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Biomedical subjects

R Clark

Publications and source records attributed to R Clark.

At least 55 records · Page 3Linked to original sources
PubMed1999

Investigation of recombinant human insulin-like growth factor type I in thymus regeneration in the acute stage of experimental FIV infection in juvenile cats.

Thymus involvement and the development of thymic lesions in HIV-1 infection is hypothesized to suppress thymus function and limit T cell maturation and replenishment of the peripheral lymphoid pool. Therapeutic modulation to protect or enhance thymus function may therefore ameliorate peripheral lymphocytopenia and retard disease progression. Thymotrophic agents, such as insulin-like growth factor type I (IGF-I), may therefore represent adjunctive but important methods of treatment to protect or promote thymus function. The assessment of rhIGF-I in lentiviral infection and its impact on the thymus was performed using the feline immunodeficiency virus (FIV) model. Regeneration of the thymus in juvenile cats and amelioration of the thymic lesion after FIV infection was assessed by multiple measurements including thymic weight, stereologic analysis of the thymus cortex and medulla, histologic and immunohistologic analysis, quantitation of thymocyte and peripheral lymphocyte subsets, and quantitative competitive RT-PCR. Evidence of thymic cortical regeneration was observed in FIV-inoculated cats after 12 and 20 weeks of rhIGF-I treatment. Inflammation in the thymus was reduced during this period of treatment in this group of rhIGF-I/FIV-inoculated cats as evidenced by the reduced numbers of B cells detected. Viral replication rates in peripheral lymph nodes were not altered by rhIGF-I treatment and were decreased by 1 log in the thymus after 20 weeks of treatment. Peripheral blood CD4+ T cell counts also increased after 14 weeks of treatment. This suggests that rhIGF-I treatment can enhance thymus function and replenishment of the peripheral T cell pool.

Animals↗
PubMed1999

Breakfast cereal and caffeinated coffee: effects on working memory, attention, mood, and cardiovascular function.

This study examined the effects of breakfast cereal and caffeinated coffee on working memory, attention, mood, and cardiovascular function. One hundred and forty-four volunteers (72 male, 72 female, mean age 21 years) were assigned to one of the groups formed by combining breakfast (cereal versus no breakfast) and caffeine (caffeinated versus decaffeinated coffee) conditions. The volunteers completed a baseline session between 0800 and 0845 h. The breakfast/caffeine administration took place between 0845 and 0915 h. They then completed another test session (starting at 0945) and had a coffee break at 1045, followed by a final session starting at 1145. The results showed that those who consumed breakfast cereal had a more positive mood at the start of the test sessions, performed better on a spatial memory task, and felt calmer at the end of the test session than those in the no breakfast condition. Ingestion of caffeine had no effect on initial mood or working memory, but it did improve encoding of new information and counteracted the fatigue that developed over the test session. Caffeine increased blood pressure and pulse rate, whereas breakfast cereal consumption only had an effect on pulse. Overall, these results confirm previous findings on the effects of breakfast and caffeine, and demonstrate distinct profiles for two common examples of early-morning food and drink, breakfast cereal and caffeinated coffee.

Adult↗
PubMed1999

A fatal cytokine-induced systemic inflammatory response reveals a critical role for NK cells.

The mechanism of cytokine-induced shock remains poorly understood. The combination of IL-2 and IL-12 has synergistic antitumor activity in vivo, yet has been associated with significant toxicity. We examined the effects of IL-2 plus IL-12 in a murine model and found that the daily, simultaneous administration of IL-2 and IL-12 resulted in shock and 100% mortality within 4 to 12 days depending on the strain employed. Mice treated with IL-2 plus IL-12 exhibited NK cell apoptosis, pulmonary edema, degenerative lesions of the gastrointestinal tract, and elevated serum levels of proinflammatory cytokines and acute phase reactants. The actions of TNF-alpha, IFN-gamma, macrophage-inflammatory protein-1alpha, IL-1, IL-1-converting enzyme, Fas, perforin, inducible nitric oxide synthase, and STAT1 did not contribute to the observed toxicity, nor did B or T cells. However, toxicity and death from treatment with IL-2 plus IL-12 could be completely abrogated by elimination of NK cells. These results suggest that the fatal systemic inflammatory response induced by this cytokine treatment is critically dependent upon NK cells, but does not appear to be mediated by the known effector molecules of this cellular compartment. These data may provide insight into the pathogenesis of cytokine-induced shock in humans.

Animals↗
PubMed1999

Adeno-associated virus-mediated gene transfer to the brain: duration and modulation of expression.

Adeno-associated virus (AAV) is a promising vector for central nervous system (CNS) gene transfer, but a number of issues must be addressed if AAV is to be used for widespread delivery throughout the CNS. Our aim was to test the effect of dose, route of delivery, and hydroxyurea treatment on brain expression of beta-galactosidase activity after cerebral inoculation with an rAAV-lacZ vector (rAAV-beta-gal). We also wished to test whether an immune response appeared against the vector and the transgene product. We found in BALB/c mice that beta-Gal expression increased during the first 2 months after inoculation, then decreased slightly by 4 months, and continued out to 6, 12, and 15 months in single animals. Cerebral injection produced localized beta-Gal expression that did not diffuse to other regions despite a fivefold increase in injection volume. Intraventricular injection resulted in negligible transduction. Antibodies to AAV capsid protein and beta-Gal appeared at low levels at 2 and 4 months, but correlated poorly with beta-Gal expression and did not prevent readministration of rAAV-beta-gal. Hydroxyurea treatment did not result in increased transduction in vivo. We conclude that our study confirms rAAV vectors as having considerable potential for CNS gene transfer; however, several important problems must be addressed if this vector system is to be used for long-term transduction of the entire brain. Sustained, regulatable expression will be needed if rAAV is to be used in the treatment of chronic CNS disease. The difficulty in delivering AAV to diverse regions of the brain is an important problem that must be overcome if these vectors are to be used for anything beyond localized transduction.

Animals↗
PubMed1999

Inadvertent ketamine overdose in children: clinical manifestations and outcome.

STUDY OBJECTIVE: We sought to characterize the clinical manifestations, outcome, and etiology of inadvertent ketamine overdose in the emergency department. METHODS: We investigated cases of inadvertent ketamine overdose in children seen in the ED solicited through electronic mail subscription lists or reported to the Institute for Safe Medication Practices. The clinical manifestations, outcome, and reported cause for each case are described. RESULTS: We identified 9 cases of inadvertent ketamine overdose in children treated in the ED. Patients received either 5(n=3), 10(n=5), or 100(n=1) times the intended dose, either by the intramuscular (n=5) or intravenous (n=4) route. All 9 experienced prolonged sedation (3 to 24 hours). Four experienced brief respiratory depression shortly after administration, and assisted ventilation was performed in 2. Two children without respiratory difficulty or hypoxemia were intubated by their physicians as a precaution. In 5 children, the dosing error was not discovered until late in the sedation, often when the child was not waking at the expected time. No adverse outcomes were noted, and all children were normal neurologically on discharge and longer-term follow-up if available. CONCLUSION: No adverse outcomes were noted in 9 healthy children treated in the ED who inadvertently received 5 to 100 times the intended dose of ketamine. Toxicity manifested as prolonged sedation in all 9 and brief respiratory depression in 4. The margin of safety in ketamine overdose may be wide, although less common and more serious outcomes cannot be excluded by this small, self-reported sample.

Anesthetics, Dissociative↗
PubMed1999

Racism as a stressor for African Americans. A biopsychosocial model.

Various authors have noted that interethnic group and intraethnic group racism are significant stressors for many African Americans. As such, intergroup and intragroup racism may play a role in the high rates of morbidity and mortality in this population. Yet, although scientific examinations of the effects of stress have proliferated, few researchers have explored the psychological, social, and physiological effects of perceived racism among African Americans. The purpose of this article was to outline a biopsychosocial model for perceived racism as a guide for future research. The first section of this article provides a brief overview of how racism has been conceptualized in the scientific literature. The second section reviews research exploring the existence of intergroup and intragroup racism. A contextual model for systematic studies of the biopsychosocial effects of perceived racism is then presented, along with recommendations for future research.

Black or African American↗
PubMed1999

Maternal employment and development of the father-infant relationship in the first year.

This study investigated links between maternal employment and fathers' parenting quality when their infants were 4 and 12 months old. Sixty-three fathers were videotaped interacting with their infants and completed questionnaires regarding their involvement in caregiving, parenting stress, and marital quality, and mothers reported on children's temperament. Fathers whose wives either did not work outside the home or worked part time were more sensitive and responsive to their children when they were more involved in caregiving; men whose wives worked full time exhibited more negative affect and behavior when they participated more in child care. Men whose wives were not employed also were more positive in their interactions when they were happier with their marriage, whereas men whose wives worked either part time or full time exhibited a negative relation between parenting behavior and marital quality. Maternal work circumstances were not related to fathers' parenting stress; rather, marital quality and child temperament predicted parenting stress at 4 and 12 months for all fathers.

Father-Child Relations↗
PubMed1999

Derivation and prediction of temperamental types among preschoolers.

The number and nature of temperamental types in 488 children aged 3 years 6 months was examined on the basis of a broad set of temperamental characteristics, including positive and negative emotionality and the attentional and behavioral control domains. Configural frequency analysis methods showed clear support for two temperament types: controlled-nonexpressive and noncontrolled-expressive. These types showed meaningful differences against external criteria related to a wide range of problem behaviors from the emotional, social, and attentional domains. The reports of problem behaviors were obtained contemporaneously from fathers and caregivers. These findings replicated a year later when children were aged 4 years 6 months. Furthermore, the findings showed that infant and toddler-age temperamental characteristics differentiated these preschool-aged types. The authors discuss the implications of the results for a categorical view of temperament-personality.

Attention↗
PubMed1999

Pain and the administration of analgesia: what nurses say.

Pain of moderate to severe intensity continues to be an important problem for many hospitalized patients. Nurses spend more time with patients than any other health professional group and have a key role to play in the management of patients' pain. This paper reports the findings from a series of focus group interviews which were undertaken to explore nurses' perceptions regarding pain and the administration of narcotic analgesia. Themes identified from participants' comments related to (1) the pivotal role of nurses in pain management; (2) nursing assessment and pain management decisions (3) individual factors influencing nurses' pain management decisions and (4) the influence of others on nurses' pain management decisions.

Analgesics, Opioid↗
PubMed1999

Natural history of intestinal microsporidiosis among patients infected with human immunodeficiency virus.

A chart review of 73 human immunodeficiency virus (HIV)-infected patients with enteric microsporidiosis was conducted to define the natural history of microsporidiosis. A substantial proportion of patients remained symptomatic after 6 months (54.8% with persistent diarrhea and 51.2% with weight loss). Predictors for persistent diarrhea included high HIV RNA viral load and no initiation of protease inhibitor therapy.

AIDS-Related Opportunistic Infections↗
PubMed1999

Family protective factors among urban African American youth.

Examined the relations among family protective factors, stressful events, and behavioral adjustment of 64 African American 6th graders. The youths reported on family stressors, father-figure involvement, and kin support. Their primary caregivers reported on parenting, father-figure involvement, and family stressors. Teachers reported on child social skill deficits, acting out, and shy or anxious behavior. Based on regression analyses, stress exposure associated positively with child social skill deficits, acting out, and shy or anxious behavior. Parental warmth was associated negatively with shy or anxious behavior. Parental use of corporal punishment was associated positively with child acting out. For youth exposed to high numbers of family stressors, parental demandingness was associated negatively with child acting out and kin support was associated negatively with acting out and shy or anxious behavior, suggesting that these family factors partially shield children from the negative effects of stress.

Adolescent↗
PubMed1999

Development of capillary electrophoresis as an alternative to high resolution agarose electrophoresis for the diagnosis of multiple sclerosis.

The presence of oligoclonal bands in cerebrospinal fluid (CSF) is used as a diagnostic indicator of multiple sclerosis (MS). These bands, gamma-globulins thought to result from a restricted antibody response directed against autoantigens or viral antigens, are consistent with CSF-specific immunoglobulin synthesis when observed in the spinal fluid and not in the serum. Current methodology commonly involves electrophoresing concentrated CSF with high-resolution agarose gel electrophoresis (HRAGE) followed by protein staining in order to visualize the oligoclonal bands. Capillary zone electrophoresis (CZE) was evaluated as an alternative method. Separation of CSF and serum proteins from 54 patients in a bare silica capillary containing a high pH borate buffer allowed for resolution of the five major zones including the gamma-region and showed a 90% concordance with the results from HRAGE banding studies. Since a simple borate buffer did not provide adequate resolution of the oligoclonal bands in the gamma-region, the separation buffer was augmented with polyethylene glycol (PEG) which provided a significant enhancement in resolution of proteins in this region (24 patient study). In addition to obtaining banding information from electropherograms obtained with these separation conditions, it was feasible to calculate a CSF Index which compared favorably with the results from nephelometry. Finally, we show that zwitterionic additives such as O-phosphorylethanolamine may further enhance resolution and that capallary electrophoresis (CE) may allow oligoclonal banding information to be obtained directly from CSF without concentration.

Buffers↗
PubMed1999

Traumatic stress in HIV-infected women.

This study assesses the prevalence of specific traumatic stressors that meet criterion A for the Diagnostic and Statistical Manual of Mental Disorders' (DSM-IV) diagnosis of posttraumatic stress disorder (PTSD) and symptoms of PTSD in a representative sample of HIV-infected women. The study also assesses the impact of these stressors and symptoms on the clinical progression of HIV infection. The Life Stressor Checklist and the Impact of Events Scale-Revised were administered via interview to 67 Africa-American women beyond the initial stages of HIV infection. The ratio of CD4 t-cells to CD8 t-cells were abstracted from medical records at dates that approximated psychological interviews and were examined at two points in time 12 to 14 months apart. The prevalence of traumatic stressors and PTSD symptoms were high among HIV-infected women. Traumatic stressors were significantly associated with a lower CD4 to CD8 ratio at the 1-year follow-up. Among women who reported a traumatic event, those who also met criteria for PTSD evidenced a lower CD4 to CD8 ratio at the follow-up assessment. The study concludes that prevention and treatment efforts targeted at HIV-infected women must take into account traumatic stressors and PTSD symptoms and their potential impact on the course of the disease.

Adolescent↗