Substance use and other psychiatric disorders in first-degree relatives of opioid-dependent males: a case-controlled study from India

To assess the prevalence of substance use and other psychiatric disorders in first-degree relatives of males with opioid dependence compared to normal controls. DESIGN: Observational, case-control study using family history method. SETTING: A drug addiction treatment centre in northern India. PARTICIPANTS: First-degree relatives of 100 male probands with opioid dependence and no comorbidity (n=493) and those of 50 matched probands from normal population (n=254). Measurement Family interview of probands and family members, using the Family Interview for Genetic Studies. The main outcome measure was relative risk (expressed as odds ratio after controlling for confounding variables using logistic regression) of familial aggregation of psychiatric and substance use disorders. FINDINGS: First-degree relatives of opioid-dependent males were more likely to have a psychiatric disorder than those of normal controls [adjusted odds ratio (OR) 4.47; 95% confidence interval (CI) 1.97-10.11; P<0.001], especially for opioid use disorders in the brothers (adjusted OR 6.55; 95% CI 1.44-29.88; P=0.015) and for alcohol use disorders in the fathers of the probands (adjusted OR 5.64; 95% CI 2.39-13.24; P<0.001). Other disorders (major depression, chronic psychosis and obsessive compulsive disorder) did not have significant aggregation in the first-degree relatives of opioid-dependent subjects. CONCLUSIONS: This study provides further evidence for the higher rates of alcohol and opioid dependence in first-degree relatives of opioid-dependent patients. The exact pattern of this familial aggregation may be influenced by the gender of the relatives and their relation to the proband.     

Visceral leishmaniasis, or kala azar (KA): high incidence of refractoriness to antimony is contributed by anthroponotic transmission via post-KA dermal leishmaniasis

Individuals with visceral leishmaniasis, or kala azar (KA) and individuals with post-KA dermal leishmaniasis (PKDL) are considered to be reservoirs of transmission of Leishmania donovani in India. When intracellular amastigotes were used to assess the natural susceptibility that PKDL isolates and KA isolates have to sodium antimony gluconate (SAG), the mean ED(50) was found to be 12.0+/-2.49 and 11.0+/-1.38 microg/mL, respectively; and there was a significant correlation with the clinical response (r rank=0.99). All KA isolates, as well as a significant proportion (55%) of PKDL isolates from high-endemicity zones, were resistant to SAG. The median ED(50) for SAG-resistant PKDL isolates (20.0 microg/mL) was significantly higher (P<.05) than that for SAG-resistant KA isolates (15.7 microg/mL). SAG-resistant PKDL isolates may contribute to KA's increased refractoriness to SAG, via anthroponotic transmission of SAG-resistant strains.     

Substance‐Abusing Schizophrenics: Do They Self‐Medicate?

In spite of having been formulated nearly two decades back, there is as yet no consensus on the validity of the clinically popular self-medication hypothesis (SMH) of substance use disorders in patients with dual diagnosis. SMH broadly proposes that patients use substances in a non-random fashion so that the psychopharmacologic characteristics of particular substances are used to alleviate a variety of psychiatric symptoms and emotional distress. In order to test the SMH empirically, it was broken down to five sub-hypotheses, which were tested in a group of dual-diagnosis schizophrenia (DDS) patients vis-à-vis a group of only-schizophrenia (S) patients (n = 22 each). The DDS group scored lower than the S group regarding general and some specific psychopathology. The DDS patients ascribed reasons for substance use more often for hedonistic pursuit but also for reduction in symptoms and distress. There was a trend for alcohol to be used more for self-medication purposes compared to opioids and cannabis. The perceived effects of these three substances were significantly different on several symptom/distress dimensions. Finally, there was some degree of "match" between symptom-oriented reasons for use of substances and the effect that was perceived. All of this evidence provides a consistent but modest support for the SMH for "some patients, some substances, and some symptoms." The implications are discussed.     

Tobacco consumption in relation to causes of death in an urban population of north India

Background:

Noncommunicable diseases have become a public heath problem in India concomitant with economic development, leading to increases in tobacco consumption, obesity, and changes in diet and lifestyle. Although observation suggests that tobacco consumption is a major risk factor for deaths due to circulatory, pulmonary, and malignant diseases, such studies are not available from most populations in developing countries.

Subjects and methods:

For the period 1999–2001, we studied the randomly selected records of death of 2222 (1385 men and 837 women) decedents, aged 25–64 years, out of 3034 death records overall from the records at Municipal Corporation, Moradabad. All the families of these deceased could be contacted individually to find out the causes of death, by scientist/doctor administered, informed consented, verbal autopsy questionnaire, completed with the help of the spouse and local treating doctor practicing in the appropriate healthcare region. Social classes and tobacco intakes were assessed by a questionnaire.

Results:

The prevalence of tobacco consumption, including chewing + smoking, were 45% (n = 623) among men and 15% (n = 125) among women decedents. However, smoking was observed in 20% and tobacco chewing in 30% of male decedents, while only 6% of female decedents smoked and 10% chewed tobacco. Social class had no impact on tobacco consumption in men but did influence one subgroup >55 years among women, ie, among those who had the highest tobacco consumption. Tobacco intakes were significantly more common among decedents dying due to circulatory, malignant, and pulmonary diseases, compared with other causes (men 61.1%, 76.6%, pulmonary 77.3% vs 31%, P < 0.001; women 27.5%, 75.9%, pulmonary 24.6% vs 0.42%, P < 0.001) of mortality, respectively. Pulmonary causes included chronic bronchitis and asthma. Circulatory diseases (29.1%, n = 646) including heart attacks (10.0%), stroke (7.8%), valvular heart disease (7.2%, n = 160), sudden cardiac death and inflammatory cardiac disease, each (2.0%, n = 44) were the second most common causes of deaths, after infections (41.1%, n = 915). Malignant neoplasm (5.8%, n = 131), injury (14.0%, n = 313), and miscellaneous causes of deaths, including diabetes mellitus (2.2%, n = 49) were noted in 9.1%, (n = 202) of death records. Cancers of the lung (1.6%), oral cavity (1.5%), liver (1.1%), stomach (0.9%), breast (0.31%), uterus, cervix, and ovary (0.27%) were relatively common causes for deaths due to malignancy.

Conclusions:

This study shows that tobacco consumption appears to be a major contributor to deaths due to circulatory diseases and malignant diseases in India. Social class status had little impact on tobacco consumption in male decedents. Rapid changes in diet and lifestyle, increases in tobacco consumption, and possibly aging of the population, appear to be strongly associated with mortality due to cardiovascular diseases and cancer in this middle-income country.     

Vivo-Morpholino knockdown of αIIb: A novel approach to inhibit thrombocyte function in adult zebrafish

Knockdown of protein function by antisense oligonucleotides has been used to understand the protein function not only in development but also in human diseases. Recently, Vivo-Morpholinos, chemically modified morpholinos which penetrate the cells, have been used in adult experimental animal models to alter the splicing and thereby change the protein expression. Until now, there have been no such studies using Vivo-Morpholinos to evaluate hemostatic function in adult animals. We injected αIIb Vivo-Morpholinos intravenously into adult zebrafish. Thrombocyte function was assayed by time to aggregation assay of the citrated blood, annexin V binding to thrombocytes, and gill bleeding. The thrombocyte functional inhibition occurred in 24 h after αIIb Vivo-Morpholinos injection and reached a maximum in 48 h. However, in 72 h, the inhibition was no longer observed. Reduction of annexin V binding to thrombocytes and increased gill bleeding were observed 48 h after αIIb Vivo-Morpholino injections. The action of the αIIb Vivo-Morpholino was demonstrated by the presence of an alternatively spliced αIIb mRNA and the reduction of αIIb in thrombocytes of fish treated with αIIb Vivo-Morpholino. These results provide the first proof of principle that thrombocyte function can be inhibited by thrombocyte-specific Vivo-Morpholinos in adult zebrafish and presents an approach to knockdown thrombocyte-specific genes to conduct biochemical studies in thrombocytes. This study also provides the first antisense antithrombotic approach to inhibit thrombocyte function in adult zebrafish.     

Simultaneous ST-segment elevation in inferior and precordial leads following ingestion of a lethal dose of desipramine: a novel Brugada-like EKG pattern

The typical Brugada electrocardiographic (EKG) pattern includes ST-segment elevation in the right precordial leads (V1–V3) associated with right bundle branch block (rSR′) like morphology. Recently, a Brugada-like EKG pattern with ST-segment elevation in inferior leads called the “Brugada variant” has been reported. We report a case of simultaneous typical and variant Brugada EKG patterns with ST-segment elevation in the inferior as well as the precordial leads following ingestion of a lethal dose of desipramine.     

Psychosocial morbidity in Cushing disease: a study from India

The main objective of this article is to study the psychosocial profile of patients of Cushing disease (CD) in a developing country setting. Eighteen patients with CD underwent a cross-sectional assessment regarding their socio-demographic and clinical profile, life events, social support, coping, dysfunction, quality of life, and psychiatric morbidity. Twenty-two demographically group-matched healthy participants (free from psychological morbidity) acted as the control group. The CD group had predominance of females (71.5%) with mean age at onset of 20.38 (range 8–38) years, and mean duration of illness of 65.33 (range 4–260) months. Six subjects (i.e., GHQ positive group) scored positive on the General Health Questionnaire-12 giving a psychological morbidity rate of 33.33%, with one having an ICD-10 diagnosis. There was no difference between GHQ positive and GHQ negative groups on number of life events, social support, quality of life and dysfunction. However, GHQ positive group used significantly more of internalizing coping strategies. Psychological morbidity occurs in a significant percentage of patients with CD. Presence of psychological morbidity is associated with internalizing coping strategies.     

Incidental finding of arteria lusoria during transradial coronary catheterization: Significance in interventional cardiology

Arteria lusoria is the most common anomaly of the aortic arch with an incidence of 0.5%–2.5%. It is mostly diagnosed incidentally while performing imaging for evaluation of other unrelated medical conditions. The aberrant right subclavian artery arises beyond the origin of the left subclavian artery from the aortic arch. This results in a complex right‐subclavian‐aortic anatomy which leads to difficulty in transradial coronary angiography. This can lead to prolonged procedure time and increased use of catheters by unaware interventionists. This is even more important if this is encountered in the setting of an acute myocardial infarction. Our review takes into account clinical significance of this uncommon anomaly in the field of interventional cardiology.     

“Hands‐Free” Continuous Echocardiography during Treadmill Exercise Using a Novel Ultrasound Transducer

Background: Echocardiographic imaging using a handheld transducer in conjunction with treadmill exercise testing is commonly used for the diagnosis of coronary artery disease. Motion of the hand and the transducer during peak exercise preclude optimal imaging. To circumvent the limitations of handheld transducers, we developed a low profile transducer (CONTISON) which can be attached to the chest wall for continuous cardiac imaging. Methods and Results: This feasibility study was performed in 10 normal male subjects (28 to 36 years). The ultrasound transducer was placed in the third or fourth intercostal space at the left sternal border to permit imaging of the left ventricle in its short axis. The transducer was interfaced with a commercially available ultrasound machine. The left ventricle was imaged at rest and while subjects exercised according to a standard Bruce protocol. All segments of the left ventricular short axis were seen at rest and peak exercise. Increased left ventricular wall thickening and wall motion were seen at peak exercise. There were no complications from the procedure. Conclusion: We demonstrated the feasibility of hands‐free left ventricular imaging during treadmill exercise using the CONTISON transducer. Further evaluation of the technique to detect stress‐induced wall motion abnormalities, as a means of diagnosing myocardial ischemia, appears warranted. (ECHOCARDIOGRAPHY 2010;27:563‐566)     

Utilization of hepatitis B core antibody-positive donor liver grafts

Background

The inclusion of hepatitis B core antibody-positive (HBcAb+) liver donors is a strategy utilized to increase organ availability. This study examined HBcAb+ transplantation practices to identify specific factors influencing outcomes.

Methods

Twenty-five HBcAb+ liver transplants were identified retrospectively among 868 adult transplants performed between 1 January 1997 and 31 December 2009. Twelve (48%) recipients had hepatitis C and five (20%) had hepatitis B. Patient and donor demographics, preoperative morbidity, transplant data and outcomes were examined. Statistical analysis was completed using Student''s t-test or the Kaplan–Meier method. A P-value of <0.05 was considered significant.

Results

There was no difference in age, body mass index or comorbidities between HBcAb+ liver recipients and control subjects. Model for End-stage Liver Disease (MELD) scores of >30 were significantly more frequent in HBcAb+ liver recipients (32% vs. 15%; P = 0.04). All patients received immunoglobulin and longterm antiviral therapy as prophylaxis against graft hepatitis B resurgence. No patients who received HBcAb+ livers developed hepatitis B infection on follow-up. Overall survival at 30 days, 1 year and 5 years in HBcAb+ liver recipients was 92%, 74% and 74%, respectively, compared with 96%, 89% and 76%, respectively, in the control group (P = not significant, log-rank test). All except one of the deaths in the HBcAb+ liver recipient group occurred within 90 days postoperatively and in patients with MELD scores >30.

Conclusions

The practice of transplanting HBcAb+ grafts incurs low risk for infection using current methods of prophylaxis. The highest mortality risk was in the early postoperative period, specifically in patients with very high MELD scores. This probably reflects the practice of using positive serology grafts in emergent situations.