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Biomedical subjects

T Rogers

Publications and source records attributed to T Rogers.

At least 55 records · Page 3Linked to original sources

Telomerase expression in respiratory epithelium during the multistage pathogenesis of lung carcinomas.

To investigate the role of telomerase in the multistage pathogenesis of lung cancer, we examined 205 fresh and archival tissue samples obtained from 40 patients, 34 of whom had invasive lung carcinoma, 5 with carcinoma in situ (CIS) without invasion, and 1 without lung carcinoma. We analyzed samples for telomerase enzyme activity using the semiquantitative PCR-based telomeric repeat amplification protocol assay (131 samples) or by a radioactive in situ hybridization method for expression of the RNA component of human telomerase (hTR; 74 samples). A subset of samples was assayed by both methods, and the correlation was excellent (30 of 36; 83%). With the exception of a carcinoid tumor and a necrotic squamous cell carcinoma, all tumor cells were moderate to strongly positive for both hTR and telomerase activity, except for foci of keratinization in squamous cell carcinomas. Telomerase positivity, with weak enzyme activity and/or low hTR expression, was present in basal epithelial cells of large bronchi, both histologically normal (26%) and hyperplastic (71%), and in 23% of peripheral lung samples (in epithelium of small bronchi and bronchioles or lymphoid aggregates). More advanced epithelial changes (metaplasia, dysplasia, and CIS) were associated with telomerase dysregulation. Dysregulation in preneoplasia was manifested in three ways: almost all such lesions expressed hTR, although enzyme activity levels were several-fold lower than in the corresponding invasive tumors; cells throughout these multilayered processes expressed hTR; and intense, focal up-regulation of hTR occurred in CIS foci in the vicinity of invasive cancers. Alveolar cells and areas of atypical adenomatous hyperplasia (possible precursor lesions for peripheral adenocarcinomas) were negative. Our studies demonstrate that dysregulation of telomerase occurs early in the multistage pathogenesis of bronchogenic lung carcinomas and that intense focal localized hTR expression in CIS may indicate imminent invasion.

Carcinoma↗

Multiple Cladosporium brain abscesses in a renal transplant patient: aggressive management improves outcome.

Infection remains one of the major complications of nonspecific immunosuppression in renal transplant patients and accounts for significant morbidity and mortality. The incidence of infectious complications has been shown to be related to the degree of immunosuppression and correlated with the total steroid dosage, use of antilymphocyte serum, and number of rejection episodes. We present the case of a patient who received a large cumulative immunosuppressive load as treatment for her original disease and for numerous rejection episodes following renal transplantation, and who later developed multiple brain abscesses. These were shown to be due to the saprophytic black fungus Cladosporium bantianum. This case emphasizes the importance of aggressively pursuing the diagnosis in immunosuppressed individuals--appropriate treatment may be instituted early and may save lives. There have been no previous cases of patients surviving this condition without neurosurgical resection of the lesions.

Adult↗

Recurrent abdominal pain and Helicobacter pylori in a community-based sample of London children.

Helicobacter pylori is accepted as an important factor in the pathogenesis of peptic ulcer disease. Infection is probably most commonly acquired in early life but there is still limited information on the prevalence or symptomatology of H. pylori infection in childhood. The aim of the present study was to establish the prevalence of H. pylori infection in a large sample of urban school children and to determine its relationship, if any, to a history of recurrent abdominal pain. Using a commercial ELISA significant levels of anti-H. pylori IgG antibody were detected in 107/640 (16.7%) of school children (M, 383; F, 257; mean age 9.15 years, range 4-13). No relationship was demonstrated between H. pylori seropositivity and a personal or family history of recurrent abdominal pain or the nature of the pain.

Abdominal Pain↗

Neutrophil regulation of splanchnic blood flow after hemorrhagic shock.

OBJECTIVE: This study examines the hypothesis that neutrophils impair splanchnic blood flow during resuscitation from hemorrhage by inhibiting the release of the compensatory vasodilator PGI2 from the bowel. SUMMARY BACKGROUND DATA: Resuscitation from hemorrhagic shock is associated with neutrophil infiltration into the intestine, reduced splanchnic perfusion, and reduced release of PGI2 from the intestine. METHODS: Sprague-Dawley rats received either vinblastine (VIN) to deplete circulating neutrophils or normal saline (NS). These animals then underwent either hemorrhage and resuscitation (SK + R) or sham operation (SHAM). Superior mesenteric artery flow and splanchnic 6-keto PGF1a (metabolite of PGI2) release were measured. RESULTS: Superior mesenteric artery blood flow was significantly greater in VIN-treated animals sustaining SK + R than in those treated with NS (p < 0.05). Neutrophil depletion preserved 6-keto PGF1a release after SK + R, whereas 6-keto PGF1a release in the NS-treated, SK + R group was significantly reduced (p < 0.05). CONCLUSION: These data are compatible with the hypothesis that neutrophils may influence splanchnic perfusion after SK + R by inhibiting splanchnic PGI2 release.

Animals↗

Strengthening individual and community capacity to prevent disease and promote health: in search of relevant theories and principles.

The dominant theoretical models used in health education today are based in social psychology. While these theories have increasingly acknowledged the role of larger social and cultural influences in health behavior, they have many limitations. Theories seek to explain the causes of health problems, whereas principles of practice, which are derived from practical experience, assist intervenors to achieve their objectives. By elucidating the relationships between theory and practice principles, it may be possible to develop more coherent and effective interventions. The key research agenda for health education is to link theories at different levels of analysis and to create theory-driven models that can be used to plan more effective interventions in the complex environments in which health educators work.

Community Health Services↗

Community mobilization to reduce point-of-purchase advertising of tobacco products.

This project was designed to address the problem of point-of-purchase tobacco advertising through media advocacy and community mobilization. Precampaign assessment revealed a considerable amount and density of tobacco advertising and promotions in more than 100 stores sampled in San Jose, California. After sharing the results with community activists and other residents, a community mobilization campaign was instigated to capitalize on an existing sign control ordinance that limits store window coverage and sidewalk signs. Through presentations and media advocacy efforts, community residents were mobilized to file complaints with the city's code enforcement office when neighborhood stores were shown to be noncompliant with ordinance provisions. Relative to the baseline, significant reductions in campaign-related tobacco advertising variables were seen in the San Jose stores after the sign law campaign. No changes were seen in four smaller reference communities. Differences were noted between stores close to and farther away from schools. These results demonstrate that mobilization of community residents to activate enforcement of laws originally designed for other purposes can have a significant impact on one aspect of tobacco point-of-purchase advertising.

Advertising↗

Central nervous system angiopathy associated with cocaine abuse.

Cocaine abuse has been associated with various cerebrovascular complications, including vasculitis. We describe a patient who presented with neurologic defects associated with cocaine abuse. Although angiography raised the suggestion of vasculitis, biopsy revealed a lack of inflammatory changes, and other aspects of the clinical course also militated against inflammatory vasculitis. This case was reminiscent of recently described patients initially suspected of having primary central nervous system (CNS) vasculitis but subsequently considered to have "benign angiopathy." We suggest that benign angiopathy of the CNS can occur as a result of cocaine abuse.

Adult↗

The role of azoles in the treatment and prophylaxis of cryptococcal disease in HIV infection.

OBJECTIVE: To assess the role of azole therapy in the treatment and prophylaxis of cryptococcosis in HIV-seropositive individuals. STUDY DESIGN: Retrospective case review. SETTING: A dedicated HIV unit in London, UK. PATIENTS: Fifty individuals with a positive cryptococcal antigen or culture from any site between 1 January 1985 and 31 December 1992. RESULTS: Thirty-eight patients initially presented with meningitis and 12 with alternative disease, five of whom subsequently developed meningeal disease. The 12 patients who presented without meningitis received chronic suppressive therapy after the diagnosis of cryptococcal disease. Two patients receiving itraconazole developed meningitis as did three out of four treated with 200 mg fluconazole daily, but none of the six receiving 400 mg fluconazole daily. Treatment of cryptococcal meningitis was successful in 17 of the 19 patients given fluconazole but only three of the six receiving itraconazole. Following successful treatment of meningitis five out of seven patients given itraconazole and five out of seven given 200 mg fluconazole daily relapsed compared with three out of 25 receiving 400 mg fluconazole daily. CONCLUSION: Fluconazole is an effective treatment for cryptococcal meningitis. For prophylaxis following meningitis, a dose of 400 mg fluconazole is the preferred treatment; lower doses are associated with a higher relapse rate.

AIDS-Related Opportunistic Infections↗

Management of pulmonary aspergillosis in AIDS: an emerging clinical problem.

AIMS: To review the clinical, radiographic, and therapeutic features of 11 cases of respiratory Aspergillus infection in patients with AIDS. METHODS: All induced sputum and bronchoalveolar lavage samples obtained from HIV seropositive patients between January 1985 and March 1993 were analysed for Aspergillus species. Additionally, where appropriate, bronchial or renal biopsy specimens, or both, were taken before treatment had started. RESULTS: In 11 patients Aspergillus fumigatus was identified in alveolar samples obtained by sputum induction. This was confirmed by bronchoalveolar lavage in eight. Three patients had Aspergillus plaques in the trachea and bronchus, while a fourth patient had an aspergilloma. Risk factors for Aspergillus infection were present in all patients, including corticosteroid treatment in three cases and neutropenia in four, three of whom had received chemotherapy for Kaposi's sarcoma. Four patients had concomitant cytomegalovirus infection. Ten patients had a CD4 count of less than 50 cells/mm3 while one patient had a disseminated T cell lymphoma with a CD4 count of 242 cells/mm3. Of the three patients with samples obtained by sputum induction who did not undergo bronchoscopy, two had a normal chest x ray picture and the third had a right lobar pneumonia complicating an aggressive lymphoma. All three were treated with itraconazole 200 mg twice a day without further investigation. Survival from the time of diagnosis of Aspergillus infection was short: seven patients died within six weeks, although only one death was directly attributed to pulmonary aspergillosis. At six monthly follow up, one patient, who initially had a positive Aspergillus culture from bronchial washings and a normal chest radiograph, developed a renal aspergilloma despite the disappearance of Aspergillus sp from the sputum. CONCLUSION: Pulmonary aspergillosis is an important clinical problem in patients with AIDS with a CD4 count of less than 50 cells/mm. Furthermore, patients with Aspergillus sp in sputum induction or bronchial washings may develop disseminated disease despite adequate treatment of the primary infection.

AIDS-Related Opportunistic Infections↗

Accuracy of sex determination using morphological traits of the human pelvis.

This study assesses the accuracy and reliability of 17 individual morphological traits of the pelvis frequently used to determine the sex of human skeletal remains. A sample of 49 right and left adult hip bones and sacra of documented individuals were available from an historic church cemetery dating from the 19th century. A hypothetical ranking of the accuracy of traits was drawn from the literature. Next, individual traits were evaluated for precision and accuracy of observations, and combinations of two and three traits were evaluated for their collective effectiveness as sex indicators. The effect of age on the accuracy of traits for sex determination was also examined. Precision of traits was generally good. Several combinations of three criteria produced higher levels of accuracy than the trait list as a whole. A total of six traits was judged to be most effective as sex discriminators because of low intraobserver error levels and better than 83% accuracy rats. There was no indication of an age effect on the precision or accuracy of these traits although sample sizes are small.

Adult↗

The appropriateness of initial vancomycin dosing.

BACKGROUND: Vancomycin use has markedly increased over the past several years because of an increased incidence of resistant organisms, particularly methicillin-resistant Staphylococcus aureus. Despite the availability of dosing nomograms and the use of peak and trough levels, vancomycin dosing has remained problematic. METHODS: All intravenous vancomycin orders over a 3-month period in a community and teaching hospital were screened for appropriateness of initial dosing based on available dosing nomograms. RESULTS: Of the 48 patients who received intravenous vancomycin, only 19 (39.6%) were given initial doses that achieved the desired serum concentration. There were no significant differences in the appropriateness of initial dosing between family medicine residents, attending physicians, and private staff physicians. Older patients in our study were at higher risk for overdosing, whereas younger patients were more likely to be underdosed. In this study, nomogram use could have yielded correct initial dosages in 40 of the 48 patients (83.3%). CONCLUSIONS: Our study indicates a high percentage of inappropriate initial vancomycin dosing in a community and teaching hospital. The investigators believe inappropriate initial vancomycin dosing is common and may result in unnecessary expense, increased risk of therapeutic failures, and greater potential for adverse drug reactions. Increased use of vancomycin dosing nomograms could improve the rate of correct initial dosages.

Adult↗

Loss of transforming growth factor beta 1 receptors and its effects on the growth of EBV-transformed human B cells.

Transforming growth factor-beta (TGF-beta) is a potent negative regulator of normal human B cell growth mediated by exogenous signals, including IL-2 and low m.w. B cell growth factor 12 kDa (BCGF-12 kDa). In the present study, we investigated the regulatory linkage between viral or nonviral transformation of human B cells and the growth inhibitory effects of TGF-beta 1. A panel of EBV+ and EBV- B cell lines, derived either by in vitro EBV B cell transformation, or from cases of lymphoma was used to quantitate the negative growth effects of TGF-beta 1. The proliferative response of three EBV- B cell lines to rBCGF-12 kDa or serum was inhibited by low concentrations of TGF-beta 1 (0.2-0.5 ng/ml for 50% maximal effect), as measured by tritiated thymidine uptake and viable cellular recovery. In contrast, rBCGF-12 kDa or serum mediated proliferation of three EBV+ B cell lines was refractory to the growth inhibitory effects of TGF-beta 1. In an attempt to understand the mechanism(s) for this differential growth control in EBV+ and EBV- B cells, we studied the expression of TGF-beta 1, c-myc, and TGF-beta 1 receptors. No correlation was observed between the expression of TGF-beta 1 or c-myc gene and growth inhibition by TGF-beta 1 in the cell lines studied. Our results indicate that sensitivity or resistance to TGF-beta 1 correlated with the presence or absence (loss) of high affinity receptors for TGF-beta 1. EBV- B cell lines expressed levels of high affinity receptors similar to those found on activated normal B or T cells. In contrast, EBV+ B cell lines showed no detectable high affinity receptors. Chemical cross-linking studies with a bifunctional reagent, dissuccinimidyl suberate revealed a normal expression of type I (65-70 kDa), type II (85-90 kDa), and type III (280-300 kDa) TGF-beta 1 high affinity receptors on EBV- B cell lines. In contrast, EBV+ B cell lines did not express type I and type II receptors, whereas type III receptors were expressed but could not be inhibited by unlabeled TGF-beta 1.(ABSTRACT TRUNCATED AT 400 WORDS)

B-Lymphocytes↗

Obstacles to and future goals of ten comprehensive community health promotion projects.

Over 100 project staff, community coalition members, and other representatives from 10 comprehensive community health promotion projects in the western United States were surveyed two years into a three year funding cycle about: (1) the problems or obstacles they judged as preventing successful completion of their current goals and objectives, and (2) future goals and objectives they envisioned for their projects. The key issues confronting respondents were diverse, although issues around the process of implementing community health promotion programs were cited more frequently than issues related to the content of health promotion. When respondents were asked to prioritize Future Goals in the second survey, consensus across communities was obtained despite broad differences in the type of community surveyed and the health problem targeted. This study identifies the common organizational and community development problems faced by newly emerging community health promotion programs and has implications for other communities involved in designing, implementing, and evaluating community-wide health promotion programs.

Community Health Services↗

Large outbreak of food poisoning caused by Salmonella typhimurium definitive type 49 in mayonnaise.

An investigation was conducted to determine the vehicle of infection of an outbreak of food poisoning in a large metropolitan building early in 1988. A questionnaire was distributed to 700 people who had eaten in the building during the week of the outbreak, and attack rates for specific food were calculated. Food and stool samples, environmental samples, and eggs and environmental swabs from the egg suppliers were examined microbiologically. Altogether 474 questionnaires were returned, 120 people reporting gastrointestinal illness. The illness was significantly associated with foods containing mayonnaise. Salmonella typhimurium definitive type 49 was isolated from 76 of the 84 stool samples containing salmonella and from five of the eight samples taken from the chicken house of the main egg supplier. Mayonnaise was probably the vehicle of infection, which was caused by S typhimurium definitive type 49.

Adult↗

Isoprinosine does not influence the natural history of herpes zoster or postherpetic neuralgia.

In a double-blind randomised trial, 38 elderly patients with acute herpes zoster received either isoprinosine (IP) or placebo. IP neither shortened the acute phase of herpes zoster nor prevented postherpetic neuralgia. Transient asymptomatic hyperuricaemia affected one third of IP treated patients. Shortcomings in study design and misleading interpretation of results are common in previously published clinical trials of herpes zoster and postherpetic neuralgia. Guidelines for future studies are proposed.

Aged↗