Changes in the angle-force curve of human elbow flexors following eccentric and isometric exercise

The aim of this study was to explore and compare the magnitude and time-course of the shift in the angle-force curves obtained from maximal voluntary contractions of the elbow flexors, both before and 4 consecutive days after eccentric and isometric exercise. The maximal isometric force of the elbow flexors of fourteen young male volunteers was measured at five different elbow angles between 50° and 160°. Subjects were then divided into two groups: the eccentric group (ECC, n=7) and the isometric group (ISO, n=7). Subjects in the ECC group performed 50 maximal voluntary eccentric contractions of the elbow flexors on an isokinetic dynamometer (30°^.s^–1), while subjects in the ISO group performed 50 maximal voluntary isometric muscle contractions with the elbow flexors at a lengthened position. Following the ECC and ISO exercise protocols, maximal isometric force at the five angles, muscle soreness, and the relaxed (RANG) and flexed (FANG) elbow angles were measured at 24 h intervals for 4 days. All results were presented as the mean and standard error, and a quadratic curve was used to model the maximal isometric force data obtained at the five elbow angles. This approach not only allowed us to mathematically describe the angle-force curves and estimate the peak force and optimum angle for peak force generation, but also enabled us to statistically compare the shift of the angle-force curves between and within groups. A large and persistent shift of the angle-force curve towards longer muscle lengths was observed 1 day after eccentric exercise (P<0.01). This resulted in a ~16° shift of the optimum angle for force generation, which remained unchanged for the whole observation period. A smaller but also persistent shift of the angle-force curve was seen after isometric exercise at long muscle length (P<0.05; shift in optimum angle ~5°). ECC exercise caused more muscle damage than ISO exercise, as indicated by the greater changes in RANG and ratings of muscle soreness (P<0.05). It was suggested that the shift in the angle-force curve was proportional to the degree of muscle damage and may be explained by the presence of overstretched sarcomeres that increased in series compliance of the muscle.     

Lung growth and function in children and adolescents with idiopathic pectus excavatum

Patterns of lung growth and function were studied retrospectively in 103 patients (73 male and 30 female) with idiopathic pectus excavatum in order to determine: 1) the prevalence of restrictive lung defect and/or other lung function abnormalities; 2) the possible association between type of lung function abnormalities and age of the patient; and 3) whether the type of lung function is associated with other clinical conditions. Forty-three patients (42%) were between 5-9 years of age; 36 (35%) were between 10-14 years; and 24 (23%) were between 15-19 years. Restrictive lung disease was detected only in 5 patients (5%), whereas 42 patients (41%) had evidence of obstructive pattern, and the remaining 56 patients (54%) had a normal pattern. The mean values for lung volume (total lung capacity (TLC) and/or forced vital capacity (FVC)) were lowest in the 10-14-year group, whereas the mean values of the indices of lower airway function (forced expiratory volume at 1 sec (FEV(1)), FEV(1)/FVC, forced expiratory flow at 25-75% of forced vital capacity (FEF(25-75)), and FEF(25-75)/FVC) were higher in the younger group. Residual volume (RV) and RV/TLC were elevated in all age groups, but they declined toward normalization with increasing age. There were no significant differences between groups (stratified either by pattern of lung function or by age) with regard to their demographics or clinical characteristics (scoliosis, direction of sternal rotation, history of asthma/reactive airways disease, or exercise intolerance). We conclude that idiopathic pectus excavatum may be associated with a variety of lung function abnormalities (in particular, lower airway obstruction) even in the absence of overt clinical symptoms. There was no evidence of significant worsening of lung function with increasing age.     

Longitudinal follow-up of lung function from childhood to adolescence in prematurely born patients with neonatal chronic lung disease

We investigated whether early lung function abnormalities in prematurely born children with a history of chronic lung disease improve in late childhood and adolescence. We performed a prospective, longitudinal evaluations of pulmonary function over an 8 year period. In seventeen patients from the age (mean ± SD) of 8.2 ± 1.2 years to the age of 15.1 ± 1.6 years. They had been born at 29.1 ± 1.9 weeks of gestation, with a birthweight of 1120 ± 190 g, and they had received supplemental oxygen, with or without mechanical ventilation, for 40.4 ± 23.8 days during the neonatal period. They all had radiographic evidence of chronic lung disease at 4 weeks of age. Annual measurements of lung volumes using the helium dilution technique, and of airway function with spirometry and maximal expiratory flow-volume curves over a 5 to 8 year period, were obtained. The results indicated that total lung capacity (TLC) and vital capacity (VC) were within the predicted normal range in all patients and increased over time. In contrast, the initially abnormal residual volume (RV) and RV/TLC ratio decreased over time, suggesting gradual resolution of air-trapping. The peak expiratory flow rate (PEFR), forced expiratory volume in 1 second (FEV₁), and the ratio FEV₁/FVC remained at or above the predicted normal range in all patients. FEF_25–75, FEF₅₀, and FEF₇₅ were within normal limits in eight patients and abnormally low (more than 2 SD below the predicted normal value) in the remaining nine patients, indicating small airway obstruction. Eight of the nine patients with lower airway obstruction showed significant response to inhaled bronchodilator, and four responded to a histamine challenge. None of the eight patients with normal airway function responded to histamine, but four responded to bronchodilators. The perinatal history, family history of asthma, and exposure to smoking were similar in patients with and without airway obstruction. The height and weight were and remained within the normal range. We conclude that gradual normalization of air-trapping continues well into adolescence in virtually all patients with a history of prematurity and chronic lung disease. In contrast, airflow obstruction may persist but does not get worse later in life. Although chronic airflow obstruction probably is the consequence of injury to the small airways during the neonatal period, it is present in only some of the children, and it does not appear to be directly related to the perinatal history. Finally, there is evidence that airway hyperresponsiveness may be a contributing factor to the development and/or persistence of airflow obstruction in chronic lung disease of prematurity. Pediatr Pulmonol. 1996; 21:28–34 . © 1996 Wiley-Liss, Inc.     

Reducing dynamin 2 expression rescues X-linked centronuclear myopathy

Centronuclear myopathies (CNM) are congenital disorders associated with muscle weakness and abnormally located nuclei in skeletal muscle. An autosomal dominant form of CNM results from mutations in the gene encoding dynamin 2 (DNM2), and loss-of-function mutations in the gene encoding myotubularin (MTM1) result in X-linked CNM (XLCNM, also called myotubular myopathy), which promotes severe neonatal hypotonia and early death. Currently, no effective treatments exist for XLCNM. Here, we found increased DNM2 levels in XLCNM patients and a mouse model of XLCNM (Mtm1^–/y). Generation of Mtm1^–/y mice that were heterozygous for Dnm2 revealed that reduction of DNM2 in XLCNM mice restored life span, whole-body strength, and diaphragm function and increased muscle strength. Additionally, classic CNM-associated histological features, including fiber atrophy and nuclei mispositioning, were absent or reduced. Ultrastructural analysis revealed improvement of sarcomere organization and triad structures. Skeletal muscle–specific decrease of Dnm2 during embryogenesis or in young mice after disease onset revealed that the rescue associated with downregulation of Dnm2 is cell autonomous and is able to stop and potentially revert XLCNM progression. These data indicate that MTM1 and DNM2 regulate muscle organization and force through a common pathway. Furthermore, despite DNM2 being a key mechanoenzyme, its reduction is beneficial for XLCNM and represents a potential therapeutic approach for patients.     

Epidemiologic characteristics of hypertension in the civilians of Kosovo after the war

34th Greek regimen, which was part of the NATO forces, provided medical services to the civilians of Kosovo. We studied epidemiologic data in the population of Kosovo regarding hypertension in order to determine the prevalence and characteristics of hypertension. 830 patients (281 - 33.86% male, 62 +/- 26 yrs and 549 - 66.14% female, 49 +/- 28 yrs) were examined for different diseases. We identified 254 (30.6%) patients with hypertension (188 female and 66 male). According to the international criteria used for the classification of the severity of hypertension, more than half of the patients (51.2%) had severe hypertension, 31.5% modest and 17.3% mild. Statistically significant relation between the severity of hypertension and age or sex was not found out. Increased BMI as well as the presence of proteinuria and rheumatic diseases were significantly related to the severity of the hypertension while the coexistent heart disease, diabetes mellitus and chronic obstructive pulmonary disease (COPD) wasn't. The use of non-steroid anti-inflammatory agents (NSAIDs) was related to the severity of hypertension with a borderline significance. 31.4% of the patients were on treatment with NSAIDs and/or cortisone because of rheumatic disease or obstructive pulmonary disease. Overfunction of the sympathetic system was present in 62.99%. The mean heart rate was greater in women (84/min) than in men (72/min). 28.35% of the patients had secondary hypertension, including the patients on a drug that can elevate the blood pressure and patients with increased activity of the sympathetic nervous system. So, 8.6% of the patients had usual causes of secondary hypertension and 19.6% hypertension secondary related to the use of NSAIDs or cortisone, or due to the increased activity of the sympathetic nervous system. Antihypertensive treatment was started in 248 patients, i.e. in all of them except the ones already on treatment having their blood pressure well controlled. For antihypertensive treatment beta-blockers or central adrenergic inhibitors either as monotherapy or in combination with other agents were used most frequently combined with diuretics and Ca antagonists and ACE inhibitors. In conclusion the diagnosis and treatment of hypertension in the population of Kosovo during the post war period had certain particularities.     

Fluorometric measurements of conformational changes in glutamate transporters

Glutamate transporters remove glutamate from the synaptic cleft to maintain efficient synaptic communication between neurons and to prevent extracellular glutamate concentrations from reaching neurotoxic levels (1). It is thought that glutamate transporters mediate glutamate transport through a reaction cycle with conformational changes between the two major access states that alternatively expose glutamate-binding sites to the extracellular or to the intracellular solution. However, there is no direct real-time evidence for the conformational changes predicted to occur during the transport cycle. In the present study, we used voltage-clamp fluorometry to measure conformational changes in the neuronal excitatory amino acid transporter (EAAT) 3 glutamate transporter covalently labeled with a fluorescent reporter group. Alterations in glutamate and cotransported ion concentrations or in the membrane voltage induced changes in the fluorescence that allowed detection of conformational rearrangements occurring during forward and reverse transport. In addition to the transition between the two major access states, our results show that there are significant Na(+)-dependent conformational changes preceding glutamate binding. We furthermore show that Na(+) and H(+) are cotransported with glutamate in the forward part of the transport cycle. The data further suggest that an increase in proton concentrations slows the reverse transport of glutamate, which may play a neuro-protective role during ischemia.     

Insulin therapy for critically ill hospitalized patients: a meta-analysis of randomized controlled trials

BACKGROUND: Hyperglycemia is common in critically ill hospitalized patients, and it is associated with adverse outcomes, including increased mortality. The objective of this meta-analysis was to determine the effect of insulin therapy initiated during hospitalization on mortality in adult patients with a critical illness. METHODS: An electronic search in the English-language articles of MEDLINE and the Cochrane Controlled Clinical Trials Register and a hand search of key journals and relevant review articles were performed. Randomized controlled trials that reported mortality data on critically ill hospitalized adult patients who were treated with insulin were selected. Data on patient demographics, hospital setting, intervention (formulation and dosage of insulin, delivery method, and duration of therapy), mortality outcomes, adverse events, and methodological quality were extracted. RESULTS: Thirty-five trials met the inclusion criteria. Combining data from all trials using a random-effects model showed that insulin therapy decreases short-term mortality by 15% (relative risk [RR], 0.85; 95% confidence interval [CI], 0.75-0.97). In subgroup analyses, insulin therapy decreased mortality in the surgical intensive care unit (RR, 0.58; 95% CI, 0.22-0.62), when the aim of therapy was glucose control (RR, 0.71; 95% CI, 0.54-0.93), and in patients with diabetes mellitus (RR, 0.73; 95% CI, 0.58-0.90). A near-significant trend toward decreasing mortality was seen in patients with acute myocardial infarction who did not receive reperfusion therapy (RR, 0.84; 95% CI, 0.71-1.00). No randomized trials of insulin in the medical intensive care unit were identified. CONCLUSION: Insulin therapy initiated in the hospital in critically ill patients has a beneficial effect on short-term mortality in different clinical settings.