Association of CYP2E1 gene polymorphism with predisposition to cancer development

We summarize research results on association of cytochrome P450 2E1 (CYP2E1) genetic polymorphisms with the development of ecologically determined cancers. Cytochrome P450 monooxygenase enzyme system is involved in metabolic activation of procarcinogens, which is an important stage during normal cell transformation into a malignant one. Studies of association between CYP2E1 gene polymorphisms and the risk of cancer development are of particular interest, since the enzyme participates in bio-transformation of numerous procarcinogens. We place special emphasis on characterization of known CYP2E1 polymorphisms and analysis of their role in pathogenesis of various cancer types. Results obtained provide evidence on association of CYP2E1 genetic polymorphisms both with increased and decreased risk of development of malignant tumors. Ethnic and geographic peculiarities were also identified for frequencies of CYP2E1 variants distribution.     

Video Analysis of Sensory-Motor Features in Infants with Fragile X Syndrome at 9–12 Months of Age

This study utilized retrospective video analysis to distinguish sensory-motor patterns in infants with fragile X syndrome (FXS) (n=11) from other infants [i.e., autism (n=11), other developmental delay (n=10), typical (n=11)] at 9–12 months of age. Measures of development, autistic features, and FMRP were assessed at the time of entry into the study. Home videos collected from families were edited and coded with previously validated procedures. Findings revealed a pattern of sensory-motor features (e.g., repetitive leg movements, posturing, less sophistication/repetitive use of objects) associated with FXS, and suggest these infants were most similar to the group of infants with other developmental delays, irrespective of co-existing autistic symptoms later in life. Infant sensory-motor features in the FXS group were more predictive of an early developmental milestone (i.e., age walking) than later, more broad, developmental outcomes, or FMRP. Implications for early identification and differential diagnosis are discussed. An erratum to this article can be found at     

Treatment of war injuries of the shoulder with external fixators

In this retrospective study, 18 patients with war injuries of the shoulder were reviewed to evaluate the technical problems associated with external fixation and to analyze the incidence of infection and late functional results. The average patient age was 28.5 years. All patients were male. Thirteen patients had explosive wounds, whereas five wounds were caused by gunshot missiles. All injuries were extensive in terms of bone and soft tissue defects. Six patients presented with complex injuries involving neurovascular structures. Sixteen patients were treated with external fixation. Application of the proximal pins of the external fixator through the humeral head was possible in eight patients, the scapula served as the site of proximal fixation in four patients, only the clavicle was available for placement of pins in two patients, and both the scapula and the clavicle had to be pinned to achieve proximal stabilization in two patients. In two patients, fixation was not possible and early amputation was performed. Infection was eventually eradicated in all patients, allowing for adequate soft tissue coverage of the wounds. Analysis of functional results at an average of 6 years after the injury showed a considerable degree of functional deficit in most patients.     

Epidemiological studies of tooth wear and dental erosion in 14-year-old children in North West England. Part 1: The relationship with water fluoridation and social deprivation

OBJECTIVE: The effect of water fluoridation upon dental erosion/tooth wear in the UK has not been investigated. This study aimed to compare the prevalence of tooth wear in 14-year-old schoolchildren in non-fluoridated and fluoridated districts of North West (NW) England. The influence of deprivation and tooth brushing was also investigated. DESIGN: A random sample of 10% of the 14-year-old population in NW England was selected and stratified according to fluoridation status as determined from water authority postcode listings. METHODS: Tooth wear was scored on the labial, incisal and palatal/lingual surfaces of the 12 anterior teeth and the occlusal surfaces of the first molars. Enamel wear was scored 0, dentine was scored 1 or 2, dependent on whether less than or more than a third of the surface had exposed dentine. Secondary dentine or pulpal exposure scored 3. Townsend deprivation scores were gained from residential post codes. RESULTS: A total of 2,351 children were examined, of which 637 (27%) lived in the one fluoridated district of South Cheshire and 1,714 (73%) lived in 11 non-fluoridated districts. Fifty-three per cent of the children had exposed dentine with significantly more males affected than females (p<0.001). In the fluoridated district, significantly fewer children had exposed dentine on labial and palatal smooth surfaces (p<0.001) but no differences were found for incisal and occlusal surfaces. The interaction of fluoridation and tooth brushing twice per day resulted in a significant (30%) reduction in erosion. Smooth surface wear was more prevalent in children resident in affluent areas. CONCLUSION: Children in non-fluoridated districts are 1.5 times more likely to have smooth surface wear compared with children in fluoridated districts. Fluoridation and use of fluoridated toothpaste twice a day provide added protection from dental erosion. The risk of tooth wear is greater with increasing affluence.     

Splenic rupture in pregnancy--traumatic or spontaneous event?

Splenic rupture in pregnancy or postpartum is a rare and frequently misdiagnosed occurrence. Failure to recognise it is common, and can be fatal for both mother and child. With all our highly developed diagnostic methods and equipment, aetiology of splenic ruptures in pregnancy remains a dilemma in many cases.     

Patterns of drug-related disorders in a prospective study of men chosen for their family history of alcoholism

OBJECTIVE: Alcohol use disorders (AUDs) and abuse or dependence on illicit substances often co-exist. Most studies evaluating these phenomena have focused on less well-educated individuals, using cross-sectional designs. This study controls for several factors that might contribute to a propensity toward both alcohol and substance-related conditions in a prospective follow-up of middle-class men. METHOD: The subjects (N = 249) were white sons of alcoholics and controls, followed for 20 years using structured interviews. They were evaluated at baseline and again 10, 15 and 20 years later. RESULTS: One in five subjects developed an illicit substance-related disorder by the 20-year follow-up, most commonly abuse or dependence on cannabinoids and/or stimulants. The men with these diagnoses were more likely to be recent smokers, to also fulfill criteria for alcoholism and to have a family history of a stimulant use disorder. They were not more likely to have family histories of alcoholism, did not have a lower response to alcohol at age 20 and had no enhanced risk for independent psychiatric disorders, although they did have relatives with manic depressive disease. CONCLUSIONS: Disorders related to illicit substances were common in this well-educated, highly functional population. Substance-related comorbidity with alcoholism did not seem to reflect several factors known to predict AUDs (e.g., family history of alcoholism and a low response to alcohol). The diagnostic overlap between AUDs and illicit substance-related disorders might reflect concomitant family histories of alcoholism and substance-related conditions and, perhaps, family histories of manic depressive disease.     

Potential of progenitors from postnatal cerebellar neuroepithelium and white matter: lineage specified vs. multipotent fate

Progenitors that migrate through the white matter of the postnatal cerebellum give rise to interneurons, astrocytes, and oligodendrocytes. To investigate the lineage potential of progenitors from the neuroepithelium and the white matter, we performed an in vitro clonal analysis in the presence or absence of various growth factors. Clonal progeny of cells labeled with a green fluorescent protein (GFP)-expressing retrovirus was characterized using morphological features and lineage markers. The large majority of clones were homogeneous, containing astrocytes, oligodendrocytes, neurons, or hybrid progenitors-cells labeled with markers for astrocytes and oligodendrocytes. Heterogeneous clones consisted of astrocytes and oligodendrocytes, with only a few mixed glial-neuronal clones. The neuroepithelium contains a higher number of multipotent progenitors than the white matter, pointing to a lineage specification of most of the cerebellar progenitors before their migration to the white matter.     

The privilege to be old

BACKGROUND: Ample evidence has proven that the functional property of cells decreases over the years. Nevertheless, although it has taken decades to convince ourselves that elderly people belong to a specific age group both biologically and medicinally, and in whom special criteria have to be taken into consideration, it seems that even they themselves do not present an homogenous group. OBJECTIVE: Today we often hear of authors of studies speaking of two subpopulation groups--one group that ages by all the laws of aging that we have encountered and accepted thus far, and the other group that seems to postpone aging due to 'programmed death', or more specifically due to low mastery/low emotional support or because of additional reasons; however, the existence of the two groups seems eminent. METHODS: The identification of these two groups would allow us to find more realistic results in studies, and therefore a more efficient therapy for certain diseases. RESULTS: This hypothesis does not contradict the theories of aging that we have accepted (at least not the majority) and also does not contradict the fact that there is a large interindividual variability. This hypothesis doubts and claims there are exceptions to the initial assumption of geriatrists and gerontologists that 'parallel to the aging process, the functions of all organs and organ systems lessen.' CONCLUSION: The identification of these two groups would allow us to find more realistic results in studies, and therefore more efficient therapy for certain diseases.     

Is there a relationship between repopulation and hypoxia/reoxygenation? Results from human carcinoma of the cervix

Long overall treatment times are detrimental for cure by radiotherapy and it has been argued that this may be due to repopulation occurring during the course of treatment. However, attempts to predict treatment outcome in relation to tumour proliferation, using pretreatment measurements of kinetic parameters such as Tpot or labelling index (LI) have not met with great success. One possible reason is that hypoxia/reoxygenation is linked to the growth of the tumour and its ability to repopulate. Data from studies in animal models have provided support for this possibility. We made measurement of tumour hypoxia, reoxygenation during treatment and pretreatment measurements of both Tpot and LI in groups of patients with cervix carcinoma undergoing radical radiation treatment. The data show a relationship between pretreatment pO2 measurements and treatment outcome, but reoxygenation did not show any association with treatment outcome. There was no significant association between pretreatment kinetic parameters and treatment outcome, nor was there any evidence of a relationship between pretreatment kinetic parameters and pO2. In the small group of 28 patients whose tumours underwent measurements of both pretreatment kinetic parameters (Tpot, LI) and reoxygenation, there was no relationship between these two sets of measurements. There was also no evidence that a combination of kinetic and reoxygenation measurements could be predictive of treatment outcome.