Search

Aims: To derive low-risk gambling limits using the method developed by Currie et al. (2006) applied to longitudinal data., Design: Secondary analysis of data from the Quinte Longitudinal Study (n = 3054) and Leisure, Lifestyle and Lifecycle Project (n = 809), two independently conducted cohort studies of the natural progression of gambling in Canadian adults., Setting: Community-dwelling adults in Southeastern Ontario and Alberta, Canada., Participants: A total of 3863 adults (50% male; median age = 44) who reported gambling in the past year., Measurements: Gambling behaviours (typical monthly frequency, total expenditure and percentage of income spent on gambling) and harm (experiencing two or more consequences of gambling in the past 12 months) were assessed with the Canadian Problem Gambling Index., Findings: The dose-response relationship was comparable in both studies for frequency of gambling (days per month), total expenditure and percentage of household income spent on gambling (area under the curve values ranged from 0.66 to 0.74). Based on the optimal sensitivity and specificity values, the low-risk gambling cut-offs were eight times per month, $75CAN total per month and 1.7% of income spent on gambling. Gamblers who exceeded any of these limits at time 1 were approximately four times more likely to report harm at time 2 [95% confidence interval (CI) = 2.9-6.6]., Conclusions: Longitudinal data in Canada suggest low-risk gambling thresholds of eight times per month, $75CAN total per month and 1.7% of income spent on gambling, all of which are higher than previously derived limits from cross-sectional data. Gamblers who exceed any of the three low-risk limits are four times more likely to experience future harm than those who do not., (© 2017 Society for the Study of Addiction.)

Androgen deprivation therapy (ADT) provides palliation for most patients with advanced prostate cancer (CaP); however, greater than 80% subsequently fail ADT. ADT has been indicated to induce an acute but transient destabilization of the prostate vasculature in animal models and humans. Human re-hydrated lyophilized platelets (hRL-P) were investigated as a prototype for therapeutic agents designed to target selectively the tumour-associated vasculature in CaP. The ability of hRL-P to bind the perturbed endothelial cells was tested using thrombin- and ADP-activated human umbilical vein endothelial cells (HUVEC), as well as primary xenografts of human prostate tissue undergoing acute vascular involution in response to ADT. hRL-P adhered to activated HUVEC in a dose-responsive manner. Systemically administered hRL-P, and hRL-P loaded with super-paramagnetic iron oxide (SPIO) nanoparticles, selectively targeted the ADT-damaged human microvasculature in primary xenografts of human prostate tissue. This study demonstrated that hRL-P pre-loaded with chemo-therapeutics or nanoparticles could provide a new paradigm for therapeutic modalities to prevent the rebound/increase in prostate vasculature after ADT, inhibiting the transition to castration-recurrent growth., (© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Aims: To assess the impact of gambling above the low-risk gambling limits developed by Currie et al. (2006) on future harm. To identify demographic, behavioural, clinical and environmental factors that predict the shift from low- to high-risk gambling habits over time., Design: Longitudinal cohort study of gambling habits in community-dwelling adults., Setting: Alberta, Canada., Participants: A total of 809 adult gamblers who completed the time 1 and time 2 assessments separated by a 14-month interval., Measurements: Low-risk gambling limits were defined as gambling no more than three times per month, spending no more than CAN$1000 per year on gambling and spending less than 1% of gross income on gambling. Gambling habits, harm from gambling and gambler characteristics were assessed by the Canadian Problem Gambling Index. Ancillary measures of substance abuse, gambling environment, major depression, impulsivity and personality traits assessed the influence of other risk factors on the escalation of gambling intensity., Findings: Gamblers classified as low risk at time 1 and shifted into high-risk gambling by time 2 were two to three times more likely to experience harm compared to gamblers who remained low risk at both assessments. Factors associated with the shift from low- to high-risk gambling behaviour from time 1 to time 2 included male gender, tobacco use, older age, having less education, having friends who gamble and playing electronic gaming machines., Conclusions: An increase in the intensity of gambling behaviour is associated with greater likelihood of future gambling related harm in adults., (© 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.)

Breast cancers increase glucose uptake by increasing expression of the facilitative glucose transporters (GLUTs), mainly GLUT1. However, little is known about the relationship between GLUT1 expression and malignant potential in breast cancer. In this study, expression and subcellular localization of GLUT1 was analysed in vivo in breast cancer tissue specimens with differing malignant potential, based on the Scarff-Bloom-Richardson (SBRI, II, III) histological grading system, and in vitro in the breast cancer cell lines, MDA-MB-468 and MCF-7, and in MDA-MB-468 cells grown as xenografts in nude athymic BALB/c male mice. In situ hybridization analyses demonstrated similar levels of GLUT1 mRNA expression in tissue sections from breast cancers of all histological grades. However, GLUT1 protein was expressed at higher levels in grade SBRII cancer, compared with SBRI and SBRIII, and associated with the expression of the proliferation marker PCNA. Immunolocalization analyses in SBRII cancers demonstrated a preferential localization of GLUT1 to the portions of the cellular membrane that faced neighbouring cells and formed 'canaliculi-like structures', that we hypothesize could have a potential role as 'nutritional channels'. A similar pattern of GLUT1 localization was observed in confluent cultures of MDA-MB-468 and MCF-7, and in MDA-MB-468 cells grown as xenografts, but not in the normal breast epithelial cell line HMEC. However, no relationship between GLUT1 expression and malignant potential of human breast cancer was observed. Preferential subcellular localization of GLUT1 could represent a physiological adaptation of a subset of breast cancer cells that form infiltrative tumours with a nodular growth pattern and that therefore need a major diffusion of glucose from blood vessels.

Objective: To describe the clinical, laboratory, radiologic, and histopathologic features of methotrexate (MTX)-induced lung injury in a combined cohort of selected patients with rheumatoid arthritis (RA) and all cases reported in the English-language literature., Methods: Retrospective combined cohort review and abstraction from the medical literature. Case reports were obtained from 6 centers that had 4 or more cases of potential MTX lung injury per site. RA patients who were seen between 1981 and 1993 and who satisfied predetermined criteria for the presence of MTX lung injury were identified., Results: Twenty-seven patients satisfied the criteria for definite MTX lung injury, and 2 for probable MTX lung injury. Predominant clinical features of MTX lung injury included shortness of breath in 27 patients (93.1%), which was present for 23.5 +/- 22.3 days (mean +/- SD), cough in 24 (82.8%), present for 26.9 +/- 28.5 days, and fever in 20 (69.0%), present for 10.4 +/- 12.8 days. Five patients (17.2%) died, compared with 12 of 68 (17.6%) reported in the medical literature. Four of the 6 patients who were re-treated with MTX after an initial pulmonary event developed recurrent lung toxicity, resulting in 2 deaths, compared with a recurrence rate of 3 of 6 in the literature., Conclusion: MTX lung injury is most often a subacute process, in which symptoms are commonly present for several weeks before diagnosis. Approximately 50% of the cases are diagnosed within 32 weeks from initiation of MTX treatment. A patient who recovers from MTX lung injury should not be re-treated. Earlier recognition and drug withdrawal may avoid the serious and sometimes fatal outcome that has been observed in this and other studies.

Patients with Crohn's disease (CD, n = 61) and ulcerative colitis (UC, n = 24) were studied using an interview and a series of percept-genetic tests describing anxiety, defensive strategies, and the self-image. Attention was specifically directed at a subgroup of CD (n = 15) with its inflammation limited to the colon (colon Crohn, CC). There was also a control group (n = 43). CC had more immature parent relations than the other groups. They were more childishly concrete and more alexithymic. While CC differ from other Crohn patients in many respects, the real cleft opens up with regard to UC, in spite of location of their illness. CC patients obviously have a psychological profile of their own.

1. The metabolism of granisetron was investigated in human liver microsomes to identify the specific forms of cytochrome P450 responsible. 2. 7-hydroxy and 9'-desmethyl granisetron were identified as the major products of metabolism following incubation of granisetron with human liver microsomes. At low, clinically relevant, concentrations of granisetron the 7-hydroxy metabolite predominated. Rates of granisetron 7-hydroxylation varied over 100-fold in the human livers investigated. 3. Enzyme kinetics demonstrated the involvement of at least two enzymes contributing to the 7-hydroxylation of granisetron, one of which was a high affinity component with a Km of 4 microM. A single, low affinity, enzyme was responsible for the 9'-desmethylation of granisetron. 4. Granisetron caused no inhibition of any of the cytochrome P450 activities investigated (CYP1A2, CYP2A6, CYP2B6, CYP2C9/8, CYP2C19, CYP2D6, CYP2E1 and CYP3A), at concentrations up to 250 microM. 5. Studies using chemical inhibitors selective for individual P450 enzymes indicated the involvement of cytochrome P450 3A (CYP3A), both pathways of granisetron metabolism being very sensitive to ketoconazole inhibition. Correlation data were consistent with the role of CYP3A3/4 in granisetron 9'-desmethylation but indicated that a different enzyme was involved in the 7-hydroxylation.

We describe two cases of hard metal pulmonary disease (one fatal) in workers employed in the same area of a metal coating plant using the detonation gun process for applying a durable metal surface to metal parts. In this form of welding, a mixture of powdered metals, including tungsten carbide and cobalt, is heated by ignition of a flammable gas and propelled from the end of the "gun" at high temperature and velocity to form a welded metal coating. This process is done in an enclosed chamber and with each application, large volumes of fine aerosols are created. Inhalation exposure to hard metal may occur during the mounting and removal of the metal parts between applications, in spite of engineering controls and industrial hygiene surveillance. One of the cases presented with minimal chest x-ray abnormalities and an obstructive pattern on pulmonary function testing, although subsequent open lung biopsy showed diffuse interstitial pulmonary fibrosis. The fact that two cases of hard metal pulmonary interstitial disease occurred where thorough exposure control procedures and a surveillance program for cobalt were in place may indicate the need for revisions of the current technology used when hard metal is applied in the detonation gun process.

Five of nine active tandem mill operators exposed at work to aerosolized hydrocarbon mist were referred for evaluation of respiratory complaints. The worker with the longest exposure had reduced lung volumes; he was admitted to the hospital for detailed study. Exercise studies revealed work load limited by ventilation and arterial oxygen desaturation. Flexible fiberoptic bronchoscopy with bronchoalveolar lavage and transbronchial biopsy revealed evidence of lipoid pneumonia. Assessment of the mill revealed levels of respirable oil mist by personal samplers throughout the area far below the currently accepted standard of 5 mg/M3. These findings confirm a 20-year-old hypothesis of J.G. Jones regarding the hazard of oil mist in this industrial setting.

Prediction of suicides was made on the basis of 99 psychiatric patients included in a study of anti-depressive therapy during 1961-63. These patients were followed up until 31 December 1984. Eight of them committed suicide. The prediction was based on two test methods, the Serial Colour-Word Test (CWT), which registers style of adaptation to a conflicting situation, and the Meta-Contrast Technique (MCT), where incongruous or threatening stimulation is introduced by degrees into neutral pictures and various defense misrepresentations of the threat are spotted. Both tests could predict suicide, but MCT was most successful. The sensitivity of the test was 0.80 and the specificity 0.75. The main risk symptom appeared to be depressive retardation together with lack of functional defensive structures.

Thirty neurotic outpatients suffering from pronounced anxiety were studied and after a therapeutic period of 1.5 to 2 years. The patients were described by means of rating scales and two perceptgenetic methods, the Meta-Contrast Technique and the Afterimage Experiment. It was possible to associate original status with improvement or non-improvement of manifest anxiety. The most positive prognostic sign was sensitivity to marginal (inner and outer) cues, whereas the most negative signs were pre-psychotic discontinuities, projection, and lack of defence mechanisms.

A monoclonal antibody, which recognizes a cross-reacting idiotypic determinant present on human cold-reactive autoantibodies with anti-I or anti-i binding activity, has been found to specifically inhibit the cold agglutination of red cells. This suggests that an epitope close to the binding site of such autoantibodies is being recognized. The antibody has been used to identify tumour cells in the blood of three patients with cold haemagglutinin disease, and to analyse the heterogeneous nature of the neoplastic B-cell clone present in the bone marrow of one of the patients. Using S-phase analysis, it was found that cell proliferation was occurring in the bone marrow but not in the blood, and that the major proliferating population was that of lymphoplasmacytoid cells containing large vesicular inclusions of idiotypic IgM. It has also been possible to locate normal B-cells which are recognized by the anti-idiotypic antibody. Such cells have been found throughout the normal adult lymphoid tissue where they account for 2.9-10.8% of the B lymphocyte population. They are also present in fetal spleen at 15 weeks gestation, indicating that immunoglobulins bearing this sequence form part of the immature B-cell repertoire.

Criticizes three replications of experiments on subliminal perception for not being true replications. The lack of subliminal effects in the replications could very well be explained by a change from sensitive to insensitive instruments of measurement.