Burden of noncommunicable diseases in Pakistan

Background: Cases of noncommunicable (NCD) diseases are increasing in Pakistan. They are responsible for 58% of all deaths and information on the risk factors is lacking. Aims: To determine the prevalence of diabetes, hypertension and abnormal heart rate and their risk factors in a multiethnic, low-income area of Lahore. Methods: This was a cross-sectional study conducted in an urban settlement of Lahore in 2018–2019. Eligible participants were aged ≥ 30 years and resident in selected settlements. We used a modified World Health Organization stepwise approach to NCD risk factor surveillance (STEPS) questionnaire to collect data from a random sample of 906 residents. The modified questionnaire had a Cronbach alpha of 80.0%. Participants were interviewed in their homes and their height, weight, heart rate, and hip circumference were measured. Results: Most of the respondents were women (64.5%). The greatest proportion of the participants were aged 30–39 years (42.4%). Of all the respondents, 40.1% had hypertension, 15.8% had diabetes and 17.0% had ischaemic heart disease. Of the risk factors examined, 68.8% of the respondents were overweight or obese, 37.0% had pre-hypertension, 13.6% used tobacco, and 1.8% used alcohol. Age was the most significant risk factor for noncommunicable diseases. Body mass index was significantly associated with diabetes in women, while family history of diabetes was significantly associated with diabetes in men. Conclusion: The prevalence of hypertension and diabetes was higher among our study participants in Lahore than reported in the national statistics. Significant proportions of the respondents had pre-hypertension and pre-diabetes, making them vulnerable to serious complications of hypertension and diabetes.

Micro-organisms and risk factors associated with prosthetic joint infection following primary total knee replacement-our experience in Pakistan.

PURPOSE: To identify potential risk factors and micro-organisms associated with prosthetic joint infection following primary total knee replacement surgery. HYPOTHESIS OF STUDY: Our hypothesis is that body mass index (BMI), operative time, type of surgery, and order of surgery especially in bilateral simultaneous cases have a major impact on prosthetic joint infection (PJI). METHODOLOGY: We identified 4269 patients who underwent for primary knee replacement surgery between 2008 and 2018. We recorded patient demographics, comorbidities, order of surgery, type of surgery, causative micro-organism, and their antibiotic susceptibility. Multivariable logistic regression analysis was built to identify risk factors that are associated with prosthetic joint infection following primary total knee replacement. RESULTS: Forty-eight patients developed prosthetic joint infection. The factors that are found to be associated with prosthetic joint infection are BMI, operative time, type of surgery, order of surgery, diabetes, and rheumatoid arthritis. Methicillin-resistant Staphylococcus aureus (MRSA) was the major underlying pathogen seen in majority of cases. CONCLUSION: Despite low incidence of prosthetic joint infection following primary total knee replacement, there are patients at higher risk that would benefit by addressing modifying risk factors significantly associated with prosthetic joint infection.

Functional outcome of ACL reconstruction using patellar bone tendon bone graft.

PURPOSE: To evaluate the mid-term functional outcome using Lysholm score of anterior cruciate ligamentreconstruction using bone patella-tendon bone graft. METHODS: The retrospective study of prospectively collected data was conducted at Liaquat National Hospital, Karachi, from June 2010to June 2013, and comprised patients with complete anterior cruciate ligamenttear who were treated with diagnostic arthroscopy and open reconstruction using bone patella-tendon bone graft. All patients were operated under tourniquet control and knee immobiliser was applied. Straight leg raise procedure was started on 2nd postoperative day. One year after surgery, functional outcome was assessed using Lysholm score. RESULTS: All the 36(100%) patients in the study were males. Four (11%) patients were lost to follow-up and were excluded, while 32(89%) completed the study. Right knee was involved in 16(50%) patients while left knee was involved in 16(50%) patients. Overall, 31(97%) patients had history of contact sports injury. The average age of patients was 28.25±8.32 years. All patients were operated at an average of 17.5±10.3 weeks. The ligament tear was associated with medial meniscal tear in 16(50%) patients, while lateral meniscal tear was noted in 10(31.25%). The mean Lysholm score was 83.06±4.17at 1 year (fair to good outcome). The average range of motion 1 year after surgery was 127.5±11.25. Loss of extension <3o was noted in 20(62.5%) patients, while >3o was noted in 12(37.5%). The average loss of extension was 3.5±2.3 degrees. Two (6.25%) patients developed superficial infection which subsided with oral antibiotics. Anterior knee pain was reported by 8(25%) patients. CONCLUSIONS: Patellar bone tendon bone graft was a reliable method for reconstruction of anterior cruciate ligament.

Activation of cytosolic phospholipase A2alpha in resident peritoneal macrophages by Listeria monocytogenes involves listeriolysin O and TLR2.

Eicosanoid production by macrophages is an early response to microbial infection that promotes acute inflammation. The intracellular pathogen Listeria monocytogenes stimulates arachidonic acid release and eicosanoid production from resident mouse peritoneal macrophages through activation of group IVA cytosolic phospholipase A2 (cPLA2alpha). The ability of wild type L. monocytogenes (WTLM) to stimulate arachidonic acid release is partially dependent on the virulence factor listeriolysin O; however, WTLM and L. monocytogenes lacking listeriolysin O (DeltahlyLM) induce similar levels of cyclooxygenase 2. Arachidonic acid release requires activation of MAPKs by WTLM and DeltahlyLM. The attenuated release of arachidonic acid that is observed in TLR2-/- and MyD88-/- macrophages infected with WTLM and DeltahlyLM correlates with diminished MAPK activation. WTLM but not DeltahlyLM increases intracellular calcium, which is implicated in regulation of cPLA2alpha. Prostaglandin E2, prostaglandin I2, and leukotriene C4 are produced by cPLA2alpha+/+ but not cPLA2alpha-/- macrophages in response to WTLM and DeltahlyLM. Tumor necrosis factor (TNF)-alpha production is significantly lower in cPLA2alpha+/+ than in cPLA2alpha-/- macrophages infected with WTLM and DeltahlyLM. Treatment of infected cPLA2alpha+/+ macrophages with the cyclooxygenase inhibitor indomethacin increases TNFalpha production to the level produced by cPLA2alpha-/- macrophages implicating prostaglandins in TNFalpha down-regulation. Therefore activation of cPLA2alpha in macrophages may impact immune responses to L. monocytogenes.

Delineation of an in vivo inhibitor for Aspergillus glutamate dehydrogenase.

NADP-glutamate dehydrogenase (NADP-GDH) along with glutamine synthetase plays a pivotal role in ammonium assimilation. Specific inhibitors were valuable in defining the importance of glutamine synthetase in nitrogen metabolism. Selective in vivo inhibition of NADP-GDH has so far been an elusive desideratum. Isophthalate, a potent in vitro inhibitor of Aspergillus niger NADP-GDH [Noor S, Punekar NS. Allosteric NADP-glutamate dehydrogenase from aspergilli: purification, characterization and implications for metabolic regulation at the carbon-nitrogen interface. Microbiology 2005;151:1409-19], was evaluated for its efficacy in vivo. Dimethyl ester of isophthalate (DMIP), but not isophthalate, inhibited A. niger growth on agar as well as in liquid culture. This was ascribed to the inability of isophthalate to enter fungal mycelia. Subsequent to DMIP addition however, intracellular isophthalate could be demonstrated. Apart from NAD-GDH, no other enzyme including NAD-glutamate synthase was inhibited by isophthalate. A cross-over at NADP-GDH step of metabolism was observed as a direct consequence of isophthalate (formed in vivo from DMIP) inhibiting this enzyme. Addition of ammonium to DMIP-treated A. niger mycelia resulted in intensive vacuolation, retraction of cytoplasm and autolysis. Taken together, these results implicate glutamate dehydrogenase and NADP-GDH in particular, as a key target of in vivo isophthalate inhibition during ammonium assimilation.

Allosteric NADP-glutamate dehydrogenase from aspergilli: purification, characterization and implications for metabolic regulation at the carbon-nitrogen interface.

NADP-dependent glutamate dehydrogenase (NADP-GDH) mediates fungal ammonium assimilation through reductive synthesis of glutamate from 2-oxoglutarate. By virtue of its position at the interface of carbon and nitrogen metabolism, biosynthetic NADP-GDH is a potential candidate for metabolic control. In order to facilitate characterization, a new and effective dye-affinity method was devised to purify NADP-GDH from two aspergilli, Aspergillus niger and Aspergillus nidulans. The A. niger NADP-GDH was characterized at length and its kinetic interaction constants with glutamate (Km 34.7 mM) and ammonium (Km 1.05 mM; Ki 0.4 mM) were consistent with an anabolic role. Isophthalate, 2-methyleneglutarate and 2,4-pyridinedicarboxylate were significant inhibitors, with respective Ki values of 6.9, 9.2 and 202.0 microM. The A. niger enzyme showed allosteric properties and a sigmoid response (nH=2.5) towards 2-oxoglutarate saturation. The co-operative behaviour was a feature common to NADP-GDH from Aspergillus awamori, A. nidulans and Aspergillus oryzae. NADP-GDH may therefore be a crucial determinant in adjusting 2-oxoglutarate flux between the tricarboxylic acid cycle and glutamate biosynthesis in aspergilli.