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Biomedical subjects

G Rogers

Publications and source records attributed to G Rogers.

At least 19 recordsLinked to original sources

Developing and implementing new safe practices: voluntary adoption through statewide collaboratives.

BACKGROUND: Disseminating new safe practices has proved challenging. In a statewide initiative we developed a framework for (1) selecting two safe practices, (2) developing operational details of implementation, (3) enlisting hospitals to participate, and (4) facilitating implementation. METHODS: Potential topics were selected by a multistep process to identify candidate practices, review the evidence for efficacy and feasibility, and then select them on the basis of importance, efficacy, feasibility, and impact. A multi-stakeholder advisory group representing all constituencies selected two practices: reconciling medications (RM) and communicating critical test results (CTR). Operational details and strategies for implementation were then developed for each practice using a consensus process of discipline stakeholders led by content experts. Hospital CEOs were solicited to participate by the Massachusetts Hospital Association which made the project a "flagship" initiative. A collaborative model was used to facilitate implementation, following the IHI Model for Improvement. In addition to providing exposure to content and method experts, we gave teams a "toolkit" containing recommendations, a change package, and implementation strategies. Each collaborative met four times over an 18 month period. Results were assessed using the IHI team assessment scale and surveys of teams and hospital leaders. RESULTS: Hospital participation rate was high with 88% of hospitals participating in one or both collaboratives. Partial implementation of the practices was achieved by 50% of RM teams and 65% of CTR teams. Full implementation was achieved by 20% of teams for each. CONCLUSIONS: Major factors leading to hospital participation included the intrinsic appeal of the practices, access to experts, and the availability of implementation strategies. Team success was correlated with active engagement of a senior administrator, engagement of physicians, increased use of PDSA cycles, and attendance at collaborative meetings. The prior development of subpractices, recommendations and implementation strategies was essential for the hospital teams. These should be well worked out before hospitals are required to implement any guideline.

Communication↗

Nurses' perceptions of the working environment: a UK independent sector study.

The working environment is an important determinant of employee well-being. Previous UK studies report registered nurses' perception of the working environment using the Work Environment Scale (WES), but surprisingly few include data for nurses working in mental health or learning disability settings. One hundred and sixty-one (58.8%) registered nurses working day shifts in five specialist divisions (forensic adult mental health, adolescent mental health, elderly continuing care, adult and adolescent learning disability and brain injury rehabilitation) of a large charitable hospital comprising mostly secure (i.e. 'locked') wards completed the WES. Nurses working in separate clinical divisions differed only on the 'physical comfort' subscale. These results are discussed in the context of previous UK research: this sample of nurses scored differently on a number of subscales, with the working environment characterized by relatively high levels of support, cohesion and managerial control and slightly lower levels of autonomy. It is unclear whether the differences reflect the organizational (i.e. non-NHS) context, or a secure environment effect. Previous studies of mental health nurses are now 10 years old and we present data that may provide a benchmark of perceptions of the working environment held by nurses working in mental health and learning disability settings.

Adult↗

Sperm characteristics of endurance trained cyclists.

The purpose of this study was to investigate the influence of cycling on sperm characteristics. Twenty subjects volunteered for the study, comprising 10 long distance competitive cyclists (median 25.5 y) and 10 sedentary controls (median 24.5 y). A questionnaire was used to obtain a history of training, health, nutrition and life style. Semen analysis consisted of a detailed evaluation of sperm characteristics that included semen volume, sperm count, viability, motility and morphology. Compared to controls, the cyclists had a significantly lower proportion of spermatozoa with normal morphology (medians: 41.5 % versus 19.5 %; p < 0.01) and a significantly higher proportion of morphologically abnormal tapered forms (medians: 4.5 % versus 22.5 %; p < 0.01). No significant difference in semen volume and sperm motility, viability and count was observed between the two groups. We concluded that endurance cycling appears to be associated with a significant alteration in sperm morphology.

Adult↗

The role of septal deviation in adult chronic rhinosinusitis: a study of 500 patients.

Septal deviation is a common finding and its role in the pathogenesis of chronic rhinosinusitis remains uncertain. The aim of this study was to assess the impact of septal deviation in the region of the ostiomeatal complex with regards to sinus disease, as staged by the Lund-Mackay scoring system in a group of adult patients with symptoms of chronic rhinosinusitis. Five hundred consecutive patients who had undergone CT scanning of the paranasal sinuses for possible chronic sinus disease between Sept. 2002 and Dec. 2003 were recruited. Septal deviation at the ostiomeatal complex on coronal CT scan was evaluated using Radworks diagnostic 5.1 software (Applicare Medical Imaging BU). There were 219 patients with CT positive sinus disease. 281 of the patients had normal sinus CT scans (control group) and were therefore patients with rhinitis rather than rhinosinusitis. Our study showed no significant difference between the chronic rhinosinusitis group and the control group with regards to septal deviation. Nor were we able to demonstrate any correlation between the severity of septal deformity at the ostiomeatal complex region and the severity of sinus disease or OMC disease.

Adult↗

Juvenile angiofibroma of the maxillary sinus.

Primary extra-nasopharyngeal sites of angiofibromas are extremely unusual. We describe a rare case of extra-nasopharyngeal angiofibroma in a one year old child arising from the left maxilla and indirectly involving the lacrimal system. The initial presentation was of a swelling in the region of the left medial canthus. Only four cases of extra-nasopharyngeal angiofibromas in children below the age of two have been described. We review the literature on what is known about extra-nasopharyngeal angiofibromas.

Angiofibroma↗

Depressive disorders and unprotected casual anal sex among Australian homosexually active men in primary care.

OBJECTIVE: To examine the relationship between depressive disorders and unprotected anal intercourse with casual partners, among homosexually active men attending for primary care. METHODS: The first 460 homosexually active men enrolling in an Australian integrated primary care programme were screened for current depressive disorders using the Primary Care Evaluation of Mental Disorders (PRIME-MD) and completed questionnaires on their sexual behaviour in the prior 6 months. One hundred and sixty-two (35%) were HIV positive, 283 (62%) were HIV negative and 15 (3%) were untested. RESULTS: The prevalence of major depressive episode (MDE), as measured by the PRIME-MD, on enrollment was 28% (129/460), while the prevalence of dysthymic disorder (DD) was 26% (121/460). These include 84 men (18%) who met the criteria for both disorders ('double depression'). Neither disorder was associated with HIV status. Men with MDE were less likely to have been sexually active than the remainder of the cohort (90/129 [70%] vs. 291/331 [88%]; OR: 0.32 [95% CI: 0.19-0.52]; P<0.0001). Men with DD alone, however, were significantly more likely than men with neither disorder to report having had unprotected anal intercourse with a casual partner (11/38 [29%] vs. 43/292 [15%]; OR: 2.36 [95%CI: 1.09-5.10]; P=0.035). CONCLUSIONS: Depressive disorders were highly prevalent in this cohort and independent of HIV status. MDE was associated with reduced sexual activity. Among men without MDE, the presence of DD was independently associated with an increased likelihood of reporting unsafe anal sex with a casual partner in the prior 6 months.

Adult↗

Long-term nutrient intake and early age-related nuclear lens opacities.

OBJECTIVE: To assess the relation between usual nutrient intake and subsequently diagnosed age-related nuclear lens opacities. SUBJECTS: Four hundred seventy-eight nondiabetic women aged 53 to 73 years from the Boston, Mass, area without previously diagnosed cataracts sampled from the Nurses' Health Study cohort. METHODS: Usual nutrient intake was calculated as the average intake from 5 food frequency questionnaires that were collected during a 13- to 15-year period before the evaluation of lens opacities. The duration of vitamin supplement use was determined from 7 questionnaires collected during this same period. We defined nuclear opacities as a nuclear opalescence grade of 2.5 or higher using the Lens Opacification Classification System III. RESULTS: The prevalence of nuclear opacification was significantly lower in the highest nutrient intake quintile category relative to the lowest quintile category for vitamin C (P<.001), vitamin E (P =.02), riboflavin (P =.005), folate (P =.009), beta-carotene (P =.04), and lutein/zeaxanthin (P =.03). After adjustment for other nutrients, only vitamin C intake remained significantly associated (P =.003 for trend) with the prevalence of nuclear opacities. The prevalence of nuclear opacities was significantly lower (P<.001) in the highest vitamin C intake quintile category relative to the lowest quintile category (odds ratio, 0.31; 95% confidence interval, 0.16-0.58). There were also statistically significant trends of decreasing prevalence of nuclear opacities with increasing duration of use of vitamin C (P =.004 for trend), vitamin E (P =.03 for trend), and multivitamin (P =.04 for trend) supplements, but only duration of vitamin C supplement use remained significantly associated with nuclear opacities after mutual adjustment for use of vitamin E (P =.05 for trend) or multivitamin (P =.02 for trend) supplements. The prevalence of nuclear opacities was significantly lower (P =.004) for women who used a vitamin C supplement for 10 or more years relative to women who never used vitamin C supplements (odds ratio, 0.36; 95% confidence interval, 0.18-0.72). Plasma measures of vitamins C and E taken at the eye examination were also inversely associated with the prevalence of nuclear opacities. CONCLUSION: These results provide additional evidence that antioxidant nutrients play a role in the prevention of age-related nuclear lens opacities.

Aged↗

Member of the Ampakine class of memory enhancers prolongs the single channel open time of reconstituted AMPA receptors.

Ampakines are small benzamide compounds that allosterically produce the positive modulation of AMPA receptors and improve performance on a variety of behavioral tasks. To test if the native synaptic membrane is necessary for the effects of such positive modulators, the mechanism of action of the Ampakine 1-(1,3-benzodioxol-5-ylcarbonyl)-1,2,3,6-tetrahydropyridine (CX509) was investigated in isolated rat brain AMPA receptors reconstituted in lipid bilayers. The drug increased the open time of AMPA-induced single channel current fluctuations with an EC(50) of 4 microM. The action of CX509 was highly selective since it had no effect on the amplitude or close time of channel events. The open time effect had a maximum enhancement of 70-fold and the modulated currents were blocked by CNQX. It is concluded that the synaptic membrane environment is not necessary for Ampakine effects. In fact, CX509 was about 100 times more potent on the reconstituted AMPA receptors than on receptors in their native membrane. These findings indicate that centrally active Ampakines modulate specific kinetic properties of AMPA currents. They also raise the possibility that AMPA receptors are regulated by factors present in situ, thus explaining the more efficient modulatory effects of CX509 when acting on receptors removed from their synaptic location.

Animals↗

A unique type I keratin intermediate filament gene family is abundantly expressed in the inner root sheaths of sheep and human hair follicles.

A unique type I keratin intermediate filament group, comprising three highly related proteins and expressed in the inner root sheath of hair follicles, has been identified in both sheep and human. The first members from these species are named oIRSa1 and hIRSa1 and each encodes a protein of 450 amino acids, with compositional characteristics intermediate between those of previously described hair keratin and epidermal cytokeratin type I intermediate filaments. Detection of abundant mRNA transcripts derived from the sheep and human genes by cRNA in situ hybridization only in the inner root sheath and not in the medulla concurs with the findings of earlier ultrastructural analyses that have reported intermediate filaments only in the inner root sheath. Clustering of the IRSa keratin genes is apparent in the genomes of both species. The three hIRSa genes, known to reside on human chromosome 17, are closely linked to three further type I keratin intermediate filament genes of unknown function. This new gene complex, contained almost entirely within a 156 kb BAC (hRPK.142_H_19), is likely to lie near the type I intermediate filament cytokeratin and hair keratin gene loci at 17q12-q21. A phylogenetic analysis including all known human type I intermediate filament cytokeratins, hHa keratins, hIRSa, and hIRSa-linked keratins suggests that origin of the IRSa keratin intermediate filament linkage group preceded origin of most of the epidermal cytokeratins and all hair keratins during emergence of the keratin intermediate filament genes.

Amino Acid Sequence↗

Adjusting for patient characteristics when analyzing reports from patients about hospital care.

OBJECTIVES: To determine which patient characteristics are associated with reports and ratings of hospital care, and to evaluate how adjusting reports and ratings for hospital differences in such variables affects comparisons among hospitals. DESIGN: A telephone survey of a sample of patients hospitalized in 22 hospitals in a single city and a statewide mail survey of hospitalized patients. MEASURES: The surveys assessed: respect for patients' preferences, coordination of care, information exchange between patient and providers, physical care, emotional support, involvement of family and friends, and transition and continuity. The surveys also asked patients to rate their doctors, nurses, and other hospital staff. RESULTS: The variables with the strongest and most consistent associations with patient-reported problems were age and reported health status. Patient gender and education level also sometimes predicted reports and/or ratings. Models including these variables explained only between 3% and 8% of the variation in reports and ratings. CONCLUSIONS: The impact of adjusting for patient characteristics on hospital rankings was small, although a larger impact would be expected when comparing hospitals with more variability in types of patients. Nevertheless, we recommend adjusting at least for the most important predictors, such as age and health status. Such adjustment helps alleviate concerns about bias. It also may be useful to present data for certain groups of patients (ie, medical, surgical, obstetric) separately to facilitate interpretation and quality improvement efforts.

Age Factors↗

Characterization of Alzheimer's beta -secretase protein BACE. A pepsin family member with unusual properties.

The cerebral deposition of amyloid beta-peptide is an early and critical feature of Alzheimer's disease. Amyloid beta-peptide is released from the amyloid precursor protein by the sequential action of two proteases, beta-secretase and gamma-secretase, and these proteases are prime targets for therapeutic intervention. We have recently cloned a novel aspartic protease, BACE, with all the known properties of beta-secretase. Here we demonstrate that BACE is an N-glycosylated integral membrane protein that undergoes constitutive N-terminal processing in the Golgi apparatus. We have used a secreted Fc fusion-form of BACE (BACE-IgG) that contains the entire ectodomain for a detailed analysis of posttranslational modifications. This molecule starts at Glu(46) and contains four N-glycosylation sites (Asn(153), Asn(172), Asn(223), and Asn(354)). The six Cys residues in the ectodomain form three intramolecular disulfide linkages (Cys(216)-Cys(420), Cys(278)-Cys(443), and Cys(330)-Cys(380)). Despite the conservation of the active site residues and the 30-37% amino acid homology with known aspartic proteases, the disulfide motif is fundamentally different from that of other aspartic proteases. This difference may affect the substrate specificity of the enzyme. Taken together, both the presence of a transmembrane domain and the unusual disulfide bond structure lead us to conclude that BACE is an atypical pepsin family member.

Amino Acid Sequence↗

The norbornenyl moiety of cyclothiazide determines the preference for flip-flop variants of AMPA receptor subunits.

Cyclothiazide and two analogs in which the norbornenyl part was replaced with a cyclohexyl or a cyclohexenyl moiety were examined with regard to their preference for flop vs. flip splice variants of the (+/-)-alphaamino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunits GluR2, 3 and 4. The studies were carried out by measuring the effects of the drugs on the binding of [(3)H]AMPA or [(3)H]fluorowillardiine to membranes from HEK293 cells that stably express the AMPA receptor subunits. Cyclothiazide had four to nine times lower EC(50) values at flip than at flop receptors, as previously reported. In contrast, the two analogs showed little discrimination for GluR3 or GluR4 splice variants and a clear preference for the flop variant in the case of GluR2. These results indicate that it is the norbornenyl component of cyclothiazide which confers the selectivity vis-a-vis flip-flop variants.

Alanine↗

Expression of the homeobox gene, Barx2, in wool follicle development.

We have cloned ovine Barx2, a member of the Bar class of homeobox genes, and present the first description of Barx2 expression in wool follicle development. Barx2 is uniformly expressed in the embryonic ectoderm but is transiently downregulated during the initiation of follicle morphogenesis. Subsequently, Barx2 is expressed throughout the epithelial component of the developing follicle except for a small group of cells at the leading edge of the follicle placode. These Barx2-negative cells are destined to form the follicle bulb and are the progenitors of the inner root sheath and hair shaft. In adult follicles, Barx2 is expressed throughout the outer root sheath but not in the inner root sheath or hair shaft, or in dermal cells associated with the follicle. The pattern of Barx2 expression in follicle morphogenesis is similar to that of the cell adhesion molecule E-cadherin, a similarity that echoes Barx2 coexpression with the L1 cell adhesion molecule in other tissues during mouse embryogenesis. Barx2 is also expressed in tongue and esophagus, two other keratinizing tissues, and we speculate that Barx2 may have a general function in controlling adhesive processes in keratinizing epithelia.

Animals↗

A comparison of the indirect estimate of mean arterial pressure calculated by the conventional equation and calculated to compensate for a change in heart rate.

The standard equation used to calculate mean arterial pressure (MAP) assumes that diastole persists for 2/3 and systole for 1/3 of each cardiac cycle. This ratio is altered when heart rate increases, and therefore we investigated the efficacy of predicting MAP during exercise using non-invasive indirect methods. Eight subjects exercised on a cycle ergometer for 3 minute intervals to elicit heart rates between 100-110, 120-130, 140-150, 160-170, and 180-190 beats/min. In the last minute of each 3 min interval an ECG recording was taken and systolic (SP) and diastolic (DP) blood pressure was measured by manual auscultation. MAP was calculated for each heart rate interval by: MAP=DP+1/3(SP-DP) (method A), and MAP= DP + Fs(SP- DP) (method B), where Fs is the fraction of the cardiac cycle comprising systole, measured from the ECG. Fs increased from 0.35+/-0.049 at rest to 0.47+/-0.039 at a heart rate of 180-190 beats/min. MAP measured by method B was consistently greater than MAP calculated by method A at all heart rates greater than resting heart rate (p<0.01). The error incurred when using the standard MAP equation (method A) to derive MAP during exercise (measured as the percentage difference between method A and B) increased linearly with heart rate (r=0.98). The standard MAP equation should not be applied during exercise, as it does not account for the change in the systolic: diastolic period ratio as heart rate increases.

Adult↗

Effects of the potent ampakine CX614 on hippocampal and recombinant AMPA receptors: interactions with cyclothiazide and GYKI 52466.

R,S-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor up-modulators of the benzamide type ("ampakines") have previously been shown to enhance excitatory synaptic transmission in vivo and in vitro and AMPA receptor currents in excised patches. The present study analyzed the effects of an ampakine (CX614; 2H,3H, 6aH-pyrrolidino[2",1"-3',2']1,3-oxazino[6',5'-5,4]benz o[e]1, 4-dioxan-10-one) that belongs to a benzoxazine subgroup characterized by greater structural rigidity and higher potency. CX614 enhanced the size (amplitude and duration) of field excitatory postsynaptic potentials in hippocampal slices and autaptically evoked excitatory postsynaptic currents in neuronal cultures with EC(50) values of 20 to 40 microM. The compound blocked desensitization (EC(50) = 44 microM) and slowed deactivation of responses to glutamate by a factor of 8.4 in excised patches. Currents through homomeric, recombinant AMPA receptors were enhanced with EC(50) values that did not differ greatly across GluR1-3 flop subunits (19-37 microM) but revealed slightly lower potency at corresponding flip variants. Competition experiments using modulation of [(3)H]fluorowillardiine binding suggested that CX614 and cyclothiazide share a common binding site but cyclothiazide seems to bind to an additional site not recognized by the ampakine. CX614 did not reverse the effect of GYKI 52466 on responses to brief glutamate pulses, which indicates that they act through separate sites, a conclusion that was confirmed in binding experiments. In sum, these results extend prior evidence that ampakines are effective in enhancing synaptic responses, most likely by slowing deactivation, and that their effects are exerted through sites that are only in part shared with other modulators.

Alanine↗

Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE.

Cerebral deposition of amyloid beta peptide (Abeta) is an early and critical feature of Alzheimer's disease. Abeta generation depends on proteolytic cleavage of the amyloid precursor protein (APP) by two unknown proteases: beta-secretase and gamma-secretase. These proteases are prime therapeutic targets. A transmembrane aspartic protease with all the known characteristics of beta-secretase was cloned and characterized. Overexpression of this protease, termed BACE (for beta-site APP-cleaving enzyme) increased the amount of beta-secretase cleavage products, and these were cleaved exactly and only at known beta-secretase positions. Antisense inhibition of endogenous BACE messenger RNA decreased the amount of beta-secretase cleavage products, and purified BACE protein cleaved APP-derived substrates with the same sequence specificity as beta-secretase. Finally, the expression pattern and subcellular localization of BACE were consistent with that expected for beta-secretase. Future development of BACE inhibitors may prove beneficial for the treatment of Alzheimer's disease.

Alzheimer Disease↗

Serum total homocysteine concentrations in the third National Health and Nutrition Examination Survey (1991-1994): population reference ranges and contribution of vitamin status to high serum concentrations.

BACKGROUND: The concentration of circulating total homocysteine is a sensitive marker of inadequate folate and vitamin B12 status. Elevated homocysteine concentrations are associated with an increased risk for vascular disease. OBJECTIVE: To identify reference ranges for serum total homocysteine concentration in U.S. residents and quantify the contribution of circulating vitamin concentrations to high homocysteine concentrations. DESIGN: Cross-sectional prevalence study. SETTING: United States. PATIENTS: A nationally representative sample of 3563 male participants and 4523 female participants 12 years of age or older who participated in the third National Health and Nutrition Examination Survey. MEASUREMENTS: Reference ranges (5th and 95th percentiles) for the total homocysteine concentration were defined among participants who were folate- and vitamin B12-replete and had normal creatinine concentrations. A high total homocysteine concentration was defined as one that exceeded the sex-specific 95th percentile for the reference sample (participants 20 to 39 years of age). The population attributable risk percentage was calculated to determine the contribution of low folate (<11 nmol/L) and vitamin B12 (<185 pmol/L) concentrations to a high homocysteine concentration. RESULTS: Reference ranges for serum total homocysteine concentration increased with age; these ranges were 4.3 to 9.9 micromol/L for male participants and 3.3 to 7.2 micromol/L for female participants 12 to 19 years of age and from 5.9 to 15.3 micromol/L for men and 4.9 to 11.6 micromol/L for women 60 years of age or older. A high homocysteine concentration was defined as at least 11.4 micromol/L for male participants and at least 10.4 micromol/L for female participants. Approximately two thirds of the cases of high homocysteine concentrations were associated with low vitamin concentrations. CONCLUSIONS: Upper reference limits for the serum total homocysteine concentration increased with age and were higher for male participants than for female participants at all ages. In most cases, high homocysteine concentrations were associated with low serum vitamin concentrations.

Adolescent↗