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Biomedical subjects

A Glass

Publications and source records attributed to A Glass.

At least 19 recordsLinked to original sources

[24-hour pH monitoring of the hypopharynx in 545 patients with special regard to a critical data evaluation].

BACKGROUND: Although a number of reports exist on 24-hour pH monitoring of the hypopharynx, no consensus has been reached about evaluation standards. In particular the influence of food and beverages is still different estimated. The parameters which are used to analyze the data of pharyngeal pH monitoring are not consistent. PATIENTS AND METHODS: 545 patients underwent esophagopharyngeal 24-hour pH monitoring in the Department of Otorhinolaryngology at the University of Rostock from February 1996 to December 2003. A score was calculated by excluding technical artefacts and pH drop caused by ingestion. RESULTS: Pharyngeal acid exposure was detected in 228 patients. The values of the reflux score ranged between 0 - 62,4 with a median value of zero. The left skewed score distribution shows a high abundance of patients with a minimum score and a limited amount of patients with high score values. The results were compared to reports of other authors. CONCLUSIONS: Evaluation standards are necessary for a reproducible analysis of pharyngeal pH monitoring data and for the comparison of different reports. A qualified score for the analysis and the comparison of pharyngeal pH monitoring data is suggested.

Adult↗

Cognitive functions in survivors of primary central nervous system lymphoma.

BACKGROUND: The standard treatment for primary CNS lymphoma (PCNSL) involves high-dose methotrexate-based (MTX) chemotherapy and whole brain radiotherapy (WBRT). This combined regimen prolongs patient survival, but also carries a substantial risk for delayed neurotoxicity particularly in the elderly. However, cognitive outcome evaluations have not been included in most clinical trials. OBJECTIVE: To assess cognitive functioning and quality of life in PCNSL survivors treated either with WBRT +/- MTX-based chemotherapy or chemotherapy alone. METHODS: Twenty-eight PCNSL patients in disease remission received a post-treatment baseline neuropsychological evaluation, and a subset of patients were available for an 8-month follow-up evaluation. Assessment of quality of life and extent of white matter disease on MRI were also performed. RESULTS: Patients displayed mild to moderate impairments across several cognitive domains. These were of sufficient severity to reduce quality of life in half of the patient sample. Comparisons according to treatment type revealed more pronounced cognitive impairment, particularly in the memory and attention/executive domains, among patients treated with WBRT +/- chemotherapy. Extent of white matter disease correlated with attention/executive, memory, and language impairment. CONCLUSIONS: PCNSL survivors treated with WBRT +/- chemotherapy displayed more pronounced cognitive dysfunction than patients treated with MTX-based chemotherapy alone.

Adult↗

EEG differences and cognitive style.

Individuals differences in information processing related to cognitive style were investigated by EEG recording during cognitive tasks. Fifteen adults received the Cognitive Styles Analysis which assessed their positions on two dimensions: the wholist-analytic and the verbal-imagery. The EEG from midline, paramedial and lateral electrode clusters was recorded, while subjects viewed words presented at different rates. A button was pressed when a word was in a target conceptual category. Off-line analysis produced spectral powers for delta, theta, alpha, beta 1, beta 2 and gamma bands. For the midline, the wholists had higher output than analytics in theta and alpha, but lower in gamma. In the paramedial cluster, verbalisers had greater right power than imagers for all bands except alpha. Further, the overall power was greater on the right for imagers than verbalisers frontally, and the converse occipitally. In the lateral grouping, the wholist-verbalisers had greater overall power left antero-temporally than other sub-groups.

Adolescent↗

A role for perforin in downregulating T-cell responses during chronic viral infection.

Cytotoxic T cells secrete perforin to kill virus-infected cells. In this study we show that perforin also plays a role in immune regulation. Perforin-deficient (perf -/-) mice chronically infected with lymphocytic choriomeningitis virus (LCMV) contained greater numbers of antiviral T cells compared to persistently infected +/+ mice. The enhanced expansion was seen in both CD4 and CD8 T cells, but the most striking difference was in the numbers of LCMV-specific CD8 T cells present in infected perf -/- mice. Persistent LCMV infection of +/+ mice results in both deletion and anergy of antigen-specific CD8 T cells, and our results show that this peripheral "exhaustion" of activated CD8 T cells occurred less efficiently in perf -/- mice. This excessive accumulation of activated CD8 T cells resulted in immune-mediated damage in persistently infected perf -/- mice; approximately 50% of these mice died within 2 to 4 weeks, and mortality was fully reversed by in vivo depletion of CD8 T cells. This finding highlights an interesting dichotomy between the role of perforin in viral clearance and immunopathology; perforin-deficient CD8 T cells were unable to clear the LCMV infection but were capable of causing immune-mediated damage. Finally, this study shows that perforin also plays a role in regulating T-cell-mediated autoimmunity. Mice that were deficient in both perforin and Fas exhibited a striking acceleration of the spontaneous lymphoproliferative disease seen in Fas-deficient (lpr) mice. Taken together, these results show that the perforin-mediated pathway is involved in downregulating T-cell responses during chronic viral infection and autoimmunity and that perforin and Fas act independently as negative regulators of activated T cells.

Animals↗

The Oregon Health Plan: development and implementation of an innovative method of delivery of health care services to the medically indigent.

BACKGROUND: Health care for the medically indigent under the federal Medicaid system often provides care for only a fraction (ranging from 20% to 80%) of the poor who nominally qualify for care. Oregon has developed a unique system that replaces such a system with one that provides a comprehensive complement of medical care for all the poor but limits the care to conditions and procedures on a prioritized list. METHODS: The Health Services Commission, a group of physicians, nurses, and public representatives, developed a list of over 740 diagnoses-treatment pairs and, with considerable public input, prioritized them in order of importance. The principal values used to develop the list were the prevention of death and the cost of the disease and its treatment. In the final ordering of the diagnosis-treatment pairs, public health and prevention of morbidity was also considered. Cancer diagnoses, and indeed all diseases, were not singled out for special consideration in this process. The Oregon Health Plan was implemented in 1994 with funds to cover 606 of 743 listed diagnoses. Diagnoses involving cancer were nearly all covered within these 606 items. The principal exception was coverage for Curative Treatment for Cancer when the likelihood for success was less than 5%. RESULTS: The prioritized list has met its goal of comprehensive medical care for the indigent population. The number of medically uninsured Oregonians has fallen significantly, and there have been few complaints about the Plan. Cancer care has been delivered to Oregon Health Plan clients with very few complaints or appeals of decisions concerning coverage. Palliative care is provided under a number of covered lines, as are curative medical and surgical treatment. CONCLUSIONS: The Oregon Health Plan represents an alternative method for delivering medical care, including the full range of cancer care, to the indigent. As there are limited funds in all state systems, the citizens of Oregon have decided to provide care using a prioritized list to allow provision of medical care to the entire Medicaid population. Such a plan represents a viable alternative to the more common method of providing everything but only to a limited number of poor citizens.

Cancer Care Facilities↗

Delivery of comprehensive cancer care at Kaiser Permanente.

BACKGROUND: Kaiser Permanente (KP) is a large health maintenance organization (HMO) operating in 14 states and caring for 8,000,000 members in hundreds of facilities staffed by thousands of physicians and support personnel. Cancer care is provided to these KP members as part of the health care package. METHODS: KP insures members for all their health care needs and provides needed services in their own facilities except in rare circumstances. Professional services are provided by physicians of the Permanente Medical Groups, locally governed groups of physicians contractually bound to Kaiser Permanente by capitation agreements. These agreements cover the full range of services for cancer and all other diseases. KP uses evidence-based guidelines to rationalize the provision and delivery of medical care for its members. A large investment in technology has allowed these guidelines to be generally available on local intranets and has facilitated the development of a computerized medical record and linkages to multiple clinical and administrative databases for all providers. Several of the KP regions have strong commitments to research in the public domain and have integrated this effort into the clinical practice of oncology, particularly in clinical trials in cancer treatment and prevention. Research efforts also exist in the areas of cancer epidemiology and outcomes. RESULTS: Cancer care is integrated fully into the comprehensive medical care provided the KP member. Health benefits cover the full range of cancer prevention and treatment without distinction by diagnosis. CONCLUSIONS: Within the broad range of health care options in the U.S., KP represents a good example of the value of a large HMO to deliver comprehensive general medical and oncologic care.

Comprehensive Health Care↗

Mailing strategies and costs of recruiting heavy smokers in CARET, a large chemoprevention trial.

Recruitment costs represent a major portion of the budget for large clinical trials during the initial years of the study. Further, the rate of recruitment affects allocation of resources in future years. To learn about the costs and yields of recruiting from different populations and under different mailing strategies, we monitored recruitment yields of eligible heavy smokers for the Carotene and Retinol Efficacy Trial (CARET) at the Portland Study Center. Yields from the mailings, measured by response rate, percent of potential participants randomized, and related costs per randomization varied both by mailing strategy and by population targeted. Yield and cost varied significantly across population sources. Less variation was observed among various mailing strategies. Tracking the recruitment process yield provided useful information that allowed us to adjust recruitment approaches and achieve our randomization goals quickly and economically.

Aged↗

The CARET asbestos-exposed cohort: baseline characteristics and comparison to other asbestos-exposed cohorts.

The Carotene and Retinol Efficacy Trial (CARET) was a double-blind, placebo-controlled trial of the daily administration of 25,000 IU vitamin A and 30 mg beta-carotene for the prevention of lung cancer. Of close to 18,500 participants, more than 4,000 were asbestos-exposed men recruited from shipyard and construction trades at five study centers in the United States. While the primary endpoint of the trial was the incidence of lung cancer, a number of questions about the natural history of asbestos-related disease will also be addressed. The mean age at entry into the trial was 57 years and the mean duration of follow-up on active intervention was 4 years. With the exception of 133 never-smoker pilot participants (3%), all subjects recruited were by intention current (38%) or ex-smokers (58%), with a mean cumulative smoking exposure at entry of 43 pack-years. Mean years from first asbestos exposure were 35, and mean duration of asbestos exposure in a high-risk trade was 19 years. The distribution of radiographic abnormalities was as follows: normal, 34%; parenchymal opacities (ILO profusion score > 1/0) alone, 18%; pleural thickening alone, 27%; both parenchymal opacities and pleural thickening, 21%. The CARET cohort, when compared to previously reported asbestos-exposed cohorts, is characterized by substantial asbestos exposure and high proportion of asbestos-related radiographic findings. The active intervention was halted in 1996, after a mean duration of 40 years. Passive follow-up of the cohort will continue until the year 2000.

Asbestos↗

Serum zinc levels and goitre epidemiology in Germany.

Zinc is an essential element involved in many basic biochemical reactions. Animal experiments and clinical data support the hypothesis that in the presence of inadequate iodine supply zinc deficiency may be a stimulus for the development of goitre. Within the framework of a study to record goitre prevalence and iodine supply of Germany we determined the serum zinc levels in 5932 clinically healthy persons. The mean value was 13.1 +/- 1.75 mumol/l. There were no differences neither in age, in sex nor in regional distribution. Furthermore there were no correlations between serum zinc level, thyroid volume and urinary iodide excretion. Only 1% of all cases had low zinc levels (< 10 mumol/l). Older people (> 40 years) with lowered serum zinc levels showed significantly larger thyroids. We conclude that there is no relevant undersupply of zinc and therefore the trace element is not involved in the goitre endemy of Germany.

Adult↗

Occupational exposure to antineoplastic agents and self-reported infertility among nurses and pharmacists.

Although infertility has been identified as an effect of chemotherapy for some cancer patients, the association of infertility with occupational exposure has not been investigated. This case-control study investigated the relationship of infertility with occupational handling of chemotherapy drugs by nurses and pharmacy personnel. Data were gathered by questionnaire from 4659 staff at facilities participating in the National Surgical Adjuvant Breast and Bowel Project collaborative clinical trials network of the National Cancer Institute. The 405 subjects reporting infertility were each matched by sex and age with three control subjects and compared for history of chemotherapeutic drug handling. Results for the total sample and for women showed a significantly elevated odds ratio (OR = 1.5; CI = 1.1 to 2.0) for self-reported infertility associated with occupational handling of chemotherapeutic drugs prior to onset of infertility. For men, the odds ratio was similar but not statistically significant. This worker population, with a mean age of 37, is in the prime of reproductive life. Prevention of chemotherapy side effects by use of available protection is preferable to risking infertility.

Adult↗

Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial.

BACKGROUND: Evidence has accumulated from observational studies that people eating more fruits and vegetables, which are rich in beta-carotene (a violet to yellow plant pigment that acts as an antioxidant and can be converted to vitamin A by enzymes in the intestinal wall and liver) and retinol (an alcohol chemical form of vitamin A), and people having higher serum beta-carotene concentrations had lower rates of lung cancer. The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate (vitamin A) taken daily against placebo in 18314 men and women at high risk of developing lung cancer. The CARET intervention was stopped 21 months early because of clear evidence of no benefit and substantial evidence of possible harm; there were 28% more lung cancers and 17% more deaths in the active intervention group (active = the daily combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate). Promptly after the January 18, 1996, announcement that the CARET active intervention had been stopped, we published preliminary findings from CARET regarding cancer, heart disease, and total mortality. PURPOSE: We present for the first time results based on the pre-specified analytic method, details about risk factors for lung cancer, and analyses of subgroups and of factors that possibly influence response to the intervention. METHODS: CARET was a randomized, double-blinded, placebo-controlled chemoprevention trial, initiated with a pilot phase and then expanded 10-fold at six study centers. Cigarette smoking history and status and alcohol intake were assessed through participant self-report. Serum was collected from the participants at base line and periodically after randomization and was analyzed for beta-carotene concentration. An Endpoints Review Committee evaluated endpoint reports, including pathologic review of tissue specimens. The primary analysis is a stratified logrank test for intervention arm differences in lung cancer incidence, with weighting linearly to hypothesized full effect at 24 months after randomization. Relative risks (RRs) were estimated by use of Cox regression models; tests were performed for quantitative and qualitative interactions between the intervention and smoking status or alcohol intake. O'Brien-Fleming boundaries were used for stopping criteria at interim analyses. Statistical significance was set at the .05 alpha value, and all P values were derived from two-sided statistical tests. RESULTS: According to CARET's pre-specified analysis, there was an RR of 1.36 (95% confidence interval [CI] = 1.07-1.73; P = .01) for weighted lung cancer incidence for the active intervention group compared with the placebo group, and RR = 1.59 (95% CI = 1.13-2.23; P = .01) for weighted lung cancer mortality. All subgroups, except former smokers, had a point estimate of RR of 1.10 or greater for lung cancer. There are suggestions of associations of the excess lung cancer incidence with the highest quartile of alcohol intake (RR = 1.99; 95% CI = 1.28-3.09; test for heterogeneity of RR among quartiles of alcohol intake has P = .01, unadjusted for multiple comparisons) and with large-cell histology (RR = 1.89; 95% CI = 1.09-3.26; test for heterogeneity among histologic categories has P = .35), but not with base-line serum beta-carotene concentrations. CONCLUSIONS: CARET participants receiving the combination of beta-carotene and vitamin A had no chemopreventive benefit and had excess lung cancer incidence and mortality. The results are highly consistent with those found for beta-carotene in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study in 29133 male smokers in Finland.

Anticarcinogenic Agents↗

Regulation of the Fas lytic pathway in cloned CTL.

Cloned murine CTL activated via the TCR or by PMA and ionomycin up-regulate surface Fas ligand and show an increased ability to kill non-Ag-specific Fas+ target cells. This up-regulation starts after 45 to 60 min and has a t1/2 for reversal of about 90 min. Up-regulation of lytic function is accompanied by up-regulation of Fas ligand on the CTL surface, which can be blocked by protein synthesis inhibitors. When up-regulation of Fas lytic function was induced by PMA and ionomycin, EGTA blocked both activation of lytic function and expression of Fas ligand detected by FACS analysis. However, when up-regulation was induced by specific Ag, EGTA blocked activation of lytic function, but not up-regulation of Fas ligand. Moreover, EL-4 cells have very high levels of surface Fas ligand, although they are not cytotoxic. Thus, expression of surface Fas ligand may be required, but not sufficient, for Fas-mediated lysis.

Animals↗

Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease.

BACKGROUND: Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of lung cancer, were compared with those of placebo. RESULTS: A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up (mean length of follow-up, 4.0 years). The active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57; P=0.02), as compared with the placebo group. There were no statistically significant differences in the risks of other types of cancer. In the active-treatment group, the relative risk of death from any cause was 1.17 (95 percent confidence interval, 1.03 to 1.33); of death from lung cancer, 1.46 (95 percent confidence interval, 1.07 to 2.00); and of death from cardiovascular disease, 1.26 (95 percent confidence interval, 0.99 to 1.61). On the basis of these findings, the randomized trial was stopped 21 months earlier than planned; follow-up will continue for another 5 years. CONCLUSIONS: After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.

Aged↗

The beta-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: smokers and asbestos-exposed workers.

CARET is a multicenter, two-armed, double-masked randomized chemoprevention trial in Seattle, Portland, San Francisco, Baltimore, Connecticut, and Irvine, to test whether oral administration of beta-carotene (30 mg/day) plus retinyl palmitate (25,000 IU/day) can decrease the incidence of lung cancer in high risk populations, namely, heavy smokers and asbestos-exposed workers. The intervention combines the antioxidant action of beta-carotene and the tumor suppressor mechanism of vitamin A. As of April 30, 1993, CARET had randomized 1,845 participants in the 1985-1988 pilot phase plus 13,260 "efficacy" participants since 1989; of these, 4,000 are asbestos-exposed males and 11,105 are smokers and former smokers (44% female). Accrual is complete everywhere except Irvine, which was the last center added (1991), and the safety profile of the regimen to date has been excellent. With 14,420 smokers, 4,010 asbestos-exposed participants, and 114,100 person-years through February 1998, we expect CARET to be capable of detecting a 23% reduction in lung cancer incidence in the two populations combined and 27, 49, 32, and 35% reductions in the smokers, female smokers, male smokers, and asbestos-exposed subgroups, respectively. CARET is highly complementary to the alpha-tocopherol-beta-carotene study in Finland and the Harvard Physicians Health Study (beta-carotene alone) in the National Cancer Institute portfolio of major cancer chemoprevention trials.

Aged↗

EEG coherence as a predictor of spike propagation.

The relationship between resting EEG coherence and the propagation of spike activity from an experimental cortical focus was investigated in 6 rats. EEG was collected from an array of 6 epicortical electrodes positioned over the posterior hind limb sensorimotor (HL) and frontal (Fr1, Fr2) cortices. Coherence decreased non-linearly for all frequency bands with increasing interelectrode distance. The greatest decrement in coherence occurred in the region corresponding to the junction between hind limb (HL) and frontal (Fr1) cortices. The decrease in coherence was greatest for the highest frequency band for all interelectrode pairs. A spike focus was induced in all 6 animals following the application of bicuculline at the most posterior electrode of the cortical array. In 5 of the 6 animals spike propagation was delayed at the junction of HL and Fr1 cortices, where the greatest decrease in coherence was observed. In one animal spike activity never advanced across this region. These results demonstrate an association between intracortical coherence and the spatial propagation of spike activity. The function of short and long cortico-cortical pathways as mediators of both EEG coherence and cortical spike propagation are discussed.

Action Potentials↗

Antineoplastic drug handling protection after OSHA guidelines. Comparison by profession, handling activity, and work site.

Although Occupational Safety and Health Administration (OSHA) issued antineoplastic drug handling guidelines in 1986, literature reports indicated that use of protection in the early 1980s did not meet OSHA standards. This study investigated the use of protection by pharmacy and nursing staff in a national sample of facilities participating in the National Surgical Adjuvant Breast and Bowel Project collaborative clinical trials network of the National Cancer Institute. Extent of handling, handling activity, and use of protection are compared by work setting and profession. Use of protection by the study sample in 1988 to 1989 is compared with their past use, with use of protection in previous studies, and with OSHA guidelines. In general, pharmacists are better protected than are nurses, and hospital staff are better protected than staff in outpatient settings who also tend to handle more drugs. Although improving over time, protective garment use does not meet OSHA guidelines, particularly among nurses when administering agents or handling patient excreta.

Antineoplastic Agents↗