Dose-response studies and 'no-effect-levels' of N-nitroso compounds: some general aspects

One major problem in the evaluation of potential carcinogenic food additives and contaminants is that of thresholds or, better, of 'no-adverse-effect-levels'. Arguments in favor of the postulated 'irreversibility' of carcinogenic effects are based on dose-response studies, single dose and multigeneration experiments as well as on the concept of somatic mutation as the first step in carcinogenesis with subsequent transmittance of induced defects during cell replication. The problem of extrapolation of results of animal experiments using high doses to low exposure and low incidences in man is not yet solved satisfactorily. Possible practical consequences include zero tolerance, acceptable thresholds at low risk and safety factors. Acceptable intakes should never be considered constants but should be changeable as soon as new facts in regard to the safety evaluation are available.     

Brain-derived growth factor: current aspects

INTRODUCTION: The neurotrophins are a family of proteins which are closely related structurally and functionally and include nerve growth factor (NGF), brain derived nerve factor (BDNF) and neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4/5) and more recently neurotrophin-6 (NT-6). BDNF is one of the most important endogenous proteins for control of survival, growth and differentiation of certain neurone populations both in the peripheral and central nervous systems. DEVELOPMENT: The ARNmt of the BDNF is found in nearly all regions of the brain. The highest levels are those of the hippocampus and cerebral cortex. The large number of effects attributed to BDNF are probably due to the union of this protein to its specific receptor on the cell surface, which leads to the formation of a complex which enables transmission of the signal caused by activation of the specific neurone pathway. Since discovery, BDNF has been detected and/or measured by different methods from biological assay to the application of molecular biology techniques. These methods have permitted analysis of the biochemical characteristics of this factor and its behaviour in different tissues. CONCLUSIONS: In this paper we review the most relevant aspects of distribution, biological actions of BDNF on different neurone populations, its clinical usefulness in neurological disorders, routes of administration and side effects.     

Comparative outcome studies of psychotherapy: Methodological issues and strategies.

Considers design issues and strategies by comparative outcome studies, including the conceptualization, implementation, and evaluation of alternative treatments; assessment of treatment-specific processes and outcomes; and evaluation of the results. It is argued that addressing these and other issues may increase the yield from comparative outcome studies and may attenuate controversies regarding the adequacy of the demonstrations. (64 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Peritonitis in acute appendicitis: prognostic aspects, personal results

One of the most frequent causes for peritonitis is acute appendicitis. Extent and degree of peritonitis determine the further course of the disease. A retrospective analysis of acute appendicitis with concomitant peritonitis relates pre- and intraoperative findings to the postoperative development. Resulting aspects may simplify therapy in special cases and permit a more reliable prognosis.     

Methodological issues in mammography double reading studies

Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus cultures were treated with ethanol and tested for viability and beta-galactosidase activity. Exposure of the biomass of test cultures to 30%-55% ethanol (vol/vol) caused a 100% loss of viability and up to 15-fold increase in measurable beta-galactosidase activity in both streptococci and lactobacilli. Ethanol-treated cell suspensions could be stored for up to 6 months without loss of enzyme activity. The nonviable permeabilized biomass of the more active S. thermophilus was used to achieve up to 80% hydrolysis of lactose in aqueous solutions and non-fat milk.     

Mixed oligoastrocytomas: a survival and prognostic factor analysis

Seventy-one patients with supratentorial mixed oligoastrocytomas underwent surgery only (5 patients) or surgery with postoperative radiation therapy (66 patients) between 1960 and 1982. The median survival for these 71 patients was 5.8 years and the 5-, 10-, and 15-year survival rates were 55, 29, and 17%, respectively--values significantly different from those of an age- and sex-matched normal reference population. Uni- and multivariate survival analyses were applied to 14 possible prognostic factors, including the following: patient factors--age, sex, and seizures; tumor factors--site, size, side, computed tomographic enhancement, and calcification; pathological factors--tumor grade and dominant cellular component; and treatment factors--extent of surgical resection, lobectomy, and radiation dose and field. Of these factors, tumor grade, as determined by the Kernohan method, was the most strongly associated with survival. The 60 patients with Grades 1 and 2 tumors had a median survival of approximately 6.3 years and 5- and 10-year survival rates of 58% and 32%, respectively, compared with 2.8 years (36 and 9%, respectively) for the 11 patients with Grades 3 and 4 tumors. Age < 37 years, gross total resection, partial brain radiation, and radiation dose > or = 5000 cGy were other factors significantly associated with improved survival in both uni- and multivariate models. Three of five patients not receiving postoperative radiation therapy experienced tumor recurrence and died. Seven of eight patients from whom tissue was obtained at the time of tumor progression demonstrated anaplastic transformation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genetic aspects of some orofacial anomalies

The increased importance of congenital anomalies in childhood disease is stressed. It is suggested that treatment and research in congential craniofacial anomalies would benefit from centralized registration. Their clinical management should be delegated to centres with a multidisciplinary team. Some problems related to genetic counselling and identification of microforms are illustrated by cleft lip and palate. An account is given of some orofacial anomalies.     

Methodological aspects of the application of the Naka-Rushton equation to clinical electroretinogram

The nonlinear relation between stimulus intensity and response amplitude of the electroretinogram (ERG) scotopic b wave can be described by a curve based on the Naka-Rushton (NR) equation. Up to now, the NR equation has been used to assess the features of the normal and pathological ERG, but the best approach for a correct evaluation of the parameters is still debatable. The parameters are thought to be related to the different conditions of retinal activities. The method is well known in experimental laboratories but is quite unusual at the clinical level. In the present paper the derivative analysis of the NR function is proposed as an easier approach to understand the variations of the NR parameters in selected pathologies.     

Clinical and prognostic aspects of adrenocortical neoplasms in childhood

BACKGROUND: A retrospective study of 54 children was undertaken to define the clinical presentation and secretory patterns of adrenal tumors and to evaluate the outcome of surgical resection and medical therapy. PROCEDURES: Different factors were studied in univariate and multivariate analysis by using the Cox proportional hazard model. RESULTS: Median age at diagnosis was 4 years. Boys and girls were affected equally. The disease was revealed by virilization (61%) or by a palpable mass (39%) with a 0.1-5.5 year delay from initial symptoms. At initial examination, we found that 76% of children were virilized. Ninety-four percent of the tested tumors secreted androgens, which were associated with glucocorticoids in 36%. Adrenal tumors in children were smaller than in adults. Half of them measured less than 10 cm. There were recurrences in 40% of children. The survival rate at 5 years was 49%, 70% if resection was microscopically complete and 7% if not (P < 0.001). CONCLUSIONS: In children, rare adrenal tumors have different diagnostic and prognostic characteristics than in adults; however, recurrences remain frequent. The efficacy of chemotherapy, mainly o,p'-DDD (Mitotane), remains to be evaluated in comparative trials.     

Ruptured hepatocellular carcinoma: treatment strategy and prognostic factor analysis

BACKGROUND: The prognosis of ruptured hepatocellular carcinoma (HCC) is generally poor, but few studies have focused on the analysis of prognostic factors of this catastrophic event. METHODS: Eighty-four consecutive patients with ruptured HCC were included. Twenty-nine clinical and laboratory variables were correlated to prognosis by using uni- and multivariate analyses. RESULTS: Epigastralgia and/or right upper quadrant abdominal pain was the most common initial presentation (70%), followed by shock (42%), abdominal distension (27%) and others (17%). Of these 84 patients, 50 patients were treated by supportive measure, 21 by operation and 13 by transcatheter arterial embolization (TAE). The median survival was 13, 30 and 202 days in each group, respectively, and 24 days overall. TAE showed the lowest hemostatic failure rate (20%). Univariate analysis showed that active treatment (operation or TAE), group I tumor with a solitary nodule or single nodule with proliferation into surrounding area, serum creatinine (< or = 1.2 mg/ml), alkaline phosphatase (< or = 95 U/L), alanine aminotransferase (ALT, < or = 40 U/L), total bilirubin (< or = 1.6 mg/ml), initial systolic blood pressure (> or = 90 mmHg), and absence of main portal vein thrombosis were correlated with a survival longer than 90 days (p < 0.05) in univariate analysis. Active treatment, ALT level and initial systolic blood pressure were still significant in multivariate analysis (p < 0.05). CONCLUSIONS: TAE may help stop the tumor bleeding. Treatment regimen, ALT levels and initial blood pressure are correlated with the prognosis of ruptured HCC.     

Methodological issues in the use of biological markers in cancer epidemiology: cohort studies

In this chapter we summarize the major strengths and weaknesses of cohort studies; consider how these characteristics influence the use of biomarkers in cohort studies; briefly review considerations of statistical power, design and the influence of measurement error in cohort studies; and discuss some of the emerging ethical considerations that relate to the use of biomarkers in prospective studies.     

Medical and biological aspects of artificial gravity: animal studies

In the review there analyzed the results of ground-based studies of rotation effects (at a gravity value near 1 g) on the animals, the experimental findings to determine a minimum effective value of artificial gravity as well as the data of biosatellite experiments. The major trends of animal studies in the artificial gravity area is presented.