Premenopausal women with idiopathic low-trauma fractures and/or low bone mineral density.

INTRODUCTION: In men, idiopathic osteoporosis (IOP) is often associated with low serum insulin-like growth factor (IGF-1) and reduced bone formation. The characteristics of premenopausal women with IOP are not well defined. We aimed to define the clinical, reproductive, and biochemical characteristics of premenopausal women with unexplained osteoporosis. METHODS: This is a cross-sectional study of 64 women with unexplained osteoporosis, 45 with fragility fractures, 19 with low bone mineral density (BMD; Z-score less than or equal to -2.0) and 40 normal controls. The following are the main outcome measures: clinical and anthropometric characteristics, reproductive history, BMD, gonadal and calciotropic hormones, IGF-1, and bone turnover markers (BTMs). RESULTS: Subjects had lower BMI and BMD than controls, but serum and urinary calcium, serum estradiol, vitamin D metabolites, IGF-1, and most BTMs were similar. Serum parathyroid hormone (PTH) and the resorption marker, tartrate-resistant acid phosphatase (TRAP5b), were significantly higher in both groups of subjects than controls and directly associated in all groups. Serum IGF-1 and all BTMs were directly associated in controls, but the association was not significant after controlling for age. There was no relationship between serum IGF-1 and BTMs in subjects. There were few differences between women with fractures and low BMD. CONCLUSIONS: Higher serum TRAP5b and PTH suggest that increased bone turnover, possibly related to subclinical secondary hyperparathyroidism could contribute to the pathogenesis of IOP. The absence of differences between women with fractures and those with very low BMD indicates that this distinction may not be clinically useful to categorize young women with osteoporosis.

Metabolic effects of interventions to increase exercise in adults with type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this meta-analysis was to integrate the results of primary research testing the effect of diabetes self-management interventions that included recommendations to increase exercise on metabolic outcomes among adults with type 2 diabetes. MATERIALS AND METHODS: Extensive literature searching strategies were used to identify published and unpublished intervention studies that measured glycated haemoglobin outcomes. Primary study results were coded. Fixed- and random-effects meta-analytic procedures included moderator analyses. RESULTS: Data were synthesised across 10,455 subjects from 103 research reports. The overall mean weighted effect size for two-group comparisons was 0.29 (higher mean for treatment than control). This effect size is consistent with a difference in HbA1c means of 0.45% (e.g. 7.38% for treatment subjects vs 7.83% for control subjects). For single-group studies, the overall mean weighted effect size was 0.32-0.34. Control group subjects experienced no improvement in metabolic control during participation in the studies. Interventions that targeted multiple health behaviours resulted in smaller effect size estimates (0.22) than interventions that focused only on exercise behaviours (0.45). Funded studies reported greater improvements in metabolic controls. Studies with a greater proportion of female subjects reported lower effect sizes. Baseline HbA1c and BMI were unrelated to metabolic outcomes. CONCLUSIONS/INTERPRETATION: These findings suggest that self-management interventions that include exercise recommendations improve metabolic control, despite considerable heterogeneity in the magnitude of the intervention effect. Interventions that emphasise exercise may be especially effective in improving metabolic control. Primary research testing interventions in randomised trials to confirm causal relationships would be constructive.

Environmental, genetic and social factors affecting the expression of estrus in beef cows.

Genetic, social and environmental factors affecting behavioral estrus were evaluated in Angus (n = 10), Brahman (n = 10) and Senepol (n = 10) cows during a PGF2alpha synchronized estrus and subsequent spontaneous estrus. Cows were equally stratified by breed to two groups of 15. Both groups were pre-synchronized with a modified two-injection PGF2alpha protocol. At the start of the experiment, cows were treated with 25 mg PGF2alpha followed by a second and third administration of 12.5 mg PGF2alpha, 11 and 12 days later to induce synchronized estrus. The subsequent estrus was designated as spontaneous estrus. Behavioral estrus data including the onset and end of estrus, estrous duration and the total number of mounts received for the synchronized and spontaneous estruses were collected using HeatWatch". Interval from the third PGF2alpha, treatment to the onset of a HeatWatch" estrus occurred earlier (P < 0.05) in Angus (31 +/- 5 h) than Brahman (53 +/- 7 h) or Senepol (53 +/- 4 h) cows, with dominant Senepol and Brahman cows taking longer to exhibit estrus after PGF2alpha than subordinate cows. The duration of the synchronized estrus tended to be shorter (P < 0.06) in Senepol (12 +/- 3 h) than in Angus (19 +/- 2 h) or Brahman (17 +/- 2 h) cows. Behavioral estrus data between the two periods were confounded by greater temperature-humidity index (THI) values during spontaneous estrus. The THI during spontaneous estrus appeared (P = 0.09) to affect the duration of estrus (9 +/- 1 h versus 16 +/- 1 h) and did affect (P < 0.0001) the total number of mounts received (8 +/- 4 mounts versus 34 +/- 4 mounts) during spontaneous estrus compared to synchronized estrus. Breed had no effect (P > 0.10) on the duration and total number of mounts received during synchronized and spontaneous estruses. In conclusion, type of estrus (synchronized or spontaneous), THI, social dominance and breed exerted significant effects on characteristics associated with behavioral estrus in beef cattle in subtropical environments.

Prediction of 'highly skin smear positive' cases among MB leprosy patients using clinical parameters.

Although 'highly skin smear positive' MB leprosy cases are known to be at high risk of relapse after release from treatment, and have been recommended to receive 'prolonged duration' MDT, government field-based control programmes without skin smear facilities have no simple alternative method to detect such cases. This study reports a significant prevalence of 'highly smear positive' cases amongst 2374 new multibacillary cases recently surveyed by skin smears in Nepal, and retrospectively analyses 555 newly detected, previously untreated BL and LL cases to identify clinical and laboratory parameters that may be associated with a 'highly positive skin smear'. While some parameters showed high sensitivity in predicting 'highly positive smear' status, none showed both high sensitivity and high specificity simultaneously.

Effectiveness of GnRH plus prostaglandin F2alpha for estrus synchronization in cattle of Bos indicus breeding.

Postpartum and lactating crossbred cows containing a percentage of Bos indicus breeding at three locations were studied to determine the efficacy of GnRH + PGF2alpha combinations for synchronization of estrus and(or) ovulation. Cows were equally distributed to each of three treatments by body condition score at the start of the experiment (d 0). All cows received 100 microg of GnRH on d 0 and 25 mg of PGF2alpha 7 d later. The three insemination protocols included 1) AI 12 h after exhibiting estrus during d 7 to 12 of the experiment (Select-Synch; n = 197); 2) timed-AI + 100 microg of GnRH on d 9 of the experiment (CO-Synch; n = 193); 3) AI 12 h after exhibiting estrus during d 7 to 10 of the experiment. Cows not exhibiting estrus by d 10 were timed-AI and injected with 100 microg of GnRH on d 10 of the experiment (Hybrid-Synch; n = 200). The percentage of cows exhibiting estrus during d 7 to 12 of the experiment was lower (P < 0.05) for CO-Synch (17.6%) cows than for Select-Synch or Hybrid-Synch (45.2 and 33.0%, respectively) cows, which did not differ (P > 0.05). For the Select-Synch and Hybrid-Synch cows that exhibited estrus during d 7 to 10 of the experiment and were artificially inseminated, conception rates were similar across treatments (50.5%). Pregnancy rates were greater (P < 0.01) for CO-Synch and Hybrid-Synch (31.0 and 35.5%, respectively) cows than for Select-Synch (20.8%) cows. A greater (P < 0.01) percentage of cycling cows became pregnant (34.5%) than noncycling cows (25.9%) across all treatments. The CO-Synch and Hybrid-Synch synchronization protocols resulted in greater pregnancy rates compared with the Select-Synch protocol in postpartum and lactating crossbred cows containing a percentage of Bos indicus breeding.

Disoriented and ataxic pilgrims: an epidemiological study of acute mountain sickness and high-altitude cerebral edema at a sacred lake at 4300 m in the Nepal Himalayas.

OBJECTIVE: To determine the incidence of high-altitude cerebral edema (HACE), acute mountain sickness (AMS), and high-altitude pulmonary edema (HAPE) in pilgrims. Although it is well known that western trekkers suffer from acute mountain sickness (AMS) in the Himalayas, not much is documented about the incidence of AMS in the local population of Nepal that go to high altitude. METHODS: The design was a randomized study set at a sacred high-altitude lake at 4300 m at Gosainkund in the Nepal Himalayas. There was a control study at 1300 m at Pashupatinath in Kathmandu, Nepal. The subjects were pilgrims of different ethnic Nepali backgrounds. The Lake Louise consensus for AMS, HACE, and HAPE was used, and oxygen saturation with a pulse oximeter was performed on HACE subjects. RESULTS: Out of 5000 pilgrims, 228 were randomly chosen. Sixty-eight percent had AMS, 31% had HACE, and 5% had HAPE. The mean oxygen saturation of HACE subjects at that altitude was 77%, 87% being normal for 4300 m altitude. Seventy-three percent of the study population were men, yet women had a significantly higher rate of AMS (odds ratio, 4.34; 95% confidence interval, 1.83-10.68), HACE (odds ratio 3.15, confidence interval 1.62-6.12), and HAPE (odds ratio, 5.2; 95% confidence interval, 1.24-24.73). CONCLUSIONS: Such a high incidence of HACE in an epidemiological study using the Lake Louise criteria has, to our knowledge, not been reported before. High-altitude pilgrims, especially women pilgrims in this study, seem to be a very susceptible group. Preventive measures in these pilgrims need to be adopted to avoid AMS, specifically life-threatening HACE and HAPE.

Interferon-gamma responses to candidate leprosy skin-test reagents detect exposure to leprosy in an endemic population.

New tools for the detection of leprosy exposure in a community will be necessary for the eradication of leprosy. Candidate leprosy skin-test antigens derived from the fractionation of the leprosy bacillus into cytoplasmic and cell-wall proteins free of immuno-inhibitory mycobacterial lipoglycans and carbohydrates were used in an overnight blood test to determine whether exposure to leprosy can be detected by the production of the cytokine interferon gamma (IFN-gamma). Strong IFN-gamma responses were detected in leprosy contacts to both skin-test antigens compared with control subjects from the same endemic communities. There was little response in patients with tuberculosis. Responses were greatest in contacts with recent leprosy exposure. The implications of these findings for the application of these reagents in a field trial as skin tests to detect exposure to leprosy are discussed in light of the strong association between overnight IFN-gamma to PPD and the tuberculin skin-test responses previously reported.

Risk factors for erythema nodosum leprosum.

A retrospective study of new borderline lepromatous and lepromatous patients reporting for multidrug therapy (MDT) for leprosy at the Anandaban Leprosy Hospital, Kathmandu, Nepal, over an 8-year period was conducted to determine the prevalence of erythema nodosum leprosum (ENL), the time and frequency of reactions, and clinical and laboratory parameters associated with ENL. An overall prevalence of ENL in this cohort of 19% was found. One third of these reactions occurred in patients before MDT was given, one third in the first 6 months and one third after 6 months of treatment. Nearly 1 in 10 of the ENL reactions occurred in patients who had completed 2 years of MDT; 45% of patients with ENL had more than one episode. Data collected at the patients' first presentation was used to identify four major risk factors. Patients with lepromatous disease, skin infiltration or a bacterial index (BI) of > 4+ were at significantly increased risk. Patients older than 40 were at significantly decreased risk of ENL. There was a linear relationship in the risk of ENL with an increasing BI and an inverse relationship to increasing age. These observations should enable clinicians to recognize patients at first presentation who will be likely to develop ENL.

Everest or bust: a cross sectional, epidemiological study of acute mountain sickness at 4243 meters in the Himalayas.

BACKGROUND: Thousand of tourists trek in the Himalayas every season and risk acute mountain sickness (AMS). Prior studies have shown that the rate of ascent is one of the primary risk factors for the development of AMS but the role of body hydration, age, gender, alcohol and medication usage, body weight, and altitude of residence continues to be in question. This study estimates the incidence of AMS at 4234 m at Pheriche in the Everest region, explores a number of risk factors predisposing trekkers to a diagnosis of AMS and attempts to quantify the relationship between the Lake Louise AMS diagnostic criteria and oxygen saturation. METHODS: Demographic data and information about risk factors felt to place trekkers at increased risk of AMS was collected from 550 trekkers for 1 mo in the fall of 1996 at 4234 m in the Everest region. RESULTS: Diagnosis of AMS was made in 29.8% (159 trekkers) of the study population. Low water intake (odds ratio 1.57; 95% confidence interval,1.02-2.40), the presence of respiratory symptoms (odds ratio 2.21; 95% confidence interval, 1.43-3.40), and an oxygen saturation below 85% at 4243 m (odds ratio 2.35; 95% confidence interval, 1.55-3.56) were identified as independent risk factors for AMS diagnosis in this sample. In addition, AMS risk decreased 18.7% (95% confidence interval, 3.8-31.2%) for each additional night spent between Lukla (2804 m) and the study site at 4243 m. CONCLUSION: Increased reported fluid intake decreased the risk of AMS in this cross sectional prospective study. Further studies need to be done to confirm this finding before recommendations can be made. In addition the rise in the risk of AMS as the rate of ascent increased along this popular Everest trek was quantified for the first time. Finally, AMS was also associated with respiratory symptoms and with a lower oxygen saturation.

Percutaneous papillary balloon dilatation as a therapeutic option for cholecystocholedocholithiasis in the era of laparoscopic cholecystectomy.

The present study was conducted to evaluate the effectiveness of percutaneous papillary balloon dilatation (PPBD) as a therapeutic option for cholecystocholedocholithiasis, in combination with laparoscopic cholecystectomy (LC). A total of 15 patients with both bile duct and gallbladder stones were clinically investigated. In 14 patients, PPBD was performed 2 to 7 days prior to LC, while in the remaining patient, PPBD was performed immediately after LC under general anesthesia in one continuous session. The bile duct stones were successfully pushed out into the duodenum in all the patients, seven of whom required two sessions for complete stone clearance, while the other eight needed only one session. Two patients had bile duct stones larger than 12 mm in diameter, necessitating electrohydraulic lithotripsy under cholangioscopy. The insertion of a percutaneous transhepatic biliary drainage tube did not cause intra-abdominal adhesions severe enough to contraindicate the use of LC. The operation times for LC varied from 80 to 184 min, with a mean operation time of 132 min, and the average postoperative and overall hospital stays were 9 and 26 days, respectively. There were no deaths or major complications, apart from transient hyperamylasemia. The findings of this study indicate that PPBD combined with LC is a safe and effective therapeutic option for cholecystocholedocholithiasis.

Ovulation and estrus characteristics in crossbred Brahman heifers treated with an intravaginal progesterone-releasing insert in combination with prostaglandin F2alpha and estradiol benzoate.

Crossbred Brahman heifers (n = 60) were studied to determine the effect of a 7-d intravaginal progesterone-releasing insert (INSERT) in combination with PG (Lutalyse; 25 mg i.m.) and estradiol benzoate (EB; .5 mg i.m.) on time of ovulation and estrous behavior. In Phase I, heifers at unknown stages of the estrous cycle were assigned by BW and body condition score to one of the three treatments on d 0: 1) INSERT for 7 d and PG on d 7 (CONTROL; n = 10); 2) INSERT for 7 d, PG on d 7, and EB 24 h after INSERT removal (EB24; n = 10); or 3) INSERT for 7 d, PG on d 7, and EB 48 h after INSERT removal (EB48; n = 10). Blood samples were collected every 8 h after INSERT removal. Also, blood sampling and ultrasonography began 8 h after the onset of estrus, determined with HeatWatch devices, and every 4 h thereafter to detect ovulation. In Phase II, Phase-I treatments (n = 10/treatments) were replicated, but only behavioral estrus data were collected to minimize handling of heifers. Frequent handling of heifers did not influence (P > .1) the interval from INSERT removal to the onset of HeatWatch and visual estrus and duration of estrus, so behavioral estrus data were combined for Phases I and II. Interval from INSERT removal to HeatWatch estrus was decreased (P < .05) in EB24 (45.5 h) vs EB48 (55.9 h) and CONTROL (59.2 h). Interval from INSERT removal to ovulation differed (P < .04) between CONTROL, EB24, and EB48 (93.5, 74.5, and 78.9 h, respectively). Ovulatory follicle size was similar (P > .1) between CONTROL, EB24, and EB48 (14.4, 12.5, and 14.1 mm, respectively). Duration of estrus was similar for CONTROL, EB24, and EB48 (14.0, 15.1, and 17.6 h, respectively). No difference (P > . 1) was observed in number of mounts received between CONTROL, EB24, and EB48 (28.0, 25.7, and 39.4, respectively), but number of mounts received increased in Phase II vs Phase I (40.0 and 22.2, respectively; P < .05). In conclusion, EB hastened the interval from INSERT removal to ovulation without altering duration of estrus or number of mounts received. Frequent handling of heifers did not affect interval to first mount received after INSERT removal or duration of estrus, but it decreased the total number of mounts received.

Effects of administration of oxytocin on embryonic survival in progestogen supplemented cattle.

Embryonic survival after administration of oxytocin (OT) was examined in 42 beef cows. All cows were bred (Day 0) and randomly assigned to receive either 25 mL saline (CON; n = 10), 100 IU OT + 20 mL saline (OT; n = 12), 100 IU OT + 1 g flunixin meglumine (OT + FM; inhibitor of prostaglandin endoperoxide synthase; n = 10), or 100 IU OT + lutectomy (OT + LUT; n = 10) administered (i.m.) at 8-h intervals on Days 5-8 after mating. Lutectomies were performed by transrectal digital pressure prior to initiation of treatments (0600, Day 5). All cows were fed 4 mg/head/day of melengesterol acetate (an orally administered exogenous progestogen) through Days 3-30 and were bled by jugular venipuncture at 0600 and 0700 h on Day 5 for determination of 13,14-dihydro-15-keto-PGF2a (PGFM). Pregnancy rates, as determined by transrectal ultrasonography at Day 30, were reduced in OT (33.3%) and OT + LUT (30%) groups compared to CON and OT + FM (80%; p < or = 0.03). Number of short cycles were increased in OT (n = 6/12) group compared to CON (n = 0/10; p < or = 0.009) and OT + FM (n = 1/10; p < or = 0.045). Mean change in PGFM from the 0600 to 0700 h bleed was different (p < or = 0.01) between the OT + LUT (31.6 +/- 11.0 pg/mL) group versus CON (-11.2 +/- 10.6 pg/mL) and OT + FM (-13.8 +/- 10.6 pg/mL) groups. Administration of oxytocin appears to decrease embryonic survival by stimulating uterine PGF2a. Thus, previous reports indicating that removal of the corpus luteum during progestogen supplementation and prior to PGF2a administration increases embryonic survival can be explained through interruption of the luteal oxytocin-uterine PGF2a feedback loop.

Effects of elevated concentrations of prostaglandin F2 alpha on pregnancy rates in progestogen supplemented cattle.

An experiment was performed to determine the effect of elevated prostaglandin F2 alpha (PGF2 alpha) on pregnancy rates of progestogen-treated bred cows in the presence or absence of luteal tissue. Ninety-one beef cows were bred (Day 0) and assigned randomly to receive either 3 mL saline (CON), 15 mg PGF2 alpha, or 15 mg PGF2 alpha + lutectomy (P + L) administered intramuscularly (i.m.) at 8 h intervals on either Days 5-8, 10-13, or 15-18 postbreeding. Lutectomies were performed by transrectal digital pressure before initiation of treatment on Day 5, 10, or 15 for the respective treatment groups. All cows were fed 4 mg/day of melengesterol acetate from two days prior to initiation of treatment until Day 30 postbreeding. Mean concentrations of 13,14-dihydro-15-keto-PGF2 alpha (PGFM) were increased in cows administered PGF2 alpha and P + L treatments (398 +/- 23 and 413 +/- 22 pg/ml, respectively; p < 0.01) compared to the CON group (80 +/- 29 pg/ml) regardless of treatment group. Mean concentrations of oxytocin (OT) were increased in cows given PGF2 alpha on Day 10 and 15 (p < or = 0.0001) and tended to be increased on d 5 when compared to CON and P + L treatment groups on Day 5. Pregnancy rates were reduced (p < or = 0.03) in the PGF2 alpha treatment group (23%) and by Day 5-8 compared to CON (72%). Lutectomy tended to improve pregnancy rate in P + L (5-8; 55%) compared to PGF2 alpha (5-8; p = 0.1). Pregnancy rates tended (p < or = 0.07) to increase in the PGF2 alpha treatment groups on Days 5-8 treatment (23%, 50%, and 60% for Days 5-8, 10-13, and 15-18, respectively). The later the treatments were initiated pregnancy rates did not differ between treatments given on Days 10-13 and 15-18. In conclusion, the most susceptible period of embryonic growth to the negative effects of PGF2 alpha was during morula to blastocyst development. Removal of luteal tissue diminishes the negative effects of PGF2 alpha through interruption of the luteal oxytocin-uterine PGF2 alpha feedback loop.

The quality of life after major thermal injury in children: an analysis of 12 survivors with greater than or equal to 80% total body, 70% third-degree burns.

Twenty-one children admitted between December 1981 and May 1985, with greater than 80% total body surface area burn (TBSAB), underwent total excision and grafting of all of their wounds within 72 hours of injury. Twelve survivors (with an average TBSAB of 89%, 82% third degree) were studied in detail describing the length of hospital stay (77 +/- 10 days), number of operative procedures (7.8 +/- 0.8), total blood loss (12 +/- 2 blood volumes), the number of patients who experienced septic episodes (three), the number of patients who required amputation (four), range of motion, degree of scarring, ability to perform daily activities, and psychological adjustment. Physical impairment, according to standard scales, was approximately 60%; however, 50% of the children old enough to be tested were completely independent in activities of daily living. One third of the children had excessive fear, regression, and neurotic and somatic complaints, but all of them showed remarkable energy in adapting to their disabilities. We conclude that the final outcome, for these patients, can only be assessed as they achieve late adolescence and young adulthood.