 and 03 mg/kg, i.p.) inhibited the prolongation of myoclonic seizure latency and antagonized the reduction of myoclonic seizure duration induced by thymoquinone (40 and 80 mg/kg) in the PTZ model. Moreover, thymoquinone (40 and 80 mg/kg) did not have any hypnosis effect in the pentobarbital-induced hypnosis, but impaired the motor coordination and reduced the locomotor activity. These results indicate that thymoquinone may have anticonvulsant activity in the petit mal epilepsy probably through an opioid receptor-mediated increase in GABAergic tone.