Effects of continuous darkness on ERG correlates of disc shedding in rabbit retina.

The electroretinogram (ERG) was recorded in the dark from photo-entrained albino rabbits, using a constant-intensity, 500-nm, 50- or 100-msec stimulus at 1-min intervals. Under these conditions, the b-wave of the ERG was previously shown to decrease in amplitude at the time of the morning rod photoreceptor disc shedding event. We have extended our observations to rabbits housed in continuous darkness. The present data show that in constant darkness the change in retinal sensitivity continues to occur, but with a period slightly less than 24 hr. Unilateral dark adaptation, achieved by eyepatching, alters the timing of the event only in the retina of the occluded eye. Thus, the change in retinal sensitivity shares the characteristics of endogenous rhythmicity and intraocular control that have been demonstrated by histologic methods for mammalian rod disc shedding. We also report elongation of rod outer segments in some regions of the albino rabbit retina after continuous darkness.     

A comparison of tympanic thermometer readings to pulmonary artery catheter core temperature recordings

The purpose of this study was to determine the accuracy of FirstTemp (Intelligent Medical Systems, Carlsbad, CA) tympanic thermometer readings compared with core body temperatures obtained via pulmonary artery catheter (PAC). Five measurements were obtained on 19 cardiovascular surgery patients. Tympanic thermometer measurements tended to be higher than PAC measurements. However, most of the differences were not clinically significant. Differences found between right and left ear measurements were most likely due to poor measurement technique. When the correct technique is used, nurses can be confident that tympanic temperature readings are clinically accurate.     

The Association of Different Measures of Insulinaemia with Vascular Risk Factors in Healthy Normoglycaemic Normotensive Non-obese Men and Women

Hyperinsulinaemia is said to be a risk factor for cardiovasculardisease, but the extent to which different insulinaemic measuresare associated with vascular risk factors in ostensibly healthyindividuals, and whether they operate independently in men andwomen, remains uncertain. The association between risk factors and various insulinaemicmeasures was examined in 148 men and 118 women who were normoglycaemic,normotensive, and non-obese (body mass index in men <27,in women <25). A 75 g glucose tolerance test was administeredafter blood sampling for fibrinogen, lipids, lipoproteins andinsulin. Insulin was also measured after 1 and 2 hours. Significantunivariate correlations (p<0.01) were most consistently recordedbetween insulinaemic measures and fasting serum triglyceridesin men and women, whilst systolic blood pressure only correlatedwith insulinaemia in women, and diastolic blood pressure correlatedwith fasting and 2 hour insulinaemic measures in men and women.Inconsistent associations were noted with total serum cholesterolin men and women, with high density lipoprotein cholesterol,body mass index, apoprotein B and A1 in men, and with fibrinogenin women. Age was not correlated with any insulinaemic measurein men or women. Differences in vascular risk factors between quintiles of theinsulinaemic measures were examined, after correction for bodymass index. The dominant association with fasting and post-glucoseload insulinaemic measures was with triglycerides, especiallyin women, with less frequent graded differences between quintilesobserved for total cholesterol, and diastolic and systolic bloodpressures in men and women. The incidence of other risk factors often only differed in thelowest or highest quintile in comparison to other quintiles,suggesting a threshold rather than a graded effect. Furthermore,differences in HDL cholesterol and apoprotein B were only recordedfor top quintiles of post-glucose challenge/integrated insulinaemicmeasures in men, whilst serum fibrinogen concentrations onlydiffered significantly in women in the top insulinaemic areaunder the curve quintile. In the absence of additional risk factors such as diabetes,hypertension and obesity, insulinaemic measures are not consistentlyrelated to blood pressure and measures of lipid metabolism andcoagulation, and are thus a weak predictor of other cardiovascularrisk factors. The vascular risk profile associated with insulinappears somewhat different in apparently healthy men and women.     

Evaluation of hypothesis testing for comparing two populations using NONMEM analysis

In a simulation study of inference on population pharmacokinetic parameters, two methods of performing tests of hypotheses comparing two populations using NONMEM were evaluated. These two methods are the test based upon 95% confidence intervals and the likelihood ratio test. Data were simulated according to a monoexponential model and, in that context, power curves for each test were generated for (i)the ratio of mean clearance and (ii)the ratio of the population standard deviations of clearance. To generate the power curves, a range of these parameters was employed; other pharmacokinetic parameters were selected to reflect the variability typically present in a Phase II clinical trial. For tests comparing the means, the confidence interval tests had approximately the same power as the likelihood ratio tests and were consistently more faithful to the nominal level of significance. For comparison of the standard deviations, and when the volume of information available was relatively small, however, the likelihood ratio test was more able to detect differences between the two groups. These results were then compared to results on parameter estimation in order to gain insight into the question of power. As an example, the nonnormality of estimates of the ratio of standard deviations plays an important role in explaining the low power for the confidence interval tests. We conclude that, except for the situation of modeling standard deviations with only sparse information, NONMEM produces tests of significance that are effective at detecting clinically significant differences between two populations.Partial support from the Upjohn Company, NIH-BRSG SO RR 07066, and the Burroughs Wellcome Foundation.     

A randomized, prospective trial of postoperative somatostatin analogue in patients with neuroendocrine tumors of the pancreas.

BACKGROUND. Pancreatic surgery is not uncommonly complicated by prolonged pancreatic drainage and fistula. Octreotide decreases pancreatic exocrine function and has been reported to improve closure of pancreatic and intestinal fistulae. This randomized, prospective trial was designed to evaluate the efficacy of postoperative octreotide in reducing pancreatic drainage and complications after resection of neuroendocrine tumors of the pancreas. METHODS. Patients with neuroendocrine tumors of the pancreas were entered into the study and randomized after operation to receive octreotide 150 micrograms subcutaneously every 8 hours or saline solution subcutaneously every 8 hours in a double-blinded fashion. Daily pancreatic drainage, total drainage, number of days to drain removal, and complications were recorded. RESULTS. Ten patients were given octreotide; eleven patients were given saline solution. The number of days to drain removal, daily drainage, and total drainage were not significantly different. Complications related to pancreatic drainage were not significantly different. CONCLUSIONS. Octreotide is not indicated for the routine postoperative management of patients with neuroendocrine tumors of the pancreas.     

Anterior spinal hernia: an increasingly recognised cause of thoracic cord dysfunction.

Two cases of anterior spinal hernia are presented. The medical literature is reviewed, the syndrome characterised, and its cause and treatment discussed. The patient is typically middle aged with a history of stepwise slowly progressive mid-thoracic anterior hemicord syndrome manifesting as hemianalgesia below the affected segment, followed by contralateral lower limb spasticity that develops into an asymmetric paraparesis with sparing of dorsal column sensation. Radiological investigation demonstrates an enlarged dorsal arachnoid space in association with an apparently focally narrowed thoracic cord, kinked towards the anterior dura. At operation the cord is found to be prolapsed into an anterolateral dural diverticulum. The most likely cause of this syndrome is anterior spinal artery segmental branch ischaemia, in a cord chronically incarcerated in a congenital anterior meningocele. This readily treatable condition should be considered in all cases of thoracic cord dysfunction and surgical repair effected early to prevent stepwise progression to paraplegia.     

Xenopus Tadpole Melanophores Are Controlled by Dark and Light and Melatonin Without Influence of Time of Day

Melanophores were studied in tadpoles of the South African clawed toad, Xenopus laevis , during the first week after hatching (stages 46–49) at 25°C. The tadpoles had melanophores with dispersed melanosomes in the light and punctate melanophores in the dark in LD12:12. The melanophores remained punctate in constant dark and the melanosomes remained dispersed in constant light. Lights-out (in the light-time of LD12:12) caused the melanophores to become punctate, which occurred more quickly than the dispersion of melanosomes, which commenced when the lights were turned on (in the dark-time of LD12:12). Melanophores with dispersed melanosomes in tadpoles (in constant light) became punctate in response to a series of melatonin concentrations (0.2–5 ng/ml) in their bathing water irrespective of the time of day melatonin was administered. An image-analysis technique for assessing melanophore responses was tested.     

Receptor subtypes mediating facilitation by serotonin of excitability of spinal motoneurons

Serotonin receptor ligands, with differential affinity for subtypes of serotonin (5-HT) receptors, were administered intravenously or iontophoretically to urethane-anesthetized rats and the effects of these compounds on glutamate-evoked firing of spinal motoneurons were tested. The excitability of spinal motoneurons was markedly enhanced after intravenous administration of the selective 5-HT1A ligand 8-hydroxy-2-(di-n-propylamino) tetralin (DPAT) in rats with acute spinal transections at C1. However, local application of DPAT, directly into the ventral horn by microiontophoresis, inhibited the glutamate-evoked firing of motoneurons in direct contrast to the facilitatory effects of iontophoretically applied 5-HT. The DPAT-induced inhibition may have been nonspecific, since it was not antagonized by methysergide. Other 5-HT agonists, with relatively selective affinity for 5-HT1B, 5-HT1C and 5-HT2 receptors, increased the excitability of spinal motoneurons when applied iontophoretically or intravenously. The excitatory effect of iontophoretically applied 5-HT was antagonized by the nonselective 5-HT antagonist, methysergide and by ketanserin and ritanserin, which have relatively selective affinity for 5-HT1C and 5-HT2 receptors. These results indicate that 5-HT1A receptors do not mediate facilitation of excitability of motoneurons produced by local application of 5-HT directly into the vicinity of the motoneurons. However, the marked increase in firing of motoneurons that was caused by intravenous administration of DPAT in spinal transected rats, suggests that 5-HT1A receptors in the spinal cord may participate in 5-HT-induced enhancement of somatomotor outflow, at sites presynaptic to the motoneurons. The iontophoretic results suggest that 5-HT1B, 5-HT1C and 5-HT2 receptors may all play a role in facilitation of the excitability of spinal motoneurons by locally applied 5-HT. Differentiation between these subtypes of receptor awaits the development of more completely selective agonists and antagonists.