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Biomedical subjects

R Dawson

Publications and source records attributed to R Dawson.

At least 19 recordsLinked to original sources
PubMed1997

Attenuation of leptin-mediated effects by monosodium glutamate-induced arcuate nucleus damage.

Leptin is a protein secreted by adipocytes that is important in regulating appetite and adiposity. Recent studies have suggested the presence of leptin receptors in the arcuate nucleus of the hypothalamus (ANH). Neonatal administration of monosodium glutamate (MSG) damages the ANH, resulting in obesity and neuroendocrine dysfunction. Neonatal administration of MSG was utilized to test the hypothesis that the anatomic site for many of leptin's actions is the ANH. Female control (n = 6) and MSG-treated rats (n = 7) were implanted for 14 days with osmotic minipumps containing phosphate-buffered saline or leptin (1 mg.kg-1.day-1). Leptin suppressed (P < 0.05) body weight gain in controls but did not suppress weight gain in MSG-treated rats. Leptin decreased (P < 0.05) fat depots in controls but had no effect in MSG-treated rats. Night feeding was suppressed (P < 0.05) in leptin-treated control rats. MSG-treated rats showed a suppression in food intake that was of a smaller magnitude and appeared later in the course of leptin treatment. These findings suggest that leptin mediates some physiological actions related to fat mobilization via receptors located in the ANH.

Adipose Tissue↗
PubMed1997

Determinants of behavior in homeless and low-income housed preschool children.

OBJECTIVES: To describe the characteristics of homeless and low-income preschool-aged children, and to identify family and environmental determinants of their behavior. METHODS: An unmatched case-control design was used to recruit a sample of sheltered homeless families and a comparison group of low-income housed families who were never homeless in Worcester, Massachusetts. Seventy-seven sheltered homeless and 90 low-income housed mothers with preschool-age children were assessed using a comprehensive interview protocol. Information about mothers' housing, income, service use, par-enting practices, and children's father was obtained. Data about children's background, health, and life events were included. Standardized instruments were administered to assess mothers' mental health and their children's behavior. Comparisons of homeless and low-income housed families were used to describe the sample of 167 preschoolers. Multiple linear regression was used to examine the association of various stressors, such as homelessness, and family factors with their behavior. RESULTS: Although homeless preschoolers were significantly more likely to have experienced stressful life events, undergone a care and protection investigation, and been placed in foster care when compared with low income preschoolers, differences in adverse behaviors were minimal. Although homeless children scored higher than housed children on the internalizing, externalizing, and total problem score on the Child Behavior Checklist (CBCL) (52.5 vs 49.9, 54.8 vs 51.2, and 54.4 vs 51.1, respectively), approximately equal numbers of children from both groups scored in the clinical range. With regard to determinants of behavior, mothers' emotional status was one of the strongest independent predictors of negative behavioral outcomes on both subscales. Foster care placement and death of a child's friend were predictors of adverse internalizing behavioral outcomes on the CBCL. After controlling for housing status, parenting practices, child's age, child's history of physical abuse, and specific life stressors predicted adverse externalizing behavioral outcomes. For both subscales, housing status and behavior were only marginally associated in the multivariate model. CONCLUSIONS: Both homeless and low-income children experienced significant adversity in their lives, with homeless preschool children facing more stress. However, differences in behavior as measured by the CBCL were minimal. Mothers' emotional status, in addition to various stressors, strongly predict children's negative outcomes for both CBCL subscales. These findings emphasize the importance of preventive family-oriented interventions that address the needs of preschoolers and their mothers.

Black or African American↗
PubMed1997

Homelessness in female-headed families: childhood and adult risk and protective factors.

OBJECTIVES: To identify risk and protective factors for family homelessness, a case-control study of homeless and low-income, never-homeless families, all female-headed, was conducted. METHODS: Homeless mothers (n = 220) were enrolled from family shelters in Worcester, Mass. Low-income housed mothers receiving welfare (n = 216) formed the comparison group. The women completed an interview covering socioeconomic, social support, victimization, mental health, substance use, and health domains. RESULTS: Childhood predictors of family homelessness included foster care placement and respondent's mother's use of drugs. Independent risk factors in adulthood included minority status, recent move to Worcester, recent eviction, interpersonal conflict, frequent alcohol or heroin use, and recent hospitalization for a mental health problem. Protective factors included being a primary tenant, receiving cash assistance or a housing subsidy, graduating from high school, and having a larger social network. CONCLUSIONS: Factors that compromise an individual's economic and social resources are associated with greater risk of losing one's home.

Adolescent↗
PubMed1997

Effects of a carfentanil-xylazine combination on cardiopulmonary function and plasma catecholamine concentrations in female bongo antelopes.

OBJECTIVE: To determine the effects of an i.m. administered carfentanil-xylazine combination on cardiopulmonary variables and plasma catecholamine concentrations and to validate use of pulse oximetry in bongo antelopes. ANIMALS: 8 healthy adult females. PROCEDURE: Antelopes were immobilized with carfentanil citrate (8.3 micrograms/kg of body weight, i.m.) and xylazine hydrochloride (0.79 mg/kg, i.m.). Hematologic values and plasma biochemical and catecholamine concentrations were determined at the beginning and end of immobilization. Immediately after induction of immobilization and every 15 minutes thereafter, cardiopulmonary variables were determined. RESULTS: Induction time after carfentanil-xylazine administration was 6 +/- 2 minutes. At 15 and 45 minutes after immobilization and thereafter, significant decrease in heart and respiratory rates, respectively, were observed. After 15 minutes of immobilization, all antelopes had developed mild hypoxemia, which resolved after nasal insufflation with 100% oxygen. Pulse oximetry readings underestimated arterial blood gas values, but reliably indicated trends in arterial oxygen desaturation. Antelopes developed hypoxemia after oxygen administration was terminated at the end of the procedure, prior to reversal of immobilization. Norepinephrine concentrations increased significantly (P < 0.05), and 3,4-dihydroxyphenylacetic acid concentrations decreased significantly at the end of the anesthetic event. Immobilization of all antelopes was reversed, using antagonists naltrexone and yohimbine hydrochloride. Time to standing was 3 +/- 1 minutes, and renarcotization was not observed. CONCLUSIONS AND CLINICAL RELEVANCE: The carfentamil-xylazine combination at the dosage used induced hypoxemia, pronounced arterial hypertension, and significant increase in plasma norepinephrine and decrease in plasma 3,4-dihydroxyphenylacetic acid concentrations in bongo antelopes. Supplemental administration of oxygen is recommended. Pulse oximetry is a useful tool to monitor trends in arterial oxygen desaturation, but does not substitute for arterial blood gas analysis.

Analgesics, Opioid↗
PubMed1996

CD59 and CD48 expressed by rat retinal pigment epithelial cells are major ligands for the CD2-mediated alternative pathway of T cell activation.

The alternative CD2-mediated pathway of T cell activation, which is independent of MHC/peptide recognition by the TCR/CD3 complex, is dependent upon two signals being received by the CD2 molecule. The natural ligand for CD2 is CD58, but controversy exists over alternative or additional ligands that could deliver the second signal in vivo. We have used rat retinal pigment epithelial cells (RPE), which lack temperature-insensitive ligands for CD2 adhesion, to study Ag-independent T cell activation. Rat RPE cells expressed high levels of CD59 and low levels of another potential CD2 ligand, CD48, both in vitro and in the in vivo model of experimental autoimmune uveoretinitis. When increasing numbers of syngeneic T cells were added to microwell cultures of rat RPE cells, the T cells, even in the absence of any exogenous stimulant in the cultures, underwent spontaneous proliferation. This effect required metabolically active RPE cells, and was IL-2 driven and enhanced in the presence of indomethacin. Proliferation was modulated by phosphatidylinositol-phospholipase C treatment of the RPE, and blocked by mAbs to CD59. Ab cross-linking of CD48 but not CD59 on the RPE was found to induce messenger RNA expression for IL-1 beta, which together with constitutively expressed IL-6 are required costimulatory factors for T cell activation through CD2. This is the first demonstration in a fully syngeneic system that bi-directional signaling involving CD59 and CD48 molecules expressed by physiologically normal, nonhematopoietic, cells can trigger T lymphocyte activation and proliferation through autocrine IL-2 production in the absence of Ag.

Animals↗
PubMed1996

Monitoring program for mycotoxin contamination in Uruguayan food and feeds.

A pilot study for monitoring mycotoxin contamination in food and feeds was implemented by the Technological Laboratory of Uruguay (LATU) with the technical assistance of the Food and Agriculture Organization of the United Nations (FAO). The scope of the study was to determine the potential hazard posed by priority food-contaminant and feed-contaminant combinations. The choice of foods and contaminants to be monitored was based on the importance of the food in the total diet, the economic importance of the product and the potential health risk posed by the specific combination. The principal commodities selected were wheat, barley and rice. Also included were com, soy, dairy products, feeds, dried fruits and legumes, oil seeds, cocoa beans and organ meats. Mycotoxins analyzed (TLC/densitometry) were aflatoxins, zearalenone, ochratoxin A, deoxynivalenol (DON) and ergot alkaloids. The survey results (1993-95) showed differences in both incidence and levels of mycotoxin content for the principal commodities. Of all food/feed categories analyzed, feed had the highest values for all mycotoxins. Samples containing DON in levels above 1000 ng/g were found in all groups. Ochratoxin A was not detected in any of the samples. Rice and soy beans were the categories with lowest aflatoxin incidence. Uruguayan regulatory limits for all toxins analyzed were exceeded for wheat, barley and rice in less than 3, 9 and 7% of samples, respectively. The data on actual mycotoxin levels in different foods will help identify sources of contaminations and areas where control measures should be improved, enable better risk assessment by proper estimation of mycotoxin intake, assist in the establishment of tolerances and adequate guidelines, aid in the implementation of a national program and provide economic benefits by improving grain quality.

Aflatoxins↗
PubMed1996

Isolated hyperthermic limb perfusion chemotherapy in Merkel cell tumour: a case report.

Merkel cell carcinoma of the skin is a rare malignant tumour first described in 1972 by Toker. The optimal management of this disease has not been clearly defined, especially that of advanced locoregional disease. Surgery, radiotherapy and chemotherapy have been advocated separately or in combination, with less-than-optimal results. Localized high-dose chemotherapy has never been tried, although it would seem to be the logical step forward.

Aged↗
PubMed1995

A multiple imputation strategy for clinical trials with truncation of patient data.

Clinical trials of drug treatments for psychiatric disorders commonly employ the parallel groups, placebo-controlled, repeated measure randomized comparison. When patients stop adhering to their originally assigned treatment, investigators often abandon data collection. Thus, non-adherence produces a monotone pattern of unit-level missing data, disabling the analysis by intent-to-treat. We propose an approach based on multiple imputation of the missing responses, using the approximate Bayesian bootstrap to draw ignorable repeated imputations from the posterior predictive distribution of the missing data, stratifying by a balancing score for the observed responses prior to withdrawal. We apply the method and some variations to data from a large randomized trial of treatments for panic disorder, and compare the results to those obtained by the original analysis that used the standard (endpoint) method.

Adult↗
PubMed1995

Excitotoxins, aging, and environmental neurotoxins: implications for understanding human neurodegenerative diseases.

We are an aging society and current demographic trends point to a likely increase in age-related neurodegenerative diseases. The aged population may have a number of unique risk factors that result in a predisposition to neuronal damage from environmental neurotoxins. This symposium addressed the involvement of excitatory amino acids as final common mediators of neuronal death associated with various types of neurotoxic insult. The roles of oxidative stress, mitochondrial energy metabolism, and disruption of calcium homeostasis were discussed in relation to excitoxicity and several experimental models of human neurodegenerative diseases. The neurotoxic actions of kainic acid, 3-nitropropionic acid, cyanide, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and methamphetamine were examined for their relevance as models of human neurodegenerative disorders. The mechanisms of action of excitotoxins in experimental models of Huntingtons's disease and Parkinson's disease were explored in light of the enhanced susceptibility and potential vulnerability of the aged nervous system to neurotoxins that perturb cellular metabolism and homeostatic processes. Bioenergetic defects and oxidative stress were found to be critical links in a neurotoxic cascade of events that trigger the sustained release of excitotoxic amino acids. The interrelationships among the aging process, the pathophysiology of neurodegenerative diseases, and the mechanism of action of various neurotoxins were addressed from the unifying perspective of the excitotoxic hypothesis of neuronal death.

Aging↗
PubMed1995

Endogenous excitatory amino acid release from brain slices and astrocyte cultures evoked by trimethyltin and other neurotoxic agents.

Trimethyltin (TMT) is a toxic alkyltin compound that is known to produce neuronal necrosis in the CNS. The present study examined the effects of TMT on the release of excitatory amino acids (EAA) from cortical slices prepared from adult and aged (24 months old) rats. The calcium dependence of TMT-induced EAA efflux was evaluated and compared to other neurotoxic agents. The actions of TMT were also evaluated in an astrocyte culture model to assess glial contributions to TMT-induced EAA efflux. TMT (10-1000 microM) evoked a dose-related increase in GLU and ASP efflux during a 30 min incubation period and this efflux was sustained or slightly higher during a 15 min recovery period. TMT-stimulated GLU efflux was not altered in aged rats. TMT-induced GLU efflux was significantly reduced by removing extracellular calcium and including 10 microM EGTA in the incubation media. Calcium channel blockers (nifedipine, verapamil, flunarizine, amiloride, neomycin) and MK-801 did not significantly attenuate TMT-induced GLU efflux. Diltiazem (25 microM) produced modest but inconsistent reductions in TMT-induced GLU efflux from brain slices, and significantly inhibited the leakage of lactate dehydrogenase (LDH) from TMT-treated astrocyte cultures. TMT did not increase GLU efflux from glial cultures during a 30 min incubation period, but did significantly elevate GLU efflux during the 15 min recovery period. TMT evoked the release of EAA by both calcium dependent and independent mechanisms in brain slices. TMT at high concentrations also produced a delayed increase in glial GLU efflux. These studies suggest that excitotoxic mechanisms may contribute to TMT-induced neurotoxicity.

Aging↗
PubMed1995

Glutamate efflux from rat brain slices and cultures: a comparison of the depolarizing agents potassium, 4-aminopyridine, and veratrine.

The major excitatory amino acid neurotransmitter in the mammalian brain is glutamate (GLU). GLU release from nerve terminals is both calcium-dependent and -independent, yet these mechanisms of release are not fully understood. Potassium, 4-aminopyridine (4-AP) and veratrine are commonly used depolarizing agents that were studied for their ability to stimulate GLU efflux from brain slices. These agents produced significant regional variations in GLU efflux from rat brain slices. Potassium was the most potent of the three secretogogues tested. 4-AP produced a significant GLU efflux only in the cerebellum. Veratrine produced consistent stimulation of GLU efflux from all brain regions tested. Potassium was the only depolarizing agent tested that stimulated GLU release from primary astroglial cultures of rat cerebral cortex. All three agents also demonstrated an ability to inhibit GLU reuptake in brain slice preparations. This data suggest that both GLU release and uptake are modulated in a regionally selective manner, and that commonly used depolarizing agents affect not only calcium-dependent neuronal release, but also uptake and glial responses.

4-Aminopyridine↗
PubMed1995

Mechanism of sodium nitroprusside-mediated inhibition of aromatic amino acid decarboxylase activity.

The effects of sodium nitroprusside (SNP) on dopamine synthesis in a porcine renal epithelial cell line (LLC-PK1) were evaluated. Subsequent studies examined the actions of the degradation products of SNP (cyanide, ferrous ion and nitric oxide) on aromatic amino acid decarboxylase (AAAD) activity in tissue supernatants from LLC-PK1 cells and rat renal cortex. SNP (10-500 mumol/l) significantly inhibited dopamine production in LLC-PK1 cells in a dose-related manner. The activation of guanylate cyclase by nitric oxide was not found to be the mechanism whereby SNP inhibited dopamine synthesis in LLC-PK1 nor did the antioxidant glutathione attenuate the actions of SNP. Ferrous sulfate (0.5 mmol/l) and SNP (0.5 mmol/l) were found to inhibit dopamine synthesis in LLC-PK1 cells and to directly inhibit cytosolic AAAD activity from LLC-PK1 cells. A series of studies were conducted using AAAD from rat renal cortex and confirmed that SNP could directly inhibit the conversion of L-dopa to dopamine by AAAD. Furthermore, potassium ferricyanide (1 mmol/l) and potassium cyanide (1 mmol/l) could produce greater than 80% reductions in AAAD activity. Iron (0.5-1 mmol/l) was found to increase rat kidney AAAD activity. Kinetic analysis revealed that potassium cyanide was a potent (Ki = 40-50 mumol/l) noncompetitive/mixed noncompetitive inhibitor of AAAD. SNP was also found to be a noncompetitive inhibitor of AAAD with a Ki of approximately 300-500 mumol/l. In contrast, ferrous sulfate (0.5 mmol/l) was a competitive inhibitor (Ki = approximately 650 mumol/l) that actually increased the Vmax of AAAD. The results of these studies support that cyanide released from SNP can potently inhibit AAAD, although SNP has somewhat more complex interactions with AAAD due to the presence of ferrous ion.

Animals↗
PubMed1994

Causal estimation of time-varying treatment effects in observational studies: application to depressive disorder.

Clinicians recognize three phases of the treatment of major depression: an acute phase to control disabling symptoms, a continuation phase to avoid relapses of a single episode, and a preventive phase to avoid recurrences of new episodes over time. With no directly measurable trace of the underlying pathological process, the distinction is based arbitrarily on the passage of time in remission. The clinician who has successfully treated a patient with antidepressant medications in the acute phase has a critical clinical decision to make for the continuation and preventive phases: whether to continue to prescribe the medication, for how long, and at what dose. This decision, like most clinical decisions in psychiatry, is not yet completely determined by the results of randomized clinical trials. Only a handful of such trials have been completed, covering just a fraction of the possible maintenance strategies (defined by treatment drop times). For many reasons, observational studies of the outcome of naturally occurring treatment choices play an important supporting role, helping to extend the reach of completed studies and to design new studies. Causal inference from observational studies has usually been considered in the context of a decision among a few fixed alternatives at a single time. The particular causal effect of interest in the maintenance of remission dictates that treatment be studied over remission time. This challenges the causal analysis of the observational study. We present issues arising from assessing temporal treatment effects due to nonrandomized treatment assignment over time. We use data from a large observational study of the course of affective illness, to illustrate an approach to this problem.

Bias↗
PubMed1994

Intranasal sumatriptan for the acute treatment of migraine. International Intranasal Sumatriptan Study Group.

Two double-blind, placebo-controlled, randomised, multicentre, multinational, parallel-group studies were carried out to identify the optimum dose of intranasal sumatriptan for the acute treatment of migraine. Study medication was taken as a single dose through one nostril in the first study, and as a divided dose through two nostrils in the second study. Totals of 245 and 210 patients with a history of migraine were recruited into the one- and two-nostril studies, respectively. In both studies, headache severity had significantly improved at 120 min after doses of 10-40 mg sumatriptan compared to placebo (P < 0.05) and the greatest efficacy rates were obtained with 20 mg sumatriptan. With 20 mg sumatriptan 78% and 74% of patients experienced headache relief in one- and two-nostril studies respectively. Sumatriptan was generally well tolerated, the most frequently reported event being taste disturbance. The results of the two studies are similar and indicate that administering sumatriptan as a divided dose via two nostrils confers no significant advantage over single-nostril administration.

Acute Disease↗