First assessment of menstrual cycle function and reproductive endocrine status in Samoan women.

BACKGROUND: American Samoa and Samoa are now characterized by one of the world's highest levels of adult overweight and obesity. Our objective was to investigate patterns of menstrual cyclicity reported by Samoan women and examine the relationship to adiposity and select hormone levels. METHODS: A cross-sectional analysis was performed among Samoan women, aged 18-39 years (n = 322), using anthropometric and biomarker measures of adiposity and reproductive health, including insulin, adiponectin, testosterone, sex hormone-binding globulin, free androgen index (FAI) and mullerian-inhibiting substance (MIS). Menstrual regularity was assessed from self-reported responses. Multivariable models were estimated to adjust for potential confounding of the associations between menstrual patterns and other measures. RESULTS: A high proportion of the women (13.7%) reported oligomenorrhea or amenorrhea (OM/AM). More than three-quarters, 80.7%, of women were either overweight or obese, using Polynesian-specific criteria, and OM/AM was significantly associated with higher BMI. Abdominal circumference and insulin levels were significantly higher, and adiponectin levels were lower, in those who reported OM/AM versus regular menstruation. The FAI was higher in women with increased BMI. MIS levels declined with age, more slowly in those reporting OM/AM. CONCLUSIONS: Self-reported OM/AM was associated with an elevated BMI, abdominal adiposity and serum insulin, and with reduced adiponectin levels. These findings support a high rate of metabolic syndrome, and perhaps PCOS and reproductive dysfunction, among Samoan women.

Health utilities associated with hemoglobin levels and blood loss in postmenopausal women: the Women's Health Initiative.

OBJECTIVES: The purpose of our study was to use health-related quality of life data from the Women's Health Initiative to calculate health-related utility weights and examine differences in these health utility weights across different hemoglobin (Hgb) levels. These utility weights could then be used in future cost-effectiveness studies. METHODS: Health utility weights were measured by the Short Form-6D (SF-6D), a health utility index derived from the Short Form Medical Outcomes questionnaire. Adjusted least square means were calculated for each level of Hgb at baseline and in longitudinal regression analysis the relationship between change in Hgb and change in the SF-6D was examined. Both baseline and longitudinal analyses were performed for all postmenopausal women and separately for those with self-reported heart failure, cancer, and osteoarthritis. RESULTS: Women with Hgb in the anemic range had lower health utility weights than those with higher Hgb levels. Longitudinally, a loss of of 2 g/dl Hgb or more was associated with a statistically significant and clinically meaningfully decline in SF-6D in all participants and also in the group of participants with cancer and osteoarthritis, but not in those with heart failure. CONCLUSIONS: Lower levels of Hgb and a loss of Hgb are associated with a statistically significant and clinically meaningful decrement in health utility in all postmenopausal women we studied and also in those with chronic conditions.

Macrophage complement and lectin-like receptors bind Leishmania in the absence of serum.

We have examined the relative roles of the macrophage (M phi) plasma membrane receptor for the cleaved third complement component (iC3b, CR3) and of the mannosyl/fucosyl receptor (MFR) in binding and ingestion of Leishmania donovani. In the absence of exogenous complement, the binding and ingestion of promastigotes, which are good activators of the alternative complement pathway, were inhibited by the anti-CR3 monoclonal antibody M1/70, by the Fab portion of an anti-C3 antibody, or by the nucleophile, sodium salicyl hydroxamate, an inhibitor of C3 fixation. This provides strong evidence that M phi-derived, cleaved C3 (iC3b) present on the promastigote surface mediates binding to CR3. Equivalent inhibition of promastigote binding and ingestion was also observed using the soluble inhibitors of MFR activity, mannan or ribonuclease B. No additive effect for blocking the two M phi receptors simultaneously was observed. For amastigotes, which are poor activators of the alternative pathway, a lesser but nevertheless equivalent effect was observed for the three soluble inhibitors of CR3-mediated binding vs. the two soluble inhibitors of MFR-mediated binding. Modulation experiments in which either CR3 or MFR had been rendered inaccessible demonstrated that both receptors must be present on the segment of M phi membrane to which the parasite binds. The combined function of these two distinct M phi receptors may provide a general mechanism for recognition and ingestion of other pathogenic protozoa known to activate the alternative pathway.

Two hominin incisor teeth from the middle Pleistocene site of Boxgrove, Sussex, England.

In 1995-1996 two isolated hominin lower incisors were found at the middle Pleistocene site of Boxgrove in England, with Lower Palaeolithic archaeology. Boxgrove 2 is a permanent lower right central incisor and Boxgrove 3 a permanent lower left lateral incisor. They were found separately, but close to one another and appear to belong to the same individual. The Boxgrove 1 tibia discovered in 1993 came from a different stratigraphic context and is thus believed to represent a different individual. This paper describes the morphology of the incisors, which is similar to other middle Pleistocene hominin specimens and, as with the tibia, suggests that they could be assigned to Homo heidelbergensis (recognising that the taxonomic status of this species is still a matter of debate). The incisors show substantial attrition associated with secondary dentine deposition in the pulp chamber and clearly represent an adult. They also show extensive patterns of non-masticatory scratches on the labial surfaces of both crown and root, including some marks which may have been made postmortem. The roots were exposed in life on their labial sides by a large dehiscence, extending almost to the root apex. This is demonstrated by deposits of calculus, polishing, and scratching on the exposed surfaces. The dehiscence may have been caused by repeated trauma to the gingivae or remodelling of the tooth-supporting tissues in response to large forces applied to the front of the dentition.

The effect of phenobarbitone pretreatment on the narcotic antagonistic potency of naloxone in mice.

Pretreatment with phenobarbitone (5.0-20.0 mg/kg, s.c.) did not alter the antinociceptive effect (tail-flick assay) of morphine measured 4.5 h later. However, naloxone was more potent in antagonising this antinociceptive effect in phenobarbitone-pretreated mice than in saline-retreated animals. Concomitant administration of naloxone in the pretreatment regime did not alter the effect of phenobarbitone. The enhanced naloxone potency was related to the amount of phenobarbitone given, and was observable at 3.0 and 4.5 h after pretreatment. It was no longer apparent at 6.0 h. Because of a difference in time course and in the ability of naloxone to block the phenomenon, it is suggested that the mechanisms underlying the increase in naloxone potency induced by phenobarbitone pretreatment and morphine pretreatment may not be the same.

Effect of morphine and naloxone on intestinal transit in mice.

Morphine caused a dose-dependent slowing of the rate of intestinal transit in mice. This inhibitory effect of morphine was antagonised by naloxone administration. Pretreatment with a single dose of morphine did not induce any detectable tolerance to the inhibitory effect of a second dose of morphine given 5 h later. However, naloxone was more effective in antagonising this inhibitory effect of morphine in morphine-pretreated mice than in saline-pretreated animals. Molecular sieve morphine pellet implantation for 24 h induced detectable tolerance to the inhibitory effect of morphine administered 3 h after removal of the pellet. In addition, the antagonistic effect of naloxone was also augmented when compared with blank pellet-implanted control animals. The present study has shown that the enhanced naloxone potency against the inhibitory effect of morphine was intestinal transit was observalbe before the development of overt tolerance, and that tolerance to the effect of morphine on the small intestine could be induced by implantation of a molecular sieve morphine pellet for 24 h.

The effect of aspirin and paracetamol on the increased naloxone potency induced by morphine pretreatment.

Using the abdominal constriction test in mice, it was shown that pretreatment with a single dose of morphine given 3 h previously caused a marked increase in the antagonistic effect of naloxone without any change in the antinociceptive action of morphine itself. Pretreatment with either paracetamol (10.0-20.0 mg/kg, s.c.) or aspirin (5.0-10.0 mg/kg, s.c.) caused a small but significant antagonism of the antinociceptive effect of morphine, while the antagonistic action of naloxone remained unaffected. However, when aspirin or paracetamol was administered with morphine in the pretreatment regime, the ability of morphine to induce an increase in naloxone potency was much attenuated. This inhibitory effect was dependent on the dose of aspirin or paracetamol used in the pretreatment regime. The antinociceptive effect of aspirin and paracetamol was also studied. In the doses used, they did have a mild antinociceptive effect, but the analgesic effect of morphine was not affected by the administration of these drugs 30 min beforehand. It is suggested that the antinociceptive effect of morphine is probably not dependent on prostaglandin, but that the induction of increased naloxone potency is likely to be mediated through prostaglandin synthesis.

Evaluation of motivationally tailored vs. standard self-help physical activity interventions at the workplace.

PURPOSE: This study compares the efficacy of a self-help intervention tailored to the individual's stage of motivational readiness for exercise adoption with a standard self-help exercise promotion intervention. DESIGN: Interventions were delivered at baseline and 1 month; assessments were collected at baseline and 3 months. SETTING: Eleven worksites participating in the Working Healthy Research Trial. SUBJECTS: Participants (n = 1559) were a subsample of employees at participating worksites, individually randomized to one of two treatment conditions. INTERVENTION: Printed self-help exercise promotion materials either (1) matched to the individual's stage of motivational readiness for exercise adoption (motivationally tailored), or (2) standard materials (standard). MEASURES: Measures of stage of motivational readiness for exercise and items from the 7-Day Physical Activity Recall. RESULTS: Among intervention completers (n = 903), chi-square analyses showed that, compared to the standard intervention, those receiving the motivationally tailored intervention were significantly more likely to show increases (37% vs. 27%) and less likely to show either no change (52% vs. 58%) or regression (11% vs. 15%) in stage of motivational readiness. Multivariate analyses of variance showed that changes in stage of motivational readiness were significantly associated with changes in self-reported time spent in exercise. CONCLUSIONS: This is the first prospective, randomized, controlled trial demonstrating the efficacy of a brief motivationally tailored intervention compared to a standard self-help intervention for exercise adoption. These findings appear to support treatment approaches that tailor interventions to the individual's stage of motivational readiness for exercise adoption.

An improved implantation pellet for rapid induction of morphine dependence in mice.

A new type of morphine implantation pellet for the rapid induction of physical dependence in mice can be prepared by absorbing 7 mg morphine sulphate onto molecular sieves Type 4A (BDH). The small cylindrical pellets can be implanted subcutaneously without trauma and the need for anaesthesia, and are easily removed at any time from the animals. The peak of physical dependence is reached 24 h after implantation, and mortality is negligible. Withdrawal symptoms can be precipitated by intraperitoneal injection of naloxone, without removal of the pellet, and up to 70% of a group of mice show the characteristic urge to jump off a raised platform. This type of pellet has definite advantages over some other sustained-release preparations used in studies on morphine addiction in small animals.

Colorectal cancer screening: language is a greater barrier for Latino men than Latino women.

Colorectal cancer screening (CRC) disparities between non-Latino Whites and Latinos remain, and may have increased. The goal of this analysis was to examine the association between Latino race/ethnicity, gender, and English-proficiency and CRC screening. Analysis of the CDC's BRFSS 2008 survey. We estimated crude and adjusted screening rates and odds ratios of respondents' reported CRC test receipt stratified by self-reported Latino ethnicity, gender, and limited English proficiency (LEP) as determined by language of survey response (English vs Spanish). Of 99,883 respondents included in the study populations, LEP Latino men had the lowest adjusted screening rates (48.2%) which were lower that all other Latinos subgroups including Latina women with LEP (56.2%). Compared to non-Latino White men, LEP Latino men were 0.47 times as likely to report receiving CRC screening tests (AOR 0.47; 95% CI 0.35-0.63). Disparities in CRC screening are most dramatic for LEP Latino men.

Immunomodulation of murine visceral leishmaniasis by administration of monoclonal anti-Ia antibodies: differential effects of anti-I-A vs. anti-I-E antibodies.

On a B10 genetic background noncure and cure phenotypes for murine visceral leishmaniasis are controlled by H-2. In this report results are presented which show the effects of administering specific anti-I-A and anti-I-E monoclonal antibodies to B10.D2/n (H-2d) noncure mice prior to and during 85 days of infection with Leishmania donovani LV9. The effects of the two anti-Ia antibodies were precisely equivalent in diminishing circulating anti-leishmanial IgG levels throughout infection, possibly as a direct effect of the anti-Ia antibodies in reducing the splenic B cell population. In terms of resolution of liver and spleen parasite loads, which is known to be dependent upon induction of a cell-mediated immune response, dramatically different results were obtained with the two anti-Ia antibodies. Anti-I-A treatment resulted in prolonged exacerbation of disease in liver and spleen. Anti-I-E treatment was associated with enhanced clearance of liver and spleen parasite loads beyond 30 days of infection. The results are consistent with the hypothesis that blocking major histocompatibility complex-restricted antigen presentation by one class II molecule allows T cell responses controlled by the other to predominate. Hence, in H-2d mice, I-E controls suppressor activity while I-A is associated with helper activity for cell-mediated control of infection. The results offer some prospect for the development of haplotype- and class II molecule-specific immunotherapeutic regimens in the host which might prevent the undesirable expansion of T cell populations which exacerbate disease without compromising development of a curative cell-mediated immune response.

The effects of L-histidine and of specific histamine receptor agonists, on the expression of morphine tolerance and physical dependence in mice.

The effects of L-histidine, and of the specific histamine receptor agonists 2-methylhistamine and 4-methylhistamine, on the expression of morphine tolerance and physical dependence have been studied in mice. These agents were administered during the "withdrawal" phase of development. All of them significantly increased tolerance but reduced the degree of physical dependence. The effects of 2-methylhistamine, which has predominantly H1-receptor activity, were completely abolished by the prior administration of the H1-antagonist mepyramine. The H2-antagonist metiamide, on the other hand, did not alter the action of 2-methylhistamine on physical dependence, though tolerance was restored to its original level. The effects of 4-methylhistamine, which is a specific H2-receptor agonist, were inhibited by metiamide, but mepyramine was unable to reverse the actions of this agonist. The effects of L-histidine, the major precursor of brain histamine, were unaltered by mepyramine, but partially inhibited by metiamide. These experimental findings are discussed in detail, and are considered to give further support to the view that histamine is implicated in some way in the mechanisms of the "withdrawal" phase of morphine tolerance and physical dependence in mice, with H2-receptors probably playing the more important role.

The possible role of brain histamine and H1 and H2 receptors in the development of morphine tolerance and physical dependence in mice.

The possible role of brain histamine in the mechanisms of morphine tolerance and physical dependence is under investigation in mice. L-histidine and histamine, given during the 'withdrawal' phase, significantly increase tolerance to the analgesic effects of morphine but reduce the degree of physical dependence. Metiamide significantly inhibits tolerance but has no consistent effect on physical dependence. These results suggest that H2 receptors may be involved in the development of morphine tolerance. Mepyramine does not significantly affect tolerance, and with regard to dependence there is an effect only on body weight loss, which is increased. However, combined treatment with metiamide and mepyramine inhibits tolerance significantly more than metiamide alone; and withdrawal jumping is also reduced more significantly by combined treatment than by the separate administration of these drugs. It is suggested that brain histamine is definitely implicated in the mechanisms of the 'withdrawal' phase of morphine tolerance and physical dependence in mice, with H2 receptors probably playing the more important part.

The effects of 4-imidazolyl-3-amino-2-butanone (McN-A-1293), a specific histidine decarboxylase inhibitor, on the expression of morphine tolerance and physical dependence in mice.

McN-A-1293, a specific histidine decarboxylase inhibitor administered intracisternally in the 'withdrawal' phase, significantly suppressed the expression of morphine tolerance. Severity of withdrawal, assessed by percentage body weight loss, was significantly enhanced although incidence of jumping was unaltered. The opposite effects of this compound on morphine tolerance and withdrawal suggest that tolerance and physical dependence are based on different underlying mechanisms.

The effects of D-histiding on the expression of morphine tolerance and physical dependence in mice.

D-Histidine, administered in the 'wthdrawal' phase of morphine addiction, failed to modify the expression of tolerance and physical dependence in mice. L-Histidine, on the contrary, can enhance tolerance and inhibit physical dependence. Whole brain histamine is markedly increased by L-histidine administration, but only minimally by D-histidine. This confirms that the actions of L-histidine on morphine addiction are stereospecific, and so can be more confidently correlated with the increase in brain histamine levels produced by the natural amino acid precursor.

A study of the differential respiratory burst activity elicited by promastigotes and amastigotes of Leishmania donovani in murine resident peritoneal macrophages.

Acridine orange and ethidium bromide and a combination of fluorescent and transmitted light microscopy used in conjunction with the qualitative nitroblue tetrazolium assay for superoxide anion (O2-) release demonstrated dramatic differences in the binding of and respiratory burst (RB) activity elicited by promastigotes and amastigotes of Leishmania donovani in resident peritoneal macrophages (M phi) from C57BL/10ScSn mice. When amastigotes were incubated with M phi for 30 min the number of parasites per 100 M phi was 2-4-fold higher, a higher proportion of M phi became infected and the mean number of parasites per infected M phi was higher than in promastigote infections. RB activity was higher for promastigotes than amastigotes both in terms of the percentage of infected M phi containing formazan positive parasites and the percentage of individual formazan positive parasites. In an attempt to explain the differential response to promastigotes and amastigotes, RB activity was examined for sodium azide-treated, glutaraldehyde-fixed and heat-killed parasites and for various transformation intermediates between amastigotes and promastigotes. Binding and RB activity were also examined in conjunction with competitive binding assays designed to determine the specific receptors involved in ligand binding of both forms of the parasite to the M phi. The results indicate that, while amastigotes may possess an azide-sensitive mechanism which either competes for O2- produced or causes localized inactivation of RB activity, this cannot account for the full magnitude of the difference between the two forms of the parasite. The transformation and competitive binding studies suggest that the more likely explanation lies in both qualitative and quantitative differences in the distribution of surface ligands involved in binding the parasite to the M phi plasma membrane and that the well characterized mannose/fucose receptor may be important in promastigote, but not amastigote, binding and RB activity.

Preliminary studies on increased naloxone potency and its relationship to morphine tolerance and dependence in mice.

1. Morphine pretreatment (8.0 mg/kg s.c.) induced no overt tolerance to its antinociceptive effect in mice 4 h later, but enhanced the antagonistic potency of naloxone. 2. A molecular sieve morphine pellet implanted for 24 h induced measurable tolerance, but the relative potency of naloxone was not significantly different from that observed after single-dose morphine pretreatment. The development of tolerance and increased naloxone potency do not, therefore, run parallel. 3. Naloxone-precipitated withdrawal symptoms were observed after single-dose morphine and after pellet implantation. However, molecular sieve morphine pellet implantation induced a higher degree of dependence as compared with single dose morphine pretreatment. 4. These results indicate that the rate of development of increased naloxone potency and of morphine tolerance and dependence do not run parallel. This implies that caution must be exercised in regarding increased naloxone potency as a sensitive indicator of the initiation and development of tolerance and dependence to morphine.

The use of prostaglandins as local antithrombotic agents in microvascular surgery.

The effectiveness of Prostaglandin E2 and Prostacyclin as a local antithrombotic agent in microvascular anastomoses was tested experimentally in a controlled double-blind trial in rats. Prostaglandin E2 was found to be ineffective whereas Prostacyclin was found to be very effective.