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Biomedical subjects

D A Clark

Publications and source records attributed to D A Clark.

At least 451 records · Page 25Linked to original sources
PubMedDate not supplied

Human herpesvirus 6.

Human herpesvirus 6 (HHV-6), a member of the beta-herpesvirinae subfamily, is highly seroprevalent, has a worldwide distribution, and infection usually occurs within the first two years of life. In this age group, HHV-6 causes febrile illness including exanthem subitum with seizures a recognised complication. The virus is predominantly T lymphotropic although it can infect a variety of cell types in vitro and CD46 has recently been identified as a cellular receptor. The virus persists in the host, with a latent state proposed in monocytes and bone marrow progenitor cells, and chronic infection in salivary glands. The virus is pathogenic in the post transplantation period and may be a cofactor in the progression of HIV disease. The virus has also been associated with multiple sclerosis (MS), with the virus detected in oligodendrocytes particularly in plaque regions. The role of HHV-6 in MS remains controversial and a more extensive understanding of its neurotropism and association with disease is required. Two variants of HHV-6 exist (A and B) and comparison of their complete nucleotide sequences shows the genomes to be colinear, with a high degree of homology. Variation in specific regions of the genome is more extensive and probably accounts for biological and pathological differences. Almost exclusively, variant B is associated with febrile illness in childhood and is the predominant variant detected in healthy individuals. The epidemiology of HHV-6A infection needs to be better defined, although it is significantly less prevalent. Biological, genetic, epidemiological and pathological findings suggest that the two variants are divergent.

Adolescent↗
PubMedDate not supplied

Multiple vessel coronary angioplasty: classification, results, and patterns of restenosis in 494 consecutive patients.

We report the immediate results and 6 month follow-up data of 494 consecutive patients who underwent coronary angioplasty in two or more major epicardial arteries. Clinical success was achieved in 95% of the 494 patients. The technical success rate of the 1,117 vessels dilated was 89%, defined as at least a 35% reduction (mean = 53%) of the initial percent diameter stenosis and a decrease in the transstenotic gradient to less than or equal to 15 mmHg (mean = 9 mmHg). Complications of the procedure included emergency bypass surgery (2.8%), myocardial infarction (3.0%), and hospital death (0.4%) inclusive. At least one of these complications (major cardiac event) occurred in 3.8% of patients. Prior to angioplasty, 46% of patients were in Canadian Cardiovascular Society Class II, 42% in Class III, and 12% in Class IV. Follow-up clinical evaluation (mean follow-up period of 16.9 months) showed 83% of patients in Class I, 14% in Class II, and 3% in Class III. Of the 286 successful patients who have reached 6 month follow-up plateau (mean follow-up period of 20.5 months), 164 (57%) have so far had repeat coronary angiography and exhibited three different patterns: all lesions patent (N = 54), some lesions restenosed (N = 60), and all lesions restenosed (N = 32). There were 18 patients with new vessel lesions (not previously dilated). Logistic regression analyses demonstrated that clinical factors including diabetes (P less than .05), hypercholesterolemia, (P less than .01), new onset angina (P less than .05), current smoking (P less than .01), and morphologic and technical factors such as preangioplasty diameter stenosis greater than 95% (P less than .05) and higher balloon inflation pressure (P less than .05) were predictive of increased risk of recurrence. Patients were classified into two groups based on the anatomy of the target lesions. In Group A (N = 217), patients had a single lesion in each of the vessels to be dilated; Group B (N = 277) patients had a complex lesion in at least one of the vessels dilated. Group B patients were more likely to develop recurrence (P less than .05). Of the original 494 patients, 488 (99%) are alive. Coronary angioplasty (either initially or with repeat PTCA) has been the definitive treatment in 453 of the 494 patients for an overall success of 92%.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMedDate not supplied

Recurrence after coronary angioplasty.

Recurrence (restenosis) after coronary angioplasty has undermined the initial success of the procedure and has compromised, to some extent, the attractiveness of the technique in the treatment of ischemic heart disease. Assessment of recurrence predictors has been problematic due to lack of coordination of angioplasty recurrence research and includes: incomplete angiographic documentation, variations in definitions of restenosis anatomically and the results of restenosis physiologically (ie, myocardial ischemia), the dirth of morphologic specifications of subsets under investigation and late outcome pathology, limitations in statistical analyses used, and minimal efforts to classify the available data on recurrence. A review of the literature suggests that all findings regarding recurrence after angioplasty can be organized in four categories: clinical, morphologic, technical (or procedural), and pharmacologic. The reported findings with high concordance as risk factors for recurrence after angioplasty include the clinical factors of diabetes mellitus, hyperlipidemia, and angina of short duration or unstable presentation. Morphologic factors which have been corroborated vis-à-vis recurrence include stenoses with diameter reduction of greater than 90% before and greater than 30% after angioplasty, residual trans-stenotic pressure gradients of greater than 20 mmHg after angioplasty, and lesions that are diffuse, long, eccentric, or calcified. Technical factors associated with recurrence include lower balloon/vessel (or graft) ratios and the absence of (uncomplicated) "intimal dissection." The category most deficient in research regarding recurrence after angioplasty is pharmacologic. Since there are statistically documented and reproducible factors predictive of restenosis, to ignore or minimize these findings or resist further evaluation (because of the ease and safety of performing repeat angioplasty) is to deny the opportunity to understand the mechanisms and favorably affect the incidence of recurrence. This review concludes with two major implications of the restenosis research: certain clinical, technical, and pharmacologic factors, if addressed, may predictably decrease the rate of restenosis and certain clinical and morphologic factors may increase the risk of restenosis; these factors may be less readily modified (eg, diabetes, lesion calcification) and thus must be considered in the decision for angioplasty.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMedDate not supplied

Protease inhibitors suppress in vitro growth of human small cell lung cancer.

The effect of the protease inhibitors Bowman Birk inhibitor (BBI) and aprotinin on the in vitro clonal growth of two human small cell lung cancer (SCLC) cell lines was investigated. In addition, the effect of BBI on the growth factor processing of proGRP by SCLC cells and on mRNA levels for prohormone convertase 1 and 2 (PC1 and PC2) in SCLC cells was examined. The protease inhibitors BBI and aprotinin significantly decreased growth in both SCLC cell lines studied. In NCI-H345 cells, BBI appears to inhibit the processing of proGRP to GRP, as indicated by Western blot analysis. NCI-H345 cells, when treated with BBI (100 micrograms/ml), also showed highly significant decreases of mRNA for PC1 and PC2 of about 50%. These data suggest that proteases serve an important role in the growth regulation of SCLC and that inhibitors of these proteases may be potent suppressors of SCLC growth at the level of the gene.

Aprotinin↗
PubMedDate not supplied

The relationship between health care reform and nurses' interest in union representation: the role of workplace climate.

Market-based reforms are rapidly changing the landscape of the American health care system. Over the last decade, a great deal of attention has been paid to these reforms, particularly the advent and rapid growth of managed care and the vertical and horizontal integration of provider institutions. The ramifications of these changes on both individual and institutional consumers has also been widely considered by scholars and policymakers. Yet, although these market reforms are driving the massive restructuring of work in hospitals and other health care organizations, comparatively little attention has been paid to the impact these changes have on health care employees and the environment in which they work. This article reports the results of an exploratory study examining the relationship between health care market reforms, nurses' perceptions of the climate for patient care in hospital settings, and nurses' interest in union representation. A model is proposed to help explain nurses' support for union representation in the presence of market-based reforms.

Health Care Reform↗
PubMedDate not supplied

'Spin, cool, and filter' red cells prepared in a regional blood center.

Red cells depleted of leukocytes by the "spin, cool, and filter" (SCF) method are effective in preventing most febrile, nonhemolytic transfusion reactions (FNHTR). To determine whether red cell concentrates may be centrifuged in a blood center and filtered subsequently at an outlying facility, the authors examined how leukocyte removal was affected by the transport and storage of centrifuged red cells before microaggregate filtration (MAF). One hundred fourteen red cell units were each divided into two aliquots. After centrifugation, one aliquot from each unit was retained in the blood center, and the other was transported on a truck for 2 to 12 hours. Aliquots were stored for variable periods, after which the residual leukocytes were counted. Neither transportation nor storage significantly affected leukocyte removal by MAF. However, an unacceptable proportion of all SCF units failed to meet American Red Cross standards for leukocyte-poor blood and studies of factors influencing leukocyte depletion were undertaken. A relative centrifugal force of 6700 X g was needed to produce consistently acceptable units when blood was 8 to 15 days old. These results show that making SCF red cells is a practical, inexpensive way for blood centers to provide hospitals with products that prevent most FNHTR; however, each facility that prepares these products must perform quality control carefully.

Blood Banks↗
PubMedDate not supplied

Critical analysis of intravenous immunoglobulin therapy for recurrent miscarriage.

Critical analysis of intravenous immunoglobulin therapy for recurrent miscarriage An alloimmune abnormality is believed to be the cause of recurrent miscarriage in couples in whom no other cause can be identified. Because of its immunosuppressive properties, intravenous immunoglobulin (IVIG) is used as a treatment for this disorder. The purpose of this study was to determine whether IVIG improves the chance of successful pregnancy in women with recurrent miscarriage by using individual patient data from efficacy trials. Detailed information on each patient enrolled in these trials was obtained to evaluate the efficacy of IVIG and investigate the effect of clinical variability on pregnancy outcome. Data from 125 patients in the IVIG group and 115 patients in the placebo group were available for analysis. Although the number of previous miscarriages and female age were both negative prognostic factors for successful outcome, there was no significant improvement in successful pregnancy or live birth rate with IVIG. Subgroup analyses indicated that timing of IVIG administration may be important. The results of the present study highlight the importance of stratification for known confounders, so that the role of IVIG can be evaluated in more detail. The collective evidence thus far indicates that IVIG does not have a therapeutic effect that is clinically meaningful.

Abortion, Habitual↗
PubMedDate not supplied

Unexplained sporadic and recurrent miscarrage in the new millennium: a critical analysis of immune mechanisms and treatments.

There have been important advances in basic science investigation of mechanisms underlying spontaneous miscarriages which lend support to empirical treatments such as intravenous immunoglobulin G and allogeneic leukocyte immunotherapy. The results from clinical trials of these and other proposed treatments have been problematic. There is only one published meta-analysis of sufficient power and appropriate stratification to qualify as Level 1 evidence, and that deals only with leukocyte immunotherapy. Here we critically review current trials and their flaws, update the meta-analysis, and comment on potential new approaches. Inadequate sample size, better definition of heterogeneity, and proper stratification to minimize the effects of heterogeneity remain as problems. Verification that the experimental or test treatment was active in producing the expected alteration in immunophysiology in the recipient is lacking in most trials; use of stored rather than fresh allogeneic leukocytes appears problematic. Hidden biases that affect trial significance emerge with critical analysis, and the focus on apparent 'high quality' of design in published reports may be misleading. We conclude that there seem to be enough patients to conduct clinical trials of sufficient size to achieve adequate power to test therapies showing promise in pilot studies, but at present, the only Level 1 evidence concerns leukocyte immunotherapy which appears to increase the chance of a live birth if given to appropriate patients.

Abortion, Habitual↗