Does hypertension confer a hypercoagulable state in stroke-prone spontaneously hypertensive rats?

OBJECTIVE: To verify whether hypertension confers a hypercoagulable state in a hypertensive animal model. DESIGN: The parameters of blood coagulation were compared between stroke-prone spontaneously hypertensive rats (SHR-SP) and Wistar-Kyoto (WKY) rats. Each rat group consisted of a younger subgroup at 8-12 weeks old (n = 12) and an older subgroup at 16-20 weeks old (n = 12). METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT), fluorogenic PT, fibrinogen, fibrin/fibrinogen degradation products (FDP), thrombin-anti-thrombin III complex (TAT), factor Xa activity, anti-thrombin III (AT-III), tissue factor pathway inhibitor (TFPI), protein C and C1 inhibitor were measured in both rat groups. RESULTS: There was no significant difference in FDP and TAT levels between SHR-SP and WKY rats even at 16-20 weeks when SHR-SP developed severe hypertensive vascular lesions. Contrary to expectations, fluorogenic PT and factor Xa activity were significantly lower in SHR-SP than in WKY rats. While there was no significant difference in AT-III, TFPI and protein C activities between SHR-SP and WKY rats, C1 inhibitor activity was significantly higher in SHR-SP than in WKY rats. The elevated C1 inhibitor activity was inversely correlated with the reduced factor Xa activity. Gel-filtered fractionated plasma with C1 inhibitor activity had an inhibitory effect on the purified rat factor Xa, and immunodepletion of C1 inhibitor from the fractionated plasma attenuated the inhibitory effect CONCLUSION: These results suggest that SHR-SP get into a hypocoagulable state rather than a hypercoagulable state, and that the reduction of factor Xa activity in SHR-SP may be related to the elevation of C1 inhibitor activity.     

Does oxidative stress modulate limb muscle atrophy in severe COPD patients?

Oxidative stress may differentially regulate protein loss within peripheral muscles of severe chronic obstructive pulmonary disease (COPD) patients exhibiting different body composition. Oxidation levels of proteins, myosin heavy chain (MyHC) and myonuclei, superoxide anion, antioxidants, actin, creatine kinase, carbonic anhydrase-3, ubiquitin-proteasome system, redox-signalling pathways, inflammation and muscle structure, and damage were quantified in limb muscles of severe COPD patients with and without muscle wasting, and in sedentary controls. Compared with controls, in the quadriceps of muscle-wasted COPD patients, levels of protein carbonylation, oxidation of MyHC and myonuclei, superoxide anion production, superoxide dismutase, total protein ubiquinitation, E2(14k), atrogin-1, FoxO1 and p65 were higher, while content of MyHC, creatine kinase, carbonic anhydrase-3, myogenin, and fast-twitch fibre size were decreased. Importantly, in nonwasted COPD patients, where MyHC was more oxidised than in controls, its content was preserved. Muscle inflammation and glutathione levels did not differ between patients and controls. In all patients, muscle structure abnormalities were increased, while muscle force and exercise capacity were reduced. In severe COPD, while muscle oxidative stress increases regardless of their body composition, protein ubiquitination and loss of MyHC were enhanced only in patients exhibiting muscle atrophy. Oxidative stress does not seem to directly modulate muscle protein loss in these patients.     

Does heart failure confer a hypercoagulable state? Virchow's triad revisited

It is well-recognized that patients with congestive heart failure are at an increased risk of stroke and venous thromboembolism. Nevertheless, stroke, thromboembolism and myocardial infarction have generally been regarded to be end points of secondary importance in large heart failure trials, when compared with mortality or hospital readmissions. It may well have been that the incidence of thrombotic events are underestimated. The problem of thrombus formation (thrombogenesis) in heart failure may therefore be a much more significant problem than is currently recognized. The pathophysiology of thrombogenesis in heart failure could well be explained in the context of Virchow's original triad. In addition to "abnormal flow" through low cardiac output, dilated cardiac chambers and poor contractility, patients with heart failure also demonstrate abnormalities of hemostasis and platelets (that is "abnormal blood constituents") and endothelial dysfunction ("vessel wall abnormalities"). These abnormalities contribute to a prothrombotic or hypercoagulable state, which increases the risk of thrombosis in heart failure and impaired left ventricular systolic function. Some observational data are available on the role of anticoagulants in heart failure, and there is sound evidence to support the use of antithrombotic therapy in patients with heart failure and atrial fibrillation. However, there are no large-scale prospective randomized controlled trials of antithrombotic therapy in patients with heart failure who remain in sinus rhythm, although important studies are in progress. Although the results of these studies are awaited, measurement of suitable markers of thrombogenesis might prove to be valuable in identifying "high risk" patients and in determining the nature, duration and intensity of such treatment. Further information is also needed on the predictive value of various markers of hypercoagulability in patients with heart failure, the association between hemostatic variables and the severity of heart failure, and the effects of different treatments.     

Does bloody aspirate reflect the state of upper gastrointestinal mucosa in a critically ill newborn?

Background and study aimsCritically ill newborns have many risk factors to develop stress related mucosal lesions (SRML). We used upper endoscopy to evaluate the presence of SRML in these neonates, to know the specificity and sensitivity of the bloody gastric aspirate to detect SRML and to identify the risk factors associated with the presence of SRML and bloody gastric aspirate.Patients and methodsThis is a cross-sectional study done on 100 critically ill newborn after becoming clinically stable. SRML were diagnosed if there is hyperaemia, erosions or ulcers in the oesophagus, stomach, and/or the duodenum.ResultsSRML were found in 77% of neonates in the NICU though frank bloody aspirate was detected in only 22% of neonates. The presence of bloody aspirate showed low sensitivity (24.68%) and high specificity (86.96%) for the presence of SRML. The presence of bloody gastric aspirate showed a double fold risk for the presence SRML (OR = 2.184, CI = 0.584–8.171). Factors associated with SRML included respiratory distress (p = 0.000, risk = 4.006), the use of nasogastric tube (p = 0.017, OR = 3.281) and the use of triple antibiotics (p = 0.001, risk = 1.432). Factors associated with the presence of bloody gastric aspirate included the use of nasogastric tube (OR = 1.629, p = 0.000) and the presence of haemostatic disorders (OR = 3.143, p = 0.039). It was also associated with lower haemoglobin levels (p = 0.000).ConclusionSRML represents an under-diagnosed problem in NICUs. Absence of bloody gastric aspirate does not exclude the presence of SRML.     

Does hereditary metabolic disease modulate senescence and ageing?

Hereditary metabolic diseases in the context of evolutionary biology elicit interesting questions about ageing and senescence: Will persons successfully treated for inborn errors of metabolism, age and die prematurely because of compromised longevity? Because some unhealthy longevity has its origins in germline and somatic mutational processes, and in an inability to withstand metabolic stress, are there lessons to be learned about senescence from hereditary metabolic disease? Why are ageing, senescence and death necessary for Homo sapiens and how do they happen? These questions form the theme upon which several variations are played during the course of this essay. The theory of the disposable soma recognizes genomic and environmental events, well-seasoned by Chance, as determinants of ageing and senescence. Together, they cause the somatic damage that results in death. Genomics will reveal genes involved in longevity, both healthy and unhealthy. There will be schedules of gene expression behind our life-history traits. As in the field of hereditary metabolic disease, analogous genetic enquiries about ageing can be formulated. For example, how will heterozygotes age? Will association studies in centenarians reveal 'longevity genes'? Will disparate longevity in sib pairs reveal genetic factors? If there are 'ageing' mutations, of what types and with what effects? Will these initiatives lead to healthier longevity? A deeper question yet remains: why has human biology invested so greatly in grandparenthood?     

Does glutamine reduce bacterial translocation? A study in two animal models with impaired gut barrier

 Failure of intestinal barrier function and subsequent translocation of bacteria from the gut are believed to play a decisive role in the development of systemic septic complications, for example, following major trauma or major abdominal surgery. This study evaluated: (a) the effect of glutamine on colonic microcirculation and electrophysiological parameters reflecting gut barrier function, (b) the translocation of live bacteria to extraintestinal organs, and (c) disease outcome in two animal models with impaired gut barrier function. Severe acute pancreatitis or colitis was induced in rats randomized for therapy with or without glutamine (0.5 g/kg daily). After 48 h one animal group was prepared for intravital microscopy of colonic capillary blood flow and electrophysiological measurement of gut permeability; another was killed after 96 h for histological and microbiological examination. In animals with pancreatitis, glutamine (Gln) supplementation significantly improved gut permeability, i.e., Gln increased colonic transmucosal resistance from 67±7 to 92±3 Ω/cm² and decreased mannitol flux through the epithelium by 53%. Capillary blood flow in the colonic mucosa was improved by 25%. The prevalence of pancreatic infections was reduced from 86% in animals on standard parenteral nutrition to 33% in animals given the Gln-enriched diet (P<0.05); mortality decreased by 32%. In colitis, Gln had no significant effect on these parameters except for improving colonic capillary blood flow in colon segments not adjacent to the major injury site. Glutamine supplementation improves colonic capillary blood flow, stabilizes gut permeability, and reduces secondary pancreatic infections and mortality in severe rodent pancreatitis, but it is not helpful in colitis. This confirms previous reports that glutamine stabilizes gut barrier function only in certain diseases. Our experimental data strongly suggest that acute pancreatitis (rather than colitis) is one of the diseases with gut barrier dysfunction in which glutamine substitution may be helpful to reduce bacterial translocation and should therefore be tested in a controlled clinical trial. Accepted: 16 March 1999     

Does testosterone have a role in erectile function?

Purpose

Despite the well-established role of testosterone in enhancing libido, its exact contribution to erections in men remains unclear. The main objectives of this review are to clarify the role of testosterone in erectile function and evaluate its therapeutic value in men with erectile dysfunction (ED).

Methods

Review of the relevant literature (English, French, and Spanish) from 1939 to June 2005 was conducted using data sources from MEDLINE, endocrinology text books, and hand searching of cross-references from original articles and reviews. Clinical trials, animal studies, case reports, reviews, and guidelines of major associations were included.

Results

Animal and preliminary human studies suggest that testosterone may facilitate erection by acting as vasodilator of the penile arterioles and cavernous sinusoids. Following castration, most, but not all, men had partial or complete loss of erection. Hypogonadism is not a common finding in ED, occurring in about 5% of cases, and in general, there is lack of association between serum testosterone levels, when present in normal or moderately low levels, and erectile function. Most trials using testosterone for treatment of ED in hypogonadal men suffer from methodological problems and report inconsistent results, but overall, suggest that testosterone may be superior to placebo. Erectile function is more likely to improve with testosterone therapy in patients with severe degrees of hypogonadism. Testosterone treatment may ameliorate the response to the phosphodiesterase 5 (PDE5) inhibitors in hypogonadal men and men with low-normal serum testosterone. Repeated measurement of morning serum total testosterone is a fairly accurate and easy method to evaluate androgenecity, but measurement of free or bioavailable testosterone is recommended in conditions that alter the levels of sex-hormone-binding globulin (SHBG), such as in the elderly and in obesity.

Conclusions

Available data suggest that in most men circulating levels of testosterone, well below the normal range, are essential for normal erection and that higher levels of serum testosterone may not have major impact on erectile function. Screening for hypogonadism in all men with ED is necessary to identify cases of severe hypogonadism and some cases of mild to moderate hypogonadism, who may benefit from testosterone treatment.     

Can we modulate physical activity in children?

There is concern that interventions that use physical activity to prevent obesity in children might be undermined by an 'Activitystat', which exerts an effect to maintain a low set point for physical activity. The present critique summarises evidence from systematic reviews of interventions, from empirical tests of the Activitystat hypothesis, from studies on the heritability of physical activity in childhood and the physical activity of children of and adolescents across a wide range of physical and cultural environments. This body of evidence is inconsistent with the Activitystat hypothesis in its current form, and suggests that the emphasis on physical activity in obesity prevention interventions in children should be increased, not reduced.     

Does Helicobacter pylori have a pathogenic role in bronchiectasis?

AIM: To investigate the presence of Helicobacter pylori (H. pylori) in bronchial biopsies of patients with bronchiectasis, by histochemical and immunochemical staining. SETTING: 800-bed tertiary university hospital. METHODS: Observational study. Patients: forty-six patients with bronchiectasis in a stable clinical condition and 8 control patients. Interventions: Serum samples determination of IgG levels for H. pylori by ELISA. Immunostaining with an anti-H. pylori antibody (NCL-HPp, Novocastra) of bronchial mucosa obtained by fiberoptic bronchoscopy from both patients with bronchiectasis and controls. RESULTS: Twenty-one out of 46 patients with bronchiectasis (46%) had positive serology for H. pylori. We obtained 40 bronchial biopsies in patients with bronchiectasis and 8 bronchial biopsies in control patients. No evidence of H. pylori was obtained in the bronchial samples of both patients and controls. CONCLUSIONS: The results of our study could not demonstrate the presence of H. pylori in bronchial specimens from patients with bronchiectasis.     

Does fluoroscopic imaging still have a role in colonoscopy?

GOAL: To assess the use and value of fluoroscopic imaging in difficult colonoscopy. BACKGROUND: Few endoscopy centers have easy access to fluoroscopy to facilitate difficult colonoscopy. Its benefits are therefore unclear. Although interest in colonoscope imaging has recently been stimulated by magnetic imaging techniques, these are expensive and unlikely to be widely available for some time. STUDY: During routine colonoscopy lists, a mobile fluoroscopy unit was used when colonoscopy could not be completed in the absence of stricturing despite changes in patient position and application of external pressure. This retrospective review assesses the percentage of procedures completed with and without fluoroscopy. RESULTS: A series of 1551 procedures in adult patients without colon resection and with satisfactory bowel preparation was analyzed. The cecal intubation rate was 95.1% (1475/1551), rising to 96.5% (1475/1528) when impassable strictures were excluded. Fluoroscopy was used in 61 (4%) of the 1528 procedures without stricture, but allowed completion in only 13% (8/61). In the absence of stricture, fluoroscopy improved completion rate by only 0.5% (from 96.0% to 96.5%). CONCLUSIONS: Fluoroscopy is seldom required and even then contributes little to success. Magnetic imaging, which provides continuous 3-dimensional images, may be more likely to speed and facilitate completion.