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Biomedical subjects

T Rogers

Publications and source records attributed to T Rogers.

At least 37 records · Page 2Linked to original sources

Macroscopic and microscopic details of the cartilaginous nasal pyramid.

PURPOSE: The purpose of this investigation was to ascertain the macroscopic and microscopic details at rhinion and throughout the cartilaginous nasal pyramid in 35 white cadavers. MATERIALS AND METHODS: Demographic information on 35 white cadavers was collected. This included sex, height, weight, brief medical history, age at death, and cause of death. All soft tissues were removed from the nasal bones, lateral nasal cartilages, and alar cartilages and the overlap between bone and cartilage was measured at 4 sites. The lateral nasal cartilage (LNC) was measured for width and length. The relationship between the caudal end of the LNC, and the anterior septal angle was also noted. The septum and LNC were removed en bloc randomly from 25 of the cadavers. These specimens were fixed in formalin, processed, embedded in paraffin, and coronally sectioned every 3 mm, and prepared for microscopic examination. RESULTS: The LNC was 22.51 mm long and 13.71 mm wide on average. It underlapped the nasal bone 14.97 mm on average from the nasal septum laterally. The cephalocaudal underlapping was greatest in the midline (mean, 8.63 mm) and least (2.77 mm) about halfway down the nasal bone. Microscopic examination showed extreme variation in the attachment of the septum and LNC. This ranged from no cartilaginous connection to complete fusion. Thirty-two percent of the specimens showed the caudal edge of the LNC to be coincident with the anterior septal angle. CONCLUSIONS: At the time of aesthetic, functional, or post-traumatic nasal surgery, one must be prepared to deal with diverse attachments between the septum and the LNC.

Adult↗

Extension of a pilot study: impact from the cytochrome P450 2D6 polymorphism on outcome and costs associated with severe mental illness.

The influence of cytochrome P450 2D6 (CYP2D6) genetic variability was examined in psychiatric inpatients by evaluating adverse drug events (ADEs), hospital stays, and total costs over a 1-year period in an extension of a previously published brief report. One hundred consecutive psychiatric patients from Eastern State Hospital in Lexington, Kentucky, were genotyped for CYP2D6 expression. ADEs were evaluated by a neurologic rating scale, modified Udvalg for Kliniske Undersogelser Side Effect Rating Scale, or chart review. Information on total hospitalization days and total costs were gathered for a 1-year period. Forty-five percent of the patients received medications that were primarily dependent on the CYP2D6 enzyme for their elimination. When the analysis was restricted to just those patients in each group receiving medication heavily dependent on the CYP2D6 enzyme, the following were observed: (1) a trend toward greater numbers of ADEs from medications as one moved from the group with ultrarapid CYP2D6 activity (UM) to the group with absent CYP2D6 activity (PM); (2) the cost of treating patients with extremes in CYP2D6 activity (UM and PM) was on average $4,000 to $6,000 per year greater than the cost of treating patients in the efficient metabolizer (EM) and intermediate metabolizer (IM) groups; and (3) total duration of hospital stay was more pronounced for those in CYP2D6 PM group. Variance of hospital stays and costs calculated from these preliminary data suggests that 1,500 to 2,000 patients must be evaluated over at least a 1-year period to determine whether the CYP2D6 genetic variation significantly alters the duration of hospital stay and costs.

Antipsychotic Agents↗

Opinion leaders' support for tobacco control policies and participation in tobacco control activities.

OBJECTIVES: Because opinion leaders hold positions from which they may influence tobacco control efforts, this study examined their support for tobacco control policies and their involvement in tobacco control activities. METHODS: A telephone survey was administered to 712 California opinion leaders who were randomly selected from constructed lists representing 8 types of organizations: health, education, law enforcement, media, government, business, ethnic, and youth. Hierarchical regression analysis was used to identify predictors of support for and participation in tobacco control activities. RESULTS: Approximately one half to two thirds of opinion leaders supported the tobacco control policies queried; 60% reported involvement in tobacco control-related activities during the previous year. Organizational affiliation was a strong predictor of support and involvement, with leaders from health and educational organizations reporting the highest levels and business and media leaders reporting the lowest. Tobacco issue involvement variables (e.g., having a friend or family member with a smoking-related illness) were significantly associated with the outcomes, while sociodemographics, for the most part, were not. CONCLUSIONS: Study results can be used to mobilize opinion leaders' support for tobacco control more effectively.

Analysis of Variance↗

Absence of linkage and linkage disequilibrium to chromosome 15q11-q13 markers in 139 multiplex families with autism.

Chromosomal region 15q11-q13 has been implicated to harbor a susceptibility gene or genes underlying autism. Evidence has been derived from the existence of cytogenetic anomalies in this region associated with autism, and the report of linkage in a modest collection of multiplex families. Most recently, linkage disequilibrium with the marker GABRB3-155CA2 in the candidate locus GABRB3, located in this region, has been reported. We searched for linkage using eight microsatellite markers located in this region of chromosome 15 in 147 affected sib-pairs from 139 multiplex autism families. We also tested for linkage disequilibrium in the same set of families with the same markers. We found no evidence for excess allele sharing (linkage) for the markers in this region. Also, we found no evidence of linkage disequilibrium, including for the locus GABRB3-155CA2. Thus, it appears that the role of this region of chromosome 15 is minor, at best, in the majority of individuals with autism.

Adolescent↗

Effect of diabetes mellitus on endotoxin-induced lung injury.

OBJECTIVE: To examine the effects of diabetes mellitus on lipopolysaccharide (LPS)-induced pulmonary edema and alveolar neutrophil recruitment and activation. HYPOTHESIS: Zucker diabetic fatty rats are resistant to the effects of intratracheal LPS on the extravasation of plasma proteins into the lungs. DESIGN: Zucker diabetic fatty (ZDF) rats (genotype fa/fa) were used as a model of diabetes mellitus, while their normoglycemic heterozygous littermates served as controls. Lipopolysaccharide (Escherichia coli 0111: B4; 100-200 microg) or vehicle (0.25 mL of isotonic sodium chloride solution) was instilled into the airways of ZDF and control rats. Four hours later, pulmonary microvascular dysfunction was assessed by measuring the extravasation of Evans blue dye into the lung. Lipopolysaccharide-induced neutrophil recruitment was assessed by counting the number of neutrophils within the bronchoalveolar lavage fluid and measuring their expression of CD11b/CD18 by fluorescence-activated cell analysis sorting. RESULTS: The LPS (200 microg) induced a 32% increase in Evans blue dye extravasation into the lungs of controls (P = .008) but had no such effect in diabetic animals. Pulmonary extravasation of Evans blue dye in controls was greater than that of ZDF rats both at baseline (P = .002) and in response to 200 microg of LPS (P<.001). The LPS upregulated neutrophil CD11b/CD18 expression in diabetic and nondiabetic groups and induced a greater than 50-fold increase in the number of neutrophils within the airways of both control and diabetic groups (P<.001). CONCLUSION: Despite the recruitment of a large number of neutrophils into the lung, the LPS-induced change in pulmonary microvascular permeability in diabetic animals is substantially less than that of nondiabetic controls.

Animals↗

Exclusion of linkage to the HLA region in ninety multiplex sibships with autism.

Several studies have suggested a role for the histocompatibility complex of loci (HLA) in the genetic susceptibility to autism. We have tested this hypothesis by linkage analysis using genetic marker loci in the HLA region on chromosome 6p in multiplex families with autism. We have examined sharing of alleles identical by descent in 97 affected sib pairs from 90 families. Results demonstrate no deviation from the null expectation of 50% sharing of alleles in this region; in fact, for most marker loci, the observed sharing was less than 50%. Thus, it is unlikely that loci in this region contribute to the genetic etiology of autism to any significant extent in our families.

Adolescent↗

Chronic K depletion inhibits renal brush border membrane Na/sulfate cotransport.

BACKGROUND: The purpose of this study was to determine if dietary potassium (K) deficiency regulates renal proximal tubular sodium gradient-dependent sulfate transport (Na/Si cotransport) in the rat and, furthermore, determine if the regulation takes place at the level of the recently cloned Na/Si cotransport system (NaSi-1). Methods and Results. Rats treated chronically (seven days) with a K-deficient diet had a significant decrease in serum Si levels and an increase in fractional excretion of ultrafilterable Si, which paralleled a significant decrease in brush border membrane (BBM) Na/Si cotransport activity. The decrease in BBM Na/Si cotransport activity was associated with decreases in BBM NaSi-1 protein and renal cortical NaSi-1 mRNA abundance. In addition, in Xenopus oocytes injected with mRNA from kidney cortex slices of K-deficient rats, there was a significant reduction in the induced Na/Si cotransport, whereas there was no alteration in l-leucine uptake, suggesting that in K-deficient rats, there is a specific decrease in functional mRNA encoding the NaSi-1 mRNA. CONCLUSION: These findings indicate that chronic K deficiency leads to a reduction in serum Si levels and an increase fractional excretion of Si, and reduces Si reabsorption by down-regulating the expression of the proximal tubular Na/Si-1 cotransporter protein and mRNA.

Animals↗

A genomic screen of autism: evidence for a multilocus etiology.

We have conducted a genome screen of autism, by linkage analysis in an initial set of 90 multiplex sibships, with parents, containing 97 independent affected sib pairs (ASPs), with follow-up in 49 additional multiplex sibships, containing 50 ASPs. In total, 519 markers were genotyped, including 362 for the initial screen, and an additional 157 were genotyped in the follow-up. As a control, we also included in the analysis unaffected sibs, which provided 51 discordant sib pairs (DSPs) for the initial screen and 29 for the follow-up. In the initial phase of the work, we observed increased identity by descent (IBD) in the ASPs (sharing of 51.6%) compared with the DSPs (sharing of 50.8%). The excess sharing in the ASPs could not be attributed to the effect of a small number of loci but, rather, was due to the modest increase in the entire distribution of IBD. These results are most compatible with a model specifying a large number of loci (perhaps >/=15) and are less compatible with models specifying </=10 loci. The largest LOD score obtained in the initial scan was for a marker on chromosome 1p; this region also showed positive sharing in the replication family set, giving a maximum multipoint LOD score of 2.15 for both sets combined. Thus, there may exist a gene of moderate effect in this region. We had only modestly positive or negative linkage evidence in candidate regions identified in other studies. Our results suggest that positional cloning of susceptibility loci by linkage analysis may be a formidable task and that other approaches may be necessary.

Adolescent↗

Store tobacco policies: a survey of store managers, California, 1996-1997.

OBJECTIVE: To identify store tobacco policies and retailer perception and beliefs that may have contributed to changes in compliance with youth access laws in California. DESIGN: In the winter of 1996-7, a cross sectional, follow up telephone survey was conducted of California store managers whose stores were anonymously surveyed for illegal tobacco sales in the summer of 1996 (that is, 1996 Youth Tobacco Purchase Survey, YTPS). SETTING: A simple random sample of stores from a list of California stores likely to sell tobacco, used in the 1996 YTPS. PARTICIPANTS: 334 managers (77%) of the 434 stores surveyed in 1996 responded to the survey. After eliminating stores that stopped selling tobacco or were under new management or ownership, 320 responses of store managers were included in the analysis. The stores were analysed by type of ownership: chain, which included corporate managed (n = 61); franchise owned (n = 56); and independent (n = 203). MAIN OUTCOME MEASURES: Responses of store managers were linked with the 1996 YTPS outcomes. Manager responses were compared by chi2 tests. Logistic regression analyses were conducted to identify store factors associated with illegal tobacco sales. RESULTS: A lower likelihood of illegal sales rate was associated with the chain stores when compared with the independent stores (odds ratio (OR) = 0.4, 95% confidence interval (CI) 0.2 to 0.9). A lower likelihood of illegal tobacco sales was found in stores that implemented tobacco related activities in the previous year such as changing tobacco displays (OR = 0.5, 95% CI 0.2 to 0.9) or adding new warning signs (OR = 0.7, 95% CI 0.4 to 1.2). Store managers' beliefs that youth were sent to their stores to do compliance checks also resulted in a lower likelihood of illegal sales (OR = 0.7, 95% CI 0.4 to 1.1). CONCLUSIONS: Store tobacco youth access policies, and managers' beliefs about the extent of youth access enforcement in the community, are important in reducing illegal tobacco sales to minors.

Adolescent↗

Metabolic acidosis regulates rat renal Na-Si cotransport activity.

Recently, we cloned a cDNA (NaSi-1) localized to rat renal proximal tubules and encoding the brush-border membrane (BBM) Na gradient-dependent inorganic sulfate (Si) transport protein (Na-Si cotransporter). The purpose of the present study was to determine the effect of metabolic acidosis (MA) on Na-Si cotransport activity and NaSi-1 protein and mRNA expression. In rats with MA for 24 h (but not 6 or 12 h), there was a significant increase in the fractional excretion of Si, which was associated with a 2.4-fold decrease in BBM Na-Si cotransport activity. The decrease in Na-Si cotransport correlated with a 2.8-fold decrease in BBM NaSi-1 protein abundance and a 2.2-fold decrease in cortical NaSi-1 mRNA abundance. The inhibitory effect of MA on BBM Na-Si cotransport was also sustained in rats with chronic (10 days) MA. In addition, in Xenopus laevis oocytes injected with mRNA from kidney cortex, there was a significant reduction in the induced Na-Si cotransport in rats with MA compared with control rats, suggesting that MA causes a decrease in the abundance of functional mRNA encoding the NaSi-1 cotransporter. These findings indicate that MA reduces Si reabsorption by causing decreases in BBM Na-Si cotransport activity and that decreases in the expression of NaSi-1 protein and mRNA abundance, at least in part, play an important role in the inhibition of Na-Si cotransport activity during MA.

Acidosis↗

Chemopreventive effects of tea extracts and various components on human pancreatic and prostate tumor cells in vitro.

Pancreatic and prostate cancers pose serious problems to human health. To determine the potential for chemopreventive intervention against pancreatic and prostate cancers, black and green tea extracts and components of these extracts were examined in vitro for their effect on tumor cell growth. Components included a mixture of polyphenols from green tea (GTP), mixtures of polyphenols (BTP) and of theaflavins (MF) from black tea, and the purified components epicatechin-3-gallate (ECG) and epigallocatechin-3-gallate (EGCG). Two human cell lines, pancreatic adenocarcinoma (HPAC) and prostate tumor (LNCaP), were exposed to these agents for 24 hours. Results showed inhibition (approx 90%) of cell growth in pancreatic tumor cells by black and green tea extracts (0.02%). GTP (10 micrograms/ml) and MF (100 micrograms/ml) significantly inhibited growth (approx 90%); ECG and EGCG inhibited growth as well (approx 95%). Black and green tea extracts, GTP, and EGCG decreased the expression of the K-ras gene, as determined by reverse transcription-polymerase chain reaction. Green and black tea extracts decreased the multidrug-resistant gene (mdr-1), although GTP and EGCG increased expression. Similar data were obtained in the prostate cell line LNCaP. All agents significantly inhibited growth. These agents increased expression of the mdr-1 gene. This study suggests that components from black and green tea extracts can modulate the expression of genes known to play a role in the carcinogenesis process and, therefore, may be potential agents for chemoprevention against pancreatic cancer.

Anticarcinogenic Agents↗

A pilot study on risperidone metabolism: the role of cytochromes P450 2D6 and 3A.

BACKGROUND: The limited available information on plasma risperidone levels shows a stable relationship between daily doses of risperidone and total plasma concentration (risperidone plus its active metabolite 9-hydroxyrisperidone). The ratio between risperidone and 9-hydroxyrisperidone characterizes cytochrome P450 2D6 (CYP2D6) status. According to the manufacturer, the CYP2D6 genotype or drugs that influence CYP2D6 or other cytochrome P450 isoenzyme activity are not expected to be clinically significant. One case report suggests that CYP3A participates in the metabolism of risperidone. METHOD: A case series of 13 risperidone patients (the initial case and 12 new cases) who were genotyped for CYP2D6 were followed, and another 20 risperidone patients from a case-control study for the CYP2D6 genotype were reviewed. RESULTS: The CYP2D6 poor metabolizers, who are enzyme deficient (2/13 in the case series and 3/20 in the case-control study), did not appear to tolerate risperidone well. Drugs affecting CYP3A, in particular powerful inducers and inhibitors, resulted in at least a 2-fold decrease or increase in plasma risperidone levels. CONCLUSION: The anecdotal nature of this study is clearly a limitation. Drugs influencing CYP3A and CYP2D6 metabolic activity may significantly affect risperidone levels. Thus, plasma level monitoring of risperidone in a clinical setting may be useful, especially if patients are taking multiple medications or a CYP2D6 deficiency is suspected. New prospective studies under more controlled conditions are needed to verify these hypotheses.

Adolescent↗

The sarcoplasmic reticulum Ca2+ pump: inhibition by thapsigargin and enhancement by adenovirus-mediated gene transfer.

The role of the sarcoplasmic reticulum Ca2+ pump in the excitation-contraction coupling of cardiac muscle fibers was evaluated in experiments on SR ATPase inhibition with thapsigargin or, alternatively, on Ca2+ pump enhancement by SR ATPase transgenic expression. We found that thapsigargin, a highly specific and potent inhibitor of the SR ATPase, produces a strong reduction of cytosolic Ca2+ transient and contractile activation in neonatal rat myocytes, in the absence of any other functional effect. On the other hand, Ca2+ pump enhancement by ATPase transgenic expression affects dramatically Ca2+ transient and twitches, resulting in shorter duration and more rapid decay rates. Of particular interest is gene transfer mediated by recombinant adenovirus vectors under control of a cell-specific promoter, resulting in transgenic expression of all myocytes in culture, and no expression in fibroblasts.

Adenoviridae↗

Epidemiology, diagnosis and treatment of systemic Candida infection in surgical patients under intensive care.

The incidence of systemic Candida infections in patients requiring intensive care has increased substantially in recent years as a result of a combination of factors. More patients with severe underlying disease or immunosuppression from anti-neoplastic or anti-rejection chemotherapy and at risk from fungal infection are now admitted to the ICU. Improvements in supportive medical and surgical care have led to many patients who would previously have died as a result of trauma or disease surviving to receive intensive care. Moreover, some therapeutic interventions used in the ICU, most notably broad-spectrum antibiotics and intravascular catheters, are also associated with increased risks of candidiasis. Systemic Candida infections are associated with a high morbidity and mortality, but remain difficult to diagnose and ICU staff need to be acutely aware of this often insidious pathogen. A number of studies have identified risk factors for systemic Candida infection which may be used to identify those at highest risk. Such patients may be potential candidates for early, presumptive therapy. Here we review the epidemiology, pathogenesis, morbidity and mortality of systemic Candida infections in the ICU setting, and examine predisposing risk factors. Antifungal treatment, including the use of amphotericin B, flucytosine and fluconazole, and the roles of early presumptive therapy and prophylaxis, is also reviewed.

Antifungal Agents↗

Pilot study of the cytochrome P450-2D6 genotype in a psychiatric state hospital.

OBJECTIVE: The authors conducted a pilot study to develop preliminary data on the frequency of cytochrome P450-2D6 (CYP2D6) genotypes in state psychiatric hospital patients and to establish population sizes needed to determine potential clinical relevance in therapeutic outcome. METHOD: One hundred consecutive inpatients at Eastern State Hospital in Kentucky who provided informed consent were genotyped at the CYP2D6 locus during their hospital stay. RESULTS: Twelve of the patients were CYP2D6 deficient, and four carried the *1Xn or *2Xn allele associated with ultrarapid metabolism; all of these patients were Caucasian (N=87). The rate of deficiency in CYP2D6 expression in these Caucasian state psychiatric hospital patients (14%) was twice that of the U.S. population (7%). The patients with CYP2D6 deficiency also appeared more likely to experience side effects in response to CYP2D6 medications. CONCLUSIONS: This study, limited by a small number of subjects, suggests that one-fifth of Caucasians admitted to a state hospital in Kentucky had genotypes associated with extremes in CYP2D6 activity that may have affected their response to CYP2D6 medications.

Adult↗

Barriers to the doctor as patient role. A cultural construct.

BACKGROUND: The fact that few doctors have their own GP may help explain doctors' poor health outcomes. Barriers to the doctor as patient role may arise from problematic perceptions of the 'doctor' subject position and from its subjugation of 'other-than-doctor' positions. Medical culture appears to foster and construct inappropriate health seeking behaviour of doctors. OBJECTIVE: A behaviour model is proposed--delusion, denial and delay; self-investigation, self-diagnosis, self-treatment and self-referral. Application of a behaviour change model could facilitate the doctor as patient role. DISCUSSION: Literary theory and sociology critiques may help peel off the social construction of 'doctor'. The realisation of such myths may allow access to medical care enjoyed by the general community.

Attitude of Health Personnel↗