The effectiveness of albendazole against hookworm infections and the impact of bi-annual treatment on anaemia and body mass index of school children in the Kpandai district of northern Ghana.

The impact of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) (initiated in 2000 in Ghana and ran for 12 years) in mitigating soil-transmitted helminth (STH) infections in LF-endemic areas is unknown. During a 1-year hiatus which ensued between 2011 and 2012, a longitudinal study was conducted to determine GPELF effect on hookworm infections in selected communities involved in the programme since its inception, while measuring the effectiveness of biannual ALB treatments on schoolchildren living in such communities. A total of 399 school children aged 3 to 18 years were randomly selected from four communities in the Kpandai district of northern Ghana. Each presented a single stool sample at baseline, 21 days post-treatment, at the 3rd and 6th months, 21 days post-second intervention (i.e. following sample collection and treatment with ALB in the 6th month), and in the ninth month of the study period. Haemoglobin (hb) levels were also measured at all time points using finger prick blood samples and a URIT digital test kit. Each participant submitting a sample, was treated with a single-dose ALB (400mg) at baseline and in the sixth month. Stool samples were processed by preparing duplicate Kato-Katz slides per sample, and examined by microscopy. The Body Mass Index-for-age z-scores (BAZ) of participants were assessed following the determination of BMIs at each time point by measuring their height and weight with a stadiometer and weighing scale. Overall hookworm prevalences were 25.68% (95% CI = 20.51-31.75) at baseline, 11.18% (95% CI = 7.87-15.41) 21 days post-treatment, 11.78% (95% CI = 8.38-16.11) and 6.95% (95% CI = 4.41-10.43) in the 3rd and 6th months, 0.91% (95% CI = 0.19-2.65) 21 days post-second intervention, and 8.46% (95% CI = 5.62-12.23) in the ninth month. Observed overall faecal egg count reduction rates (ERRs) were 94.21% (95% CI = 81.50%- 100.00%) 21 days after baseline treatment, 97.70% (95% CI = 85.08-100.00) and 96.95% (95% CI = 84.18%- 100.00%) in the 3rd and 6th months, 99.98% (95% CI = 86.42%- 100.00%) 21 days post-second intervention, and 17.18% (95% CI = 14.07%- 20.67%) in the 9th month. Respective cure rates (CRs) were 62.35% (95% CI = 46.71-81.56%), 85.88% (95% CI = 67.32-100.00%), 87.06% (95% CI = 68.36%- 100.00%), 98.82% (95% CI = 78.83%- 100.00%), and 36.36% (95% CI = 9.91%- 93.11%). Additionally, increases in the percent frequency of 'normal hb' (p < 0.01) were observed across the study time points, whilst 'normal BAZ' cases remained high (from 94.87% to 98.87%) throughout the study period. These findings primarily indicate satisfactory effectiveness of ALB which may be maintainable in mass drug administration programmes by the modification of treatment strategies from annual to bi-annual regimes. This could minimize the likelihood of emerging poorly-responding hookworm phenotypes in Ghana. Additionally, a positive impact of bi-annual treatment on participant anaemia status is herein indicated with particular regard to the school children in our cohort.

Detecting Schistosoma mansoni infections among pre-school-aged children in southern Ghana: a diagnostic comparison of urine-CCA, real-time PCR and Kato-Katz assays.

BACKGROUND: In Ghana, pre-school-aged children (PSAC) are at risk of intestinal schistosomiasis and are living in need of praziquantel treatment. To better assess the infection burden within this vulnerable demographic group, we have provided a comparative assessment of the prevalence of Schistosoma mansoni in pre-school-aged children by urine circulating cathodic antigen (CCA) dipsticks, real-time PCR Taqman® faecal assays and Kato-Katz coproscopy. METHODS: In all, 190 pre-school-aged children were sampled from three endemic communities (viz. Tomefa, Torgahkope/Adakope, and Manheam) around Weija dam, Southern Ghana. Fresh stool and urine samples were collected from all participants for diagnosis. RESULTS: Among all the three communities, the urine-CCA assay recorded the highest prevalence values of 90.5% (95% CI 80.4-96.4), 87.9% (95% CI 76.7-95), and 81.2% (95% CI 69.9-89.6) in Tomefa, Torgahkope/Adakope, and Manheam respectively. Prevalence by real-time PCR was 50% (95% CI 35.5-64.5), 8% (95% CI 2.2-19.2) and 16.7% (95% CI 8.3-28.5), while by Kato-Katz was 55.6% (95% CI 42.5-68.1), 8.6% (95% CI 2.9-19) and 11.6% (95% CI 5.1-21.6) respectively. Children aged 1 year and over were found to be positive with the urine-CCA assay; by the ages of 3-4, over 50% were urine-CCA patent. The sensitivity and specificity of the POC-CCA dipsticks, when compared against the combined results of Kato-Katz/TaqMan results was found to be 84.1% (95% CI = 72.7-92.1) and 12.9% (95% CI = 6.6-22) respectively. CONCLUSIONS: We propose that the urine-CCA dipstick may be a useful rapid diagnostic tool to estimate the prevalence of intestinal schistosomiasis in PSAC, particularly in rapid identification of at-risk areas. However, our assessment has shown that it possible to record false positives when compared to combined Kato-Katz and qPCR results. To guide PSAC praziquantel treatment needs, we propose the urine CCA assay should be included in routine surveillance of intestinal schistosomiasis alongside other diagnostics such as Kato-Katz and urine filtration.

Serological evidence of flaviviruses infection among acute febrile illness patients in Afghanistan.

INTRODUCTION: Current published reports on the causative agents of acute febrile illness (AFI) in Afghanistan are scarce, and the burden of disease due to flaviviruses is unknown. METHODOLOGY: A hospital-based surveillance study for AFI was established in 2008 through 2010 to determine the seroepidemiology of West Nile virus (WNV), tick-borne encephalitis virus (TBEV) and dengue viruses (DENV) using commercial ELISA kits. Due to major logistical challenges, only acute sera were collected. RESULTS: Serological analysis for IgG were as follows: WNV 30.4% (277/913); TBEV 23.4% (214/913); DENV 19.7% (180/913). Single positive IgG reactions for WNV, TBEV and DENV were noted in 11% (100/913), 7.2% (66/913), and 5% (47/913), respectively. Reactivity for all three screened flaviviruses was detected in 44.5% (406/913) of sera. IgM positivity was uncommon, with only 0.5% (5/913), 2.2% (20/913) and 2.6% (8/312) of samples positive for WNV, TBEV, and DENV, respectively. Serological findings were confirmed in random positive samples by neutralization assay. CONCLUSIONS: These serological results suggest circulation of WNV, TBEV, and DENV within Afghanistan, with evidence of current or prior infection noted in a significant proportion of patients seeking care for AFI. Obtaining additional information on the prevalence of these and other causes of AFI is paramount for improving the distribution of available limited syndromic treatment and improving the existing health protection policy in Afghanistan.

Enteric fever burden in North Jakarta, Indonesia: a prospective, community-based study.

INTRODUCTION: We undertook a prospective community-based study in North Jakarta, Indonesia, to determine the incidence, clinical characteristics, seasonality, etiologic agent, and antimicrobial susceptibility pattern of enteric fever. METHODOLOGY: Following a census, treatment centre-based surveillance for febrile illness was conducted for two-years. Clinical data and a blood culture were obtained from each patient. RESULTS: In a population of 160,261, we detected 296 laboratory-confirmed enteric fever cases during the surveillance period, of which 221 (75%) were typhoid fever and 75 (25%)  were paratyphoid fever.  The overall incidence of typhoid and paratyphoid cases was 1.4, and 0.5 per thousand populations per year, respectively. Although the incidence of febrile episodes evaluated was highest among children under 5 years of age at 92.6 per thousand persons per year, we found that the burden of typhoid fever was greatest among children between 5 and 20 years of age. Paratyphoid fever occurred most commonly in children and was infrequent in adults. CONCLUSION: Enteric fever is a public health problem in North Jakarta with a substantial proportion due to paratyphoid fever. The results highlight the need for control strategies against enteric fever.

Building military influenza surveillance capacity in West Africa.

Militaries are especially susceptible to operationally important outbreaks of acute respiratory infections such as pandemic and seasonal influenza. In addition, militaries play important roles for State Parties working to meet International Health Regulations 2005, particularly in developing countries. In 2009, the U.S. Naval Medical Research Unit No. 3 joined with the Noguchi Memorial Institute for Medical Research and the armed forces of Ghana, Burkina Faso, and Côte d'Ivoire to create or improve influenza surveillance capacities within the militaries. This article describes the process undertaken to achieve this goal. In the Ghana Armed Forces, influenza surveillance for outpatients was instituted at seven medical stations throughout the country and for inpatients at the tertiary referral hospital in Accra. As a result, military sites now contribute around half of the influenza cases detected in Ghana and reported weekly to the World Health Organization. Samples were also collected by the militaries of Côte d'Ivoire and Burkina Faso, although political instability slowed progress. This effort is part of an ongoing strategy to build influenza surveillance capacity within West African militaries in support of military services, global outbreak investigations, International Health Regulations-2005, and the development of country-specific pandemic preparedness plans.

Troop education and avian influenza surveillance in military barracks in Ghana, 2011.

BACKGROUND: Influenza A viruses that cause highly pathogenic avian influenza (HPAI) also infect humans. In many developing countries such as Ghana, poultry and humans live in close proximity in both the general and military populations, increasing risk for the spread of HPAI from birds to humans. Respiratory infections such as influenza are especially prone to rapid spread among military populations living in close quarters such as barracks making this a key population for targeted avian influenza surveillance and public health education. METHOD: Twelve military barracks situated in the coastal, tropical rain forest and northern savannah belts of the country were visited and the troops and their families educated on pandemic avian influenza. Attendants at each site was obtained from the attendance sheet provided for registration. The seminars focused on zoonotic diseases, influenza surveillance, pathogenesis of avian influenza, prevention of emerging infections and biosecurity. To help direct public health policies, a questionnaire was used to collect information on animal populations and handling practices from 102 households in the military barracks. Cloacal and tracheal samples were taken from 680 domestic and domesticated wild birds and analysed for influenza A using molecular methods for virus detection. RESULTS: Of the 1028 participants that took part in the seminars, 668 (65%) showed good knowledge of pandemic avian influenza and the risks associated with its infection. Even though no evidence of the presence of avian influenza (AI) infection was found in the 680 domestic and wild birds sampled, biosecurity in the households surveyed was very poor. CONCLUSION: Active surveillance revealed that there was no AI circulation in the military barracks in April 2011. Though participants demonstrated good knowledge of pandemic avian influenza, biosecurity practices were minimal. Sustained educational programs are needed to further strengthen avian influenza surveillance and prevention in military barracks.

Delayed 2009 pandemic influenza A virus subtype H1N1 circulation in West Africa, May 2009-April 2010.

To understand 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) circulation in West Africa, we collected influenza surveillance data from ministries of health and influenza laboratories in 10 countries, including Cameroon, from 4 May 2009 through 3 April 2010. A total of 10,203 respiratory specimens were tested, of which 25% were positive for influenza virus. Until the end of December 2009, only 14% of all detected strains were A(H1N1)pdm09, but the frequency increased to 89% from January through 3 April 2010. Five West African countries did not report their first A(H1N1)pdm09 case until 6 months after the emergence of the pandemic in North America, in April 2009. The time from first detection of A(H1N1)pdm09 in a country to the time of A(H1N1)pdm09 predominance varied from 0 to 37 weeks. Seven countries did not report A(H1N1)pdm09 predominance until 2010. Introduction and transmission of A(H1N1)pdm09 were delayed in this region.

Etiology of acute, non-malaria, febrile illnesses in Jayapura, northeastern Papua, Indonesia.

We conducted a prospective, inpatient fever study in malaria-endemic Papua, Indonesia to determine non-malaria fever etiologies. Investigations included malaria blood films, blood culture, paired serologic samples analysis for dengue, Japanese encephalitis, leptospirosis, scrub typhus, murine typhus, and spotted fever group rickettsia. During 1997-2000, 226 patients (127 males and 99 females) 1-80 years of age (median age = 25 years) were enrolled. Positive blood cultures (n = 34, 15%) were obtained for Salmonella Typhi (n = 13), Escherichia coli (n = 8), Streptococcus pneumoniae (n = 6), Staphylococcus aureus (n = 5), Streptococcus pyogenes (n = 1), and Klebsiella pneumoniae (n = 1). Twenty (8.8%) patients were positive for leptospirosis by polymerase chain reaction. Eighty (35.4%) of 226 patients had ≥ 1 positive serology, diagnostic for 15 rickettsial and 9 dengue cases. Acid-fast bacilli-positive sputum was obtained from three patients. Most common confirmed (81 of 226, 35.8%)/suspected diagnoses were typhoid fever (n = 41), pneumonia (n = 29), leptospirosis (n = 28), urinary tract infections (n = 20), rickettsioses (n = 19), dengue (n = 17), and meningitis/encephalitis (n = 15). There were 17 deaths, 7 (46.7%) were caused by meningitis/encephalitis. Multiple positive serologic results and few confirmed diagnoses indicate the need for improved diagnostics.

The burden of diarrhoea, shigellosis, and cholera in North Jakarta, Indonesia: findings from 24 months surveillance.

BACKGROUND: In preparation of vaccines trials to estimate protection against shigellosis and cholera we conducted a two-year community-based surveillance study in an impoverished area of North Jakarta which provided updated information on the disease burden in the area. METHODS: We conducted a two-year community-based surveillance study from August 2001 to July 2003 in an impoverished area of North Jakarta to assess the burden of diarrhoea, shigellosis, and cholera. At participating health care providers, a case report form was completed and stool sample collected from cases presenting with diarrhoea. RESULTS: Infants had the highest incidences of diarrhoea (759/1,000/year) and cholera (4/1,000/year). Diarrhea incidence was significantly higher in boys under 5 years (387/1,000/year) than girls under 5 years (309/1,000/year; p < 0.001). Children aged 1 to 2 years had the highest incidence of shigellosis (32/1,000/year). Shigella flexneri was the most common Shigella species isolated and 73% to 95% of these isolates were resistant to ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol and tetracycline but remain susceptible to nalidixic acid, ciprofloxacin, and ceftriaxone. We found an overall incidence of cholera of 0.5/1,000/year. Cholera was most common in children, with the highest incidence at 4/1,000/year in those less than 1 year of age. Of the 154 V. cholerae O1 isolates, 89 (58%) were of the El Tor Ogawa serotype and 65 (42%) were El Tor Inaba. Thirty-four percent of patients with cholera were intravenously rehydrated and 22% required hospitalization. V. parahaemolyticus infections were detected sporadically but increased from July 2002 onwards. CONCLUSION: Diarrhoea causes a heavy public health burden in Jakarta particularly in young children. The impact of shigellosis is exacerbated by the threat of antimicrobial resistance, whereas that of cholera is aggravated by its severe manifestations.

Antimicrobial resistance of bacterial pathogens associated with diarrheal patients in Indonesia.

The antimicrobial susceptibility patterns for 2,812 bacterial pathogens isolated from diarrheal patients admitted to hospitals in several provinces in the cities of Jakarta, Padang, Medan, Denpasar, Pontianak, Makassar, and Batam, Indonesia were analyzed from 1995 to 2001 to determine their changing trends in response to eight antibiotics: ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol, tetracycline, cephalothin, ceftriaxone, norfloxacin, and ciprofloxacin. Vibrio cholerae O1 (37.1%) was the pathogen most frequently detected, followed by Shigella spp. (27.3%), Salmonella spp. (17.7%), V. parahaemolyticus (7.3%), Salmonella typhi (3.9%), Campylobacter jejuni (3.6%), V. cholerae non-O1 (2.4%), and Salmonella paratyphi A (0.7%). Of the 767 Shigella spp. isolated, 82.8% were S. flexneri, 15.0% were S. sonnei, and 2.2% were S. dysenteriae (2.2%). The re-emergence of Shigella dysenteriae was noted in 1998, after an absence of 15 years. Shigella spp. were resistant to ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline. Salmonella typhi and Salmonella paratyphi A were susceptible to all antibiotics tested, while Salmonella spp. showed various resistance patterns according to species grouping. A small number of V. cholerae O1 were resistant to ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline; however, they were still sensitive to ceftriaxon, norfloxacin, and ciprofloxacin. Similar results were shown for V. cholerae non-O1. Campylobacter jejuni showed an increased frequency of resistance to ceftriaxone, norfloxacin, and ciprofloxacin, but was susceptible to erythromycin. This study shows that except for C. jejuni and V. parahaemolyticus, which appeared to be resistant to ciprofloxacin, the majority of the enteric pathogens tested were still susceptible to fluoroquinolones.

Surveillance of bacterial pathogens of diarrhea disease in Indonesia.

Emerging or reemerging infections due to bacterial disease may be a local, regional or global problem. Bacterial acute gastroenteritis is a potential cause of substantial morbidity in travelers and deployed U.S. military personnel. A surveillance study was conducted over a two-year period in Indonesia among 6760 patients with debilitating diarrheal diseases. Of the 6,760 patients, 587 (9%) of the patient stools were positive for bacteria. The proportions of bacteria isolated from the 587 patients were: Shigella flexneri (39%), Salmonella spp. (26%), Vibrio spp. (17%), S. sonnei (7%), Campylobacter jejuni (4.4%), Salmonella typhi (3%) and S. dysenteriae (2.3%). Shigella flexneri was the most prevalent pathogen isolated, over Vibrio spp. No V. cholerae was isolated in the cities of Pontianak, Padang or Batam in Indonesia. Shigella dysenteriae reemergence was noted in Bali, Kalimantan, Batam and Jakarta after an absence of 15 years. Isolation of a high proportion of S. flexneri, and Vibrio spp. occurred during the rainy months. All bacterial isolates were susceptible to quinolones, with the exception of C. jejuni and Salmonella spp., which were resistant to ciprofloxacin, norfloxacin and nalidixic acid. Our findings highlight the decline of V. cholerae, the rise of S. flexneri and the reemergence of S. dysenteriae in Indonesia. The study also documents the emergence of quinolone-resistant Campylobacter spp. in the Indonesia archipelago.

Enteropathogens associated with acute diarrhea in community and hospital patients in Jakarta, Indonesia.

The prevalence of bacteria, parasite and viral pathogens in 3875 patients with diarrhea in community and hospital settings from March 1997 through August 1999 in Jakarta, Indonesia was determined using routine bacteriology and molecular assay techniques. Bacterial pathogens isolated from hospital patients were, in decreasing frequency, Vibrio cholerae O1, Shigella flexneri, Salmonella spp. and Campylobacter jejuni, while S. flexneri, V. cholerae O1, Salmonella spp. and C. jejuni were isolated from the community patients. V. cholerae O1 was isolated more frequently (P<0.005) from the hospital patients than the community patients. Overall, bacterial pathogens were isolated from 538 of 3875 (14%) enrolled cases of diarrhea. Enterotoxigenic Escherichia coli were detected in 218 (18%) of 1244 rectal swabs. A small percentage of enterohemorrhagic E. coli (1%) and of Clostridium difficile (1.3%) was detected. Parasitic examination of 389 samples resulted in 43 (11%) positives comprising Ascaris lumbricoides (1.5%), Blastocystis hominis (5.7%), Giardia lamblia (0.8%), Trichuris trichiura (2.1%) and Endolimax nana (0.5%). Rotavirus (37.5%), adenovirus (3.3%) and Norwalk-like virus (17.6%) were also detected. Antimicrobial resistance was observed among some isolates. Bacterial isolates were susceptible to quinolones, with the exception of some isolates of C. jejuni which were resistant to ciprofloxacin, nalidixic acid and norfloxacin. Data obtained from this community- and hospital-based study will enable the Indonesian Ministry of Health to plan relevant studies on diarrheal diseases in the archipelago.

Spectrum of vibrio species associated with acute diarrhea in North Jakarta, Indonesia.

Vibrio spp was isolated from 1024 (21.2%) of 4820 diarrhea patients admitted to a community hospital in North Jakarta from 1996 through 1998. Vibrio cholerae O1 (49.5%) and V. parahaemolyticus (30.1%) comprised the major species isolated, followed by V. cholerae non-O1 (16.9%), and V. fluvialis (9.4%). In 938 (19.4%) patients, Vibrio was found as single isolate. Multiple infections were detected in 86 (1.8%) patients. A small number of V. furnisii, V. metschnikovii, V. mimicus and V. hollisae were also isolated. No V. cholerae O139 was detected. The majority of patients with Vibrio spp. infections were adults between the ages of 20 to 45 years. No Vibrio spp. was isolated from infants <1 year old in this study. In vitro antibiotic susceptibility testing revealed no antibiotic resistance associated with the 507 V. cholerae O1 isolates tested, except for colistin (100%). These data implicate Vibrio spp. as a major cause of diarrhea in this region.

Reproductive history in relation to plasma hormone levels in healthy post-menopausal women.

OBJECTIVES: We sought to examine the relationship between reproductive history and measures of selected gonadotrophins and steroid hormones among post-menopausal women. Previous studies have suggested that there is a negative correlation between parity and post-menopausal serum estrogens, which may be a mechanism by which pregnancies protect women from the development of breast cancer. METHODS: We analyzed women who experienced a natural menopause within the Healthy Women Study cohort both 1 and 8 years after menopause. Lifetime reproductive history was obtained and blood was assayed for estrone, estradiol, androstenedione, testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) at 1 year post-menopause and for many of these steroid hormones at 8 years post-menopause. Also at 8 years post-menopause, a hip bone mineral density measure was obtained. RESULTS: Age at menopause related to a modest increase in estrone at 1 year but a decrease in estrone and estradiol at eight years. Adjustment for body mass index (BMI), oral contraceptive use, alcohol use, cigarette smoking, and education had little impact on these findings. There were no other internally consistent relationships between reproductive variables and steroid hormones or hip-bone mineral density. CONCLUSIONS: These observations do not support the hypothesis that parity acts to diminish endogenous levels of post-menopausal estrogens.

Thyroid function and perimenopausal lipid and weight changes: the Thyroid Study in Healthy Women (TSH-W).

We designed a prospective observational trial to study the relationship of thyroid function to cholesterol and weight changes at menopause. Subjects were participants in the ongoing Healthy Women Study, a prospective study of cardiovascular risk factor change through menopause. Healthy premenopausal women were recruited from a random sample of licensed drivers in selected ZIP codes of Allegheny County, Pennsylvania. Participants had to be 42-50 years of age, have menstruated within the last 3 months, not have had surgical menopause, have diastolic blood pressure < 100 mm Hg, and not be taking medications (including insulin, estrogen, lipid-lowering drugs, or thyroid or antihypertensive medications) at the baseline examination. The substudy included three groups of women who were premenopausal at baseline and were categorized according to change noted at follow-up regarding menopausal status and use of hormone replacement therapy (HRT). The groups comprised 95 women who remained premenopausal, 96 postmenopausal women not on HRT, and 61 postmenopausal women using HRT. The main outcome measures were baseline and follow-up measurements for serum levels of thyroid-stimulating hormone (TSH), thyroid peroxidase, and thyroglobulin, as well as serum cholesterol, total high-density lipoprotein (HDL) cholesterol, triglycerides, and calculated low-density lipoprotein (LDL) cholesterol, height, and weight. Covariates included cigarette smoking and alcohol intake. The prevalence of thyroid antibodies in this healthy population was high at both time points (range 27%-31%) and did not differ by menopausal status. The presence of thyroid antibodies was associated with increased TSH concentration. Women with antibodies at both time points had lower levels of total and LDL cholesterol compared with those with no antibodies, significant only for those women who remained premenopausal during the follow-up period. Thyroid function during menopause in this healthy population is unlikely to account for the observed changes in levels of serum lipoprotein and body weight. The presence of thyroid antibodies may be associated with lower total and LDL cholesterol, possibly through an underlying inflammatory disorder.

Urinary markers of estrogen metabolism 2- and 16 alpha-hydroxylation in premenopausal women.

There is considerable scientific interest in whether measurement of the major estrogen metabolites 2- and 16 alpha-hydroxyestrone will shed light on the role of estrogen in the risk of breast cancer. These have been difficult to measure in large numbers because of the need for radiolabeled tracers, but a new assay is able to utilize spot urine samples. The main objective of this study was to assess the reliability of a newly developed enzyme immunoassay (EIA) for the measurement of 2- and 16 alpha-hydroxyestrone in urine samples collected from a large group of healthy premenopausal women enrolled in a clinical trial A secondary objective was to assess the impact of several factors such as body weight on the urinary estrogen metabolite ratios. The study cohort included 174 women aged 44-50, who were enrolled in the Cardiovascular Risk Factors and Menopause Trial, also referred to as the Women's Healthy Lifestyle Project (WHLP), an ongoing 5-year clinical trial of 535 premenopausal women randomized either to an intensive dietary life-style intervention group or to an assessment-only control group. Measurements of 2- and 16 alpha-hydroxyestrone showed a high intraclass correlation for blind duplicate urine samples (R = 0.94 and R = 0.80), cross-sectionally and over time (R = 0.79 and R = 0.62), in this population of healthy premenopausal women. The intervention diet (of 25% of total calories from fat) did not appear to influence the estrogen metabolite ratio. This new estrogen metabolite EIA demonstrates good reliability and thus may be appropriate for use in large epidemiologic studies of estrogen-related diseases. There was no relation between dietary fat reduction, weight loss, and increased exercise and change in the ratio among premenopausal women in this study.

Effects of fluoridated drinking water on bone mass and fractures: the study of osteoporotic fractures.

To determine if optimal fluoridation of public water supplies influences bone mass and fractures, we studied 2076 non-black women, all aged > or = 65 years recruited into the Study of Osteoporotic Fractures at the Pittsburgh clinic. Information on fluoride exposure was limited to community water supplies. The variable used in the analysis was years of exposure to fluoridated water in community drinking water supplies. Bone mineral density (BMD) was measured at the spine and hip using dual energy X-ray absorptiometry and at the midpoint and ultradistal radius and calcaneus using single photon absorptiometry. Prevalent and incident vertebral fractures were determined by morphometry. Incident nonspine fractures were ascertained every 4 months and confirmed by radiographic report. Exposure to residential fluoridated water had no effect on bone mass. Women exposed to fluoride for > 20 years had similar axial and appendicular bone mass to women not exposed or women exposed for < or = 20 years. There was some suggestion that women exposed to fluoride for > 20 years had a lower relative risk of nonspine fractures (relative risk, RR, = 0.73; 95% confidence interval [CI] 0.48-1.12), osteoporotic fractures, RR = 0.74 (CI 0.46-1.19), and hip fractures, RR = 0.44 (CI 0.10-1.86), compared with women not exposed, but none of these relative risks was statistically significant. There was no association with wrist or spinal fractures. Our results do not support the findings from recent ecological studies which showed an increased risk of hip fracture among individuals exposed to fluoridated public water.

Prevalence of thyroid antibodies among healthy middle-aged women. Findings from the thyroid study in healthy women.

Autoimmune thyroiditis is the most common cause of subclinical hypothyroidism in North America, is more common in women than men, and is a risk factor for the development of coronary heart disease (CHD). We measured thyroid-stimulating hormone (TSH) and two thyroid antibodies, thyroid peroxidase and thyroglobulin, in stored sera of the participants (aged 44 to 54 years) of the Healthy Women Study. We selected 254 samples from the premenopausal baseline examination in 1983 to 1985 and from a follow-up examination that occurred an average of 5.7 years later (range, 3 to 7.7 years). At follow-up, 95 women remained premenopausal, 98 had ceased menstruating for at least 12 months, and 61 were taking postmenopausal hormone therapy. Overall, the prevalence of the thyroid antibodies in this healthy population was high at both time points (21 to 26%). Women with antibodies had higher TSH concentrations than did those with no antibodies (2.68 +/- 1.3 versus 1.51 +/- .73 mU/L, P < 0.001); this relationship was statistically significant even after excluding those with subclinical hypothyroidism (TSH > 6.0 mU/L). TSH and antibody levels did not differ by menopausal status or hormone therapy use at follow-up. Given the high prevalence of thyroid antibodies among healthy middle-aged women, long-term follow-up is warranted to ascertain whether the presence of antibodies is associated with subsequent excess risk of disease, in particular, CHD.

Persistent effects of antidepressants: EEG sleep studies in depressed patients during maintenance treatment.

Electroencephalographic (EEG) sleep studies represent a research tool that can be used to examine depressed patients over different phases of their illness. We examined the long-term effects of imipramine on EEG sleep in 27 subjects who completed 3 years of maintenance treatment on imipramine without experiencing a recurrence. The analyses were performed on EEG sleep data collected prior to acute treatment, after 3 months in maintenance, and every 3 months thereafter. The major aim was to examine specific changes in rapid eye movement (REM) and slow-wave sleep (SWS) as they unfolded over the course of illness and recovery during long-term drug maintenance. The acute changes in the sleep profile produced by antidepressants remained essentially the same throughout the entire period of drug administration. The REM sleep parameters, which were affected immediately, remained essentially unchanged thereafter, even as long as 3 years into maintenance treatment. A rapid redistribution of slow-wave sleep in the first part of the night was also observed without an increase in the total amount of slow-wave sleep throughout the night. The application of spectral analysis confirmed that the sleep changes following drug administration remained stable throughout all phases of drug treatment. Thus, it appears that sustained clinical improvement is accompanied by persistent sleep alterations on tricyclic antidepressant medication.

Electroencephalographic sleep studies in depressed patients during long-term recovery.

Analytic electroencephalographic (EEG) sleep procedures were used to examine specific changes in rapid eye movement (REM) and slow wave sleep (SWS) as they unfolded during depressive illness and recovery. The subjects were 15 patients with recurrent depression who remained well during 3 years of nonpharmacologic maintenance treatment without a recurrent episode of major depression. The analyses were performed on EEG sleep studies conducted before acute treatment, after 3 months in maintenance treatment, and every 3 months thereafter for 3 full years of maintenance treatment. There was no change between the index sleep and sleep during the first year of maintenance treatment as determined by period analysis or visual inspection of REM sleep parameters, except that average REM counts decreased over time. Thus, it is possible that REM parameters may represent one indicator of long-term recovery from depression. Finally, a significantly higher amount of 12-20 Hz spectral power density was found during the index episode than during the period of remission.