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Biomedical subjects

M Stevenson

Publications and source records attributed to M Stevenson.

At least 73 records · Page 4Linked to original sources

An overview of the injury severity score and the new injury severity score.

OBJECTIVE: The research was undertaken to describe the injury severity score (ISS) and the new injury severity score (NISS) and to illustrate their statistical properties. DESIGN: Descriptive analysis and assessment of the distribution of these scales. METHODS: Three data sources--the National Pediatric Trauma Registry; the Massachusetts Uniform Hospital Discharge Data Set; and a trauma registry from an urban level I trauma center in Massachusetts--were used to describe the distribution of the ISS and NISS among injured patients. RESULTS: The ISS/NISS was found to have a positively skewed distribution and transformation did not improve their skewness. CONCLUSION: The findings suggest that for statistical or analytical purposes the ISS/ NISS should not be considered a continuous variable, particularly if ISS/NISS is treated as a continuous variable for correlation with an outcome measure.

Adolescent↗

Intestinal disappearance and mesenteric and portal appearance of amino acids in dairy cows fed ruminally protected methionine.

An experiment was conducted to compare the rates of disappearance of amino acids (AA) from the small intestine and their net appearance in the blood draining only the small intestine (mesenteric-drained viscera) and the whole gastrointestinal tract (portal-drained viscera) of cows fed a silage-based diet supplemented or not with ruminally protected Met. Five lactating dairy cows (118+/-4 DIM) equipped with duodenal and ileal cannulae (n = 2) or a duodenal cannula only (n = 3), two of which were multicatheterized, were fed a TMR top dressed with 0 or 72 g of ruminally protected Met per day. The addition of ruminally protected Met to the diet increased the duodenal flux of Met leading to a higher apparent digestibility of Met in the small intestine. Sixty-six percent of Met from ruminally protected Met bypassed the rumen and 82% of that Met disappeared from the small intestine. Arterial plasma Met concentrations numerically increased with ruminally protected Met (45 vs. 18 microM), while total AA concentration decreased. Feeding ruminally protected Met resulted in higher concentrations of urea-N and glucose in arterial plasma. Milk production and milk composition were unaffected. The disappearance of essential AA across the small intestine was equivalent (101%) to their flux through the mesenteric-drained viscera while the portal:mesenteric-drained viscera flux ratio for each essential AA varied from 38% for Thr to 76% for Phe. The portal:mesenteric-drained viscera flux ratio for Met was 66%. These results confirm observations made with pigs and sheep.

Amino Acids↗

General practice out-of-hours service, variations in use and equality in access to a doctor: a cross-sectional study.

BACKGROUND: There is increasing dissatisfaction among general practitioners (GPs) with their 24 hour commitment despite the demand for GP services outside ordinary working hours. The creation of out-of-hours co-operatives has been welcomed by participating GPs and their families and patient satisfaction is generally high. However, there have been concerns about the lack of patient consultation in their development and on the quality of care provided. OBJECTIVES: To examine geographical variation in the rates of out-of-hours calls and to see if there is any systematic variation in how the co-operative that covers the area responds to calls. DESIGN OF STUDY: A secondary data analysis of 110,357 calls received by the co-operative during the second year of its operation. SETTING: A co-operative with four centres providing out-of-hours care for one mostly rural Health Board in Northern Ireland. METHOD: Deprivation score and mortality and long-term illness ratios provided indicators of need at an area level. Proximity to the four co-operative centres was measured as the distance in kilometres and estimated travel time (in minutes) along the road network. RESULTS: Out-of-hours call ratios were proportional to the area deprivation score and proximity to the co-operative centres, though not to area indicators of ill health. Older patients were more likely to be seen by the GP and females over the age of 15 years were more likely to receive telephone advice only (adjusted odds ratio [OR] = 0.785, 95% confidence intervals [CI] 0.756-0.816, P < 0.001). Each kilometre from the centres reduced the likelihood of seeing the GP (OR = 0.978, 95% CI = 0.976-0.979, P < 0.001). Even after controlling for potential confounders a large difference remained in how centres responded to calls. CONCLUSIONS: It is not certain whether these inequalities in services delivery represent inequity as the apposite level or type of response cannot be determined until more is known about the appropriateness of the demand for out-of-hours medical care.

Adolescent↗

Telerheumatology--diagnostic accuracy and acceptability to patient, specialist, and general practitioner.

This study examines the diagnostic accuracy and acceptability of telemedicine in the field of rheumatology. One hundred patients had a telephone and televisual consultation and the results were compared with a face-to-face consultation. While the telephone consultations were often unsatisfactory, the televisual consultations were highly accurate (97%) and acceptable to patients, general practitioners, and specialists.

Adult↗

DepoFoam technology: a vehicle for controlled delivery of protein and peptide drugs.

A major challenge in the development of sustained-release formulations for protein and peptide drugs is to achieve high drug loading sufficient for prolonged therapeutic effect coupled with a high recovery of the protein/peptide. This challenge has been successfully met in the formulation of several peptide and protein drugs using the DepoFoam, multivesicular lipid-based drug delivery system. DepoFoam technology consists of novel multivesicular liposomes characterized by their unique structure of multiple non-concentric aqueous chambers surrounded by a network of lipid membranes. The objective of this paper is to demonstrate that DepoFoam technology can be used to develop sustained-release formulations of therapeutic proteins and peptides with high loading. DepoFoam formulations of a protein such as insulin, and peptides such as leuprolide, enkephalin and octreotide have been developed and characterized. The data show that these formulations have high drug loading, high encapsulation efficiency, low content of free drug in the suspension, little chemical change in the drug caused by the formulation process, narrow particle size distribution, and spherical particle morphology. Drug release assays conducted in vitro in biological suspending media such as human plasma indicate that these formulations provide sustained release of encapsulated drug over a period from a few days to several weeks, and that the rate of release can be modulated. In vivo pharmacodynamic studies in rats also show a sustained therapeutic effect over a prolonged period. These results demonstrate that the DepoFoam system is capable of efficiently encapsulating therapeutic proteins and peptides and effectively providing controlled delivery of these biologically active macromolecules.

Animals↗

Child pedestrian injury prevention project: student results.

BACKGROUND: Few comprehensive pedestrian safety interventions for primary-school-age children have been developed and evaluated. This paper reports the impact of the 3-year (1995-1997) Child Pedestrian In jury Prevention Project (CPIPP) on a cohort of 1603 children followed from age 6 to 9 years. This multicomponent project comprised an educational intervention for students, their parents and teachers, and the local community, as well as several environmental interventions. The primary aim of CPIPP was to improve children's road-related behavior and to enhance the safety of their road environment. METHODS: Three communities were assigned to the treatment conditions: (1) high-education, community, and environmental interventions; (2) moderate-education intervention only; and (3) comparison (usual road safety education). Children's pedestrian knowledge and road crossing and playing behaviors were assessed using a pre- and posttest self-report questionnaire. Their self-reported road crossing behaviors were validated using an observational schedule and brief interview. RESULTS: Children in the high and moderate intervention groups were significantly more likely to cross the road with adult supervision (P = 0.013) and play away from the road (P = 0.000) than the comparison group. No differences were detected in children's pedestrian safety knowledge between the intervention and comparison groups. CONCLUSIONS: While several methodological limitations may have influenced the study outcomes, these data nonetheless indicate that in the study sample the CPIPP educational intervention deaccelerated the natural increase in children's pedestrian-related risk behavior.

Accident Prevention↗

New targets for inhibitors of HIV-1 replication.

Despite the success of protease and reverse transcriptase inhibitors, new drugs to suppress HIV-1 replication are still needed. Several other early events in the viral life cycle (stages before the viral genome is inserted into host cell DNA) are susceptible to drugs, including virus attachment to target cells, membrane fusion and post-entry events such as integration, accessory-gene function and assembly of viral particles. Among these, inhibitors of virus-cell fusion and integration are the most promising candidates.

Anti-HIV Agents↗

Persistence of episomal HIV-1 infection intermediates in patients on highly active anti-retroviral therapy.

Treatment of HIV-1-infected individuals with a combination of anti-retroviral agents results in sustained suppression of HIV-1 replication, as evidenced by a reduction in plasma viral RNA to levels below the limit of detection of available assays. However, even in patients whose plasma viral RNA levels have been suppressed to below detectable levels for up to 30 months, replication-competent virus can routinely be recovered from patient peripheral blood mononuclear cells and from semen. A reservoir of latently infected cells established early in infection may be involved in the maintenance of viral persistence despite highly active anti-retroviral therapy. However, whether virus replication persists in such patients is unknown. HIV-1 cDNA episomes are labile products of virus infection and indicative of recent infection events. Using episome-specific PCR, we demonstrate here ongoing virus replication in a large percentage of infected individuals on highly active anti-retroviral therapy, despite sustained undetectable levels of plasma viral RNA. The presence of a reservoir of 'covert' virus replication in patients on highly active anti-retroviral therapy has important implications for the clinical management of HIV-1-infected individuals and for the development of virus eradication strategies.

Anti-HIV Agents↗

Distribution of atrophy in Helicobacter pylori-infected subjects taking proton pump inhibitors.

BACKGROUND: Gastric atrophy is associated with Helicobacter pylori infection. Conflicting results have been obtained as to whether acid suppressant therapy hastens the development or changes the distribution of atrophy in the stomach. The aim of this study was to investigate whether concomitant proton pump inhibitor (PPI) therapy in H. pylori-infected individuals resulted in an increase or an alteration in atrophy distribution and whether this was reflected by the plasma gastrin. METHODS: Multiple gastric biopsy specimens were taken from the antrum and corpus from 46 H. pylori-infected subjects, 18 of whom were taking PPIs, and assessed histologically by the updated Sydney System. The control group was age- and sex-matched to the index group. Fasting gastrin levels were measured. RESULTS: In the control group there was no significant tendency for either antral or corpus atrophy to predominate (P = 0.44). In the treatment group there was a significant tendency for corpus as opposed to antral atrophy to develop (P < 0.001). There was no significant difference in the overall atrophy score between the treated and untreated groups (P = 0.76). Fasting gastrin levels were significantly higher in the treated group (P < 0.001). CONCLUSIONS: Treatment with PPIs in H. pylori-infected subjects does not lead to an overall increase in gastric atrophy. It does, however, result in an increased prevalence of corpus as opposed to antral atrophy. This is associated with a significantly higher gastrin level.

Adult↗

The effect of superstition on the day of discharge from maternity units in Northern Ireland: "a Saturday flit is a short sit".

The impetus for evidence-based practice arose from the science of maternity and childcare. Yet this has to coexist with patient preferences which are often based on a belief system far removed from science. This paper shows how a superstition, which suggests that moving on a Saturday is unlucky, affects a large proportion of discharges from maternity units in Northern Ireland. This is a descriptive study of the 77 018 patients admitted to maternity units in Northern Ireland between 1994/95 and 1996/97. Overall 3819 (35.7%) fewer patients than expected were discharged on Saturday and 2445 (23.2%) and 1834 (17.4%) more than expected were discharged on Friday and Sunday respectively. This means that at least 8097 patients were probably affected by the superstition. In an evidence-based world patient preferences are still evident.

Journal Article↗

Inverse relationship between the expression of the human papillomavirus type 16 transcription factor E2 and virus DNA copy number during the progression of cervical intraepithelial neoplasia.

The human papillomavirus type 16 (HPV-16) status of 43 cervical biopsies, which had been characterized histologically as normal, various grades of cervical intraepithelial neoplasia (CIN) and invasive squamous cell carcinoma, was examined by using (i) a novel antibody against the HPV-16 E2 protein, (ii) sensitive HPV-16 DNA in situ hybridization and (iii) microdissection/PCR for the E2 ORF. The data indicate that E2 protein expression is highest in koilocytes in lower-grade CIN (I), but decreases with increasing grade, whereas the detection of HPV DNA is delayed until CIN I/II, rising to the highest levels in carcinoma cells. Co-localization of E2 with HPV-16 DNA-positive cells was most commonly observed in koilocytes in CIN II lesions. PCR analyses of microdissected epithelium from the same or serial sections indicated that E2 ORFs were retained in an intact form in a number of higher-grade CIN lesions and invasive carcinomas.

Carcinoma, Squamous Cell↗

Early therapy of vertical human immunodeficiency virus type 1 (HIV-1) infection: control of viral replication and absence of persistent HIV-1-specific immune responses.

Studies of potent antiretroviral combination regimens were undertaken in young infants to evaluate the potential for long-term suppression of viral replication and to evaluate the immune consequences of such therapies. Early combination antiretroviral therapy led to a loss of plasma viremia, cultivable virus, and labile extrachromosomal replication intermediates. Despite preservation of immune function, persistent human immunodeficiency type 1 (HIV-1)-specific immune responses were not detected in most infants. The absence of detectable, persisting immune responses in most HIV-1-infected infants treated early contrasts with what is typically seen in adults who are treated early. These results are consistent with the notion that early combination antiretroviral therapy of HIV-1-infected infants allows the long-term suppression of viral replication.

Anti-HIV Agents↗

How much interest is the Internet to patients?

OBJECTIVES: To assess the accessibility of the internet, the level of interest from patients attending genitourinary (GU) medicine clinics, and explore potential concerns about confidentiality. METHODS: Questionnaire based survey of patients attending five GU medicine clinics in England. RESULTS: 41% of GU medicine clinic patients in 1999 had access to the internet (range 31%-52%) with access more common in younger age groups, and less common in women and black Caribbean patients. One in 10 patients (with internet access) had used the internet to find out more about the problem with which they had come to the clinic. 60% of patients replied that information on sexual health on the internet was of interest to them and a high proportion of patients said they would use the internet to access information about GU clinics (64%), book an appointment (64%) or get test results (63%). Almost a quarter of patients who made additional suggestions wanted an interactive website. CONCLUSIONS: A high proportion of patients attending GU clinics have access to the internet with potential uses for health education and service delivery.

Adolescent↗

Could a low-cost audio-visual link be useful in rheumatology?

We have investigated prospectively the diagnostic accuracy, specialist satisfaction and patient-specialist rapport of a low-cost audio-visual link between a junior doctor with a patient and a consultant rheumatologist. Using a telephone link and subsequently a video-phone link, 20 patients, with various rheumatological problems, were presented by a junior doctor to the consultant rheumatologist for provisional diagnosis. All patients were then seen face to face by the consultant, when a final diagnosis was made. An independent consultant rheumatologist made a 'gold standard' diagnosis. Thirty-five per cent of diagnoses were made correctly over the telephone and 40% over the video-phone--there was no significant difference in the diagnostic accuracy between these two methods of communication. Rapport over the video-phone was universally poor. Where it was important, clinical signs could not be visualized over the video-phone and in more than 85% of cases small joint swellings could not be seen clearly.

Adolescent↗

Comparison of the in situ and in vivo intestinal disappearance of ruminally protected methionine.

We designed a switchback expriment to compare the intestinal disappearance of ruminally protected Met determined in situ or in vivo over three consecutive periods. Four nonlactating Holstein heifers (477+/-36 kg) with cannulae in the rumen, duodenum, and ileum were fed a diet based on timothy silage to meet requirements for maintenance (dry matter intake = 8.72+/-0.15 kg). A total of 16 bags, containing 1.5 g of ruminally protected Met, were incubated in the rumen (4.5 h) of each cow and transferred to an acid-pepsin solution to simulate the abomasum (2.5 h). Following each incubation, bags were recovered and three bags were dried at 55 degrees C and analyzed for Met. Remaining bags were introduced directly into the duodenal or ileal cannula for the in situ method, while for the in vivo method, the content of remaining bags was transferred into gelatin capsules before their introduction in the duodenal or ileal cannula. Spot samples of digesta were collected during a 96-h period, with Co-EDTA and Cr-mordanted fiber used as indigestible markers to estimate in vivo digestibility. The disappearance of Met in the small intestine determined in vivo tended to be higher than in situ (74.45 vs. 43.65+/-1.79%). Our results indicate that when used to assess intestinal availability of ruminally protected Met, the mobile nylon bag technique can underestimate the true bioavailability of Met.

Animals↗

A novel nuclear export activity in HIV-1 matrix protein required for viral replication.

An important aspect of the pathophysiology of human immunodeficiency virus type-1 (HIV-1) infection is the ability of the virus to replicate in non-dividing cells. HIV-1 matrix (MA), the amino-terminal domain of the Pr55 gag polyprotein (Pr55), bears a nuclear localization signal that promotes localization of the viral preintegration complex to the nucleus of non-dividing cells following virus entry. However, late during infection, MA, as part of Pr55, directs unspliced viral RNA to the plasma membrane, the site of virus assembly. How MA can mediate these two opposing targeting functions is not understood. Here we demonstrate that MA has a previously undescribed nuclear export activity. Although MA lacks the canonical leucine-rich nuclear export signal, nuclear export is mediated through the conserved Crm1p pathway and functions in both mammalian cells and yeast. A mutation that disrupts the MA nuclear export signal (MA-M4) mislocalizes Pr55 and genomic viral RNA to the nucleus, thereby severely impairing viral replication. Furthermore, we show that MA-M4 can act in a dominant-negative fashion to mislocalize genomic viral RNA even in the presence of wild-type MA. We conclude that the MA nuclear export signal is required to counteract the MA nuclear localization signal, thus ensuring the cytoplasmic availability of the components required for virion assembly.

Biological Transport↗