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Biomedical subjects

L Singer

Publications and source records attributed to L Singer.

At least 19 recordsLinked to original sources

Cis- and trans-acting elements required for constitutive and cytokine-regulated expression of the mouse complement C3 gene.

The third component of complement (C3) is an important mediator of inflammation. Murine and human genomic cosmid clones were isolated, characterized and sequenced 5' to the complement C3 gene transcriptional initiation sites to determine cis elements that participate in constitutive and regulated C3 gene expression. The murine and human 5' flanking regions are 51% identical overall, with positions -36 to -1 and -146 to -68 showing 80% identity. Four TATA boxes were identified upstream of the murine transcriptional initiation site, but deletion and transfection analysis using reporter gene constructs in HepG2 cells indicated that only the TATA element at position -30, together with sequences -395 to -111, are essential for constitutive expression of murine C3 in hepatocytes. Deletion analysis also suggested that sequences between -1457 and -800 contain regulatory elements that are involved in suppressing basal expression. Sequences between -90 to -41 confer both enhancer activity and interleukin-1/-6 (IL-1/IL-6)-responsiveness. Mutation analyses showed that both sequences between -88 and -83 and -77 to -72 are essential for enhancer activity and responsiveness to IL-1, but only sequences between -88 and -83 are necessary for IL-6-responsiveness. A gel-retardation assay showed that several nucleoproteins, perhaps of the C/EBP family, from HepG2 cells bound to sequences between -88 to -83. Collectively, these results localize cis-acting elements involved in constitutive and IL-1/IL-6-regulated murine C3 gene expression and provide evidence for specific transacting factors.

Animals

Effects of chlorpromazine and lorazepam on explicit memory, repetition priming and cognitive skill learning in healthy volunteers.

To assess the influence of neuroleptics on explicit memory and two forms of implicit memory, repetition priming and cognitive skill learning, the effects of two low doses of chlorpromazine (12.5 and 25 mg orally) were contrasted to those of lorazepam (2.5 mg orally) and of a placebo using a free-recall task, a word-completion task and repeated testing on the Tower of Toronto puzzle, a version of the Tower of Hanoi puzzle. Seventy-two healthy volunteers took part in this double-blind study. Chlorpromazine spared free-recall and word-completion performance, but impaired the acquisition of a cognitive routine in the subjects who completed the first trials of the Tower of Toronto puzzle efficiently. Lorazepam induced an opposite pattern of memory disruption. These preliminary results suggest that chlorpromazine and lorazepam induced a double dissociation between priming and the acquisition of a cognitive routine. They provide evidence that the two forms of implicit memory rely upon distinct neurochemical systems, the latter, but not the former, being dependent upon dopaminergic systems.

Adult

Differential effects of diazepam and lorazepam on repetition priming in healthy volunteers.

The effects of two benzodiazepines, diazepam (15 or 20 mg orally) and lorazepam (1.75 or 2.5 mg orally), and a placebo on explicit memory, lexical priming and perceptual priming were assessed using a free-recall, a word-completion and a picture-completion test. The picture-completion test included two different study conditions intended to manipulate the magnitude of the priming effect. Sixty healthy volunteers took part in this double-blind study. Free-recall performances were altered by both drugs. Lorazepam impaired word-completion and picture-completion performance, whereas diazepam only exhibited a deleterious effect on the more sensitive of the two measures of the picture-completion test. These results indicate that the two benzodiazepines have differential amnestic effects. It is suggested that these differential effects could be accounted for by a different cortical distribution of the two benzodiazepines.

Adult

Childhood medical and behavioral consequences of maternal cocaine use.

Reviewed available studies of the impact of fetal cocaine exposure on child medical and developmental outcome, as well as the current status of clinical psychological interventions and research strategies. Current studies are inconclusive but suggest that prenatal exposure to crack-cocaine can have significant effects on the growth and neurological development of the infant, with the potential of later learning and behavioral disabilities. Social-environmental correlates of maternal cocaine use are confounding factors with known negative effects on child outcome. Large, population-based studies using multivariate analyses are needed to determine the independent effects of cocaine on child outcome relative to other confounding variables.

Child, Preschool

Pediatric management of Robin sequence.

The care of infants with Robin sequence is discussed with special reference to upper airway obstruction and feeding difficulties. The use of nasopharyngeal tubes is recommended initially to alleviate the immediate consequences of hypoxia. Modifications in feeding procedures are minor and involve enlarging the hole in the nipple and keeping the nipple and infant positioned appropriately.

Airway Obstruction

Upper airway obstruction and the Robin sequence.

Both the etiology of Robin sequence and the mechanisms of upper airway obstruction are heterogeneous. As a result, generalizations about the care of newborns with the combination of micrognathia, cleft palate, and airway obstruction cannot be made. Management of the airway obstruction should be based on the results of direct endoscopic observation of the site of obstruction and not on the presumptive diagnosis of glossoptosis. It should not be assumed that "catch-up growth" of the mandible will occur and lead to spontaneous resolution of either the airway obstruction or the micrognathia. The presentation of the child with Pierre Robin sequence should not be the end of the diagnostic search, but rather the beginning.

Airway Obstruction

Pharyngeal flap surgery: postoperative complications.

Using a protocol specifically designed to decrease the risk factors for postoperative morbidity and upper airway obstruction, we have essentially eliminated major complications after pharyngeal flap surgery while maintaining excellent speech results. The protocol includes inserting a short pharyngeal flap into a tissue "sandwich" and keeping an NP tube in place for 48 hours postoperatively. The complications reduced by use of this protocol include apnea and other upper respiratory complications, as well as bleeding. In addition, postoperative discomfort is decreased with the current protocol. Using this approach, pharyngeal flap surgery is highly effective in improving speech and is associated with low morbidity.

Adolescent

Oxygen desaturation complicates feeding in infants with bronchopulmonary dysplasia after discharge.

Recurrent episodes of hypoxemia may affect the growth, cardiac function, neurologic outcome, and survival of infants with bronchopulmonary dysplasia (BPD). As oral feeding might stress these infants by compromising pulmonary function even after hospital discharge, we measured oxygen saturation (SaO2) via pulse oximetry before, during the initial 10 minutes of, and immediately after oral feeding in 11 patients with BPD, 12 very low birth weight infants, and 23 healthy full-term infants. All infants with BPD had been previously discharged from the hospital after weaning from supplemental oxygen. Studies were done at a mean postconceptional age of 43 weeks while the infants were fed at home by one of their parents. Levels of SaO2 for the three groups were comparable before and during feeds. After feeding, the infants with BPD had significantly lower mean levels of SaO2 (84 +/- 8% [SD] vs 93 +/- 4% and 93 +/- 3%, respectively; P less than .01). They also spent more time after feeding with an SaO2 less than 90% (64 +/- 34% of time vs 27 +/- 33% for the very low birth weight and 22 +/- 20% for the term group; P less than .01) and greater time with an SaO2 less than 80% (37 +/- 28% vs 4 +/- 10% and 4 +/- 8%, respectively; P less than .01). Desaturation in infants with BPD was related to larger volume and faster oral intake during feeding. Thus, the data indicate that desaturation after feeding remains a recurrent problem for survivors of BPD after discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Weight

Explicit memory and repetition priming in depression. Preliminary findings.

Explicit memory and repetition priming, a form of implicit memory, were examined in depressed patients and controls. Explicit memory of depressed patients was severely impaired, whereas repetition priming was intact. These results are consistent with the hypothesis that the impairment of memory in depression is linked to a failure of effort-demanding cognitive processes. Repetition priming might be useful in differentiating between depression and dementia.

Dementia

Intraventricular insulin reduces food intake and body weight of marmots during the summer feeding period.

The study presented below describes experiments that investigate the ability of insulin to inhibit food intake in awake, active marmots during the summer season. Our results suggest that increasing intraventricular insulin concentration during the summer active feeding period will cause a decrease in food intake and body weight of marmots. When infused with insulin into their lateral ventricles (Alzet #2002 minipumps), animals had significantly lower food intake as compared to their food intake during the control period. In addition, these animals lost body weight during the period of the insulin infusion. We suggest that during the summer when marmots are not hibernating and are actively feeding, brain insulin levels may play a role in regulating food intake.

Adipose Tissue

Seasonal changes in CSF insulin levels in marmots: insulin may not be a satiety signal for fasting in winter.

Plasma insulin (PI) reportedly crosses the blood-brain barrier in mammals and acts with the central nervous system (CNS) to reduce food intake. Animals that hibernate (hibernators) eat little or no food from early winter (November) to spring (April). This lack of food intake may be due to elevated PI concentrations acting within the CNS. In this study, we determined whether hibernators have altered insulin levels within the CNS at different times during the circannual cycle of metabolism and feeding. Plasma and cerebrospinal fluid (CSF) immunoreactive insulin concentrations were measured in marmots (Marmota flaviventris) during the feeding phase of the body weight cycle and during the fasting period (hibernation). Basal plasma and CSF samples were collected in September, November, January, and April. In addition, plasma and CSF insulin levels were monitored during a 2-h intravenous infusion of glucose (20% wt/vol) that stimulated pancreatic B-cell production of insulin. During the spring feeding period, we found that as PI levels rise, so do CSF insulin concentrations. However, in fall and winter when marmots are fasting, very little insulin entered the CSF even when PI levels were significantly elevated. Furthermore, the longer the fast, the lower was the CSF insulin under both basal and infusion conditions. These results lead us to conclude that elevated CSF insulin is not a likely cause of suppressed food intake in fasting marmots.

Animals

Effects of scopolamine, trimipramine and diazepam on explicit memory and repetition priming in healthy volunteers.

The effects of scopolamine, an anticholinergic drug, of trimipramine, a tricyclic antidepressant with both anticholinergic and sedative properties, of diazepam and a placebo, on explicit memory and repetition priming were assessed using a free-recall task and a word-stem completion task. Forty-eight healthy volunteers took part in this double-blind study. Diazepam provoked a dissociation between free recall, which was profoundly impaired, and word completion, which was spared. No significant changes in memory performances were observed in the scopolamine group; however, a significant correlation between explicit and implicit memory performances was observed in this group. At the low dose used, the effects of trimipramine on memory were mild. The results suggest that the cholinergic system is involved in the priming effect.

Adult

Diazepam induces a dissociation between explicit and implicit memory.

The effects of 0.2 mg/kg orally administered diazepam and of a placebo on explicit memory, implicit and knowledge memory were assessed using a free recall task, a word-stem completion task and two category-generation tasks. Twenty four healthy volunteers took part in this double-blind study. Diazepam impaired explicit but not implicit memory. The drug also spared knowledge memory. Explicit memory was linked with the diazepam-induced sedation and with the self-rated affective load of to-be remembered words, but implicit memory was not. The diazepam-induced dissociation between explicit and implicit memory supports the notion of two distinct forms of memory and reproduced the dissociation observed in organic amnesia.

Adult

Psychological practice in a pediatric rehabilitation hospital.

Described 127 consecutive referrals to a newly formed psychological consultation service in a pediatric rehabilitation hospital. This setting served children whose needs for comprehensive care and long-term hospitalization could not be met effectively elsewhere in the community. The complex patient population included children with permanent mental and/or physical handicaps who had survived due to advances in medical technology, those with traumatic or congenital brain injury, failure to thrive, feeding problems, apnea, tracheostomy, child abuse, and psychosomatic disorders. A range of psychological services were offered, including specialized assessments and treatment planning for rehabilitation, home and school placement, direct treatment and monitoring of behavioral progress, and consultation with staff. Implications for the practice of pediatric psychology and service delivery to patients in pediatric rehabilitation settings are discussed.

Adolescent

Vitamin A in Stevens-Johnson Syndrome.

A 9-year-old boy was admitted to the Pediatric Department with high fever, severe photophobia, and a rash on his face, eyelids, and neck. Two days before admission he received injections of penicillin. During the night his general condition worsened, and his fever rose to 40 degrees C. He began to hallucinate, and clear fluid-filled blisters appeared on his skin and mouth. Severe photophobic epiphora, conjunctival injection, and punctate keratitis were also observed. Several hours after local administration of corticosteroids and antibiotic eye drops, his eyelids swelled severely, the corneas became covered by pseudomembranes, and later, in attempting to open the eyelids, the skin peeled off and the eye lashes fell out. Treatment consisted of artificial tear eye drops, and intravenous antibiotics and steroids. His condition improved gradually, visual acuity became 6/15 in both eyes, and a superficial punctate staining of the cornea was observed. The Schirimer test showed lacrimal hyposecretion. A tarsal conjunctival biopsy showed a complete absence of goblet cells. Vitamin A was administered topically and systemically. After three months of treatment with Vitamin A, tear secretion was almost normal, and conjunctival biopsy indicated a regeneration of goblet cells.

Adrenal Cortex Hormones