Duration of opiate exposure as a determinant of arterial stiffness and vascular age in male opiate dependence: a longitudinal study.

WHAT IS KNOWN AND OBJECTIVE: Despite intriguing initial and associational studies, there remains little research on opiate-related arterial dysfunction and no longitudinal studies. As opiates act potently via P16INK4A/CDKN2A identified on GWAS screens, and as arterial ageing is a surrogate for organismal ageing, this area is of general concern. METHODS: Thirty-eight male controls compared with 198 opiate-dependent male patients were studied longitudinally using SphygmoCor pulse wave analysis. RESULTS AND DISCUSSION: Healthy male controls and opiate-dependent male patients were studied on 125 and 625 occasions, respectively. The mean (±SEM) chronological age (CA) was 42·32 ± 2·22 for controls and 35·04 ± 0·61 for opiate dependent (P = 0·0029). 94·4% and 13·2% smoked tobacco (P < 0·0001). Controlling for BMI and CA, there was a significant time: addictive status interaction for vascular age (P = 0·0127) and central augmentation pressure and index (both P < 0·02). Central systolic and diastolic pressures were also worse over time by addictive status (P < 0·005). At repeated measures multiple regression adjusted for classical risk factors, opiate dose and duration of opiate use remained significant. The dose-duration effect was significant in 8 terms and by time. A similar model quadratic in opiate duration was more powerfully predictive, suggesting the salience of the duration of opiate treatment (AIC 191·6898 and 191·5966, P = 0·0116). WHAT IS NEW AND CONCLUSION: Data suggest that increased length of opiate dependence is associated with advanced vascular stiffness and ageing and are therefore consistent with accelerated ageing organismally. The superiority of power functions of the opiate duration of exposure underscores the significance of the duration of treatment and of putative senescence induction.

Dentition of addiction in Queensland: poor dental status and major contributing drugs.

BACKGROUND: Although it is said that drug addiction is associated with poor dental health, there is little research in this area. In particular, there is little work comparing the effects of the different drugs of addiction. METHODS: A cross-sectional patient survey of dental health was undertaken in a family practice comparing opiate and other drug addicts (DA) with non-addicts (NA). The age range was restricted to 19-45 years. Damaged teeth were counted and a semi-quantitative score applied to severity to allow the calculation of an overall dental index. A medical review only was undertaken; recognized dental diagnostic criteria were not applied. RESULTS: There were 233 and 47 respondents in the DA and NA groups, respectively. The mean ages and gender ratios were similar in both groups. DA used more addictive drugs than NA (all P < 0.001). DA had more absent, traumatized, major cavitated and extracted teeth (all P < 0.05). Addicts had a worse severity index (P < 0.02) and dental index (13.13 + 24.00 vs. 4.74 +/- 16.03; P < 0.005). Furthermore, dental pathology developed in DA at younger ages than in NA with 56.8% vs. 5.4% of patients younger than 38 years having dental indices more than 10 respectively (OR = 22.98, 95% CI = 5.57-200.65, P < 0.0000001). At multivariate analysis age, gender, and dose and/or duration of tobacco, methadone, morphine, and alcohol were significantly associated with these pathologies. CONCLUSION: These data are consistent with published dental reports and basic science information that drug addiction has a deleterious effect on dental health, that in addiction this effect is rapid and severe, and that tobacco, methadone, morphine and alcohol contribute importantly to these changes.

Serum ionic dysequilibria in clinical opioid dependence: Cross-sectional and longitudinal studies.

INTRODUCTION: Despite an increasing awareness that the activity of excitable membranes is determined by the underlying ionic gradients across them, and their importance in drug dependency, we were not able to identify any reports of comparing the electrolyte composition of opioid-dependent and non-addicted controls. METHODS: Linear regression was used to compare clinical pathology blood results taken from 2699 opioid-dependent patients (ODP) and 5307 medical control (MC) patients on a total of 21,734 occasions for the period 1995-2015. The presence of a hepatitis C antibody test was used to separate OPD and MC patients. RESULTS: The mean age among ODP and MC was 33.51 ± 0.16 and 37.99 ± 0.23 years, respectively ( p < 0.0001). The groups were 71.5% and 54.2% male ( p < 0.0001). Drug use in this cohort has been reported previously. Analysis of sodium, haemoglobin and albumin were used to exclude marked effects of haemodilution/haemoconcentration. Repeated measures linear regression against age and time showed depressed levels of bicarbonate ( p < 0.0001) and potassium ( p < 0.05) and elevated levels of chloride ( p < 0.025) and anions ( p < 0.01) in ODP in both sexes. Multiple regression in mixed-effects models showed that these effects were all worse in females ( p = 0.0001). CONCLUSION: This data shows that opioid dependence is associated with significant changes in chloride, potassium, bicarbonate and anions in both sexes, and worse in females. This likely has implications for the electrophysiological properties of excitable membranes. It is consistent with the reported impairment of potassium-chloride exchangers in opioid dependence. Explication of the mechanisms responsible must await further studies.

Hepatic iron in the control of iron absorption in a rat liver transplantation model.

Rat liver transplantation was utilized to study the effect of hepatic iron on the control of iron absorption. Six iron-loaded and six normal livers were transplanted into normal or iron-loaded animals. Iron absorption was measured pretransplant and 10 days posttransplant by total-body counting (59Fe). The animals were loaded with oral carbonyl iron to produce a predominantly parenchymal hepatic iron distribution and with parenteral iron dextran to produce a predominantly reticuloendothelial iron distribution. The carbonyl iron-loaded livers contained 175 +/- 6.6, the iron dextran livers 180 +/- 41, and the normal livers 6.6 +/- 2.8 mumol FE/g dry wt. Iron absorption was unchanged by the insertion of normal livers into normal animals. The transplantation of carbonyl iron-loaded livers into normal animals caused a marked decrease in iron absorption posttransplant from 7.2 +/- 0.9% to 0.3 +/- 0.4% (P less than .001) posttransplant. Neither the transplantation of iron dextran-loaded livers into normal animals nor the transplantation of normal livers into iron-loaded animals significantly altered iron absorption at 10 days posttransplant. These results are consistent with the hypothesis that hepatocyte iron stores are a major determining factor controlling iron absorption.

An intriguing association between dental and mental pathology in addicted and control subjects: a cross-sectional survey.

BACKGROUND: Recent clinical studies suggest that substance use may be associated with an acceleration of the ageing process, possibly related to a deficit of stem cell number or function. As this clinic had access to both medical and drug dependent patients, we tested the hypothesis that there may be an association between previously identified deficits. METHODS: A cross-sectional survey was performed looking at both dental and mental dysfunction. Both a dental index (DI) and a mental index (MI) were defined as previously described and utilised as summary measures of such pathology. FINDINGS: From 249 substance use disorder (SUD) and 134 general medical controls (N-SUD), 248 and 91 patients were selected with ages less than 57 years as the primary focus of analysis. The mean (+/- S.D.) ages (32.59 +/- 7.98 vs 35.65 +/- 15.45 years) were similar. The DI was found to correlate with the MI in a significant manner in SUD (R = 0.14, p = 0.03), N-SUD (R = 0.27, p = 0.009) and in the whole group (R = 0.17, p = 0.001). The (univariate) association of MI with DI (p = 0.019) and DI with MI (p = 0.0037) remained highly significant at multivariate regression after adjustment for psychiatric diagnoses and measures of dose-duration exposure to common addictive drugs. The qualitative appearance of the surfaces of best fit for the relationship between age, DI and MI was different in the two groups. CONCLUSIONS: These results suggest that the robust statistical association between dental and mental pathology may be related to common underlying pathophysiological mechanisms such as a progeroid or stem cell deficiency process in clinical addiction.

Psychosocial and treatment correlates of opiate free success in a clinical review of a naltrexone implant program.

BACKGROUND: There is on-going controversy in relation to the efficacy of naltrexone used for the treatment of heroin addiction, and the important covariates of that success. We were also interested to review our experience with two depot forms of implantable naltrexone. METHODS: A retrospective review of patients' charts was undertaken, patients were recalled by telephone and by letter, and urine drug screen samples were collected. Opiate free success (OFS) was the parameter of interest. Three groups were defined. The first two were treated in the previous 12 months and comprised "implant" and "tablet" patients. A third group was "historical" comprising those treated orally in the preceding 12 months. RESULTS: There were 102, 113 and 161 patients in each group respectively. Groups were matched for age, sex, and dose of heroin used, but not financial status or social support. The overall follow-up rate was 82%. The Kaplan Meier 12 month OFS were 82%, 58% and 52% respectively. 12 post-treatment variables were independently associated with treatment retention. In a Cox proportional hazard multivariate model social support, the number of detoxification episodes, post-treatment employment, the use of multiple implant episodes and spiritual belief were significantly related to OFS. CONCLUSION: Consistent with the voluminous international literature clinically useful retention rates can be achieved with naltrexone, which may be improved by implants and particularly serial implants, repeat detoxification, meticulous clinical follow-up, and social support. As depot formulations of naltrexone become increasingly available such results can guide their clinical deployment, improve treatment outcomes, and enlarge the policy options for an exciting non-addictive pharmacotherapy for opiate addiction.

Surgical anatomy of donor extended right trisegmentectomy before orthotopic liver transplantation in children.

Liver transplantation is now accepted as the treatment of choice for children with end stage liver disease. A major constraint has been the shortage of donor organs of appropriate size. The use of reduced size adult organs has partially alleviated this problem but the previous technique employed was limited to a donor:recipient body-weight disparity of not greater than 3:1. Recently a new technique has been described that allows safe transplantation with a donor:recipient weight ratio of greater than 10:1. This should greatly increase the paediatric donor pool. Anatomical landmarks and techniques necessary for donor reduction hepatectomy are described from the dissection of 50 adult cadaveric livers. Variations in all important biliary and vascular structures necessitated adjustments in operative technique.

Rationale for simultaneous carotid endarterectomy and aortocoronary bypass.

Seventy-eight patients were treated for coexistent carotid and coronary stenosis by simultaneous reconstructions. Five patients died (6.4%), one from a stroke contralateral to the carotid reconstruction. Four others suffered a perioperative stroke (total stroke incidence 6.4%). Three myocardial infarctions occurred (3.8%) including one fatal infarct. Analysis of the most recent 36 combined reconstructions indicates that the extramorbidity in this group increased the stroke or death rate for all carotid endarterectomies carried out in the same period by only 1%. Alternatively if these patients had been operated upon by aortocoronary grafting alone the mortality would have increased by 0.1% assuming no neurologic complications. Since these 36 patients had severe carotid stenosis and would have been refused carotid endarterectomy as an isolated procedure the results seem better than would have been achieved by staged operations.