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Biomedical subjects

A Robb

Publications and source records attributed to A Robb.

At least 19 recordsLinked to original sources

Oral streptogramins in the management of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections.

OBJECTIVES: Chronic methicillin-resistant Staphylococcus aureus (MRSA) infections in debilitated patients are difficult to treat. We studied the clinical efficacy and safety of an oral streptogramin, pristinamycin, for these patients. PATIENTS AND METHODS: Patients were admitted consecutively to receive pristinamycin, usually with doxycycline, for 7-21 days. Fifty-six patients (average age 75 years) from hospital and community were treated for skin, soft tissue, chest and other infections. RESULTS: The overall clinical response rate was 39 of 53 patients (74%; 95% CI: 60%, 85%) cured or substantially improved, from 53 of 56 (95%) patients clinically and 49 of 56 (87.5%) patients bacteriologically evaluable. Toxic effects comprised gastrointestinal disturbances in eight patients (14%) and one (2%) possible skin rash. CONCLUSION: This study suggests that oral streptogramins may be useful in the management of debilitated patients with MRSA infections.

Administration, Oral↗

The use of childhood injury surveillance within a general accident and emergency department.

The prevention of accidental injury is a government priority in the United Kingdom. Following the recent Government White Paper, towards a Healthier Scotland (Scottish Office 1999), the issue of poverty and inequalities in health has come to prominence. This study, at Glasgow Royal Infirmary, looked at the socio-economic context of injuries and aimed to identify if there was a relationship between the frequency of injuries and the deprivation status of the patient. This paper examines one method of data collection, the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) which is currently being used at the local children's hospital. The practical difficulties of collecting this data within a busy, general Accident and Emergency (A&E) department are examined. The questionnaire uses narrative and sequence text to provide descriptive information relating to the injury and the events leading up to it. Findings demonstrated that a large percentage of children's injuries were treated at the child's local general hospital. Differences between the two hospitals were also found relating to the children's ages and where the injuries took place. Results also showed that the socio-economic distribution of childhood accidents is still a major problem in this city. Therefore, this study recommends that injury data should be collected at all A&E departments to establish an accurate picture of the pattern of injuries within the city.

Accident Prevention↗

Protein transport: two translocons are better than one.

The translocon is the gateway to the endoplasmic reticulum (ER). In yeast this is the Sec61p complex. However, new evidence suggests that a second translocon containing the Sec61p homolog Ssh1p provides important flexibility to the ER translocation machinery.

Endoplasmic Reticulum↗

Alternatively activated macrophages induced by nematode infection inhibit proliferation via cell-to-cell contact.

The cytokine microenvironment is thought to play an important role in the generation of immunoregulatory cells. Nematode infections are commonly associated with Th2 cytokines and hyporesponsive T cells. Here we show that IL-4-dependent macrophages recruited in vivo by the nematode parasite Brugia malayi actively suppress the proliferation of lymphocytes on co-culture in vitro. These alternatively activated macrophages block proliferation by cell-to-cell contact, implicating a receptor-mediated mechanism. Further, the proliferative block is reversible and is not a result of apoptosis. Suppressed cells accumulate in the G1 and G2/M phase of the cell cycle. Interestingly, the G1 and G2/M block correlates with increased levels of Ki-67 protein, suggesting a mechanism that affects degradation of cell cycle proteins. We also show that, in addition to lymphocyte cell lines of murine origin, these suppressive cells can inhibit proliferation of a wide range of transformed human carcinoma lines. Our data reveal a novel mechanism of proliferative suppression induced by a parasitic nematode that acts via IL-4-dependent macrophages. These macrophages may function as important immune regulatory cells in both infectious and noninfectious disease contexts.

Animals↗

Trends in prenatal diagnosis of Down syndrome and other autosomal trisomies in Scotland 1990 to 1994, with associated cytogenetic and epidemiological findings.

The present report summarizes findings on 670 cases of autosomal trisomy diagnosed in Scotland, with actual or expected dates of delivery in 1990 to 1994 inclusive. Cases were notified by cytogenetic service laboratories. There were 277 prenatal and 369 postnatal diagnoses and 24 spontaneous losses. Excluding the latter, numbers diagnosed with trisomy 21, trisomy 18, trisomy 13, and other trisomies were, respectively, 470 (72.8%), 108 (16.7%), 36 (5.6%), and 32 (5.0%). Estimated maternal age-specific birth rates for trisomy 21 were close to published values from other jurisdictions. However, comparisons with a clinically based national register of congenital anomalies suggested that 3-4% of Down syndrome births were never karyotyped, most being early neonatal deaths. There was a striking increase over the period in the proportion of cases detected prenatally, associated with increased maternal serum screening in mothers <35 years old. Over the 3 final years (1992-1994), prenatal screening followed by elective termination was estimated to reduce the birth rate in trisomy 21 by 24% in mothers aged <35 years, by 57% in older mothers, and by 35% in all mothers. The crude incidence per 1,000 births fell from 1.08 in 1990-1991 to 0.77 in 1992-1994, in spite of an upward shift in the overall maternal age distribution. For trisomies 18 and 13, the estimated overall reductions in the birth rate over the whole 5-year period were respectively, 26 and 17%. In free trisomy 18, there was a significant reduction in the sex ratio (male/female) to 0.65, in line with earlier studies.

Abnormalities, Multiple↗

Malaria and pregnancy: the implementation of interventions.

The choice of interventions for improving malaria control during pregnancy depends on several factors. These include the efficacy of the intervention, consumer acceptability and compliance, provider acceptability, cost, safety, integration with other interventions and the local system of health-care delivery, and the degree of combination of these factors. For successful implementation the following should be recognized: appropriate policy formulation based on a process of advocacy, research and demonstration programmes; regulation and legislation; resource mobilization; consumer awareness; and appropriate delivery, targeting, monitoring and evaluation. Malaria in pregnancy is a priority area for control and a major public-health problem. Improved control of such disease requires better integration into health-care practices.

Africa↗

Serine/threonine protein phosphatases and regulation of K-Cl cotransport in human erythrocytes.

Activation of K-Cl cotransport is associated with activation of membrane-bound serine/threonine protein phosphatases (S/T-PPases). We characterize red blood cell S/T-PPases and K-Cl cotransport activity regarding protein phosphatase inhibitors and response to changes in ionic strength and cell size. Protein phosphatase type 1 (PP1) activity is highly sensitive to calyculin A (CalA) but not to okadaic acid (OA). PP2A activity is highly sensitive to CalA and OA. CalA completely inhibits K-Cl cotransport activity, whereas OA partially inhibits K-Cl cotransport. Membrane PP1 and membrane PP2A activities are elevated in cells suspended in hypotonic solutions, where K-Cl cotransport is elevated. Increases in membrane PP1 activity (62 +/- 10% per 100 meq/l) result from decreases in intracellular ionic strength and correlate with increases in K-Cl cotransport activity (54 +/- 10% per 100 meq/l). Increases in membrane PP2A activity (270 +/- 77% per 100 mosM) result from volume increases and also correlate with increases in K-Cl cotransport activity (420 +/- 47% per 100 mosM). The characteristics of membrane-associated PP1 and PP2A are consistent with a role for both phosphatases in K-Cl cotransport activation in human erythrocytes.

Anemia, Sickle Cell↗

Performance-based assessment of clinical ethics using an objective structured clinical examination.

PURPOSE: To further examine the objective structured clinical examination (OSCE) as a performance-based assessment method for clinical ethics. METHOD: In the spring of 1993, a volunteer sample of 88 final-year medical students from all five Ontario medical schools took a four-station OSCE that used standardized patients and involved decisions to forego life-sustaining treatment. Performance was scored on a checklist of behaviors unique to each case. Data were analyzed for reliability using intraclass correlation coefficients and the Spearman-Brown prophecy formula. RESULTS: Reliability of the test was only .28 as a result of a low average inter-station correlation of .07. To achieve a test reliability of .8, 41 stations (almost seven hours of testing time) would be required. CONCLUSION: Because of its low test reliability, the OSCE is not a feasible stand-alone method for summative evaluation of clinical ethics. This performance-based evaluation method should be combined with other, more reliable evaluation methods. The OSCE has promise for formative evaluation.

Educational Measurement↗

Evaluation of a multicenter ethics objective structured clinical examination.

The purpose of this study was to evaluate a six-station ethics objective structured clinical examination (OSCE) on a volunteer sample of 66 medical students and 33 residents from three Ontario medical schools. The internal consistency reliability was 0.46 and the median interrater reliability was 0.675 (range 0.30 to 0.89). The residents' scores were higher than those of the medical students (F = 2.24, 0.046). Also, the scores differed among the three schools (F = 3.19, p = 0.0004). The ethics OSCE has adequate interrater reliability and construct validity, but low internal consistency reliability. There are differences among the schools that may assist in ethics curriculum evaluation and development.

Brain Death↗

The ethics objective structured clinical examination.

OBJECTIVE: To develop objective structured clinical examination (OSCE) stations to assess the ability of physicians to address selected clinical-ethical situations, and to evaluate inter-rater agreement in these stations. DESIGN: Two ten-minute OSCE stations were developed using video-taped encounters between attending physicians and standardized patients. One scenario involved a daughter requesting a do-not-resuscitate (DNR) order for her competent mother without the mother's knowledge; the other involved a competent elderly woman requesting not to be re-intubated if her congestive heart failure worsened. The scenarios were evaluated using foreign medical graduates taking an OSCE. Each candidate was scored on his or her interaction with a standardized patient in the two OSCE stations by two independent observers. PARTICIPANTS: Eight attending physicians from the Division of General Internal Medicine at the Toronto Hospital were used to develop the OSCE stations, and 69 foreign medical graduates taking the University of Toronto Pre-Internship Program OSCE were used to evaluate the stations. RESULTS: The inter-rater reliability coefficients for the DNR and intubation scenarios were 0.79 (95% CI 0.69-0.87) and 0.75 (95% CI 0.62-0.84), respectively. For the DNR station, the scores of the two examiners, on a scale of 0 to 10, agreed exactly for 34 candidates (50%), within one mark for 59 candidates (87%), and within two marks for 65 candidates (96%). For the intubation station, the scores of the two examiners agreed exactly for 27 candidates (40%), within one mark for 56 candidates (84%), and within two marks for 63 candidates (94%). CONCLUSIONS: The authors produced ethics OSCE stations with face and content validity and satisfactory inter-rater agreement. Ethics OSCE stations may be suitable for evaluating the ability of medical students and residents to address selected clinical-ethical situations.

Analysis of Variance↗

Cyclosporin A binding to calmodulin: a possible site of action on T lymphocytes.

Cyclosporin A, a potent immunosuppressive agent, has been widely used to treat patients with solid organ transplants. Although its precise mechanism of action is unknown, it appears to inhibit subsets of T lymphocytes at an early stage in cell activation. Fluorescent, fully active derivatives of cyclosporin A and calmodulin, a protein that binds calcium and is therefore essential to normal cell function, were utilized to demonstrate that cyclosporin A binds to calmodulin. Flow cytometry showed that the calmodulin inhibitors R24571 and W-7 competitively inhibited binding of cyclosporin A to cloned T lymphocytes. Cyclosporin A inhibited the calmodulin-dependent activation of phosphodiesterase in a dose-dependent manner. Binding of cyclosporin A to calmodulin may prevent the latter's role in the activation of the second messengers and enzymes required for effective cell proliferation and function in the immune response.

Binding, Competitive↗