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Biomedical subjects

N Becker

Publications and source records attributed to N Becker.

At least 55 records · Page 3Linked to original sources

[Hemichorea-hemiballism associated to cryptococcal granuloma in a patient with AIDS: case report].

Movement disorders are not common in acquired immunodeficiency syndrome. Hemichorea-hemiballism (HC-HB) is the most common of them all, and it is usually related to oportunistic toxoplasmosis of the basal ganglia. We present a 28-year-old man, HIV positive with HC-HB caused by a right subthalamic granuloma, which did not respond to treatment for toxoplasmosis. Cryptoccococic antigen was positive in the cerebrospinal fluid and antifungic therapy led to clinical and radiologic improvement, thus the diagnosis of a granulomatous lesion by Cryptococcus neoformans was established. Current literature on HC-HB and its relationship with AIDS is subsequently reviewed.

AIDS-Related Opportunistic Infections↗

Transcriptional repression of TRH promoter function by T3: analysis by in vivo gene transfer.

We consider how an integrated in vivo model can be used to study the specific transcriptional effects of specific receptors in neuroendocrine systems. Our example is the role of thyroid receptor (TR) isoforms in mediating negative feedback effects of T3 on TRH (thyrotropin releasing hormone) expression. The in vivo transfection method employed polyethylenimine (PEI) to introduce genes directly into specific regions of the brains of mice, rats, and Xenopus tadpoles. In the mouse model, the technique has served to examine TR effects on TRH transcription and on the pituitary-thyroid axis end point: thyroid hormone secretion. When a TRH-luciferase construct is introduced into the hypothalami of newborn mice TRH-luciferase transcription is regulated physiologically, being significantly increased in hypothyroidism and decreased in T3-treated animals. When various T3-binding forms of TRbeta or TRalpha are expressed in the hypothalamus, all TRbeta isoforms give T3-dependent regulation of TRH transcription, whereas TRalpha isoforms block T3-dependent transcription. Moreover, TR transcriptional effects are correlated with physiological consequences on circulating T4. Thus, somatic gene transfer shows TR subtypes to have distinct, physiologically relevant effects on TRH transcription. The approach is an appealing alternative to germinal transgenesis for studying specific neuroendocrine regulations at defined developmental stages in different species.

Animals↗

Impact of bacillus thuringiensis var. israelensis On larvae of chironomus thummi thummi and psectrocladius psilopterus (Diptera: chironomidae)

Chironomid larvae, especially species of the subfamily Chironominae, are known to be sensitive to the mosquitocidal bacterium Bacillus thuringiensis var. israelensis (B.t.i.). In this study, bioassays and electron microscopic investigations were carried out with third- and fourth-instar larvae of Chironomus thummi thummi Kieffer (subfamily Chironominae) and Psectrocladius psilopterus Kieffer (subfamily Orthocladiinae) in order to study the sensitivity of species belonging to different chironomid subfamilies. Both species showed susceptibility to increased B.t.i. concentrations, with LC50 values (24 h) ranging from about 40- to 60-fold the LC50 for Aedes aegypti (LC50 (24 h) is 0.77 mg/L for C. thummi thummi and 1.17 mg/L for P. psilopterus). C. thummi thummi was shown to be twice as sensitive as P. psilopterus. Ultrastructural investigations of the anterior midgut showed cellular alterations in larvae exposed to a high B.t.i. concentration (2.8 mg/L, about 50-fold the LC50 for A. aegypti), such as swelling of mitochondria, dilatation of intercellular spaces and basal labyrinth, fenestration or disorganization of the Golgi complex, concentric arrangement of rough endoplasmic reticulum, and an increase of lysosomes and myelin figures. Electron-lucent regions within the cell, cell protrusion, and, in some cases, swelling or lysis of cells were further effects observed in treated animals. Most effects were found in both species, though they seemed to be more severe in C. thummi thummi. The alterations coincide with those known from target organisms (Culicidae, Simuliidae). This study shows that there is a difference in sensitivity to B.t.i. between chironomid species from different subfamilies and that the susceptibility of chironomid larvae to the bacterial toxins is due to damage of the midgut epithelium as it is in target organisms. Copyright 1999 Academic Press.

Journal Article↗

Opioid rotation in chronic non-malignant pain patients. A retrospective study.

BACKGROUND: The clinical advantage of opioid rotation is probably due to incomplete cross-tolerance favouring analgesia more than adverse effects. The objectives of opioid rotation in chronic non-malignant patients are 1): rotation between different long-acting opioids (LAO) to improve analgesia and reduce side-effects, and 2): rotation from short-acting opioids (SAO) to LAO to establish stable analgesia in order to minimise withdrawal symptoms, risk of tolerance and addiction. METHODS: A retrospective analysis of 37 rotations between different LAO and 59 rotations from SAO to LAO. RESULTS: The main reason for opioid rotation was insufficient pain relief. Opioid rotations resulted in significantly better pain control in 59% (CI95=49-76%) of the patients rotated between different LAO and 73% (CI95=60-84%) of the patients rotated from SAO to LAO. During rotations symptoms of withdrawal and overdosing were relatively frequent in both groups. No significant dose changes were seen when rotating between different LAO. However, the consequence of rotation from SAO to LAO was a 74% increase in the opioid dose (CI95=30-117%). CONCLUSION: Opioid rotations between different LAO resulted in better pain control and fewer side-effects at dose levels predicted to be equianalgesic. The majority of the patients rotated from SAO to LAO obtained improved analgesia, but the cost was a 74% increase in the opioid dose.

Adult↗

Cancer mortality among arc welders exposed to fumes containing chromium and nickel. Results of a third follow-up: 1989-1995.

For the historical follow-up study among arc welders exposed to chromium and nickel, which was started in 1980 in Germany, a third follow-up extending the observation period to the years 1989 through 1995 has been carried out. By 1995, of the 1213 welders and 1688 turners (control group) who were originally included in the study, 274 welders and 448 turners had died. Death certificates could be obtained for approximately 96% of the deceased. Results of the evaluation presented in this article showed that cancer mortality remains significantly increased, compared with the general population and the control group, by approximately 35%. There was an elevation of approximately 50% or 60% in mortality from cancers of the respiratory tract, which is also statistically significant. However, this increase is predominantly due to a large excess in mortality from mesothelioma, which is known to be caused chiefly by asbestos exposure. Lung cancer mortality is nonsignificantly increased by approximately 20% to 30%. An indirect assessment of asbestos-related lung cancers and total cancer indicates that the observed increase of mortality might be mainly due to asbestos exposure. Beyond that, no indication of an elevated cancer risk specifically associated with the exposure to welding fumes containing chromium and nickel could be determined.

Adult↗

Mortality in a cohort of toluene exposed employees (rotogravure printing plant workers).

Since the beginning of the 1960s, toluene has been used as a solvent in all German rotogravure printing plants in a high degree of purity. These particular exposure conditions allow the investigation of the potential carcinogenicity of long-term toluene exposure. A historical cohort study was performed that included 6830 German men from 11 plants who were exposed to toluene from 1960 to 1992 in three work areas with different exposure levels. Overall, 466 deaths were observed, which provided a standardized mortality ratio (SMR) of 91.3 for overall mortality. A significantly decreased SMR for total mortality was seen in one of the three work areas (SMR = 67). Mortality from cancer did not differ substantially from the expected level, but in one of the work areas, mortality from cancers of the bone (Ninth Revision of the International Classification of Disease [ICD]-9 170; SMR = 813) and connective tissue (ICD-9 171; SMR = 631) was significantly elevated. In the entire cohort, mortality from lung cancer was increased by about 35% above total mortality, and by about 95% in one work area with low toluene exposure (not statistically confirmed). The SMR for death from alcohol dependence was statistically significantly increased (ICD-9 303; SMR = 314).

Aged↗

EPIC-Germany--A source for studies into diet and risk of chronic diseases. European Investigation into Cancer and Nutrition.

The 'European Investigation into Cancer and Nutrition (EPIC)' represents one of the main scientific activities of the EU program 'Europe against Cancer' and is a large-scale cohort study on diet and chronic diseases, especially cancer, with approximately 475,000 study participants. The German contribution amounted to 53,000 study participants recruited between 1994 and 1998. The study instruments of the baseline examination included self-administered questionnaires for optical reading, PC-guided interviews, and physical examinations. These instruments covered different aspects of lifestyle, with a particular focus on diet. In addition, about 95% of the participants provided 30 ml of blood. The blood was stored in liquid nitrogen for further use, preferentially in nested case-control studies. All interviews and examinations were conducted by trained interviewers in examination centers established for this study in local health offices. Every 2 years, a follow-up questionnaire is mailed to the study participants. The follow-up questionnaires will be used as the major source of outcome information and to update exposure information. The self-reported diseases are verified by medical data. In the future, record linkage with local cancer registries will help to support the identification and collection of incident cancer cases. Only an outline of hypotheses was formulated at the very beginning of EPIC in 1992. In the future, each etiological study will be based on detailed research hypotheses according to the existing knowledge and identified research gaps. These studies will be conducted on cancer at the international level and on non-cancer diseases at the national or local level.

Adult↗

Dietary habits in the German EPIC cohorts: food group intake estimated with the food frequency questionnaire. European Investigation into Cancer and Nutrition.

In the baseline assessment of the two EPIC-Germany cohorts Heidelberg and Potsdam, dietary information was obtained with an identical food frequency questionnaire (FFQ). The optically readable FFQ was designed to assess the usual food and nutrient intake of individuals during the past 12 months. The present analysis was based on dietary data from 25,212 participants in Heidelberg (11,776 men, 13,436 women) and 26,270 participants in Potsdam (10,249 men, 16,021 women). This paper presents the first results of a descriptive dietary analysis on a food group level based on 16 food groups and selected subgroups. Each of these food groups and subgroups was divided into quintiles, and the age-adjusted mean intake for each quintile was calculated. The comparison of dietary habits between the two cohorts, as well as the comparison between men and women within each cohort showed clear differences both in the quintiles of most food groups as well as in the range between the lowest and highest quintile. Except for the food groups non-alcoholic and alcoholic beverages, sugar and confectionery, sauces, and soups, men and women participating in Potsdam reported higher intakes of all the other food groups. The amount of food intake was generally lower in women than in men, with the exception of vegetables, fruit, dairy products, and non-alcoholic beverages. Further differences between the study centers were observed regarding the use of cooking fat for meat and vegetable preparation. In conclusion, the dietary variation, e.g. the exposure variation, was increased by recruiting two geographically distinct cohorts, instead of only one, in Germany.

Adult↗

Patterns of past alcohol consumption in the EPIC-Germany cohorts. European Investigation into Cancer and Nutrition.

Information on life-long history of alcohol consumption might be more relevant to chronic diseases than current intake. The aim of this study was to describe past alcohol intake and consumption patterns in the EPIC-Germany cohorts, by sex and age, from 1949 to 1998. Past daily consumption of alcoholic beverages - beer, wine, and spirits - was assessed through a lifestyle questionnaire administered to 27,099 subjects of the EPIC-Potsdam and 25,449 subjects of the EPIC-Heidelberg cohort. Recruitment of the cohorts concentrated on men aged 40-64 and on women aged 35-64. For each alcoholic beverage, the consumption at ages 20, 30, and 40 was asked. The data were used to calculate previous mean consumption in 10-year intervals from 1949 to 1998. Alcohol intake was observed to be higher in the Heidelberg than in the Potsdam cohort. Differences between cohorts were most marked for wine consumption which was considerably higher in the Heidelberg cohort. Men consumed approximately 3 times the amount of alcohol of women. Men preferred to drink beer, women preferred to drink wine. For the Potsdam cohort, alcohol intake was observed to increase since 1949. For the Heidelberg cohort, a recent decrease in alcohol intake in males and females of 30 and 40 years of age was noted. The data indicate that collection of alcohol consumption data at various discrete points in time is essential to depict life-long history of alcohol consumption.

Adult↗

Optimisation of polyethylenimine-based gene delivery to mouse brain.

Polyethylenimine (PEI) is proving to be an efficient and versatile vector for gene delivery in vivo. However, a limiting factor is the relatively short duration of gene expression in some sites. Given the particularly high levels of expression seen in the short term we postulated that loss of expression could result from overloading the nucleus with foreign DNA. To address this problem we first followed DNA delivery and localisation with digoxin-labelled plasmid DNA complexed with 22 kD linear PEI and used these complexes for intraventricular injection into brains of anaesthetised newborn mice. At 24 h post-injection, labelled DNA was found exclusively in the nuclear and perinuclear regions. We next carried out a dose response curve using decreasing amounts of DNA, either in a constant volume (2 microl) or at a constant concentration (500 ng/microl). In both conditions, transgene expression yield was maximum at 100 ng DNA per injection. Using this optimal amount of DNA increased yield of transgene expression significantly at 24 h and one week post-injection as compared to 1 microg DNA. A final point addressed was whether co-expressing an anti-apoptotic gene could enhance gene expression in the longer term. Co-expressing bcl-X(L) with luciferase or LacZ significantly increased expression of both these genes at one week post-injection.

Animals↗

Smoking prevalence and lung cancer mortality in Germany.

From investigations of smoking habits, which included information about onset of smoking, we have extrapolated gender- and age-specific smoking prevalence in Germany back to the 1920s. The exploration of these data, together with an analysis of lung cancer mortality by age-period-cohort models shows that the increase of smoking and lung cancer is modulated by factors related to the country-specific socio-economic environment and that it proceeds in waves. Though recent data indicate a decline in the prevalence of smoking among both sexes, Germany is now on the way to having a similar smoking-related cancer mortality to those countries in the world which previously had a much higher rate, but have intervened vigorously. The refusal in Germany to adopt actions such as those successfully implemented to save lives in these countries means that the German population is exposed to avoidable risks, whose effects can be counted in the terms of the thousands of lives that might have been saved each year.

Adolescent↗

[Pain epidemiology and health-related quality of life in patients with chronic non-malignant pain].

This paper presents the results of a detailed study of the pain epidemiology and health related quality of life (HRQL) in 150 chronic non-malignant pain patients referred to a Danish multidisciplinary pain centre. Mean pain intensity was 71.6 (SD 18.5) on the VAS scale. HRQL was evaluated using the questionnaires: SF-36, HAD and PGWB. Compared with the normal population (NP) both physical, psychological and social well-being was severely reduced, and 58% were found to have a depressive or anxiety disorder. Sixty-three percent of the patients had neurogenic pain conditions. Of these, only 25% were treated with antidepressants or anticonvulsants. At referral 73% were treated with opioids. Mean opioid consumption was 64 mg of morphine per day. Patients had used the health care system five times more often than the NP (p < 0.001). The study showed that HRQL of chronic non-malignant pain patients is among the lowest observed for any medical condition.

Adult↗

Cancer mortality and prevention in the European Union.

In the European Union (EU), approximately one in four people dies from cancer (27% of men and 21% of women) and one in three contracts the disease. In recent years, however, trends in cancer mortality appear to have changed, at least in some European countries. Standardized mortality rates among men have declined since the late 1980s or early 1990s. Among women, a continuous decrease in mortality has been observed over some decades. Nevertheless, due to population increase in the EU and the ageing population, the increase in the absolute numbers of new cancer cases continues. Lifestyle plays a crucial role in the aetiology of cancer and, because it is at least a principally modifiable determinant, we can assume that cancer could be avoided to a considerable extent via primary prevention.

Cause of Death↗

Potency of products based on Bacillus thuringiensis var. israelensis: interlaboratory variations.

Six quality-control laboratories in 4 countries independently bioassayed aliquots of a flowable formulation of Bacillus thuringiensis var. israelensis (B.t.i.) against the international standard powder IPS-82. All laboratories substantially followed World Health Organization or U.S. Department of Agriculture standard protocols. Significant differences were found in resulting potency values between laboratories. Factors that may have influenced results, such as age, stage, and strain of larvae used, amount and type of food provided to larvae, and processing of samples were examined. Use of different rearing temperatures, different strains of Aedes aegypti L., or late 3rd instars vs. the recommended early 4th instars did not explain the inconsistencies. The slope of the dose-response curve of the IPS-82 powder was influenced by particle size, which varied with the nature and duration of sample homogenization. Laboratories using low-intensity processing obtained a greater slope in the dose-response curve for the flowable product than for the powder standard. The type and quantity of food provided to larvae affected susceptibility. Larvae fed an excess of protein-rich food became 4th instars in 3 days and were less susceptible to B.t.i. than those fed smaller quantities of carbohydrate-rich food that became 4th instars in 5-7 days. Overall, deviations from standard protocols with regard to larval stage, holding temperature, and lighting regime may not be as important as differences in sample processing and pretest rearing conditions. The need to improve standardization in these areas, which are not clearly specified in current protocols, is discussed.

Aedes↗

Improved outcome of young children on nightly automated peritoneal dialysis.

We reviewed our center's experience with nightly automated peritoneal dialysis (APD) as maintenance renal replacement therapy (RRT) for infants and children under the age of 5 years and compared it with national dialysis and transplant data. A retrospective chart review of 19 consecutive patients with the onset of end-stage renal disease (ESRD) before 5 years of age (mean = 1.8 years) between June 1988 and June 1994 was performed. All patients received nightly APD, supplemental feedings, calcitriol, erythropoietin, and 10 of 19 were on growth hormone (rhGH) therapy. The growth of our patients was maintained or improved during the study period, with the 10 of 19 on rhGH gaining a mean of one standard deviation in height when followed for 2 years. Our school-age children were all in age-appropriate classes. There were no deaths in our group; the incidence of peritonitis was lower than in national data. We conclude that APD is a realistic option for the treatment of ESRD in the 0- to 5-year-old child. Because of the improved graft and patient survival in older children, APD in a specialized center might be the RRT of choice in this age group, allowing good growth and development while maximizing the chances of an eventual and successful renal transplant.

Child, Preschool↗