A healthy patient with positive mantoux test but negative quantiferon Gold assay and no evidence of risk factors - to treat or not to treat?

A 56-year-old woman who vaccinated as a child with the Bacillus Calmette-Guerin (BCG), now tests positive to the tuberculin skin test (TST) but test negative to the Quantiferon Gold assay. She has no history of tuberculosis contact and is asymptomatic. This dilemma now is, should be treated for tuberculosis or not, based only on the TST results? To prevent these falsepositive results with TST and avoid treatment with isoniazid (INH) it may be helpful to use interferon-gamma release assay (IGRA) instead, which unlike the TB skin test is not affected by prior BCG vaccination.

Impact of CYP2D6 on venlafaxine metabolism in Trinidadian patients with major depressive disorder.

AIM: This study aimed to assess the impact of CYP2D6 and CYP2C19 variation on venlafaxine (VEN) at steady state in patients from Trinidad and Tobago of Indian and African descent with major depressive disorder. PATIENTS & METHODS: Patients were phenotyped with dextromethorphan, genotyped for CYP2D6 and CYP2C19, and metabolic ratios for VEN obtained at 2-week intervals. RESULTS: Of 61 patients, 55 were genotyped and phenotyped and 47 completed 8 weeks of VEN treatment. The majority of patients had metabolic ratios for VEN that were consistent with those for dextromethorphan and genotype-predicted phenotype using activity scores. One subject presented with a novel no-function allele, CYP2D6*99. No correlations were observed with CYP2C19 genotype. CONCLUSION: CYP2D6 genotype analysis provides valuable information to individualize drug therapy with VEN.

Subjective response to alcohol and ADH polymorphisms in a select sample of young adult male East Indians and Africans in Trinidad and Tobago.

OBJECTIVE: Level of response to alcohol has been associated with risk of alcohol dependence in a number of ethnic groups. In the present study, subjective and objective responses to alcohol were evaluated in Indo-Trinidadians (Indo-T) and Afro-Trinidadians (Afro-T). Associations of alcohol dehydrogenase polymorphisms with response to alcohol, using the Subjective High Assessment Scale (SHAS), and breath alcohol concentrations (BrAC) were tested. METHOD: Regular male drinkers without alcohol dependence (n = 112) ages 18-25 years participated in alcohol challenge sessions consisting of placebo and two doses of alcohol (target BrAC: 0 g/dl for placebo, .04 g/dl low dose, and .08 g/dl high dose) and genotyped for variants in ADH1B*3 and ADH1C*2. RESULTS: Indo-T had significantly higher BrAC, pulse rates, and cortisol levels when compared with Afro-T but did not have significantly higher SHAS values. Higher responses on the SHAS items muddle/confused and nauseated were significantly associated with the presence of at least one ADH1B*3 allele following the high dose of alcohol in Afro-T. Indo-T with at least one ADH1C*2 allele displayed significantly different Drug × Time interactions for the SHAS item effects of alcohol at the low dose and for the SHAS items clumsy, muddle/confused, effects of alcohol, floating, drunk, and total at the high dose from Indo-T with two ADH1C*1 alleles. CONCLUSIONS: This is the first study that has investigated individual sensitivity to alcohol in a Caribbean population and in people of East Indian descent. Indo-T with at least one ADH1C*2 allele may be at higher risk for heavy drinking by feeling less of the effects of alcohol, including nausea. In Afro-T, having at least one ADH1B*3 allele appears to exert a protective effect by enhancing the unpleasant effects of alcohol, such as nausea and confusion.

Characterization of the CYP2D6 gene locus and metabolic activity in Indo- and Afro-Trinidadians: discovery of novel allelic variants.

BACKGROUND: The highly polymorphic CYP2D6 gene has extensively been studied in many populations, but there is a void of knowledge regarding CYP2D6 pharmacogenetics and activity in populations with unique ancestries and admixture, such as those residing in Trinidad and Tobago. MATERIALS & METHODS: 167 healthy Indo- and 103 Afro-Trinidadians were phenotyped with dextromethorphan and extensively genotyped. Gene resequencing was performed to resolve cases with genotype/phenotype discordance. RESULTS: CYP2D6 activity did not differ between the Indo-Trinidadians and Afro-Trinidadians. Poor metabolizers were, however, more frequent in the Indo-Trinidadians (4.19 vs 1.94%), and unique allele frequency patterns were observed. Two novel nonfunctional allelic variants were found among the Indo-Trinidadians in two discordant cases. CYP2D6*100 is characterized by a single nucleotide deletion and CYP2D6*101 by a 19-bp deletion; both cause frameshifts. CONCLUSION: Our study underscores the importance of thoroughly characterizing the genetic make up of unique populations when considering pharmacogenetic testing for individualized therapy.

Efectos de la administración materna de teofilina en la organogénesis de las crias de ratones / Effects of maternal administration of theophylline in the organogenesis of mice litter

La teofilina, una metilzantina, fue evaluada para determinar la producción de anomalías esqueléticas y viscerales en crías de ratones BALB/c. La droga fue administrada del día 8 al 14 de la gestación , ambos incluidos, en dosis de 7,5 y 3 mg/kg por vía oral y parenteral; también se utilizó en grupo control al que se suministró suero fisiológico. A todos los grupos de crías se les realizó estudio visceral aplicando la técnica de Wilson y estudio esquelético con empleo de la técnica de Dawson. La teofilina produjo disminución del peso y la talla en fetos cuyas madres fueron tratadas con dosis de 7 mg/kg. No se encontró embriotoxicidad ni fetotoxicidad

Alteraciones farmacocinéticas durante el embarazo / Pharmacokinetic alterations during pregnancy

Durante el embarazo ocurren cambios fisiológicos sustenciales en la madre, necesarios para el éxito del embarazo, pero que alteran la farmacocinética de muchas drogas. Estas alteraciones deben ser consideradas por el médico práctico para asegurar una terapéutica adecuada y segura tanto para la madre como para el producto que ésta gesta. En este trabajo resumimos las principales variaciones que ocurren y sus posibles consecuencias en ambos sistemas biológicos

Alteraciones farmacocinéticas durante el embarazo / Pharmacokinetic alterations during pregnancy

Durante el embarazo ocurren cambios fisiológicos sustenciales en la madre, necesarios para el éxito del embarazo, pero que alteran la farmacocinética de muchas drogas. Estas alteraciones deben ser consideradas por el médico práctico para asegurar una terapéutica adecuada y segura tanto para la madre como para el producto que ésta gesta. En este trabajo resumimos las principales variaciones que ocurren y sus posibles consecuencias en ambos sistemas biológicos

Efectos de la administración materna de teofilina en la organogénesis de las crias de ratones / Effects of maternal administration of theophylline in the organogenesis of mice litter

La teofilina, una metilzantina, fue evaluada para determinar la producción de anomalías esqueléticas y viscerales en crías de ratones BALB/c. La droga fue administrada del día 8 al 14 de la gestación , ambos incluidos, en dosis de 7,5 y 3 mg/kg por vía oral y parenteral; también se utilizó en grupo control al que se suministró suero fisiológico. A todos los grupos de crías se les realizó estudio visceral aplicando la técnica de Wilson y estudio esquelético con empleo de la técnica de Dawson. La teofilina produjo disminución del peso y la talla en fetos cuyas madres fueron tratadas con dosis de 7 mg/kg. No se encontró embriotoxicidad ni fetotoxicidad