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Biomedical subjects

A Smith

Publications and source records attributed to A Smith.

At least 235 records · Page 13Linked to original sources

The biological significance of HLA-DP gene variation in haematopoietic cell transplantation.

Although it has been over 25 years since HLA-DP was mapped to the major histocompatibility complex (MHC), its biological functions remain ill-defined. We sought to test the hypothesis that HLA-DP functions in a manner similar to that of other class II genes by measuring the risk of clinically severe grades III-IV acute graft-vs.-host disease (GVHD) associated with recipient HLA-DP disparity after haematopoietic cell transplantation. HLA-DPB1 exon 2 was sequenced in 205 patients who underwent transplantation from HLA-A, -B, -C, -DRB1 and -DQB1 allele-matched unrelated donors. HLA-DPB1 mismatched recipients experienced a significantly increased risk of acute GVHD compared with HLA-DP-identical transplants. Patients who were mismatched for a single HLA-DPB1 allele had an odds ratio (OR) of 1.0 (0.5, 2.2; P = 0.99) and patients who were mismatched for two alleles had an OR of 2.2 (1.0, 4.9; P = 0.06) for developing acute GVHD. Compared with matched and single-allele mismatched transplants, patients who were mismatched for two DPB1 alleles had an OR of 2.2 (1.2, 4.1; P = 0.01). HLA-DP plays an important role in the alloimmune response. A threshold effect of multiple HLA-DP disparities is evident in determining the risk of acute GVHD after haematopoietic cell transplantation from unrelated donors.

Adolescent↗

Mucosal T cells regulate Paneth and intermediate cell numbers in the small intestine of T. spiralis-infected mice.

Secretions of Paneth, intermediate and goblet cells have been implicated in innate intestinal host defense. We have investigated the role of T cells in effecting alterations in small intestinal epithelial cell populations induced by infection with the nematode Trichinella spiralis. Small intestinal tissue sections from euthymic and athymic (nude) mice, and mice with combined deficiency in T-cell receptor beta and delta genes [TCR(beta/delta)-/-] infected orally with T. spiralis larvae, were examined by electron microscopy and after histochemical and lineage-specific immunohistochemical staining. Compared with uninfected controls, Paneth and intermediate cell numbers increased significantly in infected euthymic and nude mice but not infected TCR(beta/delta)-/- mice. Transfer of mesenteric lymph node cells before infection led to an increase in Paneth and intermediate cells in TCR(beta/delta)-/- mice. In infected euthymic mice, Paneth cells and intermediate cells expressed cryptdins (alpha-defensins) but not intestinal trefoil factor (ITF), and goblet cells expressed ITF but not cryptdins. In conclusion, a unique, likely thymic-independent population of mucosal T cells modulates innate small intestinal host defense in mice by increasing the number of Paneth and intermediate cells in response to T. spiralis infection.

Animals↗

Characteristics of an Accident and Emergency liaison mental health service in East London.

AIM OF THE STUDY: To analyse the work of a liaison mental health service at the Accident and Emergency (A & E) department of a hospital in East London. BACKGROUND: The English National Service Frameworks (NSF) for Mental Health recommend that A & E departments provide liaison mental health services and this study reports how a service in East London is responding to this challenge. RESEARCH METHODS: Data were collected during a 14-month period using a specially designed audit form. RESULTS: The typical referral was aged 36, of either sex, United Kingdom (UK) non-White with a diagnosis of depression. The majority of referrals were in the afternoon and seen immediately. A slight majority were known to mental health services; many were new referrals. Older and male clients were more likely, and Bengali and other Asian clients were less likely, to be registered with a psychiatrist. There were seasonal variations in referral type. Emergency referrals tended to have a diagnosis of schizophrenia; urgent and non-urgent referrals were more likely to be depressed. The outcome for the majority of referrals was referral to appropriate community services. The majority of non-clinical referrals were for advice, information and support. DISCUSSION AND CONCLUSIONS: The service seems a useful resource for A & E staff, and clients with mental health problems. The service is a channel through which people access mental health services and appears to address the NSF for Mental Health.

Adult↗

Phylogeography of Cape Verde Island skinks (Mabuya).

The Cape Verde Islands are of volcanic origin with most having appeared between the early Miocene and mid-Pleistocene. They contain six known species of Mabuya skinks. Phylogeographical relationships within and among the relatively widespread taxa M. stangeri, M. spinalis and M. delalandii were inferred, based on approximately 1 kbp of the cytochrome b gene (mitochondrial DNA). Reciprocal monophyly of M. spinalis and M. stangeri was established, which may have arisen from an early Pliocene/late Miocene cladogenetic event. Considerable between-island sequence divergence was detected among M. spinalis, which appears to have colonized the older islands (Sal and Boavista) first. Much lower sequence divergence was found in M. delalandii, indicating a more recent range expansion. Here, evidence points to colonization of the younger islands of Brava and Fogo soon after appearance. There are similarities between some of the described patterns and those seen in lizards from the Canary Islands.

Africa, Western↗

Non-invasive markers of bone turnover and plasma cytokines differ in osteoporotic patients with multiple myeloma and monoclonal gammopathies of undetermined significance.

AIMS: To determine whether various markers of bone turnover and/or plasma cytokines differ in patients with multiple myeloma (MM) compared with patients with monoclonal gammopathies of undetermined significance (MGUS). METHODS: We studied 22 MM patients and 18 MGUS patients presenting over an 18-month period and compared their data with those from 20 age- and sex-matched patients presenting with primary osteoporosis. According to the Salmon and Durie classification, there were eight patients with stage I, nine with stage II and five with stage III disease. All patients had densitometric evidence of osteoporosis and were classified according to bone marrow evidence of plasma cell dyscrasia. Measured variables included markers of bone formation and bone resorption, and plasma cytokines. RESULTS: Patients with MM and MGUS did not differ with respect to their mean age, male : female sex ratio, height, weight, serum calcium, 25-hydroxyvitamin D and parathyroid hormone concentrations. Patients with MM had significantly lower concentrations of haemoglobin (109 vs 135 g/L) and serum transforming growth factor (TGF)-beta (261 vs 348 pg/mL) than patients with MGUS, and higher concentrations of serum paraproteins (31.1 vs 7.4 g/L), beta2-microglobulin (3.5 vs 2.2 g/L), % plasma cell numbers (35.3 vs 2.1%) and urinary deoxypyridinoline excretion rates (u-DPYD; 7.7 vs 5.9 nmol/mmol creatinine; P < 0.05 for all comparisons). In multivariate analysis, the serum paraprotein (beta coefficient = -0.067; 95% confidence intervals (CI), -0.019 to -0.005; P = 0.0012), u-DPYD excretion rates (beta coefficient = -0.012; 95% CI, -0.113 to -0.02; P= 0.0058) and serum TGF-beta concentrations (beta coefficient = -0.002; 95% CI, -0.0002 to -0.02; P= 0.02) were the most important variables differentiating between MM and MGUS, after excluding lytic bone lesions, % plasma cell numbers and haemoglobin concentrations. CONCLUSIONS: The well-established criteria for diagnosing MM include the presence of lytic bone lesions, plasmacytosis, haemoglobin and paraprotein concentrations. The u-DPYD excretion rate, a sensitive non-invasive marker of bone resorption, may help in differentiating between MM and MGUS, as well as serving as a marker of underlying bone disease activity in these patients.

Aged↗

Tonsillar metastasis: A rare presentation of gastric carcinoma.

Metastatic carcinoma of the tonsil is uncommon. Tonsillar metastases rarely become apparent before the diagnosis of the primary neoplasm. We describe only the second reported case of tonsillar metastasis as a presenting feature of gastric carcinoma. A review of the literature is also discussed.

Aged↗

Defining a pulmonary exacerbation in cystic fibrosis.

OBJECTIVES: Despite the central importance of pulmonary exacerbations (PExs) as an outcome measure in cystic fibrosis clinical trials, no standardized definition of PEx exists. We conducted a prospective, multicenter study to establish a standardized PEx definition and score for use in clinical trials, based on clinical status rather than on treatment decisions. STUDY DESIGN: Subjects were 246 patients enrolled in the placebo arm of a randomized, controlled trial of tobramycin for inhalation. Physician-investigators completed PEx questionnaires on all subjects at scheduled intervals during the 6-month study, indicating new or worsening symptoms, physical examination findings, and impression of PEx status (presence or absence and severity). Logistic regression was used to assess the relative importance of each of the characteristics in predicting a PEx. RESULTS: We developed 2 PEx scores that use easily ascertained symptoms and chest examination findings; one also includes change in forced expiratory volume in 1 second over the preceding month. Both scores were sensitive and specific for predicting the presence of a PEx (sensitivity, 86%; specificity, 86%). The scores were validated in subjects in the intervention arm of the trial. CONCLUSION: We hope that the proposed PEx score might serve as a standardized outcome measure for future clinical trials in cystic fibrosis, allowing meaningful comparisons of study results.

Administration, Inhalation↗

Combined free tissue transfer and infrainguinal bypass graft: an alternative to major amputation in selected patients.

OBJECTIVES: The purpose of this study was to document outcome and adverse prognostic factors in patients requiring combined free tissue transfer and distal bypass grafting for otherwise nonreconstructible infrainguinal arterial occlusive disease and advanced tissue necrosis. METHODS: Between July 1990 and November 1999, 65 patients, all of whom would have required at least below-knee amputation, underwent free tissue transfer in conjunction with infrainguinal bypass grafting at the University of Rochester. Preoperative variables were assessed for their influence on outcome with chi(2) and outcome with life-table analysis with Cox proportionate hazard testing. RESULTS: Free tissue transfer was performed synchronously with arterial reconstruction with autologous vein in 49 patients and after a previous functioning venous bypass graft in 16 patients. The 30-day mortality rate was 5%, and major complications occurred in another 16% of patients. Flap location, weight-bearing status, preexisting osteomyelitis, and the timing of bypass grafting relative to flap construction had no effect on outcome. All five free flap failures occurred within the first 30 days. All other flaps subsequently survived, even in seven patients whose bypass grafts thrombosed. Five-year limb salvage and patient survival rates were 57% and 60%, respectively, and 65% of patients regained meaningful ambulation. The combination of diabetes and dialysis-dependent renal failure was the strongest predictor of overall limb loss (P <.005; relative risk = 4.0), and diabetes alone was the strongest predictor of death (P <.02; relative risk = 5.2). CONCLUSION: Free tissue transfer combined with infrainguinal bypass grafting in selected patients is safe and effective. The combination of diabetes and chronic renal insufficiency, particularly the need for dialysis, is a powerful predictor of failure and should be considered a strong contraindication for this procedure.

Amputation, Surgical↗

Using program theory to develop key performance indicators for child and adolescent mental health services.

Key Performance Indicators are used increasingly by health services, but their relevance and utility may be questionable. In this article, Program Theory is used to model the irreducible stages in the system of clinical care in Child and Adolescent Mental Health Services, define the major program operations in each of these stages, and specify the intermediate outcomes of each stage and the final outcomes sought. National and State policy standards are used, with practice experience, to identify key program operations and intermediate outcomes sought. Systematic criteria are then applied to select KPIs that are measurable, reliable, valid for our program theory, utilitarian, and relevant to clinicians, clients and managers.

Adolescent↗

OmpA genotypic evidence for persistent ocular Chlamydia trachomatis infection in Tanzanian village women.

BACKGROUND: Trachoma is still a significant problem in the developing world. Adult women are at higher risk of developing scarring and trichiasis, the potentially blinding sequelae, compared to men. In part, the higher risk may be due to more frequent infections in women because of their frequent contact with children, the main reservoir of C. trachomatis infection. However, other factors associated with infection, particularly constant infection, in adult women need to be identified. METHODS: A group of 118 women who were infected with C. trachomatis and 118 women who were not infected, but of similar age and trachoma status, were identified in 1996 from a population-based sample of women age 16 and older from eleven villages in Kongwa, Tanzania. This group of 236 was re-contacted three years later to ascertain trachoma status and determine infection status using polymerase chain reaction-enzyme immunoassay (PCR-EIA). Positive samples at both time points were examined for serovar and genotype shift, using ompA sequencing information. RESULTS: Of the original 236 women, 165 (70%) completed exams in 1999. Fifty-eight (35%) of the 165 women were excluded from this analysis because they received antibiotic treatment for trachoma in the six months prior to the second exam. Infection at baseline was the most important predictor of infection three years later (Age-adjusted odds ratio (95% confidence interval) 6.6 (1.8-24.4)). A total of 17 women (16%) were infected at the two examinations, and of the 15 for whom genotyping could be done, 11 (73%) were infected with the same ompA genotype at both time points. Chronically infected women were more likely to have trichiasis, scarring, and active trachoma at baseline than those never infected or infected only once. Only 41% of the chronically infected women were living in houses with infected pre-school children, but 24% were in houses with no children. Four of ten women with trichiasis developed incident corneal opacity over the three years. CONCLUSIONS: The data provide evidence for persistence of infection in a sub-group of women. The strongest predictor of infection at follow-up was baseline infection, and most were infected with the same genotype at both time points. For women with persistent infection, at least half were either not living with children or not living with infected children, suggesting that continual re-exposure from a close family member was less likely. Chronic infection is likely related to both exposure and immunological factors, and these need to be further identified. Inclusion of women in community-based treatment programs, regardless of whether a child is present in the house, is likely to be important in preventing the progression of inflammatory trachoma and scarring to trichiasis.

Adolescent↗

Antibiotic prescribing knowledge of National Health Service general dental practitioners in England and Scotland.

The inappropriate use of antibiotics has contributed to the worldwide problem of antimicrobial resistance. Information on the knowledge, understanding and training of dental practitioners in the use of antibiotics in clinical practice is scarce. This study assessed the level of knowledge of general dental practitioners and the need for educational initiatives. An anonymous postal questionnaire was sent to National Health Service dental practitioners working in 10 Health Authorities in England (1544) and four Health Boards in Scotland (672). Each correct answer to the questionnaire was given a score of one mark; there were 84 questions. The scores for each section of the questionnaire were compared. Responses were received from 1338 (60.4%) of practitioners, of whom 22.1% had attended postgraduate courses in the previous 2 years on antibiotic prescribing. Practitioners who had attended courses had a significantly greater knowledge of antibiotic use (P < 0.05) than those who had not. There was no significant difference in knowledge between all age groups under 60 years of age. There were significant differences in knowledge between dentists practising in English Health Authorities and Scottish Health Boards (P < 0.01). Knowledge was good for clinical signs that are indicators for prescribing antibiotics and for a number of non-clinical factors, e.g. patient expectation. Knowledge of therapeutic prescribing for commonly presenting clinical conditions and prophylactic prescribing for medically compromised patients, however, was generally poor. This study has shown that an urgent review of dental undergraduate and postgraduate education in antibiotic prescribing is required. Provision of prescribing guidelines may improve knowledge and encourage the appropriate use of antibiotics in clinical dental practice.

Anti-Bacterial Agents↗

Prospective randomized clinical trial of the value of intraperitoneal drainage after pancreatic resection.

OBJECTIVE: To test the hypothesis that routine intraperitoneal drainage is not required after pancreatic resection. SUMMARY BACKGROUND DATA: The use of surgically placed intraperitoneal drains has been considered routine after pancreatic resection. Recent studies have suggested that for other major upper abdominal resections, routine postoperative drainage is not required and may be associated with an increased complication rate. METHODS: After informed consent, eligible patients with peripancreatic tumors were randomized during surgery either to have no drains placed or to have closed suction drainage placed in a standardized fashion after pancreatic resection. Clinical, pathologic, and surgical details were recorded. RESULTS: One hundred seventy-nine patients were enrolled in the study, 90 women and 89 men. Mean age was 65.4 years (range 23-87). The pancreas was the tumor site in 142 (79%) patients, with the ampulla (n = 24), duodenum (n = 10), and distal common bile duct (n = 3) accounting for the remainder. A pancreaticoduodenectomy was performed in 139 patients and a distal pancreatectomy in 40 cases. Eighty-eight patients were randomized to have drains placed. Demographic, surgical, and pathologic details were similar between both groups. The overall 30-day death rate was 2% (n = 4). A postoperative complication occurred during the initial admission in 107 patients (59%). There was no significant difference in the number or type of complications between groups. In the drained group, 11 patients (12.5%) developed a pancreatic fistula. Patients with a drain were more likely to develop a significant intraabdominal abscess, collection, or fistula. CONCLUSION: This randomized prospective clinical trial failed to show a reduction in the number of deaths or complications with the addition of surgical intraperitoneal closed suction drainage after pancreatic resection. The data suggest that the presence of drains failed to reduce either the need for interventional radiologic drainage or surgical exploration for intraabdominal sepsis. Based on these results, closed suction drainage should not be considered mandatory or standard after pancreatic resection.

Adult↗

Detection of peptostreptococcus micros DNA in clinical samples by PCR.

Peptostreptococcus micros is a gram-positive anaerobic coccus which, although considered to be a natural commensal of the human oral cavity, is associated with periodontal, endodontal and peritonsillar infections. Identification of the organism has to date relied upon conventional culture methods and biochemical analyses. The purpose of this study was to develop a PCR method for rapid and specific identification of this organism in clinical samples. A pair of primers was selected, each of which was specific at the 3' end for P. micros DNA; they were used in the PCR assay, resulting in a 1074-bp product. The primers were shown to be specific for P. micros DNA as no PCR products were obtained when genomic DNA extracts from a wide range of other Peptostreptococcus species and other oral bacteria were used as templates. The PCR assay was then applied to the identification of P. micros DNA in subgingival plaque samples from adult periodontitis patients and pus samples from subjects with acute dento-alveolar abscesses. Confirmation of specific amplification of P. micros DNA was obtained by digestion of PCR products with the restriction endonuclease RsaI, which gives a unique restriction profile for P. micros, and DNA sequencing. Sixty-eight subgingival plaque samples from 18 patients were analysed, of which 19 (28%) were positive for P. micros DNA; the proportion of patients carrying P. micros DNA in at least one sampled site was 11 (61%) of 18. Twenty (71%) of 28 pus samples analysed by PCR contained P. micros DNA. These results confirm that P. micros may be involved in the aetiology of acute dentoalveolar abscesses and adult periodontitis. The PCR assay provides a more rapid and reliable alternative to conventional methods for identification of P. micros in clinical samples.

Adult↗

Analyzing variety by environment data using multiplicative mixed models and adjustments for spatial field trend.

The recommendation of new plant varieties for commercial use requires reliable and accurate predictions of the average yield of each variety across a range of target environments and knowledge of important interactions with the environment. This information is obtained from series of plant variety trials, also known as multi-environment trials (MET). Cullis, Gogel, Verbyla, and Thompson (1998) presented a spatial mixed model approach for the analysis of MET data. In this paper we extend the analysis to include multiplicative models for the variety effects in each environment. The multiplicative model corresponds to that used in the multivariate technique of factor analysis. It allows a separate genetic variance for each environment and provides a parsimonious and interpretable model for the genetic covariances between environments. The model can be regarded as a random effects analogue of AMMI (additive main effects and multiplicative interactions). We illustrate the method using a large set of MET data from a South Australian barley breeding program.

Analysis of Variance↗

Fruit and vegetable intakes of Australians aged 2-18 years: an evaluation of the 1995 National Nutrition Survey data.

OBJECTIVE: To evaluate the fruit and vegetable intakes of 2 to 18-year-old Australians. METHODS: Intake data were collected as part of the National Nutrition Survey 1995 representing all Australian States and Territories, urban, rural and remote areas. Dietary intake of 3,007, two to 18-year-olds was assessed using a 24-hour structured diet recall method. Intake frequency was assessed as the percentage of participants consuming fruit and vegetables on the surveyed day, and variety was assessed as the number of sub-groups of fruit and vegetables eaten. Intake levels were compared with the recommendations of the Australian Guide to Healthy Eating, the 1993 Goals and Targets for Australia's Health in 2000 and beyond, and intakes of the 1985 National Dietary Survey. RESULTS: One-quarter of children and adolescents did not eat fruit on the day of survey and one fifth did not eat vegetables. Adolescents were less likely to include fruit (65%) than young children (80%) but slightly more adolescents (85%) included vegetables than young children (77%). Less than 50% of all participants (<25% of adolescents) had an adequate fruit intake, and only one-third of children and adolescents met the vegetable intake recommendations. CONCLUSIONS: Fruit and vegetable intakes of Australian children and adolescents fall well below recommendations and appear to have declined in the past 10 years. IMPLICATIONS: Strategic approaches involving a broad range of sectors are urgently needed to create a supportive environment for consuming recommended levels of a wide variety of fruit and vegetables.

Adolescent↗