Explaining Poorer Stroke Outcomes in Women: Women Surviving 3 Months Have More Severe Strokes Than Men Despite a Lower 3-Month Case Fatality

BackgroundWomen who survive stroke are more disabled and more often institutionalized than men.ObjectiveWe explore this phenomenon by studying case fatality and stroke severity in stroke survivors separately for men and women.MethodsA Danish stroke registry (2000−2007) contains information about 26,818 patients with first-ever ischemic stroke, including stroke severity (Scandinavian Stroke Scale, 0 worst to 58 best), computed tomography scan, cardiovascular risk factors, and death 3 months after stroke. We modeled stroke severity by generalized additive linear model and 3-month case fatality with logistic model adjusting for age and cardiovascular risk factors.ResultsMale to female ratio was 51.5% to 48.5%. Mean age was 68.8 (SD 12.6) years in men; 73.7 (13.8) years in women. Stroke was more severe in women (mean [SD] Scandinavian Stroke Scale, 42.2 [16.0]) than in men (mean [SD] Scandinavian Stroke Scale, 45.6 [14.2]) also after adjustment for age and cardiovascular risk factors; significant in patients older than 75 years. In survivors at 3 months, stroke was more severe in women than men, given same age and cardiovascular risk factor profile; significant in patients older than 75 years. More women (11.9%) had died within 3 months than men (8.6%). However, adjusting for age, stroke severity, and risk factor profile, 3-month case fatality was lower in women than men; significant in patients older than 78 years.ConclusionsAlthough 3-month case fatality was lower in women than men, strokes were more severe among survivors at 3 months in women than in men. In addition, strokes were more severe in women. Our data help elucidate why women survive stroke better but have poorer functional outcomes that require more care than men.     

Associations between Cognition,Gender and Monocyte Activation among HIV Infected Individuals in Nigeria

The potential role of gender in the occurrence of HIV-related neurocognitive impairment (NCI) and associations with markers of HIV-related immune activity has not been previously examined. In this study 149 antiretroviral-naïve seropositive subjects in Nigeria (SP, 92 women and 57 men) and 58 seronegative (SN, 38 women and 20 men) were administered neuropsychological testing that assessed 7 ability domains. From the neuropsychological test scores was calculated a global deficit score (GDS), a measure of overall NCI. Percentages of circulating monocytes and plasma HIV RNA, soluble CD163 and soluble CD14 levels were also assessed. HIV SP women were found to be younger, more educated and had higher CD4+ T cell counts and borderline higher viral load measures than SP men. On the neuropsychological testing, SP women were more impaired in speed of information processing and verbal fluency and had a higher mean GDS than SN women. Compared to SP men, SP women were also more impaired in speed of information processing and verbal fluency as well as on tests of learning and memory. Numbers of circulating monocytes and plasma sCD14 and sCD163 levels were significantly higher for all SP versus all SN individuals and were also higher for SP women and for SP men versus their SN counterparts. Among SP women, soluble CD14 levels were slightly higher than for SP men, and SP women had higher viral load measurements and were more likely to have detectable virus than SP men. Higher sCD14 levels among SP women correlated with more severe global impairment, and higher viral load measurements correlated with higher monocyte numbers and sCD14 and sCD14 levels, associations that were not observed for SP men. These studies suggest that the risk of developing NCI differ for HIV infected women and men in Nigeria and, for women, may be linked to effects from higher plasma levels of HIV driving activation of circulating monocytes.     

Mortality of bereavement.

The death rate of a group of 87 widowers and 279 widows was followed for two years from the death of their spouses. The life tables for England and Wales 1970-2 indicated that the expected number of deaths would be 6 men and 11 women. The actual numbers (9 men and 11 women, 5.5%) were not significantly different, though there were more widowers'' deaths during the first six months of bereavement. There was no significantly greater mortality among those whose spouses had died in hospital; but when this had occurred the health of the second spouse was likely to have been poorer than that of those whose spouses had died at home.     

Human male pair bonding and testosterone

Previous research in North America has supported the view that male involvement in committed, romantic relationships is associated with lower testosterone (T) levels. Here, we test the prediction that undergraduate men involved in committed, romantic relationships (paired) will have lower T levels than men not involved in such relationships (unpaired). Further, we also test whether these differences are more apparent in samples collected later, rather than earlier, in the day. For this study, 107 undergraduate men filled out a questionnaire and collected one saliva sample (from which a subject’s T level was measured) at various times across the day. As in previous studies, men involved in committed, romantic relationships had lower salivary T levels, though only during later times of the day. Furthermore, additional analysis of the variation among unpaired subjects indicated that men without prior relationship experience had lower T levels than experienced men. Finally, while paired men as a group had lower T levels than unpaired men, those men at the earliest stage (less than six months) of a current relationship had higher T levels than unpaired men as well as men in longer-term relationships. These results suggest that variation in male testosterone levels may reflect differential behavioral allocation to mating effort. Peter Gray recently completed his Ph.D. in biological anthropology at Harvard with a dissertation entitled, "Human Male Reproductive Strategies: Cross-Cultural and Endocrine Aspects." He is now a postdoctoral fellow at Charles Drew University of Medicine and Science, working with Dr. Shalender Bhasin on human androgen research. Judith Flynn Chapman and Matthew McIntyre are Ph.D. candidates inbiological anthropology at Harvard University. Judith Flynn Chapman focuses on variation in human ovarian function. Matthew McIntyre studies the role of testosterone in psychological development. Terry Burnham is an economist at the Harvard Business School. He studies economic behavior in a framework based in evolution by natural selection. Susan Lipson is a Lecturer in Anthropology and director of the Reproductive Ecology Laboratory at Harvard University. Her research includes work on the effects of age and energy balance on female reproductive function, and on hormonal correlates of conception and cancer risk. Peter Ellison is John Cowles Professor of Anthropology and Dean of the Graduate School of Arts and Sciences at Harvard University. He studies hormones, behavior, and the reproductive ecology of humans and nonhuman primates.     

C-Reactive Protein for Predicting Prognosis and Its Gender-Specific Associations with Diabetes Mellitus and Hypertension in the Development of Coronary Artery Spasm

Background

While hypertension is negatively associated with coronary artery spasm (CAS), scarce data are available on diabetes mellitus in relation to CAS. In addition, outcome prediction in patients with CAS is challenging due to the lack of appropriate biomarkers. Therefore, we sought to identify the roles that gender, high-sensitivity C-reactive protein (hs-CRP), diabetes mellitus and hypertension play in CAS development and prognosis.

Methodology/Prinicpal Findings

Patients (350 women and 547 men) undergoing diagnostic coronary angiography with or without proven CAS but without obstructive stenosis were evaluated at long-term follow-up (median 102 months). Diabetic women and diabetic men with low hs-CRP levels had a low and high risk of CAS (odds ratio [OR]: 0.16, 95% confidence interval [CI]: 0.01–1.88 and OR: 5.02, 95% CI: 1.03–24.54, respectively). The ORs of CAS in both women and men with the highest hs-CRP tertile (>3 mg/L) reduced from 4.41 to 1.45 and 2.98 to 1.52, respectively, if they had diabetes mellitus, and from 9.68 to 2.43 and 2.60 to 1.75, respectively, if they had hypertension. Hypertension had a more negative effect on CAS development in diabetic than non-diabetic women, which was not observed in men. The highest hs-CRP tertile was an independent predictor of adverse outcomes. Patients with the highest hs-CRP tertile had more coronary events than patients with the lowest hs-CRP tertitle (p = 0.021, log-rank test).

Conclusions

Diabetes mellitus contributes to CAS development in men with low hs-CRP levels, but not in women. There are negative effects of diabetes mellitus and hypertension on CAS development in patients with high hs-CRP levels and especially in women. Elevated hs-CRP level independently predicts adverse outcomes.     

Men in committed, romantic relationships have lower testosterone

Variation in human male testosterone levels may reflect, and effect, differential behavioral allocation to mating and parenting effort. This proposition leads to the hypothesis that, among North American men, those involved in committed, romantic relationships will have lower testosterone levels than men not involved in such relationships. Our study is the first to examine whether being in such a relationship (rather than being married) is the meaningful predictor of male testosterone levels. To test this hypothesis, 122 male Harvard Business School students filled out a questionnaire and collected one saliva sample (from which testosterone level was measured). Results revealed that men in committed, romantic relationships had 21% lower testosterone levels than men not involved in such relationships. Furthermore, the testosterone levels of married men and unmarried men who were involved in committed, romantic relationships did not differ, suggesting that, at least for this sample, male pair bonding status is the more significant predictor of testosterone levels than is marital status.     

Non-employment and changes in smoking,drinking, and body weight.

OBJECTIVE--To assess the effect of unemployment and early retirement on cigarette smoking, alcohol consumption, and body weight in middle aged British men. DESIGN--Prospective cohort study (British regional heart study). SETTING--One general practice in 24 towns in Britain. SUBJECTS--6057 men aged 40-59 who had been continuously employed for five years before the initial screening. Five years after screening 4412 men had been continuously employed and 1645 had experienced some unemployment or retired. MAIN OUTCOME MEASURES--Numbers of cigarettes smoked and units of alcohol consumed per week and body mass index (kg/m2). RESULTS--An initial screening significantly higher percentages of men who subsequently experienced non-employment smoked or had high alcohol consumption than of men who remained continuously employed: 43.0% versus 37.0% continuously employed for cigarette smoking (95% confidence interval for difference 3.2% to 9.0%) and 12.1% versus 9.0% for heavy drinking (1.3% to 5.1%). There was no evidence that men increased their smoking or drinking on becoming non-employed. Men non-employed through illness were significantly more likely to reduce their smoking and drinking than men who remained continuously employed. Men who experienced non-employment were significantly more likely to gain over 10% in weight than men who remained continuously employed: 7.5% versus 5.0% continuously employed (0.9% to 4.0%). CONCLUSIONS--Loss of employment was not associated with increased smoking or drinking but was associated with an increased likelihood of gaining weight. The long term effects of the higher levels of smoking and alcohol consumption before nonemployment should be taken into account when comparing mortality and morbidity in groups of unemployed and employed people.     

Serum heat shock protein 70 and oxidized LDL in patients with type 2 diabetes: does sex matter?

Several studies suggest that the response to various stressors differs between the sexes. We aimed to study serum HSP70 and levels of oxidized-LDL (ox-LDL) as markers of oxidative stress in men and women with type 2 diabetes. We quantified serum HSP70 and levels of ox-LDL in three cohorts; patients with newly diagnosed diabetes, patients with long-standing diabetes and normal controls. The cohort of patients with newly diagnosed diabetes was followed up for 3 months under glucose-lowering therapy with metformin. Our findings showed that serum HSP70 level was increased in women with long-standing diabetes in comparison with men. HSP70 did not decrease after glucose lowering therapy in women with newly diagnosed diabetes, but it did decrease in men. There was no significant difference on ox-LDL between men and women in any of the studied cohorts. It decreased significantly in the cohort of patients with newly diagnosed diabetes after treatment, regardless of sex. There was no significant correlation between HSP70 and ox-LDL in any of the studied cohorts except among normal women. We suggest that diabetes induces an immune response and impairs cellular defense mechanisms against oxidative stress more commonly in women with type 2 diabetes than in men.     

Sural Nerve Interposition Grafting during Radical Prostatectomy

In 1997, autologous sural nerve grafting to reconstruct bilaterally resected cavernosal nerves was successfully performed in patients undergoing radical retropubic prostatectomy. After 12 months, one third of these patients had erections sufficient for intercourse. Since that time, patients who have had neurovascular bundle resection and sural nerve grafting have continued to show promising results. For example, within one large cohort of men who had unilateral, nerve-sparing radical prostatectomy, significantly more men who had sural nerve grafting regained potency, and did so in less time, than men who did not have grafting. More importantly, however, with better predictions of the presence of extracapsular disease, nerve-sparing surgery can be performed more selectively, reserving wide resection and sural nerve grafting for patients likely to have extracapsular extension. A multicenter, randomized clinical trial is needed to substantiate the positive outcomes observed with sural nerve grafting.     

Lipid profile of a French-Canadian population: 1. Association of plasma lipid and lipoprotein levels with age,relative body weight and education

Plasma lipid and lipoprotein levels were determined in a randomly selected population of 1169 French-Canadian men in the Quebec City area. The mean levels of total plasma cholesterol and triglycerides were 224.0 and 166.5 mg/dL respectively. The mean level of low-density lipoprotein cholesterol was higher and the mean level of high-density lipoprotein (HDL) cholesterol lower than those reported in a recent study in English-Canadian men. The mean HDL₂ and HDL₃ levels were lower than those reported in American men. Stratification of plasma triglyceride levels for all age groups showed that mean HDL₂ levels decreased rapidly with moderate rises in triglyceride levels. Less than 9% of the variation in lipid or lipoprotein levels was related to age or relative body weight. Education had no significant effect on the levels.     

Plasma lipoprotein levels and the prevalence of hyperlipoproteinemia in a Canadian working population

The lipids and lipoproteins — cholesterol (C), triglyceride (TG) and high-density, low-density, very-low-density and sinking pre-β-lipoprotein cholesterol (HDL-C, LDL-C, VLDL-C and SPB-C) — in plasma samples from 1620 fasting white adults and children from the Toronto—Hamilton area were analysed. The mean concentration of HDL-C was about 45 mg/dl in men and about 60 mg/dl in women, and the levels were constant throughout adult life in both sexes. Boys had higher mean HDL-C levels than men, but girls had lower mean HDL-C levels than women. Mean LDL-C levels, like total C levels, increased with age, from about 87 mg/dl in boys to 136 mg/dl in men, and from about 91 mg/dl in girls to 145 mg/dl in women. The mean levels of VLDL-C followed the TG patterns for age and sex, rising from about 7 mg/dl in boys to 26 mg/dl in men, and from about 11 mg/dl in girls to 19 mg/dl in women. SPB-C was detectable visually in 39% of the population and with the aid of densitometry in 54%; the levels were not related to age, sex or oral contraceptive use, and the median level was 3 mg/dl.Prevalence estimates of hyperlipoproteinemia showed that type IV was the most common, and it was found more than three times as often in men as in women. This was in part due to the customary use of plasma TG cut-off points that do not reflect the large difference in TG levels between males and females. Type IIA hyperlipoproteinemia was found in about 2% of the adults and type IIb in a further 1%. Types I, III and V were all rare. The prevalence of types II and IV hyperlipoproteinemia was four times greater in women using oral contraceptives than in nonusers in the same age range.     

Multiple applications for vocational training rotations: can we improve the system?

Questionnaires were sent to 392 doctors who had applied for 10 vocational training rotations in South West Thames Region nine months previously. These 392 doctors had made 607 such applications in south west Thames during this time. Replies were received from 260 (66%) of those circulated. These doctors together had made roughly 4000 job applications nationwide, or 15 each: two thirds had found a post that was satisfactory for vocational training within the nine months, three quarters of them on organised rotations. There was no difference between men and women regarding success in finding a job. Both married and single women were more specific than men about the area in which they wanted to train and had made fewer job applications. Of those who answered the questionnaires, roughly three quarters thought that the present system of applying for training posts was unsatisfactory, and suggestions for improvements are made. It is concluded that although a regional clearing house scheme would help administration in the regions, only a national scheme would substantially help the applicants. To avoid frustration doctors might be more selective and limit their applications without harming their chances of success.     

Sex differences in outcomes and associated factors among stroke patients with small artery occlusion in China

Background

Sex differences in outcomes after small artery occlusion (SAO) stroke have not been well described, particularly in a Chinese population. We aimed to assess sex differences in outcomes and related risk factors among patients with SAO.

Methods

All consecutive patients with SAO were recruited between May 2005 and September 2014. Clinical features and risk factors were recorded. The mortality, recurrence, and dependency rates at 3 months after stroke were assessed.

Results

A total of 2524 patients with SAO were included in this study. There was a higher frequency of mild stroke, current smoking, and alcohol consumption in men than in women. Women were more likely than men to be older, to have diabetes and obesity, and to have higher total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels. There were worse outcomes in men than in women at 3 months after stroke (P?<?0.05). There were more independent risk factors of poor outcome in men than in women. Older age was a common predictive factor of outcome both in men and in women. In men, low triglyceride levels and high fasting plasma glucose levels were independent risk factors for mortality; in addition, a high low-density lipoprotein cholesterol level was associated with recurrence. Moreover, in men, moderate and severe stroke, and high total cholesterol and fasting plasma glucose levels were risk factors for dependency. A negative association was found between low-density lipoprotein cholesterol level and risk of mortality and between total cholesterol level and risk of recurrence in women.

Conclusions

These findings suggest that it is crucial to control conventional risk factors and fasting plasma glucose and lipid levels among patients with SAO, especially male patients, to reduce the burden of stroke in China.

     

Serum lipid levels in thyroid dysfunction with special reference to transient elevation during treatment in hyperthyroid Graves' disease

Lipid metabolism was examined in patients with hyper- or hypothyroidism. Compared with corresponding age and sex matched controls, serum total cholesterol (T-chol), low density lipoprotein cholesterol (LDL-chol), phospholipid (PL) and LDL levels were significantly low and free fatty acid (FFA) levels were high with apparently normal triglyceride (TG), very low density lipoprotein (VLDL) and high density lipoprotein cholesterol (HDL-chol) levels in 61 hyperthyroid patients, while T-chol, LDL-chol, TG, PL, VLDL and LDL levels were high with normal FFA and HDL-chol levels in 31 hypothyroid patients. Serum lipid levels were then repeatedly measured in 7 men and 7 women with hyperthyroid Graves' disease before treatment (stage I), just after the patients became euthyroid with anti-thyroid drug (stage II) and more than 2 months after the patients remained euthyroid (stage III). Serum T-chol, LDL-chol, PL and LDL levels were low at stage I, significantly elevated at stage II and then normalized at stage III. Transient but significant elevation of serum TG, VLDL and HDL-chol levels at stage II were also observed in men. Accelerated catabolism and anabolism of lipid has been reported in hyperthyroidism. Transient elevation of serum lipid levels suggests a more rapid improvement in catabolism than in anabolism of lipid in an early stage of the medical treatment for hyperthyroidism.     

Analysis of the Sperm Head Protein Profiles in Fertile Men: Consistency across Time in the Levels of Expression of Heat Shock Proteins and Peroxiredoxins

We investigated the identity and quantitative variations of proteins extracted from human sperm heads using a label-free Gel-MS approach. Sperm samples were obtained from three men with high sperm counts at three different time points. This design allowed us to analyse intra-individual and inter-individual variations of the human sperm head proteome. Each time point was analyzed in triplicate to minimize any background artifactual effects of the methodology on the variation analyses. Intra-individual analysis using the spectral counting method revealed that the expression levels of 90% of the common proteins identified in three samples collected at various time-points, separated by several months, had a coefficient of variation of less than 0.5 for each man. Across individuals, the expression level of more than 80% of the proteins had a CV under 0.7. Interestingly, 83 common proteins were found within the core proteome as defined by the intra- and inter-variation analyses set criteria (CV<0.7). Some of these uniformly expressed proteins were chaperones, peroxiredoxins, isomerases, and cytoskeletal proteins. Although there is a significant level of inter-individual variation in the protein profiles of human sperm heads even in a well-defined group of men with high sperm counts, the consistent expression levels of a wide range of proteins points to their essential role during spermatogenesis.     

Randomised controlled trial of general practitioner intervention in patients with excessive alcohol consumption.

OBJECTIVE: To determine effectiveness of advice from general practitioners to heavy drinkers to reduce their excessive alcohol consumption (35 U or more a week for men, 21 U or more for women). DESIGN: Randomised, controlled double blind trial over 12 months with interim assessment at six months. SETTING: Group practices (n = 47; list size averaging 10,000) recruited from Medical Research Council''s general practice research framework, mostly in rural or small urban settings. PATIENTS: Patients recruited after questionnaire survey. Of total of 2571 (61.2%) of 4203 patients invited for interview who attended, 909 (35.4%) stated that in past seven days they had drunk above the limits set for study and had not received advice; they were randomised to control and treatment groups. INTERVENTIONS: Patients in treatment group were interviewed by general practitioner (who had had a training session) and received advice and information about how to reduce consumption and also given a drinking diary. END POINT: Study aimed at detecting a reduction in proportion of men with excessive alcohol consumption of 30% in treatment group and 20% in control group (for women 40% and 20%, respectively) with a power of 90% at 5% level of significance. In addition, corroborative measures such as estimation of gamma-glutamyltransferase activity were included. MEASUREMENTS AND MAIN RESULTS: At one year a mean reduction in consumption of alcohol of 18.2 (SE 1.5) U/week had occurred in treated men compared with a reduction of 8.1 (1.6) U/week in controls (p less than 0.001). The proportion of men with excessive consumption at interview had dropped by 43.7% in the treatment group compared with 25.5% in controls (p less than 0.001). A mean reduction in weekly consumption of 11.5 (1.6) U occurred in treated women compared with 6.3 (2.0) U in controls (p less than 0.05), with proportionate reductions of excessive drinkers in treatment and control groups of 47.7% and 29.2% respectively. Reduction in consumption increased significantly with number of general practitioner interventions. At one year the mean value for gamma-glutamyltransferase activity had dropped significantly more in treated men (-2.4 (0.9)IU/l) than in controls (+1.1(1.0)IU/l; t = 2.7, p less than 0.01). Reduction in gamma-glutamyltransferase activity tended to increase with number of intervention sessions in men. Changes in gamma-glutamyltransferase activity in women and changes in other indicators in both sexes did not differ significantly between treatment and control groups. CONCLUSIONS: If the results of this study were applied to the United Kingdom intervention by general practitioners could each year reduce to moderate levels the alcohol consumption of some 250000 men and 67500 women who currently drink to excess. General practitioners and other members of the primary health care team should therefore be encouraged to include counselling about alcohol consumption in their preventive activities.     

Long-term Treatment of Galactorrhoea and Hypogonadism with Bromocriptine

Seventeen women and four men with galactorrhoea and associated hypogonadism have been treated with bromocriptine for 2 to 28 months. In 18 patients the gonadal status became normal as the galactorrhoea improved. The gonadally unresponsive patients had either pituitary tumours or premature menopause. Prolactin levels fell with treatment; withdrawal of the drug was associated with an increase in serum prolactin and a recurrence of the galactorrhoea and hypogonadism. Two patients tried to become pregnant on treatment and both succeeded. Raised prolactin levels appear to block the actions of the gonadotrophins at a gonadal level rather than prevent their synthesis or release; lowering prolactin secretion with bromocriptine allows resumption of normal gonadal function. Bromocriptine appears to be the treatment of choice for inappropriate lactation in association with hypogonadism on a long-term basis.     

Physical training and plasma intermediate density lipoprotein cholesterol levels in men with hypertriglyceridemia

Plasma lipoprotein lipid levels including IDL cholesterol concentration, physical fitness parameters, and anthropometric data were measured in 10 men with primary hypertriglyceridemia during a 12 week program of moderate physical training. Reduced pulse rate at submaximal workload and increased work performed on the treadmill indicated that the men had increased their physical fitness during the training period. Body weight (-4.9%) and total skinfold thickness (-15.6%) fell during the training program. A characteristic fall (-23%) in plasma triglyceride levels was seen over the first 8 weeks training. Plasma IDL cholesterol concentration fell (-18%) after 2 weeks training but then rose after 8 weeks to levels which tended to be higher than baseline values. Our data suggest that regular physical exercise is more likely to raise levels of the "proatherogenic" IDL than to lower them in hypertriglyceridemic patients.