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Biomedical subjects

D G Smith

Publications and source records attributed to D G Smith.

At least 109 records · Page 6Linked to original sources

Issues of importance reported by persons with lower limb amputations and prostheses.

The purpose of this paper is to report prosthesis-related issues of importance that were identified by a diverse group of persons living with lower limb amputations (LLA) and prostheses. These perceptions and themes validate some old assumptions and challenge others, report both common and unusual experiences, and indirectly identify the information level of our respondents concerning prostheses. Persons with LLA were identified from computerized rosters at a level one regional trauma center and at the VA Puget Sound Health Care System-Seattle, Division. Inclusion criteria specified that respondents were to: 1) be one or more years post-unilateral amputation at the Syme's level (ankle disarticulation) or higher, 2) use their prosthesis at least 5 days a week, 3) read English, and 4) be able to provide informed consent. Respondents completed the Prosthesis Evaluation Questionnaire-field version (PEQ) and the standard form (SF)-36, a health status measure. Of 114 persons who agreed to participate, 92 (85% male, mean age 55 years) responded to the questionnaire and graded the personal importance of various characteristics and qualities of their prosthesis. The number of years since their last amputation ranged from 1 to 53 years. Four Themes of Interest were identified from responses to open-ended questions about living with a prosthesis. These themes included the fit of the socket with the residual limb, aspects of the mechanical functioning of the prosthesis, other nonmechanical qualities, and advice about adaptation to life with a prosthesis with support from others. Future research is recommended to adjust aspects of the fit of the prosthesis with the residual limb. Implementing periodic check-up visits could uncover problems and eliminate unnecessary suffering.

Activities of Daily Living↗

Step activity monitor: long-term, continuous recording of ambulatory function.

In many areas of research and medicine, objective data describing an individual's ambulatory function are sought as useful indicators of that person's condition. Normally, detailed measurements are taken over short periods of time within a controlled laboratory setting. To complement this approach, Prosthetics Research Study has developed a small, unobtrusive instrument that continuously records a simple measure--step counts per unit time--as an individual goes about normal daily life. The Step Activity Monitor (SAM) is approximately the size and weight of a pager and is worn at the ankle. It can detect steps with better than 99% accuracy across a wide range of gait styles for adults, children, and large animals. During monitoring, step counts are recorded at consecutive, adjustable time intervals over weeks to months at a time. Recording at 1-min intervals for a minimum of 2 weeks is recommended. Once monitoring is completed, the data are transferred to a computer, and the levels and patterns of step activity can be analyzed. This article provides a detailed description of the SAM, guidelines for use, results of accuracy and reliability testing, case study descriptions demonstrating the ability to measure differences that result from medical interventions or changes in health status, and a discussion of considerations pertinent to long-term monitoring of activity.

Activities of Daily Living↗

Diabetic amputations in the VA: are there opportunities for interventions?

Lower limb amputation (LLA) is a devastating complication experienced by some veterans with diabetes. The Veterans Affairs (VA) Healthcare system has identified the prevention of LLA as a priority goal. This study was designed to describe the sources of outpatient care received by veterans with diabetes who have undergone LLA, to determine whether these persons would have been impacted by a VA amputation prevention program. This study was also designed to describe prior amputation history, footwear history, and the pivotal events that led to these amputations. We found that the vast majority of these subjects identified the VA as their primary source of care, and thus would have been available for enrollment in a prevention program. Since over one-half of them had had a prior amputation, diabetics with a prior amputation should be particularly targeted for foot care interventions. Lastly, prescription of protective footwear has the potential to reduce the incidence of shoe-related ulcers and amputations.

Adult↗

CD23 (FcepsilonRII) release from cell membranes is mediated by a membrane-bound metalloprotease.

CD23 (low-affinity IgE receptor, FcepsilonRII) is expressed as a Type II extracellular protein on a variety of cells such as B-cells, monocytes and macrophages and is cleaved from the cell surface to generate several distinct fragments. The expression of CD23 on the cell surface as well as the generation of soluble fragments of CD23 has been shown to be involved in the regulation of IgE synthesis. Here we report that the release of CD23 from the cell surface is mediated by a metalloprotease. An assay utilizing purified CD23 and an neo-epitope antibody specific for one of the known cleavage products is described and used to demonstrate unambiguously the cleavage of CD23 by a distinct protease. Characterization of the mechanism of CD23 processing shows that the protease exists as an integral membrane protein with a functional molecular mass of approx. 63 kDa as determined by gel-filtration chromatography. The CD23-cleaving activity found in enriched plasma membranes from RPMI 8866 cells is inhibited by the metalloprotease inhibitors 1, 10-phenanthroline and imidazole and by the matrix metalloprotease inhibitor batimastat, but not by inhibitors of cysteine proteases, serine proteases or acid proteases. The same or a similar activity that cleaves CD23 to the known 33 kDa fragment and is inhibited by batimastat is present in diverse cell types such as unstimulated fibroblasts and monocytic cell lines not expressing CD23, as well as in the Epstein-Barr virus-transformed B-cell line, RPMI 8866, which constitutively expresses CD23.

Animals↗

Use of metronidazole in equine acute idiopathic toxaemic colitis.

Sixteen cases of acute idiopathic toxaemic colitis developed in a veterinary hospital over a period of three years. Before the onset of colitis, 15 horses had received antibiotics, 11 had undergone general anaesthesia and various surgical procedures, and 10 had been treated with non-steroidal anti-inflammatory drugs. The horses had acute onset, profuse watery diarrhoea, profound depression, mild to moderate abdominal pain, reduced intestinal borborygmi, tachycardia, dehydration and endotoxic shock. Leucopenia, neutropenia and pyrexia were common early indicators of impending colitis. Metronidazole appeared to be an effective treatment; eight horses treated with metronidazole survived whereas five of seven horses that received other treatments, but no metronidazole, died or had to be euthanased. The aetiology of the colitis could not be determined, but the clinicopathological features resembled those of colitis attributed to an intestinal overgrowth of Clostridium perfringens type A. No Salmonella species were isolated from 52 samples of faeces, colonic contents and colonic mucosa which were collected from the horses antemortem and postmortem.

Animals↗

A decision analysis of mandatory compared with voluntary HIV testing in pregnant women.

BACKGROUND: The benefit of antiretroviral therapy in reducing maternal-fetal transmission of HIV during pregnancy has caused a public policy debate about the relative benefits of mandatory HIV screening and voluntary HIV screening in pregnant women. OBJECTIVE: To evaluate the benefits and risks of mandatory compared with voluntary HIV testing of pregnant women to help guide research and policy. DESIGN: A decision analysis that incorporated the following variables: acceptance and benefit of prenatal care, acceptance and benefit of zidovudine therapy in HIV-infected women, prevalence of HIV infection, and mandatory compared with voluntary HIV testing. MEASUREMENTS: The threshold deterrence rate (defined as the percentage of women who, if deterred from seeking prenatal care because of a mandatory HIV testing policy, would offset the benefit of zidovudine in reducing vertical HIV transmission) and the difference between a policy of mandatory testing and a policy of voluntary testing in the absolute number of HIV-infected infants or dead infants. RESULTS: Voluntary HIV testing was preferred over a broad range of values in the model. At baseline, the threshold deterrence rate was 0.4%. At a deterrence rate of 0.5%, the number of infants (n = 167) spared HIV infection annually in the United States under a mandatory HIV testing policy would be lower than the number of perinatal deaths (n = 189) caused by lack of prenatal care. CONCLUSIONS: The most important variables in the model were voluntary HIV testing, the deterrence rate associated with mandatory testing compared with voluntary testing, and the prevalence of HIV infection in women of child-bearing age. At high levels of acceptance of voluntary HIV testing, the benefits of a policy of mandatory testing are minimal and may create the potential harms of avoiding prenatal care to avoid mandatory testing.

Anti-HIV Agents↗

Hydroxamate-based inhibitors of low affinity IgE receptor (CD23) processing.

A series of hydroxamic acids related to the non-selective matrix metalloprotease inhibitor Batimastat is described, which inhibits the proteolytic cleavage of the low affinity IgE receptor from cell membrane preparations. Limited SAR studies suggest that the structural requirements for effective inhibition are distinct from those required for the inhibition of collagenase.

Humans↗

Selective inhibition of low affinity IgE receptor (CD23) processing.

A series of hydroxamic acids related to the non-selective matrix metalloproteinase inhibitor Batimastat has been prepared, some members of which are potent inhibitors of the processing of the low affinity IgE receptor (CD 23). Increased activity is obtained by appropriate substitution at the alpha-position, whilst selectivity is gained by use of a P1' benzyl group in conjunction with a C-terminal primary amide.

Hydroxamic Acids↗

Fin duplications and deletions induced by disruption of retinoic acid signaling.

Retinoic acid (RA), a derivative of vitamin A, plays a critical role as a signaling molecule in axial patterning of vertebrates. Here we report that RA exposure of zebrafish (Danio rerio) and mummichog (Fundulus heteroclitus) embryos during gastrulation results in homeotic duplications of the pectoral fins in up to 94% of fish. We have observed three to four pairs of fins in an individual fish. Although some duplications are partial, many represent complete axial duplications of the pectoral girdle and fin and include coracoscapulae, proximal radials, and dermal fin elements. Fin duplications are observed only at a defined dose of RA. Inhibition of RA synthesis by exposure to citral during a narrow developmental window leads to fish which lack pectoral fins but can be rescued by addition of exogenous RA, suggesting that RA signaling is critical to fin specification during early development. The ability to consistently induce multiple fins in a large number of vertebrate embryos should contribute to the understanding of genetic regulation of the normal positioning of limbs during embryogenesis.

Animals↗

Prosthesis evaluation questionnaire for persons with lower limb amputations: assessing prosthesis-related quality of life.

OBJECTIVE: To develop a self-report questionnaire for persons with lower limb amputations who use a prosthesis. The resulting scales were intended to be suitable to evaluate the prosthesis and life with the prosthesis. The conceptual framework was health-related quality of life. DESIGN: Multiple steps of scale development, terminating with test-retest of the Prosthesis Evaluation Questionnaire (PEQ) by mail. SOURCE OF SAMPLE: Records from two Seattle hospitals. PATIENTS: Ninety-two patients with lower limb amputations who varied by age, reason for amputation, years since amputation, and amputation level. MAIN OUTCOME MEASURES: The 10 scales used were 4 prosthesis function scales (Usefulness, Residual Limb Health, Appearance, and Sounds), 2 mobility scales (Ambulation and Transfers), 3 psychosocial scales (Perceived Responses, Frustration, and Social Burden), and 1 Well-being scale. Validation measures were the Medical Outcomes Study Short Form-36, the Social Interaction subscale from the Sickness Impact Profile, and the Profile of Mood States-short form. RESULTS: Nine PEQ scales demonstrated high internal consistency. All met test-retest criteria for comparing group results. Validity was described based on methods used to gather original items, distribution of scores, and comparison of scores with criterion variables. CONCLUSIONS: The PEQ scales displayed good psychometric properties. Future work will assess responsiveness of PEQ scales to changes in prosthetic components. We conclude that they will be useful in evaluation of prosthetic care.

Activities of Daily Living↗

Activity-based cost management. Part II: Applied to a respiratory protection program.

To demonstrate the relevance of activity-based cost management (ABCM) for the occupational and environmental health community, the investigators used data generated by an ABCM model of a respiratory protection program (RPP) to develop options for solving a business problem. The RPP manager in this hypothetical but realistic business scenario is faced with a 25% budget cut and a 10% increase in demand for RPP services. The manager's dilemma is to maintain the integrity of the RPP while absorbing a significant budget cut. Various cost savings options are developed, and the assumptions under which these options operate are presented. It is emphasized that the RPP manager's primary responsibility is to assure worker health and safety by first understanding the technical issues, merits, and implications of any cost-cutting option that may be considered. It is argued that only then should the manager consider the financial merits of the possible solutions to this business problem. In this way worker health and safety, and environmental protection goals, can continue to be achieved in an economic climate of cost cutting and downsizing.

Accounting↗

The cost of reaching National Cholesterol Education Program (NCEP) goals in hypercholesterolaemic patients. A comparison of atorvastatin, simvastatin, lovastatin and fluvastatin.

OBJECTIVE: Recognising the importance of treating hyperlipidaemia, the National Cholesterol Education Program (NCEP) has established widely accepted treatment goals for low density lipoprotein cholesterol (LDL-C). Medications used most commonly to achieve these LDL-C goals are HMG-CoA reductase inhibitors. The relative resource utilisation and cost associated with the use of reductase inhibitors of different LDL-C lowering efficacy are unknown, but are major health and economic concerns. The objective of this study was to determine the mean total cost of care to reach NCEP goals with various reductase inhibitors. DESIGN: In a randomised, 54-week, 30-centre controlled trial we compared resources used and costs associated with treating patients to achieve NCEP goals using 4 reductase inhibitors: atorvastatin, simvastatin, lovastatin and fluvastatin. PATIENTS AND PARTICIPANTS: The trial studied 662 patients; 318 had known atherosclerotic disease. INTERVENTIONS: Reductase inhibitor therapy was initiated at recommended starting doses and increased according to NCEP guidelines and package insert information. For patients who did not reach the goal at the highest recommended dose of each reductase inhibitor, the resin colestipol was added. MAIN OUTCOME MEASURES AND RESULTS: Patients treated with atorvastatin, compared-with other reductase inhibitors, were more likely to reach NCEP goals during treatment (p < 0.05), required fewer office visits (p < 0.001) and less adjuvant colestipol therapy (p = 0.001). Consequently, the mean total cost of care (1996 values) to reach NCEP goals was lower with atorvastatin [$US1064; 95% confidence interval (CI): $US953 to $US1176] compared with simvastatin ($US1471, 95% CI: $US1304 to $US1648), lovastatin ($US1972; 95% CI: $US1758 to $US2186) and fluvastatin ($US1542; 95% CI: $US1384 to $US1710). Results were similar for patients with or without known atherosclerotic disease. CONCLUSIONS: In patients requiring drug therapy for hypercholesterolaemia, NCEP LDL-C goals are achieved significantly more often using fewer resources with atorvastatin compared with simvastatin, lovastatin or fluvastatin.

Aged↗

Complications and maintenance requirements of implant-supported prostheses provided in a UK dental hospital.

AIM: To assess the nature, timing and frequency of complications associated with implant therapy and to assess maintenance requirements of implant-supported prostheses. DESIGN: Retrospective analysis. SETTING: The Dental Hospital in Newcastle upon Tyne. METHOD: Dental records of 60 patients provided with implant-supported prostheses were examined. Data were compiled on the number of fixtures placed per patient, the type of prosthesis provided, complications during the surgical and prosthodontic phases, and peri-implant soft tissue complications. RESULTS: 66 prostheses were placed on 236 fixtures over a 6-year period. Surgical complications included fixture loss (n = 6), dysaesthesia (n = 12), and the need for a guided tissue regeneration procedure (n = 10). Common maintenance requirements were tightening of components (n = 11), clip replacement (n = 7) and repair of conventional prostheses opposing implant supported prostheses (n = 7). Plaque control was unsatisfactory with almost half of the subjects requiring intensive oral hygiene instruction and scaling at the first post placement review. CONCLUSIONS: Prosthodontic maintenance requirements were high, particularly during the first year. Surgical complications were relatively infrequent. A case was made for a rigorous oral hygiene programme to reduce the potential for fixture loss through neglect. The financial cost associated with the maintenance of implant-supported prostheses should be incorporated in their overall funding.

Dental Clasps↗

Postgraduate education in sedation--a new development.

Although demand for sedation courses has continued to increase, the traditionally theoretical format has tended to leave participants without the necessary clinical skills to practice sedation techniques with confidence. This article describes a new model of sedation course, introduced at Newcastle Dental Hospital and School, which has managed to overcome this problem.

Anesthesia, Dental↗

Fat embolism syndrome. A 10-year review.

BACKGROUND: The effect of recent advances in critical care and the emphasis on early fracture fixation in patients with fat embolism syndrome (FES) are unknown. OBJECTIVE: To better define FES in current practice by conducting a 10-year review of the experiences at our level I trauma center. DESIGN: The medical records of all patients in whom FES was diagnosed from July 1, 1985, to July 1, 1995, were reviewed for demographics, injury severity and pattern, diagnostic criteria, and management. SETTING: A level I trauma center. RESULTS: Twenty-seven patients with clinically apparent FES were identified. This resulted in an incidence of 0.9% of all patients with long-bone fractures. The mean injury severity score was 9.5 (range, 4-22). The diagnosis of FES was made by clinical criteria, including hypoxia, 26 patients (96%); mental status changes, 16 patients (59%); petechiae, 9 patients (33%); temperature higher than 39 degrees C, 19 patients (70%); tachycardia (heart rate > 120 beats per minute), 25 patients (93%); thrombocytopenia (platelet count < 150 x 10(9)/L), 10 patients (37%); and unexplained anemia, 18 patients (67%). Thirteen patients (48%) had multiple long-bone fractures, and 14 patients (52%) had a single long-bone fracture. Seven patients (26%) had open fractures, 15 (56%) had closed fractures, and the remaining 5 (18%) had both. Of the total fracture population, the distribution was 81% closed, 15% open, and 4% both. Management included ventilatory support for 12 (44%) of the patients; early operative fixation was emphasized, and 74% of the fractures were stabilized within 24 hours of injury. This was comparable with 76% of the total fracture population. There were 2 deaths, for a mortality of 7%. CONCLUSIONS: (1) Fat embolism syndrome remains a diagnosis of exclusion and is based on clinical criteria. (2) Clinically apparent FES is unusual but may be masked by associated injuries in more severely injured patients. (3) No association could be identified between FES and a specific fracture pattern or location. (4) Early intramedullary fixation does not increase the incidence or severity of FES. (5) While FES seems to have a direct effect on survival, the management of FES remains primarily supportive.

Adolescent↗

Simple sequence repeat (SSR) polymorphisms for colony management and population genetics in rhesus macaques (Macaca mulatta).

Cross-species amplification of 72 SSR (predominantly tetranucleotide) loci from the DNA of six rhesus macaques of diverse regional origins was conducted using human primers for the polymerase chain reaction (PCR). Thirteen of these primer pairs, which consistently and unambiguously amplified polymorphic fragments from these six samples and which exhibited Mendelian properties, were also used to amplify SSR loci for 176 male rhesus macaques that are founders of six different captive breeding colonies. These include four groups of macaques originating in India and one group of macaques each that originated in China and Thailand. Gene diversity based on the SSR loci provided a reliable estimate of average heterozygosity but was between two and four times higher than that for 9 protein coding loci. Based on the SSR loci, Chinese rhesus were more genetically diverse and unique than were rhesus from India or Thailand, a conclusion not consistent with data based on protein coding loci. The six most informative SSR loci are unlinked and provide probabilities of single parent exclusion and genetic identity exceeding 0.99 and one in one million, respectively, both of which are reasonable standards for colony management purposes.

Animals↗

In-vitro interactions of Lawsonia intracellularis with cultured enterocytes.

Strains of the obligately intracellular bacterium Lawsonia intracellularis, the etiologic agent of porcine proliferative enteropathy, were co-cultured in rat enterocyte cell cultures (IEC-18) and examined ultrastructurally. No regular surface arrays typical of surface or S-layers were visible on any bacterial strain, with or without Triton-X-100 detergent treatment. In separate experiments, there was no difference in the ability of L. intracellularis to attach and enter enterocytes with or without the presence of added bovine plasma fibronectin, or the peptide Arg-Gly-Ser. Interestingly, there was an increase in the invasiveness of L. intracellularis in the presence of the peptide Arg-Gly-Asp (RGD), in a dose-related manner. A reduction was observed in the ability of L. intracellularis to invade enterocytes in the presence of monovalent fragments of IgG monoclonal antibodies to an outer surface component of L. intracellularis. This neutralization showed an antibody concentration-dependent titration effect and was not apparent with co-cultures incorporating control antibodies. The exact nature of ligand and cell receptor interactions for L. intracellularis remain to be determined.

Animals↗