Accuracy and cost-effectiveness of single-view echocardiographic screening for suspected mitral valve prolapse.
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Biomedical subjects
Publications and source records attributed to R Scott.
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AIMS: To examine changes in drug-related behaviour in opiate-dependent injectors treated with oral methadone, in a shared care scheme where consumption of the daily dose is usually supervised by a community pharmacist. DESIGN: One-year cohort study. SETTING: Recruitment from the main routes into methadone prescribing in Glasgow during 1996: General Practitioner Drug Misuse Clinic Scheme and the Drug Problem Service. PARTICIPANTS: Current opiate injectors entering methadone treatment. FINDINGS: Among the 204 injectors recruited, 148 (73%) were re-interviewed at 6 months and 118 (58%) at both 6 and 12 months. Twenty-nine per cent of the cohort remained continuously on methadone for 12 months. In that group, over the 12-month period, self-reported daily opiate injecting reduced from 78% to 2%; overdose in the previous 6 months from 24% to 2%; mean daily drug spend from 50 Pounds to 4 Pounds; and mean monthly number of acquisitive crimes reduced from 13 to three. Assuming participants lost to follow-up were unchanged, significant improvements in the total cohort were seen in daily opiate injecting (from 80% at recruitment to 43% at 12 months), overdose (from 27% to 15%), mean daily drug spend (from 63 Pounds to 38 Pounds) and mean monthly number of acquisitive crimes (from 18 to 11). Discontinuation of treatment was mainly due to imprisonment (39%) or sanctions by the prescriber (33%). CONCLUSION: Treatment of opiate-dependent drug injectors with methadone in a community-wide general practitioner-centred scheme, with supervised daily consumption, was associated with major beneficial change for a substantial proportion of patients.
Groin lymphorrhea is an uncommon but serious complication of vascular and cardiac surgery as well as interventional procedures that cannulate the femoral vessels. Treatment options are somewhat controversial. For lymphocutaneous fistulas, a commonly used current modality is early surgical ligation with the assistance of blue-dye staining of the lymphatic anatomy. The purpose of this case series is to give the first description of a new, less invasive, approach using subatmospheric pressure dressing therapy for the treatment of the challenging problem of lymphocutaneous fistulas of the groin.
OBJECTIVE: Multiple strategies to achieve some degree of myocardial revascularization are available. In some, less complete revascularization is accepted to limit invasiveness. To examine the issues of incomplete revascularization, we assessed the long-term impact of additional non-left anterior descending coronary artery stenoses in patients undergoing only grafting of the left internal thoracic artery to the left anterior descending coronary artery. METHODS: A total of 2067 patients underwent primary isolated grafting of the left internal thoracic artery to the left anterior descending coronary artery from 1971 to 1997. Of these, 26% and 13% had 2- and 3-system disease, respectively. Multivariable analyses of survival and reintervention were performed in the hazard function domain for 27,683 patient-years of follow-up (mean 14 +/- 6.7). RESULTS: Survival was 99%, 88%, and 62% at 1, 10, and 20 years. Right coronary artery or left circumflex system disease of 50% or more (P =.02) and particularly high-grade (>/=70%) left circumflex (P =.01) and proximal right coronary artery disease (P =.01), as well as any degree of left main trunk stenosis (P <.0001), were associated with reduced long-term survival. Compared with 75% 20-year survival in patients with no non-left anterior descending disease, those with either left circumflex or left main trunk disease experienced a 44% survival, and those with proximal right coronary artery disease, 42%. The most common stated reason for incomplete revascularization was small vessel size. Freedom from reintervention was 89% and 65% at 10 and 20 years, respectively. High-grade left main trunk disease, but, in contrast, mid or distal disease of the right coronary artery, and not left circumflex disease, were risk factors for reintervention. CONCLUSIONS: These findings call into question the long-term appropriateness of interventions whose strategy includes leaving unrevascularized segments in territories not in the distribution of the left anterior descending coronary artery.
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Although a pregnant woman can now refuse any medical treatment needed by the fetus, the Court of Appeal has acknowledged that ethical dilemmas remain, adverting to the inappropriateness of legal compulsion of presumed moral duties in this context. This leaves the impression of an uncomfortable split between the ethics and the law. The notion of a pregnant woman refusing medical treatment needed by the fetus is troubling and it helps little simply to assert that she has a legal right to do so. At the same time, the idea that a pregnant woman fails in her moral duty unless she accepts any recommended treatment or surgery--however great the burden--is also not without difficulty. This article seeks to find a way between these two somewhat polarized positions by arguing that, instead of being a question primarily about whether legally to enforce moral obligations, the 'maternal-fetal conflict' begins with previously unrecognized difficulties in determining when a woman's prima facie moral rights invoked in the treatment context should 'give way' to the interests of the fetus. This difficulty is mirrored within the law. Thus, how can we tell when a pregnant woman has the moral or legal duty to submit to a caesarean section? Seen in this way, the conflict is a problem which lies at the interface between moral and legal rights and duties, showing that there are important conceptual links between the ethics and the law. Against this background, this article explores the limits of a pregnant woman's right to bodily integrity by focusing upon the idea of her moral duty to aid the fetus through her body. Here we find difficulties in determining the existence and extent of this somewhat extraordinary duty. Such a duty is contrasted with both negative and positive duties toward others in the course of 'general conduct.' Attention to the social context of pregnancy and the refusal of treatment within this is also instructive. Overall, the purpose is to foster understanding and acceptance of the current legal position.
OBJECTIVE: To compare intubation skill level and success rate between interfacility transport team members. DESIGN: Prospective collection of data. SETTING: University affiliated children's hospital interfacility transport team. PATIENTS: One hundred thirty-two pediatric patients (age range 4 days to 11 years) intubated prior to transport by a specialized team. INTERVENTIONS: None. METHODS: Prospective data was gathered from June 1992 November 1996. In 3616 transports reviewed, 132 intubations were performed by the team at the referring facility. Patient ages ranged from 4 days to 11 years with a mean age of 23 months. We compared resident physicians and respiratory care practitioners (RCPs) to a standard threshold of 1 attempt per successful intubation. An attempt was defined as passage of the endotracheal tube into the oropharynx in an effort to pass it through the vocal cords. Patients were sedated and paralyzed for the procedures. The physicians were 2nd and 3rd year pediatric or emergency medicine residents. They received intubation training in Pediatric Advanced Life Support (PALS), Neonatal Resuscitation Program (NRP), and during rotations through neonatal and pediatric intensive care units. RCPs had an average of 3.5 years of experience overall on the transport team. They received training primarily on mannequins and written tests while in school. They were certified in PALS and NRP and required to participate in annual skill laboratories, which consisted of mannequin intubations and a written examination. RESULTS: The results showed the RCPs to have greater overall success as well as greater success of intubation on first attempt compared to the resident physicians. CONCLUSION: In our experience, RCPs on the interfacility transport team were very successful in performing endotracheal intubations and were more successful than resident physicians. RCPs are established members of not only the transport team, but also the intensive care units and, therefore, should be considered qualified to routinely perform endotracheal intubations in those settings as well.
Focusing on the notable 1964 case of Application of the President and Directors of Georgetown College and subsequent cases, the author explores the connections between parents' and children's interests in ways which tend to support a parent's autonomy and hence a parent's refusal of life-sustaining treatment.
There is currently little agreement between hospital protocols when treating convulsive status epilepticus in children, and a working party has been set up to produce a national evidence based guideline for treating this condition. This four step guideline is presented in this paper. Its effectiveness will be highlighted and its use audited in a number of centres.
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This article addresses the increasing need within urban communities for effective, culturally relevant HIV prevention programs. The recruitment efforts of a family-based prevention program aimed at promoting health and preventing HIV risk exposure in urban, African American fourth and fifth grade children living in a community with high rates of HIV infection is detailed. The program, referred to as the CHAMP (Chicago HIV Prevention and Adolescent Mental Health Project) Family Program, is overseen by a collaborative partnership of community parents, school staff, and university-based researchers (Paikoff & McKay, 1995). The recruitment strategies developed as a result of this community-research collaboration are described. Preliminary results of the project's efforts to reach out to families within the targeted, inner-city community are presented.
The p75 neurotrophin receptor (p75NTR) binds all known neurotrophins and has been suggested to either function as a coreceptor for the trk receptor tyrosine kinases or be involved in independent signaling leading to cell death. We have analyzed the effects of nerve growth factor (NGF) on the growth of cultured hippocampal pyramidal neurons and examined the possibility that the effects of NGF are mediated via generation of ceramide produced by neutral sphingomyelinase (N-SMase). During the initial hour of culture, the only detectable NGF receptor is p75NTR, which by comparative Western blot is expressed at 50- to 100-fold lower levels than on PC12 cells. At this early stage of culture, NGF accelerates neurite formation and outgrowth and induces ceramide formation in a dose-dependent manner. An NGF mutant that is deficient in p75NTR binding has no effect on neuronal morphology or ceramide formation. Furthermore, two anti-p75NTR antibodies (REX and 9651), which are known to compete with NGF for binding to p75NTR, mimic the effects of NGF, whereas a monoclonal antibody (MC192) targeted against a different epitope does not. Finally, scyphostatin, a specific N-SMase inhibitor, blocks the effects of NGF. We propose that a neurotrophin-p75NTR-ceramide signaling pathway influences outgrowth of hippocampal neurons. This signaling role of p75NTR may be distinct from other signaling pathways that lead to apoptosis.
omega-Conotoxin TxVII is the first conotoxin reported to block L-type currents. In contrast to other omega-conotoxins, its sequence is characterized by net negative charge and high hydrophobicity, although it retains the omega-conotoxin cysteine framework. In order to obtain structural information and to supply material for further characterization of its biological function, we synthesized TxVII and determined its disulfide bond pairings. Because a linear precursor with free SH groups showed a strong tendency to aggregate and to polymerize, we examined many different conditions for air oxidation and concluded that a mixture of cationic buffer and hydrophobic solvent was the most effective for the folding of TxVII. Synthetic TxVII was shown to suppress the slowly inactivating voltage-dependent calcium current in cultured Lymnaea RPeD1 neurons and furthermore to suppress synaptic transmission between these neurons and their follower cells. In contrast, TxVII did not block calcium flux through L-type channels in PC12 cells, suggesting a phyletic or subtype specificity in this channel family. Disulfide bond pairings of TxVII and its isomers were determined by enzymatic fragmentation in combination with chemical synthesis, thus revealing that TxVII has the same disulfide bond pattern as other omega-conotoxins. Furthermore, the CD spectrum of TxVII is similar to those of omega-conotoxins MVIIA and MVIIC. The precursor sequence of TxVII was determined by cDNA cloning and shown to be closest to that of delta-conotoxin TxVIA, a sodium channel inactivation inhibitor. Thus TxVII conserves the structural fold of other omega-conotoxins, and the TxVIA/TxVII branch of this family reveals the versatility of its structural scaffold, allowing evolution of structurally related peptides to target different channels.
Glial cell line-derived neurotrophic factor (GDNF) has been shown to signal through a multicomponent receptor complex consisting of the Ret receptor tyrosine kinase and a member of the GFRalpha family of glycosylphosphatidylinositol-anchored receptors. In the current model of GDNF signaling, Ret delivers the intracellular signal but cannot bind ligand on its own, while GFRalphas bind ligand but are thought not to signal in the absence of Ret. We have compared signaling pathways activated by GDNF in two neuronal cell lines expressing different complements of GDNF receptors. In a motorneuron-derived cell line expressing Ret and GFRalphas, GDNF stimulated sustained activation of the Ras/ERK and phosphatidylinositol 3-kinase/Akt pathways, cAMP response element-binding protein phosphorylation, and increased c-fos expression. Unexpectedly, GDNF also promoted biochemical and biological responses in a line of conditionally immortalized neuronal precursors that express high levels of GFRalphas but not Ret. GDNF treatment did not activate the Ras/ERK pathway in these cells, but stimulated a GFRalpha1-associated Src-like kinase activity in detergent-insoluble membrane compartments, rapid phosphorylation of cAMP response element-binding protein, up-regulation of c-fos mRNA, and cell survival. Together, these results offer new insights into the dynamics of GDNF signaling in neuronal cells, and indicate the existence of novel signaling mechanisms directly or indirectly mediated by GFRalpha receptors acting in a cell-autonomous manner independently of Ret.
We report on the transplantation of a cardiac allograft from a donor with prolonged exposure to anorexigens. This event allowed us to not only examine the early pathological alterations that characterize anorexigen-induced valvular damage, but to also study the posttransplantation outcome after the donor heart had been removed from the offending milieu. A donor history of anorexigen use should be sought, and if detected, careful evaluation for underlying valvular disease should be entertained. Early valvulopathy may appear clinically mild yet pathologically significant. Our single-case experience also suggests that anorexigen-induced valvulopathy may be a progressive disorder despite removal of the heart from the causative environment.
Individuals with type 2 diabetes mellitus (n = 105; age 36-71 years) on diet therapy alone, and with quite good glycaemic control (mean HbA1c approximately 7.0%) were randomized to receive acarbose (100 mg three times daily) or placebo for 16 weeks, and changes in clinical and metabolic parameters indicative of Syndrome X were monitored. Fasting levels of glucose, glycosylated haemoglobin (HbA1c), true insulin, proinsulin, fibrinogen and lipids were measured four times weekly, and glucose, insulin, proinsulin and triglyceride responses to a standardized 1.6 MJ breakfast were determined at 0, 1 and 2 h post meal. Analysis was on an intention-to-treat basis. Fasting levels of glucose (P < 0.0001), triglycerides (P = 0.03) and HbA1c (P = 0.003) were reduced by acarbose over the 16 weeks of treatment. The mean change in HbA1c from week 0 to 16 differed by 0.4% (P = 0.003) between the two groups. Insulin (P = 0.06), proinsulin (P = 0.07) and glucose (P < 0.0001) responses to the standard meal were reduced. These data show that acarbose reduces fasting glucose and triglyceride levels, lowers HbA1c and limits the glycaemic and insulin response to food in individuals with type 2 diabetes mellitus with Syndrome X. Pharmacological agents that improve the metabolic environment and reduce insulin resistance have the potential to limit the progression of atherogenesis associated with type 2 diabetes mellitus.
Ultrafiltration, diffusion, osmotic shifts, blood-membrane interactions, and psychological factors have all been implicated in the pathogenesis of postdialysis fatigue (PDF). To identify responsible factors, we performed a prospective, randomized, crossover analysis of fatigue scores (scale, 0 to 4) in 12 maintenance hemodialysis subjects with PDF. Fatigue scores were evaluated on nondialysis days (baseline) and after the following procedures on midweek treatment days: standard dialysis using either a 135- to 140-mEq/L sodium bath (routine hemodialysis) or a 150- to 155-mEq/L sodium bath (hypernatric hemodialysis); isolated ultrafiltration; isolated diffusion; and sham procedures with (isolated membrane) or without (recirculation) exposure to a dialysis membrane. Maximal fatigue scores are expressed as mean and 95% confidence intervals (CIs). The highest scores were recorded by patients who had just undergone routine hemodialysis (mean score, 2. 6; 95% CI, 1.7 to 3.4), isolated ultrafiltration (mean score, 2.1; 95% CI, 1.3 to 2.9), and isolated diffusion (mean score, 2.4; 95% CI, 1.5 to 3.2). There were no significant differences in fatigue scores between baseline periods and isolated membrane and recirculation procedures (mean score, 1.3; 95% CI, 0.4 to 2.2). Fatigue scores after hypernatric hemodialysis occupied an intermediate position (mean score, 1.7; 95% CI, 0.8 to 2.6). These results suggest that rapid hydraulic and molecular flux have a greater role in the pathogenesis of PDF than psychological stress and blood-membrane interactions. Use of a high-sodium bath may ameliorate PDF. We conclude that appropriate adjustments in both ultrafiltration and sodium profiling remain the most important means for controlling PDF in patients on short-duration hemodialysis.
Almost 2700 samples of human renal cortex have been collected from throughout the UK over a 16 year period from 1978 to 1993. The mean Cd concentration was 19 micrograms g-1 and the median 16 micrograms g-1. Smokers were, on average, about 5 micrograms g-1 higher than non-smokers. Cd increased from low concentration in the young to a maximum of 23 micrograms g-1 in middle age followed by a decrease in old age. Subjects who had died of renal disease had lower Cd concentrations. Geographical variations in the UK are small and the concentrations appear to be static over the 16 year period. Some 3.9% of the population had Cd concentrations > 50 micrograms g-1, the critical level at which beta 2-microglobulin appears in urine.