Case-control association analysis of polymorphisms in the δ-opioid receptor, OPRD1, with cocaine and opioid addicted populations.

BACKGROUND: Addiction susceptibility and treatment responsiveness are greatly influenced by genetic factors. Sequence variation in genes involved in the mechanisms of drug action have the potential to influence addiction risk and treatment outcome. The opioid receptor system is involved in mediating the rewarding effects of cocaine and opioids. The µ-opioid receptor (MOR) has traditionally been considered the primary target for opioid addiction. The MOR, however, interacts with and is regulated by many known MOR interacting proteins (MORIPs), including the δ-opioid receptor (DOR). METHODS: The present study evaluated the contribution of OPRD1, the gene encoding the DOR, to the risk of addiction to opioids and cocaine. The association of OPRD1 polymorphisms with both opioid addiction (OA) and cocaine addiction (CA) was analyzed in African American (OA n=336, CA n=503) and European American (OA n=1007, CA n=336) populations. RESULTS: The primary finding of this study is an association of rs678849 with cocaine addiction in African Americans (allelic p=0.0086). For replication purposes, this SNP was analyzed in a larger independent population of cocaine addicted African Americans and controls and the association was confirmed (allelic p=4.53 × 10(-5); n=993). By performing a meta-analysis on the expanded populations, the statistical evidence for an association was substantially increased (allelic p=8.5 × 10(-7)) (p-values non-FDR corrected). CONCLUSION: The present study suggests that polymorphisms in OPRD1 are relevant for cocaine addiction in the African American population and provides additional support for a broad role for OPRD1 variants in drug dependence.

Biochemical measures in the diagnosis of alcohol dependence using discriminant analysis.

BACKGROUND: Alcohol dependence often cannot be diagnosed based on self-report alone. Various biochemical and haematological parameters have been used to screen alcohol use disorders. AIM: To develop discriminant equations based on lipid and liver measures independently for identifying alcohol dependent and non-dependent subjects. SETTINGS AND DESIGN: Case control study in a tertiary care hospital. METHODS AND MATERIALS: One hundred subjects fulfilling the criteria of alcohol dependence and seventy healthy controls were included. The socio-demographic details, caloric intake, height, weight and blood pressure were recorded. Samples were analysed for various lipid measures as well as liver function. STATISTICAL ANALYSIS USED: Diagnostic values such as sensitivity, specificity, positive predictive value (PV+), negative predictive value (PV-) and discriminant analysis. RESULTS: Using discriminant analysis, two equations were constructed based on liver and lipid measures independently. 84.7% of the subjects on the basis of total cholesterol (TC), apolipoprotein B (ApoB) and low density lipoprotein/high density lipoprotein-cholesterol (LDL/HDL-c and 89.1% on the basis of aspartate amino transferase (AST) and gamma glutamyl transferase (GGT) were correctly classified into their respective groups. CONCLUSIONS: This study demonstrates the ability of TC, ApoB and LDL/HDL-c (among lipid measures) and AST and GGT (among liver measures) in discriminating alcohol dependents from non-dependent subjects.

Validity of self-report of recent opiate use in treatment setting.

Self-report validity of recent drug use among heroin abusers depends on many factors including the population being studied and the setting in which the study is carried out. This study was conducted by the treating physicians to assess the self-report validity of recent heroin use by heroin dependent patients in the outdoor setting using 'thin layer chromatography' (TLC) and two highly sensitive methods of urinalysis viz. 'gas liquid chromatography' (GLC) and 'high performance liquid chromatography' (HPLC). Out of seventy-six heroin dependent patients who entered the study, 64 provided urine sample on the same day. Patients' self-report about recent opiate use was found to have a moderate agreement with urinalysis report. However, it is important to validate it with urinalysis during the treatment process because a substantial proportion of patients fails to report recent opiate use. It is recommended that all drug dependence treatment centres should be equipped with a sensitive urinalysis facility. Otherwise, the outcome of the treatment process should be considered with caution.

Genetic basis of schizophrenia: trinucleotide repeats. An update.

1. Recent developments in technologies permit systematic screening of the entire human genome as a strategy for identification of susceptibility genes of small effect that influence risk to complex traits, like schizophrenia (Schz), inflammatory bowel disease, bipolar affective disorder (BPAD) etc. 2. Schizophrenia is known to have a high heritability and a complex inheritance pattern. Several studies provide evidence that both genes and environment play a role in the etiology of schizophrenia. Linkage studies have observed racial and sex bias in the genetic constitution of schizophrenia. Schizophrenia also manifests clinical anticipation and genomic imprinting. 3. "Dynamic mutations" or "tandem repeat expansions" in DNA, explain a number of observations associated with clinical anticipation and genomic imprinting. In patient populations, the repeat expands well beyond the normal range, altering the biological function of the gene. These sequence are unstable and increase in size between family members in successive generations, giving rise to greater severity of disease. 4. Several workers have reported an association of trinucleotide repeat length with adult- and child-onset schizophrenia. One such expanded allele has been found at the CTG18.1 locus on the 18th chromosome. Other genes known to have similar mutation are SEF2-1, which codes for a helix-loop-helix protein, hSKCa3 gene, which codes for a calcium-activated potassium channel and the transthyretin gene. In schizophrenic patients, significant difference in allele frequency distribution of these genes has been reported. 5. Population based genetic research would not only help identify different subgroups of this of schizophrenia.

An experimental study of tolerance among alcohol dependent individuals.

BACKGROUND & OBJECTIVES: Continued alcohol use leads to tolerance, however, some dependent individuals lose tolerance despite continued alcohol consumption. The exact mechanism for this is not known. This study evaluated tolerance in alcohol dependent patients in a treatment centre using multiple measures. METHODS: Male patients with alcohol dependence (DSM III R criteria) were chosen and detoxified in an inpatient setting. On day 14 of detoxification, each subject was given ethanol (0.75 g/kg body wt) mixed in an equal amount of placebo (cola) drink once and an equivalent amount of placebo (cola) during the other occasion in a single blind, randomised, cross over manner. Assessment of each subject was made using multiple measures (clinical, neuro-psychological tests, scales for subjective effect and blood alcohol levels), 30 min after intake of each drink. RESULTS: The subjects (n = 26) did not very under the two conditions (alcohol/placebo) as regards subjective effects, tests on logical memory and Bender Gestalt test (BGT). Cognitive screening scores though different under the two conditions, were within the normative range. Of these 26 subjects, 50 per cent showed clinical signs of intoxication after consumption of alcohol. These two groups (impaired vs unimpaired) were comparable on all base-line clinical parameters, assessment of euphoria and sedation, and various neuropsychological tests except BGT under the two conditions (placebo/alcohol). The non-tolerant (impaired) group scored significantly (P < 0.05) worse on BGT after alcohol consumption. INTERPRETATION & CONCLUSIONS: The study suggests that clinical tests were more sensitive in detecting intoxication. Further studies are needed to understand the mechanism of loss of tolerance.

Urinary net charge in hyperchloremic metabolic acidosis.

OBJECTIVE: (i) To examine the usefulness of urinary net charge (UNa + UK - UCl) in the evaluation of hyperchloremic metabolic acidosis secondary to diarrhea, distal RTA and proximal RTA and (ii) To characterize the type of distal RTA on the basis of the underlying defect. SETTING: Pediatrics division of a tertiary referral center. SUBJECTS: Thirty four children with hyperchloremic metabolic acidosis secondary to diarrhea (n = 16), distal RTA (n = 11) and proximal RTA (n = 7). Ten normal children with ammonium chloride induced acidosis were also studied. METHODS: All subjects underwent urine collection of 30-60 minutes duration for measurement of Na, K, Cl, pH and pCO2. The measurements were also made on the blood samples collected at the midpoint of urine collection. The urinary net charge was calculated by subtracting Cl values from the sum of the Na and K. RESULTS: Patients with proximal and distal RTA had a positive urine net charge. Patients with diarrhea and ammonium chloride induced acidosis showed negative urine net charge. Patients with diarrhea with extremely low urine sodium levels showed an inappropriately high urine pH despite persistent metabolic acidosis. All patients with distal RTA were found to have a secretory type of defect. CONCLUSION: Measurement of urine net charge is helpful in the initial evaluation of a patient with hyperchloremic metabolic acidosis.

The earliest case of extracranial aneurysm of the vertebral artery.

A lesion is described on the body of C4 from the skeleton of an adult male recovered from a 15th century site in Gloucester. The most plausible explanation for the lesion is that it represents the negative image of an extracranial aneurysm of the vertebral artery and thus is the earliest case described.

Urinary excretion of minerals, oxalate, and uric acid in north Indian children.

Urinary excretion of calcium, magnesium, phosphate, uric acid, oxalate, and creatinine was measured in 208 children (aged 8-15 years, 124 boys, 84 girls), living in a residential school near New Delhi. Levels were reduced compared with those reported from developed countries. The 95th percentile value of 24-h creatinine excretion was 33.4 mg/kg, calcium 2.2 mg/kg, magnesium 2.9 mg/kg, phosphate 9.4 mg/kg, uric acid 4.4 mg/kg, and oxalate 1.5 mg/kg. The 95th percentile value of the urine calcium/creatinine ratio was 0.15 and oxalate/creatinine 0.06. The dietary intake of proteins, calcium, and other nutrients in these children was less than recommended and explained the reduced urinary excretion observed. Physicians need to be aware of the regional patterns of normal urinary excretion of these constituents.

Lipid profile in alcohol dependence.

Fifty three patients of alcohol dependence were studied for lipid profile at Drug Dependence Treatment Centre, A.I.I.M.S. Statistically significant differences were observed on most of lipid profile indicators when compared to control group. Ratio of Apo A-I & Apo B appeared to be better indicator than Apo A1 or Apo B. The findings of the study are discussed in context of other studies from India and other countries.

Profile of liver dysfunction in alchohol dependence.

Ninety two patients of alcohol dependence were studied for liver function at a specialised drug dependence treatment centre. Biochemical laboratory evidence of liver dysfunction was found in a very large number of patients, including the patients who had no clinical signs or symptoms. The findings from this retrospective study are discussed in the context of the earlier studies from other settings in India.

Plasma levels of apolipoproteins A-1 and B in Indian patients with angiographically defined coronary artery disease.

Apolipoproteins A-1 and B concentration were measured in 201 Indian patients (32 females; 169 males) undergoing elective diagnostic coronary arteriography in order to assess the predictive power of apolipoproteins as a 'marker' of coronary artery disease (CAD). This association was also compared to that of other traditional risk factors: age, hypertension, diabetes, family history, smoking and plasma levels of total cholesterol, triglycerides, low and high density lipoproteins. The apolipoprotein (Apo) A-1 levels averaged 82.9 +/- 18.9 mg/dl in the normal coronary group (n = 43) and 76.0 +/- 18.1 mg/dl in the group with coronary artery disease (n = 158). The average Apo B levels in the normal coronary group and coronary artery disease group were 67.8 +/- 17.7 mg/dl and 78.9 +/- 19.5 mg/dl, respectively. Overall Apo B and triglyceride levels (of all lipid measures) showed larger univariate difference between the normal group (no coronary artery disease) and the group with coronary artery disease. The variable with strongest predictive power for coronary artery disease was the ratio of Apo A-1 to Apo B. These findings were confirmed using multiple logistic regression analysis adjusting for age and other traditional risk factors. Our results indicate that the measurement of apolipoproteins A-1 and B provide a better marker for predicting the presence of coronary artery disease as compared to traditional lipid measures. Overall the levels of these apolipoproteins seem to be lower in Indian population as compared to those reported from the West.