Towards evidence based emergency medicine: best BETS from the Manchester Royal Infirmary. Negative urine analysis to exclude urinary tract infection.
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Biomedical subjects
Publications and source records attributed to B Martin.
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PURPOSE: In vitro models suggest that Heidelberg retina flowmeter (HRF) measurements are affected by changes in photodetector sensitivity. We measured blood flow in a single volume of human retinal tissue in vivo at various sensitivity (DC) levels. METHODS: The peripapillary retinal regions of 12 normal subjects were examined by HRF under five different sensitivity settings: (1) average DC range below 100; (2) average DC range below 125; (3) average DC range near 150 (normal sensitivity); (4) average DC range above 175; and (5) average DC range above 200 or extremely overexposed. The distributions of flow values were examined by pointwise analysis. All pixels from a common tissue location were analyzed, and the effect of their brightness on the flow measurement was evaluated by ANOVA with Fisher's protected least significant difference model. RESULTS: ANOVA analysis of image DC level showed that significantly different DC levels were achieved for each of the five sensitivity settings (P < 0.0001). Flow values decreased with increasing DC for each of the 25th percentile, 50th percentile (P: < 0.0001 for each), 75th percentile (P: = 0.0026), 90th percentile (P: = 0.0216), and mean (P: = 0.0004) flow values. The percentage of pixels with values of zero (avascular tissue) increased with increasing photodetector sensitivity (P< 0.0001). CONCLUSIONS: Improper sensitivity settings alter the detected percentage of avascular tissue and the blood flow measurements in tissue containing capillaries. Consistent assessment of retinal blood flow requires consistent photodetector sensitivity settings between longitudinal images.
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PURPOSE: Determine the short-term effects of creatine supplementation on performance of military tasks, thermoregulation, and health risks. METHODS: Male military personnel were randomly assigned to a creatine (CR; N = 8) or a placebo (CON; N = 8) supplementation group. Testing was conducted at baseline, after a 6-day load phase (20 g/d), and after 4 weeks of taking 6 g/d. Measurements included body composition, liver/kidney function tests, core body temperatures during a 10-mile march and 5-mile run, and performance on physical tasks. RESULTS: Serum and urine creatine increased significantly in the CR group. Body mass and number of pull-ups performed increased significantly in the CR group but not the CON group by week 4. No significant differences between the CR and CON groups were found for other performance measures, body composition, core body temperature, or other biochemical measures. CONCLUSION: Creatine supplementation increased body mass and pull-up performance but did not cause acute health problems. Creatine did not increase core temperature compared with placebo under the environmental conditions of the study, and it is unlikely that creatine will enhance the overall readiness or performance of soldiers.
In January of 2000 an outbreak of influenza-like illness (ILI) was identified by Health Centre nursing staff in the remote island Inuit community of Sanikiluaq, Nunavut. A staged approach to an intervention strategy was adopted and an intervention team dispatched within 48 hours with diagnostic, prophylactic, and therapeutic capabilities and the intent to evaluate the response as well. The presence of influenza virus was determined on site in 3 out of thirteen initial cases of ILI using portable kit based rapid detection. This permitted the use of zanamivir (an inhaled neuraminidase inhibitor) for prophylaxis in 201, and for treatment in 12 persons. Amantadine was only used in 16 and 52 were ineligible for medical intervention, mostly because they fell outside of the window of opportunity or for maternal/reproductive reasons. The intervention strategy framework adopted was felt to be successful and is presented for consideration in future intervention initiatives.
The synthesis, structure-activity relationships, and biological properties of a novel series of potent and selective phosphodiesterase type 4 (PDE4) inhibitors are described. These new aminodiazepinoindoles displayed in vitro PDE4 activity with submicromolar IC(50) values and PDE4 selectivity vs PDE1, -3, and -5. Specifically, one compound (CI-1044, 10e) provided efficient in vitro inhibition of TNFalpha release from hPBMC and hWB with IC(50) values of 0.34 and 0.84 microM, respectively. This compound was found to exhibit potent in vivo activity in antigen-induced eosinophil recruitment in Brown-Norway rats (ED(50) = 3.2 mg/kg po) and in production of TNFalpha in Wistar rats (ED(50) = 2.8 mg/kg po). No emetic side effects at therapeutic doses were observed in ferrets.
Methyl beta-carboline-3-carboxylate (beta-CCM) is a ligand for the benzodiazepine (BZD) binding site of the GABA-A receptors with convulsive properties. We provided evidence for the involvement of a fragment of mouse chromosomes 4 and 13 in beta-CCM-induced seizures in a previous paper. Here, we analyzed, through [3H]-flumazenil binding, whether central BZD binding sites could be involved in the physiological processes underlying these differences of genetic sensitivities. In the JE/Le strain, where the effects of the chromosome 4 fragment can be analyzed, we found associations between [3H]-flumazenil binding and the convulsive action of beta-CCM. On the contrary, this no longer holds true in C3XtEso strain, where the effects of the chromosome 13 fragment were observed.
The reversible acetylation of histones is associated with structural alterations in the chromatin fiber that affect various DNA-related activities. Here we show that the histone acetyltransferase p300 specifically acetylates HMG-14, a nonhistone structural protein that binds to nucleosomes and reduces the compactness of the chromatin fiber. We identify 7 major acetylation sites, 6 of which are novel and have not been known to be acetylated in either HMG-14 or the closely related HMG-17 protein. All the acetylation sites involve evolutionarily conserved residues: 3 within the HMG-14/-17 nucleosomal binding domain and 4 in or near the bipartite nuclear localization domains of the proteins. In tissue culture cells the acetylation pattern is indicative of a selective process in which a subfraction of HMG-14 is preferentially acetylated. We find that the nucleosomal binding domain is a major target for acetylation in vivo and that the specific acetylation of HMG-14 by p300 weakens its interaction with nucleosome cores. Our results suggest that p300 modulates the interaction of HMG-14 with nucleosomes. Thus, p300 may affect chromatin-related activities not only by modifying histones or transcription factors but also by targeting structural nonhistone proteins.
Vibriosis is a major disease problem in shrimp aquaculture. 'Syndrome 93' is a seasonal juvenile vibriosis caused by Vibrio penaeicida which affects Litopenaeus stylirostris in grow-out ponds in New Caledonia. This study assessed the toxic activities of extracellular products (ECPs) from V. penaeicida, V. alginolyticus and V. nigripulchritudo using in vivo injections in healthy juvenile L. stylirostris (= Penaeus stylirostris) and in vitro assays on shrimp primary cell cultures and the fish cell line epithelioma papulosum cyprini (EPC). Toxic effects of ECPs were demonstrated for all pathogenic Vibrio strains tested both in vivo and in vitro, but for shrimp only; no effect was observed on the fish cell line. ECP toxicity for New Caledonian V. penaeicida was found only after cultivation at low temperature (20 degrees C) and not at higher temperature (30 degrees C). This points to the fact that 'Syndrome 93' episodes are triggered by temperature drops. The assays used here demonstrate the usefulness of primary shrimp cell cultures to study virulence mechanisms of shrimp pathogenic bacteria.
BACKGROUND: While aging clearly has protean biological effects on every organ system, the differential effects of aging in women and men in the retrobulbar vasculature, to our knowledge, have never been investigated. Because glaucoma and age-related macular degeneration are closely linked to advanced age, we performed a cross-sectional study using color Doppler imaging of 4 retrobulbar vessels in both healthy women and men. OBJECTIVE: To define the influence of aging per se on ocular hemodynamics. METHODS: Women (n = 73) and men (n = 55), aged from 20 to 90 years, free of ocular and systemic disease, and with normal intraocular pressure, were recruited for this study. Postmenopausal women who were not receiving estrogen replacement therapy were also recruited. Studies involved color Doppler imaging analysis of the ophthalmic, central retinal, and nasal and temporal posterior ciliary arteries. Ophthalmic arterial peak systolic and end-diastolic velocities and a Pourcelot resistance index were determined for each vessel. RESULTS: In both sexes, ophthalmic arterial end-diastolic velocity decreased and the Pourcelot resistance index rose with advancing age (each P<. 001); peak systolic velocity in the ophthalmic vessel was age-independent. In contrast, central retinal arterial flow velocities were unaffected by age in both sexes. In the posterior ciliary arteries, in men, flow velocities and the Pourcelot resistance index were independent of age. However, in women, end-diastolic velocity decreased with age in both the nasal and temporal posterior ciliary vessel (each P<.05); peak systolic velocity was constant; the Pourcelot resistance index in each ciliary artery rose with advancing age (each P<.05). CONCLUSION: In healthy women and men, aging-induced changes in retrobulbar hemodynamics are comparable to alterations seen in patients with glaucoma or age-related macular degeneration, suggesting that vascular changes with senescence may contribute to increased risk for these diseases in older age. Arch Ophthalmol. 2000;118:1076-1080
We tested the hypothesis that Bis1, a gene involved in seizure regulation in mice which has been localized to the distal part of chromosome 4, was the same as the gene Kcnab2, encoding the beta2-subunit for voltage-dependent K+ channels. Two facts suggested this hypothesis: Kcnab2 is located in the 3.1-cM confidence interval containing Bis1 and many studies have shown an involvement of K+ channels in the genesis of seizures. DNA sequence analysis of the coding sequence for Kcnab2 from JE/Le mice revealed no structural alterations which might affect Kcnab2 function. However, several nucleotide changes were observed.
Human skin reconstructs are three-dimensional in vitro models consisting of epidermal keratinocytes plated onto fibroblast-contracted collagen gels. Cells in skin reconstructs more closely recapitulate the in situ phenotype than do cells in monolayer culture. Normal melanocytes in skin reconstructs remained singly distributed at the basement membrane which separated the epidermis from the dermis. Cell lines derived from biologically early primary melanomas of the radial growth phase proliferated in the epidermis and the basement membrane was left intact. Growth and migration of the radial growth phase melanoma cells in the dermal reconstruct and tumorigenicity in vivo were only observed when cells were transduced with the basic fibroblast growth factor gene, a major autocrine growth stimulator for melanomas. Primary melanoma cell lines representing the more advanced stage vertical growth phase invaded the dermis in reconstructs and only an irregular basement membrane was formed. Metastatic melanoma cells rapidly proliferated and aggressively invaded deep into the dermis, with each cell line showing typical invasion and growth characteristics. Our results demonstrate that the growth patterns of melanoma cells in skin reconstructs closely correspond to those in situ and that basic fibroblast growth factor is critical for progression.
OBJECTIVE: To determine whether dosages of a selective beta-blocking agent (betaxolol) and a topical carbonic anhydrase inhibitor (dorzolamide), sufficient to significantly lower intraocular pressure (IOP), have similar or disparate impact on the retinal and retrobulbar circulation. DESIGN: Counterbalanced crossover, with open-label use of medications. PARTICIPANTS: Nine persons with normal-tension glaucoma (NTG). INTERVENTION: After a 3-week drug washout, NTG patients were studied after 1 month of treatment with either dorzolamide or betaxolol, with determinations of IOP and retinal and retrobulbar hemodynamics. MAIN OUTCOME MEASURES: At baseline and after treatment with each drug, retinal arteriovenous passage time was determined by scanning laser ophthalmoscopy after fluorescein dye injection, and flow velocities in the central retinal and ophthalmic arteries were measured with color Doppler ultrasonography imaging. RESULTS: Betaxolol and dorzolamide each lowered IOP significantly, with these changes apparent and maximal after 2 weeks (each P < 0.05). In contrast, dorzolamide (but not betaxolol) accelerated arteriovenous passage of fluorescein dye in the inferior temporal quadrant of the retina (P < 0.05). Neither drug affected arteriovenous passage in the superotemporal retina or any aspect of central retinal or ophthalmic artery flow velocity after either 2 or 4 weeks. CONCLUSIONS: Although both dorzolamide and betaxolol are effective ocular hypotensive agents and their topical instillation leaves retrobulbar hemodynamics unaltered, dorzolamide alone accelerates inferotemporal retinal dye transit.
Gas chromatography olfactometry (GCO) was used to determine key aroma compounds of two red wine vinegars. Sensory analysis was performed to choose the best neutralization agent of acetic acid (NaOH or MgO) and to test representativeness of four extracts obtained by different methods (dichloromethane extraction, XAD-2, mixture of XAD-2 and XAD-7, and Extrelut resins extraction). Neutralization with NaOH followed by dichloromethane extraction was selected to extract volatile compounds of vinegars. Key odorant compounds were determined by GCO based on detection frequency with 13 people. In the two red wine vinegars, 13 odors were perceived by at least 70% of the panelists, and 8 compounds among the 13 were identified: acetic acid, 3-methylbutyric acid, 2-phenyl-1-ethanol, 2, 3-butanedione, butyric acid, 2-methylbutyric acid, mixture of 2- and 3-methyl-1-butanol, and two newly identified compounds in vinegar, 3-hydroxy-2-pentanone and 3-(methylthio)-1-propanal. Quantification of all the volatile compounds was performed by GC-FID, and 10 other compounds were identified for the first time in wine vinegar.
This study evaluated the efficacy of a contingency management (CM) procedure that provided opportunities to win prizes as reinforcers. At intake to outpatient treatment, 42 alcohol-dependent veterans were randomly assigned to receive standard treatment or standard treatment plus CM, in which they earned the chance to win prizes for submitting negative Breathalyzer samples and completing steps toward treatment goals. Eighty-four percent of the CM participants were retained in treatment for an 8-week period compared with 22% of the standard treatment participants (p < .001). By the end of the treatment period, 69% of those receiving CM were still abstinent, but 61% of those receiving standard treatment had used alcohol (p < .05). These results support the efficacy of this CM procedure. Participants earned an average of $200 in prizes. This CM procedure may be suitable for use in standard treatment settings because prizes can be solicited from the community.
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Genetic plasticity plays a central role in the biology of the human pathogen Streptococcus pneumoniae. This is illustrated by the existence of at least 90 different capsular types (the polysaccharide capsule has an essential antiphagocytic function) as well as by the rapid emergence of penicillin-resistant (PenR) pneumococcal isolates. Natural genetic transformation is believed to be essential for this genetic plasticity; capsular types can be switched by intraspecies transformation, whereas interspecies transformation is responsible for the appearance, in the PenR isolates, of mosaic pbp genes, which encode proteins with reduced affinity for penicillin. Data on the regulation of competence for transformation in S. pneumoniae, on the control of intra- and interspecies genetic exchange and on the shuffling and capture of exogenous sequences during transformation are reviewed. Possible links between transformation and changes in environmental conditions are discussed, and the adaptive 'strategy' deduced for S. pneumoniae is compared with that of Escherichia coli.