Variability in CYP2C9 allele frequency: A pilot study of its predicted impact on warfarin response among healthy South and North Indians

BackgroundWide variability exists in the frequency of pharmacogenetic markers for anticoagulant response in different populations. There is insufficient data on the prevalence of these variant genotypes in the Indian population. This study aims to determine the frequency of various genotype combinations of CYP2C9*2, *3 and VKORC1-1639G>A polymorphisms in the South and North Indians.MethodsGenotyping was carried out by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) technique in 209 North Indians (NI) and 82 South Indians (SI). Warfarin maintenance dose was predicted for all subjects based on FDA approved genotype-based dose estimates from revised COUMADIN medication guide. Fisher exact test and χ² test were applied to compare categorical data among the SI and NI groups.ResultsIn SI and NI, the allele frequency of CYP2C9*2 was 0.006 and 0.05 (significant variation; p < 0.001); of CYP2C9*3 was 0.09 and 0.11; and of VKORC1-1639A was 0.14 and 0.19 (not significant), respectively. The variation in the frequency of combined CYP2C9/ VKORC1 genotypes revealed plausible difference in warfarin response among SI and NI. Based on the FDA approved revised dosing guidelines, significantly higher percentage of NI were likely to require intermediate dose (3–4 mg/day; p = 0.015, RR = 2.16) and were also predicted to have an increased risk of bleeding episodes and over anticoagulation (p = 0.012, RR = 1.93).ConclusionsGenotype frequency of CYP2C9 and VKORC1 SNPs is variable among the two ethno-geographically distinct Indian populations. This could translate into diverse warfarin response among the Indian population.     

The use of Minilabs to improve the testing capacity of regulatory authorities in resource limited settings: Tanzanian experience

The Tanzania Food and Drugs Authority piloted the use of Minilab kits, a thin-layer-chromatographic based drug quality testing technique, in a two-tier quality assurance program. The program is intended to improve testing capacity with timely screening of the quality of medicines as they enter the market. After 1 week training of inspectors on Minilab screening techniques, they were stationed at key Ports-of-Entry (POE) to screen the quality of imported medicines. In addition, three non-Ports-of-Entry centres were established to screen samples collected during Post-Marketing-Surveillance. Standard operating procedures (SOPs) were developed to structure and standardize the implementation process. Over 1200 samples were tested using the Minilab outside the central quality control laboratory (QCL), almost doubling the previous testing capacity. The program contributed to increased regulatory reach and visibility of the Authority throughout the country, serving as a deterrent against entry of substandard medicines into market. The use of Minilab for quality screening was inexpensive and provided a high sample throughput. However, it suffers from the limitation that it can reliably detect only grossly substandard or wrong drug samples and therefore, it should not be used as an independent testing resource but in conjunction with a full-service quality control laboratory capable of auditing reported substandard results.     

The Impact of Different Diagnostic Imaging Modalities on the Evaluation of Root Canal Anatomy and Endodontic Residents' Stress Levels: A Clinical Study

Introduction

The purpose of this study was firstly to compare the impact of radiographs, cone-beam computed tomographic (CBCT) imaging, and 3D Endo software (Dentsply Sirona, Ballaigues, Switzerland) on the assessment of root canal anatomy and radiographic quality of endodontic treatment and secondly to assess stress levels in the same cohort of residents performing endodontic treatment.

Genetic Etiology for Alcohol-Induced Cardiac Toxicity

Background

Alcoholic cardiomyopathy (ACM) is defined by a dilated and impaired left ventricle due to chronic excess alcohol consumption. It is largely unknown which factors determine cardiac toxicity on exposure to alcohol.

The stress sensitization hypothesis: understanding the course of bipolar disorder

BACKGROUND: The influence of psychosocial stress on the course of bipolar disorder has been increasingly recognized. The authors tested hypotheses about both stress and early adversity "sensitization" on the course of bipolar disorder over a one-year period. METHODS: The participants were 58 adults (29 male and 29 female) with a diagnosis of bipolar I disorder. They were evaluated every three months for one year. Stressful life events and the presence of early adversity were assessed by structured interview. RESULTS: There was no significant interaction between stress and episode number in the prediction of bipolar recurrence. The interaction of early adversity severity and stressful life events significantly predicted recurrence in a manner consistent with the sensitization hypothesis. Participants with early adversity reported lower levels of stress prior to recurrence than those without early adversity. Individuals with early adversity also had a significantly younger age of bipolar onset. LIMITATIONS: The sample size was small and the number of past episodes was determined retrospectively, mainly through self-report. CONCLUSIONS: Severe early adversity may result in a greater effect of stress on bipolar recurrence and earlier onset of bipolar disorder, suggesting the need for further studies of stress mechanisms in bipolar disorder and of treatments designed to intervene early among those at risk.     

Personality disorders and violence among female prison inmates

The current study seeks to expand our understanding of the increasingly well-documented relationship between mental disorder and violence, specifically by examining the relationship between Axis II disorders and community and institutional violence among a cohort of 261 incarcerated women. Drawing from an initial screening of 802 female inmates in maximum security, we sampled to identify 200 nonpsychotic women who met criteria for one of the four Cluster B personality disorders, and 50 nonpsychotic women who did not meet criteria for these disorders. Each inmate was interviewed with the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II). Information regarding instant offense and institutional behavior was obtained from prison files and a self-report inventory. The analyses indicated a high degree of comorbidity between the various Cluster B diagnoses and a significant association with various types of violent crime and nonviolent criminality. Significant relationships were found between Antisocial Personality Disorder and institutional violence, and Narcissistic Personality Disorder and incarceration for a violent crime. Cluster A diagnosis was unexpectedly found to be associated with both incarceration for a violent crime and incarceration for prostitution.     

Metastatic epithelioid angiosarcoma of the heart in peritoneal fluid

Angiosarcoma is the most common malignant neoplasm of the heart. Recurrent pericardial effusions are a common manifestation of cardiac angiosarcomas. The diagnosis of metastatic disease in effusions is often established histologically; few cases have been described in exfoliative cytology. We report a case of metastatic cardiac epithelioid angiosarcoma in peritoneal fluid.     

Determination of the differences in 2-h plasma glucose values after ingestion of carbohydrate foods and oral glucose in Caribbean non-diabetic subjects

It has been reported that mixed meals are used in clinics in developing and developed countries in screening and diagnosis of diabetes. Thus, we aimed to determine the differences in 2-h plasma glucose values after non-diabetic subjects ingested 75 g pure glucose and its equivalent content in frequently consumed carbohydrate foods in Caribbean subjects. Twenty-seven apparently healthy non-diabetic subjects (nine males, 18 females) consumed 75 g pure glucose and its carbohydrate equivalent in three ethnic test foods (bread, rice and roti) at 7 days apart. Plasma glucose and insulin levels were determined in blood samples collected before and after 60, 90, 120 and 150 min of ingestion of these foods. In comparison with each of the test foods, the postprandial 1-h and 2-h plasma glucose values and the 60, 90, 120 and 150 min incremental glucose concentrations after oral glucose load were significantly higher than the corresponding values for each of the test foods (all P<0.01). In spite of these higher postprandial glucose concentrations, the postprandial insulin responses following the oral glucose load and the test foods did not significantly differ at any time point (all P>0.05). However, the test food, roti, tended to stimulate higher absolute and incremental insulin secretions than pure glucose or any other test food (all P>0.05). Generally, the correlation between 2-h plasma glucose value after the ingestion of the pure glucose and each of the test foods was significant (all correlation coefficients were greater than 0.70, P<0.01). In conclusion, different ethnic mixed meals could serve as an alternative to glucose in routine screening and diagnosis of diabetes if its available carbohydrate content is known and quantified.