The Role of Peroxisome Proliferator Activated Receptor γ (PPARγ) Ligands on Foam Cells Formation Derived From Murine Norovirus-1 (MNV-1) Infected Macrophage

Abstract@#Introduction: Atherosclerosis is a chronic inflammatory disease initiated by the accumulation of macrophage derived foam cells in the intima layer of artery. In mice model of atherosclerosis, murine norovirus-4 has been shown to accelerate atherogenesis. In cells, lipid biometabolism is regulated by peroxisome proliferator activated receptor γ (PPARγ). Since PPARγ is predominantly expressed in macrophages and mice macrophages are MNV-1 proliferation-permissive host, we hypothesised that PPARγ ligands may regulate atherogenesis. Methods: MNV-1 was generated via RNA-based recovery system and used to infect the RAW 264.7 cells, then subjected to oxidized low-density lipoprotein (oxLDL)-loaded and treated with ciglitazone or 15-deoxy-Delta(12,14)-PGJ(2)(15d-PGJ2). Foam cell formation was evaluated and the MNV-1 infection in all treatments was confirmed using virus titration (50% tissue culture infective dose; TCID50) and polymerase chain reaction (PCR). Results: Increment of lipid droplets was observed in all oxLDL treatment involving MNV-1 infection, ciglitazone or 15d-PGJ2 in the cytosol of RAW 264.7 cells over time compared to non-oxLDL treated cells. From the cholesterol ester (CE) content analysis amongst the oxLDL-loaded cells however, we found MNV-1 did not elicit increment of CE content. Treatment with 15d-PGJ2 resulted in increase of the CE content in oxLDL-treated cells. Interestingly, MNV-1 and ciglitazone had synergistic effect in reducing the CE content in oxLDL-treated cells. Conclusion: oxLDL stimulates foam cells formation in RAW 264.7 cells. However, MNV-1 infection did not contribute to RAW 264.7 cells derived-foam cells formation. On the other hand, 15d-PGJ2 promotes foam cells formation whilst ciglitazone inhibits the formation of foam cells derived from MNV-1-infected macrophages.

case of vogt-koyanagi-harada syndrome mimicking optic neuritis

Vogt-Koyanagi-Harada syndrome is a rare disease that occurs commonly in pigmented individuals of Asian origin. A 25-year female presented in medical outpatient department [OPD] of Al-Khidmat Teaching Hospital, Mansoora, Lahore with headache and neck stiffness. She was referred to eye OPD for the complaint of decreased vision. On examination, there was 6/24 vision, sluggish pupillary reaction and disc hyperemia in both eyes. She was treated as a case of optic neuritis. Few days later, she developed bilateral panuveitis, shallow exudative detachments and alopecia. Clinical picture with normal magnetic resonance imaging [MRI] and laboratory tests helped us in reaching the diagnosis of Vogt-KoyanagiHarada syndrome

P16INK4a: A Potential Diagnostic Adjunct For Prediction Of Highgrade Cervical Lesions In Liquid-Based Cytology: With HPV Testing And Histological Correlation

Human papillomavirus (HPV) is a necessary cause of cervical cancer and its precursors. Increased expression of high-risk hrHPV viral oncogenes in abnormal cells might increase the expression of p16INK4a. We aimed to determine the role of p16INK4a in detecting hrHPV-transformed epithelial cells in liquid-based cervical cytology, and compared the results with hrHPV DNA testing by realtime polymerase chain reaction (RT-PCR). Fifty-seven cytological samples were tested for p16INK4a immunomarker and hrHPV DNA. Test performance of both tests was determined by comparing sensitivity, specificity and predictive values using available histological follow-up data as gold standard. Of 57 samples, 36 (63.2%) showed immunoreactivity for p16INK4a and 43 (75.4%) were hrHPV-infected. A fairly low concordance rate (k = 0.504) between p16INK4a immunolabelling and hrHPV DNA status was noted. For prediction of cervical intraepithelial neoplasia (CIN) II and worse lesions, p16INK4a had a sensitivity and specificity of 93.5% and 60%; whereas hrHPV DNA testing had a sensitivity and specificity of 100% and 20%. Dual testing by combining p16INK4a and hrHPV showed sensitivity and specificity of 100% and 33.3%. In conclusion, p16INK4a is useful in predicting severity of the cytological abnormalities. Although p16INK4a is more specific but less sensitive than hrHPV in detecting high-grade cervical lesions, a combination of both tests failed to demonstrate significant improvement in diagnostic sensitivity, specificity and predictive value. Larger-scale prospective studies are required to assess further whether this biomarker should be routinely used as primary screening tool independently or in combination with hrHPV testing to improve diagnostic accuracy in cervical cytology.

Tuberculosis diagnosis and treatment; qualitative study on the coping mechanisms for economic consequences

Pakistan is eighth among countries with high burden of tuberculosis [TB]. In Pakistan free-of-charge TB diagnosis and treatment services are available. The objective of qualitative exploratory study was to understand how TB patients and their families cope with the lost earnings and increased expenditures [other than diagnosis and treatment cost] related with disease and its treatment. The research methods included literature review, focus group discussion using vignettes and in-depth interviews with TB patients. The study was done in the rural areas of Lahore District with the support of district and local health facility staff. The study revealed that, Results like in many other developing countries, TB patients rely mainly on financial and physical support of family members and friends. Conclusion The study also highlighted the need for developing institutional mechanisms to help patients cope with economic consequences of tuberculosis

Multiple pesticide residues; in spinach and associated health risk

In past, no work has been done regarding the pesticide residues in spinach targeting peri-urban area of district Faisalabad. Keeping in view the persistent nature and cumulative behavior as well potential toxic effects of pesticides as a result of consumption of vegetable this is planned. Food safety is a major public concern worldwide. This is serious problem in the whole world especially in economically poor countries like Pakistan. The production of safe food is an important aspect of food quality assurance as well as human health. The people are demanding fresh, hygienic and quality food. To study the level of pesticide residues in spinach grown in peri-urban area of district Faisalabad and compare the level of contaminants respective their maximum residues limits [MRLS]. Ten farmers were selected randomly for spinach in the peri-urban area of district Faisalabad and vegetable samples were collected at optimum maturity in triplicate and transported to the laboratory of National Institute of Food Science and Technology, University of Agriculture, Faisalabad for further processing. The residues of pesticide were determined by GC-ECD. The results regarding pesticide residues in different spinach samples showed variations and residues varied as deltamethrin 0.024 to 0.143 mg Kg[-1], permethrin 0.159 to 0.573 mg Kg[-1], cypermethrin 0.098 to 0.503 mg Kg[-1], profenofos 0.016 to 0.425 mg Kg[-1], chlorpyrifos 0.009 to 0.212 mg Kg[-1], bifenthrin 0.012 to 0.623 mg Kg[-1], endosulfan 0.043 to 0.103 mg Kg[-1], dimethoate 0.077 to 0.515 mg Kg[-1], respectively. The chlorpyriphos has no residues in any sample of spinach. The spinach samples are found to be contaminated with a number of different pesticides and these pesticides are not applied judiciously according to good agricultural practices and recommended doses. The farmers are unaware of pesticide use and other agricultural practices due to lack of extension as result causes of serious problems to all community

Attitude and preferences of surgical patients towards female surgeons

To assess patient preferences towards gender of operating surgeon so as to predict acceptance of female surgeons in the segment of Pakistani population. Cross sectional survey. Department of Surgery Shifa College of Medicine and Shifa International Hospital Islamabad, from January 2012 to December 2013. Patients of both genders, who were scheduled for any general surgical procedure were included. Patients below 18 year of age were excluded. Questionnaire included statements related to choice of gender of operating surgeon, type of surgery performed, qualification, age, marital status of the patient and area [rural/urban] of origin. Results were analyzed using SPSS version 17. Chi-square test was used for calculating significance of categorical variables. Out of total 324 patients 182[56.2%] were males and 137[42.3%] females. Eight patients did not mention about their gender. Majority [46.6%] of the patients had no preference for gender of the operating surgeon while 113 [34.9%] preferred male surgeons. Fifty-two [16%] however had preference for female surgeons. Slight preponderance was noted for gender preference either male or female. The surgeon gender consideration was only based upon type of the procedure performed

Ondansetron versus combined dexamethasone and metoclopramide in prevention of nausea and vomiting after laparoscopic cholecystectomy

To compare the efficacy of combined metoclopramide and dexamethasone with ondansetron in preventing nausea and vomiting after laparoscopic cholecystectomy. Randomized controlled trial. Surgical Unit I Combined Military Hospital Rawalpindi, from 1[st] June 2010 to 3[rd] January 2011. A total of 120 patients were observed for 24 hours after elective laparoscopic cholecystectomy for nausea and vomiting and divided into two groups of 60 patients each. Nausea and vomiting was rated by the patients according to a three point scale [O=no nausea and vomiting, 1= nausea, 2= retching or vomiting]. Early postoperative nausea and vomiting was not present in 31[51.7%] patients of group 1 and 40[66.7%] of group 2 [score = 0]. In 11[18.3%] patients of group 1 and 12 [20.0%] of group 2 only nausea was present [score = 1], while 18[30.0%] patients in group 1 and [13.3%] in group 2 scored 2.The late postoperative nausea and vomiting was not present in 21[35.0%] patients in group 1 and 37[61.7%] in group II [score = 0]. In 28 [46.7%] patients in group 1 and 22[36.7%] in group 2 nausea was present [score = 1] while 11[18.3%] patients of group 1 and 1[1.7%] in group 2 scored 2. Ondansetron was effective as compared to combined metoclopramide and dexamethasone in prevention of post-laparoscopic cholecystectomy nausea and vomiting

Common carotid artery intima-media thickness in patients with ischaemic and haemorrhagic stroke

An increase in the intima-media thickness of the common carotid after [CCA-IMT] is generally considered as an early marker of atherosclerosis and has been associated with a higher risk of stroke and myocardial infarction. Cross-sectional Study. This study was conducted in Department of Medicine at Karachi Medical and Dental College and Abbasi Shaheed Hospital from June 2011 to December 2011. We determined cross-sectionally the diagnostic ability of CCA-IMT to distinguish between brain infarction and intracerebral haemorrhage. Total 150 patients aged >40 years of both sexes with hemorrhagic and ischaemic stroke were included, while patients with history of endartectomy, head injury, space occupying lesion and on anticoagulation were excluded. All information was recorded on proforma. Thickness of common carotid artery of >/= 0.5 mm was considered significant. Analysis was performed through SPSS-10.0. Frequencies and percentages were computed to present categorical variables including stroke type and wall thickness of common carotid artery in terms of [ 0.5 mm]. Chi-square test was applied to see association of increased CCA-IMT with stroke type. Statistical significance was taken at p < 0.05. Among 150 patients of stroke, 13 [8.7%] patients of left and 8 [5.3%] patients of right had increased CCA-IMT. The CCA-IMT was significantly higher in patients with ischemic stroke patients [p=0.001]. The present results demonstrate the possible predictive power of non-invasive measure meant of CCA-IMT with respect to brain infarction versus intracerebral hemorrhage and deserve further investigation. Despite high prevalence of hypertension in patients with haemorrhagic stroke, increased CCA-IMT which is considered as an early marker of atherosclerosis is strongly related to ischaemic stroke than haemorrhagic stroke

Treatment supporters and their impact on treatment outcomes in routine tuberculosis program conditions in Rawalpindi district, Pakistan

Tuberculosis [TB] is a major cause of mortality affecting millions of people in third world countries. In DOTS monitoring of patients is facility based and treatment supporter-based; by these two ways patients' compliance to treatment is monitored. The aim of this study was to evaluate the role of treatment supporters and their impact on patients' treatment outcomes. The study was a cross-sectional survey in the routine TB control program operational context. All sputum smear positive TB patients that were diagnosed and registered by the public sector in the urban and rural diagnostic centers in 2008 with available outcomes were included in the study. Data of 451 patients were collected during August-October 2010 from 15 health facilities. The majority of patients [89.6%] were provided with treatment supporters. Of 404 [89.6%] cases with treatment supporters, in 203 [50.2%] the supporters were lady health workers, in 46 [11.4%] were community health workers and health facility workers, and in 155 [38.4%] were family members and community volunteers. A total of 384 [85.1%] were categorized as "treatment success", 31 [6.9%], as "transferred out", 17 [3.8%], as "expired", 16 [3.5%] as "defaulted" and three [0.7%] as "treatment failure". The treatment success rates in patients supervised by Lady health workers, community health workers and health facility workers, and family members and community volunteers were 93.1%, 89.1% and 73.5%, respectively. We found a significantly higher treatment success rate [93.1%] in patients supervised by lady health workers compared to others. The overall treatment success rate was 85.1%

Hypertensive encephalopathy: a rare presentation of Williams-Beuren syndrome

A male child of four years is reported with Williams-Beuren Syndrome [WBS]. It was not recognized initially when he presented with odd facies and developmental delay since early infancy. The diagnosis was established later when he developed hypertensive encephalopathy secondary to bilateral renal artery stenosis, a congenital anomaly that must be looked for in such patients. No echographic evidence of congenital heart disease was found. Blood pressure estimation on routine physical examination of every child is emphasized. The diagnosis is mainly clinical as the definitive chromosomal studies are presently not available in Pakistan

Gall stone ileus; a serious complication of cholelithiasis in an elderly

Gallstone ileus [GSI] is an uncommon cause of intestinal obstruction. The formation of a fistula between the gall bladder and the bowel wall may allow a gallstone to enter the intestinal tract. Plain abdominal films, abdominal ultrasound and abdominal computed tomography aid in the diagnosis. Surgery is the treatment of choice in cases of gallstone ileus rate. We describe the case of a 68-year-old man who presented with symptoms and signs of intestinal obstruction. Diagnostic evaluation revealed a large gallstone impacted in the ileum. The patient was scheduled for exploratory laparotomy. At the time of surgery stone was found in the sigmoid colon. It was milked down and brought out through the rectum

Dermatofbrosarcoma protuberans presenting in young male

Dermatofibrosarcoma protuberans [DFSP] is a rare tumour of skin and soft tissue. A 35 years old male presented in December, 2005 with a recurrent soft tissue swelling on the left anterior chest wall which had been increasing in size for the last one year. He had a nodule removed from same site 6 years back. The soft tissue swelling on biopsy turned out to be Dermatofibrosarcoma protuberans [DFSP]. Case history is presented with review of literature

Effect of cast immobilization on contractile characteristics of skeletal muscles of uromastix

Cast immobilized [Imb] mammalian skeletal muscles exhibits reduced tension generation ability with morphometric changes and atrophy. However, controversies still exist with respect to changes in muscle mechanics in different positions of immobilization [IMB]. In addition, reptilian muscles have been ignored generally, and for the effects of IMB, specially. This study was carried out to observe the effects of different positions of IMB on contraction parameters of Uromastix skeletal muscles. Left hind limb was Imb in stretched knee and flexed ankle position for 20 days, right being the control [Cont]. After 20 days Sartorius [Sar], Gastrocnemius [Gas]. Peroneus Longus [PL] and Peroneus Brevis [PB] muscles were isolated to record the isometric twitch and tetani for the measurements of tension, rate of rise of tension [dp/dt] and duration of active state [DAS]. After IMB, morphometric parameter does not change significantly in any muscle except the stretched and flexed lengths in Gas. The tensions however, reduced significantly in Imb Sar and Gas which were non-significantly greater in the Imb PL and PB. The dp/dt parameters and DAS reduced in Imb Sar, Gas and PL. It was however, significantly higher in Imb PB. Skeletal muscle mechanics differ for different positions of IMB in reptilian muscle model as well. The earlier reported controversies probably indicate differences in IMB induced stretch, dimensions and anatomy of individual muscle of different animal models

Evaluation of hyperpolarization potentials and nerve conduction parameters in axonal neuropathic patients

Neuropathies are diagnosed on the basis of some specific parameters of compound motor unit action potential [CMAP]. The slowing of conduction velocity along with relatively, preserved amplitude considered an indication of demyelination. While, amplitude reduction and slightly slowed conduction velocity, referred to axonal degeneration. Further, CMAP shape and distal latencies are also important for the diagnosis of neuropathies. Although, hyperpolarization is one of the important phase of CMAP but, it is mentioned only in the cases of nerve conduction block and never considered to identify other neuropathies. Therefore, in the present study the hyperpolarization phase of CMAP has been compared and evaluated in terms of its amplitude and duration and its occurrence in axonal neuropathy. The CMAP records of normal subjects and axonal neuropathic patients; randomly selected from OPD cases and evaluated for the occurrence of hyperpolarization, its amplitude, duration, latencies, CMAP amplitude and NCV. The recordings were obtained from the stimulation of median and tibial nerves [both distally and proximally] with recordings of CMAP from Abductor Pollicis Brevis and Abductor Hallucis muscles, respectively. The amplitude and duration of hyperpolarization and other parameters measured from both, median and tibial nerves were significantly lesser in neuropathic patients than the normal ones. Hyperpolarization reduces significantly in axonal neuropathy and this phase of CMAP may also be considered for the evaluation in other neuropathies. Further, criteria may be formulated for the diagnosis of various neuropathies using hyperpolarization phase of CMAP

Obesity among schoolchildren in Kuala Selangor: a cross-sectional study

Childhood obesity is an established problem in many countries and emerging in others. Epidemiological data on obesity in children is essential in order to plan public health policy and services. A study was conducted to determine the prevalence of obesity in schoolchildren in the fifth grade of elementary school (10-12 years old) in the district of Kuala Selangor. Ten schools of which five are in urban and five in rural areas were selected consisting of 699 eleven year old schoolchildren from the three major ethnic groups. Using international cut-off points for obesity, we report an overall prevalence of obesity of 7.2%. Prevalence of obesity in urban children is 7.2% whereas in rural children it is 7.0 %. Analysed by gender, there were 8.9% obese boys and 5.3% obese girls. Among the 3 major ethnic groups, the Malays had the highest prevalence of obesity at 9.3% followed by the Chinese with 6.6% while among Indians 3.0%. The data obtained from this study suggests that obesity in Kuala Selangor children is a cause for concern in urban and rural areas.

Pre-operative evaluation of ovarian mass: risk of malignancy index

To evaluate the risk of malignancy index [RMI] for pre-operative diagnosis of ovarian mass. Design: Observational study. Place and Duration of Study: Department of Chemical Pathology and Endocrinology at Armed Forces Institute of Pathology [AFIP], Rawalpindi from January 2001 to January 2002. Subjects and The study consisted of 100 female patients consecutively admitted for surgical exploration of ovarian mass. Pre-operatively ultrasonic evaluation of ovarian mass, menopausal status and serum cancer-associated antigen 125 [CA 125] levels were carried out. Postoperatively histopathology of the resected ovarian mass was done to confirm the diagnosis. To increase the sensitivity and specificity of CA 125 for early detection of ovarian cancer, a combination of serum CA 125 with ultrasonography and menopausal status, designated as risk of malignancy index [RMI] for each patient, was calculated. The sensitivity and specificity of CA 125 alone for the diagnosis of ovarian cancer, at cutoff level of 35 U/ml, were 83% and 82% respectively. Using RMI, at cutoff level of 125, the sensitivity was 87%, and specificity was 88%. Receiver operating characteristic [ROC] curves reveal that RMI was a better discriminant than CA 125 alone for differentiating between benign lesions and malignant ovarian tumors. The risk of malignancy index [RMI] is a better diagnostic marker as compared to CA 125 alone because of its high specificity and sensitivity in differentiating ovarian cancer from ovarian benign lesions. It is a simple scoring system and, therefore, its application is recommended to evaluate ovarian masses in clinical practice

Neoadjuvant chemotherapy in stage IV ovarian malignancy

A 57 years old woman was diagnosed to have stage IV ovarian malignancy on the basis of ascitic fluid cytology, tumor marker and imaging. Neoadjuvant chemotherapy was administered before surgery. Four months after surgery no evidence of malignancy was found on laparotomy and histopathology. She is under surveillance for any signs of recurrence

Hyperhomocysteinemia as a risk factor for ischemic heart disease

To determine association of hyperhomocysteinemia with myocardial infarction and conventional risk factors for ischemic heart disease. Design: A non-interventional comparative case control study. Place and Duration of Study: The study was conducted at the department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi and Armed Forces Institute of Cardiology / National Institute of Heart Diseases, Rawalpindi from January 2001 to June 2001. Patients and A total of 100 hospitalized patients having myocardial infarction [MI] were randomly selected comprising 85 males and 15 females. The average age of the patients was 53 +/- 4.5 years. A similar number of age and gender-matched healthy controls were also selected. The demographic details, history and clinical examination of both patients and controls were recorded and their blood was collected in fasting state for estimation of serum total cholesterol, plasma glucose and serum total homocysteine. Serum total homocysteine level in controls was significantly lower [10.8 +/- 4.1 mmol/L] as compared to patients [18.0 +/- 5.9 mmol/L] [p < 0.0001]. Smoking showed statistically significant association with hyperhomocysteinemic patients [p = 0.04]. Ischemic heart disease was associated with moderate hyperhomocysteinemia in our patients and it was also associated with smoking

Stress hyperglycemia

Stress hyperglycemia is commonly encountered condition in a wide variety of clinical settings. It represents body response to stress by various neurohumoral mechanisms. Elevation of stress hormones, epinephrine and cortisol occurs during stress, that is accompanied with elevation of corticotrophin, growth hormone and glucagon. These changes are responsible for hyperglycemia and hypercatabolism seen in stressful conditions. Depending upon the nature of stress, hyperglycemia varies from mild to severe with no upper limit and disappears once the stress is over. Although, not an entirely innocuous condition, yet, it is a marker of bad prognosis in certain clinical states which should be closely monitored. Stress hyperglycemia must be differentiated from diabetes mellitus for proper management of the patient