Plasma levels of efavirenz and frequency of the CYP2B6 516G>T polymorphism in people living with HIV-1 in Mexico.

Efavirenz (EFV) is a widely used antiretroviral, due to its safety, efficacy, and low cost. However, plasma concentrations have been related with an increased risk of virological failure and the appearance of serious adverse reactions. EFV is metabolized by Cytochrome P450, the main isoenzyme involved is CYP2B6 and the most relevant genetic polymorphisms found in several populations has been the CYP2B6 516G> T. The aim of this study was to identify the frequency of the CYP2B6 516G>T polymorphism and its effect on the plasma concentration of efavirenz (EFV) in a group of people living with HIV (PLWH) and undergoing EFV treatment in Morelos, Mexico. Ninety-six PLWH undergoing EFV treatment, at a daily dose of 600 mg orally in combination with other antiretrovirals (ARVs), were included in this study. The CYP2B6 516G>T polymorphism was detected using PCR-RFLP. The plasma concentrations of EFV were evaluated by high-resolution liquid chromatography coupled to a mass-mass detector, using a protein precipitation method. The median plasma EFV concentration was 4.6 µg/mL (IQR = 4.64) and 64.6% of the subjects had concentrations above the therapeutic range. The CYP2B6 516G>T genotype findings were as follows: 46.9% of the population presented the wild-type genotype (GG), while 45.8 % and 7.3 % showed the heterozygote (GT) and the polymorphic homozygote (TT) genotype, respectively. The homozygote G had the lowest plasma concentrations of EFV (median = 4.1 µg/mL and IQR = 1.7 µg/mL), followed by those with the GT genotype (median = 5.1 µg/mL and IQR = 3.0 µg/mL). Participants with the homozygous T genotype had the highest EFV concentrations (median = 9.7 µg/mL and IQR = 5.8 µg/mL). In conclusion, the CYP2B6 516G>T polymorphism was associated with plasma levels of EFV in PLWH undergoing ARV treatment. EFV plasma concentrations at 600mg doses were outside the therapeutic range in most subjects.

Update on Dietary Compliance, Nutritional Status, and Neuropsychological Functioning in the Chilean Phenylketonuria cohort

Abstract Since 1992, Chile has had a Newborn Screening Program for Phenylketonuria (PKU), which currently has an incidence of 1:18,916 newborns. The objective of the current study was to describe the 2020 follow up of the Chilean PKU cohort. The variables analyzed were: nutritional status, dietary compliance and neuropsychological functioning. We conducted a descriptive cross-sectional statistical analysis. The 271 subjects with PKU had an average age of diagnosis of 17±8 days and a phenylalanine (Phe) level of 1122±546 umol/L. Approximately 80% of protein requirement came from a protein substitute. For those <18 years of age, 80% had good dietary compliance with Phe level between 120-360 umol/L and those >18 years had a median of 522 umol/L (95%CI 468 - 636). Forty-four percent of the active PKU cohort had overweight/obesity. Eighty-five percent of the cohort >4 years of age had a normal intelligence quotient (IQ) (score 80-120). We observed a negative correlation (p <0.001; 95% CI: - 0.5, -0.2) between IQ score and Phe level. The Chilean protocol and protein substitute subsidy for life, together with the follow-up and continuous education carried out by the clinical team has encouraged compliance.

Spontaneous intramural atrial hematoma presenting as a left atrial mass.

We describe an unusual case of spontaneously occurring intramural atrial hematoma with no communication with either atrium. The diagnosis of left atrial mass was made from transthoracic echocardiography. Subsequent examination with transesophageal echocardiography confirmed a large mass essentially filling the whole left atrium but failed to provide an etiologic diagnosis, which was eventually made at surgery.

Assessment of acute right ventricular dysfunction induced by right coronary artery occlusion using echocardiographic atrioventricular plane displacement.

Right ventricular (RV) systolic function analysis by echocardiography has traditionally required RV endocardial border definition with subsequent tracing and is often inaccurate or impossible in technically poor studies. The atrioventricular plane displacement (AVPD) method attempts to use the descent of the tricuspid annular ring, a reflection of the longitudinal shortening of the right ventricle, as a surrogate marker for RV systolic function. We hypothesized that RV ischemia induced during right coronary artery occlusion proximal to the major right ventricular branches would result in severe right ventricular systolic dysfunction detectable by the AVPD method. During this pilot study, seven patients undergoing elective proximal RCA angioplasty had echocardiographic measurement of RV AVPD performed at baseline (i.e., immediately prior to RCA balloon inflation), during the last 30 seconds of first RCA balloon inflation, and at 1 minute after balloon deflation (recovery). Lateral and medial RV AVPD were significantly reduced from baseline values during intracoronary balloon inflation. (Lateral: 2.45 cm +/- 0.22 vs 1.77 cm +/- 0.13, P < 0.001; medial: 1.46 cm +/- 0.37 vs 1.28 cm +/- 0.32, P < 0.05). Additionally, lateral and medial RV AVPD significantly returned towards baseline values during recovery. (Lateral: 2.39 cm +/- 0.20, P < 0.001; medial: 1.58 cm +/- 0.27, P = 0.01). At baseline, all lateral RV AVPD values were > 2.0 cm, whereas during balloon inflation all were < 2.0 cm. No such clear distinction was found in medial RV AVPD values. Proximal RCA angioplasty is associated with a significant reduction in lateral and medial RV AVPD. Thus RV AVPD may serve as a marker for RV systolic dysfunction.

[Platelet aggregation model in vivo (rabbits)]. / Modelo de agregación plaquetaria in vivo (conejos).

The purpose of this study was to establish a blood platelet aggregation model that would permit "in vivo" (New Zealand rabbits) evaluation of hemodynamic and microscopic parameters. The platelet aggregation was induced by the administration of collagen I.V. 75 micrograms/kg/min, which produced a decrease of systolic arterial pressure from mean = 69 to mean = 55 mm Hg and diastolic pressure from mean = 43 to mean = 27 mm Hg, with ventricular increase from mean = 25 to mean = 41 mm Hg. Aspirin, dypiridamol or sulfinpyrazone was administered 10 mg/kg, half hour before the administration of collagen and prostacycline 100 mg/kg/min starting 3 minutes before until 10 minutes after the collagen injection. With the joint administration of collagen and aspirin, collagen and dypiridamol both systolic and diastolic arterial pressure were lowered with no modification in the ventricular values. No hemodynamic changes were observed with the joint administration of sulfinpyrazone-collagen or prostacycline-collagen. Histology demonstrated multiple vascular lung thrombosis with the administration of collagen and in less intensity when jointly administered with an antiaggregant drug. This model permits to measure hemodynamically and histologically pro and antiaggregant substances.