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Biomedical subjects

K Kelley

Publications and source records attributed to K Kelley.

At least 19 recordsLinked to original sources

Practice parameter: diagnostic assessment of the child with status epilepticus (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.

OBJECTIVE: To review evidence on the assessment of the child with status epilepticus (SE). METHODS: Relevant literature were reviewed, abstracted, and classified. When data were missing, a minimum diagnostic yield was calculated. Recommendations were based on a four-tiered scheme of evidence classification. RESULTS: Laboratory studies (Na(++) or other electrolytes, Ca(++), glucose) were abnormal in approximately 6% and are generally ordered as routine practice. When blood or spinal fluid cultures were done on these children, blood cultures were abnormal in at least 2.5% and a CNS infection was found in at least 12.8%. When antiepileptic drug (AED) levels were ordered in known epileptic children already taking AEDs, the levels were low in 32%. A total of 3.6% of children had evidence of ingestion. When studies for inborn errors of metabolism were done, an abnormality was found in 4.2%. Epileptiform abnormalities occurred in 43% of EEGs of children with SE and helped determine the nature and location of precipitating electroconvulsive events (8% generalized, 16% focal, and 19% both). Abnormalities on neuroimaging studies that may explain the etiology of SE were found in at least 8% of children. RECOMMENDATIONS: Although common clinical practice is that blood cultures and lumbar puncture are obtained if there is a clinical suspicion of a systemic or CNS infection, there are insufficient data to support or refute recommendations as to whether blood cultures or lumbar puncture should be done on a routine basis in children in whom there is no clinical suspicion of a systemic or CNS infection (Level U). AED levels should be considered when a child with treated epilepsy develops SE (Level B). Toxicology studies and metabolic studies for inborn errors of metabolism may be considered in children with SE when there are clinical indicators for concern or when the initial evaluation reveals no etiology (Level C). An EEG may be considered in a child with SE as it may be helpful in determining whether there are focal or generalized epileptiform abnormalities that may guide further testing for the etiology of SE, when there is a suspicion of pseudostatus epilepticus (nonepileptic SE), or nonconvulsive SE, and may guide treatment (Level C). Neuroimaging may be considered after the child with SE has been stabilized if there are clinical indications or if the etiology is unknown (Level C). There is insufficient evidence to support or refute routine neuroimaging in a child presenting with SE (Level U).

Anticonvulsants↗

Transgenic rescue of Krabbe disease in the twitcher mouse.

The twitcher mouse is a natural model of Krabbe disease caused by galactocerebrosidase (GALC) deficiency. Previous attempts at rescuing the twitcher mouse by bone marrow transplantion, viral transduction, or transgenesis were only partially successful. Here, we report the transgenic (tg) rescue of the twitcher mouse with a BAC clone harboring the entire GALC. The twi/twi/hGALC tg mice exhibited growth, motor function, and fertility similar to those of nonaffected animals. These animals had normal levels of GALC activity in brain and were free of the typical twitcher demyelinating pathology. Surprisingly, GALC expression in twi/twi hGALC tg kidneys was low and galactocerebroside storage was only partially cleared. Nonetheless, these mice have been maintained for over 1 year without any sign of disease. Since pathological damage associated with GALC deficiency is confined to the nervous system, our work represents the first successful rescue of the twitcher mouse and opens the possibility of developing novel therapeutic approaches.

Animals↗

Gene therapy: reality or myth for the global bleeding disorders community?

In recent years, five different human gene therapy clinical studies have been initiated in the United States, covering a broad spectrum of gene transfer technologies. Both in vivo and ex vivo studies have been performed, and a variety of target organs/tissues have been studied. The results of this early human clinical research indicate that there is still much to be done before a safe and effective gene therapy procedure becomes commercially available, but there is strong evidence that the obstacles that remain will not prove insurmountable. Small increases in circulating clotting factor levels have been achieved in some patients without significant side-effects, providing proof of the principle that gene therapy can provide a therapeutic benefit for patients with haemophilia. Still unclear is whether gene therapy, when it becomes available, will be accessible to the global haemophilia community. As seen with recombinant and other high purity factor concentrates, technological advances do not always lead to improvements in care for the majority of the world's haemophilia patients. In fact, advances in technology can potentially increase the gulf in care if newer processes displace existing manufacturing technologies. A modified vaccine production model should be considered to make gene therapy more widely available to those who presently have inadequate access to treatment.

Blood Coagulation Disorders↗

Characterization of interleukin-1 receptor antagonist isoform expression in the brain of lipopolysaccharide-treated rats.

The endogenous interleukin-1 receptor antagonist is the natural inhibitor of the biological effects of interleukin-1 during inflammation. Interleukin-1 receptor antagonist refers to three isoforms: one secreted and two intracellular forms (types I and II). The objective of the present study was to investigate the expression of interleukin-1 receptor antagonist isoforms in the rat brain in vivo in response to an i.p. injection of lipopolysaccharide. The interleukin-1 receptor antagonist was studied at the messenger and protein levels by reverse transcription-polymerase chain reaction and western blot analysis, respectively. Interleukin-1 receptor antagonist messenger RNA was constitutively expressed in the brain and its expression increased in response to lipopolysaccharide. The three interleukin-1 receptor antagonist protein isoforms were up-regulated after lipopolysaccharide treatment in a time-dependent manner. Their relative expression differed according to the isoform and brain region studied. Double immunofluorescence staining revealed interleukin-1 receptor antagonist positive neurons and microglia in hippocampus 24h after lipopolysaccharide stimulation. These results demonstrate for the first time that brain cells are able to produce interleukin-1 receptor antagonist isoforms in response to a peripheral immune challenge with a predominance of the secreted over intracellular forms.

Blotting, Western↗

Coronary artery bypass grafting in Native Americans: a higher risk of death compared to other ethnic groups?

BACKGROUND: While the efficacy and safety of coronary artery bypass grafting (CABG) has been established in several clinical trials, little is known about its outcomes in Native Americans. MEASUREMENTS AND MAIN RESULTS: We assessed clinical outcomes associated with CABG in 155 Native Americans using a national database of 18,061 patients from 25 nongovernmental, not-for-profit U.S. health care facilities. Patients were classified into five groups: 1) Native American, 2) white, 3) African American, 4) Hispanic, and 5) Asian. We evaluated for ethnic differences in in-hospital mortality and length of stay, and after adjusting for age, gender, surgical priority, case-mix severity, insurance status, and facility characteristics (volume, location, and teaching status). Overall, we found the adjusted risk for in-hospital death to be higher in Native Americans when compared to whites (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.5 to 9.8), African Americans (OR, 3.4; 95% CI, 1.1 to 9.9), Hispanics (OR, 7.1; 95% CI, 2.5 to 20.3), and Asians (OR, 2.8; 95% CI, 1.1 to 7.0). No significant differences were found in length of stay after adjustment across ethnic groups. CONCLUSIONS: The risk of in-hospital death following CABG may be higher in Native Americans than in other ethnic groups. Given the small number of Native Americans in the database (n = 155), however, further research will be needed to confirm these findings.

Black or African American↗

Validation of a modified GTNM classification in peri-junctional oesophago-gastric carcinoma and its use as a prognostic indicator.

AIM: A modified GTNM classification (with additional T and N subdivisions) has been used for many years. The aim of this paper was to validate this classification in a group of patients with oesophago-gastric carcinoma and to see if the more detailed information may be useful. METHOD: The 3-year survival of 139 consecutive patients who survived resection has been related to the individual values of the modified and international classifications. RESULTS: A step-wise reduction in the survival was found with increasing values of G, T, N and M. The international T3 value yielded a 17.7% survival rate, when subdivided, rates of 37.5%, 17.3% and 3.2% were found. The international N1 value yielded a rate of 12.9% which subdivided into rates of 25.0%, 18.7% and 7.5%. CONCLUSION: If these results are repeated in a larger and more detailed study, this modified classification may provide added information when discussing prognosis and management.

Carcinoma↗

College smoking policies and smoking cessation programs: results of a survey of college health center directors.

College students' cigarette smoking rose dramatically during the 1990s. Little is known about what colleges do to address the problem. Health center directors at 393 4-year US colleges provided information (response rate: 65.1%) about college policies addressing smoking and the availability of smoking cessations programs. Of the health center directors surveyed, 85% considered students' smoking a problem; yet only 81% of colleges prohibit smoking in all public areas and only 27% ban smoking in all indoor areas, including students' rooms in dormitories and in private offices. More than 40% of the respondents reported that their schools did not offer smoking cessation programs and that the demand for existing program was low. Colleges need to do more to discourage student tobacco use. Recommended actions include campus-wide no-smoking policies that apply to student residences and identification of new ways of providing smoking prevention and cessation services.

Administrative Personnel↗

Physician specialty and the outcomes and cost of admissions for end-stage liver disease.

OBJECTIVES: Chronic liver disease is a frequent cause of morbidity and mortality. The aim of this study was to characterize the effects of physician specialty on length of stay, mortality, and costs during hospitalizations for end-stage liver disease. METHODS: We used data from the HBS International EXPLORE database. Patients hospitalized for treatment of variceal hemorrhage, spontaneous bacterial peritonitis, or hepatic encephalopathy were identified from primary discharge diagnoses. Patients were characterized by the specialty of the attending physician and by whether a gastroenterology consultation was obtained. Procedures performed were identified using ICD-9CM procedure codes. Costs were computed using proprietary HBS International Standard Transaction Codes. Linear and logistic regression analyses were used to examine the effect of physician specialty and consultation on length of stay, in-hospital mortality, and costs. RESULTS: Attending gastroenterologist care was associated with a shorter length of stay compared to nongastroenterologist attending care (median 4 vs 5 days, p = 0.01), which persisted after adjustment for differences in patient age, comorbidity, and number of procedures performed. There was a strong trend toward greater in-hospital mortality for patients without a gastroenterology attending or consultant (adjusted OR 1.72; 95% CI = 0.99, 2.98) compared to patients with a gastroenterology attending. Costs of hospital care were not significantly different between physician groups. CONCLUSIONS: Gastroenterologist involvement in inpatient care for end-stage liver disease was associated with shorter length of stay and a strong trend toward improved survival. Hospital costs were similar for patients cared for by the different physician groups.

Gastroenterology↗

Effective approaches to persuading pregnant women to quit smoking: a meta-analysis of intervention evaluation studies.

OBJECTIVES: The study aimed to: (1) assess the effectiveness of prenatal smoking cessation interventions, (2) clarify whether the psychological changes targeted by interventions are related to their effectiveness, (3) identify specific intervention components associated with greater effectiveness, and (4) establish whether aspects of evaluation methodology are associated with a greater effectiveness. DESIGN: Differences in proportions of women quitting and odds ratios were calculated for the intervention and control groups. Interventions were categorized in relation to the main intervention target (i.e. cognitive preparation versus increased threat perception), use of follow-up contact, use of individual cessation counselling and other characteristics. Methodological approaches to evaluation were also categorized. METHODS: A systematic literature review generated 36 controlled evaluations, including one unpublished study. A meta-analysis was used to relate study classifications to effectiveness. This involved univariate analyses and a multivariate model of the relationship between observed univariate effects. RESULTS: A weighted mean odds ratio of 1.93 indicated a good overall effectiveness. Cognitive preparation interventions achieved higher quit rates (6.5%) compared to interventions focusing on threat perception (2.2%). However, this effect was not maintained in the multivariate analysis. CONCLUSION: Interventions should employ follow-up, but further research is required to assess the impact of one-to-one counselling. Clarification of the psychological change processes underlying the observed effectiveness of these interventions is required. Future research should seek to identify the active ingredients and cognitive mediators of successful interventions.

Journal Article↗

Dietary n-3 polyunsaturated fat increases the fractional catabolic rate of medium-sized HDL particles in African green monkeys.

We have previously described a novel pathway for the metabolism of HDL subfractions in which small [2 apolipoprotein (apoA-I) molecules per particle] HDL particles are converted in a unidirectional manner outside the plasma compartment to medium (3 apoA-I molecules per particle) or large (4 apoA-I molecules per particle) HDL particles, which are subsequently removed from the circulation by the liver (Colvin et al. 1999. J. Lipid Res. 40: 1782;-1792; Huggins et al. 2000. J. Lipid Res. 41: 384;-394). The purpose of the present study was to determine whether the reduction in concentration of medium HDL in African green monkeys consuming n-3 polyunsaturated versus saturated fat diets resulted from decreased in vivo production or increased catabolism. Tracer small LpA-I (HDL containing only apoA-I) were isolated, without ultracentrifugation, by gel filtration and immunoaffinity chromatography and radiolabeled. After injection, the specific activity of apoA-I in small, medium, and large HDL was determined, and the kinetic data were analyzed using our previously published multicompartmental model for HDL subfraction metabolism. We found a significant reduction of apoA-I concentration in medium HDL in the animals fed n-3 polyunsaturated fat (31.2 +/- 0.7 mg/dl) compared with animals fed saturated fat (85.4 +/- 11.9 mg/dl; P = 0.002). The production rates of apoA-I in small, medium, and large HDL were similar in both diet groups; however, there was a significant increase in the fractional catabolic rate of apoA-I in medium HDL in the animals fed n-3 polyunsaturated fat (2.188 +/- 0.501 pools/day) compared with animals fed saturated fat (0.714 +/- 0.191 pools/day; P = 0.02). We conclude that n-3 polyunsaturated fat reduces HDL cholesterol concentration by increasing the fractional catabolic rate of medium-sized HDL particles in African green monkeys.

Animals↗

Nicotine effects on proliferation and the bombesin-like peptide autocrine system in human small cell lung carcinoma SHP77 cells in culture.

OBJECTIVES: To determine whether nicotine affects the proliferation and expression of the bombesin-like peptide autocrine system in human small cell lung carcinoma (SCLC) SHP77 cells compared with nonmalignant human bronchial epithelial BEAS 2B cells as non-neuroendocrine controls. METHODS: Human lung cells were cultured in defined serum-free medium with various concentrations of nicotine added for various times. Proliferation was measured by cell counts and colorimetric assay, bombesin-like peptide receptor expression was assayed by specific binding assays and quantitative competitive PCR, and bombesin-like peptides determined by ELISA. RESULTS: Nicotine significantly stimulated the growth of human SCLC SHP77 and NCI-H865 cells, but not BEAS 2B cells. Bombesin-like peptide receptor specific binding and mRNA expression were not affected by nicotine exposure in SHP77 cells or BEAS 2B cells. An increase in SHP77 cellular bombesin-like peptide content was observed. CONCLUSIONS: Human SCLC SHP77 cells express the components of the bombesin-like peptide autocrine system. Increased proliferation in the presence of nicotine may be due in part to increased levels of bombesin-like peptides in SHP77 cultured in nicotine. Nicotine effects on nonmalignant pulmonary neuroendocrine cells may provide additional insight into how nicotine itself may promote lung carcinogenesis.

Binding, Competitive↗

Clinical and economic effects of pulmonary artery catheterization in nonemergent coronary artery bypass graft surgery.

OBJECTIVE: To examine the association between use of pulmonary artery catheterization with hospital outcomes and costs in nonemergent coronary artery bypass graft (CABG) surgery. DESIGN: Retrospective cohort study. SETTING: Fifty-six community-based hospitals in 26 states. PARTICIPANTS: A total of 13,907 patients undergoing nonemergent CABG surgery between January 1, 1997, and December 31, 1997. MEASUREMENTS AND MAIN RESULTS: Discharge abstracts for each patient were examined. Stratified and multivariate analyses were used to assess the impact of pulmonary artery catheters (PACs) on in-hospital mortality, length of stay in the intensive care unit, total length of stay, and hospital costs. Outcomes were adjusted for patient demographic factors, hospital characteristics, and hospital volume of PAC use in the year of analysis. Fifty-eight percent of the patients received a PAC. After adjustment, the relative risk of in-hospital mortality was 2.10 for the PAC group compared with the patients who did not receive a PAC (95% confidence interval [CI], 1.40 to 3.14; p < 0.001). The mortality risk was significantly higher in hospitals with the lowest third of PAC use (odds ratio, 3.35; 95% CI, 1.74 to 6.47; p < 0.001) and not significantly increased in the highest two thirds of users (odds ratio, 1.62; 95% CI, 0.99 to 2.66; p = 0.09). Days spent in critical care were similar; however, total length of hospital stay was 0.26 days longer in the PAC group (p < 0.001). Hospital costs were $1,402 higher in the PAC group. CONCLUSION: In the setting of nonemergent CABG surgery, pulmonary artery catheterization was associated with an increased risk of in-hospital mortality, greater length of stay, and higher total costs, particularly in hospitals with low volume of PAC use.

Adult↗

What colleges are doing about student binge drinking. A survey of college administrators.

In 1999, the Harvard School of Public Health College Alcohol Study surveyed 734 US college administrators to learn what colleges were doing to prevent binge drinking. Respondents rated the severity of student alcohol-abuse problems and described prevention efforts and institutional investments in prevention infrastructure. Prevention practices were widespread in the areas of general education about alcohol, use of policy controls to limit access to alcohol, restricting advertising at home-game sporting events, and allocation of living space to alcohol-free dormitories. Programming was less prevalent for more targeted alcohol education, outreach, and restrictions on alcohol advertising in campus media. Nationally, most of the surveyed colleges reported having a campus alcohol specialist, many had task forces, and about half were performing in-house data collection. Less common were program evaluations, community agreements, or neighborhood exchanges. Prevention practices varied with institutional characteristics and the surveyed administrators' perceptions of the severity of alcohol problems.

Administrative Personnel↗

Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine expression.

The present study was designed to determine the role of endogenous brain interleukin (IL)-1 in the anorexic response to lipopolysaccharide (LPS). Intraperitoneal administration of LPS (5-10 microgram/mouse) induced a dramatic, but transient, decrease in food intake, associated with an enhanced expression of proinflammatory cytokine mRNA (IL-1beta, IL-6, and tumor necrosis factor-alpha) in the hypothalamus. This dose of LPS also increased plasma levels of IL-1beta. Intracerebroventricular pretreatment with IL-1 receptor antagonist (4 microgram/mouse) attenuated LPS-induced depression of food intake and totally blocked the LPS-induced enhanced expression of proinflammatory cytokine mRNA measured in the hypothalamus 1 h after treatment. In contrast, LPS-induced increases in plasma levels of IL-1beta were not altered. These findings indicate that endogenous brain IL-1 plays a pivotal role in the development of the hypothalamic cytokine response to a systemic inflammatory stimulus.

Analysis of Variance↗

Interleukin-4 and interleukin-10 regulate IL1-beta induced mouse primary astrocyte activation: a comparative study.

The pro-inflammatory cytokine interleukin-1beta (IL-1beta) is strongly expressed during brain injury and is able to induce severe cellular brain damage via the production of soluble factors. Different processes regulate IL-1 biological activities, like the production of anti-inflammatory cytokines such as interleukin-4 (IL-4) and interleukin-10 (IL-10). In this report, we describe the sequential effects of IL-4 and IL-10 on the production of interleukin-6 (IL-6) induced by IL-1beta in mouse primary astrocytes and compare these effects to those of the synthetic glucocorticoid agonist, dexamethasone. IL-6 secretion and IL-6 mRNA expression were determined by ELISA assay and a comparative RT-PCR method, respectively. Incubation of mouse astrocytes in primary culture simultaneously with IL-1beta (10 ng/ml) + IL-10 (10 ng/ml) or IL-1beta + dexamethasone (10(-6) M) markedly reduced IL-1beta induced IL-6 secretion and IL-6 mRNA expression, respectively, whereas simultaneous addition of IL-4 (10 ng/ml) did not alter the induction of IL-6 by IL-1beta. In contrast, after 24 h of IL-1beta treatment, the level of IL-6 was decreased below constitutive levels, and this change was reversed by addition of IL-4. IL-6 production in IL-1beta pretreated cells was also increased by addition of IL-4, whereas IL-10 and dexamethasone had no effects. The delayed time dependent effect of IL-4 might be partially explained by the induction of IL-4 receptor alpha-chain mRNA expression by IL-1beta. Therefore, we conclude that IL-10 and dexamethasone have rapid immunosuppressive effects on the astrocyte response to IL-1beta stimulation, whereas IL-4, which has a delayed action, acts as an immune inducer.

Animals↗