Effects of angiotensin-converting enzyme inhibitor therapy on levels of inflammatory markers in response to exercise-induced stress: studies in the metabolic syndrome

The authors sought to determine whether the angiotensin-converting enzyme (ACE) inhibitor perindopril has beneficial effects on vascular markers of inflammation in patients with the metabolic syndrome when exposed to exercise-induced stress. Thirty patients with the metabolic syndrome were randomized to perindopril (4 mg/d) or placebo in a double-blind fashion for 4 weeks. Prior to treatment, the patients underwent an exercise treadmill study to a level of 8 metabolic equivalents. Circulating monocyte CD11b expression, levels of soluble interleukin 6 (sIL-6), and levels of vascular cell adhesion molecule-1 (VCAM-1) were measured. After the treatment period, exercise treadmill study and measurement of markers were repeated. Treatment with perindopril reduced sIL-6 levels at pre-exercise by 22% and at 1 and 30 minutes by 30% and 33%, respectively (P<.005). Levels of soluble VCAM-1 in perindopril-treated patients were reduced at pre-exercise by 25% and at 1 and 30 minutes by 31% and 37%, respectively. Treatment with perindopril reduced monocyte CD11b expression by 25%. In response to exercise-induced physical stress, the addition of an ACE inhibitor differentially regulates markers of inflammation, thereby providing potential vascular protection in the metabolic syndrome.     

Germline BRCA mutation evaluation in a prospective triple-negative breast cancer registry: implications for hereditary breast and/or ovarian cancer syndrome testing

NCCN guidelines recommend genetic testing for all triple-negative breast cancer (TNBC) patients aged ≤60 years. However, due to the lack of prospective information in unselected patients, these guidelines are not uniformly adopted by clinicians and insurance carriers. The aim of this study was to determine the prevalence of BRCA mutations and evaluate the utility of NCCN guidelines in unselected TNBC population. Stage I–IV TNBC patients were enrolled on a prospective registry at academic and community practices. All patients underwent BRCA1/2 testing. Significant family history (SFH) was defined >1 relative with breast cancer at age ≤50 or ≥1 relative with ovarian cancer. Mutation prevalence in the entire cohort and subgroups was calculated. 207 TNBC patients were enrolled between 2011 and 2013. Racial/ethnic distribution: Caucasian (80 %), African–American (14 %), Ashkenazi (1 %). Deleterious BRCA1/2 mutations were identified in 15.4 % (32/207) of patients (BRCA1:11.1 %, BRCA2:4.3 %). SFH reported by 36 % of patients. Mutation prevalence in patients with and without SFH was 31.6 and 6.1 %, respectively. When assessed by age at TNBC diagnosis, the mutation prevalences were 27.6 % (≤50 years), 11.4 % (51–60 years), and 4.9 % (≥61 years). Using SFH or age ≤50 as criteria, 25 and 34 % of mutations, respectively, were missed. Mutation prevalence in patients meeting NCCN guidelines was 18.3 % (32/175) and 0 % (0/32) in patients who did not meet guidelines (p = .0059). In this unselected academic and community population with negligible Ashkenazi representation, we observed an overall BRCA mutation prevalence rate of 15.4 %. BRCA testing based on NCCN guidelines identified all carriers supporting its routine application in clinical practice for TNBC.     

Vertical transmission of hepatitis C virus in low to middle socio-economic pregnant population of Karachi

Purpose  

To determine the rate of vertical transmission (transmission from mother to child) of hepatitis C virus in low to middle socio-economic pregnant women.     

Heritability of genetic variants of resistin gene in patients with coronary artery disease: a family-based study

ObjectiveThe resistin gene (RETN) ?420 C > G and + 299 G > A polymorphism was investigated in a case-control study from forty complex Pakistani families with coronary artery disease (CAD) history. Heritability of the susceptible/variant alleles was investigated from parent–offspring trios in these families.MethodResistin levels were determined from 239 individuals by enzyme-linked immunosorbent assay. Genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism.ResultsElevated resistin levels were observed from CAD cases vs. controls (p < 0.0001). The RETN ? 420 C > G and + 299 G > A polymorphism was more prevalent in cases vs. controls (p < 0.0001). The transmission disequilibrium test revealed a significant association of the ? 420 and + 299 polymorphism with CAD (χ² = 34.4, p < 0.0001 and χ² = 31.6, p < 0.0001, respectively).ConclusionElevated resistin, and the RETN ?420 C > G and + 299 G > A polymorphism may contribute to familial CAD. The ? 420 and + 299 variant alleles are transmitted more frequently from parent to affected offspring. This is the first report on the association of the RETN + 299 G > A polymorphism with CAD.     

Epidemiology and Outcome of Sepsis in a Tertiary Care PICU of Pakistan

Objective

To determine the epidemiology and outcome of sepsis in children admitted in pediatric intensive care unit (PICU) of a tertiary care hospital.

Methods

Retrospective review of children 1?mo to 14?y old, admitted to the PICU with severe sepsis or septic shock from January 2007 through December 2008 was done. Demographic, clinical and laboratory features of subjects were reviewed. The primary outcome was mortality at the time of discharge from PICU. The independent predictors of mortality were modeled using multiple logistic regression.

Results

In 2?years, 17.3% (133/767) children admitted to the PICU had sepsis. Median age was 18?mo (IQR 6–93?mo), with male: female ratio of 1.6:1. Mean PRISM III score was 9 (±7.8). One third had culture proven infection, majority (20%) having bloodstream infection. The frequency of multi-organ dysfunction syndrome (MODS) was 81% (108/133). The case specific mortality rate of sepsis was 24% (32/133). Multi-organ dysfunction (Adjusted OR 18.0, 95% CI 2.2–144), prism score of >10 (Adjusted OR 1.5, 95% CI 0.6–4.0) and the need for?>?2 inotropes (Adjusted OR 3.5, 95% CI 1.3–9.2) were independently associated with mortality due to sepsis.

Conclusions

The presence of septic shock and MODS is associated with high mortality in the PICU of developing countries.     

Antibacterial efficacy of the seed extracts of Melia azedarach against some hospital isolated human pathogenic bacterial strains

Objective

To investigate the antibacterial potential of the polar and non-polar extracts of the seeds of Melia azedarach (M. azedarach) L. (Meliaceae) against eighteen hospital isolated human pathogenic bacterial strains.

Methods

Petrol, benzene, ethyl acetate, methanol, and aqueous extracts at five different concentrations (1, 2, 5, 10 and 15 mg/mL) were evaluated. Disk diffusion method was followed to evaluate the antibacterial efficacy.

Results

All extracts of the seeds demonstrated significant antibacterial activity against tested pathogens. Among all extracts, ethyl acetate extract revealed the highest inhibition comparatively. The present study also favored the traditional uses reported earlier.

Conclusions

Results of this study strongly confirm that the seed extracts of M. azedarach could be effective antibiotics, both in controlling gram-positive and gram-negative human pathogenic infections.     

Dengue fever in the Indian Subcontinent: an overview

The Indian Subcontinent has emerged as a scene of many mosquito-borne infectious diseases, including malaria and dengue fever. After the 1990s, the rate of malaria declined owing largely to preventive measures, but at the same time dengue fever (DF) and dengue hemorrhagic fever (DHF) were increasing in the region. Outbreaks were recorded in all countries of the Indian Subcontinent with India, Pakistan, Bangladesh and Sri Lanka on the forefront and suffering from the largest number of cases and deaths. We discuss annual cases of DF/DHF in these four countries and possible factors involved in DF outbreaks. We also discuss prevalent serotypes in this region where data suggest the emergence of DEN2 and DEN3 as the most dominant and lethal serotypes. Climate is an important factor influencing DF outbreaks, and rainfall, temperature and humidity play a pivotal role in DF outbreaks. Finally the economic impact of DF/DHF cases is discussed showing that direct and indirect economic loss due to DF/DHF reaches millions of USD each year.     

The outcomes of pars plana vitrectomy without endotamponade for tractional retinal detachment secondary to proliferative diabetic retinopathy

AIM: To evaluate the outcomes of pars plana vitrectomy (PPV) without the use of an ocular tamponade in patients having tractional retinal detachment (TRD) secondary to proliferative diabetic retinopathy (PDR).METHODS: It was an interventional study conducted at the Department of Ophthalmology, B.V. Hospital, Bahawalpur, Pakistan, from July 2011 to July 2012. A total of 75 patients (84 eyes) having TRD secondary to PDR were treated by PPV without using an ocular tamponade. All patients included in the study had a tractional retinal detachment secondary to proliferative diabetic retinopathy but didn’t have or develop retinal breaks before or during the study period. The surgical procedure included a PPV combined with the removal of the tractional retinal membranes and the application of endolaser photocoagulation to the retina. The mean follow-up period was 12 months.RESULTS:Successful retinal reattachement was observed in 78 of the operated eyes (92.8%). In these patients, the retina remained attached till the end of the one year follow-up period. Improvement in best corrected visual acuity (BCVA) was seen in 63 eyes (75%). The visual acuity remained unchanged in 9 eyes (10.7%). Mean improvement in BCVA was 2.00+1.24 at baseline to 1.24+1.22 (P<0.05) at the end of the follow-up period.CONCLUSION: In the absence of the retinal breaks, a TRD secondary to PDR can be successfully treated by pars plana vitrectomy without the use of an ocular tamponade.     

Tactile spatial acuity is reduced by skin stretch at the human wrist

The skin is an elastic organ that is continuously distorted as our limbs move. The hypothesis that the precision of human tactile localisation is reduced when the skin is stretched, with concurrent expansion of receptive fields (RFs) was tested. Locognosic acuity over the dorsal wrist area was quantified during application of background stretch by (a) Wrist-Bend (skin stretch combined with non-cutaneous proprioceptor activation) and (b) Skin-Pull (skin stretch alone). Participants identified the perceived direction (distal or proximal) of brief test stimuli, applied along a 7-point linear array, relative to a central reference locus. Performance was significantly reduced during the large amplitude compared to the small amplitude of tonic skin stretch, but there was no effect of stretch mode (Wrist-Bend, Skin-Pull), nor was the effect of stretch amplitude modulated by the mode of stretch. Locognosic acuity was poorer than baseline accuracy for the large amplitude skin stretches, for both application modes, but did not differ significantly from baseline for either of the small amplitude stretches. We interpret these observations as corroborating the long-held assumption that tactile localisation is primarily dependent upon the RF dimensions, and associated innervation densities, of regional touch units. The finding that performance was reduced to a similar extent under Skin-Pull and Wrist-Bend conditions suggests that non-cutaneous proprioceptors had rather little tonic modulatory effect.