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Biomedical subjects

R King

Publications and source records attributed to R King.

At least 37 records · Page 2Linked to original sources

Model selection for integrated recovery/recapture data.

Catchpole et al. (1998, Biometrics 54, 33-46) provide a novel scheme for integrating both recovery and recapture data analyses and derive sufficient statistics that facilitate likelihood computations. In this article, we demonstrate how their efficient likelihood expression can facilitate Bayesian analyses of these kinds of data and extend their methodology to provide a formal framework for model determination. We consider in detail the issue of model selection with respect to a set of recapture/recovery histories of shags (Phalacrocorax aristotelis) and determine, from the enormous range of biologically plausible models available, which best describe the data. By using reversible jump Markov chain Monte Carlo methodology, we demonstrate how this enormous model space can be efficiently and effectively explored without having to resort to performing an infeasibly large number of pairwise comparisons or some ad hoc stepwise procedure. We find that the model used by Catchpole et al. (1998) has essentially zero posterior probability and that, of the 477,144 possible models considered, over 60% of the posterior mass is placed on three neighboring models with biologically interesting interpretations.

Animals↗

A preliminary evaluation of a prospective study of pulmonary function studies and symptoms of hypoventilation in ALS/MND patients.

There is still no consensus as to which physiologic marker should be used as a trigger for the initiation of non-invasive positive pressure ventilation (NPPV) in patients with amyotrophic lateral sclerosis (ALS). Current practice parameters recommend that the decision to begin treatment be based upon forced vital capacity (FVC) measurements. A prospective, randomized study was performed in 20 ALS patients who had an FVC of 70-100%. Patients received baseline assessments including: ALS functional rating scale-respiratory version (ALSFRS-R), pulmonary symptom scale, Short form 36 (SF-36), FVC%, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and nocturnal oximetry. Patients were randomized to receive NPPV based upon nocturnal oximetry studies suggesting oxygen desaturation <90% for one cumulative minute ("early intervention") or a FVC <50% ("standard of care"). At enrollment, there was no significant correlation between FVC% and the ALSFRS-R, symptom score, MEP, MIP, or duration of nocturnal desaturation <90%. An increase in the vitality subscale of the SF-36 was demonstrated in 5/6 patients randomized to "early intervention" with NPPV. Our data indicate that FVC% correlates poorly with respiratory symptoms and suggests that MIP and nocturnal oximetry may be more sensitive measures of early respiratory insufficiency. In addition, intervention with NPPV earlier than our current standard of care may result in improved quality of life.

Disease Progression↗

Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age.

The National Marrow Donor Program (NMDP) maintains a registry of approximately 4 million volunteer unrelated donors for patients in need of a stem cell transplant. When several comparably HLA-matched volunteers are identified for a patient, various criteria are used to select a donor. A retrospective analysis of 6978 bone marrow transplantations facilitated by the NMDP from 1987 to 1999 was conducted to study the effects of various donor characteristics on recipient outcome. The evaluation addressed possible effects of donor age, cytomegalovirus serologic status, ABO compatibility, race, sex, and parity on overall and disease-free survival, acute and chronic graft-versus-host disease (GVHD), engraftment, and relapse. Age was the only donor trait significantly associated with overall and disease-free survival. Five-year overall survival rates for recipients were 33%, 29%, and 25%, respectively, with donors aged 18 to 30 years, 31 to 45 years, and more than 45 years (P =.0002). A similar effect was observed among HLA-mismatched cases (28%, 22%, and 19%, respectively). A race mismatch between recipient and donor did not affect outcome. The cumulative incidences of grade III or IV acute GVHD were 30%, 34%, and 34%, respectively, with donors aged 18 to 30 years, 31 to 45 years, and more than 45 years (P =.005). The corresponding incidences of chronic GVHD at 2 years were 44%, 48%, and 49% (P = 0.02). Recipients with female donors who had undergone multiple pregnancies had a higher rate of chronic GVHD than recipients with male donors (54% versus 44%; P <.0001). The use of younger donors may lower the incidence of GVHD and improve survival after bone marrow transplantation. Age should be considered when selecting among comparably HLA-matched volunteer donors.

Adolescent↗

Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia: strong graft-versus-leukemia effect and risk factors determining outcome.

Between 1988 and 1999, 127 patients with poor-risk acute lymphoblastic leukemia (ALL) received a matched unrelated donor transplant using marrow procured by National Marrow Donor Program (NMDP) collection centers and sent out to 46 transplant centers worldwide. Poor risk was defined by the presence of the translocations t(9;22) (n = 97), or t(4;11) (n = 25), or t(1;19) (n = 5). Sixty-four patients underwent transplantation in first remission (CR1), 16 in CR2 or CR3, and 47 patients had relapsed ALL or primary induction failure (PIF). Overall survival at 2 years from transplant was 40% for patients in CR1, 17% in CR2/3, and 5% in PIF or relapse. Treatment-related mortality (TRM) and relapse mortality, estimated as competing risk factors, were 54% and 6%, respectively, in CR1, 75% and 8% in CR2/3, and 64% and 31% in PIF or relapse. Currently 23 CR1 patients are alive and free of disease with a median follow-up of 24 months (range, 3-97). Multivariable analysis showed that CR1, shorter interval from diagnosis to transplantation, DRB1 match, negative cytomegalovirus (CMV) serology (patient and donor), and presence of the Philadelphia chromosome, t(9;22), were independently associated with better disease-free survival (DFS). Transplantation in CR and presence of t(9;22) were associated with lower risk of relapse. Shorter interval from diagnosis to transplantation, DRB1-match, negative CMV, higher marrow cell dose, and Karnofsky score of 90 or higher were associated with less TRM. These results indicate that, despite a relatively high TRM, the low relapse rate resulted in a 37% +/- 13% DFS for CR1 patients, comparing favorably to results obtained with chemotherapy alone and matching results following HLA-identical sibling transplantation.

Actuarial Analysis↗

Genome-wide linkage analyses of total serum IgE using variance components analysis in asthmatic families.

Variance components models were used to analyze total IgE levels in families ascertained though the Collaborative Study of the Genetics of Asthma (CSGA) using a genome-wide array of polymorphic markers. While IgE levels are known to be associated with clinical asthma and recognized to be under strong genetic control (here the heritability was estimated at 44-60% in the three racial groups), specific genes influencing this trait are still largely unknown. Multipoint analysis of 323 markers yielded little indication of specific regions containing a trait locus controlling total serum IgE levels (adjusted for age and gender). Although a number of regions showed LOD statistics above 1.5 in Caucasian families (chromosome 4) and in African-American families (chromosomes 2 and 4), none yielded consistent evidence in all three racial groups. Analysis of total IgE adjusted for gender, age and Allergy Index (a quantitative score of skin test sensitivity to 14 common aeroallergens) was conducted on these data. In this analysis, a much stronger signal for a trait locus controlling adjusted log[total IgE] was seen on the telomeric end of chromosome 18, but only in Caucasian families. This region accounted for most of the genetic variation in log[total IgE], and may represent a quantitative trait locus for IgE levels independent of atopic response. Oligogenic analysis accounting simultaneously for the contribution of this locus on chromosome 18 and other chromosomal regions showing some evidence of linkage in these Caucasian families (on chromosomes 2, 4 and 20) failed to yield significant evidence for interaction.

Asthma↗

Development of PMMA-precoating metal prostheses via injection molding: residual stresses.

Injection molding polymethylmethacrylate (PMMA) was developed as a potential metal prosthesis precoating method for surgical implantation. However, residual stresses generated in the injection-molded PMMA affect the mechanical performance of the coating polymer. This study used plane polariscope testing to demonstrate the residual stress distribution in the injection-molded polymer. Slitting and strain gages were combined with finite element analysis to give a quantitative measure of the residual stresses. The residual stress testing indicated that the highest circumferential residual stress in the injection-molded PMMA was approximately 5 MPa in tension. Two methods, water soaking and slitting, were developed for reducing residual stresses. A series of four surgical implantation simulation processes were designed. The two methods for reducing residual stress were used in the simulations.

Animals↗

Use of a novel nitrification inhibitor to reduce nitrous oxide emission from (15)N-labelled dairy slurry injected into soil.

Recent recommendations for environmentally sound use of liquid animal manure often include injection of slurry into soil. Two of the most important undesired side effects, ammonia (NH(3)) volatilisation and odour emissions, are usually significantly reduced by slurry injection. On the other hand, because of the higher amount of nitrogen (N) remaining in soil, the risk of nitrate (NO(3)(-)) leaching and nitrous oxide (N(2)O) emissions is increased. Thus, the reduction of local effects caused by NH(3) deposition, e.g. N enrichment and soil acidification, may be at the cost of large-scale effects such as ozone depletion and global warming as a result of emitted N(2)O. In this context, nitrification inhibitors can contribute significantly to a reduction in NO(3)(-) leaching and N(2)O production. A field experiment was carried out at IGER, North Wyke, which aimed to evaluate the effect of the new nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP/ENTEC). For this experiment, (15)N enriched dairy slurry was used and the isotopic label in soil N as well as in N(2)O were studied. After slurry injection into the grassland soil in August 2000, the major emissions of N(2)O occurred during the first ten days. As expected, high N(2)O emission rates and (15)N content of the emissions were concentrated on the slurry injection slots, showing a steep decrease towards the untreated centre-point between slurry injection slots. The nitrification inhibitor DMPP proved to be very efficient in reducing N(2)O emissions. At a rate of 2 kg DMPP ha(-1), the total amount of N(2)O emitted was reduced by 32%, when compared with slurry injection without DMPP. The isotopic label of the emitted N(2)O showed that during the 22-day experimental period, emissions from the slurry N pool were strongly reduced by DMPP from 0.93 kg N(2)O-N ha(-1) (-DMPP) to 0.50 kg N(2)O-N ha(-1) (+DMPP), while only a minor effect on emissions from the soil N pool was observed (0.69 to 0.60 kg N(2)O-N ha(-1); -DMPP, +DMPP, respectively).

Algorithms↗

In vivo detection of experimental ulcerative colitis in rats using fiberoptic confocal imaging (FOCI).

Fiberoptic confocal imaging (FOCI) is a noninvasive microscopic technique that enables subsurface imaging of living tissue in vivo. The aim of the present study was to assess the suitability of FOCI for the in vivo detection of early subsurface changes in the mucosal architecture of the colon in a rat model of ulcerative colitis. Mild colitis was induced in Sprague-Dawley rats (180-250 g) by the oral ingestion of 5% (w/v) dextran sulfate sodium (DSS; Mr 40,000 Da) in drinking water. Control animals were provided with water ad libitum. After three, five or seven days of oral consumption of DSS, the mucosal surface of the colon of anesthetised rats was surgically exposed. Morphological changes in the mucosa were examined (Optiscan F900e personal confocal system with rigid endomicroscope attachment; excitation 488 nm argon ion laser, detection above 515 nm) following the topical application of a fluorescent dye (fluorescein, eosin, or acridine orange). Confocal images were correlated with conventional histology and clinical parameters including occult blood and stool consistency. Histological evaluation of colon sections demonstrated that DSS-induced colitis was characterized by focal loss of mucous crypts, loss of epithelial cells, and neutrophilic infiltration into the mucosa. The extent of mucosal damage was positively correlated with the time of ingestion of DSS. Morphological changes associated with disease activity could be detected microscopically in vivo using FOCI but were not evident by visual inspection of the colon surface. Acridine orange enabled imaging of the colonic crypts at the surface of the mucosa. Morphological changes associated with colitis, including inflammatory cell infiltrate, crypt loss, and crypt distortion, could be detected using this fluorophore. Application of fluorescein and eosin enabled subsurface imaging of the lamina propria surrounding the crypts; however, no change in structure was detected in association with colitic disease activity. This study has shown that the topical application of acridine orange enables in vivo imaging of early colitis in a rat model. FOCI may be suitable for the diagnosis and monitoring of human inflammatory bowel disease.

Animals↗

The leisure satisfaction of people with psychiatric disabilities.

Leisure is considered to be an important part of life for every individual. This is even more so for people who have limited employment prospects and life options. The primary handicaps associated with mental illness create problems with social relationships and can hinder individuals from participating in or enjoying leisure pursuits. The aim of this exploratory study was to examine leisure satisfaction in a sample of one hundred adults with a mental illness who were clients of an Australian community mental health rehabilitation service. The Leisure Satisfaction Survey and the Life Skills Profile were administered to these clients to determine their leisure satisfaction and general functioning. Contrary to expectations, results indicated that the clients of mental health rehabilitation services believe that their leisure pursuits provide them with intellectual stimulation, enjoyable relationships with others and relaxation, suggesting that they are very satisfied with the activities they engage in during their leisure time. In general, these clients were more satisfied with their leisure than the normative population. Consistent with expectations, clients with lower disability and in particular with high capacity for social contact were most satisfied with their leisure pursuits. The significance of these results and the utility of the Leisure Satisfaction Survey with this population are discussed.

Adult↗

Tracheal gas insufflation apparatus. Performance of a novel phase-specific device.

Tracheal gas insufflation is a technique in which gas is injected intratracheally during positive pressure ventilation. The fresh gas rinses expired gas from the tracheal tube and anatomical dead space, aiding carbon dioxide elimination. This reduces ventilatory volume and pressure, helping to reduce ventilator-induced lung damage. Complications of tracheal gas insufflation include interference with ventilator function, tracheal damage and barotrauma. Expiratory washout is a variation of tracheal gas insufflation. We designed and constructed an original expiratory washout system and evaluated its safety and performance in lung and animal models. We found that expiratory limb and tracheal tube occlusion tests caused the device to disable itself at acceptable intratracheal pressures. We also demonstrated up to 31% reduction in tidal volume compared with conventional ventilation, supporting the possibility of using this device clinically to lessen volutrauma. We concluded that aspects of this design might alleviate many of the safety concerns of using tracheal gas insufflation.

Animals↗

Exploration of xenon as a potential cardiostable sedative: a comparison with propofol after cardiac surgery.

Xenon anaesthesia is thought to have minimal haemodynamic side-effects. It is, however, expensive and requires special delivery systems for economic use. In this randomised cross-over study, we: (i) investigated the haemodynamic profile and recovery characteristics of xenon compared with propofol sedation in postoperative cardiac surgery patients, and (ii) evaluated a fully closed breathing system to minimise xenon consumption. We demonstrated a significantly faster recovery from xenon (3 min 11 s) than propofol sedation (25 min 23 s). Relative to propofol, xenon sedation produced no change in heart rate or mean arterial pressure and there were significantly higher mean values for central venous pressure (10.6 vs. 8.9 mmHg), pulmonary artery occlusion pressure (11.2 vs. 9.5 mmHg), mean pulmonary artery pressure (20.1 vs. 18.3 mmHg) and systemic vascular resistance index (2170 vs. 1896 dyn.s.cm-5.m-2). The haemodynamic profile seen with propofol reflected its known vasodilator effects. This was supported by the almost identical left ventricular stroke work indexes seen with both methods of sedation.

Aged↗

Antibodies to selected canine pathogens and infestation with intestinal helminths in golden jackals (Canis aureus) in Israel.

Blood and fecal samples, collected from 46 healthy adult free-ranging golden jackals captured in two different locations in Israel, were examined. A serological Study was conducted to investigate the prevalence of circulating antibodies reacting with four common canine pathogens: canine distemper virus (CDV), canine parvovirus (CPV), Ehrlichia canis and Leishmania infantum. Faecal flotation and haematological tests were also performed. The seroprevalence of CPV, E. canis, CDV, and L. infantum were 72.3% (34/47), 54.3% (25/46), 52.2% (24/46), and 6.5% (3/46) respectively. Faecal flotation tests revealed a high prevalence of Ancylostoma caninum (13/17, 76%) and a low prevalence of Dipilidium caninum infestation. Examination of blood smears revealed Hepatazoon canis gamonts in one jackal. Golden jackals are among the most common free-ranging carnivores in Israel and neighboring countries. Their habitats are in proximity to densely populated areas and they bear close phylogenic relation to the domestic dog. These facts, combined with the high prevalence of the jackals' exposure to the major canine pathogens demonstrated in this study, suggest that they may serve as a reservoir for the transmission of certain diseases to domestic dogs.

Animals↗

Herpesvirus infection of seborrheic keratoses.

We present three examples of patients with seborrheic keratoses complicated by necrotizing herpesvirus infection. Two patients had localized cutaneous herpetic infections, and the third patient had a generalized cutaneous herpesvirus infection. Two of the lesions were thought to be squamous cell carcinoma. The third was clinically identified as inflamed seborrheic keratosis. Herpesvirus infection was not clinically suspected in two of the patients. The histologic changes were similar in all cases. Epidermal proliferation was accompanied by hyperkeratosis and pseudo horn cyst formation. Extensive keratinocyte necrosis was present along with balloon degeneration of keratinocytes, herpetic viral inclusions, and multinucleated giant cells. Viral lesions of molluscum contagiosum and human papillomavirus have been observed in benign skin proliferations. Nevertheless, we were unable to find descriptions of herpesvirus involvement in seborrheic keratosis in a Medline search. Necrotic seborrheic keratoses should be carefully examined for the possibility of herpesvirus infection, a condition that may be improved by prompt medical intervention as demonstrated in one of our cases.

Aged↗

Microphthalmia transcription factor expression in cutaneous benign, malignant melanocytic, and nonmelanocytic tumors.

The protein encoded by the microphthalmia (mi) gene is a transcription factor essential for the development and survival of melanocytes. Using a monoclonal antibody generated against human Mi transcription factor protein (Mitf) the authors previously demonstrated that Mitf expression is conserved in primary and metastatic malignant melanomas, and appears to be a highly sensitive and specific melanocytic marker. Mitf expression in various cutaneous nevi and cutaneous nonmelanocytic tumors has not been documented systematically. The authors evaluated Mitf immunostaining in 62 benign nevi, 58 primary cutaneous melanomas, and 53 nonmelanocytic tumors. Mitf immunostaining was conserved in all benign nevi, with Spitz nevi and neurotized nevi demonstrating decreased staining intensity. With the exception of desmoplastic melanomas, all primary cutaneous melanomas were immunopositive regardless of the cell type. Only one of 14 desmoplastic melanomas was Mitf positive. None of the nonmelanocytic tumors was immunopositive, including those lesions that may resemble melanoma histologically (spindle cell carcinomas, atypical fibroxanthomas, and leiomyosarcomas). The results demonstrate that Mitf antibody expression is conserved in the majority of benign and malignant melanocytic lesions, and that it may be helpful in the diagnosis of primary melanocytic skin lesions. Its use in desmoplastic melanomas is limited and is reflective of other melanocyte-associated antigens. Mitf discriminates between spindle cell nonmelanocytic tumors and melanomas with a spindle cell morphology, and is useful in a panel with other appropriate antibodies.

Antigens, Neoplasm↗

Immunohistochemical and reverse transcription-polymerase chain reaction expression analysis of tyrosinase and microphthalmia-associated transcription factor in angiomyolipomas.

Angiomyolipomas (AMLs) show a characteristic immunoreactivity with melanocyte differentiation markers such as monoclonal antibody (mAb) HMB45, which detects melanocyte differentiation antigen gp100 and mAb A103 reacting with Melan-A/MART-1. Monoclonal antibody T311 to tyrosinase (a key enzyme of melanogenesis) and mAb D5 to the microphthalmia (Mitf) antigen are two newly available markers of melanocytic differentiation. The authors tested 15 AMLs with T311 and D5 by immunohistochemistry and a subset of 3 cases by reverse transcription-polymerase chain reaction for their expression of tyrosinase and Mitf mRNA. T311 showed poor sensitivity in AMLs because only focal staining was seen in 1 out of 15 cases, although tyrosinase mRNA was found in all tested cases. Mitf mRNA was present in 3 of 3 tested cases, and D5 was positive in 15 of 15 AMLs. However, D5 immunostaining often was focal and not as homogeneous as A103, which was analyzed in a previous study. D5 staining also could be seen in other cell types such as normal renal tubular cells, macrophages, and renal cell carcinoma. The current results show that in contrast with HMB45 and A103, T311 has little or no value in the diagnosis of AMLs. D5 may be useful in a panel of antibodies in the diagnosis of AMLs.

Angiomyolipoma↗