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Biomedical subjects

A Short

Publications and source records attributed to A Short.

At least 19 recordsLinked to original sources

In vivo measurement of volumetric wear of a total knee replacement.

A new Roentgen Stereophotogrammetric Analysis (RSA) system is reported; it can measure penetration of the metallic femoral component of a Total Knee Replacement (TKR) prosthesis into the polyethylene bearing on the tibial component. This system was used to analyse a study group of six Anatomic Graduated Components (AGC) knee prostheses more than 6 years post-implantation, and to compare with a control group of six newly implanted AGC prostheses. The volumetric loss of polyethylene was estimated by imaging each prosthesis at a series of different knee flexion angles. The mean difference between the RSA measured polyethylene bearing thickness and the manufacturer's quoted values for the control group was -0.03 mm (SD 0.17). The estimated linear penetration at 6.4 years in this prosthesis was determined to be 0.1 mm/year. Volumetric wear was estimated to be 600-700 mm(3)/year at 6.4 years, equating to approximately 100 mm(3)/year. This does not appear to be clinically significant amount of wear as this prosthesis has excellent survival at 10 years.

Aged↗

A novel method for in vivo knee prosthesis wear measurement.

Wear remains an important cause of failure in knee replacement. Of the current methods of early performance assessment or prediction, simulators have been un-physiological, single X-ray film analyses remain limited by accuracy and retrieval and survival methods have a prohibitive time scale. An accurate method is needed to allow a timely assessment of polyethylene component wear in vivo, when a new design is introduced, in order to predict likely outcome. We present a new method for measuring wear in vivo that we believe will allow this prediction of long-term wear. X-ray film pairs were taken of implanted prosthetic metal components. When the X-ray system was calibrated, projections of the appropriate Computer Aided Design (CAD) model could be matched to the shapes on the scanned X-ray films to find component positions. Interpenetration of the metal femoral component into the polyethylene component could then be established and represents our estimate of "wear". This method was used to measure in vivo prosthesis wear to an accuracy of 0.11 mm.

Arthroplasty, Replacement, Knee↗

Ten-year in vivo wear measurement of a fully congruent mobile bearing unicompartmental knee arthroplasty.

Polyethylene particulate wear debris continues to be implicated in the aetiology of aseptic loosening following knee arthroplasty. The Oxford unicompartmental knee arthroplasty employs a spherical femoral component and a fully congruous meniscal bearing to increase contact area and theoretically reduce the potential for polyethylene wear. This study measures the in vivo ten-year linear wear of the device, using a roentgenstereophotogrammetric technique. In this in vivo study, seven medial Oxford unicompartmental prostheses, which had been implanted ten years previously were studied. Stereo pairs of radiographs were acquired for each patient and the films were analysed using a roentgen stereophotogrammetric analysis calibration and a computer-aided design model silhouette-fitting technique. Penetration of the femoral component into the original volume of the bearing was our estimate of linear wear. In addition, eight control patients were examined less than three weeks post-insertion of an Oxford prosthesis, where no wear would be expected. The control group showed no measured wear and suggested a system accuracy of 0.1 mm. At ten years, the mean linear wear rate was 0.02 mm/year. The results from this in vivo study confirm that the device has low ten-year linear wear in clinical practice. This may offer the device a survival advantage in the long term.

Adult↗

In vivo measurement of total knee replacement wear.

Polyethylene wear is one of the most important causes of failure of total knee replacements (TKRs). Currently, wear can only be accurately measured by retrieval studies. There is a need for a method to measure wear accurately in vivo. We have developed a Roentgen stereophotogrammetric analysis (RSA) system that can measure penetration of the metallic femoral component into the polyethylene of the tibia. We have used this system to study six AGC TKRs at 6 years postoperatively and six control AGC TKRs at 2 weeks postoperatively. The mean difference between the RSA measured bearing thickness and the manufacturer's quoted values for the control group was -0.03 mm (S.D. 0.17). The average linear penetration in the study group was 0.8 mm (S.D. 0.46). This was significantly (P<0.0001) different from the control group. The average linear penetration rate was 0.13 mm per year (S.D. 0.08). We would expect the penetration to deepen with time. In young active patients, this could be a cause for concern, particularly with a thin bearing. The current system is accurate enough to measure wear at 5 years post TKR. It has the potential for predicting long-term wear problems with new designs of TKR and new materials within 2 years.

Aged↗

Prospective cohort study showing changes in the monthly incidence of Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia (PCP) remains a serious opportunistic infection in HIV infected individuals. Seasonal changes in climate are associated with changes within individual susceptibility to infection. The possibility of monthly variability in the incidence of PCP was therefore examined by means of a cohort study of a database of 8640 HIV infected individuals attending the Chelsea and Westminster Hospital. There were 792 cases of PCP diagnosed since 1985. A marked decline was observed in the incidence of PCP in mid-1992 coincident with the introduction of PCP prophylaxis. There was a further decline in 1996 after the introduction of highly active antiretroviral therapy. Despite no significant monthly variation in the mean attendance to clinic and CD4 count, both new and all cases of PCP were higher in January than in other months (15.9% and 14.5% of all cases, respectively). A correlation with low rainfall in January and new cases of PCP was observed. These data are consistent with an influence of climatic conditions on the presentation of PCP. The diagnosis of PCP is more common in winter months suggesting that this is a transmissible infection.

AIDS-Related Opportunistic Infections↗

Re-admissions to the State Hospital at Carstairs, 1992-1997.

OBJECTIVE: To examine the incidence and characteristics of re-admissions to the State Hospital over the six year inclusive period of January 1992 to December 1997. RESONS FOR THE STUDY: RISK ASSESSMENT: A re-admission to a high-security setting may be the result of a failed risk assessment at the time of discharge. An analysis of re-admissions might reveal facts that will improve risk prediction. In this context every re-admission to maximum security should qualify for critical incident appraisal. A re-admission could also indicate prudent risk management where the patient is readmitted prior to the occurrence of any new incident. Our analysis may give an indication how risk prediction and risk management is functioning in the Forensic Psychiatry setting. HEALTH ECONOMICS: Patient numbers at the State Hospital have exceeded planning predictions. In the early 1990s the prediction was that numbers would level off at around 200 patients. Instead admission rates continued to rise and the State Hospital in-patient population has on occasion reached its maximum. This trend has continued throughout the decade with the daily patient numbers averaging 236, 248, 252 and 249 in the last four years (1997-2000). In this context the role played by re-admissions is an important health economics issue. DESIGN: Data gathered from the medical records department and examination of medical case files, entered into a database, and subsequently analysed using a variety of tools. Descriptive statistics for the total State Hospital patient population between 1992-1994 were taken from a published survey. Other comparative analyses were undertaken using data from previously published studies. SETTING: The data originate from the State Hospital, Carstairs, Lanarkshire, which is the only psychiatric hospital in Scotland to offer maximum-security care. Patients are admitted from ordinary psychiatric hospitals as well as from a penal setting. The maximum number of staffed beds is currently 257. These comprise an admission unit, two rehabilitation units including one with flatlet accommodation, a specialist learning difficulties unit, an all female unit and six male wards. The Hospital is staffed by psychiatrists, GPs, psychologists, social workers, psychiatric nurses including nurse specialists, occupational therapists, and other specialist staff employed in the education, occupations and recreation departments. RESULTS AND CONCLUSIONS: Annual re-admission rate, averaged over 1992-1997 is 22.3% of all patient discharges in the hospital. This is broadly in line with other studies quoted in the literature. The re-admission rate co-varied with first admission rate at an almost constant ratio of 0.38 over the six-year period of study. There is no apparent systematic reason for this phenomenon. The most apparent risk factor was a previous admission to the State Hospital of less than a years duration. Compared with the current average length of stay of five years, this must be considered a short admission. Patients with an above average length of stay were rarely readmitted. Most re-admissions returned during the first year after discharge and nearly all had returned within a three-year period. State patients on a Restriction Order who will be subject to conditional discharge with ongoing supervision fared best and were least likely to be re-admitted. However such patients are also likely to have an above average length of stay. Convicted prisoners and remanded offenders were most likely to be readmitted. There was almost no crossover between the civil and criminal populations when their status was reviewed on re-admission. This raises the question, whether these two patient groups should be perceived and managed differently. The recent move to build medium secure units in Scotland, such as the Orchard Clinic in Edinburgh, now makes this a practical option. This finding also suggests that, in Scotland, bed closures in Mental Hospitals are not leading to a decant of mentally disordered patients into the penal system, at least at the level of more serious offending. Violence was overall the most common reason for return to the State Hospital. Violence was the predominant reason for re-admission from a local hospital whereas relapse of symptoms, where such symptoms were associated with dangerous behaviour in the past, was rarely given as a reason. In contrast, relapse was the predominant reason for return from prison. This may be related to inadequate prison hospital facilities rather than good risk prediction.

Adult↗

Differential activities of decapeptide agonists of human C5a: the conformational effects of backbone N-methylation.

Analogues of the potent, conformationally biased, decapeptide agonist of human C5a anaphylatoxin, C5a(65-74)Y65,F67,P69,P71,D-Ala73 (YSFKPMPLaR, peptide 54), were synthesized with methyl groups occupying specific amide nitrogen atoms along the peptide backbone. This N-methylation induced crucial extended backbone conformations in a manner similar to the two Pro residues, but without eliminating the contributions made by the side-chain of the residue for which Pro was substituted. The presence of backbone N-methyl groups on peptide 54 analogues had pronounced detrimental effects on the ability to bind and activate C5aRs expressed on human PMNs, but not on the ability to contract smooth muscle of human umbilical artery. Several N-methylated analogues of peptide 54 (peptides 56, 67, 124, 125, and 137) were significantly more selective for smooth muscle contraction, which is mediated by tissue resident macrophages, than for enzyme release from PMNs. Indeed, peptide 67, YSFKDMP(MeL)aR was almost 3000-fold more selective for smooth muscle contraction than for PMN enzyme release. Consistent with these differential activities was the observation that peptide 67 expressed a significantly greater binding affinity to C5aRs expressed on rat macrophages than on rat PMNs. This differential activity was also observed in vivo in the rat where peptide 67 induced a hypotensive response similar to peptide 54 and rhuC5a, but without accompanying neutropenia.

Animals↗

Glycosylation deficiency phenotypes resulting from depletion of GDP-mannose pyrophosphorylase in two yeast species.

The genes encoding GDP-mannose pyrophosphorylase from Saccharomyces cerevisiae (SRB1/PSA1) and Candida albicans (CaSRB1) were expressed under the control of the tightly regulated promoters of MET3 and CaMET3 respectively. Northern analysis showed that the addition of methionine effectively blocks the transcription of pMET3-SRB1/PSA1 and pCaMET3CaSRB1 expression cassettes, which had been integrated into the genomes of appropriate mutants. Methionine-mediated repression of CaSRB1 caused loss of viability in C. albicans, demonstrating that, as in S. cerevisiae, the gene is essential for growth. Depletion of GDP-mannose pyrophosphorylase had a highly pleiotropic effect in the two yeasts. The major phenotypes observed were lysis, failure of cell separation and/or cytokinesis, impaired bud growth and bud's site selection, clumping and flocculation, as well as increased sensitivity to a wide range of antifungal drugs and cell wall inhibitors, and impaired hyphal switching ability. These phenotypes resulted from defects in glycosylation, as demonstrated by reduced affinity for Alcian blue and sensitivity to hygromycin B. Our results provide new information about the roles of protein glycosylation in yeast and, in particular, the steps that require GDP-mannose in the fungal pathogen C. albicans.

Candida albicans↗

Randomised placebo controlled trial of nebulised corticosteroids in acute respiratory syncytial viral bronchiolitis.

OBJECTIVE: To evaluate short and long term effects of giving nebulised budesonide early in respiratory syncytial viral (RSV) bronchiolitis. DESIGN: A multicentre randomised double blind placebo controlled trial. SUBJECTS: Infants admitted to hospital with their first episode of RSV positive bronchiolitis. INTERVENTION: Randomisation to receive either 1 mg of nebulised budesonide (Bud) or placebo (Pla) twice daily from admission until 2 weeks after discharge. Follow up was for 12 months. MAIN OUTCOME MEASURES: Duration of hospital admission, time taken to become symptom free, re-admission rates, general practitioner consultation rates, and use of anti-wheeze medication during follow up. RESULTS: 161 infants were studied. Both arms were similar with respect to initial clinical severity, age, sex, socioeconomic class, and tobacco exposure. Median time from first nebulisation to discharge: Bud and Pla, 2 days. Median number of days for 50% of infants to be symptom free for 48 hours: Bud, 10 days; Pla, 12 days. Respiratory re-admission rates in the 12 month follow up: Bud, 16%; Pla, 18%; median difference (95% confidence interval (CI)), -2 (-14 to 10). Median respiratory related general practitioner attendances: Bud, 4.0; Pla, 4.5; median difference (95% CI), -1 (-2 to 0). Percentage of infants receiving at least one prescription for anti-wheeze medication during follow up, corticosteroids: Bud, 50%; Pla, 60%; difference (95% CI), -10 (-26 to 6); bronchodilators: Bud, 60%; Pla, 67%; difference (95% CI), -7 (-22 to 8). CONCLUSIONS: There are no short or long term clinical benefits from the administration of nebulised corticosteroids in the acute phase of RSV bronchiolitis.

Acute Disease↗

The role of physician communication in improving compliance with mammography screening among women ages 50-79 in a commercial HMO.

Despite its efficacy, mammography is substantially underutilized by older women, even those who have access to regular health care. The factors influencing mammogram compliance status are distinctively examined in this study using a commercial health maintenance organization (HMO) population of women ages 50-79 in which there are no known barriers (financial, access, or knowledge) to mammogram compliance. Two variables were significant predictors of compliance status based on logistic regression analyses: belief that a woman should get a mammogram one or more times per year, and willingness to get a mammogram if the physician recommends it. Issues surrounding consistent physician referral are discussed.

Aged↗

Effects of a new C5a receptor antagonist on C5a- and endotoxin-induced neutropenia in the rat.

A new C5a receptor antagonist, the cyclic peptide Phe-[Orn-Pro-D-cyclohexylalanine-Trp-Arg], (F-[OPdChaWR]), was tested for its ability to antagonize the neutropenic effects of both C5a and endotoxin in rats. Human recombinant C5a (2 microg kg(-1) i.v.) caused rapid neutropenia, characterized by an 83% decrease in circulating polymorphonuclear leukocytes (PMNs) at 5 min. Administration of F-[OPdChaWR] (0.3-3 mg kg(-1) i.v.), did not affect the levels of circulating PMNs but, when given 10 min prior to C5a, it inhibited the C5a-induced neutropenia by up to 70%. Administration of E. Coli lipopolysaccharide (LPS, 1 mg kg(-1) i.v.) also caused neutropenia with an 88% decrease in circulating PMNs after 30 min. When rats were pretreated with F-[OPdChaWR] (0.3 - 10 mg kg(-1) i.v.) 10 min prior to LPS, there was a dose-dependent antagonism of the neutropenia caused by LPS, with up to 69% reversal of neutropenia observed 30 min after LPS administration. These findings suggest that C5a receptor antagonists may have therapeutic potential in the many diseases known to involve either endotoxin or C5a.

Animals↗

Career characteristics among graduates of a Midwestern M.H.S.A. program: variation by gender and length of time since graduation.

This study examined whether differences occur in the careers of men and women graduating from a Midwestern Master's degree program in hospital/health services administration (M.H.S.A.) during the calendar years of 1986-1997. These alumni were divided into two cohorts: 1986-90 and 1991-97, so that temporal differences could be examined. Men and women M.H.S.A. graduates of the 1986-90 cohort are currently working in similar settings. The most common setting is in acute care organizations. Men and women M.H.S.A. graduates in the 1991-97 cohort tend to be working more outside of acute care organizations than the 1986-90 graduates. The 1986-90 group of women graduates are currently in significantly different positions than their male counterparts. Compared to their male colleagues, these women are more likely to be in middle management positions, or out of the work force. A higher percentage of men from the 1986-90 cohort hold senior management positions (such as CEO or vice-president). The 1991-97 cohort of women graduates do not currently hold significantly different types of positions than their male colleagues, though about twice as many women were not working.

Career Choice↗

Confidential inquiry into quality of care before admission to intensive care.

OBJECTIVE: To examine the prevalence, nature, causes, and consequences of suboptimal care before admission to intensive care units, and to suggest possible solutions. DESIGN: Prospective confidential inquiry on the basis of structured interviews and questionnaires. SETTING: A large district general hospital and a teaching hospital. SUBJECTS: A cohort of 100 consecutive adult emergency admissions, 50 in each centre. MAIN OUTCOME MEASURES: Opinions of two external assessors on quality of care especially recognition, investigation, monitoring, and management of abnormalities of airway, breathing, and circulation, and oxygen therapy and monitoring. RESULTS: Assessors agreed that 20 patients were well managed (group 1) and 54 patients received suboptimal care (group 2). Assessors disagreed on quality of management of 26 patients (group 3). The casemix and severity of illness, defined by the acute physiology and chronic health evaluation (APACHE II) score, were similar between centres and the three groups. In groups 1, 2, and 3 intensive care mortalities were 5 (25%), 26 (48%), and 6 (23%) respectively (P=0.04) (group 1 versus group 2, P=0.07). Hospital mortalities were 7 (35%), 30 (56%), and 8 (31%) (P=0.07) and standardised hospital mortality ratios (95% confidence intervals) were 1.23 (0.49 to 2.54), 1.4 (0.94 to 2.0), and 1.26 (0.54 to 2.48) respectively. Admission to intensive care was considered late in 37 (69%) patients in group 2. Overall, a minimum of 4.5% and a maximum of 41% of admissions were considered potentially avoidable. Suboptimal care contributed to morbidity or mortality in most instances. The main causes of suboptimal care were failure of organisation, lack of knowledge, failure to appreciate clinical urgency, lack of supervision, and failure to seek advice. CONCLUSIONS: The management of airway, breathing, and circulation, and oxygen therapy and monitoring in severely ill patients before admission to intensive care units may frequently be suboptimal. Major consequences may include increased morbidity and mortality and requirement for intensive care. Possible solutions include improved teaching, establishment of medical emergency teams, and widespread debate on the structure and process of acute care.

Adult↗

A controlled study of peer relationships of children surviving brain tumors: teacher, peer, and self ratings.

OBJECTIVE: Evaluate the behavioral reputation and peer acceptance of children diagnosed and treated for brain tumors. METHOD: Twenty-eight children surviving brain tumors (8-18 years of age) were compared to 28 nonchronically ill, same classroom, same gender comparison peers (COMP). Peer, teacher, and self-report data were collected. RESULTS: Relative to COMP, children who had been diagnosed with brain tumors received fewer friendship nominations from clasmates and were described by peer, teacher, and self-report as socially isolated. Although they were no longer receiving therapy for their disease, peers perceived brain tumor survivors as being sick, more fatigued, and often absent from school. CONCLUSIONS: These data suggest that children surviving brain tumors are at risk for social difficulties even after treatment ends, although the specific cause(s) for this vulnerability were not investigated in the current study.

Absenteeism↗

Randomised controlled double blind study of role of recombinant erythropoietin in the prevention of chronic lung disease.

AIM: To evaluate the role of recombinant human erythropoietin (R-HuEpo) in reducing iron infusion, which may exacerbate free radical damage, leading to chronic lung disease. METHODS: A multicentre, randomised, placebo controlled, double blind study was carried out in four neonatal intensive care units in Yorkshire. Infants were randomly allocated and received either R-HuEpo (480 U/kg/wk) or placebo by twice weekly subcutaneous injection. The primary outcome measure was the number of days on respiratory support and a secondary outcome the number of blood transfusions required. RESULTS: Forty two very low birthweight (VLBW) infants were randomly allocated. There was little difference in the need for respiratory support one month after randomisation, but subsequently there was a trend towards a reduction in the proportion requiring respiratory support in the R-HuEpo group (difference at three months -0.50, 95% confidence interval -1.00, 0.17). During stay in hospital, the median number of blood transfusions was lower for infants in the R-HuEpo group (difference in medians -2, 95% CI -4, 0). The study was stopped early because of failure to recruit babies at the expected rate. CONCLUSIONS: R-HuEpo seems to reduce the number of days in oxygen for ill VLBW infants. These data could be used to construct a larger multicentre study to evaluate this effect further.

Blood Transfusion↗

Molecular characteristics of anti-self antibody fragments against neutrophil cytoplasmic antigens from human V gene phage display libraries.

Recently it has been demonstrated that human antibody fragments with binding activities against self antigens can be isolated from repertoires of rearranged V genes from non-immunized humans. We have applied phage display technology to study the B cell repertoire for antibody activity against neutrophil cytoplasmic antigens. These antibodies may play an important role in Wegener's granulomatosis (WG) and related forms of vasculitides. Autoantibodies in patients with WG are directed against proteinase 3. The immunodominant antigen in other forms of vasculitis is myeloperoxidase, but the B cell response can also be directed against other neutrophil enzymes, e.g. lysozyme, human neutrophil elastase, lactoferrin and cathepsin G. We show here that anti-self reactivity against neutrophil cytoplasmic antigens can be detected in the rearranged V gene repertoire of healthy individuals and that the reactivity can be directed against structural related epitopes which are present on different neutrophil cytoplasmic antigens. The scFv with binding activities were sequenced and the V gene usage, the level of somatic mutations and the immunoserological characteristics of the antibody fragments are discussed. Further evidence is presented that antibody fragments consisting only of a heavy chain variable domain can recognize neutrophil cytoplasmic antigens in a specific manner. These single-domain antibody fragments were used in experiments designed to establish the relative role of the light chain variable domains in antigen binding.

Amino Acid Sequence↗