Vasodilating mechanisms of testosterone.

The increased incidence of cardiovascular disease in man compared with premenopausal women suggests an unfavourable effect of male sex hormone testosterone on the cardiovascular system. However, numerous clinical and epidemiological studies reported a controversial relationship between testosterone and cardiovascular disease. Furthermore, an increasing amount of evidence indicate that testosterone can exert acute vasorelaxing effects, VIA non-genomic mechanisms. These effects involve primarily the vascular smooth muscle, without requiring the presence of endothelium, although an endothelial contribution is apparent in some studies. To date, the mechanism behind the vasodilatory action of testosterone is still under debate and might be through either activation of K (+) channels or blockade of Ca (2+) channels in vascular muscle cells. The purpose of this article is to review the evidence regarding the vasodilating effect of testosterone as well as its mechanism of action.     

Impact of Vitamin D Status on Cardiometabolic Complications among Children and Adolescents with Type 1 Diabetes Mellitus

Objective:

There is an ongoing interest in the relationship between vitamin D status and diabetes control and complications. However, data from Saudi Arabia are limited. To determine the impact of vitamin D status on glycemic control and cardiometabolic complications of children and adolescents with type 1 diabetes mellitus (T1DM) attending a tertiary care diabetes clinic in Saudi Arabia.

Methods:

Demographic, clinical, and laboratory data of 301 children and adolescent subjects with T1DM (53.5% females) of a mean age of 13.9 years attending King Abdulaziz Medical City-Jeddah during 2010-2013 were retrospectively collected. Relationships between vitamin D status and frequency of hypoglycemia, hemoglobin A1c (HbA1c) level, body mass index (BMI), blood pressure, and lipid profile were evaluated.

Results:

The mean duration of diabetes was 7.7±3.7 years. Mean BMI value was 21.1±4.5 kg/m2 and HbA1c was 9.6±1.9% in both genders. Only 26.2% of the patients had a satisfactory HbA1c level. The mean level of 25-hydroxyvitamin D [25(OH)D] was 35.15 and that of cholesterol was 4.75. Vitamin D deficiency [25(OH)D≤37.5 nmol/L] was detected in 63.6% of the male and 67.7% of the female subjects. In males, it was inversely associated with frequency of hypoglycemia (p<0.01), BMI (p<0.05), diastolic blood pressure (p<0.05), and triglyceride levels (p<0.01), while in females, it was inversely associated with current age (p<0.05), age at diagnosis (p<0.01), and triglyceride levels (p<0.01). No significant correlation between HbA1c and vitamin D deficiency was observed.

Conclusion:

Vitamin D deficiency was highly prevalent in our study sample and was found to be associated with frequency of hypoglycemic episodes and with adverse cardiometabolic control.     

Application of the vena contracta method for the calculation of the mitral valve area in mitral stenosis

OBJECTIVES: The vena contracta is the narrowest region of the regurgitant or stenotic jet just downstream the orifice and reflects the size of that orifice. This study was performed to assess the accuracy of the vena contracta width (VCW) in evaluating the severity of mitral stenosis (MS) and to compare the mitral valve area (MVA) determined by VCW with MVAs obtained by other more traditional echocardiographic methods. METHODS: We studied 59 patients (43 females, 42 +/- 14 years) with MS. VCW was measured in the apical four chamber view by Doppler color flow mapping. The largest diameter of the VCW during diastole was measured for at least three cardiac cycles and averaged. MVA was calculated from the following equation: pir(2), where r = VCW/2. MVA was also determined by planimetry, the pressure half-time method, and by the Gorlin formula. RESULTS: In this study, the width of the vena contracta ranged from 0.89 to 1.73 cm (mean 1.30 +/- 0.21). MVA, calculated based on the VCW, ranged from 0.63 to 2.35 cm(2) (mean 1.36 +/- 0.41). MVA by VCW (1.36 +/- 0.41 cm(2)) showed good correlations with three comparative techniques: (1) the cross-sectional area by planimetry (1.35 +/- 0.36 cm(2), mean difference = 0.21 +/- 0.16 cm(2), y = 0.91x + 0.14, r = 0.79, SEE = 0.26 cm(2), p < 0.001); (2) the area derived from the Doppler pressure half-time (1.27 +/- 0.32 cm(2), mean difference = 0.22 +/- 0.19 cm(2), y = 0.97x + 0.13, r = 0.76, SEE = 0.27 cm(2), p < 0.001), and (3) the area derived from the Gorlin equation in the 18 patients who underwent catheterization (1.27 +/- 0.35 cm(2), mean difference = 0.19 +/- 0.16, y = 0.98x + 0.05, r = 0.81, SEE = 0.26 cm(2), p < 0.001). CONCLUSIONS: These findings suggest that Doppler color flow imaging of the MS jet in the vena contracta can provide an accurate estimation of MVA and appears to be potentially applicable in the assessment of the severity of MS.     

Is the Change of Late Potential Over Time Related to Enzyme Levels?Ichemic Burden in Acute Myocardial Infarction

Background: The ventricular late potential (VLP) detected using the technique of signal average electrocardiography (SAECG) interacts with several factors, primarily time. Method: In this study, we examined the interaction, over time, of VLP with the initial ischemic burden and enzyme levels in acute myocardial infarction. Patients diagnosed as having acute myocardial infarction were included in the study. On the first day, the patients underwent enzyme analysis and electrocardiography (ECG) follow‐up every 6 hours. A 24‐hour ambulatory ECG was performed on the seventh day in order to determine the ischemic burden. SAECG findings (TQRS, RMS, LAS were obtained on the seventh day, in the first and third months. The study was continued with the patients who did not require angioplasty as decided with angiographic evaluation in the first month. Results: The study included 30 patients with acute myocardial infarction (mean age 51 ± 12, 28 males and 2 females). The initial mean CK‐MB levels and the mean ischemic burden were 98 ± 31 U/L and 44 ± 96 minutes. The TQRS (ms), LAS (ms), and RMS (μV) values (mean ± SD) obtained at day 7, month 1, and month 3 are 97 ± 12, 96 ± 9, 103 ± 11, P = 0.01; 31 ± 10, 31 ± 11, 32 ± 10, P = 0.46; 43 ± 28, 41 ± 26, 33 ± 25, P = 0.01, respectively. We observed that the TQRS and RMS values changed significantly with time, but these levels of significance disappeared when adjusted for the initial ischemic burden and CK‐MB levels (P = 0.06; P = 0.53). The VLP frequency was 33% at day 7 and 23% at month 3. Unlike the CK‐MB level, the initial ischemic burden was significantly different between the patients with and without VLP at month 3 (150.85 ± 149.28, 12.34 ± 26.48, P = 0.001). When tested together with age and gender, it was found that the high initial ischemic burden increased the possibility of VLP (OR: 24, Cl: 2.09–279.52, P = 0.01) at month 3. Conclusion: SAECG findings in patients with myocardial infarction changed with time; however, this change occurred depending on the initial ischemic burden and CK‐MB levels. Of these, only the initial ischemic burden, especially in high levels, was a determinant for the presence of VLP in the late period of myocardial infarction. A.N.E. 2002;7(3):242–246     

Prevalence of tuberculosis infection and its relationship to stunting in children (under five years) household contact with new tuberculosis cases

BackgroundChildren who inhabit the same house with tuberculosis (TB) patients are at high risk for infection and illness with TB. Nutritional status (stunting) in children is related to the child's ability to withstand MTB (Mycobacterium Tuberculosis). This study aims to estimated the prevalence of tuberculosis infection and its relationship to stunting in children (under five years) with household contact (HHC) with new TB cases.MethodsA cross-sectional design was implemented. Conducted in July 2018–April 2019 at 13 Public Health Center in Makassar City. The sample size was calculated using one sample situation-about precision formula. Samples were children under five who had contact with new diagnosed TB cases. Tuberculosis infection was measured by TST (tuberculin skin test). Logistic regression with causal model to examine TB infection relationship with stunting and covariate variable, analyzed using Stata/MP 13.0 software.ResultsOne hundred twenty-six (126) eligible children. Prevalence of tuberculosis infection was 38.10%. Frequency of stunted was 31 children (24.60%). Stunted nutritional status (aPR): 2.36, 95% CI 1.60–3.44), boys (aPR: 1.47, 95% CI 0.96–2.25), not getting BCG immunization (aPR: 1.58, 95%) CI 0.89–2.82), and high contact intensity (aPR: 2.62, 95% CI 1.10–6.22) best predicted the tuberculosis infection in children with TB case household contacts with a model contribution of 64%.ConclusionStunted nutritional status (moderate and severe), boys, not getting BCG immunization, and high contact intensity are the determinants of TB infection transmission in children HHC with TB. Children under five years of age who have close contact with TB cases should be targeted for priority interventions to prevent the transmission of TB infection and progressing to TB cases.     

Human papillomavirus subtype 16 is common in Pakistani women with cervical carcinoma.

INTRODUCTION: Human papillomavirus (HPV) is recognized as a major causative agent for cervical carcinomas. Based on their oncogenic potential, HPV subtypes have been divided into high- and low-risk. In Pakistan, screening for HPV in female patients is not commonly practiced, and as a consequence, the degree of HPV prevalence and its correlation with cervical cancer is unknown. OBJECTIVE: In this study, we have attempted to estimate the prevalence of HPV infection, and also the HPV subtype profile, among Pakistani women with cervical cancer from varied geographical, racial, and social backgrounds within Pakistan. METHODOLOGY: Women visiting two tertiary care hospitals in Karachi, diagnosed with carcinoma of the cervix within the past 15 years, were analyzed for HPV subtypes in their cancer specimens. Retrospectively, 60 paraffin-embedded cervical cancer biopsies were examined for the presence of HPV DNA. After DNA extraction from these samples, polymerase chain reaction (PCR) was used to amplify the HPV L1 gene using the consensus (general) primers, and primers specific for subtypes 16 and 18. RESULTS: Of the 60 samples analyzed, only one sample was HPV negative; the rest of the samples were positive for the presence of HPV. Of the 59 HPV positive samples, 56 showed the presence of HPV16 and one sample was positive for HPV18; HPV subtype could not be determined in two samples. CONCLUSION: Our results show a strong relationship between HPV infection and cervical cancer among Pakistani women. These results underscore the need to implement regular HPV screening for Pakistani women. An early diagnosis of HPV infection will allow better health management to reduce the risk of developing cervical cancer.     

Tobacco smoke exposure, wheeze, and atopy

We investigated the effect of in utero and postnatal environmental tobacco smoke (ETS) exposure on respiratory symptoms and atopy in the first 3 years of life in children at high risk of allergic disease (both parents atopic). Three hundred and sixty-nine children were followed from birth and reviewed at ages 1 and 3 years (respiratory questionnaire, skin testing). Parental smoking questionnaires were administered, and plasma cotinine in cord and peripheral blood (at age 1 year) was measured (capillary column gas-liquid chromatography). Wheezing starting in the first year of life was significantly more common in children of smoking mothers (54.2% vs. 39.5%, P = 0.017), but not wheezing starting after age 1 year (10.8% vs. 10.9%, smoking and nonsmoking mothers, P = 0.99). Detectable cord cotinine was not associated with wheeze. More frequent wheeze in infancy was significantly more common in those with detectable 1-year cotinine (e.g., wheeze without colds, 17.8% vs. 5.6%, P = 0.02; wheeze most days, 6.5% vs. 0%, P = 0.04). ETS exposure was not associated with atopy. In the multivariate regression analysis, maternal smoking during pregnancy and/or in the first year of life remained associated with wheeze in the first year of life (odds ratio, 1.88; 95% confidence interval, 1.14-3.12; P = 0.01). ETS exposure in "high-risk" infants increases the risk of wheezing starting in the first year of life, but not after age 1 year. However, ETS exposure has little or no effect on the development of atopy. Measurement of plasma cotinine was no more useful than tobacco exposure assessment by questionnaire in our cohort.     

LC-ESI-MS/MS reveals the formation of reactive intermediates in brigatinib metabolism: elucidation of bioactivation pathways

Brigatinib (BGB) is a newly approved anaplastic lymphoma kinase (ALK) inhibitor. On April 28, 2017, BGB was approved by the U.S. FDA for the treatment of metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer. The toxicity profile of BGB includes nausea, fatigue, diarrhea, elevated lipase, dyspnoea, hypertension, hypoxia, pneumonia, elevated amylase, pulmonary embolism, elevated ALT, hyponatraemia and hypophosphatemia. Using LC-MS/MS, we investigated the in vitro phase I metabolism of for BGB in rat liver microsomes (RLMs). In the in vitro metabolism of BGB, iminium reactive intermediates were trapped by potassium cyanide forming a stable complex that can be characterized by LC-MS/MS. Four BGB in vitro phase I metabolites were identified. In vitro phase I metabolic pathways were N-dealkylation, α hydroxylation and α oxidation. Additionally, three iminium reactive metabolites were found and the bioactivation mechanisms were proposed. A piperidine ring was found to be responsible for BGB bioactivation. The presence of these three reactive metabolites may be the main reason for BGB side effects. A literature review showed no previous article reported the in vitro phase I metabolism study of BGB or structural identification of the formed reactive metabolites.

Four phase I BGB metabolites and three cyano adducts for BGB were detected using LC-MS/MS. The piperidine ring was found to be responsible for BGB bioactivation and the bioactivation pathways are proposed.     

Incidental findings in multislice computed tomography prior to transcatheter aortic valve implantation: frequency,clinical relevance and outcome

Multislice computed tomography (MSCT) has emerged as the mainstay in patients planned for transcatheter aortic valve implantation (TAVI). Incidental findings (IF) in MSCT are common. However, the exact incidence, clinical relevance and further consequences of IF are unclear and it is controversial whether IF adversely affect patients’ outcome. We analyzed MSCT data of 1050 patients screened for TAVI between January 2011 and December 2014. Median follow-up of patients was 20 months. In total, 3194 IF were identified, which were classified into clinically non-relevant IF (2872, 90%) and clinically relevant IF (322, 10%). In 25% of patients (258/1050) at least one clinically relevant IF was present. Age (80?±?7 vs. 80?±?7 years; p?=?0.198) and EuroSCORE II (3.6% [2.1–5.7] vs. 3.6% [2.1–5.9]; p?=?0.874) was similar between patients with and without a clinically relevant IF. TAVI was performed less frequently in patients with a clinically relevant IF (76% vs. 85%; p?<?0.001), with more patients receiving surgical aortic valve replacement in that group (14% vs. 11%; p?=?0.042), possibly due to the high rate of incidental aneurysms of the ascending aorta (n?=?48). If TAVI was performed mortality did not differ (30-days: 4% vs. 3%; p?=?0.339, 1-year: 11% vs. 14%; p?=?0.226) between patients with and without a clinically relevant IF. Our study is the largest study to analyze prevalence, clinical relevance and therapeutic consequences of IF during screening for TAVI. IF in pre-procedural MSCT are common and clinically relevant in one-quarter of patients. However, these findings had no impact on overall mortality.