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Biomedical subjects

S Petersen

Publications and source records attributed to S Petersen.

At least 73 records · Page 4Linked to original sources

The health of students in institutes of higher education: an important and neglected public health problem?

BACKGROUND: A survey of students in three UK higher education establishments was undertaken to obtain information about students' physical and emotional well-being, their attitudes to, and beliefs about health, and the prevalence of risk factors for future ill health. METHODS: Health was measured by the prevalence of longstanding illness and by the SF-36 health status measurement tool. Survey results were compared with equivalent data for 18- to 34-year-olds in the local population. The prevalence of long-standing illness was also compared with two national surveys. RESULTS: The survey achieved a 49 per cent response rate. More than one-third of respondents reported a long-standing illness, a higher prevalence than in all comparison surveys. Students scored significantly worse than their peers in the local population on all eight SF-36 dimensions. The greatest difference was for role limitations as a result of emotional problems. The main sources of emotional distress were study or work problems and money. CONCLUSION: The poor response rate in this survey dictates the need for caution in interpretation of the results. However, they suggest that the health of students is poor relative to that of their peers, and that their emotional health is more of a problem than their physical health. Public health practitioners might want to pay more attention to the health of this important and relatively neglected group. Worries about studies and money appear to be affecting students' academic work, and this should be of concern to higher education establishments.

Adolescent↗

Chromosomal imbalances in brain metastases of solid tumors.

Metastases account for approximately 50% of the malignant tumors in the brain. In order to identify structural alterations that are associated with tumor dissemination into the central nervous system we used Comparative Genomic Hybridization (CGH) to investigate 42 brain metastases and 3 primary tumors of 40 patients. The metastases originated from lung cancer (14 cases), melanomas (7), carcinomas of breast (5), colon (5), kidney (5), adrenal gland (1) and thyroid (1). In addition, tumors of initially unknown primaries were assessed in 3 cases. The highest incidence of DNA gains were observed for the chromosomal regions 1q23, 8q24, 17q24-q25, 20q13 (>80% of cases) followed by the gain on 7p12 (77%). DNA losses were slightly less frequent with 4q22, 4q26, 5q21, 9p21 being affected in at least 70% of the cases followed by deletions at 17p12, 4q32q34, 10q21, 10q23-q24 and 18q21-q22 in 67.5% of cases. Two unusual narrow regional peaks were observed for the gain on 17q24-q25 and loss on 17p12. The incidence at individual loci can be viewed at our CGH online tumor database at http:// amba.charite.de/cgh/. The metastases of each tumor type showed a recurrent pattern of changes. In those cases with primary tumor and metastases available, the CGH pattern exhibited a high degree of conformity. In conclusion, our data suggests that specific genetic lesions are associated with tumor dissemination into the nervous system and that CGH analysis may be a useful supplementary tool for classification of metastases with unknown origin.

Brain Neoplasms↗

An epidemiological study of the relative importance of damp housing in relation to adult health.

STUDY OBJECTIVE: To examine the association between damp housing and adult health, taking into account a wide range of other factors that may influence health and could confound this relation. PARTICIPANTS AND SETTING: A general population sample of adults, aged 18-64, from Oxfordshire, Buckinghamshire, Berkshire and Northamptonshire. DESIGN: Secondary analysis of responses to a postal questionnaire survey carried out in 1997 with a 64% response rate (8889 of 13 800). Housing dampness was assessed by self report. Health was measured by responses to a series of questions including presence of asthma and longstanding illness generally, use of health services and perceived health status (the SF-36). The effect of damp was examined using the chi(2) test and one way analysis of variance. Significant associations with the various health outcomes were further explored taking into account 35 other housing, demographic, psychosocial and lifestyle variables using stepwise logistic and linear regression. MAIN RESULTS: Bivariate analyses indicated that damp was associated with the majority of health outcomes. Regression modelling however, found that being unable to keep the home warm enough in winter was a more important explanatory variable. Worry about pressure at work and to a lesser extent about money, showed an independent association with perceived health status equal to or greater than that of the housing environment, including cold housing, and that of health related lifestyles. CONCLUSIONS: This study shows that being unable to keep the home warm enough in winter is more strongly associated with health outcomes than is damp housing. However, as cold and damp housing are closely related, it is likely that their combined effects are shown in these results. The importance of worry as an independent predictor of health status needs testing in other studies. Its prevalence and relative importance suggest that it may be a significant determinant of public health.

Adolescent↗

Diet and bone mineral content at term in premature infants.

Premature infants are at risk of developing metabolic bone disease mainly because of low calcium and phosphorus intake. We have examined the effect of different mineral supplements on bone mineral content at term in 127 premature infants with gestational age <32 wk in a double-blinded randomized trial. We used either phosphate supplementation of human milk as recommended by the European Society of Pediatric Gastroenterology and Nutrition or fortified supplementation with protein, calcium, and phosphorus or preterm formula as recommended by the American Academy of Pediatrics. The intervention period was from 1 week old until 36 wk of gestational age, and the infants were fed approximately 200 mL x kg(-1) x d(-1). Bone mineral content was measured at term by dual-energy x-ray absorptiometry scan. Surprisingly, neither phosphate, fortifier, nor preterm formula supplementation had any significant effect on bone mineral content at term compared with infants fed their own mother's milk only. There was a tendency to higher total bone mineral content in infants fed preterm formula compared with infants fed their own mother's milk only (p = 0.05), but when the bone mineral content was corrected for the size of the infant, there was no difference (p = 0.68). Infants fed preterm formula had a significantly higher weight at term compared with infants fed their own mother's milk only (p = 0.02), but did not differ significantly in length or head circumference. In a regression analysis, the amount of supplemented phosphorus was significantly associated with weight at term (p = 0.008). We conclude that when feeding 200 mL x kg(-1) x d(-1), mineral supplementation of human milk or use of preterm formula does not significantly improve bone mineralization outcome at term.

Absorptiometry, Photon↗

Critique of recent empirical research on insight and symptomatology in schizophrenia.

During the past decade there has been a resurgence of interest in investigating the relationship between insight and symptomatology among clients with schizophrenia. The breadth and depth of the articles have dramatically increased over the past 10 years, including the number of empirical research studies. This article summarizes the strengths and limitations of the empirical research focused on the association between insight and severity of psychotic symptoms and published between 1990 and 1999.

Awareness↗

In vivo enhancement of tumor radioresponse by C225 antiepidermal growth factor receptor antibody.

Overexpression of epidermal growth factor receptor (EGFR) has been correlated with tumor resistance to cytotoxic agents, including radiation (T. Akimoto et al., Clin. Cancer Res., 5: 2884-2890, 1999), and thus is a candidate target for anticancer treatment. This study investigated whether treatment with C225 anti-EGFR antibody would improve tumor response to radiotherapy. Nude mice bearing 8-mm-diameter A431 tumor xenografts in the hind leg were treated with C225 antibody, 18 Gy of single-dose local tumor irradiation, or both. C225 was given i.p. at a dose of 1 mg/mouse 6 h before irradiation or 6 h before and 3 and 6 days after irradiation. Delay in tumor growth was the treatment end point. C225 dramatically improved the efficacy of local tumor irradiation, particularly when multiple injections of C225 were administered. Tumor radioresponse was enhanced by a factor of 1.59 by a single dose and by a factor of 3.62 by a doses of C225. Histological analyses of tumors revealed that C225 caused a striking increase in central tumor necrosis associated with hemorrhage and vascular thrombosis when combined with radiotherapy. In addition, C225 induced heavy tumor infiltration with granulocytes, increased tumor cell terminal differentiation, and inhibited tumor angiogenesis. We conclude that C225 anti-EGFR antibody enhances tumor radioresponse by multiple mechanisms that may involve direct and indirect actions on tumor cell survival.

Animals↗

[Experiences with reconstruction of large abdominal wall cicatricial hernias using Stoppa-Rives pre-peritoneal mesh-plasty].

BACKGROUND: The observed recurrence-rate up to 20-50% of conventional incisional-hernia repair might be improved by alloplastic hernia repair in "sublay-technique" described by Stoppa and Rives. METHODS: From 12/94 to 12/97 122 pt. underwent surgery of incisional hernia of whom 50 had a very large abdominal wall defect so that hernia repair by alloplastic technique was necessary. All 50 pt. had mesh-implantation in subfascial plane, 28 pt. by ePTFE-patch (Gore-Tex) and 22 pt. by polypropylen-mesh (Prolene). RESULTS: The implantation-procedure required a mean time of 165 min. (range 55-345 min.). There were pulmonary complications in 2 patients (4%) of whom one had to be ventilated over 34 days, prosthesis-infection occurred in 3 pt. (6%). Follow-up on average 19 months (range 5-44 months) postoperatively revealed 5 hernia-recurrences (10.4%) in 48 patients. CONCLUSION: Mesh-implantation for hernia repair in sublay-technique requires intensive preparation of preperitoneal plane. Thus it took approximately 3 hours for mesh-implantation in this study. From our data Stoppa-Rives-procedure seems to be effective for 4-repair of large incisional hernias and allows immediate abdominal wall stress.

Adult↗

Enhancement of intrinsic tumor cell radiosensitivity induced by a selective cyclooxygenase-2 inhibitor.

The antitumor effects of the selective cyclooxygenase (COX)-2 inhibitor SC-236 alone and in combination with radiation were investigated using the human glioma cell line U251 grown in monolayer culture and as tumor xenografts. On the basis of Western and Northern blot analyses, these cells express COX-2 protein and mRNA to levels similar to those in the human colon carcinoma cell line HT29. Treatment of U251 cells in monolayer culture with 50 microM SC-236 resulted in a time-dependent decrease in cell survival as determined by a clonogenic assay. The cell death induced by SC-236 was associated with apoptosis and the detachment of cells from the monolayer. After 2 days of drug treatment, the cells that remained attached were exposed to graded doses of radiation, and the clonogenic assay was performed. Comparison of the survival curves for drug-treated and untreated cultures revealed that SC-236 enhanced radiation-induced cell death. In these combination studies, SC-236 treatment resulted in a dose-enhancement factor of 1.4 at a surviving fraction of 0.1, with the surviving fraction at 2 Gy (SF2) reduced from 0.61 to 0.31. These data indicate that in vitro SC-236 induces U251 apoptotic cell death and enhances the radiosensitivity of the surviving cells. To extend these investigations to an in vivo situation, U251 glioma cells were grown as tumor xenografts in the hind leg of nude mice, and SC-236 was administered in drinking water. SC-236 alone slowed tumor growth rate, and when administered in combination with local irradiation, SC-236 caused a greater than additive increase in tumor growth delay. These in vitro and in vivo results suggest that the selective inhibition of COX-2 combined with radiation has potential as a cancer treatment.

Animals↗

Urokinase gene expression indicates early invasive growth in squamous cell lesions of the uterine cervix.

The plasminogen activating system plays a key role in the cascade of tumour-associated proteolysis leading to extracellular matrix degradation and stromal invasion. Changes in the expression of this system, consisting of urokinase- and tissue-type plasminogen activators (uPA and tPA, respectively), plasminogen activator inhibitors (PAI-1, PAI-2) and uPA receptor, have been associated with tumour aggressiveness in a variety of solid malignant tumours. This paper describes a study of squamous intraepithelial lesions (SILs, n=36), squamous cell carcinomas (SCCs, n=42), and normal mucosa (n=5) of the uterine cervix by in situ hybridization with (35)S-labelled RNA probes. uPA transcripts were absent from normal mucosa and non-invasive lesions, but present in atypical epithelial cells of all microinvasive carcinomas ( n=19) and in some of the more advanced invasive carcinomas (n=11). PAI-1 transcripts were found in stromal cells of most tissue samples with, however, significantly increased levels in invasive SCC compared with SIL, microinvasive SCC, and normal mucosa. uPA-positive invasive carcinomas often displayed additional PAI-1 expression by tumour cells. At variance with uPA, tPA transcripts were found in atypical epithelial cells of low- and high-grade SILs. In the majority of SCCs tested (27/29 cases), the HPV 16 E6/E7 oncogene and uPA transcription were correlated. uPA and PAI-1 expression indicates invasive growth when expressed by atypical epithelial cells of squamous cervical lesions. Moreover, the presence of uPA transcripts is indicative of early invasive growth. uPA and tPA seem to have different functions in the development of invasive properties in uterine cervical squamous epithelium.

Carcinoma, Squamous Cell↗

[Delayed toxicity of brief preoperative irradiation and risk-adjusted postoperative radiotherapy of operative rectal carcinoma. Results of a randomized prospective study].

AIM: Analysis of a randomized study of preoperative radiation therapy for operable carcinoma of the rectum with regard to late sequelae. Results of tumor control and survival, which have already been published in detail are summarized for comparison and for confirmation of the conclusions. PATIENTS AND METHODS: Between January 1988 and October 1993 94 patients with operable carcinoma of the rectum were included in a randomized trial. Fourty-seven patients were treated with 5 x 3.3 Gy (field size 16 x 16 cm, 9 MeV photons) 24 to 48 hours prior to surgery; 46 patients did not receive preoperative irradiation. If risk factors (T4-stage, R1/R2 resection, intraoperative tumor perforation) were present, postoperative irradiation was performed after CT-planning. Total postoperative doses of 41.4 Gy (preoperative irradiation) or 59.8 Gy (surgery only) were applied with doses per fraction of 1.8 to 2.0 Gy. Local control, survival, and pattern of side effects were analyzed at 5 years after conclusion of the trial. RESULTS: The frequency of local recurrence was markedly reduced by preoperative irradiation of R0-resected patients (24% vs 13%, p = 0.08). The time to recurrence was delayed (1.9 vs 3 years). The 5-year actuarial survival rate was significantly higher in the preoperatively irradiated group compared to the not pre-irradiated group (40% vs 28%, p = 0.027). Multivariate analysis revealed UICC-grading as the only independent parameter for local control (p = 0.0003), while preoperative irradiation (p = 0.07) and T-stage (p = 0.08) only displayed a trend. For patient survival, age (p = 0.0003). R-status (p = 0.01) and UICC-score (p = 0.001) were significant prognostic factors. Preoperative irradiation had a non-significant effect only (p = 0.078). Radiation-induced side effects with a LENT-SOMA score > 2 were observed neither during frequent follow-up nor at an additional examination of those patients still alive in 1998 (n = 25). Of 4 pre- and postoperatively irradiated patients with risk factors, 3 had side effects grade 1 or 2, predominantly rectal changes, at 5 to 11 years after treatment. CONCLUSIONS: A positive effect on tumor control and survival is achieved with preoperative irradiation with the doses used in this study, with moderate side effects.

Actuarial Analysis↗

Inflammation does not decrease intraluminal pH in chronic inflammatory bowel disease.

Intestinal inflammation may influence intraluminal pH. Profiles of the gastrointestinal pH were evaluated in 15 patients with active Crohn's disease of the ileocecal area. In addition, five patients with moderate (1) or severe (4) ulcerative colitis were studied. Fifteen healthy subjects served as controls. Intraluminal pH of the different parts of the gastrointestinal tract was measured by a free-floating pH-sensitive telemetering capsule. A metal sphere was attached to the capsule for exact localization by a metal detector. Physiological patterns of pH were maintained throughout the gastrointestinal tract including the inflamed segments. Median pH in the terminal ileum of the patients with Crohn's disease was 7.5 vs. 7.7 and in the rectum in ulcerative colitis 7.8 vs. 7.2 in the controls. In conclusion, intraluminal pH is not decreased by inflammatory changes in Crohn's disease and ulcerative colitis, allowing eudragit-coated pH-controlled-release formulations of mesalazine to dissolve in diseased areas also.

Acid-Base Equilibrium↗

Assessment of the SF-36 version 2 in the United Kingdom.

OBJECTIVES: To introduce the UK SF36 Version II (SF36-II), and to (a) gain population norms for the UK SF36-II in a large community sample as well as to explore the instrument's internal consistency reliability and construct validity, and (b) to derive the Physical Component Summary (PCS) and Mental Component Summary (MCS) algorithms for the UK SF36-II. DESIGN: Postal survey using a questionnaire booklet, containing the SF-36-II and questions on demographics and long term illness. SETTING: The sample was drawn from General Practitioner Records held by the Health Authorities for Berkshire, Buckinghamshire, Northamptonshire, and Oxfordshire. SAMPLE: The questionnaire was sent to 13,800 randomly selected subjects between the ages of 18-64 inclusive. OUTCOME MEASURES: Scores for the eight dimensions of the UK SF36-II and the PCS and MCS summary scores. RESULTS: The survey achieved a response rate of 64.4% (n = 8889). Internal consistency of the different dimensions of the questionnaire were found to be high. Normative data for the SF-36 are reported, broken down by age and sex, and social class. Factor analysis of the eight domains produced a two factor solution and provided weights for the UK SF36-II. CONCLUSION: The SF36-II domains were shown to have improved reliability over the previous version of the UK SF36. Furthermore, enhancements to wording and response categories reduces the extent of floor and ceiling effects in the role performance dimensions. These advances are likely to lead to better precision as well as greater responsiveness in longitudinal studies.

Adolescent↗

Distinct regions of allelic imbalance on chromosome 10q22-q26 in squamous cell carcinomas of the lung.

The genetic mechanisms underlying the progression to the metastatic phenotype of lung cancer are poorly understood. We recently showed that small cell lung cancer (SCLC) and metastasizing squamous cell carcinomas are characterized by an increased incidence of allelic loss on chromosome 10q. In the present study we performed a deletion mapping using 24 polymorphic markers on chromosome 10q22-q26 in 39 squamous cell carcinomas (SCC) of the lung identifying 14 metastatic carcinomas (74%) and three non-metastatic SCC (15%) with allelic imbalance. The allelotype analysis indicated three regions of allelic loss that were clustered at the loci Afm086/D10S541, D10S185 and D10S1782/D10S169. A localized microsatellite instability was observed in two carcinomas for the markers D10S1686 and D10S1782. In addition the PTEN/MMAC1 gene was analysed by direct DNA sequencing and Southern blot analysis in 25 and 28 carcinomas, respectively, without detecting any genomic alterations. Similarly, no altered transcript was detected in 15 tumor cell lines and 20 primary tumors by Northern blot analysis or RT-PCR. In summary, three distinct regions of allelic imbalance were identified suggesting that multiple tumor suppressor genes on chromosome 10q contribute to tumor progression and metastases formation of lung cancer.

Alleles↗

Preferential accumulation of single-stranded regions in telomeres of human fibroblasts.

We have demonstrated recently that chronic hyperoxic treatment accelerates the rate of aging of fibroblasts and the rate of telomere shortening in parallel. It was hypothesized that accelerated telomere shortening is due to preferential accumulation of oxidative damage in telomeres. To test this hypothesis, we measured the accumulation of sites sensitive to S1 nuclease treatment in telomeres, in minisatellites, and in the bulk of the genome of fibroblasts under different models of oxidative stress as well as after treatment with the alkylating agent, N-methyl-N'-nitro-N-nitrosoguanidine. A comparison with qualitative data obtained by alkaline electrophoresis reveals that the sites transferred to double-strand breaks by treatment with low concentrations of S1 nuclease are, in fact, single-stranded regions in the DNA. These regions may resemble single-stranded overhangs, gaps, or conventional single-strand breaks. The frequency of single-stranded regions is significantly higher in telomeres than in minisatellites or in the bulk of the genome under all conditions tested. Those regions induced in minisatellites or in the overall genome by a bolus dose of hydrogen peroxide are completely repaired within 24 h. On the other hand, 50 +/- 12% of H2O2-induced single-stranded regions remain unrepaired for at least 19 days in telomeres of human fibroblasts, leading to a significant increase of the telomeric steady-state level of these lesions. This preferential accumulation might significantly contribute to telomere shortening.

Cell Line↗