An evaluation of the predictive validity and reliability of ventilatory threshold

PURPOSE: To identify a valid and reliable method to determine 40-km time trial (40K) performance in a laboratory setting. METHODS: Part 1: Ventilatory threshold (VT) and 40K performance were determined on two occasions (February/September) using two subsets of cyclists (N = 15 each; VO(2max) 67.6 +/- 4.2/71.5 +/- 3.0 mL x kg(-1) x min(-1)) to determine the predictive validity of VT assessments. Variables of interest were power output at VT, peak power output (MaxVT(w)), and average power output during 40K (40K(avgwatts)). For VT determination we used: breakpoint of VE/VO2; breakpoint of VE/VCO2; V-slope; RER = 1; and RER = 0.95. In part 2, test-retest reliability of VT and MaxVT(w) were examined in 20 subjects (VO(2max) 64.8 +/- 8.0 mL x kg(-1) x min(-1)) on two occasions, separated by 48 h. RESULTS: Regression analyses between power outputs at VTs and 40K(avgwatts) showed significant predictive validity for (February/September): V-slope (r = 0.79/0.84; SEE 155/13.3W), VE/VO2 (r = 0.80/0.81; SEE 15.2/14.2W), RER0.95 (r = 0.73/0.58; SEE 17.4/21.2W), RER1 (r = 0.75/0.74; SEE 16.8/16.7W), and MaxVT(w) (r = 0.81/0.73; SEE 15.0/17.1W). Paired t-tests between power outputs at VTs and the 40K(avgwatts) indicated that mean power outputs at VE/O2 (261 +/- 29W; P = 0.33) and RER0.95 (274 +/- 55W; P = 0.93) in February and VE/VO2 (274 +/- 37W; P = 0.79) in September were not significantly different from the respective 40K(avgwatts) (277 +/- 30W/281 +/- 30W). Test-retest reliability analysis yielded the following intraclass correlation and relative test-retest errors: V-slope: 0.98, 2.6%; VE/VO2: 0.95, 5.3%; RER0.95: 0.87, 9.8%; RER1: 0.94, 5.7%; VE/VCO2: 0.87, 12.1%; MaxVT(w): 0.98, 2.6%. CONCLUSION: The high test-retest reliability and consistent ability to accurately predict athletes' 40K(avgwatts) across a competitive season indicated that VE/VO2 was superior to the other evaluated methods.     

Beta adrenergic inhibition of capsaicin-induced, NK1 receptor-mediated nerve growth factor biosynthesis in rat skin

Excitation of primary afferent neurons stimulates the expression of cytokines and nerve growth factor (NGF) in innervated tissues. Since NGF is a neurotrophic and immunomodulatory factor contributing to inflammatory hyperalgesia and tissue response to injury, this study was conducted in order to investigate the mechanisms by which afferent neuron stimulation by topical application of capsaicin increases NGF in the rat skin. Thereby it was sought to identify possible targets for pharmacological modulation of NGF biosynthesis. Topical capsaicin (>1 mg/ml ethanol) caused a concentration- and time-dependent increase in the concentration of NGF in rat skin. The capsaicin-induced increase of NGF was not significantly affected by indomethacin administered at a dose (2 mg/kg) that abolishes prostaglandin E2 biosynthesis. The NGF increase was suppressed by treatment of rats with the selective tachykinin NK1 receptor antagonist SR140333 (0.1 mg/kg), and by the beta adrenergic agonist terbutaline (0.3 mg/kg). The effect of terbutaline was reversed by the beta adrenergic antagonist propranolol (1 mg/kg). Terbutaline also inhibited the increase in NGF caused by intraplantar injection of the NK1 receptor agonist substance P (SP), but did not significantly affect that caused by carrageenan. The results show that topical administration of capsaicin causes a primarily NK1 receptor-dependent increase in the NGF content of rat skin, which is susceptible to inhibition by beta adrenergic agonists. These observations not only suggest regulation of skin NGF biosynthesis by afferent neuronal and adrenergic mechanisms, but also indicate possible targets for pharmacological modulation of skin NGF biosynthesis.     

Medical research in paediatrics: ethical issues

Since 1947 (the Nuremberg Code), the ethics of experimentation on human beings is based on the principle of the informed consent of the subjects participating in the research. In this context, research in paediatrics raised particular and difficult problems. International regulations have evolved in a way that has permitted paediatric research, within strict limits. However, recent studies have shown that the level of clinical paediatric research remains weak. There are economic reasons for this. But it also reveals the persistence of an ethical conflict: some people fear that a relativisation of the principle of consent (proxy consent) will lead to weakened protection for the most vulnerable subjects, including children. The ethics of responsibility requires a balance between the protection of the child as an individual (who should never become a medical guinea-pig) and the protection of children as a group (who should never be deprived of the benefits of the medical research).     

Visceral leishmaniasis: consequences to women in a Bangladeshi community

Visceral leishmaniasis (VL) or kala-azar (KA) affects the rural poor, causing significant morbidity and mortality. We examined the epidemiological and social impact of KA in an affected village in Bangladesh. A population-based survey of the village residents showed a case fatality rate of 14.7% among females and 5.3% among males. Before initiation of the study, female patients were ill longer than males before they received treatment. Future work needs to focus on understanding the implications of KA on women and to develop sustainable strategies for appropriate and timely access to treatment.     

Nierenbefunde bei Paraproteinämien und fibrillären Glomerulopathien

The term “paraproteinemia” or dysproteinemia” refers to a group of diseases caused by specific proteins that very often leads to kidney disease. In these cases a kidney biopsy is often the first diagnostic procedure leading to the diagnosis of a systemic disease. Due to the very variable presentation of the kidney disease in paraproteinemias a diagnosis is often very difficult without specific clinical data. Therefore, we recommend systematic investigation of the kidney biopsy including routine immunohistochemical stains for κ- and λ-light chains and electron microscopy in elderly patients with proteinuric kidney disease of unknown origin. In the following we will briefly discuss renal manifestations and clinical symptoms in multiple myeloma with light- or heavy chain deposition (LCDD: light chain deposition disease, HCDD: heavy chain deposition disease), macroglobulinemia Waldenström (Morbus Waldenström), primary amyloidosis or so called monoclonal gammopathy of uncertain dignity (benign monoclonal gammopathy) and fibrillary glomerulopathies.     

EEG abnormalities associated with antipsychotics: a comparison of quetiapine, olanzapine, haloperidol and healthy subjects

In this study the effects of the atypical antipsychotics quetiapine and olanzapine, and the typical antipsychotic haloperidol on EEG patterns were retrospectively investigated in 81 patients under stable monotherapy with either drug (quetiapine: n=22, olanzapine: n=37, haloperidol: n=22). These three subgroups were compared with a control group of healthy subjects (n=30) which were matched regarding sex and age. Diagnoses of patients were schizophrenia (DSM-IV 295.xx, n=61), brief psychotic disorder (DSM-IV 298.8, n=9), schizoaffective disorder (DSM-IV 295.70, n=8) and delusional disorder (DSM-IV 297.1, n=3). There were no statistically significant differences regarding demographic characteristics between the groups. Digital EEG recordings were retrieved from a database and visually assessed by two independent investigators, and one blinded regarding medication. One patient from the quetiapine group (5%), 13 olanzapine patients (35%), five of the haloperidol patients (23%) and two subjects of the control group (7%) had an abnormal EEG. Epileptiform activity was observed in four patients (11%) of the olanzapine group, and none in the others. EEG abnormalities were statistically significantly increased with dose in the olanzapine group, in contrast to patients treated with haloperidol, quetiapine or healthy subjects. In conclusion, EEG abnormalities seem to occur rarely in patients treated with quetiapine comparable to the control group, but significantly more often with haloperidol and olanzapine, possibly due to different receptor profiles of these substances. To our knowledge, this is the first electrophysiological investigation comparing the new atypical antipsychotics quetiapine, haloperidol, olanzapine with healthy subjects.     

Competition between acetylcholine and a nondepolarizing muscle relaxant for binding to the postsynaptic receptors at the motor end plate: simulation of twitch strength and neuromuscular block

The goal of the study was to simulate twitch strength and neuromuscular block produced by nondepolarizing muscle relaxants. Methods: In the proposed model, affinities of the two binding sites at a single postsynaptic receptor for acetylcholine (A) and the muscle relaxant (D) define the formation of three complexes with A only, three complexes with D only, and two complexes with both A and D. Twitch strength was postulated to be a function of the receptors with both binding sites occupied by A, and two constants. Neuromuscular block (NMB) was calculated from NMB=1-twitch. Results: Stimulus-induced release of A results in rapid, but transient, changes in the concentrations of free A, the eight complexes, and the unoccupied receptors. Muscle relaxants that display either a congruous or an inverse pattern of affinities for the binding sites relative to those of A produce NMB vs. [D] curves with slightly different slopes but markedly different estimates for IC50. Depending on the number of activated receptors at the end plates of muscle fibers, the simulations represent the distributions of contracting fibers in a whole muscle. Conclusion: Simulations of competition between A and D for binding to two sites at a receptor reveal that the potencies of muscle relaxants, defined by IC50, and the slopes of the NMB vs. [D] curves depend on (1) the affinities of D for the two binding sites, (2) the orientation of the affinities relative to those of A, and (3) the affinities of A for the same two sites.     

The effects of nifedipine on ventricular fibrillation mean frequency in a porcine model of prolonged cardiopulmonary resuscitation

We assessed the effects of a calcium channel blocker versus saline placebo on ventricular fibrillation mean frequency and hemodynamic variables during prolonged cardiopulmonary resuscitation (CPR). Before cardiac arrest, 10 animals were randomly assigned to receive either nifedipine (0.64 mg/kg; n = 5) or saline placebo (n = 5) over 10 min. Immediately after drug administration, ventricular fibrillation was induced. After 4 min of cardiac arrest and 18 min of basic life support CPR, defibrillation was attempted. Ninety seconds after the induction of cardiac arrest, ventricular fibrillation mean frequency was significantly (P < 0.01) increased in nifedipine versus placebo pigs (mean +/- SD: 12.4 +/- 2.1 Hz versus 8 +/- 0.7 Hz). From 2 to 18.5 min after the induction of cardiac arrest, no differences in ventricular fibrillation mean frequency were detected between groups. Before defibrillation, ventricular fibrillation mean frequency was significantly (P < 0.05) increased in nifedipine versus placebo animals (9.7 +/- 1.2 Hz versus 7.1 +/- 1.3 Hz). Coronary perfusion pressure was significantly lower in the nifedipine than in the placebo group from the induction of ventricular fibrillation to 11.5 min of cardiac arrest; no animal had a return of spontaneous circulation after defibrillation. In conclusion, nifedipine, but not saline placebo, prevented a rapid decrease of ventricular fibrillation mean frequency after the induction of cardiac arrest and maintained ventricular fibrillation mean frequency at approximately 10 Hz during prolonged CPR; this was nevertheless associated with no defibrillation success. IMPLICATIONS: This study evaluates the effects of a calcium channel blocker on ventricular fibrillation mean frequency, hemodynamic variables, and resuscitability during prolonged cardiopulmonary resuscitation (CPR) in pigs. Nifedipine, but not saline placebo, prevented a rapid decrease of ventricular fibrillation mean frequency after the induction of cardiac arrest and maintained ventricular fibrillation mean frequency at approximately 10 Hz during prolonged CPR but did not improve resuscitability.