Electroencephalography findings in patients with acute post coronary artery bypass graft encephalopathy

Objectives:

To determine the EEG findings associated with acute post coronary artery bypass graft encephalopathy (aPCE), and to study the demographics and neuroimaging findings.

Methods:

We reviewed the EEG in all patients with the diagnosis of PCE between February 2006 and December 2011.

Results:

We identified 21 (20 males, and one female) patients with aPCE. The mean age (±SD) was 64 (±11.2) years. Thirteen patients had altered level of consciousness, and 8 presented with confusion out of which 3 had acute seizures. The EEG patterns observed were: a) generalized theta plus intermixed diffuse delta in 7 (33%); b) generalized theta with focal epileptiform discharges in 5 (24%); c) generalized triphasic pattern in 3 (14%); d) generalized theta with lateralized delta in 3 (14%); e) generalized theta with periodic lateralized epileptiform discharges (PLEDs), and bilateral synchronous periodic epileptiform discharges (BIPLEDs) in 2 (10%); and f) one patient (5%) with electrographic seizures. On EEG/neuroimaging correlation, the EEGs that showed generalized slowing and generalized triphasic patterns had no acute changes on imaging, while the EEGs that showed lateralized slowing, focal epileptiform discharges, electrographic seizures and PLEDs had fresh infarcts. Patients with BIPLEDs had unremarkable imaging.

Conclusion:

The EEG features such as lateralized slowing, PLEDs, and electrographic seizure were associated with acute cerebral insults. An altered level of consciousness was the most common symptomatology in our cohort, and could possibly be related to hypoxic/toxic-metabolic etiology. Electrographic seizure detected by EEG may clinically present as aPCE.Acute post coronary artery bypass graft encephalopathy (aPCE) varies widely from 8-32% of patients,1 and can be a major factor for prolonging hospital stay.2 Common factors predicting aPCE can vary from old age, history of hypertension, diabetes mellitus, carotid artery disease, and metabolic derangements.3 The aPCE is usually associated with short term and long term neurocognitive complications,3 so early recognition and appropriate treatment can help in better management of these patients. Electroencephalography (EEG) can ascertain a degree of encephalopathy, and also identify regional and global dysfunction that may help to point toward an underlying etiology. The EEG is most commonly used in patients with encephalopathies. Digital/computer EEG’s are perspective tools for mild ischemic brain changes in the postoperative period appearing as cognitive dysfunction.4 The aim of this study was to determine EEG findings in delirious patients post coronary artery bypass graft (CABG) in an acute setting.     

Standardization of pathology laboratories in Pakistan: Problems and prospects

A Total Quality Management System with an internationally recognized accreditation process is the only guarantee of a reliable pathology service. However in a developing country like Pakistan nearly 90% of labs are small and without adequate physical and man power infrastructures. A modified plan may have to be tailored for them. A two tier system has been formulated. Accreditation based on ISO 15189 is to be introduced on voluntary basis. The labs which do not qualify for international standardization would be brought into quality net through a registration process. All such labs will be initiated into a simplified quality management system. Participation in proficiency testing program will be mandatory. They will be provided education and training to become eligible for accreditation. It is hoped that this simplified system will provide an impetus for evolving a workable and comprehensive mechanism through which pathology laboratories in the country will be able to offer better and more reliable services.     

In Silico Identification and Conservation Analysis of B-cell and T-Cell Epitopes of Hepatitis C Virus 3a Genotype Enveloped Glycoprotein 2 From Pakistan: A Step Towards Heterologous Vaccine Design

Background:

Hepatitis C virus (HCV) is known for the eminent global disease burden responsible for encumbering public health. Development of an effective vaccine is the major need of the day; however, several obstacles loom ahead of this objective. One of the major barriers is that as a RNA virus, it mutates rapidly resulting in high sequence divergence and several viral isolates in the world. Theglycoprotein 2 (gpE2) is the primary component of HCV envelope with direct interaction with the host cell surface receptors; it is an indispensable target of neutralizing antibodies and hence, should be a fundamental component of vaccine design.

Objectives:

This study focused on B-cells and T-cells epitopes prediction in HCV gpE2, particularly in 3a genotype, in Pakistan and identification of the conserved epitopes among various 3a isolates at global level, principally conserved across HCV major genotypes.

Materials and Methods:

Epitope finding was done by using online available bioinformatics tools including Immune Epitope Database (IEDB), ProPred-I, and ProPred. Conservation of these epitopes was found by aligning selected gpE2 sequences using MultAlin online software and conservancy analysis tool available at IEDB.

Results:

Many B-cell and T-cell epitopes predicted in gpE2 were found conserved among HCV 3a genotypes whereas few were conserved in other genotypes anticipating these epitopes as potential candidates of producing strong B-cell and T-cell response against HCV 3a and other genotypes.

Conclusions:

HCV gpE2 is an ideal target for HCV vaccine. Prediction of epitope immunogenicity and characterization on the basis of peptide sequences will be significantly helpful for development of a heterologous vaccine against HCV variants.     

Evaluation of developmental toxicity of guaifenesin using pregnant female rats

Objectives:Guaifenesin possesses expectorant, muscle relaxant, and anticonvulsive properties. To the best of our knowledge, the promising data regarding the developmental toxicity of guaifenesin are scarce. The current study investigates the developmental toxic effects of guaifenesin in detail using female rats.Results:A significant reduction in maternal weight, and food/water intake, was observed, however, no mortality and morbidity were observed. About 14 dead fetuses were found in Group-3 and -4 each, while 26 in Group 5. Morphological analysis revealed 21.2%, 45.4%, 67.2%, and 86.9% of total fetuses having hemorrhagic spots in Group-2, -3, -4, and -5, respectively. Dropping wrist/ankle and kinky tail were found in Group-4 and -5 only. Morphometric analysis showed a significant decline in fetal weight, full body length, skull length, forelimb length, hindlimb length, and tail length in all guaifenesin treated groups. Skeletal examination displayed that only Group 5 fetuses had increased intercostal space between 7^th and 8^th rib. We also observed improper development of carpals, metacarpals, tarsals, and metatarsals of the Group 5 fetuses.Conclusion:Guaifenesin showed a significant developmental toxicity at selected test doses; therefore, a careful use is suggested during pregnancy.KEY WORDS: Developmental toxicity, embryotoxicity, fetotoxicity, guaifenesin, teratogen, toxicology     

Virulent and multidrug‐resistant Klebsiella pneumoniae from clinical samples in Balochistan

Klebsiella pneumoniae is an important pathogen causing hospital‐acquired infections in human beings. Samples from suspected patients of K pneumoniae associated with respiratory and urinary tract infections were collected at Bolan Medical Complex, Quetta, Balochistan. Clinical samples (n = 107) of urine and sputum were collected and processed for K pneumoniae isolation using selective culture media. Initially, 30 of 107 isolates resembling Klebsiella spp. were processed for biochemical profiling and molecular detection using gyrase A (gyrA) gene for conformation. The K pneumoniae isolates were analysed for the presence of drug resistance and virulence genes in their genomes. The 21 of 107 (19.6%) isolates were finally confirmed as K pneumoniae pathogens. An antibiogram study conducted against 17 different antibiotics showed that a majority of the isolates are multidrug resistant. All the isolates (100%) were resistant to amoxicillin, cefixime, amoxicillin‐clavulanic acid, cefotaxime, and ceftriaxone followed by tetracycline (95.2%), ciprofloxacin and gentamicin (76.2%), sulphamethoxazol (66.7%), nalidixic acid (61.9%), norfloxacine (42.9%), piperacillin‐tazobactam (23.8%), cefoperazone‐sulbactam (19%), and cefotaxime‐clavulanic acid (33.3%), whereas all the isolates showed sensitivity to amikacin, chloramphenicol, and imipenem. The presence of tetracycline, sulphamethoxazol‐resistant genes, and extended‐spectrum beta‐lactamase was reconfirmed using different specific genes. The presence of virulence genes fimH1 and EntB responsible for adherence and enterobactin production was confirmed in the isolates. The high virulence and drug resistance potential of these Klebsiella isolates are of high public health concern. Multidrug resistance and virulence potential in K. pneumoniae are converting these nosocomial pathogens into superbugs and making its management harder.     

Immunobiochemical analysis of paraoxonase1 (anti‐oxidant), xanthine oxidase (oxidant) enzymes and lipid profile of cardiac disease patients in Lahore Metropolitan,Pakistan

Cardiac diseases are the major cause of death. Paraoxonase1 (PON1) is known as free radicals scavenger/anti‐atherosclerosis, whereas xanthine oxidase (XO) is a free radicals generator. This study was undertaken to determine and compare the Paraoxonase and arylesterase activities of PON1 enzyme and activity of XO enzyme. The concentration of XO and PON1 enzymes along with lipid profile, lipid peroxides, and thiol level in plasma of cardiac patients (n=200) and healthy persons (n=200) of Lahore metropolitan, Pakistan was also determined. Anti‐PON1 and anti‐XO antibodies were developed, purified, and used to measure the concentration of PON1 and XO by competitive ELISA. It is observed that low paraoxonase (P=0.0073)/arylesterase activity (P=0.0038) of PON1 enzyme and its low concentration (P=0.0049) were observed in cardiac patients, whereas elevated level of XO activity (P=0.0129) and its concentration (P=0.0097) was observed in cardiac patients as compared with healthy persons. Low levels of HDL (P=0.0013), thiol (P=0.0014) and high level of cholesterol (P=0.0025), triglycerides (P=0.0018), LPO (P=0.0014), and LDL level (P=0.05) were observed in cardiac patients admitted in intensive care unit as compared with hypertensive patients and control subjects. It is concluded that overall low PON1 and high XO activities do cause imbalance of free radical system which ultimately leads to or enhance the cardiac pathological conditions. J. Clin. Lab. Anal. 24:348–356, 2010. © 2010 Wiley‐Liss, Inc.     

Evolution of efficacious pangenotypic hepatitis C virus therapies

Hepatitis C compromises the quality of life of more than 350 million individuals worldwide. Over the last decade, therapeutic regimens for treating hepatitis C virus (HCV) infections have undergone rapid advancements. Initially, structure-based drug design was used to develop molecules that inhibit viral enzymes. Subsequently, establishment of cell-based replicon systems enabled investigations into various stages of HCV life cycle including its entry, replication, translation, and assembly, as well as role of host proteins. Collectively, these approaches have facilitated identification of important molecules that are deemed essential for HCV life cycle. The expanded set of putative virus and host-encoded targets has brought us one step closer to developing robust strategies for efficacious, pangenotypic, and well-tolerated medicines against HCV. Herein, we provide an overview of the development of various classes of virus and host-directed therapies that are currently in use along with others that are undergoing clinical evaluation.