Functional characterization of the H-current in SCN neurons in subjective day and night: a whole-cell patch-clamp study in acutely prepared brain slices

Neurons of the rat suprachiasmatic nucleus (SCN) exhibit a circadian rhythm in spontaneous firing rate. In this whole-cell patch-clamp study in slices, we examined the possibility that H-current (I_H) contributes to the spontaneous firing rate of SCN neurons. Most of our experiments were performed during the subjective day, because this is the time epoch during which one would expect the largest excitatory effect of I_H if it were to fluctuate in a circadian rhythm. Current-clamp experiments showed that blockade of I_H by Cs⁺ (1 mM) did not influence the spontaneous firing rate and resting membrane potential. Voltage-clamp experiments revealed that I_H, when activated at the resting membrane potential, is probably too small in magnitude and too slow in activation to make a significant contribution to the spontaneous firing rate. Both results suggest that I_H does not significantly contribute to the spontaneous firing of SCN neurons. In addition, we investigated whether the kinetics and voltage dependence of I_H were modulated in a circadian manner. However, no substantial day–night differences in I_H were found. We conclude that I_H, as recorded in whole-cell mode, does not contribute significantly to spontaneous firing in most SCN neurons and that this current, is more likely to be involved in `rescuing' SCN neurons from large and long-lasting hyperpolarizations by depolarizing the membrane.     

Role of prolactin in changes of parasitism induced by lactation

In order to establish the role played by prolactin in lactation during the evolution of Strongyloides ratti in the female rat, the authors tried to reproduce the effects of this physiological state by treatment with sulpiride (substituted benzamide), of which the prolactinogenic effect is intense in the female rat. Low doses partially reproduced the effects of lactation on parasitism by diminishing its intensity and delaying the onset of rejection, although without preventing it. The pharmacological action of sulpiride, which acts by blocking the dopamine receptors, explains why only low doses are active and why their action is limited to the onset of parasitism. This experiment lends weight to the hypothesis that prolactin plays a fundamental role in modifications of the evolution of Strongyloides ratti during lactation.     

Outcome in a post-cardiac surgery population with acute renal failure requiring dialysis: does age make a difference?

BACKGROUND: Acute renal failure (ARF), requiring dialysis (ARF-d), develops in 1-5% of patients undergoing cardiac surgery and is associated with higher in-hospital mortality. Age is one of the known risk factors for the development of ARF. As the ageing population is increasing, the nephrologist will be faced with a large population of elderly patients requiring dialysis following cardiac surgery. The aim of our study was to evaluate the influence of age on and the risk factors for in-hospital mortality. METHODS: Eighty-two patients with ARF following cardiac surgery and requiring dialysis between January 1997 and October 2001 were included. Two groups of patients were studied: the younger population (<70 years, 42 patients, mean age 59+/-10) and an elderly population (>/=70 years, 40 patients, mean age 76+/-4). Severity of disease was evaluated using the SAPS (Simplified Acute Physiology Score), the Liano score and the SHARF (Stuivenberg Hospital Acute Renal Failure) score. RESULTS: Overall mortality in the population with ARF-d was 56.1%. No difference in mortality rate was found between the younger (61.9%) and elderly patient group (50.0%). The two groups were very similar in baseline and procedural characteristics with exception of body weight (P=0.02) and preoperative glomerular filtration rate (P=0.0001). No significant difference was found in the scoring systems between the old and the young (SAPS P=0.52; Liano P=0.96; SHARF T0 P=0.06; SHARF T48 P=0.15). Mortality in the elderly was significantly correlated with hypotension before starting renal replacement therapy (RRT) (P=0.002), mechanical ventilation (P=0.002), presence of multiorgan failure (MOF) (P=0.0001) and higher scores in the severity models (SAPS: P=0.01; Liano: P<0.0001 and SHARF: P<0.0001). CONCLUSION: The outcome in the elderly requiring dialysis due to ARF post-cardiac surgery is comparable with the outcome in a younger population. No significant difference was found in severity of disease between the elderly and the younger. Variables predicting mortality in the elderly are the presence of MOF, mechanical ventilation and hypotension 24 h before starting RRT. These findings indicate that at the time the nephrologist is called for an elderly patient requiring dialysis due to ARF following cardiac surgery, age per se is not a reason to withhold RRT.     

Exercise-induced ventricular tachycardia: A rare manifestation of digitalis toxicity

Digitalis intoxication is one of the most common adverse drug reactions. Although some arrhythmias are seen more frequently than others, virtually any rhythm disturbance, including ventricular tachycardia, may occur. However, to our knowledge, exercise-induced ventricular tachycardia as a complication of digitalis therapy has never been described before. This case presents a patient with a digitalis-induced ventricular tachycardia occurring exclusively during exercise.     

Anatomy changes in radiotherapy detected using portal imaging.

BACKGROUND AND PURPOSE: Localisation images normally acquired to verify patient positioning also contain information about the patient's internal anatomy. The aim of this study was to investigate the anatomical changes observed in localisation images and examples of dosimetric consequences. PATIENTS AND METHODS: Localisation images were obtained weekly prior to radiotherapy with an electronic portal imaging device (EPID). A series of 'difference images' was created by subtracting the first localisation image from that of subsequent fractions. Images from 81 lung, 40 head and neck and 34 prostate cancer patients were classified according to the changes observed. Changes were considered relevant if the average pixel value over an area of at least 1cm(2) differed by more than 5%, to allow for variations in linac output and EPID signal. Two patients were selected to illustrate the dosimetric effects of relevant changes. Their plans were re-calculated with repeat CT scans acquired after 4 weeks of treatment and compared with the difference images of the corresponding days. RESULTS: Progressive changes were detected for 57% of lung and 37% of head and neck cancer patients studied. Random changes were observed in 37% of lung, 28% of head and neck and 82% of prostate cancer patients. For a lung case, an increase of 10.0% in EPID dose due to tumour shrinkage corresponded to an increase of 9.8% in mean lung dose. Gas pockets in the rectum region of the prostate case increased the EPID dose by 6.3%, and resulted in a decrease of the minimum dose to the planning target volume of 26.4%. CONCLUSIONS: Difference images are an efficient means of qualitatively detecting anatomical changes for various treatment sites in clinical practice. They can be used to identify changes for a particular patient, to indicate if the dose delivered to the patient would differ from planning and to detect if there is a need for re-planning.     

Impact of internal capsule lesions on outcome of motor hand function at one year post-stroke.

OBJECTIVE: To investigate the association between damage to different levels of the corticofugal tract and long-term hand motor recovery. DESIGN: Prospective cohort study. PATIENTS: Seventy-five first-ever middle cerebral artery stroke survivors. METHODS: Hand motor function was assessed with the Fugl-Meyer Motor Assessment Scale at one year post-stroke. Localization of the corticofugal tract was assessed on axial magnetic resonance imaging slices using a corticofugal mask defining involvement of the motor cortex, corona radiata or internal capsule and combinations of these structures, adjusted for lesion volume. RESULTS: Longitudinal involvement of all 3 levels of the corticofugal tract and partial involvement of the internal capsule were associated with a significant probability of poor motor hand function recovery. The probability of regaining hand function ranged from 54% if the corticofugal tract was only partly affected to 13% if both motor cortex and internal capsule were affected. CONCLUSION: At one year post-stroke, lesions of the internal capsule were associated with a significantly lower probability of return of isolated hand motor function than lesions of the cortex, subcortex and corona radiata. Since recovery of isolated hand and finger movements is important for regaining a functional upper limb in everyday living, these patients should be identified early post-stroke in order to evaluate specific hand function training.     

The what, when, whether model of intentional action

The question of how we can intentionally control our behavior has an enduring fascination for philosophers, psychologists, and neurologists. Brain imaging techniques such as functional MRI have recently provided new insights into the functional and brain mechanisms involved in intentional action. However, the literature is rather contradictory and does not reveal a consistent picture of the functional neuroanatomy of intentional action. Here the authors argue that this confusion arises partly because intentional action has been treated as a unitary concept within neuroscience, even though experimental studies may focus on any of a number of different aspects of intentional action. To provide a heuristic framework for the investigation of intentional action, the authors propose a model that distinguishes three major components: a component related to the decision about which action to execute (what component), a component that is related to the decision about when to execute an action (when component), and finally the decision about whether to execute an action or not (whether component). Based on this distinction, the authors review some key findings on intentional action and provide neuroscientific evidence for the What, When, Whether (WWW) model of intentional action.