Sterile water moisturizer of the skin of extremely low birth weight infants.

OBJECTIVE: To assess the feasibility of sterile water application to the skin of the extremely low birth weight (ELBW) newborns in the first week of life and examine its effects on their skin integrity and outcomes. DESIGN: Pilot randomized controlled trial. SETTING: Open-bay, 18 bed Level III NICU in the Eastern United States. PARTICIPANTS: Twenty-eight ELBW neonates. Two newborns expired, sixteen newborns remained in the intervention group and twelve newborns in the control group. METHODS: ELBW neonates were either assigned to receive frequent sterile water wash to skin or not during care for the first week of life. Using the Neonatal Skin Condition Scale (NSCS), assessments were performed twice a day during the first week. Fluid intake, serum electrolytes, culture proven sepsis and other morbidities, and length of stay (LOS) were compared while controlling for confounding variables using multiple regression analysis. RESULTS: There was no difference in the demographic or clinical characteristics between both groups. Sterile water wash application to skin was not associated with differences in skin health indices or fluid intake. However, it was associated with higher median sodium level and with early regression of bilirubin level when compared to controls. CONCLUSION: Frequent skin washes with sterile water are feasible and safe. However, they may not be associated with improved skin integrity or fluid intake.

Measurement of D{0}-D[-over]{0} mixing from a time-dependent amplitude analysis of D{0}-->K+pi{-}pi{0} decays.

We present evidence of D{0}-D[-over ]{0} mixing using a time-dependent amplitude analysis of the decay D{0}-->K+pi{-}pi;{0} in a data sample of 384 fb{-1} collected with the BABAR detector at the PEP-II e+e{-} collider at the Stanford Linear Accelerator Center. Assuming CP conservation, we measure the mixing parameters x{Kpipi{0}}{'}=[2.61{-0.68}{+0.57}(stat)+/-0.39(syst)]%, y{Kpipi;{0}}{'}=[-0.06{-0.64}{+0.55}(stat)+/-0.34(syst)]%. This result is inconsistent with the no-mixing hypothesis with a significance of 3.2 standard deviations. We find no evidence of CP violation in mixing.

Postural asymmetry and movement disorder after unilateral microinjection of adrenocorticotropin 1-24 in rat brainstem.

A unilateral microinjection of adrenocorticotropin 1-24 in the rat brainstem in the region of the locus ceruleus resulted in postural asymmetry and movement disorder that resembled human dystonia, the severity and duration (2 to 3 days) being dose-dependent. These results show for the first time that neuropeptides in the brainstem may modulate posture and movement, and they suggest that some forms of movement disorder such as dystonia may be due to a disordered regulation of postural and locomotor mechanisms by adrenocorticotropin 1-24.

Selective loss of hippocampal granule cells in the mature rat brain after adrenalectomy.

Adrenalectomy of adult male rats resulted in a nearly complete loss of hippocampal granule cells 3 to 4 months after surgery. Nissl and immunocytochemical staining of hippocampal neurons revealed that the granule cell loss was selective; there was no apparent loss of hippocampal pyramidal cells or of gamma-amino butyric acid (GABA)-, somatostatin-, neuropeptide Y-, calcium binding protein-, or parvalbumin-containing hippocampal interneurons. The hippocampal CA1 pyramidal cells of adrenalectomized animals exhibited normal electrophysiological responses to afferent stimulation, whereas responses evoked in the dentate gyrus were severely attenuated. Corticosterone replacement prevented both the adrenalectomy-induced granule cell loss and the attenuated physiological response. Thus, the adrenal glands play a role in maintaining the structural integrity of the normal adult brain.

Triiodothyronine and thyroxine in the serum and thyroid glands of iodine-deficient rats.

Triiodothyronine (T(3)) and thyroxine (T(4)) were measured by immunoassay in the serum and thyroid hydrolysates of control (group A), mildly iodine-deficient (group B), and severely iodine-deficient rats (group C). These results were correlated with changes in thyroidal weight, (131)I uptake and (127)I content as well as with the distribution of (131)I in Pronase digests of the thyroid. There was a progressive increase in thyroid weight and (131)I uptake at 24 h with decrease in iodine intake. The (127)I content of the thyroids of the group B animals was 44% and that of the group C animals 2% of that in group A. The mean labeled monoiodotyrosine/diiodotyrosine (MIT/DIT) and T(3)/T(4) ratios in group A were 0.42+/-0.07 (SD) and 0.12+/-0.01, 0.59+/-0.06 and 0.11+/-0.03 in group B, and 2.0+/-0.3 and 1.8+/-0.9 in the group thyroid digests.Mean serum T(4) concentration in the control rats was 4.2+/-0.6 (SD) mug T(4)/100 ml, 4.5+/-0.3 mug/100 ml in group B animals, and undectectable (<0.5 mu(4)/100 ml) in group C animals. There was no effect of iodine deficiency on serum T(3) concentrations, which were 44+/-9 (Mean+/-SD) ng/100 ml in A animals, 48+/-6 ng/100 ml n B animals, and 43+/-6 ng/100 ml in the C group. Thyroidal digest T(3) and T(4) concentrations were 39 and 400 ng/mg in group A animals and were reduced to 5 and 1% of this, respectively, in group C. The molar ratio of T(3)/T(4) in the thyroid digests of the groups A and B animals was identical to the ratio of labeled T(3)/T(4) and was slightly less (1.0+/-0.9) than the labeled T(3)/T(4) ratio in the group C animals. The mean ratio of labeled T(4) to labeled T(3) in the serum of the severely iodine-deficient animals 24 h after isotope injection was 11+/-1 (SEM). With previously published values, it was possible to correlate the ratio of labeled T(4)/T(3) in the thyroid digest with the labeled T(4)/T(3) ratio in the serum of each iodine-deficient animal. This analysis suggested that the labeled thyroid hormones in the severely iodine-deficient rat were secreted in the ratio in which they are present in the gland. Kinetic analysis of total iodothyronine turnover indicated that two-thirds of the T(3) utilized per day by the iodine-sufficient rat arises from T(4). If the T(4)-T(3) conversion ratio remains the same in iodine deficiency, then the analysis suggests that about 90% of the T(3) arises directly from the thyroid. Therefore, it would appear that absolute T(3) secretion by the thyroid increases severalfold during iodine deficiency. The fact that serum T(3) remains constant and T(4) decreases to extremely low levels, combined with previous observations that iodine-deficient animals appear to be euthyroid, is compatible with the hypothesis that T(4) in the normal rat serves primarily as a precursor of T(3).

Evidence for regional catecholamine uptake and storage sites in the transplanted human heart by positron emission tomography.

Positron emission tomography in combination with the newly introduced catecholamine analogue [11C]hydroxyephedrine ([11C]HED) enables the noninvasive delineation of sympathetic nerve terminals of the heart. To address the ongoing controversy over possible reinnervation of the human transplant, 5 healthy control subjects and 11 patients were studied after cardiac transplant by this imaging approach. Regional [11C]HED retention was compared to regional blood flow as assessed by rubidium-82. Transplant patients were divided into two groups. Group I had recent (less than 1 yr, 4.4 +/- 2.3 mo) surgery, while group II patients underwent cardiac transplantation more than 2 yr before imaging (3.5 +/- 1.3 yr). [11C]HED retention paralleled blood flow in normals, but was homogeneously reduced in group I. In contrast, group II patients revealed heterogeneous [11C]HED retention, with increased uptake in the proximal anterior and septal wall. Quantitative evaluation of [11C]HED retention revealed a 70% reduction in group I and 59% reduction in group II patients (P less than 0.001). In group II patients, [11C]HED retention reached 60% of normal in the proximal anterior wall. These data suggest the presence of neuronal tissue in the transplanted human heart, which may reflect regional sympathetic reinnervation.

Search for the rare decay B-->pil+ l-.

We have performed a search for the flavor-changing neutral-current decays B-->pil+ l-, where l+ l- is either e+ e- or mu+ mu-, using a sample of 230 x 10(6) Upsilon(4S)-->BB decays collected with the BABAR detector. We observe no evidence of a signal and measure the upper limit on the isospin-averaged branching fraction to be B(B-->pil+ l-)<9.1 x 10(-8) at 90% confidence level. We also search for the lepton-flavor-violating decays B-->pie+/- mu-/+ and measure an upper limit on the isospin-averaged branching fraction of B(B-->pie+/- mu-/+)<9.2 x 10(-8) at 90% confidence level.

Prevalence of biopsy-proven non-alcoholic fatty liver disease in severely obese subjects without metabolic syndrome.

Obesity is a major risk factor for non-alcoholic fatty liver disease (NAFLD). NAFLD encompasses simple fatty liver (FL) and non-alcoholic steatohepatitis (NASH) in its spectrum. NASH can progress to liver cirrhosis and is associated with liver cancer. Not all obese subjects have insulin resistance (IR) or develop metabolic syndrome (MS). This study evaluates the prevalence of NAFLD in severely obese subjects without MS. We retrospectively reviewed 445 charts from our database of severely obese subjects with clinical suspicion of NAFLD and who were selected for laparoscopic Roux-en-Y gastric bypass surgery. One hundred five subjects who did not have MS, as defined by the International Diabetes Foundation, based on comprehensive pre-operative metabolic evaluation were included. Liver biopsy specimens were evaluated for NAFLD. 24% of morbidly obese (mean body mass index [BMI] 48 kg m(-2) ) adult subjects (mean age 38 years) who underwent bariatric surgery did not have MS. NAFLD was identified in 77 (73%) on liver biopsy, out of which 59 (56%) were labelled as FL and 18 (17%) had histological diagnosis of NASH. Age, gender, race and BMI were the same among all groups. Among NAFLD subjects, 22% did not have any additional metabolic component of MS, while 36% had low high-density lipoprotein, 27% had hypertension, 8% had high triglycerides and 6% had hyperglycaemia. IR calculated by HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) and diagnosis of hyperglycaemia was statistically higher in NASH group compared to those who did not have NASH. NAFLD is highly prevalent in morbidly obese individuals who undergo bariatric surgery despite the absence of MS. Diagnosis of hyperglycaemia in such subjects suggests the presence of IR and may have underlying NASH, which is a progressive form of NAFLD.

Intramural methotrexate therapy for the prevention of neointimal thickening after balloon angioplasty.

OBJECTIVES: The study was performed to test the hypothesis that high local, intramural concentrations of antineoplastic agents at the site of balloon injury inhibit vascular smooth muscle cell proliferation without systemic toxicity. BACKGROUND: The predominant mechanism for recurrent stenosis after coronary balloon angioplasty is neointimal thickening due to medial smooth muscle cell proliferation. The clinical use of potent antiproliferative agents to prevent restenosis has been limited by the potential for severe systemic side effects. Local therapy with these agents may be effective and free of systemic complications. METHODS: After bilateral balloon angioplasty of the carotid arteries of 14 juvenile farm pigs, the dilated arterial segments were treated locally with methotrexate (6.25 mg/ml, total dose 25 mg) or 0.9% saline solution through a perforated balloon catheter. The animals were then killed 30 days after balloon injury to determine the effects of this therapy on neointimal thickness. In an additional six animals, tritium-labeled methotrexate was used to determine the concentration and duration of detectability of methotrexate in the wall of the treated arteries and in the systemic circulation. RESULTS: Two hours after drug instillation the concentration of labeled drug was greater than 1,000-fold greater in the wall of the treated artery than in circulating blood, and this ratio remained between 50 and 100 for at least 7 days. Despite this difference, the mean intimal thickness 30 days after the procedure was similar in the 10 methotrexate-treated arteries and the 18 saline-treated arteries (59 +/- 30 vs. 56 +/- 25 microns, p = 0.6). The morphologic appearance of the neointima was similar in each group and suggested an important role for mural thrombus in the genesis of the intimal thickening. CONCLUSIONS: Treatment with intramural methotrexate, delivered through a perforated balloon catheter at the selected concentration and total dose, failed to prevent intimal thickening after balloon injury. Nonetheless, the perforated balloon catheter appears to be a promising means of delivering a high local concentration of drugs with potentially life-threatening systemic side effects. The optimal concentrations and combinations of candidate drug therapies warrant further evaluation.

Superoxide dismutase does not cause scar thinning after myocardial infarction.

Previous studies demonstrated that treatment with superoxide dismutase, a scavenger of superoxide anions, limits the extent of myocardial injury in a canine preparation of regional myocardial ischemia and reperfusion. Little is known, however, about the effects of superoxide dismutase on the healing of a myocardial infarct. Therefore, this study was performed to determine whether treatment with superoxide dismutase during myocardial ischemia impairs formation of scar tissue after infarction. Dogs received 2 hour infusions of superoxide dismutase or albumin (controls) by way of the left atrium beginning 15 minutes before and ending 15 minutes after a 90 minute occlusion of the left circumflex coronary artery. Six weeks later the animals were killed. Two-dimensional echocardiography was performed before surgery and before induced death. Wall thickening in the central ischemic zone was decreased at 6 weeks compared with baseline studies (p less than 0.05), but the decrease was similar for both groups. The hydroxyproline concentrations (microgram/mg dry weight) of the scar tissue in the superoxide dismutase and control groups, respectively, were 35.3 +/- 3.8 and 28.7 +/- 5.0 (p less than 0.05). The ratios of the scar thickness to normal wall thickness were superoxide dismutase 0.91 +/- 0.03 and control 0.89 +/- 0.03 (p greater than 0.05). Thus, superoxide dismutase had no adverse effect on wall thickening or scar formation assessed 6 weeks after myocardial infarction, and may be useful to limit oxygen radical-mediated damage during reperfusion of the ischemic myocardium.

Induction of Lipid and Oleosin Biosynthesis by (+)-Abscisic Acid and Its Metabolites in Microspore-Derived Embryos of Brassica napus L.cv Reston (Biological Responses in the Presence of 8[prime]-Hydroxyabscisic Acid).

Microspore-derived (MD) embryos of Brassica napus L. cv Reston were used to test the effects of (+)-abscisic acid ([(+)-ABA]) and its metabolites, 8[prime]-hydroxyabscisic acid (8[prime]-OH ABA) and (-)-phaseic acid (PA), on the accumulation of very long-chain monounsaturated fatty acids (VLCMFAs) and induction of genes encoding a 19-kD oleosin protein and a [delta]15 desaturase during embryogenesis. Developing early to mid-cotyledonary MD embryos at 16 to 19 d in culture were treated with 10 [mu]M hormone/metabolite for 4 d. At various times during incubation, embryos and medium were analyzed to determine levels of hormone/metabolite, VLCMFAs, and oleosin or [delta]15 desaturase transcripts. The VLCMFAs, 20:1 and 22:1, primarily in triacylglycerols, increased by 200% after 72 h in the presence of (+)-ABA and 8[prime]-OH ABA relative to the control. In contrast, treatment with PA for 72 h had little effect (20% increase) on the level of VLCMFAs. The first 24 to 72 h of (+)-ABA treatment were critical in the induction of VLCMFA biosynthesis, with 8[prime]-OH ABA lagging slightly behind (+)-ABA in promoting this response. The accumulation of VLCMFAs was positively correlated with an increase in elongase activity. (+)-ABA and its 8[prime]-OH ABA metabolite induced the accumulation of a 19-kD oleosin transcript within 2 to 4 h in culture. In addition, both (+)-ABA and 8[prime]-OH ABA induced the same level of [delta]15 desaturase transcript by 8 h. PA had no effect on the induction of either oleosin or [delta]15 desaturase transcripts. To our knowledge, this is the first report of the biological activity of 8[prime]-OH ABA and of stimulatory effects of (+)-ABA and 8[prime]-OH ABA on lipid and oleosin biosynthesis.

Neurotensin neurons in the rat hypothalamus: an immunocytochemical study.

Neurotensin was localized in the hypothalamic tissues of adult Sprague-Dawley rats by immunoperoxidase techniques. Visualization of perikarya was greatly enhanced by intraventricular administration of colchicine. Many perikarya containing neurotensin-like immunoreactivity were seen in the medial preoptic area, the periventricular hypothalamus, the parvocellular portion of the paraventricular nucleus, the arcuate nucleus, and the lateral hypothalamus in the perifornical area. There were moderate numbers of cell bodies in the ventral portion of the anterior hypothalamus, the dorsomedial nucleus, and the posterior hypothalamus. No positive cells were seen in the suprachiasmatic, ventromedial, or mammillary nuclei. Reactive fibers were generally distributed in the same regions as cell bodies. Additional dense collections were seen in the lateral part of the zona externa of the median eminence, the pituitary stalk, the posterior mammillary nucleus, and the most lateral portions of the hypothalamus at the medial edge of the crura cerbri. There were smaller numbers of fibers found in the pre-mammillary and posterior hypothalamic nuclei and the posterior pituitary gland. These results indicate that the neurotensin system in the hypothalamus is very extensive and complex, as it is in many other brain regions. Neurons and fibers are found in many hypothalamic areas, including projections to the hypophysial portal system in the median eminence, suggesting that neurotensin may affect neuroendocrine mechanisms at several levels, including the anterior pituitary gland.

The luteinizing hormone-releasing hormone pathways in rhesus (Macaca mulatta) and pigtailed (Macaca nemestrina) monkeys: new observations on thick, unembedded sections.

Immunocytochemical procedures on thick, unembedded tissue sections were used to study the localization of LHRH neurons and fibers in the diencephalon and mesencephalon of rhesus and pigtailed macaques. Cell bodies were visualized in large numbers. Much of their dendritic arborization was also filled with reaction product. Cell bodies were present in the preoptic area, the periventricular hypothalamic zone from the level of the anterior hypothalamus to the premammillary nuclei, the infundibular nucleus, supraoptic nucleus, several septal nuclei, the nervus terminalis, and the amygdala. The localization of LHRH cells in several of these areas represents new observations. LHRH axons were observed to innervate the portal vessels in the median eminence, the organum vasculosum of the lamina terminalis, the median eminence, the organum vasculosum of the lamina terminalis, the medial mammillary nuclei, the epithalamus, and the amygdala. These observations are discussed in relationship to the regulation of gonadotropin secretion in the primate.

Hypothalamic or central obesity is associated with an early rise in plasma insulin concentration.

Insulin levels in a 7-year-old boy with hyperphagia and obesity following an episode of meningoencephalitis were studied sequentially during the course of progressive weight gain. High fasting insulin levels (1183 pmol/L) and strikingly high insulin release in response to glucose (7892 pmol/L) were found within weeks of the onset of the illness. The abnormality in insulin secretion occurred prior to the marked weight gain. Hyperinsulinemia was not accompanied by hypoglycemia. Early hyperinsulinemia may be a primary event in the development of hyperphagia and obesity following hypothalamic injury.

Landry-Guillain-Barré syndrome with abnormal pupils and normal eye movements: a case report.

A 66-year-old woman with acute idiopathic polyneuritis (Landry-Guillain-Barré [LGB] syndrome) had normal extraocular movements, but her pupils did not react to light or accommodation. This is the first such case to be reported. Pharmacologic testing pointed to postganglionic involvement of parasympathetic and sympathetic nerves.

Hypothalamic oxytocin: a cerebrovascular modulator in man?

Immunocytochemical studies in normal rats show an association between oxytocin (OT) neurons and cerebral blood vessels. This is supported by the finding of neurophysin (NP) immunoreactivity in blood vessels and pia-arachnoid tissue of rats with hereditary vasopressin (VP) and VP-NP deficiency. OT and OT-NP fibers were visualized in pia-arachnoid and blood vessels at the base of the brain and, to a lesser extent, over the dorsal surface. OT constricts human basilar artery with a threshold response in the 10(-10) M range, and an ED50 of 4.8 X 10(-9) M. These observations suggest that extrahypothalamic projections of OT neurons may modulate cerebrovascular function.

Immunocytochemical studies of human peripheral nerve with serum from patients with polyneuropathy and paraproteinemia.

Immunohistochemical binding of IgM paraproteins to nerve was studied using the immunoperoxidase technique with serum from 10 patients with benign plasma cell dyscrasia and neuropathy. We stained the myelin sheaths of peripheral nerves and roots fo five patients who had myelin-absorbable IgM paraproteins. Two patients with IgM paraproteins that did not react with myelin showed predominant staining of axons, while three were completely negative. Serum specimens from normal volunteers and patients with paraproteinemias or ALS were also unreactive. Immunocytochemical methods can detect IgM paraproteins with an affinity for nerve antigens and may assist in the diagnosis and classification of plasma cell dyscrasia associated neuropathy.

Cerebral cysticercosis.

Five patients with cerebral cysticercosis, two within the year preceding the date of this article, were seen at the New York Neurological Institute. The patients presented with mental changes, seizures, and symptoms of increased intracranial pressure, and had a history of having immigrated from an area endemic for cysticercosis. They were found to have parenchymal or intraventricular cysticercosis cysts. The interval from immigration to onset of symptoms was as long as 3 years. Plain radiograms of the skull and soft tissues, ventriculograms, and especially the CT scan, as well as the CSF examination, were useful in making the diagnosis. Surgical removal of an intraventricular cyst was curative in two patients and seizures were controlled with anticonvulsants in the other three.

Immunocytochemical distribution of corticotropin (ACTH) in monkey brain.

The distribution of adrenocorticotropin (ACTH) in monkey brain was examined by immunoperoxidase immunohistochemistry. An antiserum to ACTH that recognized the C-terminal portion of the molecule was used. Immunoreactive ACTH was visualized as an intraneuronal constituent with a widespread distribution throughout the brain. Reactive cell bodies were seen only in the region of the arcuate nucleus of the hypothalamus. Dense axonal networks were seen in the hypothalamus, mesencephalic gray, and in the region around the anterior commissure. No staining was seen in the cerebral cortex, cerebellum, hippocampus, or striatum. ACTH or fragments of ACTH may function as neurotransmitters or neuromodulators in primate brain.

Neuropathy and anti-MAG antibodies without detectable serum M-protein.

Anti-MAG IgM antibodies were detected by ELISA in a patient with slowly progressive peripheral neuropathy. Serum IgM content was normal, and no M-protein was detected by serum protein electrophoresis, immunoelectrophoresis, or immunostaining. By immunoblot analysis, the anti-MAG antibodies were IgMk; they reacted with human and bovine MAG but not with mouse MAG. The data suggest that there was an anti-MAG IgM M-protein in concentration too low to be detected by conventional techniques. Tests for anti-MAG antibodies should be done in patients with slowly progressive neuropathy of unknown etiology, even in the absence of detectable serum M-protein.