Biomedical subjects
W J Smith
Publications and source records attributed to W J Smith.
Regulation of dikaryon-expressed genes by FRT1 in the basidiomycete Schizophyllum commune.
The gene FRT1 has previously been shown to induce homokaryotic fruiting in transformation recipients of the basidiomycete Schizophyllum commune. In this paper, we demonstrate by gene disruption experiments that FRT1 is dispensable for dikaryotic fruiting. Nonfruiting homokaryotic FRT1 disruptant strains exhibited enhanced aerial growth of mycelia compared to wild type. Introduction of a functional FRT1 allele into the disruptant restored the wild-type colony morphology. Transcript abundance of the dikaryon-expressed SC1 and SC4 hydrophobin genes and the SC7 gene were greatly elevated in homokaryotic FRT1 disruptant strains. Growth of the disruptant strains under continuous light was found to inhibit the elevation of SC1 and SC4 transcript levels, but not of SC7 mRNA. These data suggest that the role of FRT1 in vegetatively growing homokaryons is to act as a negative regulator of dikaryon-expressed genes.
Appetitive and consummatory sexual behaviors of female rats in bilevel chambers. I. A correlational and factor analysis and the effects of ovarian hormones.
This study investigated measures of sexual behavior displayed by female rats in bilevel chambers, the statistical relationships among the measures, and their dependency on hormone priming. Normative data from a standard 35-min test of sexual behavior were gathered from 82 fully primed sexually experienced Long-Evans females and subjected to multiple correlational and factor analyses. Several consummatory measures of copulation were related significantly, whereas appetitive level changing was statistically independent of consummatory measures. Factor analyses were conducted using orthogonal rotations of correlational matrices derived either from (a) measures of female behavior alone or (b) measures of female and male behavior together. The first analysis revealed five factors that accounted for 84% of the intersubject variance: Receptivity, Pacing, Appetitive Level Changing, Lordosis Reflex, and Solicitation. The second factor analysis with male data included revealed seven factors that accounted for 95% of the intersubject variance: Pacing, Copulatory Rate, Mount Count, Receptivity, Appetitive Level Changing, Solicitation, and Lordosis Reflex. Subsequently, subsets of these females were maintained on different steroid priming regimens (oil, low estrogen, high estrogen, high estrogen and progesterone) prior to a standard test of sexual behavior. Although the expression of all sexual behaviors required estrogen priming, appetitive level changing, solicitation, and pacing required progesterone for their full expression. Finally, appetitive level changing developed following hormone treatment alone, regardless of whether the females received access to sexually active males, inactive castrated males, or other females. Use of bilevel chambers allows complex patterns of sexual behavior to be observed in female rats and may thus facilitate the identification of neurochemical or endocrine mechanisms associated with different aspects of female sexual motivation and performance.
The cost-effectiveness of cervical screening.
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The HealthCare Chaplaincy, Inc., New York, New York.
The HealthCare Chaplaincy is a not-for-profit center for health-related pastoral care, clinical education and research. With a professional staff of 24 chaplains and 11 CPE Supervisors, "The Chaplaincy," as it is called, has developed a multifaith, multi-institutional "Partnership Model" providing pastoral care leadership for a growing number of medical and health-related facilities (see the appendix for a current list). At the same time, these institutions constitute a campus for educating annually over 250 students representing 30 or more different denominations and faith groups. In connection with its new, seven-floor center in the heart of Manhattan, it has recently begun specialized community outreach programs, including sponsorship of a Jewish Institute for Pastoral Care, seminars for local clergy, and bereavement as well as other support groups. In a 13-year period of growth, the budget has risen from less than $300,000 per year to over $4 million in 1998.
CT of the brain: a comparison of transportable and fixed-platform scanners.
OBJECTIVE: The purpose of this study was to determine whether an in-hospital transportable CT scanner can provide diagnostic brain images and to compare the quality of these images with those from a conventional fixed-platform CT scanner. SUBJECTS AND METHODS: Twenty-seven patients with known or suspected intracranial pathology underwent imaging on a transportable scanner and a fixed-platform scanner within 1 hr of each other. Images from each CT examination were evaluated independently by two neuroradiologists who were unaware of patient history. Conspicuousness of intracranial pathology and normal anatomy were rated on a 5-point scale (1 point, optimal; 5 points, poor or not visualized). Statistical comparisons were made using nonparametric tests. RESULTS: Seven CT scans were interpreted as showing normal findings and 20 scans revealed intracranial pathology on both CT scanners. Image quality was higher on the fixed scanner (average rating, 2.42 points; SE = .12) than on the transportable scanner (average rating, 3.10 points; SE = .12) (p = .001). Depiction of the cerebellum, midbrain, and supratentorial gray-white matter was better on the fixed scanner (p < .05). However, we found no significant differences in detection of intracranial pathology between scanners. Both radiologists found images from both scanners to be diagnostic in all 27 patients. CONCLUSION: Images of the brain on the transportable CT scanner were less clear than those on a fixed scanner. However, images from the transportable CT scanner were diagnostic in 27 consecutive patients. The implications of this finding are important for the provision of CT services for critically ill patients who cannot be transported to the radiology department.
Storm warnings over Oregon.
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Assisted suicide: the tip of the iceberg.
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Tail-biting and tail-docking in pigs.
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Tail-biting and tail-docking in pigs.
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Investigations into field cases of porcine colitis with particular reference to infection with Serpulina pilosicoli.
Investigations into the possible causes of colitis and typhlocolitis were carried out on 85 pig units in the United Kingdom between 1992 and 1996. Serpulina pilosicoli was identified most commonly, occurring as the suggested primary agent on 21 (25 per cent) of the units but forming part of mixed infections on another 23 (27 per cent) of the units, the main co-infections being Yersinia pseudotuberculosis (eight units), proliferative enteropathy (six units), Salmonella species (four units) or Serpulina hyodysenteriae (two units). 'Atypical' Serpulina species, S hyodysenteriae, Salmonella typhimurium, Y pseudotuberculosis and Lawsonia intracellularis (proliferative enteropathy) were the suggested primary agents on seven, six, four, four and three units, respectively. Various combinations of mixed infections involving the latter organisms and other possibly incidental agents were recorded on another 10 units. Investigations on a further six units failed to detect any recognised pathogens. On units where S pilosicoli was the suggested primary agent, pigs ranging between 20 to 40 kg (eight to 16 weeks of age), but occasionally up to 50 kg, had diarrhoea and grew poorly over a period of two to three weeks. The prevalence was estimated to be between 5 and 15 per cent in affected batches, with a mortality of approximately 1 per cent. The clinical signs usually developed seven to 14 days after the moving and mixing of pigs. At postmortem examination, affected pigs had liquid contents in their colon, which contained accumulations of mucus in some chronic cases. Gross and histological lesions of colitis were prominent in the mid-spiral region of the colon. In mixed infections with Y pseudotuberculosis, Salmonella typhimurium or S hyodysenteriae, lesions were more extensive and affected the caecum as well as the colon. In the colon, lesions of proliferative enteropathy were usually confined to the proximal half of the ascending spiral but mixed infection with S pilosicoli caused more extensive colitis. Mixed infections were reported to prolong the time taken for pigs to recover naturally and to have a more detrimental effect on growth rates than S pilosicoli infection alone. Despite the successful treatment of batches of pigs with tiamulin or lincomycin, S pilosicoli infection persisted as a chronic problem on many units, with diarrhoea and colitis in successive batches of pigs unless prophylactic medication was used.
Economic analyses in obstetrics and gynecology: a methodologic evaluation of the literature.
OBJECTIVE: To evaluate the methodology of the cost-effectiveness and cost-benefit literature in obstetrics and gynecology. DATA SOURCES: We performed a MEDLINE search of the general and subspecialty obstetrics and gynecology journals for the years 1990 through 1996. METHODS OF STUDY SELECTION: Original investigations including cost-effectiveness or cost-benefit were evaluated by two reviewers for adherence to ten minimum methodologic standards derived by a review of guidelines for medical economic analyses. The major criteria considered included: 1) provision of comparative options, 2) statement of analytic perspective, 3) presentation of cost data, 4) identification of outcome measure, 5) use of summary measure of economic effectiveness or benefit, and 6) performance of a sensitivity analysis. The minor criteria evaluated included: 1) statement of source of cost data, 2) inclusion of long-term costs, 3) use of discounting, and 4) calculation of an incremental summary measure. TABULATION, INTEGRATION, AND RESULTS: Ninety-eight articles that included cost-benefit or cost-effectiveness analyses were identified. The mean number of major and minor principles adhered to were 3.6 and 1.0, respectively. Five publications (5.1%) conformed to all ten major and minor criteria, whereas nine (9.2%) articles used all six major criteria. The provision of cost data (94.8%) and statement of comparative options (96.9%) were the major principles most frequently adhered to, whereas the use of discounting (10.2%) and statement of analytic perspective (19.3%) showed the lowest compliance. Agreement between the reviewers was excellent (kappa .87). CONCLUSION: Published economic analyses in the obstetrics and gynecology literature seldom adhere to all recommended methodologic guidelines. Further training in the methodology of cost-effectiveness analysis is needed within the specialty.
Prevention of chickenpox in reproductive-age women: cost-effectiveness of routine prenatal screening with postpartum vaccination of susceptibles.
OBJECTIVE: To evaluate economic and clinical outcomes of a program of routine prenatal serotesting for varicella and postpartum vaccination of seronegative women. METHODS: An analytic cost-effectiveness model was constructed to compare the current strategy of no serotesting with 1) selective serotesting of pregnant women without a prior history of chickenpox and 2) serotesting of all pregnant women. In both serotesting strategies, seronegative women were vaccinated postpartum. The model followed a hypothetical cohort of 4 million women over 20 years. Costs and chickenpox disease outcomes during and outside of subsequent pregnancies were considered. The incremental cost-effectiveness (cost per adult chickenpox case prevented) of selective serotesting compared with the current strategy was measured. RESULTS: Compared to no testing, selective serotesting would prevent 43% (48,577 of 112,654) of adult chickenpox cases, save $21.8 million in discounted medical and work loss costs from the societal perspective, and cost $1126 per case prevented from the health payer's perspective (medical costs only). The model was sensitive to varicella seroprevalence and incidence of chickenpox among susceptible women but was relatively insensitive to the cost of serologic testing and vaccination. Compared with selective serotesting, the serotest-all strategy would prevent an additional 15,645 cases, at a societal cost of $7653 per additional case prevented. CONCLUSION: The selective serotesting strategy could prevent nearly half of chickenpox cases among this cohort and is cost-saving from the societal perspective. From the health payer's perspective, it compares favorably with other generally accepted preventive practices. It should be considered for prevention of chickenpox among women of childbearing age.
Economic analyses of radiological procedures: a methodological evaluation of the medical literature.
OBJECTIVE: Increasing pressure to curb health care costs has led to considerable interest in economic analyses, including both cost-effectiveness and cost-benefit analyses. Numerous economic analyses of radiological procedures have appeared in both the radiology and non-radiology literature. The objective of this study was to evaluate the methodological quality of economic analyses of radiological procedures published in the non-radiology medical literature during the years 1990 1995. METHODS: Original investigations from the medical (non-radiological) literature that include economic analyses of radiological interventions were identified from a computerized literature search. Each economic analysis article was evaluated by two independent reviewers for adherence to ten methodological criteria. The criteria were derived from review of the medical and radiological economic analysis methodology literature and consisted of the following: (1) Comparative options stated; (2) perspective of analysis defined; (3) outcome measure identified; (4) cost data included; (5) source of cost data stated; (6) long term costs included; (7) discounting employed; (8) summary measure provided; (9) incremental computation method used; and (10) sensitivity analysis performed. The results were compared to a previous study that evaluated the radiological literature. RESULTS: Of the 56 articles in the medical literature that included economic analyses of radiological procedures, only eight (14%) conformed to all ten methodological criteria. The cost data (98%) and comparative options (89%) criteria exhibited high compliance, while the perspective of analysis (25%) and discounting (32%) criteria had relatively low compliance. Agreement between the reviewers was excellent (kappa = 0.88). CONCLUSIONS: Published economic analyses of radiology procedures usually do not meet accepted methodological standards.
Sulfur mustard exposure enhances Fc receptor expression on human epidermal keratinocytes in cell culture: implications for toxicity and medical countermeasures.
Sulfur mustard (HD) is a chemical warfare blister agent. The biochemical basis of HD-induced vesication is unknown, and no antidote currently exists. Basal epidermal cells are a major site of HD toxicity in vivo, with inflammation and HD-increased proteolytic activity implicated as factors that contribute to HD pathology. Fc receptors (FcR) bind to the Fc region of antibody to mediate many effector and regulatory functions that can influence inflammatory responses. FcR are found on all types of immune cells and are also expressed on the surface of human keratinocytes. Assay by fluorescent antibodies demonstrated significantly enhanced CD32 (FcRII) and CD16 (FcRIII) on human epidermal keratinocyte (HEK) cell cultures at 8 to 24 h after exposure to HD (50, 100 and 200 micromol/L). The enhanced CD32 was time- and concentration-dependent and agreed well with the time course of increased proteolysis and cutaneous pathology observed during HD vesication. HD-increased FcR on the surface of HEK might be a mechanism of vesication.
Histopathologic and immunohistochemical features in human skin after exposure to nitrogen and sulfur mustard.
N-methyl-2,2'-dichlorodiethylamine (HN2)is a topical chemotherapeutic agent used as therapy for cutaneous T-cell lymphomas (CTCL). Di(2-chloroethyl)sulfide (SM), and less often HN2, have been used as chemical weapons, with the skin being a principle target. The mechanisms by which these chemicals produce their therapeutic and toxic effects in skin, however, are not clearly defined. We exposed human skin explants to two doses of HN2 and SM. At 18 hours after exposure, histopathologic features were compared. In addition, immunohistochemical markers to basement membrane proteins were used to evaluate the effects of both chemicals on the basement membrane zone. Gross vesication was not seen. Pyknotic nuclei with or without dyskeratotic changes within epidermal keratinocytes were present at both doses. These changes varied more between skin specimens than they did between doses. Ballooning degeneration was more marked after SM exposures. Diffuse dermal-epidermal separation was present only at high-dose exposures and did not appear to correlate with the degree of changes locally in the overlying epidermis. Antibodies to laminin-5 showed decreased immunoreactivity after exposure to HN2 and SM. Immunoreactivity for laminin- was decreased to a lesser extent, and immunoreactivity for collagen IV and VII was unchanged. HN2 and SM produce similar histopathologic and immunohistochemical features after cutaneous exposure. These features suggest that part of mechanism of action of HN2 and SM is a direct effect on the basement membrane zone. Understanding the effects of HN2 and SM separate from their effect on DNA may be important in designing therapies and in advancing our understanding of the pathophysiologic changes induced by these chemicals when delivered topically.
Medicare to reimburse for lung cancer PET imaging.
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Update on ambulatory payment classifications.
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