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Biomedical subjects

R Warren

Publications and source records attributed to R Warren.

At least 55 records · Page 3Linked to original sources

Extended intravascular shunting in an experimental model of vascular injury.

PURPOSE: To examine the extended patency (> 24 hrs) of heparin-bonded intravascular shunts in a porcine model of vascular injury. PROCEDURES: Adult swine underwent bilateral, common iliac artery resection (n = 5) or bilateral common iliac vein resection (n = 5) and vessel replacement with interposition, heparin-bonded shunts. Three control swine had vessel dissection only. Hematologic and coagulation profiles were measured at baseline and 24 hrs. Limb perfusion was assessed at 24 hrs by clinical exam and angiography. RESULTS: At 24 hrs, all limbs in both shunt groups were well perfused. All arterial shunts were angiographically patent. No distal emboli were detected. Nine of 10 venous shunts were patent, seven were lined with non-occluding thrombus. No alterations in hematologic or coagulation profiles were noted. CONCLUSIONS: Heparin-bonded shunts remained patent in arteries for 24 hours. Shunts placed in the venous system were prone to thrombus formation but most remained patent.

Animals

Getting through ethics committees: partnerships between researchers and clinicians working with mentally ill clients.

This paper discusses principles of ethics in nursing research with people suffering from mental illness. It offers a set of protocols which have been successful in obtaining approval from ethics committees to conduct research in the area of mental illness-'getting through'. The paper argues that nurse researchers and clinicians can achieve successful outcomes in mental health nursing research by working in partnership. An important aspect of this partnership is a commitment to uphold the rights of consumers of mental health care.

Ethics Committees

Mammography screening: an incremental cost effectiveness analysis of double versus single reading of mammograms.

OBJECTIVE: To compare mammography reading by one radiologist with independent reading by two radiologists. DESIGN: An observational non-randomised trial at St Margaret's Hospital, Epping. SUBJECTS: 33 734 consecutive attenders for breast screening in the main trial and a sample of 132 attenders for assessment who provided data on private costs. INTERVENTIONS: Three reporting policies were compared: single reading, consensus double reading, and non-consensus double reading. MAIN OUTCOME MEASURES: Numbers of cancers detected, recall rates, screening and assessment costs, and cost effectiveness ratios. RESULTS: A policy of double reading followed by consensus detected an additional nine cancers per 10 000 women screened (95% confidence interval 5 to 13) compared with single reading. A non-consensus double reading policy detected an additional 10 cancers per 10 000 women screened (95% confidence interval 6 to 14). The difference in numbers of cancers detected between the consensus and non-consensus double reading policies was not significant (95% confidence interval -0.2 to 2.2). The proportion of women recalled for assessment after consensus double reading was significantly lower than after single reading (difference 2.7%; 95% confidence interval 2.4% to 3.0%). The recall rate with the non-consensus policy was significantly higher than with single reading (difference 3.0%; 2.5% to 3.5%). Consensus double reading cost less than single reading (saving 4853 pounds per 10 000 women screened). Non-consensus double reading cost more than single reading (difference 19 259 pounds per 10 000 women screened). CONCLUSIONS: In the screening unit studied a consensus double reading policy was more effective and less costly than a single reading policy.

Breast Neoplasms

Localization of impalpable breast lesions--a surgical approach.

The conventional approach to localization of impalpable breast lesions, i.e. employing a hooked wire with either stereotaxis or a perforated plate, has potential disadvantages for the operating surgeon. Often the entry point of the wire lies some distance from the site of projection of the lesion on the skin. The guide-wire should pierce the skin at, or close to, the site of any proposed surgical incision and proceed along the shortest and most direct course towards the lesion. Ideally, the wire should lie within a radial distance of between 1 and 2 cm from its target. A method is described which achieves these objectives and involves both radiological and clinical measurements. A total of 665 guide-wire localized biopsies have been carried out at the above institutions between 1 November 1987 and 31 March 1995 and between 1 January 1994 and 31 March 1996. In only 4% of cases was re-positioning of the wire required. Excision of the radiological lesion was obtained with a single biopsy in 99% of cases. A second or third biopsy was indicated in 0.7% and 0.3% of cases, respectively. Migration of the wire occurred in two patients and no cases of wire transection or pneumothorax were reported. This method of localization facilitates subsequent excision and permits the most appropriate incision consistent with optimal cosmesis.

Breast

Doctors leaving the training grades in obstetrics and gynaecology: a study of the years 1985 to 1988.

OBJECTIVES: To determine the numbers of doctors leaving the specialty after obtaining the Membership of the Royal College of Obstetricians and Gynaecologists (MRCOG), and the factors influencing their decisions to seek alternative career paths. DESIGN: Retrospective postal questionnaire based survey. PARTICIPANTS: One hundred and sixty-eight doctors who had passed the MRCOG examination between 1985 and 1988 but were not known to have achieved Consultant or Senior Registrar status in the British Isles by 1993. RESULTS: The response rate was 80%. The crude leaving rate was 31%, although 7.5% had never intended to seek consultant appointment in the specialty in the UK. The majority left shortly after obtaining the Part 2 MRCOG examination, 75% within the first two years thereafter. The perception of the lifestyle of a consultant and poor job prospects were commonly seen as the critical factors causing trainees of both sexes to leave the specialty, although hours of work was the single most commonly cited factor among female trainees. CONCLUSIONS: A consistently high rate of loss from the specialty of obstetrics and gynaecology has been demonstrated in surveys covering the period 1978 to 1988. Approximately one-quarter of this loss reflects trainees who had never intended to pursue consultant appointment in the specialty in the British Isles, half reflects factors which may improve with the implementation of the recommendations contained in the New Deal and the 'Calman' report, and one-quarter reflects loss for inevitable reasons. Loss of trainees for these reasons is therefore a crucial element in manpower calculations.

Career Mobility

The influence of hard water (calcium) and surfactants on irritant contact dermatitis.

Although the induction of irritant contact dermatitis has been extensively studied for surfactants, the role of the environmental factor water hardness (i.e., calcium content) on the induction process has not received attention. Our objective was to investigate differences in surfactant-induced irritant skin reactions from cumulative exposure to 3 different personal cleansing agents and determine whether the irritation potential can be affected by the hardness of the water. 2 commonly used exaggerated washing procedures were variously employed to evaluate representative sodium soap, triethanolamine-soap, or synthetic detergent cleansers under conditions where the water hardness varied from 0-grain to 11-grain (gr). Subjects were clinically evaluated for skin dryness, skin redness, and instrumentally for hydration. Soap binding to skin was quantified using Fourier transform infrared reflectance spectroscopy. Using the more mild wash procedure, skin sites treated under conditions of hard, 11 gr water were significantly drier, had more erythema, and were less hydrated than corresponding sites treated with deionized 0 gr water. All 3 surfactant cleanser behaved similarly. We also found the hardness of the rinse water to be the more significant factor versus that of the wash water. Effect of water hardness on soap binding to skin revealed a similar outcome. Under a more exaggerated wash condition the relationship between water hardness and irritation broke down.

Adolescent

Genotyping of Mycobacterium tuberculosis with additional markers enhances accuracy in epidemiological studies.

Two highly polymorphic Mycobacterium tuberculosis genomic domains, characterized by hybridization to the oligonucleotide (GTG)5, were identified as potential DNA fingerprinting probes. These domains were cloned [pMTB484(1) and pMTB484(2K4), respectively] and shown to be useful for genotype analysis by Southern blotting. These probes were used to genotype geographically linked strains of M. tuberculosis previously shown to have identical IS6110 fingerprints. Subsequent DNA fingerprints generated with MTB484(1) and MTB484(2K4) showed a high degree of polymorphism, allowing subclassification of IS6110-defined clusters into composites of smaller clusters and unique strains. Correlation of the molecular data with patient interviews and clinical records confirmed the sensitivity of these probes, as contacts were established only within subclusters. These findings demonstrate the requirement for multiple probes to accurately classify M. tuberculosis strains, even those with high copy numbers of IS6110. The enhanced accuracy of strain typing should, in turn, further our understanding of the epidemiology of tuberculosis.

Bacterial Typing Techniques

Cutaneous permeability barrier repair following various types of insults: kinetics and effects of occlusion.

Previous studies have shown that acute disruption of the cutaneous permeability barrier by acetone results in an initial rapid phase of repair followed by a later, slower phase. In the present study, we demonstrate that manipulations which disrupt the barrier by other mechanisms, such as tape stripping or detergent treatment, have a similar pattern of barrier repair. In all three models, the return of lipid to the stratum corneum parallels the normalization of barrier function, and occlusion immediately after disrupting the barrier blocks both the return of lipid and the normalization of function. Moreover, occlusion beginning 6-8 h following barrier disruption blocks the late, slower phase of repair, indicating that the late phase can be inhibited independently of the initial phase. Lastly, both severe and relatively minor perturbations of the barrier elicit a repair response with a similar kinetic pattern. In summary, the present study demonstrates that barrier repair responses are similar regardless of the etiology or extent of barrier disruption.

Acetone

The relationship of developmental narrowing of the cervical spinal canal to reversible and irreversible injury of the cervical spinal cord in football players.

An evaluation of forty-five athletes who had had an episode of transient neurapraxia of the cervical spinal cord revealed a consistent finding of developmental narrowing of the cervical spinal canal. The purpose of the present epidemiological study was to determine the relationship, if any, between a developmentally narrowed cervical canal and reversible and irreversible injury of the cervical cord with use of various cohorts of football players as well as a large control group. Cohort I comprised college football players who were asymptomatic and had no known history of transient neurapraxia of the cervical cord. Cohort II consisted of professional football players who also were asymptomatic and had no known history of transient neurapraxia of the cervical cord. Cohort III was a group of high-school, college, and professional football players who had had at least one episode of transient neurapraxia of the cervical cord. Cohort IV comprised individuals who were permanently quadriplegic as a result of an injury while playing high-school or college football. Cohort V consisted of a control group of male subjects who were non-athletes and had no history of a major injury of the cervical spine, an episode of transient neurapraxia, or neurological symptoms. The mean and standard deviation of the diameter of the spinal canal, the diameter of the vertebral body, and the ratio of the diameter of the spinal canal to that of the vertebral body were determined for the third through sixth cervical levels on the radiographs for each cohort. In addition, the sensitivity, specificity, and positive predictive value of a ratio of the diameter of the spinal canal to that of the vertebral body of 0.80 or less was evaluated. The findings of the present study demonstrated that a ratio of 0.80 or less had a high sensitivity (93 per cent) for transient neurapraxia. The findings also support the concept that symptoms may result from a transient reversible deformation of the spinal cord in a developmentally narrowed osseous canal. The low positive predictive value of the ratio (0.2 per cent) however, precludes its use as a screening mechanism for determining the suitability of an athlete for participation in contact sports. Developmental narrowing of the cervical canal in a stable spine does not appear to predispose an individual to permanent catastrophic neurological injury and therefore should not preclude an athlete from participation in contact sports.

Adolescent

Unexpectedly high strain diversity of Mycobacterium tuberculosis in a high-incidence community.

OBJECTIVE: To characterise Mycobacterium tuberculosis strains present in a community experiencing an epidemic, in order to establish whether a high rate of transmission results in low strain diversity. DESIGN: Sputum specimens collected for 18 months; IS6110-based DNA fingerprinting. SETTING: The communities of Ravensmead and Uitsig, Cape Town, South Africa. PARTICIPANTS: Three hundred and thirty-four pulmonary tuberculosis patients attending the Local Authority Health Care Clinic. MAIN OUTCOME MEASURE: DNA fingerprinting. RESULTS: A total of 334 M. tuberculosis isolates were characterised by IS6110-based DNA fingerprinting; 209 strains were identified, 199 having 5 or more insertions. Forty of these strains were present in 2 or more patients (clustering--126 patients in total), which indicates a recent transmission rate of 30%. The 163 unique strains suggest reactivation of latent infections. Computer analysis showed a high degree of strain diversity, and a common progenitor could only be linked to 33% of the strains. Clustering was shown in 50% of drug-resistant isolates. CONCLUSIONS: The low rate of transmission (30%) and the high degree of strain diversity (209 strains) was unexpected and unexplained, given the high burden of disease in this community. The clustering of drug-resistant strains suggests that transmission, rather than lack of compliance, drives the spread of antibiotic resistance in this community. Preliminary indications are that BCG vaccination, while having little effect on the incidence of tuberculosis in this community, may have altered the strain dynamics.

Adolescent

Homeotic genes and diversification of the insect body plan.

The homeotic genes regulate segmental identity by repressing the formation of or influencing the morphology of segmental structures during development. The specific roles these genes have played in the generation of insect diversity are discussed relative to abdominal limb formation and to the evolution of wings as novel repeated structures. Other recent findings discussed suggest possible 'homeotic' origins for the non-homeotic genes found within the homeotic complexes of higher insects.

Animals

Mammography screening: an incremental cost effectiveness analysis of two view versus one view procedures in London.

STUDY OBJECTIVE: To compare the costs and effects of routine mammography screening by a single mediolateral-oblique view and two views (mediolateral-oblique plus craniocaudal) of each breast. DESIGN: A cost effectiveness analysis of a prospective non-randomised trial comparing one and two view mammography screening was carried out at St Margaret's Hospital, Epping. All women in the study had two view mammography. The mediolateral-oblique view was always the first image read by the radiologist. After reading the films for a clinic session, the same radiologist then went back and read both the mediolateral-oblique and craniocaudal views together. Each set of films was read by two radiologists. The main outcome measures were recall rates, number of cancers detected, screening and assessment costs, and cost effectiveness ratios. SUBJECTS: A total of 26,430 women who attended for breast screening using both one and two view mammography participated. A sample of 132 women attending for assessment provided data on the private costs incurred in attending for assessment. RESULTS: There was a reduction in the recall rate from 9.1% (2404 of 26,430) after one view screening to 6.7% (1760 of 26,430) after two view screening. The results also suggest that for every 10,000 women screened an additional five cancers would be detected earlier with two view screening. The additional health service screening cost associated with two view screening was estimated to be 3.63 pounds: the costs associated with one and two view screening policies were estimated to be 41.49 pounds and 32.99 pounds respectively. Private costs incurred were estimated to be 0.35 pounds per woman screened and 32.75 pounds per woman assessed. Two cost effectiveness ratios were calculated: an incremental health service cost per additional cancer detected of 4129 pounds and an incremental health service plus private cost per additional cancer detected of 2742 pounds. The sensitivity analysis suggested that the results were sensitive to relatively large changes in a number of parameters. These included screening costs, assessment costs, equipment life, and recall rates. CONCLUSIONS: Use of two view screening increased early cancer detection and also costs. The reduction in the recall rate with two views was not sufficiently large to make the cost of two view screening neutral. While these results are not completely generalisable, a framework is provided to allow other centres to estimate the cost effectiveness of two view screening in their locality.

Breast Neoplasms

Immunity to malaria elicited by hybrid hepatitis B virus core particles carrying circumsporozoite protein epitopes.

The hepatitis B virus (HBV) nucleocapsid antigen (HBcAg) was investigated as a carrier moiety for the immunodominant circumsporozoite (CS) protein repeat epitopes of Plasmodium falciparum and the rodent malaria agent P. berghei. For this purpose hybrid genes coding for [NANP]4 (C75CS2) or [DP4NPN]2 (C75CS1) as internal inserts in HBcAg (between amino acids 75 and 81) were constructed and expressed in recombinant Salmonella typhimurium. The resulting hybrid HBcAg-CS polypeptides purified from S. typhimurium were particulate and displayed CS and HBc antigenicity, however, the HBc antigenicity was reduced compared to native recombinant HBcAg. Immunization of several mouse strains with HBcAg-CS1 and HBcAg-CS2 particles resulted in high titer, P.berghei- or P.falciparum-specific anti-CS antibodies representing all murine immunoglobulin G isotypes. The possible influence of carrier-specific immunosuppression was examined, and preexisting immunity to HBcAg did not significantly affect the immunogenicity of the CS epitopes within HBcAg-CS1 particles. Similarly, the choice of adjuvant did not significantly alter the immunogenicity of HBcAg-CS hybrid particles. Immunization in complete or incomplete Freund's adjuvant or alum resulted in equivalent anti-HBc and anti-CS humoral responses. Examination of T cell recognition of HBcAg-CS particles revealed that HBcAg-specific T cells were universally primed and CS-specific T cells were primed if the insert contained a CS-specific T cell recognition site. This indicates that the internal site in HBcAg is permissive for the inclusion of heterologous pathogen-specific T as well as B cell epitopes. Most importantly, 90 and 100% of BALB/c mice immunized with HBcAg-CS1 particles were protected against a P. berghei challenge infection in two independent experiments. Therefore, hybrid HBcAg-CS particles may represent a useful approach for future malaria vaccine development.

Animals

Stimulation of human scalp papilla cells by epithelial cells.

Evidence for the growth stimulatory properties of human keratinocyte-derived conditioned medium on human scalp dermal papilla cells and a mouse fibroblast cell line (Balb/c 3T3) is presented. There was no mitogenic effect on human keratinocytes. This conditioned medium induced a 2-5-fold increase in mitogenic activity in papilla cells relative to sham-conditioned medium as measured by 3H-thymidine incorporation. The papilla cell growth-stimulating activity of the conditioned medium was sensitive to heat, and from size exclusion the molecular weight was greater than 3000 Da.

3T3 Cells