Role of noradrenergic hyperactivity in neonatal opiate abstinence

Despite the existence of a well-defined abstinence syndrome in offspring of opiate-dependent mothers, the mechanisms involved in neonatal abstinence remain unclear. The goal of the present study was to determine the contribution of noradrenergic neurons in the opiate abstinence syndrome in neonatal rats (10 days old). First, the ability of the α2-adrenergic agonist, clonidine to attenuate the symptoms of neonatal opiate abstinence precipitated by naloxone was determined. Secondly, the activity of noradrenergic neurons was determined by measuring postmortem levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the hypothalamus, hippocampus and cortex in opiate-abstinent pups. Neonatal opiate abstinence was characterized by an increased incidence of wall climbing, tremors and mouthing. Acute treatment with morphine and naloxone in chronic saline-treated pups also produced the tremor, albeit less severe than in pups treated chronically with morphine. Clonidine (0.2 mg/kg) attenuated the expression of tremor and mouthing in neonates, but increased wall climbing. Clonidine elicited wall climbing in opiate-naive neonates. Treatment with morphine followed by naltrexone increased MHPG levels in all of the brain areas examined, irrespective of the chronic treatment, but naltrexone treatment elicited a larger increase in MHPG levels in pups treated chronically with morphine. Acute morphine treatment increased MHPG levels only in the hypothalamus. The results of the present study provide behavioral and neurochemical data supporting the hypothesis that noradrenergic hyperactivity plays a role in neonatal opiate abstinence.     

Isolated human hepatocytes in culture display markedly different gene expression patterns depending on attachment status

In vitro human hepatocyte cultures are a key tool in the investigation of xenobiotic toxicity and metabolism. In most in vitro hepatocyte studies, the cells are allowed to adhere to an extracellular matrix, such as collagen. Unfortunately, the ability of freshly isolated hepatocytes to adhere to collagen varies from donor to donor. We used microarray analysis to determine what gene expression differences exist between hepatocytes in suspension and hepatocytes attached to collagen. Results from different donors showed a considerable difference in gene expression patterns between the two hepatocyte populations. In addition, we also compared the gene expression profiles of hepatocytes in culture with liver tissue. The results showed that both hepatocytes in suspension and hepatocytes attached to collagen display significant gene expression differences compared with liver tissue. Finally, we show that both populations of hepatocytes are responsive to dexamethasone and regulate some of the same genes. Overall, our results suggest that either significant gene expression changes occur in isolated hepatocytes or that suspended and attached cells represent different populations of hepatocytes found in intact livers.     

Brain dysfunction in social drinkers

Thirty-four social drinkers who had referred themselves to the Regional Brain Damage Unit for assessment of the effects of drinking alcohol were compared with 42 volunteer control subjects of equivalent age but with low alcohol intake, using two 'learning' tests — the Rey Auditory Verbal Learning Test (RAVLT) and the Austin Button Maze. The Maze Test gave no evidence of disorder, but the two groups were significantly different on the RAVLT. No abnormalities in standard cognitive tests were apparent. These results suggest that a deficit in learning ability may be an early feature of the brain dysfunction associated with excessive alcohol consumption.     

A model for assessing information retrieval and application skills of medical students.

PURPOSE: To develop and evaluate a model for assessing information retrieval and application skills, and to compare the performances on the assessment exercises of students who were and were not instructed in these skills. METHOD: The authors developed a set of four examination stations, each with multiple subtasks, and administered the exams to students at two medical schools. Students at one school had intensive instruction in literature searching and filtering skills for information quality (instructed group), and those at the other school had minimal instruction in these areas (uninstructed group). The stations addressed pediatrics content and the skills of searching Medline and the World Wide Web, evaluating research articles, evaluating the accuracy of information from the Web, and using the information to make recommendations to patients. The authors determined the psychometric characteristics of the stations and compared the performances of the two groups of students. RESULTS: Students in the instructed group performed significantly better and with less variability than the uninstructed group on four tasks and no differently on seven tasks. There was no task on which the uninstructed group performed significantly better than the instructed group. CONCLUSION: The prototype stations showed predictable differences across curricula, indicating that they have promise as assessment tools for the essential skills of information retrieval and application.     

Lymphatic drainage from the skin of the back to retroperitoneal and paravertebral lymph nodes in melanoma patients

Background: Preoperative lymphoscintigraphy (LS) with^99mTc antimony sulphide colloid is now part of the routine management of patients with intermediate thickness melanoma at the Sydney Melanoma Unit. Over a 13-year period, 1375 patients have been examined using LS, and we have observed many unusual lymphatic drainage pathways, including direct drainage through the body wall to retroperitoneal and paravertebral lymph nodes from the skin of the back. The aim of this study was to determine the incidence of such drainage in the 542 patients who had primary melanoma sites on the posterior trunk. Methods: The lymphoscintigrams performed on these patients were examined for the presence of direct lymphatic drainage through the posterior body wall to sentinel nodes in the retroperitoneal and paravertebral regions. Results: Lymphatic drainage directly through the body wall to such lymph nodes occurred in 14 of these 542 patients. Conclusions: Preoperative knowledge of the presence of this lymph drainage pattern may influence surgical management, and follow-up investigations in these patients can be tailored to ensure that the relevant areas are examined with anatomic imaging or F18-FDG PET scans.     

Elevated hypothalamic neuropeptide Y levels in rats with dorsomedial hindbrain lesions

Lesions centered on the area postrema (AP) and adjacent nucleus of the solitary tract (AP/mNTS-lesions) are reported to result in increased consumption of highly palatable diets. Recent studies suggest that neuropeptide Y (NPY) may cause a preference for carbohydrate-rich diets. Thus, it is possible that NPY may play a role in the enhanced intake of highly palatable diets by AP/mNTS-lesioned rats. In the studies reported here, we found that lesions centered on the AP result in increased levels of NPY-immunoreactivity in the paraventricular nucleus of the hypothalamus. Additionally, steady-state NPY mRNA in the basomedial hypothalamus including the arcuate nucleus was elevated. Enhanced NPY was not found throughout the hypothalamus however, as NPY-immunoreactivity was not elevated in the lateral hypothalamus or the tissue bordering the anteroventral third ventricle. These data suggest the possibility that elevated hypothalamic NPY, particularly in the arcuate and paraventricular nuclei, may contribute to the altered food intake and energy balance observed in rats with lesions centered on the AP.