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Biomedical subjects

S Burns

Publications and source records attributed to S Burns.

At least 37 records · Page 2Linked to original sources

The Wiskott-Aldrich syndrome: disordered actin dynamics in haematopoietic cells.

The Wiskott-Aldrich syndrome protein (WASp) is a member of a unique family whose members share similar domain structures and are responsible for the transduction of signals from the cell membrane to the actin cytoskeleton. For WASp, the interactions with Rho family GTPases and the cytoskeletal organising complex Arp2/3 are critical to these functions, which when disturbed translate into abnormalities of haematopoietic cell signaling, polarisation, migration and phagocytosis. This review discusses the evidence for regulation of highly dynamic cytoskeletal structures by WASp and the consequences of disturbed function on some of these processes.

Actins↗

Wiskott-Aldrich syndrome: a disorder of haematopoietic cytoskeletal regulation.

The Wiskott-Aldrich Syndrome (WAS) is a rare inherited X-linked recessive disease characterised by immune dysregulation and microthrombocytopenia. Recently, the biological mechanisms that are responsible for the pathophysiology of WAS have been shown to be linked to the regulation of the actin cytoskeleton in haematopoietic cells. The WAS protein (WASp) is now known to be a member of a unique family that share similar domain structures, and that are responsible for transduction of signals from the cell membrane to the actin cytoskeleton. The interactions between WASp, the Rho family GTPase Cdc42, and the cytoskeletal organising complex Arp2/3 are probably critical to many of these functions, which, when disturbed, translate into measurable defects of cell polarisation and motility.

Actin-Related Protein 2↗

Transmyocardial laser revascularisation in patients with refractory angina: a randomised controlled trial.

BACKGROUND: Transmyocardial laser revascularisation (TMLR) is used to treat patients with refractory angina due to severe coronary artery disease, not suitable for conventional revascularisation. We aimed in a randomised controlled trial to assess the effectiveness of TMLR compared with medical management. METHODS: 188 patients with refractory angina were randomly assigned TMLR plus normal medication or medical management alone. At 3 months, 6 months, and 12 months after surgery (TMLR) or initial assessment (medical management) we assessed exercise capacity with the treadmill test and the 12 min walk. FINDINGS: Mean treadmill exercise time, adjusted for baseline values, was 40 s (95% CI -15 to 94) longer in the TMLR group than in the medical-management group at 12 months (p=0.152). Mean 12 min walk distance was 33 m (-7 to 74) further in TMLR patients than medical-management patients (p=0.108) at 12 months. The differences were not significant or clinically important. Perioperative mortality was 5%. Survival at 12 months was 89% (83-96) in the TMLR group and 96% (92-100) in the medical-management group (p=0.14). Canadian Cardiovascular Society score for angina had decreased by at least two classes in 25% of TMLR and 4% of medical-management patients at 12 months (p<0.001). INTERPRETATION: Our findings show that the adoption of TMLR cannot be advocated. Further research may be appropriate to assess any potential benefit for sicker patients.

Angina Pectoris↗

The incidence and prevalence of HIV infection among childbearing women living in Edinburgh city, 1982-1995.

OBJECTIVE: To track the complete course of the HIV epidemic among women from the city of Edinburgh who delivered babies during 1982-1995. METHODS: The performance of the modified Serodia HIV test on dried blood spots from archived neonatal metabolic screening cards stored for up to 11 years was evaluated by testing 221 cards from neonates whose mothers' HIV infection status was already known (100 HIV-positive, 121 HIV-negative). Unlinked anonymous HIV testing of cards from neonates born during 1982-1989 was then performed and the resulting prevalence data were combined with existing data from 1990-1995. Maximum and minimum limits of HIV incidence among women during the 36-month period prior to delivery were calculated using data held on a clinical database of HIV-infected pregnant women that had been generated under strict conditions of confidentiality; these data included the date of the woman's first HIV-positive and, if available, last HIV-negative specimen. RESULTS: The evaluation revealed a sensitivity of 91%, not clearly related to storage time, and a specificity of 100%. HIV infection first entered Edinburgh's childbearing population during the early 1980s with prevalence peaking at 0.4% in 1986 and then decreasing to 0.1% in 1995; a similar incidence profile was seen during this period. Since 1986, the first full year that HIV testing was available, 78% of all infections were known during the pregnancy, 13% were identified retrospectively, and only 10% (10 cases) remain unaccounted for. For infected cases during 1984-1987, 78% were injecting drug users (IDU) and only 22% acquired their infection sexually; this distribution had reversed by 1992-1995. CONCLUSION: HIV testing of neonatal metabolic screening cards stored for up to 11 years can yield results of sufficient accuracy for epidemiological purposes. There has been a substantial decline in the prevalence and incidence of HIV since the mid-1980s. Although new infections are still occurring, the numbers are small. The decline may largely be explained by the impact of preventive measures on the spread of HIV amongst IDU, and thus from IDU to their sexual partners.

Cohort Studies↗

Weaning from mechanical ventilatory support: refinement of a model.

The American Association of Critical-Care Nurses sponsored the third National Study Group to advance the science of weaning from mechanical ventilatory support and to guide clinical practice. The study group proposed a model of weaning in 1994 to provide an organizing framework for scientific inquiry. Since the model was first proposed, the ongoing work of the study group has led to refinement of the model. The purpose of this brief communication is to inform critical care clinicians and researchers about the refinements.

Critical Care↗

Harm reduction measures and injecting inside prison versus mandatory drugs testing: results of a cross sectional anonymous questionnaire survey. The European Commission Network on HIV Infection and Hepatitis in Prison.

OBJECTIVES: (a) To determine both the frequency of injecting inside prison and use of sterilising tablets to clean needles in the previous four weeks; (b) to assess the efficiency of random mandatory drugs testing at detecting prisoners who inject heroin inside prison; (c) to determine the percentage of prisoners who had been offered vaccination against hepatitis B. DESIGN: Cross sectional willing anonymous salivary HIV surveillance linked to a self completion risk factor questionnaire. SETTING: Lowmoss prison, Glasgow, and Aberdeen prison on 11 and 30 October 1996. SUBJECTS: 293 (94%) of all 312 inmates at Lowmoss and 146 (93%) of all 157 at Aberdeen, resulting in 286 and 143 valid questionnaires. MAIN OUTCOME MEASURES: Frequency of injecting inside prison in the previous four weeks by injector inmates who had been in prison for at least four weeks. RESULTS: 116 (41%) Lowmoss and 53 (37%) Aberdeen prisoners had a history of injecting drug use but only 4% of inmates (17/395; 95% confidence interval 2% to 6%) had ever been offered vaccination against hepatitis B. 42 Lowmoss prisoners (estimated 207 injections and 258 uses of sterilising tablets) and 31 Aberdeen prisoners (229 injections, 221 uses) had injected inside prison in the previous four weeks. The prisons together held 112 injector inmates who had been in prison for more than four weeks, of whom 57 (51%; 42% to 60%) had injected in prison in the past four weeks; their estimated mean number of injections was 6.0 (SD 5.7). Prisoners injecting heroin six times in four weeks will test positive in random mandatory drugs testing on at most 18 days out of 28. CONCLUSIONS: Sterilising tablets and hepatitis B vaccination should be offered to all prisoners. Random mandatory drugs testing seriously underestimates injector inmates' harm reduction needs.

Cross-Sectional Studies↗

Anonymous HIV surveillance with risk-factor elicitation: at Perth (for men) and Cornton Vale (for women) prisons in Scotland.

434 male and 145 female prisoners were available to participate in cross-sectional, voluntary anonymous HIV surveillance (using saliva samples) with linked self-completion questionnaire at HMP (Her Majesty's Prison) Perth on 17 May and at HMP Cornton Vale on 18 May 1995. Three hundred and four men (70%) and 136 women (94%) completed a risk-factor questionnaire and 304 and 135 samples were received for HIV antibody testing. Two hundred and eighty-two and 132 questionnaires passed logical checks. Six saliva samples from Perth (all injectors) out of 304 and none from Cornton Vale out of 134 tested were HIV antibody positive. Four were presumptively from known HIV-infected male inmates; the other 2 were local men, under 26 years, who began injecting in 1989-91, and both reported having had a recent HIV test. Overall HIV prevalence was estimated at 2% compared to a known prevalence of 1.4% (6/434), giving a 1.5 ratio of overall: disclosed HIV prevalence at HMP Perth. HIV prevalence was estimated at 7% (6/82) for injector-participants and 14% (5/35) for local injector participants. At Cornton Vale, where both known HIV-infected inmates abstained, overall and disclosed HIV prevalence, were equal at 1.4%. At Perth Prison, 29% of prisoners had injected drugs (82/278); 85% of injector-inmates reported having injected inside (some prison and 31% (25/80) had started to inject while inside, 7 during their present sentence. Of all 21 injector-inmates who first injected after 1991, 10 had started to inject inside, including one of 69 male inmates who had never been inside before. The corresponding figures for Cornton Vale, where 46% of inmates were injectors (58/132), were that 57% of injector-inmates had injected inside (32/56) but only one woman, for whom this was not her first sentence, had started to inject inside. Twenty-eight per cent of male prisoners (78/277) and 57% of male injector-inmates (47/82) had had a personal HIV test since January 1993, as had 35% of female prisoners (43/124) and 57% of female injector-inmates (30/53). A much higher proportion of Glasgow's female prisoners (64%: 38/60) were injectors than of women prisoners from the Edinburgh, Dundee and Fife area (21%: 5/26) or from elsewhere (34%: 15/45). Rape was reported by 23% of women (30/130). Women who had been raped had a more polarized distribution of male sexual partners (none to 2 plus) in the year before sentencing than other women and were more likely to report anal sex (11/30 vs 11/100, P < 0.001). Prostitution had been engaged in by 19% of female injector-inmates (11/57) and was acknowledged by one other woman. However, only 5% of women (6/130) reported ever having been treated for an STD.

Adult↗

Common foot problems.

The foot is a complex region of the body that includes the vascular, neurologic, dermatologic, and musculoskeletal organ systems. This article addresses each of these systems and the common maladies that affect them, with a view toward common presentations, evaluation, differential diagnoses, treatment alternatives, and guidelines for proper referral. Finally, a section of the article is devoted to the prevention and treatment of lower extremity problems unique to patients with diabetes.

Diabetic Foot↗

Walking aches and running pains. Injuries of the foot and ankle.

Running is enjoyed by approximately 30 million people in the United States, 10 million on a regular basis. It is common to encounter a patient who runs and expects his or her primary physician to have a degree of expertise in injuries caused by running. The primary care clinician also may experience the frustration of motivating a patient to exercise, only to have him or her return with complaints of foot or ankle pain. Running injuries occur from an overload on the muscles, tendons, bones, or joints. The knee, foot, and ankle are the most common sites of injury.

Ankle Injuries↗

Scottish national survey of tuberculosis notifications 1993 with special reference to the prevalence of HIV seropositivity.

BACKGROUND: The study sought to determine the contribution of HIV seropositivity to the arrest of decline in tuberculosis notifications in Scotland. METHODS: Survey forms relating to each tuberculosis notification in 1993 were completed by the notifying consultant. Voluntary anonymous HIV testing of tuberculosis cases aged under 65 was requested. Age, sex, ethnic status, country of birth, employment status, occupation, previous tuberculosis, contact status, risk factors for HIV infection, HIV serostatus of cases aged under 65, site, radiological extent, and bacteriological status of tuberculous disease were determined. RESULTS: Five hundred and seventy four cases of tuberculosis were originally notified, of which 77 (14%) subsequently proved to be non-tuberculous and were therefore denotified. Of the 497 cases 423 (85%) were white and 58 (12%) were from the Indian subcontinent. Eighty five per cent of patients from the Indian subcontinent were aged < 55 years whereas 64% of white patients were aged > 55 years. Pulmonary disease was found in 74%, non-pulmonary in 22%, and combined disease in 4% of patients. Of 242 HIV tests performed, three were positive and five other HIV positive patients were known, giving an HIV positivity rate of 1.6% of all tuberculosis notifications in 1993. Annual notification rates for Scotland were 9.7 per 10(5) before and 8.7 per 10(5) after exclusion of previously treated cases; rates were 8.4 per 10(5) for the white population and 179 per 10(5) for those from the Indian subcontinent. CONCLUSIONS: The study documents the distribution of tuberculous disease in Scotland by age, sex, site, and ethnic group for the first time. Notification practices, with respect to denotification, need to be improved. Infection with HIV is presently uncommon in cases of tuberculosis in Scotland but continued vigilance is essential.

Adolescent↗

Anesthesia blocks of the lower extremity. Comparing the Biojector with needle and syringe.

Podiatric surgical procedures frequently involve administration of preoperative local anesthesia, and because of the nature of these blocks, it is believed that needle-free injection could greatly enhance this aspect of clinical practice. The object of the study was to determine if needle-free injections with the Biojector were equivalent to needle and syringe injections for ankle, Mayo, neuroma, hallux, and digital anesthetic blocks. The results indicate that needle-free injection with the Biojector is equal to needle and syringe for some anesthesia blocks. More research in this area is needed to determine if technique with the Biojector has an impact on time of anesthesia onset or on level of discomfort and ecchymosis.

Adult↗

In vivo effects of angiotensin II on vascular smooth muscle contraction and blood pressure are mediated through a protein tyrosine-kinase-dependent mechanism.

The effects of in vivo angiotensin II (AII) treatment on protein tyrosine kinase (PTK) levels were examined. It was found that administration of AII to normotensive Wistar-Kyoto rats induced tyrosine phosphorylation in aorta in a time-dependent manner. There was a rapid increase in phosphotyrosine content as early as 1 min, with peak phosphorylation occurring between 5 and 10 min. The response was also dose dependent, with increases in phosphorylation levels from 1 to 1000 micrograms/kg AII. Tyrosine phosphorylation was blocked using the angiotensin type 1 receptor antagonist losartan (10 mg/kg), suggesting that the effects are receptor mediated. Tyrphostin-25 (100 microM), a selective inhibitor of PTKs, when given in vivo was also able to attenuate phosphorylation by AII, further suggesting a PTK-mediated event. To couple these biochemical changes with physiological events, we also examined the ability of AII to induce vasoconstriction and raise systolic blood pressure through a PTK-mediated mechanism. In addition to increasing phosphorylation levels, AII caused a rise in systolic pressure in vivo and induced contraction in vitro. Both of these responses could be attenuated by pretreatment with losartan or tyrphostin-25. This is the first demonstration of the effects of AII on tyrosine phosphorylation in vivo. The data suggest that AII may induce a pressor response at least in part through activation of PTKs and subsequent phosphorylation of smooth muscle contractile proteins or activation of other protein kinases.

Angiotensin II↗

Immunomagnetic CD4+ and CD8+ cell depletion for patients at high risk for severe acute GVHD.

Acute GVHD remains a major problem in allogeneic BMT, in particular when donors other than HLA-identical siblings are used. To determine the efficacy of an immunomagnetic method for depletion of CD4+ and CD8+ lymphocytes from the marrow graft, a series of 15 patients was studied. Thirteen patients had matched unrelated donors, and two patients had related donors. Cyclosporine was used as GVHD prophylaxis in combination with CD4+ and CD8+ depletion, which removed 94.1 +/- 3.2%, 97.0 +/- 5.1%, and 96.7 +/- 3.1% of CD3+, CD4+ and CD8+ cells, respectively. All patients engrafted promptly with AGC > 500/mm3 after a median of 16 days post-BMT. Acute GVHD grade II-IV developed in 0/2 related transplants and 4/13 MUD transplants; only one patient had grade III-IV acute GVHD. No late graft failure was observed. Three patients relapsed; two had advanced disease at the time of BMT. Seven patients are alive and in CCR after a median of 497 days; actuarial survival is 39% at 24 months. The fever syndrome observed with selective CD8+ cell depletion was not seen with the combined CD4+ and CD8+ cell depletion. Immunomagnetic CD4+ and CD8+ cell depletion of marrow grafts, in combination with in vivo cyclosporine, is a simple, reproducible and effective method to decrease the incidence and severity of acute GVHD in patients at high risk for this complication after allogeneic BMT.

Acute Disease↗

Progression of HIV: follow-up of Edinburgh injecting drug users with narrow seroconversion intervals in 1983-1985.

OBJECTIVE: To describe progression and survival of individuals infected with HIV by injecting drug use in Edinburgh. DESIGN AND METHODS: From 313 HIV-infected patients with retrospectively estimated narrow seroconversion intervals, 260 infected via injecting drug use in the years 1983-1985 were selected for the study group. MAIN OUTCOME MEASURES: The effects of gender, age, human leukocyte antigen (HLA) type and zidovudine (ZDV) treatment on progression and survival from seroconversion; Weibull estimates of the AIDS incubation distribution and the overall survival distribution; slopes of absolute CD4 lymphocyte loss (on the square root scale) and loss of CD4 percentage. RESULTS: The cumulative progression rates at 10 years were 68% to CDC stage IV and 31% to AIDS with a mortality rate of 25%. Three-year survival rates for AIDS and CDC stage IV cases were 25 and 72%, respectively. Gender and age effects on progression or overall survival were not found, although those aged over 30 years experienced poorer survival from AIDS. A strong HLA (A1, B8, DR3) association with faster progression and poorer survival was found. Median survival was estimated by Weibull distribution to be 12.6 years; median AIDS-free time was estimated to be 11.6 years. CD4 cell loss was approximately linear when transformed to the square root scale as was the decline in CD4 percentage. Only HLA effects on slopes were found: A1,B8, DR3 was significantly associated with faster loss of both absolute CD4 cells and CD4 percentage (P < 0.001) and B27 was significantly associated with slower loss of CD4 percentage (P = 0.01). CONCLUSIONS: Edinburgh IDU do not seem to progress more rapidly than other cohorts with predominantly different risk activities. Older age was associated with poorer survival from AIDS but no gender effect was found for progression or overall survival. The clearest significant association with AIDS progression, mortality and loss of CD4 cells was the phenotype HLA A1,B8,DR3. In contrast HLA B27 was associated with slower loss of CD4 cells.

Adult↗