Introduction: H. pylori BabA is an outer membrane protein that mediates bacterial adherence to the gastric epithelium, triggers several pathways during the course of infection, and thus contributes to the disease development. Considering the variability in the presence of BabA coding gene (babA2) among H. pylori clinical strains, the aim of this study was to assess the relationship between the genotype status of H. pylori babA2 and the severity of clinical and histopathological outcomes. Methods: Gastric mucosal biopsy specimens were collected from 30 CLO test-positive patients, 16 with gastritis and 14 with peptic ulcer disease. Polymerase chain reaction was carried out to detect the presence of H. pylori-specific glmM gene and BabA coding gene (babA2). Histopathological examination was performed to evaluate the severity of H. pylori-associated gastric disease according to the Updated Sydney Classification System. Results: The glmM and babA2 genes were present in 100% and 86.7% of the tested H. pylori strains, respectively. Although higher degrees of inflammatory activity and H. pylori density were noted in babA2-positive biopsy specimens, there was no statistically significant association between babA2 genotype status and the severity of gastric disease. Conclusion: The babA2 genotype status of H. pylori may not be considered as a sole marker for determining the infection outcomes.

OBJECTIVES: Areca nut is widely consumed in many parts of the world, especially in South and Southeast Asia, where cardiovascular disease (CVD) is also a huge burden. Among the forms of CVD, acute coronary syndrome (ACS) is a major cause of mortality and morbidity. Research has shown areca nut chewing to be associated with diabetes, hypertension, oropharyngeal and esophageal cancers, and CVD, but little is known about mortality and re-hospitalization secondary to ACS among areca nut users and non-users. METHODS: A prospective cohort was studied to quantify the effect of areca nut chewing on patients with newly diagnosed ACS by categorizing the study population into exposed and non-exposed groups according to baseline chewing status. Cox proportional hazards models were used to examine the associations of areca nut chewing with the risk of re-hospitalization and 30-day mortality secondary to ACS. RESULTS: Of the 384 ACS patients, 49.5% (n=190) were areca users. During 1-month of follow-up, 20.3% (n=78) deaths and 25.1% (n=96) re-hospitalizations occurred. A higher risk of re-hospitalization was found (adjusted hazard ratio [aHR], 2.05; 95% confidence interval [CI], 1.29 to 3.27; p=0.002) in areca users than in non-users. Moreover, patients with severe disease were at a significantly higher risk of 30-day mortality (aHR, 2.77; 95% CI, 1.67 to 4.59; p < 0.001) and re-hospitalization (aHR, 2.72; 95% CI, 1.73 to 4.26; p < 0.001). CONCLUSIONS: The 30-day re-hospitalization rate among ACS patients was found to be significantly higher in areca users and individuals with severe disease. These findings suggest that screening for a history of areca nut chewing may help to identify patients at a high risk for re-hospitalization due to secondary events.
Acute Coronary Syndrome* ; Areca* ; Asia, Southeastern ; Cardiovascular Diseases ; Cohort Studies ; Esophageal Neoplasms ; Follow-Up Studies ; Humans ; Hypertension ; Mass Screening ; Mastication* ; Mortality* ; Nuts* ; Pakistan* ; Proportional Hazards Models ; Prospective Studies

PURPOSE: Overactive bladder (OAB) is a common condition. In women, studies have shown that the prevalence of OAB is positively related to increasing body mass index (BMI). Our objective was to define a relationship between BMI and OAB through correlation with urodynamic study (UDS). METHODS: A prospective study was conducted. Ambulatory women aged 18 years or older who had symptoms of OAB for at least 3 months were enrolled. Patients answered a questionnaire, had their weight and height recorded, and underwent UDS. Patients were categorized into 3 groups as follows: group 1, BMI<25; group 2, BMI 25 to 29.9; and group 3, BMI> or =30. RESULTS: A total of 113 patients were examined (group 1, n=32; group 2, n=40; group 3, n=41). The patients' mean ages were 50, 55, and 59 years for groups 1, 2, and 3, respectively (P<0.05). Group 3 showed a significant increase in the incidence of subjective mixed leakage and the number of pads used compared with groups 1 and 2. No significant differences were seen among the groups in duration of symptoms, OAB V-8 score, or the incidence of subjective urgency or stress leakage. The UDS parameters of groups 1, 2, and 3 showed no statistically significant differences for most variables. Group 3 showed a significant increase in the incidence of urge leakage by UDS compared with group 2 only. CONCLUSIONS: Increasing BMI was age related. A BMI> or =30 showed a higher incidence of subjective urinary mixed leakage and pad use. UDS showed no significant correlation between OAB and any BMI category for most UDS parameters.
Aged ; Body Mass Index ; Female ; Humans ; Incidence ; Prevalence ; Prospective Studies ; Risk Factors ; Urinary Bladder, Overactive ; Urodynamics

We evaluated the performance of MGIT 960 system in terms of recover rate, detection time of mycobacteria and contamination rate from various human clinical specimens and compared it with already in use BACTEC 460 TB system and conventional LJ medium. This is the first reported study on MGIT 960 and its comparison with BACTEC 460 system in Pakistan. A total of 260 different clinical specimens received for the culture of mycobacteria were dealt during the six months study period. All the specimens were digested and decontaminated according to the standard N-acetyl-Lcysteine NaOH method. All the processed specimens were inoculated on both the liquid systems and solid medium and incubated for six weeks and eight weeks consecutively. A total of 44 mycobacterial isolates (Mycobacterium tuberculosis, n=43; Mycobacteria other than tuberculosis, n=1) were recovered from 260 clinical specimens. The recovery rate of M. tuberculosis complex was 97.6% on BACTEC MGIT 960 system and 93.0% on BACTEC 460 system and 83.7% on LJ medium. The mean detection time of mycobacteria on BACTEC MGIT 960 system was 11.2 days in smear positive cases, 14.2 days in smear negative cases and 14.8 days in smear positive cases on BACTEC 460 system. Contamination rates were 9.6% and 5.6% and 3.4% for BACTEC MGIT 960, BACTEC 460 system and LJ medium respectively. The non-radiometric, fully automated BACTEC MGIT 960 system has better diagnostic ability as compared with radiometric, semi-automated BACTEC 460 system and LJ medium, so it can be used as a reliable alternative in over burden laboratories.

The aim of this work was to develop, optimize and characterize a silymarin-laden polyvinylpyrrolidone (PVP)-polyethylene glycol (PEG) polymeric composite to resolve low aqueous solubility and dissolution rate problem of the drug. A number of silymarin-laden polymeric formulations were fabricated with different quantities of PVP K-30 and PEG 6000 by the solvent-evaporation method. The effect of PVP K-30 and PEG 6000 on the aqueous solubility and dissolution rate was investigated. The optimized formula-tion and its constituents were characterized using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) techniques. Both the PEG 6000 and PVP K-30 positively affected the aqueous solubility and dis-solution rate of the drug. In particular, a formulation consisting of silymarin, PVP K-30 and PEG 6000 (0.25/1.5/1.5, w/w/w) furnished the highest solubility (24.3972.95 mg/mL) and an excellent dissolution profile (～100％ in 40 min). The solubility enhancement with this formulation was ～1150-fold as com-pared to plain silymarin powder. Moreover, all the constituents existed in the amorphous state in this silymarin-laden PVP-PEG polymeric composite. Accordingly, this formulation might be a promising tool to administer silymarin with an enhanced effect via the oral route.

Schwannomas, or neurinomas, are generally benign, slow-growing, asymptomatic neoplasms originating from the Schwann cells of a nerve sheath. As a part of spindle cell mesenchymal tumours, schwannomas arising from the gastrointestinal tract (GIT) are unusual; however, when they occur, the most common site involved is the stomach, which represents 0.2% of all gastric tumours. We report the case of a 35-year-old female patient with a history of pulmonary tuberculosis presenting with a large palpable abdominal mass reaching up to the peritoneal cavity. The initial clinical impression was a tuberculous abdominal mass, a cyst, or a teratoma. However, intra-operative findings during a subtotal gastrectomy revealed an exophytic gastric serosal mass, which suggested a gastrointestinal stromal tumour (GIST). Post-operative histopathological findings showed a fascicular arrangement of neoplastic spindle cells with pallisading nuclei that showed intense positivity for S-100 protein, and were negative for CD117 and desmin in immunohistochemistry studies. These results confirmed the final diagnosis of a gastric schwannoma.

BACKGROUND AND PURPOSE: Autosomal recessive cerebellar ataxias constitute a highly heterogeneous group of neurodegenerative disorders. This study was carried out to determine the clinical and genetic causes of ataxia in two families from Pakistan. METHODS: Detailed clinical investigations were carried out on probands in two consanguineous families. Magnetic resonance imaging was performed. Exome sequencing data were examined for likely pathogenic variants. Candidate variants were checked for cosegregation with the phenotype using Sanger sequencing. Public databases including ExAC, GnomAD, dbSNP, and the 1,000 Genome Project as well as ethnically matched controls were checked to determine the frequencies of the alleles. Conservation of missense variants was ensured by aligning orthologous protein sequences from diverse vertebrate species. RESULTS: Reverse phenotyping identified spinocerebellar ataxia, autosomal recessive 1 [OMIM 606002, also referred to as ataxia oculomotor apraxia type 2 (AOA2)] and ataxia telangiectasia (OMIM 208900) in the two families. A novel homozygous missense mutation c.202 C>T (p.Arg68Cys) was identified within senataxin, SETX in the DNA of both patients in one of the families with AOA2. The patients in the second family were homozygous for a known variant in ataxia-telangiectasia mutated (ATM) gene: c.7327 C>T (p.Arg2443Ter). Both variants were absent from 100 ethnically matched control chromosomes and were either absent or present at very low frequencies in the public databases. CONCLUSIONS: This report extends the allelic heterogeneity of SETX mutations causing AOA2 and also presents an asymptomatic patient with a pathogenic ATM variant.
Alleles ; Apraxias* ; Ataxia Telangiectasia ; Ataxia* ; Cerebellar Ataxia ; DNA ; Exome ; Genome ; Humans ; Magnetic Resonance Imaging ; Movement Disorders ; Mutation, Missense ; Neurodegenerative Diseases ; Pakistan ; Phenotype ; Population Characteristics ; Spinocerebellar Ataxias ; Vertebrates

Hantaviruses can cause two types of infections in humans: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome. The old world hantaviruses, primarily Hantaan virus (HTNV), responsible for causing HFRS occurs endemically in Asia and Europe.Apodernus agraricus, a striped field mouse, is being considered as main host reservoir for HTNV. Infection in humans is typically accidental and occurs when virus-containing rodent excretions such as urine, feces, or saliva are aerosolized. The major clinical manifestations includes increased vascular permeability causing vascular leakage, acute kidney injury and coagulation abnormalities. The case fatality rate of HFRS varies around 5.0 - 10.0% depending on the causative viral agent. The direct effects of viral infection on endothelial cells, as well as the immunological response to the viral infection, have been suggested to play a key role in the pathogenesis of HFRS. This article summarizes the current knowledge of HFRS epidemiology in Korea and around the globe, etiology, host transmission, clinical presentation, pathogenesis, diagnostic techniques, treatment, and prevention.

The precise mechanism whereby granulocytes proliferate when haematopoietic colony stimulating factors (CSFs) are used in neutropenic cancer patients is poorly understood. The purpose of this study was to investigate whether these cytokines bring about leucocyte proliferation by increasing the levels of multiple forms of dihydrofolate reductase (DHFR). Blood samples were collected from 36 cancer patients (25 males and 11 females) with chemotherapy-induced neutropenia. One sample of blood from each patient was obtained before therapy either with CSF, such as granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) or with placebo, and another one at the time of resolution of neutropenia. Peripheral blood leucocytes in these blood samples were counted, separated and lysed. From lysates, cytoplasmic samples were prepared and analyzed for active DHFR by a methotrexate-binding assay and for total immunoreactive DHFR by an enzyme linked immunosorbent assay. The increase in total leucocyte count (TLC) was most prominent (P < 0.005) in the CSF group and less so (P < 0.05) in the placebo group. The mean +/- SD concentration values of active DHFR before and after stimulation with GM-CSF found were to be 0.34 +/- 0.4 ng/mg protein and 0.99 +/- 0.82 ng/mg protein, respectively, and in the group treated with G-CSF, 0.24 +/- 0.32 ng/mg protein and 1.18 +/- 2.4 ng/mg protein, respectively. This increase in active DHFR after stimulation with CSF was statistically significant (P <0.05). Similarly, concentration values of immunoreactive but nonfunctional form of DHFR (IRE) were 110 +/- 97 ng/mg protein and 605 +/- 475 ng/mg protein before and after stimulation with GM-CSF, and 115 +/- 165 ng/mg protein and 1,054 +/- 1,095 ng/ mg protein before and after stimulation with G-CSF. This increase in concentration of IRE after stimulation with GM-CSF or G-CSF was statistically significant (P < 0.005). In the control group, there was an increase in the concentration of both active DHFR and IRE after treatment with placebo. However, this was not statistically significant. Resolution of neutropenia was quicker in the groups treated with CSF compared to the control group. Results of this study indicate that colony stimulating factors (G-CSF and GM-CSF) induce white cell proliferation by increasing the levels of multiple forms of DHFR.
Adolescence ; Adult ; Cell Division/drug effects ; Child ; Female ; Granulocyte Colony-Stimulating Factor/therapeutic use ; Granulocyte Colony-Stimulating Factor/pharmacology* ; Granulocyte Colony-Stimulating Factor/adverse effects ; Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology* ; Granulocyte-Macrophage Colony-Stimulating Factor/adverse effects ; Human ; Isoenzymes/metabolism ; Isoenzymes/biosynthesis ; Leukocyte Count ; Leukocytes/pathology ; Leukocytes/enzymology ; Leukocytes/drug effects ; Male ; Middle Age ; Neoplasms/enzymology ; Neoplasms/drug therapy ; Neoplasms/blood* ; Neutropenia/metabolism* ; Neutropenia/chemically induce ; Neutropenia/blood ; Tetrahydrofolate Dehydrogenase/metabolism* ; Tetrahydrofolate Dehydrogenase/biosynthesis