Search PubMed⌕ Search

Biomedical subjects

J King

Publications and source records attributed to J King.

At least 109 records · Page 6Linked to original sources

The economic impact of esophageal variceal hemorrhage: cost-effectiveness implications of endoscopic therapy.

Esophageal variceal hemorrhage (EVH) is a serious and expensive sequela of chronic liver disease, leading to increased utilization of resources. Today, endoscopic sclerotherapy (ES) and endoscopic ligation (EL) are the accepted, community standards of endoscopic treatment of patients with EVH. However, there are no published studies comparing the economic costs of treating EVH using these interventions. As part of a prospective, randomized trial comparing ES and EL for the treatment of EVH, we estimated the direct costs of health care utilization and cost-effectiveness for the prevention of variceal rebleeding and patient survival at 1-year follow-up. Treatment groups were similar in incidence of variceal rebleeding (41.9% vs. 42.9%), variceal obliteration (41.9% vs. 40.0%), hospital days, blood transfusions, shunt requirements, and survival (71.0% vs. 60.0%). There were significantly more treatment failures for active bleeding using EL (42% vs. 0%; P =.027) and esophageal stricture formation in the ES-treated patients (19.4% vs. 2.9%; P = 0.03). Median total direct cost outcomes were similar between groups (EL = $9,696 and ES = $13,197; P =.46). EL and ES had similar cost/variceal rebleeding prevented ($28,678 vs. $29,093) and cost/survival ($27,313 vs. $23,804). In the subgroup of active bleeders, ES had a substantially lower cost/survival ($28,523 vs. $51,696). We conclude that resource utilization was similar between treatment groups and that the choice of endoscopic therapy for EVH must still rely on clinical grounds. Further studies comparing costs and resource utilization in this patient population are needed.

Cost-Benefit Analysis↗

The prognostic significance in HIV infection of immune activation represented by cell surface antigen and plasma activation marker changes.

One hundred and eighteen HIV-infected homosexual men without AIDS and 40 control seronegative homosexual men were assessed for 23 parameters reflecting immune activation to determine prognostic significance for occurrence of AIDS. Samples cryopreserved in 1987-1989 were analyzed, with AIDS occurrence determined by mid-1992. Cell surface antigens assessed on the major lymphocyte subsets were HLA-DR, CD38, CD71, and CD25. Soluble serum molecules assessed were tumor necrosis factor alpha, soluble TNFalpha receptor II, soluble IL-2 receptor alpha, neopterin, and beta2-microglobulin. Using a proportional hazards model, prognostic markers included decreased CD4 number and percentage; increased sIL-2R, neopterin, and beta2M; increased percentage HLA-DR+ total lymphocytes and CD4+ cells; increased CD38+ total lymphocytes and CD8+ cells; increased CD71+ total lymphocytes and CD4+ cells; and decreased CD25+ total lymphocytes and CD19+ cells. After adjustment for CD4 cell levels, sIL-2R, neopterin, beta2M, and CD25+ CD19 cells remained significant, indicating that additional information about AIDS risk was provided by these markers.

ADP-ribosyl Cyclase↗

Solution x-ray scattering-based estimation of electron cryomicroscopy imaging parameters for reconstruction of virus particles.

Structure factor amplitudes and phases can be computed directly from electron cryomicroscopy images. Inherent aberrations of the electromagnetic lenses and other instrumental factors affect the structure factors, however, resulting in decreased accuracy in the determined three-dimensional reconstruction. In contrast, solution x-ray scattering provides absolute and accurate measurement of spherically averaged structure factor amplitudes of particles in solution but does not provide information on the phases. In the present study, we explore the merits of using solution x-ray scattering data to estimate the imaging parameters necessary to make corrections to the structure factor amplitudes derived from electron cryomicroscopic images of icosahedral virus particles. Using 400-kV spot-scan images of the bacteriophage P22 procapsid, we have calculated an amplitude contrast of 8.0 +/- 5.2%. The amplitude decay parameter has been estimated to be 523 +/- 188 A2 with image noise compensation and 44 +/- 66 A2 without it. These results can also be used to estimate the minimum number of virus particles needed for reconstruction at different resolutions.

Bacteriophage P22↗

An analysis of first-time enquirers to the CancerBACUP information service: variations with cancer site, demographic status and geographical location.

A retrospective comparison of cancer incidence data and, where relevant, population data with 16,955 first-time users (patients, relatives and friends) of a national cancer information service (CancerBACUP) during the period April 1995 to March 1996 is presented. The number of events observed was compared with the number of events expected, were the national rates of cancer incidence and population demographics apply. Standardized incidence ratios (SIRs) (observed - expected ratios) were used to indicate any differences. Statistically significant differences (P < 0.001) in the observed and expected sex, age and primary site distribution of patients enquired about were found. Statistically significant differences (P < 0.001) were also identified for the age, employment status, socioeconomic class and geographical location of first-time enquirers (patients, relatives and friends). Enquiries about brain, testis and breast cancers and non-Hodgkin's lymphoma (NHL) were substantially higher than expected; enquiries about bladder, lung, stomach and colorectal cancers were much lower than expected. As the service is provided via a freephone number, it is available to all, and users might be expected to be randomly distributed across the variables listed. The underlying reasons for the differences identified need to be investigated, and the role of information in the care of cancer patients should be formally evaluated.

Adult↗

Limited joint mobility in the hands and feet of adolescents with Type 1 diabetes mellitus.

AIMS: Limited joint mobility (LJM) in the foot has not been assessed in adolescents with Type 1 diabetes mellitus (DM) but is associated with neuropathic ulceration in adults. This study was designed to determine the presence of LJM in adolescents with Type 1 DM and its association with microvascular disease. METHODS: The hands, feet and hips were examined in 302 diabetic adolescents and 51 nondiabetic controls (aged 11.5-20 years). LJM was defined as less than the fifth percent reference for controls. RESULTS: Reduced motion was found in 35% of diabetic adolescents at the subtalar (ST) joint, 18% at the first metatarsophalangeal (MTP) joint, 26% at the fifth metacarpophalangeal (MCP) joint and 13% had limited passive extension of the interphalangeal (IP) joints of the hands. Limited passive IP joint extension of the hands was not present in the controls. Limited active IP joint extension, a positive 'prayer sign', occurred in 35% of diabetic adolescents and 14% of controls. Diabetic adolescents showing LJM in any of these areas, except the prayer sign, were more likely to have retinopathy (odds ratio 2.53, CI: 1.53-4.18). Those with LJM in the foot were more likely to have albumin excretion rates >7.5 microg/min (OR 2.06, CI: 1.16-3.68). CONCLUSION: LJM in the feet of adolescents with Type 1 DM is associated with microvascular disease and is a useful routine clinical measure.

Adolescent↗

Safety and immunogenicity of Haemophilus influenzae-tetanus toxoid conjugate vaccine given separately or in combination with a three-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids and inactivated poliovirus vaccine for the first four doses.

The purpose of this randomized, controlled trial was to assess the safety and immunogenicity of a three-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids and inactivated poliovirus vaccine given either separately or combined as a single injection with a Haemophilus influenzae type b-tetanus toxoid conjugate vaccine. A total of 180 infants were immunized at 2, 4, and 6 months of age; 129 were given a booster dose at 16-19 months of age. Vaccine-associated adverse events were similar whether the vaccines were combined as a single injection or given separately. There were no differences in levels of antibodies to Bordetella pertussis antigens (pertussis toxoid, filamentous hemagglutinin, and pertactin), diphtheria toxoid, or the three poliovirus types. The tetanus antitoxin level after the primary three-dose series was higher in recipients of the combined vaccine (2.37 IU/mL) than in recipients of the separate injections (1.32 IU/mL; two-sided P = .0001). In contrast, combined vaccine recipients had lower levels of antibody to H. influenzae type b polysaccharide after the third dose (1.57 microg/mL) than did those given separate injections (3.22 microg/mL; two-sided P = .0026). The antibody levels were not significantly different before or 1 month after the booster dose (32.9 microg/mL vs. 47.8 microg/mL, respectively; two-sided P = .07). We conclude that the vaccines were immunogenic and well tolerated. Despite lower levels of antibody to the H. influenzae type b polysaccharide after the primary three-dose series, mixing of the vaccines in a single syringe likely induced immunologic priming, as suggested by the high antibody levels after the booster dose.

Antibodies, Bacterial↗

Lattice simulations of aggregation funnels for protein folding.

A computer model of protein aggregation competing with productive folding is proposed. Our model adapts techniques from lattice Monte Carlo studies of protein folding to the problem of aggregation. However, rather than starting with a single string of residues, we allow independently folding strings to undergo collisions and consider their interactions in different orientations. We first present some background into the nature and significance of protein aggregation and the use of lattice Monte Carlo simulations in understanding other aspects of protein folding. The results of a series of simulation experiments involving simple versions of the model illustrate the importance of considering aggregation in simulations of protein folding and provide some preliminary understanding of the characteristics of the model. Finally, we discuss the value of the model in general and of our particular design decisions and experiments. We conclude that computer simulation techniques developed to study protein folding can provide insights into protein aggregation, and that a better understanding of aggregation may in turn provide new insights into and constraints on the more general protein folding problem.

Algorithms↗

High-throughput isolation of Caenorhabditis elegans deletion mutants.

The nematode Caenorhabditis elegans is the first animal whose genome is completely sequenced, providing a rich source of gene information relevant to metazoan biology and human disease. This abundant sequence information permits a broad-based gene inactivation approach in C. elegans, in which chemically mutagenized nematode populations are screened by PCR for deletion mutations in a specific targeted gene. By handling mutagenized worm growth, genomic DNA templates, PCR screens, and mutant recovery all in 96-well microtiter plates, we have scaled up this approach to isolate deletion mutations in >100 genes to date. Four chemical mutagens, including ethyl methane sulfonate, ethlynitrosourea, diepoxyoctane, and ultraviolet-activated trimethylpsoralen, induced detectable deletions at comparable frequencies. The deletions averaged approximately 1400 bp in size when using a approximately 3 kb screening window. The vast majority of detected deletions removed portions of one or more exons, likely resulting in loss of gene function. This approach requires only the knowledge of a target gene sequence and a suitable mutagen, and thus provides a scalable systematic approach to gene inactivation for any organism that can be handled in high density arrays.

Algorithms↗

An open study of the bladder neck support prosthesis in genuine stress incontinence.

OBJECTIVE: To determine the proportion of unselected women with genuine stress incontinence in whom a bladder neck support prosthesis could be fitted successfully by three gynaecologists with no prior knowledge of the device, and to measure efficacy of the device. DESIGN: Prospective interventional study. SETTING: Two metropolitan urodynamic units. SAMPLE: Eighty women with genuine stress incontinence. MAIN OUTCOME MEASURES: Average number of leaks per day on a frequency volume chart, average number of pads worn per day, urine loss on a one-hour pad test, and urine flow rate. RESULTS: Of the 80 recruits, 11 had exclusion criteria and four could not be fitted at the first visit. Of 65 participants, 39 (58%) withdrew from the study before week four. In 20 of 39 women (51%) post-surgical scarring made fitting difficult, and six (15%) withdrew for unrelated personal or medical reasons. In five women (13%) the device was never effective; six withdrew because of adverse events and two required devices that were larger or smaller than those presently available. Thus 38 of 65 participants (58%) could be fitted by the three gynaecologists. Of 26 women who wore the device for four weeks, median leaks per day fell from 2.5 (interquartile range (IQR) 1.9-4.6) to 1.0 (IQR 0-2); median number of pads per day fell from 1.5 (IQR 0.5-3) to 0 (IQR 0-1); and median pad test loss fell from 19 g/h (IQR 8-49) to 2 g/h (IQR 0-8). Sixteen of these 26 patients (62%) achieved objective success, six (23%) were socially continent, one failed to respond and three declined to complete all outcome measures. Urine flow rates revealed no evidence of outflow obstruction. At the sixth month, 18 of 26 patients (69%) were wearing the device successfully; 15 of these women continued to the 12th month, and all but one were objectively dry. CONCLUSIONS: The bladder neck support prosthesis is a useful addition to the range of treatments available for the management of genuine stress incontinence, but may be difficult to fit in women who are oestrogen-deprived or have undergone multiple surgical procedures. The demands of the trial protocol were found to be onerous by frail elderly women.

Aged↗

Hepatic dysfunction in a population of antibody-deficient patients: prevalence, aetiology and outcome of PCR screening for hepatitis C and G viruses.

BACKGROUND AND OBJECTIVES: A group of 40 antibody-deficient patients receiving regular infusions of intravenous immunoglobulin underwent close monitoring in an attempt to identify hepatic dysfunction. The continuing risk of hepatitis virus transmission, especially hepatitis C virus via immunoglobulin products prompted this policy. We report our findings. METHODS: Screening included measurement of transaminase levels at each infusion. The patients were also tested for evidence of infection with hepatitis viruses B, C and G. RESULTS: Abnormal liver function tests were identified in 6 cases. However, a blood-borne viral aetiology was not found in any of these cases. Additional investigation allowed an alternative aetiology to be identified in most cases. One patient found to be positive for hepatitis G virus (HGV)-RNA by reverse transcriptase-polymerase chain reaction has no evidence to date of clinical problems as a result. INTERPRETATION: The results are reassuring in that definite iatrogenic hepatitis virus transmission has not been found in this cohort, despite long-term treatment with a wide range of immunoglobulin products. The source of infection of the single patient infected with HGV remains as uncertain as the pathogenic potential of this virus. However, as long as the risk of immunoglobulin-associated viral transmission continues, a strict monitoring programme such as ours should continue to facilitate prompt detection of cases with abnormal liver function. Liver dysfunction in this group requires full investigation and we cannot exclude infection with hitherto unidentified blood-borne viruses.

Adolescent↗

Denver American Indian mental health needs survey.

American Indians are at higher risk for mental health problems than other ethnic groups in the United States (Nelson, McCoy, Stetter, & Vanderwagen, 1992). Little attention has been directed towards assessing mental health problems among urban American Indians. In response to an Indian Health Service (IHS) call for proposals, this survey addressed the mental health needs of Denver urban American Indians. The purpose of the survey was to gather data from Denver American Indian adults and adolescents as well as service providers in the Denver area who work, to one degree or the other, with members of the American Indian community. These data were to provide a general idea of the breadth of mental health and other associated problems among the Denver American Indian population.

Adolescent↗

Cimetidine does not influence TIL in breast cancer.

Cimetidine is known to have immunomodulatory effects and this study aimed to examine the effect of pre-operative cimetidine treatment on lymphocytic infiltration in n = 72 women with breast cancer randomised to 400 mg bd or placebo for five days presurgery. A combined index was devised by adding infiltrating lymphocyte percentage and lymphoid score. There were no significant differences in circumferential infiltrate and lymphoid follicles in cimetidine treated patients and control patients with breast cancer.

Breast Neoplasms↗

A 3.3-Ma impact in argentina and possible consequences

Enigmatic glassy materials (escorias) and red bricklike materials (tierras cocidas) occur at a restricted stratigraphic level (the top of the Chapadmalal Formation). Materials from one locality near Mar del Plata are attributed to a mid-Pliocene impact event with a radiometric and magnetostratigraphic age of 3.3 million years ago (Ma). An extinction of endemic fauna (including the glyptodonts and flightless cariamid birds) correlates with the unit containing the impact glasses. Moreover, the age of the glasses is coincident within dating uncertainties with a pulselike change in the oxygen isotope marine record in the Atlantic and Pacific Oceans just before the late Pliocene deterioration of the climate.

Journal Article↗

The C-terminus of human bleomycin hydrolase is required for protection against bleomycin-induced chromosomal damage.

Mammalian bleomycin hydrolases (BH) are enzymes with proven exopeptidase activity responsible for deamidation of the beta-aminoalanine moiety in bleomycin and are thought to limit the therapeutic efficacy of the drug. We have recently determined that the highly conserved BH-like domain in the C-terminus of human bleomycin hydrolase (hBH) is critical both for in vitro aminopeptidase and bleomycin metabolizing activities. To determine if hBH protects mammalian cells against bleomycin clastogenic effect, we transfected CHO cells with plasmids encoding hBH or C-terminal truncated forms and evaluated the level of chromatid breaks after bleomycin exposure. CHO cells expressing hBH had 50% less chromatid breaks after bleomycin treatment compared with mock transfected cells. The eight amino acid bleomycin hydrolase-like domain in the C-terminus, which does not contain any of the putative active site amino acids, was essential for protection against bleomycin induced chromatid breaks. These results demonstrate that intracellular hBH levels can influence the clastogenic action of bleomycin and that the C-terminus has a functional role in the biological activity of hBH.

Amino Acids↗