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   Table of Contents - Current issue
Coverpage
July-September 2017
Volume 8 | Issue 3
Page Nos. 81-153

Online since Wednesday, September 27, 2017

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REVIEW ARTICLES  

An overview of the extraarticular involvement in rheumatoid arthritis and its management p. 81
Subham Das, Prasanta Padhan
DOI:10.4103/jpp.JPP_194_16  
Rheumatoid arthritis (RA) is an autoimmune systemic disease characterized by long-standing inflammation and significant joint destruction. Despite significant research and success toward the treatment modalities, complete remission still remains a challenge. Even then a number of early and late extraarticular manifestations (EAMs) of the disease further complicate the disease progression. Various EAM encountered in RA can involve more than one organ or system in the body and their clinical features also show lot of variations, mostly involving cutaneous, cardiovascular, and pulmonary systems. The mortality associated with EAM may also be quite high in RA, sometimes more than the disease itself. These EAMs are difficult to diagnose and even more difficult to treat since no clear consensus exists among the rheumatologists as to their correct classification and also due to the fact that no clearcut guidelines are available for their treatment. With this background knowledge, the present review focuses on the various EAMs of RA, their classification, clinical features, and general management overview.
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Retrospection on the role of soluble guanylate cyclase in parkinson's disease p. 87
Mohankrishna Ghanta, Elango Panchanathan, Bhaskar V. K. S Lakkakula, Anbumani Narayanaswamy
DOI:10.4103/jpp.JPP_45_17  
Soluble guanylate cyclase (sGC) is an important transducing enzyme of cyclic guanosine monophosphate (cGMP) signaling pathway in striatum which has been considered as a potential target for the treatment of Parkinson's disease. Etiology of Parkinson's disease is multifactorial, finally resulting in abnormal proteinopathies causing degeneration of nigrostriatal pathways. Understanding the pathological basis of Parkinson's disease at molecular level is still an achievable target for the researchers and clinical practitioners. sGCs may be one of the causative factors resulting in Parkinson's disease due to glutamate toxicity or other event. This review presents the literature from articles of past five decades nearly as still this enzyme protein and its role in Parkinson's disease is not that clearly understood or presented till date. Recent interventions of this protein inhibition in the treatment of Parkinson's disease preclinically gave a chance to review the literature about this enzyme and its correlation with factors causing Parkinson's disease. We explored literature using PubMed and EMBASE for the role of sGC in Parkinson's disease. Databases were searched using the following terms: Parkinson's disease, neurotoxins, guanylate cyclase, sGC-cGMP pathway, and neurodegeneration. This review listed out the factors that have probability for stimulating sGC which already have been listed as a neurotoxins causing Parkinson's disease.
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RESEARCH PAPERS Top

Biological response modifiers in rheumatoid arthritis: Systematic review and meta-analysis of safety p. 92
Nitishkumar D Tank, Bharti N Karelia, Bhavisha N Vegada
DOI:10.4103/jpp.JPP_155_16  
Objective: To analyze available evidence on the safety of different biological response modifiers which are used for a treatment of rheumatoid arthritis (RA). Materials and Methods: We searched systematically for randomized controlled clinical trials on treatment of RA with different biological response modifiers, followed by a systematic review with meta-analysis. Trials were searched from MEDLINE and Cochrane Library databases. The following safety parameters reported in the selected trials were analyzed: number of patients suffering any adverse event (AE), withdrawal due to AEs, serious AE (SAEs), infections, serious infections, infusion reactions, injection site reactions, malignancies, and overall mortality. Undesired effects were estimated using combined relative risks (RR) and number needed to harm (NNH). Heterogeneity was evaluated by Cochrane's Q and I2 statistics. Results: According to inclusion criteria, a total of 43 trials (20,504 patients) were included in this study. A total number of AEs were found more with abatacept (RR: 1.05, NNH: 21.93). Withdrawal due to AEs was found with all biologicals, highest with anakinra (RR: 3.48, NNH: 15.70). Patients receiving newer tumor necrosis factor-alpha inhibitors, golimumab, were more likely to develop SAEs (RR: 2.44, NNH: 12.72) and infection (RR: 1.25, NNH: 10.09), and in certolizumab, serious infections (RR: 2.95, NNH: 37.31) were found more. Infusion reaction develops more with rituximab (RR: 1.52, NNH: 8.47). Etanercept showed the highest risk to develop infusion site reaction (RR: 5.33, NNH: 4.65). Biologicals showed no difference to their control counterparts in malignancy and mortality risk. Conclusion: This meta-analysis helps to clarify some frequently encountered and unanswered safety questions of different biological response modifiers, a new class of drugs, in the clinical care of RA patients.
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Efficacy and tolerability of olmesartan, telmisartan, and losartan in patients of stage I hypertension: A randomized, open-label study p. 106
Mrunalini Kalikar, Kundan S Nivangune, Ganesh N Dakhale, Chaitali S Bajait, Smita D Sontakke, Vijay M Motghare, Ritu Budania
DOI:10.4103/jpp.JPP_39_17  
Objectives: To compare the efficacy and tolerability of losartan, telmisartan, and olmesartan as antihypertensive agents and evaluate and compare their effects on lipid profile and blood glucose. Materials and Methods: This was a randomized, open-label, parallel-group, comparative study conducted in sixty patients of Stage I hypertension. The eligible patients were randomly allocated into three treatment groups: (1) Tablet olmesartan (20 mg), (2) Tablet telmisartan (40 mg), and (3) Tablet losartan (50 mg). Blood pressure (BP) was assessed at an interval of 2 weeks for 3 months. Fasting blood glucose (FBG) and lipid profile were estimated at baseline and then at 12 weeks. Results: Olmesartan and telmisartan were more efficacious than losartan in reducing diastolic BP (DBP). There was a statistically significant decrease in mean blood glucose level (P < 0.02) after 12 weeks of treatment in telmisartan group when compared to baseline. Serum total cholesterol, triglycerides, and low-density lipoproteins decreased significantly after 12-week treatment with olmesartan and telmisartan. Conclusions: The most efficacious drug in reducing BP is Olmesartan whereas telmisartan and losartan show equal efficacy. Telmisartan shows the most favorable effects on FBG and lipid profile.
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Effect of lorazepam in reducing psychological distress and anticipatory nausea and vomiting in patients undergoing chemotherapy p. 112
Aloysius James, Malini Muraleedharan Nair, Dhanya Susan Abraham, Joel Sunny Kovoor, Wesley M Jose, Remya Reghu
DOI:10.4103/jpp.JPP_54_17  
Objectives: To evaluate the efficacy and safety of lorazepam in reducing psychological distress and chemotherapy-induced nausea and vomiting. Methodology: It was a prospective interventional study with seventy patients for a period of 1 year. In which, patients' anxiety, distress and status of nausea, and vomiting were assessed in the first four chemotherapy cycles before drug intervention. During the subsequent chemotherapy cycles, the outcomes of the intervention were reassessed along with patient's quality of life (QOL). Results: Out of seventy patients, 62 showed improvement in their distress level after the drug intervention and patient counseling. Lorazepam along with other antiemetic drugs reduced chemotherapy-induced delayed nausea and vomiting. During the course of the study, 15 patients experienced drowsiness as an adverse reaction to lorazepam. The overall QOL of the population was also improved with lorazepam. Conclusion: Lorazepam along with patient counseling can improve patient's psychological distress and thus their QOL. The off-labeled use of lorazepam can be utilized for controlling chemotherapy-induced nausea vomiting.
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Treatment outcome of ovulation-inducing agents in patients with anovulatory infertility: A prospective, observational study p. 116
Kinjal Prajapati, Mira Desai, Samidh Shah, Sumesh Choudhary, Rohina Aggarwal, Vineet Mishra
DOI:10.4103/jpp.JPP_43_17  
Objective: To compare different treatment regimens on pregnancy rate and outcome in patients with anovulatory infertility. Patients and Methods: A prospective observational study was conducted on patients with infertility due to anovulation. Patients treated with clomiphene citrate (CC) 50/100 mg/day from 2nd to 6th day of menstrual cycle (MC) (n = 38), short gonadotropin-releasing hormone (GnRH) agonist regimen (leuprolide [0.5 mg subcutaneous] + recombinant follicle-stimulating hormone [rFSH] [225 IU intramuscular [IM] from 2nd to 10th day of MC [n = 32]), long GnRH agonist regimen (leuprolide from 21st day followed by leuprolide + rFSH from 2nd to 10th day of MC [n = 19]), and antagonist regimen (human menopausal gonadotropin [hMG] [150 IU IM] from 2nd day followed by hMG + cetrorelix from 7th to 10th day of MC) (n = 6) were recruited and followed up for follicular size, endometrial thickness, and pregnancy test. Data were analyzed using appropriate statistical test andP < 0.05 was considered statistically significant. Results: A significant increase in follicular diameter and endometrial thickness was observed in patients treated with gonadotropin regimens as compared to CC alone (P < 0.0001). The highest number of positive pregnancy test with ultrasonographic evidence of gestational sac was observed with leuprolide + rFSH (long regimen) (10/19, 52.6%) followed by leuprolide + rFSH (short regimen) (13/32, 40.6%) while least in antagonist regimen (2/6, 33.3%) and CC (1/38, 2.63%). All regimens were well tolerated. Conclusion: Treatment outcome was better with long agonist regimen.
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Cardioprotective effect of coenzyme Q10on apoptotic myocardial cell death by regulation of bcl-2 gene expression p. 122
Najam Ali Khan, M Abid, Aftab Ahmad, Mohammed F Abuzinadah, Mohammed Basheikh, Kamal Kishore
DOI:10.4103/jpp.JPP_47_17  
Objectives: To investigate the effect of coenzyme Q10 (CoQ10) on apoptotic myocardial cell death in rat model of heart ischemia and reperfusion I/R injury. Materials and Methods: Eighteen rats (200–250 g) were divided into three groups of 6 rats in each. Group I (sham-operated control group): this is the control group. The animals received the surgical procedure without IR injury or any drug treatment. Group II (I/R group): ischemia was accomplished by the occlusion of coronary artery for 30 min followed by reperfusion for 45 min and Group-III (Coenzyme Q10treated group): Treated with CoQ10at a dose of 1 mg/kg, postoperative for 7 days before induction of IR injury. Results: The study revealed that pretreatment with CoQ10has shown protective effect on apoptotic rat heart and agreed with earlier reports that CoQ10significantly protects from oxidative stress and cytopathological changes caused by cardiac ischemia followed by reperfusion and attenuated decrease of antioxidant enzymes. Nitric oxide production in the heart of ischemic rats was significantly increased by the pretreatment with CoQ10in comparison with IR group. Conclusions: CoQ10protects against cardiac apoptosis induced by IR injury by significantly decreasing the apoptotic DNA and regulating the expression of Bcl-2 gene.
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RESEARCH LETTERS Top

Penetration of bromelain in serum and rhinosinusal mucosa in patients undergoing endoscopic sinus surgery p. 128
Desiderio Passali, Luisa Maria Bellussi, Codrut Sarafoleanu, Michele Loglisci, Claudiu Manea, Cristina Iosif, Francesco Maria Passali
DOI:10.4103/jpp.JPP_169_16  
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The basis for low-affinity herg potassium channel block by sotalol p. 130
Yi Hong Zhang, Christopher E Dempsey, Jules C Hancox
DOI:10.4103/jpp.JPP_69_17  
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Cardiac safety of high-dose micafungin p. 132
Kayla R Stover, John D Cleary
DOI:10.4103/jpp.JPP_37_17  
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COMMENTARY Top

Why the Jan Aushadhi scheme has lost its steam in India? p. 134
Vijay Thawani, Abin Mani, Neeraj Upmanyu
DOI:10.4103/jpp.JPP_38_17  
The Jan Aushadhi Scheme (JAS) initiated by the Government of India is a powerful intervention against the unjustifiable pricing of medicines by private pharmaceutical industry, to make the generic medicines available at affordable prices. The marginalized populations of India are not able to afford many branded medicines; hence, there is an urgent need for making the cheaper generics available to Indians in the best interest of populations. It has been observed that lack of awareness in the public, distribution of free medicines by state governments, lack of support for JAS, poor supply chain, and doctors not prescribing generic medicines are the major constraints faced by the JAS leading to its poor success.
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CASE SERIES Top

Sodium glucose transporter 2 inhibitors and diabetic ketoacidosis in three patients with diabetes: Underlying causation p. 137
Jordan L Kelley, Matthew Strum, Daniel M Riche, Andrew M Chandler
DOI:10.4103/jpp.JPP_20_17  
Sodium glucose transporter 2 inhibitors (SGLT2i) inhibit the reabsorption of glucose in the renal tubules reducing glycemia and increasing glucosuria. The increased glucosuria causes a shift in normal flora and colonization of pathogenic microorganisms leading to an increase in mycotic genital infections. Recent Food and Drug Administration reported cases of diabetic ketoacidosis (DKA) after initiation of SGLT2i probes the question of safety with such agents. The mechanisms of ketoacidosis and the breakdown of lipids are often misunderstood, and blame is placed on lack of insulin or on medications used to treat diabetes. However, many patients living with diabetes do not experience DKA if the proper treatment and management of concomitant comorbidities are addressed. After a retrospective chart review of 250 patients, three patients were identified with DKA while on SGLT2i, but for three distinct contrasting reasons. Assessment of the pharmacodynamics of SGLT2i and the pathophysiology of DKA infers that emphasis for prevention of SGLT2i-associated DKA should be placed on appropriate diagnosis, infection, and electrolyte abnormalities.
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CASE REPORTS Top

Ceftriaxone for the treatment of methicillin-susceptible Staphylococcus aureus Bacteremia: A case series p. 140
Rachel Amanda Lowe, Katie Elizabeth Barber, Jamie Leigh Wagner, Allison Miriam Bell-Harlan, Kayla Renay Stover
DOI:10.4103/jpp.JPP_5_17  
Methicillin-susceptible Staphylococcus aureus (MSSA) causes 45% of S. aureus bloodstream infections (BSI) and is the most important cause of BSI-associated death. The standard of care therapy is an anti-staphylococcal penicillin or cefazolin, but dosing frequencies for these agents are often infeasible; multiple daily doses tie up infusion lines and are impractical for outpatient antibiotic infusion. Ceftriaxone represents a promising alternative, with once daily dosing and a short infusion time. Currently, treatment with ceftriaxone for invasive MSSA infections is infrequent, with minimal data supporting the clinical utility of ceftriaxone for MSSA BSI. In this case series, we identified 15 patients receiving ceftriaxone for treatment of MSSA BSI, either following standard of care therapy or as initial therapy. Patients were evaluated for clinical cure (CC)(clearance of BSI and normalization of white blood cell count) and microbiological cure (MC)(clearance of blood cultures and no recurrence of organism within 60 days). CC was observed in seven patients, with MC observed in all patients. Only one patient was readmitted to the hospital. This case series provides vital data to support ceftriaxone for treatment of MSSA BSI. With few readmissions and recurrences of infection, ceftriaxone was an effective option for maintenance therapy after resolution of the BSI. Ceftriaxone appears to be a viable alternative for the treatment of MSSA BSI.
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Looking beyond the obvious: Cefepime-induced nonconvulsive status epilepticus p. 145
Vinayaka Anuhya, Sushil Kiran Kunder, Sharath Madhyastha, Veena Nayak, Raviraja V Acharya, Kusugodlu Ramamoorthi, Avinash Arivazhahan, Rahul Sai Gangula
DOI:10.4103/jpp.JPP_64_17  
Cephalosporins are a commonly used class of antibiotics in various types of infections. Cefepime, a fourth-generation cephalosporin, has been reported to cause neurotoxicity, which can present itself as varied manifestations. Nonconvulsive status epilepticus (NCSE) is a rare manifestation of this neurotoxicity. This condition often proves difficult to diagnose because it is chiefly an electroencephalogram-based diagnosis. The authors report a case of cefepime-induced NCSE in a 57-year-old female patient with compromised renal status.
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Terlipressin-induced peripheral ischemic gangrene in a diabetic patient p. 148
Phulen Sarma, Gaurav Muktesh, Narender Dhaka, Rakesh Ruhela, Abhishek Mishra, Rahul Singh, Saroj K Sinha, Bikash Medhi, Rakesh Kochhar
DOI:10.4103/jpp.JPP_42_17  
Terlipressin is used commonly in the management of hepatorenal syndrome and acute variceal bleeding. Like its parent compound vasopressin, it is also notorious for its ischemic complications. Terlipressin-induced ischemic complications can virtually affect any part of the body, but the incidence of serious complications is less than its parent compound vasopressin. Here, we report a case of terlipressin-induced peripheral ischemic gangrene in a diabetic male, which ultimately led to death of the patient.
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OBITUARY Top

A giant of indian pharmacology is no more: Rest in peace Prof. B. N. Dhawan p. 151
Syed Ziaur Rahman
DOI:10.4103/jpp.JPP_105_17  
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ERRATUM Top

Erratum: Blood sample collection in small laboratory animals p. 153

DOI:10.4103/0976-500X.215702  
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