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Biomedical subjects

R Dawson

Publications and source records attributed to R Dawson.

At least 73 records · Page 4Linked to original sources

Maintenance strategies for unipolar depression: an observational study of levels of treatment and recurrence.

BACKGROUND: This paper analyses data from a large observational study of the course of affective illness to provide insight into the duration and dose of effective maintenance therapies. METHODS: The data are 236 unipolar patients who had received antidepressants during recovery and were followed for affective recurrence for up to 5 years. Using data on the naturally selected somatic treatments, we have conducted analyses that adjust for the potential confounding effects of prognosis and treatment intensity to estimate the causal effect of level of medication on the course of recurrence. RESULTS: The results of these analyses show that it is important for patients to remain on the level of somatotherapy used to treat the acute episode for the initial 8 months after symptoms have abated. After that time, the rate of recurrence for patients with fewer than five previous episodes is approximately 1% per week or less at all levels of medication (including discontinuation). Patients who had experienced more than several recurrences are at greater risk of recurrence and continue to benefit from any level of medication during the first year after recovery. CONCLUSIONS: The CDS analyses reported here suggest that effective maintenance strategies for all but highly recurrent patients may be a middle road, opting for full-dose strategies of limited duration. These results have implications at both the policy and the clinical level, given the need to consider both monetary and nonmonetary costs (side-effects) associated with continued pharmacotherapy during remission. LIMITATIONS: The observational design of the CDS limits the degree to which cause and effect relationships can be inferred from the observed associations.

Antidepressive Agents↗

Uveitogenic epitopes of retinal S-antigen are generated in vivo via an alternative antigen-presentation pathway.

We have found that different antigen-processing pathways are involved in the induction of experimental autoimmune uveoretinitis (EAU) by the retinal autoantigens S-antigen and interphotoreceptor retinoid-binding protein (IRBP). Although in vitro T-cell proliferative responses to IRBP were completely inhibited in the presence of irreversible cysteine protease inhibitors, no significant reduction of S-antigen proliferative responses was found. Furthermore, acidic proteolysis of S-antigen by the cysteine protease cathepsin B prior to immunization radically reduced pathogenicity (disease severity). In addition, in vitro processing of S-antigen, but not IRBP, was also found to be resistant to the action of cycloheximide and lysosomotropic agents, inhibition of proliferation only occurring after extended exposure of antigen-presenting cells to methyl amine or high concentrations of chloroquine. These data indicate that an alternative pathway of antigen processing exists for S-antigen, which is independent of processing within the normal endolysosomal pathway and that uveitogenic peptides of naturally processed S-antigen bind to major histocompatibility complex class II antigens either at the cell surface or within very early endosomes where cathepsin B is inactive.

Animals↗

Iron in prenatal multivitamin/multimineral supplements. Bioavailability.

OBJECTIVE: To determine the effect of the differences in the content of essential and nonessential ingredients and of a standardized meal on iron bioavailability from four popular prenatal multivitamin/multimineral supplements. STUDY DESIGN: Iron absorption during an eight-hour period following ingestion of a multivitamin/multimineral formulation, both fasting and postprandial, after a standardized meal, was measured in five groups of 20 pregnant women (24-32 weeks of gestation) and statistically compared. The prenatal formulations were Natalins Rx, Prenatal 1/1, Stuartnatal Plus and Prenate 90. One-A-Day (without iron) was included in the study for the control group. RESULTS: The descending order of absorption, both fasting and postprandial, were Prenate 90, Stuartnatal Plus, Prenatal 1/1 and Natalins Rx. Total iron absorption for each formulation group during the postprandial phase was higher than during the fasting phase. However, the net amount of iron absorption (in both the fasting and postprandial phases) from three of the four formulations (Stuartnatal Plus, Prenatal 1/1 and Prenate 90) provided the minimal 3.0 mg of supplemental iron per day recommended by the National Academy of Science. CONCLUSION: The observed differences in iron absorption between prenatal supplements apparently reflect the effects of the various combinations of vitamins, essential minerals and additives. The absolute amount of elemental iron contained in a prenatal multivitamin/ multimineral formulation does not ensure availability.

Absorption↗

Developing and comparing treatment strategies: an annotated portfolio of designs.

Useful clinical strategies are adaptive, specifying the sequence of treatments that are alternatives, what it means for the treatment to "work," the rules for abandoning a treatment, and the subsequent treatments. Because combinatorial complexity precludes comparison of every possible whole strategy, current experiment-based methods rely on comparisons among a few options at particularly crucial decision points, and strategies are pieced together from scraps of information. Nonexperimental methods for strategy development offer a seductive alternative, but their advantages may be illusory. Clinical investigators deploy a wide range of study designs to compare treatment strategies in mental health. This article organizes the types of designs by their purpose and annotates this list with comments on the strengths and weaknesses of each type. We conclude with some general comments on the overall process of development of treatment strategies.

Humans↗

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↗

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↗

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↗

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↗

Visiting registrars in surgery: the trainees' viewpoint.

Overseas Doctors have been coming for higher surgical training to the UK for many years. Little is known about the reasons they choose to come here, what their expectations are and if the training they receive fulfils these expectations and prepares them for a career back home. The aim of this study was to address these questions and to see what changes could be suggested to make training more meaningful to visiting registrars. Questionnaires were sent to 26 trainees who were part of the 3 year surgical registrar rotation in Wales from 1992. 23 completed questionnaires were available for analysis as the others were not traceable. 83% came to the UK to obtain the FRCS and train in a specific aspect of general surgery (74%). The period of training was felt to be inadequate by 79% of trainees. 65% felt that of the total period of training, less than 75% was useful. On return to their own countries 96% were to be either solely or largely responsible for patients in their care. In conclusion, if surgical training is to remain meaningful to visiting trainees, changes would have to be made to the Calman system to enable them to continue to do the FRCS and avenues made available for them to train in their stated areas of interest with adequate supervision, regular assessment and certification.

Attitude of Health Personnel↗

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↗

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↗

Power negotiating for physician executives.

Whenever you deal with another person, you use exactly the same techniques that international negotiators use to reach agreement on world problems. Learning to improve your negotiating skills is the highest and best use of your time. You can't make money faster than you can when you're negotiating well. Presented here are negotiating gambits to use to your advantage at the bargaining table.

Humans↗

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↗