Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m²: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.     

P300-based brain computer interface: reliability and performance in healthy and paralysed participants.

OBJECTIVE: This study aimed to describe the use of the P300 event-related potential as a control signal in a brain computer interface (BCI) for healthy and paralysed participants. METHODS: The experimental device used the P300 wave to control the movement of an object on a graphical interface. Visual stimuli, consisting of four arrows (up, right, down, left) were randomly presented in peripheral positions on the screen. Participants were instructed to recognize only the arrow indicating a specific direction for an object to move. P300 epochs, synchronized with the stimulus, were analyzed on-line via Independent Component Analysis (ICA) with subsequent feature extraction and classification by using a neural network. RESULTS: We tested the reliability and the performance of the system in real-time. The system needed a short training period to allow task completion and reached good performance. Nonetheless, severely impaired patients had lower performance than healthy participants. CONCLUSIONS: The proposed system is effective for use with healthy participants, whereas further research is needed before it can be used with locked-in syndrome patients. SIGNIFICANCE: The P300-based BCI described can reliably control, in 'real time', the motion of a cursor on a graphical interface, and no time-consuming training is needed in order to test possible applications for motor-impaired patients.     

Amisulpride in the short-term treatment of depressive and physical symptoms in cancer patients during chemotherapies

Introduction Amisulpride is a substituted benzamide that, at low doses, selectively blocks D2 and D3 presynaptic dopamine receptors, enhancing dopaminergic transmission in frontal cortex and limbic areas. Many clinical studies versus placebo, tricyclic antidepressants and selective serotonin reuptake inhibitors showed amisulpride antidepressant effect, supporting its safety and rapid onset of action. In oncological population, depression is quite frequent and difficult to treat because of the particular sensitivity of cancer patients to the antidepressants’ side effects. Goals of work The aims of this study were to evaluate efficacy, safety and tolerability of low doses of amisulpride (50 mg) in oncological, depressed patients during chemotheraphy. Materials and methods One hundred six consecutive cancer outpatients with depressive symptoms were treated in a prospective, intention to treat, 4-week study, and were evaluated in single-blind with Montgomery Asberg rating scale for depression (MADRS), clinical global impression (CGI) and dosage record treatment emergent symptom scale (DOTES) to assess side effects of treatment. Main results After 4 weeks of treatment, scores of MADRS and CGI significantly improved (p < 0.002; p < 0.001, respectively), with a reduction of depressive symptoms concerning both emotional (such as apparent sadness, reported sadness, inner tension, etc.) and physical cluster (such as lack of appetite, reduction in weight, tiredness and insomnia) with good tolerability (only two patients dropped out). Conclusions This study is the first trial on the use of amisulpride in a cohort of oncological, depressed patients during chemotherapy. Amisulpride demonstrated high efficacy and safety. Controlled studies are needed to confirm these preliminary data.     

Circulating adipocytokines in non-diabetic and Type 1 diabetic children: relationship to insulin therapy, glycaemic control and pubertal development.

AIM: To determine the influence of Type 1 diabetes mellitus on circulating adipocytokines in children. METHODS: The circulating concentrations of leptin, adiponectin, resistin and tumour necrosis factor (TNF)-alpha were measured in 91 children, aged 11.1 +/- 2.7 years, with Type 1 diabetes mellitus (T1DM). Ninety-one healthy children were selected as control subjects. RESULTS: Body mass index-adjusted leptin concentrations were higher in the pubertal diabetic children compared with the control children. There was a significant positive correlation between leptin and daily insulin dose in the diabetic group. Circulating adiponectin concentrations were higher in the prepubertal diabetic children and were positively associated with HbA(1c). Resistin concentrations were lower in the prepubertal non-diabetic subjects compared with the pubertal non-diabetic children, whose values were higher than those of the diabetic children. TNF-alpha concentrations were similar in non-diabetic and diabetic children. CONCLUSIONS: Circulating concentrations of adipocytokines are abnormal in Type 1 diabetic children, although the direction of change differs by cytokine. Pubertal development, in addition to insulin treatment and glycaemic control, also influences the concentrations.     

Behavioral and biochemical evidence for a long-lasting decrease in GABAergic function elicited by chronic administration of FG 7142

Chronic treatment with the beta-carboline derivative FG 7142 (15 mg/kg i.p. twice a day for 10 consecutive days) produced a long-lasting enhancement of shock-induced suppression of drinking in rats, without affecting unpunished behaviour. This proconflict effect was observed up to 15 days after withdrawal from FG 7142. A significant sensitization to seizures induced by isoniazid, a drug known to inhibit GABAergic transmission, was also found to occur after long-term (25 days) withdrawal. Moreover, the density of low-affinity GABA receptors was decreased by 30% in the cerebral cortex of rats repeatedly injected with FG 7142 at 5 and 15 days after withdrawal. The capacity of high-affinity GABA receptors, as well as the apparent dissociation constants for both high- and low-affinity GABA receptors were unchanged. Similar modifications in [3H]GABA binding were also observed in the cerebellum. The enhancement of punishment suppressed behaviour, the sensitization to isoniazid-induced convulsions and the decrease in the density of low-affinity GABA receptors suggest that chronic administration of FG 7142 induces a persistent down-regulation of GABAergic transmission in the central nervous system.     

Characterization of T-cell subsets infiltrating post-burn hypertrophic scar tissues

In this study, skin-infiltrating cells were characterized in both the active and remission phases of post-burn hypertrophic scar biopstes. Immunohistochemistry examination of active phase samples showed an abundant presence of Langerhans cells, T cells, macrophages, a low presence of natural killer cells and the lack of B lymphocytes. In active hypertrophic scars T lymphocytes infiltrate deep into the superficial dermis and are also observed in the epidermis: CD3⁺ cells were present at about 222±107 per 0.25 mm². In particular the analysis of lymphocyte subpopulations showed that CD4⁺ T cells predominate in the dermis as well as in the epidermis of active hypertrophic scars whereas CD8⁺ cells were less well represented (CD4/CD8 ratio is 2.06). This distribution was also shown in remission phase samples and in normotrophic scar specimens, although the lymphocyte number was significantly lower. Approximately 70 per cent of T lymphocytes present in the tissue involved in active phase hypertrophic scar samples were activated (positive with anti-HLA-DR and IL-2 receptor antibodies) which is significantly higher than remission phase hypertrophic and normotrophic scars, in which positivity was 40 and 38 per cent, respectively. Upon activation, the lesional lymphocytes release several cytokines, locally and transiently, that interact with specific receptors in response to different stimulation. Central to the immune hypothesis of hypertrophic scars is that some of the T-cell lymphokines act on keratinocytes, fibroblasts and other cell types to induce changes characteristic of these scars. The presence and close proximity of activated T lymphocytes and antigen-presenting cells of various phenotypes in both the epidermis and dermis of hypertrophic tissues provides strong circumstantial evidence of a local immune response. However, the manner in which T cells achieve and maintain their activated state in hypertrophic tissues in not yet known, and both antigen-dependent and independent mechanisms may contribute.     

Dog-ears: a useful artifice in the closure of extensive wounds

BACKGROUND: Wounds too extensive to permit primary repair by suturing can be closed using a skin graft or skin flap and the choice of method depends on a series of factors. Practice and personal experience play a role, as well as the characteristics of the lesion and its site. Each case poses special problems, so it is not possible to establish firm rules. OBJECTIVE: To present a surgical technique for the closure of a circular defect located on the dorsum of the foot, which resulted from the extirpation of a melanoma by surgery. METHODS: In this case we used a mixed procedure consisting of skin flaps and a double full-thickness skin graft. For this operation we used dog-ears resulting from the circular exeresis performed for the extirpation of the tumour. RESULTS: The reconstructive results were good and there were no postoperative complications. CONCLUSIONS: We consider this procedure particularly suitable for certain anatomical sites, such as the dorsum of the foot, where the skin is less elastic and thinner; and for patients who are not willing to accept skin removal from other sites or for flaps to be made with more invasive operations and more constructed scars.     

Breast cancer early diagnosis experience in Florence: can a self referral policy achieve the results of service screening?

STUDY OBJECTIVE--To assess the impact of a breast clinic on a specific target population and evaluate early diagnosis performance indicators for breast cancer in the presence of a self referral policy. DESIGN--Women living in Florence between 1980 and 1989 who had undergone mammography at a self referral breast clinic were studied. Main outcome measures were the use of mammography in relation to age, symptoms, and the interval between two subsequent tests, and early diagnosis performance indicators were the detection rate (DR), the prevalence/incidence ratio, and the proportion of early detected cancers. Performance indicators were compared with those from formal screening programmes. SETTING--Florence, Italy. PATIENTS--All mammograms performed at the clinic from 1980-89 in 40-69 year old women living in Florence were examined (n = 42,226). Records included the date of birth and of the examination, the reason for testing (asymptomatic/presence of pain/presence of symptoms other than pain), and the TNM classification for breast cancer cases. MAIN RESULTS--The total number of mammograms performed per annum increased by 70% over the decade, but much of this was routine repeat mammography (54.1% in 1989). Rates of first examinations in asymptomatic women increased in the second half of the decade from 17 per 1000 in 1985 to 31 per 1000 in 1989. Mammographic coverage decreased with increasing age from 12.6% in 40-49 year olds to 6.0% in 60-69 years old. Performance indicators of the activity in asymptomatic women were comparable with those expected in service screening. The proportion of not advanced cancers detected in asymptomatic women was 62.3% with a DR of 5.3 per 1000, and the average prevalence/incidence ratio was 2.9. CONCLUSIONS--High quality mammography performed in a breast clinic in self referred asymptomatic women can achieve as good results as a formal invitation screening service. Only a few of these women will benefit, but those who do are likely to be younger (40-49 year old women).     

Age-related changes in the turnover rates of D1-dopamine receptors in the retina and in distinct areas of the rat brain

The steady-state density and the turnover rates of D₁-dopamine receptors were investigated in the striatum, nucleus accumbens, substantia nigra, and retina of adult (3-month-old) and aged (23-month-old) rats. The turnover rates were measured by monitoring the repopulation kinetics of D₁-dopamine receptors labeled with [³H]-SCH 23390 after the irreversible inactivation induced by a single dose of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 10 mg/kg, s.c.). In all the neural tissues examined, the repopulation of D₁ dopamine receptors could be adequately described by a theoretical model that assumes a constant rate of receptor production (i.e. zero order) and a rate of degradation that is dependent on the receptor density at any time (i.e. first order). The results obtained indicate that the reduction in the density of D₁-dopamine receptors in the striatum, nucleus accumbens and substantia nigra of aged rats is the result of a larger decrease in the receptor production rate (−44 to −60%) than in the receptor degradation rate (−21 to −46%). By contrast, the production rate of D₁-dopamine receptors in the retina of aged rats remains unchanged, whilst the degradation rate is reduced by 25%. This results in an age-related increase in the density of D₁-dopamine receptors in the rat retina.     

Age-related changes in the turnover rates of D1-dopamine receptors in the retina and in distinct areas of the rat brain.

The steady-state density and the turnover rates of D1-dopamine receptors were investigated in the striatum, nucleus accumbens, substantia nigra, and retina of adult (3-month-old) and aged (23-month-old) rats. The turnover rates were measured by monitoring the repopulation kinetics of D1-dopamine receptors labeled with [3H]-SCH 23390 after the irreversible inactivation induced by a single dose of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 10 mg/kg, s.c.). In all the neural tissues examined, the repopulation of D1 dopamine receptors could be adequately described by a theoretical model that assumes a constant rate of receptor production (i.e. zero order) and a rate of degradation that is dependent on the receptor density at any time (i.e. first order). The results obtained indicate that the reduction in the density of D1-dopamine receptors in the striatum, nucleus accumbens and substantia nigra of aged rats is the result of a larger decrease in the receptor production rate (-44 to -60%) than in the receptor degradation rate (-21 to -46%). By contrast, the production rate of D1-dopamine receptors in the retina of aged rats remains unchanged, whilst the degradation rate is reduced by 25%. This results in an age-related increase in the density of D1-dopamine receptors in the rat retina.