INNOVATIONS IN FOCUS: MECHANISTIC DISEASE THEORIES, CLIMATE DYNAMICS, AND HOST-PARASITE ADAPTATIONS.

Infectious illnesses are predicted to experience a range of intricate responses from climate change, with some likely to rise, others to fall and many expected to undergo changes in prevalence. The study uses extensive data on global temperature variations and infectious illness transmission in people and animals. We now know a lot more about how the temperature changes across the world and whether or not the spread of infectious diseases impacts people as well as animals. Three primary topics of research are investigated in this paper: improving mechanical disease modelling, investigating the role of environmental variation in sickness dynamics, and understanding the consequences of temperature imbalances between parasites and hosts. By incorporating the latest data stemming from these advancements into weather-disease models and bridging critical knowledge gaps, enhancing our ability to forecast the probable effect of rising temperatures on the prevalence of diseases among both human and animal communities is possible. Through the establishment of important information gaps and the incorporation of new findings into models of climate-disease relationships, it will be possible to predict the effects of changes in climatic averages, variations and extremes on people and wildlife health.

Mobility and muscle strength in male former elite endurance and power athletes aged 66-91 years.

The aim of this cross-sectional study was to compare mobility and muscle strength in male former elite endurance and power athletes aged 66-91 years (n = 150; 50 men in both former elite athlete groups and in their control group). Agility, dynamic balance, walking speed, chair stand, self-rated balance confidence (ABC-scale), jumping height, and handgrip strength were assessed. Former elite power athletes had better agility performance time than the controls (age- and body mass index, BMI-adjusted mean difference -3.6 s; 95% CI -6.3, -0.8). Adjustment for current leisure time physical activity (LTPA) and prevalence of diseases made this difference non-significant (P = 0.214). The subjects in the power sports group jumped higher than the men in the control group (age- and BMI-adjusted mean differences for vertical squat jump, VSJ 4.4 cm; 95% CI 2.0, 6.8; for countermovement jump, CMJ 4.0 cm; 95% CI 1.7, 6.4). Taking current LTPA and chronic diseases for adjusting process did not improve explorative power of the model. No significant differences between the groups were found in the performances evaluating dynamic balance, walking speed, chair stand, ABC-scale, or handgrip strength. In conclusion, power athletes among the aged former elite sportsmen had greater explosive force production in their lower extremities than the men in the control group.

Cardiovascular health in former elite male athletes.

To increase our knowledge on the effects of previous and current physical activity on cardiovascular health, we studied a group of Finnish male former elite athletes (endurance, n = 49; power, n = 50) and their 49 age and area-matched controls, aged 64-89 years. Body mass index (BMI), fasting serum glucose, lipids, blood pressure, and ultrasonography of cardiac and carotid artery structure and function were measured. Former endurance athletes smoked less, had lower prevalence of hypertension, and had higher intensity and volume of leisure time physical activity (LTPA) than the controls. No difference was detected in cardiac or carotid artery structure and function between these groups. Former athletes performing high-intensity LTPA were slightly younger (possible selection bias), had lower BMI and waist circumference, lower use of antihypertensives, lower prevalence of diabetes, lower pulse wave velocity, and higher carotid artery elasticity than former athletes not performing high-intensity LTPA. In conclusion, former athletes had a higher intensity and volume of LTPA than the controls. Athletes performing vigorous LTPA had more elastic arteries than athletes performing moderately or no LTPA. Vigorous LTPA through the whole lifetime associates with good cardiovascular health, although the previous medical history may play an important role.

Former male elite athletes have better metabolic health in late life than their controls.

Elite-class athletes have longer life expectancy and lower risk for chronic noncommunicable diseases possibly because of physically active and healthier lifestyle. In this study, we assessed former male Finnish elite-class athletes' (n = 392) and their matched controls' (n = 207) body composition, and risk for the metabolic syndrome (MS) and nonalcoholic fatty liver disease (NAFLD) in later life. Compared with the controls, the former athletes had lower body fat percentage (24.8% vs 26.0%, P = 0.021), lower risk for MS [odds ratio (OR) 0.57, 95% confidence interval (CI) 0.40-0.81], and NAFLD (OR 0.61, 95% CI 0.42-0.88). High volume of current leisure-time physical activity (LTPA) was associated with lower body fat percentage (P for trend < 0.001). When current volume of LTPA increased 1 MET h/week, the risk of MS and NAFLD decreased (OR 0.99, 95% CI 0.98-0.99 and OR 0.97, 95% CI 0.96-0.98, respectively). Although a career as an elite-class athlete during young adulthood may help to protect from developing metabolic syndrome, present exercise levels and volume of LTPA seem equally important as well.

Cumulative incidence of shoulder region tendon injuries in male former elite athletes.

Some types of sports are thought to include a high risk for shoulder region tendon injuries but little data exist on long-term cumulative incidence of these injuries. The aim of our study was to investigate shoulder region tendon injuries diagnosed by physicians in former elite male athletes participating in sports including maximal overhead manoeuvres (overhead athletes) and also other athletes before the age of 45 years and within the subjects' lifetime, compared to control subjects. A postal questionnaire was sent in 2002 to male former elite athletes (n=785; mean age 68 years when responding to the questionnaire; overhead athletes n=111, others n=674) and control subjects (n=416; mean age 67 years). Overhead athletes had a higher risk for shoulder region tendinopathy before the age of 45 (adjusted odds ratio (OR) 4.1, 95% confidence interval (CI) 2.0-8.4, p<0.001) and within lifetime (OR 1.8, 95% CI 1.1-3.0, p=0.027) compared to control subjects. Compared to controls the risk for tendon rupture before the age of 45 (adjusted OR 4.4, 95% CI 1.3-14.8, p=0.016) and within lifetime (OR 2.0, 95% CI 1.0-6.9, p=0.041) was also high in overhead athletes. There was no difference in the risks of shoulder region tendon injuries between the other athletes and the control subjects. Our data indicate that shoulder region injuries are common in athletes participating in sports including maximal overhead manoeuvres and the long-term consequences of these injuries for athletes' daily life and functional ability should be determined.

Repaired oesophageal atresia: respiratory morbidity and pulmonary function in adults.

Although after oesophageal atresia (OA) repair in infancy, respiratory problems are common, their natural history remains unclear. We assessed morbidity, pulmonary function (PF), and bronchial hyperresponsiveness (BHR) in adults with repaired OA respiratory. 588 patients who underwent surgery for OA during 1947-1985 were identified and those 262 who were alive and had their native oesophagus were included. Respiratory symptoms and respiratory symptom-related quality of life (RSRQoL) were assessed by questionnaire and interview, and the patients underwent spirometry, a histamine challenge test, and an exhaled nitric oxide test. For the questionnaires, we added 287 carefully matched general population-derived controls. Among the 101 (58 male) patients, median age 36 yrs (range 22-56 yrs), respiratory morbidity was significantly increased compared to controls. Patients had more respiratory symptoms and infections, as well as asthma and allergies, and more often impaired RSRQoL (p<0.001 for all). PF tests revealed restrictive ventilatory defect in 21 (21%) patients, obstructive ventilatory defect in 21 (21%) patients, and both in 36 (36%) patients. A total of 41 (41%) had BHR, and in 15 (15%), it was consistent with asthma. The most significant risk factors for restrictive ventilatory defect were thoracotomy-induced rib fusions (OR 3.4, 95% CI 1.3-8.7; p = 0.01) and oesophageal epithelial metaplasia (OR 3.0, 95% CI 1.0-8.9; p = 0.05). After repair of OA, respiratory-related morbidity, restrictive ventilatory defect and BHR extended into adulthood. Nearly half the patients had BHR and over half had a restrictive ventilatory defect. Thoracotomy-induced rib fusions and gastro-oesophageal reflux-associated oesophageal epithelial metaplasia were the strongest risk factors for restrictive ventilatory defect.

Patient-reported complications associated with Campylobacter jejuni infection.

This study aimed to investigate the occurrence of complications, especially musculoskeletal symptoms, after sporadic Campylobacter jejuni enteritis of domestic origin in Finland. This multi-centre cross-sectional study was conducted during a seasonal peak in 2002. Questionnaires were sent to Campylobacter-positive patients, representing different geographical areas, 2 months after collection of positive stool samples. Medical records were viewed in several cases. Besides antimicrobial susceptibility testing C. jejuni isolates were serotyped. A total of 235 patients (58%) returned the questionnaire and 201 C. jejuni-positive patients were finally included in the study. Musculoskeletal symptoms associated with C. jejuni enteritis were frequent (39%); joint pain was most commonly reported (81%). The incidence of reactive arthritis was 4% and that of Achilles enthesopathy and/or heel pain was 9%. Stomach ache during enteritis was associated with the later development of joint pain. Antimicrobial treatment was common but did not prevent complications.

Former athletes' health-related lifestyle behaviours and self-rated health in late adulthood.

The aim of this study was to examine the associations between self-rated health (SRH), physical activity and other lifestyle habits among former athletes and referents in late adulthood. Male athletes (N=514) who represented Finland from 1920 through 1965 and referents (N=368) who were classified healthy at the age of 20 years participated in this population-based cohort study. The present analysis was based on a questionnaire study in 2001. SRH was assessed by a single question. Univariate binary and multivariate logistic regression analyses were used to examine the associations of health-related behaviours with SRH. The majority of former athletes (64%) rated their health better than referents (48%). A higher percentage of the athletes (54%) compared to the referents (44%) belonged to the most physically active groups (MET quintiles IV-V). A high percentage of the athletes (77%) and referents (79%) were occasional or moderate alcohol users. The proportion of never smokers among athletes was 59% and among referents 37%. Among current smokers there were no differences in nicotine dependence between athletes and referents (p=0.07). In the univariate analysis the odds of reporting good SRH was 2 times higher for athletes (OR 2.01, 95% CI 1.53-2.64, p<0.001) than for referents. In multivariate logistic regression analysis, former participation in team and power athletic groups had significantly higher SRH than the referents even after adjusting for age, level of physical activity, alcohol and smoking habit, and occupation. People who participated in very active physical exercise in their youth, as indexed by participation in competitive sports by elite athletes, continue a physically active lifestyle, and maintained healthier lifestyle. They had significantly higher SRH than the referents in their senior years, which was not totally explained by their physically active and healthier lifestyles.

Brain magnetic resonance imaging of siblings from families with two or more children with learning or intellectual disabilities and need for full-time special education.

BACKGROUND: Several factors are involved in determining a child's need for special education (SE). Thus, the value of brain magnetic resonance imaging (MRI) for subjects with learning and intellectual disabilities is uncertain. PURPOSE: To evaluate the usefulness of MRI in the diagnostic process of siblings with learning and intellectual disabilities and need for full-time SE. MATERIAL AND METHODS: Altogether, 119 siblings (mean age 11.9 years) from families in which two or more children attended/had previously attended full-time SE underwent prospective brain MRI. SE grouping included three levels, from specific learning disabilities (level 1) to global intellectual disabilities (level 3). Forty-three controls (level 0, mean age 12.0 years) attended mainstream education groups. Signal intensity and structural abnormalities were analyzed, and areas of the cerebrum, posterior fossa, corpus callosum, vermis and brain stem, and diameters of the corpus callosum were measured. In analyses, all area measurements were calculated in proportion to the total inner skull area. RESULTS: Abnormal finding in MRI was more common for siblings (n=62; 52%) in SE (58% for level 3; 49% for level 2; 35% for level 1) than for controls (n=13; 16%). The siblings showed enlarged supra- (P<0.001) and infratentorial (P=0.015) cerebrospinal fluid (CSF) spaces and mild corpus callosum abnormalities (P=0.003) compared to controls. Siblings in SE had smaller inner skull area than controls (P<0.001). Further, the relative area of the mesencephalon (P=0.027) and the diameter of the body of the corpus callosum (P=0.015) were significantly smaller than in controls. In binary logistic regression analysis, enlarged supratentorial CSF spaces increased the probability of SE (odds ratio 4.2; P=0.023). CONCLUSION: Subjects with learning and intellectual disabilities commonly have more MRI findings than controls. Enlarged supratentorial CSF spaces were a frequent finding in siblings in full-time SE.

Stem cell protein BMI-1 is an independent marker for poor prognosis in oligodendroglial tumours.

AIMS: The polycomb factor BMI-1 has recently been implicated in tumorigenesis of the central nervous system in several experimental animal models. However, the significance of BMI-1 in human glioma has not been investigated. Here we describe expression of the polycomb protein BMI-1 and its downstream targets p16(Ink4a) and MDM2 in both high- and low-grade human glioma. METHODS: Tumour samples were collected from 305 adult patients treated for primary grades 2-4 gliomas between 1980 and 2006 in Finland and Germany. BMI-1, p16 and MDM2 expression was evaluated using immunohistochemistry in representative paraffin-embedded tumour tissue. The significance of observed immunoreactivity, age at onset, gender, histopathological findings and proliferative index was analysed in univariate and multivariate survival models. RESULTS: BMI-1 was expressed in all histologic types of diffuse gliomas. We found a significant correlation (P = 0.007) between the frequency of BMI-1 immunoreactive tumour cells and poor survival in World Health Organization grades II-III oligodendrogliomas and oligoastrocytomas (n = 62). The median survival of patients grouped by low, intermediate or high frequency of BMI-1 immunoreactive tumour cells was 191 months, 151 months and 68 months, respectively. This association was also significant in the Cox multivariate regression model. Nuclear p16 immunopositivity predicted better survival in astrocytomas and an inverse correlation between p16 expression and the Ki-67 mitotic index was also observed. CONCLUSIONS: BMI-1 is found in all histological types of gliomas and the relative protein expression of BMI-1 is a novel independent prognostic marker in oligodendroglial tumours.

Mechanism of action of pentagastrin on the lower esophageal sphincter.

The effects of pentagastrin on lower esophageal sphincter (LES) pressure has been studied in trained, unanesthetized dogs. LES pressure was monitored by an infusion manometric technique. Increasing doses of pentagastrin up to 3 mug/kg given as an i.v. bolus resulted in increasing rises in LES pressure; larger doses resulted in a lesser effect of shorter duration. Increasing i.v. boluses of methacholine produced greater increases in LES pressure up to a maximum of 5 mug/kg; higher doses had similar effects. Atropine (50-100 mug/kg) slightly diminished the response of the LES to 2 or 6 mug/kg of pentagastrin. In large doses (500-2,000 mug/kg), atropine did not diminish the response to pentagastrin and prolonged the response of 6 mug/kg pentagastrin. Hexamethonium (2 mg/kg i.v.) depressed the peak response to 3 mug/kg pentagastrin slightly but the response to 6 mug/kg was increased and prolonged. Propranolol (2 mg/kg i.v.) significantly prolonged the effect of 6 mug/kg pentagastrin on the LES. We conclude that the stimulatory effect of pentagastrin is mainly due to a direct action on the LES. A lesser stimulatory effect is due to an action on preganglionic cholinergic neurons. Large doses of pentagastrin have both stimulatory and inhibitory effects. The inhibitory effect is mediated at least in part via preganglionic neurons acting through adrenergic receptors. Ganglionic transmission of the effect may be through muscarinic as well as nicotinic receptors.

Relationship of sphincter of Oddi spike bursts to gastrointestinal myoelectric activity in conscious opossums.

The oppossum sphincter of Oddi (SO) exhibits peristaltic spike bursts with accompanying contraction waves that originate proximally in the sphincter of Oddi and propagate toward the duodenum. In this study we recorded myoelectrical activity of the opossum SO and upper gastrointestinal tract in six conscious animals using chronically implanted electrodes. Biopolar electrodes were implanted in the gastric antrum, duodenum, SO segment, jejunum, and ileum. During fasting the frequency of SO spike bursts, scored as number per minute, showed a cyclic pattern consisting of four phases (A to D). Phase A had a low spike burst frequency of approximately 2/min that lasted approximately 20 min. In phase B, the spike burst frequency increased progressively during a 40-45 min interval culminating in a short interval of phase C activity characterized by a maximal spike burst frequency of approximately 5/min. During phase D, the spike bursts decreased over 15 min to merge with the low frequency of phase A and the cycle repeated. Cycle length of the interdigestive SO cycle, 87+/-11 SD min, was virtually identical with that of the interdigestive migrating myoelectric complex (MMC) of the upper gastrointestinal tract. The onset of phase C activity in the SO began 1-2 min before phase III of the MMC activity in the duodenum. Feeding abolished the cyclic pattern of spike burst activity in the SO as well as in the upper gastrointestinal tract. After feeding the SO spike bursts occurred at a frequency of 5-6/min for at least 3 h. We conclude that: (a) During fasting, the oppossum SO exhibits cyclic changes in its spike burst frequency; (b) Maximal spike burst frequency of the SO occurs virtually concurrent with passage of phase III MMC activity through the duodenum and; (c) Feeding abolishes the interdigestive cyclic spike burst pattern of the SO as well as that of the gastrointestinal tract.

Motor function of the opossum sphincter of Oddi.

We studied the opossum sphincter of Oddi (SO) because in this species the SO is approximately 3 cm in length and its extraduodenal location permits recording of motor activity with negligible interference from duodenal motor activity. The SO segment of 120 animals was evaluated by one or more of the following: (a) intraluminal manometry; (b) electromyography; (c) common bile duct (CBD) flow monitored by a drop counter; (d) cineradiography of intraductal contrast medium; and (e) histologic examination. SO pull-throughs using an infused catheter of 0.6-mm o.d. invariably showed a high pressure zone (HPZ) of 18 +/- 3 SE mm Hg in the terminal 4-5 mm of the SO segment. This HPZ had a narrow lumen, 0.5-0.7 mm in diam, and prominent circular muscle. The HPZ in the terminal SO had both active and passive components. HPZ with minimal amplitude and a paucity of underlying smooth muscle were present inconstantly at the junction of the SO segment with the CBD and pancreatic duct, respectively. The dominant feature of the SO segment was rhythmic peristaltic contractions that originated in the proximal SO and propagated toward the duodenum. These contractions occurred spontaneously at a rate of 2-8/min, ranged up to 200 mm Hg in magnitude, had a duration of approximately 5 s and were not abolished by tetrodotoxin. Concurrent myoelectric and manometric recordings showed that each phasic contraction was immediately preceded by an electrical spike burst. Simultaneous recordings of cineradiography, CBD inflow of contrast medium, SO manometry, and SO electromyography indicated that rhythmic peristaltic contractions stripped contrast medium from the SO into the duodenum. During SO systole, CBD emptying was transiently interrupted, whereas SO filling occurred during the diastolic interval between SO peristaltic contractions. SO distention increased the frequency of SO peristalsis. We conclude that (a) the dominant feature of the opossum SO is rhythmic peristaltic contractions that originate in the proximal SO and propagate toward the duodenum; (b) these forceful SO peristaltic contractions are myogenic in origin and serve as a peristaltic pump that actively empties the SO segment; (c) CBD outflow occurs passively during SO diastole, but is interrupted transiently during each SO peristaltic contraction; and (d) a short HPZ with active as well as passive components exists in the distal SO segment and acts as a variable resistor to SO outflow.

Neonatal immune challenge followed by adult immune challenge induces epigenetic-susceptibility to aggravated visceral hypersensitivity.

BACKGROUND: Abdominal pain is one of the major symptoms of inflammatory Bowel Disease (IBD). The inflammatory mediators released by colon inflammation are known to sensitize the afferent neurons, which is one of the contributors to abdominal pain. However, not all IBD patients have abdominal pain, and some patients report abdominal pain during remission, suggesting contributions of other pathological factors to abdominal pain in IBD. Epidemiological studies found early-life gastrointestinal infections a risk factor for IBD symptoms and adult-life gastrointestinal infections may trigger the onset of IBD. We investigated the hypothesis that neonatal colon immune challenge followed by an adult colon immune challenge upregulates spinal cord BDNF that aggravates visceral sensitivity over and above that induced by adult colon immune challenge alone. METHODS: We induced neonatal and adult colon immune challenges by intraluminal administration of trinitrobenzene sulfonic acid to the rat colon. KEY RESULTS: We found that neonatal immune challenge triggers epigenetic programming that upregulates tyrosine hydroxylase in the locus ceruleus when these rats are subjected to an adult colon immune challenge. The upregulation of locus ceruleus tyrosine hydroxylase, upregulates norepinephrine in the cerebrospinal fluid that acts on adrenergic receptors to enhance pCREB binding to the cAMP response element, which recruits histone acetylene transferase (HAT) to the BDNF gene to enhance its transcription resulting in aggravated visceromotor response to colorectal distension. HAT and adrenergic receptor antagonists block the aggravation of visceral sensitivity. CONCLUSION & INFERENCES: HAT and adrenergic receptor inhibitors may serve as alternates to opioids and NSAIDS in suppressing abdominal pain in IBD.

Costs of diabetes medication among male former elite athletes in later life.

AIMS: Regular physical activity plays a major role, in both prevention and treatment of type 2 diabetes. Less is known whether vigorous physical activity during young adulthood is associated with costs of diabetes medication in later life. The aim of this study is to evaluate this question. METHODS: The study population consisted of 1314 former elite-class athletes and 860 matched controls. The former athletes were divided into three groups based on their active career sport: endurance, mixed and power sports. Information on purchases of diabetes medication between 1995 and 2009 was obtained from the drug purchase register of the Finnish Social Insurance Institution. RESULTS: The total cost of diabetes medication per person year was significantly lower among the former endurance (mean 81 € [95% CI 33-151 €]) and mixed group athletes (mean 272 € [95% CI 181-388 €]) compared with the controls (mean 376 € [95% CI 284-485 €]), (p < 0.001 and p = 0.045, respectively). Of the former endurance athletes, 0.4% used insulin, while 5.2% of the controls used insulin (p = 0.018). CONCLUSIONS: A career as former endurance, sprint, jumper or team game athlete seems to reduce the costs of diabetes medication in later life.

Strain and host characteristics of Campylobacter jejuni infections in Finland.

The relative importance of different risk-factors for Campylobacter infections and the role of bacterial strain and host characteristics are uncertain. Swimming in natural sources of water was recently described as a novel independent risk-factor for domestically-acquired Campylobacter infections. The present study investigated exposure factors and demographical characteristics (collected in a questionnaire), and determined whether Campylobacter jejuni serotypes could be linked to each other or to the severity of the disease in domestically-acquired sporadic C. jejuni infections during a seasonal peak in Finland. Swimming was associated positively with an age of

IgA antibodies in persisting Helicobacter pylori infection in Finnish adults.

Most individuals infected with Helicobacter pylori have elevated levels of specific IgG antibodies, but only in about two-thirds of cases does the IgA titre exceed the cut-off level. The aim of this study was to determine whether H. pylori-infected subjects with elevated IgG levels would subsequently produce IgA antibodies, and whether elevated IgA levels increased during infection. Paired sera were available from 336 adults who took part in a large population-based health survey in 1977-1980 and a follow-up study on asthma and atopic diseases in 1997-1998 (series A). Data on paired sera from 224 adults who participated in a population-based health survey in Vammala, Finland in 1973 and who gave a follow-up blood sample in 1994 (series B) were also re-analysed. H. pylori IgG and IgA levels were determined with commercially available (series A) and in-house (series B) enzyme immunoassays. Twenty-one (35%) of the 60 subjects who initially had elevated levels of IgG antibodies only were found to be IgA-positive at follow-up. In those subjects whose baseline and follow-up samples were IgG- and IgA-positive, the median IgA levels increased by 48% and 22% in series A and B (p < 0.0001 and p 0.0241), respectively, whereas the median IgG levels did not change significantly in either series. During H. pylori infection, an increase in specific IgA was reflected by the increase in the number of responders and by the rise in titres.

Chemical castration induced by adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy causes rapid bone loss that is reduced by clodronate: a randomized study in premenopausal breast cancer patients.

PURPOSE: In the majority of premenopausal breast cancer patients, an adjuvant chemotherapy-induced early menopause occurs, which is known to be a strong predictor of osteoporosis. We present data on the effect of adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy on bone mineral density (BMD) and the efficacy of clodronate on the prevention of bone loss in 148 premenopausal breast cancer patients without skeletal metastases. MATERIALS AND METHODS: Patients were randomized to receive oral clodronate 1,600 mg/d or to a control group. In addition, patients were treated with six cycles of CMF therapy. BMD of the lumbar spine and femoral neck was measured by dual-energy x-ray absorptiometry (DEXA) before therapy and at 1 and 2 years. RESULTS: Changes in the BMD of lumbar spine and femoral neck were -5.9% and -2.0% without clodronate and -2.2% and +0.9% with clodronate at 2 years (P = .0005 and .017, respectively). Patients who developed amenorrhea after chemotherapy had a rapid bone loss, which was significantly reduced by clodronate. In controls, bone loss was 9.5% in the lumbar spine and 4.6% in the femoral neck, while in the clodronate group, bone loss was 5.9% and 0.4%, respectively, at 2 years. Patients with preserved menstruation had only marginal changes in BMD. CONCLUSION: Chemotherapy-induced ovarian failure causes rapid bone loss in premenopausal breast cancer patients. Women older than 40 years are at particularly high risk. Clodronate significantly reduces this bone loss.

Idiopathic constipation: too few stools and too little knowledge.

The precise abnormalities of colonic motility patterns in idiopathic constipation, and the alterations at the cellular, neural, myogenic and biochemical levels that underlie these patterns, are not yet understood. One promising approach in the treatment of constipation seems to be to design drugs that can stimulate GMCs to produce mass movements and consequently defaecation. This could possibly be achieved with the selective 5-HT4 receptor agonists prucalopride and SDZ HTF-919, which are currently in advanced clinical trials. Other mechanisms that provide a means to induce GMCs, such as NK1 receptor agonism, deserve further exploration.

Physical activity and osteoporotic hip fracture risk in men.

BACKGROUND: Physical activity has been related to reduced risk of osteoporotic hip fractures, but the evidence among men is weak. OBJECTIVE: To determine the association between baseline leisure physical activity and future risk of osteoporotic hip fracture in men. METHODS: At baseline in 1975 our prospective study cohort included 3,262 men who were 44 years or older and did not have chronic disease restricting their ability to exercise. At baseline, physical activity was assessed by a questionnaire. Hip fractures were followed for 21 years, or from the age of 50 years for subjects who were initially younger than 50 years. RESULTS: The hazard ratio of osteoporotic hip fracture, adjusted for other possible predictors (height, body mass index, baseline diseases, smoking, use of alcohol, work-related physical activity, and occupational group), in men participating in vigorous physical activity compared with men not participating was 0.38 (95% confidence interval, 0.16-0.91) (P = .03). CONCLUSION: These results provide further evidence that there is an inverse association between baseline physical activity and future hip fracture risk among men.