Fourteen adult patients (mean age 22.5 years, range 18–35) with cystic fibrosis undertook nocturnal nasogastric feeding for a mean period of 14.7 (range 6–18) months consuming an average of 1042 ml of a high energy feed on five nights of each week. Following this protocol all patients gained weight (mean weight gain 5.4 kg, range 2–17). For the group as a whole, lung function remained stable during the period of feeding; however a significant correlation between improvement in lung function and weight gain was demonstrated. Hyperglycaemia during feeding in this adult population was common (9/14, 64%) but was easily controlled with insulin therapy. 相似文献
Previous studies in rats using the Morris water maze suggested that the processing of spatial information is modulated by corticosteroid hormones through mineralocorticoid and glucocorticoid receptors in the hippocampus. Mineralocorticoid receptors appear to be involved in the modulation of explorative behaviour, while additional activation of glucocorticoid receptors facilitates the storage of information. In the present study we used the water maze task to examine spatial learning and memory in mice homozygous and heterozygous for a targeted disruption of the glucocorticoid receptor gene. Compared with wild-type controls, homozygous and heterozygous mice were impaired in the processing of spatial but not visual information. Homozygous mutants performed variably during training, without specific platform-directed search strategies. The spatial learning disability was partly compensated for by increased motor activity. The deficits were indicative of a dysfunction of glucocorticoid receptors as well as of mineralocorticoid receptors. Although the heterozygous mice performed similarly to wild-type mice with respect to latency to find the platform, their strategy was more similar to that of the homozygous mice. Glucocorticoid receptor-related long-term spatial memory was impaired. The increased behavioural reactivity of the heterozygous mice in the open field points to a more prominent mineralocorticoid receptor-mediated function. The findings indicate that (i) the glucocorticoid receptor is of critical importance for the control of spatial behavioural functions, and (ii) mineralocorticoid receptor-mediated effects on this behaviour require interaction with functional glucocorticoid receptors. Until the development of site-specific, inducible glucocorticoid receptor mutants, glucocorticoid receptor-knockout mice present the only animal model for the study of corticosteroid-mediated effects in the complete absence of a functional receptor. 相似文献
Abstract Patients with end-stage liver disease have significant mortality often associated with intercurrent episodes of bleeding or sepsis. Intact adrenal function is essential in such situations. In order to test the hypothesis that adrenal insufficiency might be present in severe liver disease, hypothalamic-pituitary adrenal function was evaluated in patients with end-stage liver disease awaiting transplantation. The study had a prospective, open comparative design with patients restricted to those having non-alcoholic liver disease in order to avoid the confounding direct effects of alcohol on adrenocortical function. Fifty-one consecutive patients with end-stage, non-alcoholic liver disease undergoing evaluation for liver transplantation and 40 healthy controls were studied. Patients who had used corticosteroids (n= 8) or who were unable to complete the investigations (n= 5) were excluded leaving 38 patients eligible for analysis. Adrenal function was evaluated under basal conditions by single morning measurements of plasma total and free cortisol, corticosteroid-binding globulin, dehydroepiandrosterone sulfate and by adrenal stimulation indirectly using insulin-induced (0.1 U/kg, i.v.) hypoglycaemia and/or directly by adrenocorticotrophic hormone (ACTH); 250 μg tetracosactrin, i.v.) stimulation. Compared with healthy controls, patients with liver disease had a 64% reduction in maximal increments of plasma cortisol to indirect adrenal stimulation via insulin-induced hypoglycaemia and a 39% reduction to direct adrenal stimulation by ACTH (all P < 0.001). There was a significant negative correlation between the severity of underlying liver disease as assessed by Child-Pugh scores and peak control responses to ACTH (r= -0.647, P < 0.0001) and insulin-induced hypoglycaemia (r= -0.597, P < 0.0001). Patients with liver disease also exhibited significantly blunted and delayed hypoglycaemic responses to insulin (0.1 U/kg), brisker growth hormone responses of reduced magnitude and decreased corticosteroid-binding globulin levels. Baseline morning cortisol, free cortisol and dehydroepiandrosterone sulfate levels were unchanged compared with healthy controls. Patients on spironolactone had lower basal and peak cortisol responses to ACTH and hypoglycaemia, but the reductions were unrelated to spironolactone dose. Although insulin resistance and spironolactone therapy are confounding factors, it can be concluded that hypothalamic-pituitary regulation of adrenal function is defective in end-stage non-alcoholic liver disease. It is therefore possible that functional central adrenal insufficiency might contribute to the mortality of patients with end-stage liver disease and raises the question of the need for controlled studies of adrenocortical replacement therapy during acute deteriorations (sepsis and haemorrhage) in severe hepatic disease. 相似文献
BACKGROUND: Photon energy recovery (PER) is a spectral deconvolution technique validated for scatter removal in patients and phantom studies. The purpose of this study was to examine the impact of PER on left ventricular volume measurement based on myocardial perfusion single photon emission computed tomography (SPECT). METHODS AND RESULTS: SPECT acquisitions were performed by use of a static cardiac phantom and in 25 patients after a rest injection of technetium 99m sestamibi by use of multiple energy windows (126-136, 137-144, and 145-154 keV). Data were successively reconstructed with and without PER, by use of iterative reconstruction and post-processing filtering (Butterworth filter; order, 5; cutoff, 0.30 cycles/pixel). Image contrast was evaluated in reconstructed data, and volumes were calculated by use of QGS. PER increased reconstructed image contrast from 62% +/- 2.7% to 84.3% +/- 5.7% in the phantom studies (P <.0001) and from 49% +/- 2% to 73% +/- 2% in patients (P <.0001). Although it remained underestimated (P <.0001), phantom volume was higher after PER correction compared with uncorrected data (50.9 +/- 0.8 mL vs 44.6 +/- 1 mL, P <.0001). The error in volume measurement was decreased by PER correction (16.6% +/- 1.3% vs 27% +/- 1.7% [uncorrected data], P <.0001). In patients, left ventricular volume increased from 83 +/- 10 mL to 91 +/- 10 mL (P <.0001), and the PER-induced volume increase was correlated with the image contrast increase (r = 0.61, P =.001). Finally, the percentage of volume increase was higher in patients with small left ventricular volumes. CONCLUSIONS: PER has a significant impact on image contrast and left ventricular volume measurement by use of perfusion SPECT. PER improves the accuracy of phantom volume assessment. In patients, volume increase is correlated to image contrast increase and is higher in those with small ventricles. 相似文献
1. The role of angiotensin as a modulator of proximal glomerulotubular (GT) balance was investigated in anaesthetized rats by examining the relationship between glomerular filtration rate (GFR) and absolute proximal reabsorption (APR) during removal of endogenous angiotensin II (AII) and III (AIII) with enalaprilat (CEI) and then during their subsequent replacement by intravenous infusions. 2. Enalaprilat lowered mean arterial blood pressure (MABP) and increased renal blood flow (RBF), GFR, urine flow rate and sodium excretion. Filtration fraction (FF) was not altered. Absolute proximal reabsorption, derived from fractional lithium clearance, increased by only 48% of the change expected for 'perfect' GT balance. 3. Angiotensin II replacement corrected MABP, GFR and plasma renin level, but reduced RBF and increased FF; APR was decreased and GT balance was restored. Urine flow and sodium excretion remained above control values with AII. 4. Replacement with AIII did not correct the hypotension but completely reversed the renal and renin responses to enalaprilat and restored GT balance without affecting FF. 5. It was concluded that the relation between proximal reabsorption and GFR is considerably modified by the intrarenal angiotensin concentration. The findings are best explained by a direct stimulation of proximal tubular sodium transport by angiotensin at the concentrations existing in anaesthetized rats. 相似文献
Background. A major concern in evaluating dynamic cardiomyoplasty has been whether the synchronous stimulation of latissimus dorsi muscle is essential for benefit or not. We studied 10 patients to determine the efficacy of the systolic augmentation generated by the synchronous electrical stimulation of the latissimus dorsi muscle.
Methods. Left ventricular ejection fraction, end-systolic and end-diastolic volume indexes, and stroke volume index obtained during resting, peak exercise, and recovery periods (“on” values) were compared with those obtained 1 week after cessation of electrical stimulus (“off” values). Double product and estimated total body oxygen consumption at peak exercise were also calculated and compared.
Results. Higher ejection fractions (0.36 ± 0.07 versus 0.33 ± 0.06 at rest, 0.40 ± 0.07 versus 0.33 ± 0.07 peak exercise, and 0.37 ± 0.06 versus 0.31 ± 0.06 at recovery) and lower end-systolic volume indexes with relatively constant end-diastolic volume indexes were observed with the cardiomyostimulator on. Further, exercise response was better with the cardiomyostimulator on. Double product indirectly reflected better myocardial oxygen supply/demand ratio when on at peak exercise (17 ± 2.2 mm Hg × beats/min × 10−3 for on versus 19 ± 2.6 mm Hg × beats/min × 10−3 for off). Estimated total body oxygen consumption was improved at peak exercise when the cardiomyostimulator was functional (12 ± 2.7 mL · kg−1 · min−1 versus 11 ± 2.6 mL · kg−1 · min−1).
Conclusions. Current data suggest a true systolic assist during synchronous contractions of the latissimus dorsi muscle. It is thought, therefore, that synchronous electrical stimulation is essential for maximum benefit and all the beneficial effect of cardiomyoplasty certainly cannot be attributed to simple wrapping itself. 相似文献