The Cedar Project: exploring determinants of psychological distress among young Indigenous people who use drugs in three Canadian cities.

BACKGROUND: Mental health and wellbeing, including addressing impacts of historical trauma and substance use among young people, has been identified as a key priority by Indigenous communities and leaders across Canada and globally. Yet, research to understand mental health among young Indigenous people who have used drugs is limited. AIMS: To examine longitudinal risk and strengths-based factors associated with psychological distress among young Indigenous people who use drugs. METHOD: The Cedar Project is an ongoing cohort study involving young Indigenous people who use drugs in Vancouver, Prince George, and Chase, British Columbia, Canada. This study included participants who completed the Symptom Checklist-90-Revised, returned for follow-up between 2010 and 2012, and completed the Childhood Trauma Questionnaire. Adjusted linear mixed-effects models estimated effects of study variables on changes in area T-scores of psychological distress. RESULTS: Of 202 eligible participants, 53% were women and the mean age was 28 years. Among men, childhood maltreatment (emotional abuse, physical abuse, sexual abuse, physical neglect), any drug use, blackouts from drinking, and sex work were associated with increased distress. Among women, childhood maltreatment (emotional abuse, physical abuse, physical neglect), blackouts from drinking, and sexual assault were associated with increased distress, while having attempted to quit using drugs was associated with reduced distress. Marginal associations were observed between speaking their traditional language and living by traditional culture with lower distress among men. CONCLUSION: Culturally safe mental wellness interventions are urgently needed to address childhood trauma and harmful coping strategies that exacerbate distress among young Indigenous people who use drugs.

Allogeneic gene-modified tumour cells in metastatic kidney cancer. Report II.

In a limited study, comprising only ten patients, we have previously reported that allogeneic irradiated RCC-cell-line cells, engineered to produce IL-2 (ACHN-IL-2), admixed with autologous metastatic formalin-treated tumour cells were used to vaccinate MRCC patients in progression of disease and also receiving IL-2 immunotherapy. The cells, admixed to autologous TC, were administered subcutaneously. We now report an extended study on thirty patients and one hundred thirty-one controls. Patients received 4-20 injections (mean 10 +/- 4), containing an average of 92 x 10(6) +/- 45 x 10(6) ACHN-IL-2 transfected cells (a minimum of 25 x 10(6), and a maximum of 200 x 10(6)). Autologous TC, admixed to allogeneic, were also administered by 4-16 s.c. injections (mean 7 +/- 3), i.e. a total of 12 x 10(6)-160 x 10(6) cells. Vaccination was administered during 73-1451 (307 +/- 316) days, and the follow-up continued for 1122 +/- 1240 days (106-5137). Throughout this period, the patients continued receiving the previously set immunotherapy treatment. No adverse side effects related to the treatment were noticed. One complete and four partial tumour responses were observed, as well as nine cases of stable disease. Thirteen patients died in the treated group (43%) and 63 (44%) in the control group. Responding patients resumed progression in 4-11 months and died 18 and 36 months after beginning the vaccine therapy. The Gehan Wilcoxon's test showed a significantly (P < 0.01) better survival in the vaccinated patients compared to that of the controls. Thus, we confirm, in an increased number of patients and an extensive follow-up, that our vaccination protocol is safe, devoid of adverse side effects, and promising.

Allogeneic gene-modified tumour cells in metastatic kidney cancer. Preliminary report.

An allogeneic irradiated RCC cell line, engineered to produce IL-2 (ACHN-IL-2), admixed with autologous metastatic formalin-treated tumour cells, was used to vaccinate ten MRCC patients in progression of disease in spite of IL-2 immunotherapy. The cells were administered subcutaneously and/or intra-tumourally. Sixty-four MRCC patients in progressive disease, not treated by vaccination but receiving similar IL-2 immunotherapy, were considered as the control group. Patients received 4-16 injections (mean 9 +/- 4), containing an average of 10.6 x 10(7) +/- 7.7 x 10(7) ACHN-IL-2-transfected cells (a minimum of 4 x 10(7), and a maximum of 31 x 10(7)). Four patients also received intra-tumour injections. Vaccination was administered during 30-418 days, and the follow-up continued for 649 +/- 353 days (190-1342). Throughout this period, the patients continued receiving the previously set immunotherapy treatment. No adverse side effects related to the treatment were observed. One complete and one partial tumour response were observed, as well as two stable and one no-relapse disease. All but one patient died. Responding patients resumed progression in 4-11 months and died 18 and 36 months after beginning the vaccine therapy. In spite of the small number of treated patients, Wilcoxon's test showed a significant (P < 0.05) improvement of the survival in the vaccinated group compared to that of the control. The described vaccination protocol seems safe, devoid of adverse side effects and promising. It warrants further investigation.

Complement components and fibrinogen: correlations and association with previous myocardial infarction.

Serum complement levels have been found to be predictive of myocardial infarction up to 4 years before the acute event. To assess whether they are a marker of a hypercoagulable state, the serum or plasma levels of C3, C4, C3a, C4a, C1 inactivator, antithrombin III, protein S, protein C, fibrinogen and tissue plasminogen activator were measured in 31 patients with previous myocardial infarction and 33 controls (all males, 40-60 years old). C3, C4 and fibrinogen (which share the common characteristic of being acute phase proteins) were correlated and were associated with previous myocardial infarction, although this association persisted only for C4 in multivariate analysis. None of the coagulative variables directly involved in the complement system differed significantly in the two groups.

Blindness influences the growth of institutionalized prepubertal subjects.

To investigate if blindness influences the growth rate of young subjects we measured height and weight of 71 prepubertal blind subjects (33 females and 38 males) aged 7-10 yr, in Tanner stage one puberty, living at the Institute "Martuscelli" for young blind individuals in Naples, Italy. They were divided into two groups: group 1 consisting of 27 subjects (14 females and 13 males) with total blindness; group 2 consisting of 44 subjects (20 females and 24 males) having only a light perception. The distribution in quintiles of their height and weight was compared by X2 test for trend to that of an age-matched large population (7902 subjects: 3808 females and 4094 males) of primary school from the same district. A stature significantly lower than controls was evidenced in both group 1 (p = 0.0006) and in group 2 (p = 0.008). When the comparison is performed taking into account the sex of subjects, the girls of both group 1 (p = 0.0014) and group 2 (p = 0.0004) show a stature significantly lower than female controls, whereas the stature of boys of both groups did not differ from that of male controls. No statistically significant differences in weight distribution were found between controls and either group 1 and group 2. Our results suggest that total or partial blindness could influence negatively the growth of prepubertal subjects; in particular it can cause short stature or growth delay especially in female sex.

Methodological problems of direct bioluminescent ATP assay in platelets and erythrocytes.

Direct bioluminescent ATP determination in platelets and erythrocytes involves the study of different parameters which are discussed here. Some parameters are linked to the bioluminescent reaction and to the analyte (ATP); others have regard to the biological matrix. The composition of bioluminescent reagents and the preparation and conservation of the ATP standard, also in the presence of excipients, are among the first given. Matrix problems involve cell characteristics related to age and form, lysis resistance and the possible formation of aggregates (platelets) that may inhibit the complete release of ATP. For these reasons we used the most efficient ATP release agent with the lowest inhibitory effect on luciferase. The data obtained correlate well with a bioluminescent method requiring extraction with ethanol/EDTA, and therefore more time, for ATP determination in platelets and erythrocytes.

Plasma thyrotropin, thyroxine, triiodothyronine, free thyroxine, free triiodothyronine, and cortisol levels in blind prepubertal boys.

Findings on thyroid function in blind subjects are lacking. The aim of this study was to investigate the thyroid hormonal pattern in prepubertal blind subjects. Six healthy and 8 blind males, aged 7-10 yr, in Tanner stage one puberty, living at Institute "Martuscelli" for blind young subjects, Napoli, Italy, were studied. Each had a TRH (200 micrograms) test at 08:00 h after nocturnal rest. Plasma TSH, T4, T3, free T4(FT4), free T3(FT3) and cortisol (F) were measured by RIA. Our blind subjects show levels of TSH (basal values and absolute peak after TRH), T4, T3 and F normal but FT4 levels significantly higher than controls (39 pg/ml +/- 4.7 vs 12 +/- 0.6, p less than 0.001; 14 pg/ml +/- 1.3 vs 4.7 +/- 0.2, p less than 0.001, respectively). Our results, similar to those found in some patients with euthyroid hyperthyroxinemia, suggest that the prolonged inability to receive light signal could influence the metabolism of thyroid hormones and/or cause a tissue resistance to their action, even if this hypothesis must be verified by future more extensive investigations.

Oral anticoagulant therapy control: evidence that INR expression improves the inter-laboratory comparability of results--the Bologna oral anticoagulant control exercise.

The aims of the present study were: 1) interlaboratory normalization of prothrombin time (PT) testing for anticoagulant therapy control through calibration of customary thromboplastins against international reference materials, and 2) "on field" validation of the advantages offered by expression of results as International Normalized Ratio (INR) as opposed to percentage activity. PT tests were carried out over 8 days on the same normal subjects (16) and patients on oral anticoagulants (48) in the 9 laboratories of the Bologna area. The use of customary thromboplastins and coagulometers was maintained in all labs throughout the study. The main results were: 1) the interlaboratory CV of the prothrombin ratios obtained for each sample with all customary thromboplastins (5 different brands) was 15%, but was reduced to levels of 5.8 to 8.9 when using constant thromboplastin brands and batches; 2) the International Sensitivity Index (ISI) values obtained in the different labs were only slightly influenced by the use of different coagulometers; 3) comparable ISI values were obtained through direct calibration with the international reference material and through intermediate calibration with a locally selected standard; 4) use of INR values instead of percentage activity greatly reduced interlaboratory variability and significantly improved uniformity of anticoagulation level measurements, thus reducing the possibility of erroneous prescriptions. The Bologna exercise is therefore of educational value for laboratory and community doctors of the area in understanding and accepting the INR system.

Influence of blindness on plasma luteinizing hormone, follicle-stimulating hormone, prolactin, and testosterone levels in prepubertal boys.

The aim of this study was to determine if changes in LH, FSH, PRL, and testosterone (T) secretion occur in blind prepubertal boys. Eight blind and six normal boys, aged 7-10 yr, living at an institute for blind subjects in Naples, Italy, were studied. Each had a combined GnRH (100 micrograms) and TRH (200 micrograms) test at 0800 h after nocturnal rest. Plasma LH, FSH, PRL, and T levels were measured by RIA. The blind boys had basal plasma LH, FSH, and T levels significantly lower than those in the normal boys (P less than 0.01 for all three); plasma PRL basal levels were similar to those in the normal boys. The blind boys, moreover, had lower peak LH, FSH, and PRL (P less than 0.01 for all three peaks) levels in response to GnRH-TRH. Our results, similar to those found by others in patients with delayed puberty or with hypogonadotropic hypogonadism, suggest that light stimuli influence neuroendocrine-gonadal activity in humans, as in other mammals; and in blind prepubertal boys, impaired hormone secretion could cause a delay of pubertal development or more severe hypogonadism.

Effect of eosinophilia on the heterogeneity of the anticoagulant response to heparin in haemodialysis patients.

The anticoagulant response to heparin was determined, during haemodialysis, in a group of seven patients with eosinophilia and in a control group. The heparin half-life was similar in the two groups, but the heparin effect index was lower in patients with eosinophilia. The dose-response curve showed a reduced sensitivity to heparin in patients with eosinophilia. In patients with eosinophilia a significant reduction in eosinophil count was observed during cuprophan dialysis, but not during polyacrylonitrile dialysis. The hyposensitivity to heparin might be related to eosinophil degranulation, during cuprophan dialysis, with release of a major basic protein that neutralises heparin.

Interference of glucosamine and other aminosugars on blast transformation.

The effect of exogenous glucosamine and other aminosugars on the incorporation of 3H-leucine 3H-uridine and 3H-thymidine into mitogen induced lymphocytes was studied. D-glucosamine D-galactosamine and D-mannosamine inhibit the incorporation of these precursors into protein. RNA and DNA of blast cells. Glucose and pyruvate did not reverse this inhibition. Glucosamine - 6P, acetylglucosamine and acetylglucosamine and have shown a considerably lower inhibition in the uptake of these labeled precursors.

Lactate dehydrogenase isoenzymes in benign and malignant prostatic tissues.

84 prostatic tissue specimens consisted of 62 benign hyperplasias and 22 carcinomas have been studied regarding Lactate dehydrogenase isoenzymes pattern. A consistent and definite shift of the LDH5 : LDH1 ratio has been found in carcinomas respect to benign hyperplasias.

[Variation of the TG lymphocyte subpopulation in the aged]. / Variazioni della subpopolazione linfocitaria TG nei soggetti anziani.

Peripheral blood from 20 healthy subjects of whom 10 were young (15 - 30) and 10 aging (73 - 85) was examined for the proportions of TG lymphocyte population by two different methods TG cells proportions were significantly (P 0.001) increased in aging subjects when compared with the young subjects.

Anaerobic glycolysis and lymphocytes blastization.

The role of enhanced anaerobic glycolysis in the transformation of human peripheral lymphocytes induced by mitogens has been investigated. The DNA syntesis, lactate production and increment of lactate dehydrogenase isoenzyme 5 (LDH5) have been studied. In this paper we present detailed kinetic studies, which indicate that LDH5 increment correlates closely with rapid synthetic activity and is not morely part of an overall increase in enzymatic activities.

[Changes in lactate dehydrogenase isoenzyme patterns of human lymphocytes before and after blast formation]. / Variazione degli isoenzimi della lattico deidrogenasi nei linfociti umani prima e dopo blastizzazione.

The lactate dehydrogenase isoenzyme pattern of human lymphocitic cells has been determined in several people before and after stimulation by mitogenic lectins at different times after the start of the culture. A very significant change take place in the LDH 5 which can reach a greater concentration towards the other isoenzymes at the 72 h from the mitogenic stimulus, even if it starts from a smaller concentration.