Assessment of five culture media for the growth and isolation of Capnocytophaga spp.
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Publications and source records attributed to M Wilson.
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OBJECTIVE: This study was undertaken to determine the clinical implications of the finding of atypical glandular cells of undetermined significance in cervical cytologic specimens in our patient population. STUDY DESIGN: A retrospective study was performed. All cervical cytologic examinations with the diagnosis of atypical cells of undetermined significance between January 1992 and June 1997 were identified by means of a computerized database. Medical records were reviewed to identify patient demographic characteristics and to determine the presence or absence of associated pathologic conditions of the cervix and endometrium. The chi2 test and analysis of variance were applied to dichotomous and continuous variables, respectively, to determine the implications of a cytologic evaluation of atypical glandular cells of undetermined significance. RESULTS: Cytologic results reported as atypical glandular cells of undetermined significance were obtained in a patient cohort of 492. Atypical glandular cells of undetermined significance was the only cytologic diagnosis in 224 patients; 268 patients had both atypical glandular cells of undetermined significance and an additional squamous abnormality, including atypical squamous cells of undetermined significance and cervical intraepithelial neoplasia I, II, or III. Two patients were excluded because of a history of endometrial cancer. A histologic evaluation was obtained within 1 year in 353 cases. Among the 353 patients who had a histologic evaluation performed, 227 (64%) had benign cervical and endometrial findings. There were 18 glandular lesions (5%), including complex hyperplasia with atypia, adenocarcinoma in situ of the cervix, adenocarcinoma of the cervix, and adenocarcinoma of the endometrium. A squamous lesion was present in 108 patients (31%). Most squamous lesions (81%) were found in patients with atypical glandular cells of undetermined significance associated with a squamous abnormality, whereas only 19% were found in patients with atypical glandular cells of undetermined significance as the only diagnosis. Women <35 years old had a much higher frequency of histologic abnormalities than did women >50 years old (P <.0001), with most of these lesions being squamous. Women >50 years old had a much higher frequency of glandular histologic abnormalities (P <.001). CONCLUSION: More than a third of women with Papanicolaou smears reported as showing atypical glandular cells of undetermined significance will be found to have a histologic abnormality. Women <35 years old with a cytologic evaluation of atypical glandular cells of undetermined significance have a higher frequency of histopathologic findings, with most being squamous lesions. Women with a cytologic evaluation of atypical glandular cells of undetermined significance who are >50 years old have more glandular lesions than do younger women. The term atypical glandular cells of undetermined significance is a misnomer. The significance of this cytologic finding has been defined and represents a marker for serious pathologic processes.
Data are presented on the effect of the tree canopy transmittance in the visible waveband (VT), canopy width, height and height of the start of the tree canopy (CH) on the solar UV in tree shade on a horizontal plane at ground level during a Southern Hemisphere summer. Of these factors, the VT and CH have an influence on the UV irradiances in the tree shade. The shade ratios (UV in tree shade to that in full sun) for erythemal UV ranged from 0.71 to 0.42, 0.54 to 0.29 and 0.63 to 0.41 for morning, noon and afternoon, respectively, for the VT range of 0.4-1.0. Over the same VT range, the shade ratios for UVA ranged from 0.61 to 0.28, 0.50 to 0.22 and 0.49 to 0.29 for morning, noon and afternoon, respectively. The UV exposures in the tree shade decreased with the VT with a marginally higher decrease in the irradiances for the UVA compared to the erythemal UV. Despite the protection by the tree shade, significant UV in the tree shade of approximately 4 MED (minimum erythemal dose) were received for the latitude in this research on a cloud free summer day on a horizontal plane over a 2-h period centred about solar noon.
Approximately 10% of all renal cell carcinomas (RCCs) present a distinctive papillary histology. Familial papillary RCC (PRCC) has been described, but the majority of cases appear to be sporadic. Recently, germline mutations in the MET proto-oncogene on chromosome 7 have been identified in families with hereditary PRCC. We evaluated 59 patients with PRCC for the frequency of MET germline mutations to determine the value of genetic screening of this patient population. Between 1976 and 1997, 165 patients were identified with PRCC by retrospective chart review. Fifty-nine of 133 surviving patients agreed to provide a family history, a blood specimen, and informed consent for genetic research. DNA was isolated from peripheral blood leukocytes. Denaturing high-performance liquid chromatography (DHPLC) followed by genomic sequencing was performed on eight exons of the MET proto-oncogene, including exons 5-7 of the extracellular domain, exon 14, and exons 16-19 of the tyrosine kinase domain. The 59 patients in this study included 49 men and 10 women with a mean age at diagnosis of 61 years. Bilateral and/or multifocal disease was present in 13 cases (22%). No germline mutations were detected in the studied exons of the MET proto-oncogene (exons previously reported to contain deleterious mutations in familial PRCC). No pathological MET proto-oncogene germline mutations were identified in 59 patients with PRCC. The germline mutation rate in this clinic-based population of individuals with PRCC approaches 0% (CI = 0-6.18). MET proto-oncogene germline mutation screening does not appear to be clinically indicated in patients with PRCC without additional evidence for a genetic predisposition (positive family history, unusual age at onset, bilateral disease).
Chimeric proteins containing antigen linked to cytokines have shown some promise as vaccine candidates but little is known of their mechanism of action, particularly at the level of the antigen-presenting cell. We have investigated this using a chimeric protein in which an immunodominant T cell epitope from influenza hemagglutinin peptide (HA), recognized in the context of I-E(d), was fused to IL-2. Immature murine dendritic cells (DC) derived from bone marrow (BMDC) were used to present the chimeric protein to a T cell hybridoma with TCR specific for the HA peptide (A5 cell line). HA-IL-2 was found to induce significantly higher T cell activation than HA alone. Although the inclusion of IL-2 and HA separately did increase the response of A5 cells compared to HA alone, they were not as effective as the HA-IL-2 chimeric protein. When an antibody known to block IL-2 receptor alpha chain (CD25) was included, A5 activation was reduced, suggesting a role for the receptor in this process. Expression of CD25 on A5 cells was low during activation, implying that the effect was mediated by CD25(+) BMDC. Antigen uptake and processing of HA-IL-2 by BMDC was required since fixing BMDC, prior to antigen exposure, greatly reduced their ability to activate A5 cells. The function of CD25 on DC is currently unknown. Our results suggest this receptor may play a role in antigen uptake and subsequent T cell activation by receptor-mediated endocytosis of antigen attached to IL-2. This finding that may have implications for the development of a new generation of vaccines.
The Interdisciplinary Generalist Curriculum (IGC) Project was a competitive, seven-year demonstration project funded by the Health Resources and Services Administration (HRSA). It was established to determine whether specific interdisciplinary innovations in preclinical medical school curricula could affect students' selection of careers in family medicine, general internal medicine, or general pediatrics. Through collaboration among the three generalist disciplines, the IGC innovation exposed all preclinical students in ten demonstration schools to a new or significantly enhanced preclinical curriculum that included a direct supervised clinical experience with a generalist physician preceptor. The project was managed by an interdisciplinary executive committee that was codirected by one representative each from family medicine, general internal medicine, and general pediatrics. A national advisory committee with representation from the academic and professional organizations of family medicine, internal medicine, pediatrics, and osteopathy provided input to the executive committee in guiding the project. The project was externally evaluated. Major outcomes of the IGC Project include sustained curricular changes in ten institutions, prompted by relatively few dollars and demonstration of models for collaboration at institutional and national levels. This supplement describes the IGC Project's experience and outcomes so that others may draw pertinent information to apply to their own efforts in medical education.
Implementation of the Interdisciplinary Generalist Curriculum (IGC) Project involved complex processes that reflect structural, funding, and intervention design considerations. Among structural considerations, the IGC Project benefited from a national structure above the level of the demonstration schools. Governance by committee was highly effective because it harnessed and balanced power. At the national level, governance by committee was enhanced by strong central coordination, and it had a role-modeling effect for governance at the school level. The IGC experience over the seven-year course of the project suggests that it is important to revisit the role of a national advisory committee over time and to revise that role as warranted. Funding considerations, including the importance of funding evaluation for a period of time long enough to measure intended impacts and the length and amount of funding to demonstration schools, are discussed. Prescription of the IGC intervention and the focus on years one and two of medical education are critical design considerations. The authors conclude that the IGC Project used relatively few federal dollars to demonstrate a highly prescribed intervention in a limited number of medical schools toward a clear and limited goal. IGC lessons apply to programs specifically targeting primary care education, but also to other medical school curricular innovations, and perhaps, to a larger framework of multi-site educational interventions.
Recommendations on future directions, funding, and organizational and curricular issues have emerged from the complexity of the Interdisciplinary Generalist Curriculum (IGC) Project. For example, future demonstration projects aimed at innovations in medical education that are funded through the contracting mechanism are recommended, and funding intended to serve as institutional leverage for demonstrating desired curricular innovations in medical education is encouraged. Funding provided to entities that can maximize influence within the institutions is recommended. Also, the period of time over which funds are provided needs to take into consideration the breadth of the impact of the funded program on the larger curriculum and the length of time needed to measure desired outcomes. Organizational findings are that multi-site projects with administrative oversight bodies should be governed by representatives of concerned disciplines who have stakes in the demonstration of the innovations in medical education, and roles of the executive and advisory committees involved in the effort need to be made explicit at the onset and revisited over time. Similarly, the role of the funder needs to be explicit. Curricular recommendations are that medical schools are encouraged to develop longitudinal generalist preceptorship experiences early in medical education for all students, regardless of their eventual career choices. Schools should anticipate that curricular innovations in the preclinical years may require modifications of the educational process in the clinical years.
Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii. In the United States, approximately 85% of women of childbearing age are susceptible to acute infection with T. gondii. Acute infections in pregnant women may cause serious health problems when the organism is transmitted to the fetus (congenital toxoplasmosis), including mental retardation, seizures, blindness, and death. An estimated 400 to 4000 cases of congenital toxoplasmosis occur in the U.S. each year. Manifestations of congenital toxoplasmosis may not become apparent until the second or third decade of life. Serologic tests are used to diagnose acute infection in pregnant women, but false-positive tests occur frequently, therefore, serologic diagnosis must be confirmed at a reference laboratory before treatment with potentially toxic drugs should be considered. Much of congenital toxoplasmosis can be prevented by educating women of childbearing age and pregnant women to avoid eating raw or undercooked meat, to avoid cross-contamination of other foods with raw or undercooked meat, and to use proper cat-litter and soil-related hygiene.
Rotating-disc systems are used to model the flow and heat transfer that occurs inside the cooling-air systems of gas-turbine engines. In this paper, recent computational and experimental research in three systems is discussed: rotor-stator systems, rotating cavities with superposed flow and buoyancy-induced flow in a rotating cavity. Discussion of the first two systems concentrates respectively on pre-swirl systems and rotating cavities with a peripheral inflow and outflow of cooling air. Buoyancy-induced flow in a rotating cavity is one of the most difficult problems facing computationalists and experimentalists, and there are similarities between the circulation in the Earth's atmosphere and the flow inside gas-turbine rotors. For this case, results are presented for heat transfer in sealed annuli and in rotating cavities with an axial throughflow of cooling air.
Microcosm dental plaques were grown from an inoculum of human saliva in a constant-depth film fermentor. The inoculum contained four tetracycline-resistant streptococcal species, each of which contained a Tn916-like element. This element was shown to transfer to other streptococci both in filter-mating experiments and within the biofilms in the fermentor.
A Toxoplasma gondii immunoglobulin G (IgG) avidity enzyme-linked immunosorbent assay (ELISA) was developed that combines the accuracy of assays based on end point titers and the relative ease of assays based on optical density values. Like published procedures, the new assay's avidity index (AI) was based on differential T. gondii-specific IgG reactivity in serum-treated wells washed with urea buffer versus that in wells washed with control buffer; unlike previous assays, however, the IgG reactivity was measured quantitatively using a standard curve. The assay was evaluated using 24 IgG-positive and IgM-positive sera collected within 5 months of the onset of symptoms (recent-infection group) and 25 IgG-positive and IgM-negative sera (past-infection group). All sera in the recent-infection group exhibited AI values of <0.18, whereas all sera in the past-infection group exhibited AI values of >0.27. The AI values of the recent-infection group showed significant correlation with the number of days after the onset of symptoms. A subset of 16 sera (8 recent and 8 past) was tested using a commercially available T. gondii IgG avidity ELISA based on end point titration; the results of the two assays showed highly significant correlation (R(2) = 0.9125). In addition, we confirmed and extended the findings of other investigators, showing that AI values calculated using optical density values, but not AI values calculated using quantitative IgG values, varied significantly depending on the serum dilution used. This new assay should facilitate the accurate measurement of T. gondii IgG avidity in a reference laboratory setting.
A phoA fusion library of Actinobacillus actinomycetemcomitans genomic DNA has been screened to identify genes encoding exported and secreted proteins. A total of 8,000 colonies were screened, and 80 positive colonies were detected. From these, 48 genes were identified with (i) more than half having homology to known or hypothetical Haemophilus influenzae genes, (ii) 14 having no ascribed function, and (iii) 4 having very limited or no homology to known genes. The proteins encoded by these genes may, by virtue of their presence on the cell surface, be novel virulence determinants.
In response to heat stress, Bacillus subtilis activates the transcription of well over 100 different genes. Many of these genes are members of a general stress response regulon controlled by the secondary sigma factor, sigma(B), while others are under control of the HrcA or CtsR heat shock regulators. We have used DNA microarrays to monitor the global transcriptional response to heat shock. We find strong induction of known sigma(B)-dependent genes with a characteristic rapid induction followed by a return to near prestimulus levels. The HrcA and CtsR regulons are also induced, but with somewhat slower kinetics. Analysis of DNA sequences proximal to newly identified heat-induced genes leads us to propose ~70 additional members of the sigma(B) regulon. We have also identified numerous heat-induced genes that are not members of known heat shock regulons. Notably, we observe very strong induction of arginine biosynthesis and transport operons. Induction of several genes was confirmed by quantitative reverse transcriptase PCR. In addition, the transcriptional responses measured by microarray hybridization compare favorably with the numerous previous studies of heat shock in this organism. Since many different conditions elicit both specific and general stress responses, knowledge of the heat-induced general stress response reported here will be helpful for interpreting future microarray studies of other stress responses.
OBJECTIVES: To investigate the relations between quantitative diffusion coefficient MRI histograms, clinical variables, and cerebral atrophy. METHODS: Twenty two patients with clinically definite multiple sclerosis and 11 healthy volunteers were studied. Histograms of apparent diffusion coefficient (ADC) from a volume of interest that included multiple slices encompassing the lateral ventricles were processed from diffusion weighted MRI. In addition, total lesion load was measured on T2 weighted dual echo images, and cerebral volume from 3D magnetisation prepared rapid acquisition gradient echo scans. All patients underwent neurological assessment, including disability on the expanded disability status scale (EDSS). RESULTS: Histograms from the patient group showed a reduced peak height and a "right shift" compared with healthy controls. Peak height of the diffusion histogram correlated with both EDSS (r=-0.54, p=0.0101) and disease duration (r=-0.52, p=0.0140), but not with age. Brain volume correlated with peak height of the ADC histogram (r=0.55, p=0.0129), but not with disability. Total lesion load also correlated moderately with EDSS (r=0.46, p=0.03). CONCLUSIONS: This study shows for the first time that quantitative MRI measures of diffusion correlate with clinical variables (disability, disease duration) and cerebral atrophy in multiple sclerosis. Cerebral atrophy and fixed neurological deficit may be attributed to axonal loss, which would be expected to have a significant effect on ADC. Extension of this method to more patients and longitudinal studies will further elucidate its sensitivity, reproducibility, and potential role in clinical practice and treatment trials.
BACKGROUND: Clearance of inhaled technetium 99m-labelled diethylenetriamine penta-acetic acid ((99m)Tc-DTPA) from the lungs is a potential indicator of disease progression in patients with idiopathic pulmonary fibrosis (IPF). METHODS: We prospectively analysed the usefulness of this technique for predicting survival in 106 non-smoking patients with usual interstitial pneumonia (UIP) pattern IPF diagnosed by high resolution CT (HRCT) scanning or histological examination (M/F 65/41, mean (SD) age 61 (11) years). DTPA clearance was analysed according to both mono-exponential and bi-exponential models. Half times for the fast (t(0.5)F) and slow (t(0.5)S) components of clearance, the percentage contribution of the fast component (fF), and half time for mono-exponential approximation to the early part of the clearance curve (t(0.5)) were calculated. RESULTS: The patients had substantially faster t(0.5) (mean 23.9 (9.6) minutes) than normal values (>45 minutes). Thirty seven patients (35%) died during follow up (median 15 months). Univariate Cox regression analysis identified significant predictors of survival as age, forced expiratory volume in 1 second (FEV(1)), forced vital capacity (FVC), total lung capacity (TLC), % predicted TLC, carbon monoxide transfer factor (TLCO), % predicted TLCO, arterial oxygen tension (PaO(2)), oxygen saturation, t(0.5)F, and HRCT fibrosis score. Multiple stepwise Cox regression analysis identified t(0.5)F (p=0.03, hazard ratio 0.747, 95% CI 0.578 to 0.964), % predicted TLC (p=0.02, hazard ratio 0.976, 95% CI 0.956 to 0.995), % predicted TLCO (p=0.003, hazard ratio 0.960, 95% CI 0.935 to 0.986), and age (p=0.003, hazard ratio 1.062, 95% CI 1.021 to 1.104) as independent predictors of survival. CONCLUSION: These data suggest that (99m)Tc-DTPA clearance t(0.5)F measurement may predict survival in patients with UIP pattern IPF.
BACKGROUND: Although the incidence of toxoplasmosis is low in the United States, up to 6000 congenital cases occur annually. In September 1998, the Centers for Disease Control and Prevention held a conference about toxoplasmosis; participants recommended a survey of the toxoplasmosis-related knowledge and practices of obstetrician-gynecologists and the development of professional educational materials for them. METHODS: In the fall of 1999, surveys were mailed to a 2% random sample of American College of Obstetricians and Gynecologists (ACOG) members and to a demographically representative group of ACOG members known as the Collaborative Ambulatory Research Network (CARN). Responses were not significantly different for the random and CARN groups for most questions (p value shown when different). RESULTS: Among 768 US practicing ACOG members surveyed, 364 (47%) responded. Seven per cent (CARN 10%, random 5%) had diagnosed one or more case(s) of acute toxoplasmosis in the past year. Respondents were well-informed about how to prevent toxoplasmosis. However, only 12% (CARN 11%, random 12%) indicated that a positive Toxoplasma IgM test might be a false-positive result, and only 11% (CARN 14%, random 9%) were aware that the Food and Drug Administration sent an advisory to all ACOG members in 1997 stating that some Toxoplasma IgM test kits have high false-positive rates. Most of those surveyed (CARN 70%, random 59%; chi2 p < 0.05) were opposed to universal screening of pregnant women. CONCLUSIONS: Many US obstetrician-gynecologists will encounter acute toxoplasmosis during their careers, but they are frequently uncertain about interpretation of the laboratory tests for the disease. Most would not recommend universal screening of pregnant women.
We present the short- and medium-term clinical results of thermal shrinkage in selected groups of patients with multidirectional or capsular stretch-type instability. We treated 56 patients (61 shoulders) by laser-assisted capsular shrinkage (LACS) and 34 patients (38 shoulders) by radiofrequency (RF) capsular shrinkage. The two groups were followed for mean periods of 40 months and 23 months, respectively. In the LACS group the mean Walch-Duplay score improved to 90 points 18 months after the operation, but then declined to a plateau of about 80 points; 59% of patients considered their shoulders to be 'much better' or 'better' but there was a failure rate of 36.1%. For the RF group the mean Walch-Duplay and Constant scores were 80 points at the various follow-up times; 76.3% of patients considered their shoulder to be 'much better' or 'better'. RF failed in nine shoulders (23.7%). These results match some clinical series of patients with multidirectional instability, undergoing open inferior capsular shift, with a similar rate of failure. We believe that the minimal morbidity involved makes thermal shrinkage a viable alternative to open capsular shift in this difficult group of patients.