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   Table of Contents - Current issue
Coverpage
January-March 2017
Volume 8 | Issue 1
Page Nos. 1-43

Online since Friday, March 17, 2017

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EDITORIAL  

Eminence or evidence? The volatility, uncertainty, complexity, and ambiguity in healthcare p. 1
MK Unnikrishnan
DOI:10.4103/jpp.JPP_12_17  
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RESEARCH PAPERS Top

Effect of addition of fentanyl and clonidine to local anesthetic solution in peribulbar block p. 3
Poonam Nehra, Vrinda Oza, Vandana Parmar, Pooja Fumakiya
DOI:10.4103/jpp.JPP_109_16  
Objective: To compare the effect of addition of fentanyl and clonidine as adjuvants to bupivacaine and lignocaine in peribulbar block. Methods: The study was conducted on 105 adult patients of either sex, of ASA grade I and II undergoing ophthalmic surgeries. Patients were randomly divided into 3 groups of 35 each. All the patients were given peribulbuar block with 5ml lignocaine 2% +3 ml bupivacaine 0.5% +1 ml hyaluronidase (250 IU). In addition to this 1 ml normal saline was added to Group S, 25 μg fentanyl to Group F and 25 μg clonidine to Group C. Onset and duration of globe and lid akinesia, duration of sensory blockage and analgesia, hemodynamic parameters, number of rescue analgesic and visual analogue score were recorded. Results: The mean time of onset of globe and lid akinesia was significantly faster in group F and group C compared to group S, mean duration of globe and lid akinesia was longer in Group F (207.71 + 13.54 and 143.14 + 7.86 min) and group C (213.52 + 14.52 and 162.06 + 17.1 min) compared to group S (117.78 + 10.42 and 87.64 + 9.76 min). The mean duration of analgesia was significantly longer in group F (217.71 + 12.67) and C (258.82 + 14.50 min) as compared to group S (131.39 + 9.63 min). Conclusion: Addition of fentanyl or clonidine as adjuvant to local anaesthetic in peribulbar block provides faster onset and prolonged analgesia compared to local anaesthetic alone.
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Mechanism underlying linezolid-induced thrombocytopenia in a chronic kidney failure mouse model p. 8
Nao Nishijo, Yasuhiro Tsuji, Kazuhisa Matsunaga, Masahiko Kutsukake, Fumiyasu Okazaki, Shiro Fukumori, Hidefumi Kasai, Yoichi Hiraki, Ippei Sakamaki, Yoshihiro Yamamoto, Yoshiharu Karube, Hideto To
DOI:10.4103/jpp.JPP_167_16  
Objective: To investigate the relationship between renal function and linezolid (LZD)-induced thrombocytopenia and elucidate the underlying mechanism using a chronic renal disease (CRD) mouse model. Materials and Methods: CRD was induced in 5-week-old male Institute of Cancer Research (ICR) mice by 5/6 nephrectomy. After this procedure, LZD (25 and 100 mg/kg) was administered intraperitoneally once every day for 28 days. Platelet counts, white blood cell (WBC) counts, and hematocrit (HCT) levels were measured every 7 days. 2-14C-thymidine (0.185 MBq) was administrated intravenously to LZD-administered mice to evaluate the thymidine uptake ability of bone marrow. Results: Platelet counts were significantly lower in the LZD-administered CRD group than in the LZD-nonadministered groups at 14, 21, and 28 days (P < 0.05); however, these changes were not observed in LZD-administered mice with normal renal function, regardless of the duration of LZD administration. No significant changes were observed in WBC counts or HCT levels in any LZD-administered CRD mouse. Moreover, radioactive levels in bone marrow were not significantly different in each group. Conclusions: These results indicate that LZD-induced decreases in platelet counts were enhanced by renal impairment in vivo, suggesting that LZD-induced thrombocytopenia is not caused by nonimmune-mediated bone marrow suppression.
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Indocyanine green-001 (ICG-001) attenuates wnt/β-catenin-induces myocardial injury following sepsis p. 14
Nasser Ghaly Yousif, Najah R Hadi, Alaa Manea Hassan
DOI:10.4103/jpp.JPP_153_16  
Objective: To investigate the mechanistic pathway of both indocyanine green (ICG)-001 in attenuated endotoxemia-induced cardiac depression through downregulation cardiac Wnt/ β-catenin cell signaling. Materials and Methods: Adult (4–6 months) male Albino-Webster mice, their weights ranged from 25 to 30 g, were pretreated with ICG-001 i.p., following cecal ligation and puncture (CLP). Left ventricle (LV) function was assessed using a microcatheter system. Monocyte chemoattractant protein-1 (MCP-1) and cytokines mediators in plasma and myocardium were analyzed by enzyme-linked immunosorbent assay. Further, the cardiac Wnt protein measured by quantitative real-time polymerase chain reaction while β-catenin analysis through Western blotting procedure. The pathological changes and cells injury in the myocardium were examined using hematoxylin and eosin staining. Results: CLP mice displayed worse LV function. The exaggerated cardiac depression in CLP mice was associated with higher levels of MCP-1 and cytokines in plasma and myocardium together with greater cardiac levels of cardiac troponin-I and Wnt/β-catenin. Neutralization of sepsis by either ICG-001resulted in improved LV function and reductions in inflammatory mediators. Conclusion: Taken together, these data showed that ICG-001 improved LV function following sepsis through downregulation of Wnt/β-catenin and serve as a potential mechanistic pathway ICG-001 in therapeutic cardiac endotoxemia in animal model.
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Antianginal efficacy and tolerability of ranolazine as an add-on drug to concomitant medications primarily metoprolol in chronic stable angina patients: A prospective, open-label study p. 21
Anant Mahaveer Khot, HV Anuradha, VS Prakash, MC Shivamurathy
DOI:10.4103/jpp.JPP_168_16  
Objective: To evaluate the efficacy and tolerability of ranolazine as an add-on drug in chronic stable angina patients and the impact of ranolazine on the quality of life in chronic stable angina patients receiving other antianginal medications. Materials and Methods: It was a prospective, open-label, hospital-based study involving 144 patients with chronic stable angina. First group received either metoprolol 12.5 or 25 mg/day or other antianginal medications; if the symptoms persist, the dose of metoprolol was increased to 50 mg/day, and to the second group, ranolazine 500 mg BD or 1 g OD was added along with metoprolol or others if the anginal attacks were not subsiding. The patients were followed up to 6 months with electrocardiography, treadmill test, and quality of life questionnaire. Adverse events were recorded at each visit during the study. Results: There was a statistically significant reduction in weekly anginal frequency (P < 0.001) and improvement in an exercise tolerance in both the groups, but more in the ranolazine group. Adverse events reported were mild, infrequent. Conclusion: Ranolazine is could be used as an add-on drug in chronic angina patients not improved with metoprolol or antianginal medications.
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Risperidone-induced adverse drug reactions and role of DRD2 (−141 C Ins/Del) and 5HTR2C (−759 C>T) genetic polymorphisms in patients with schizophrenia p. 28
Charanraj Goud Alladi, Anbarasan Mohan, Deepak Gopal Shewade, Ravi Philip Rajkumar, Surendiran Adithan, Karthick Subramanian
DOI:10.4103/jpp.JPP_197_16  
Objective: To determine the adverse drug reaction (ADR) profile of risperidone and their association with dopamine (DRD2 − 141 C Ins/Del/rs1799732) and serotonin receptor (5HTR2C −759 C>T/rs3813929) gene polymorphisms in patients with schizophrenia. Materials and Methods: The study was conducted among 289 patients who were diagnosed with schizophrenia and were on treatment with risperidone (4–8 mg/day)-based therapy for a minimum of 4 weeks. Genotyping was carried by real-time quantitative polymerase chain reaction. All the patients were observed for the occurrences of ADRs during the study. Changes in prolactin levels and body weight were analyzed for a subgroup of 102 and 97 patients, respectively. Results: Risperidone-induced extrapyramidal symptoms (EPSs) were seen in 36.7% of patients. Among them, tremors were the most common symptom 31.8%. Risperidone-induced hyperprolactinemia and weight gain were seen in 87.2% and 53.6% in subgroup patients. Adverse effects such as sedation, gastrointestinal effects, and amenorrhea were seen in 9.7% (28/289), 5.1% (15/289), and 6.1% (7/114), respectively. Occurrence of DRD2 − 141 Ins/Del and Del/Del polymorphisms were significantly associated with increased prolactin levels in response to risperidone (odds ratio [OR] = 10.45; 95% confidence interval = 1.29–84.89,P = 0.004). No such association was observed with 5HTR2C (−759 C>T) polymorphism. Weight gain and EPS were not associated with the above genetic polymorphisms. Conclusion: Hyperprolactinemia, weight gain, and EPSs (>36.7%) were common adverse effects of risperidone. DRD2 – 141C Ins/Del and Del/Del polymorphisms were significantly associated with increased prolactin levels (OR = 10.45) in response to risperidone.
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RESEARCH LETTER Top

Methylcobalamin in vitamin B12deficiency: To give or not to give? p. 33
Ashwin Kamath, Sudhakar Pemminati
DOI:10.4103/jpp.JPP_173_16  
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CASE REPORTS Top

Severe bone marrow suppression accompanying pulmonary infection and hemorrhage of the digestive tract associated with leflunomide and low-dose methotrexate combination therapy p. 35
Caihong Qu, Ying Lu, Weimin Liu
DOI:10.4103/jpp.JPP_93_16  
A 60-year-old male patient developed hyperpyrexia, cough, expectoration with blood-stained sputum, mouth ulcers, and suppurative tonsillitis after receiving 35 days of combination treatment with leflunomide (LEF) and low-dose methotrexate (MTX) for active rheumatoid arthritis. On admission, routine blood tests showed severe thrombocytopenia, agranulocytosis, and decreased hemoglobin concentration compared with the relatively normal results of 1 month previously during the first hospitalization. Chest radiography revealed inflammation in both lungs, and a fecal occult blood test was positive. Given this presentation, severe bone marrow suppression accompanying pulmonary infection and hemorrhage of the digestive tract associated with LEF and MTX combination therapy was diagnosed. After 28 days of symptomatic treatment, the patient's complications subsided gradually. This case highlighted that bone marrow suppression associated with MTX and LEF combination therapy could be very serious, even at a normal dose or especially at the beginning of treatment. MTX and LEF combination therapy should be used with caution or be limited in those with a history of pulmonary disease, hemorrhage of the digestive tract, or other relevant diseases.
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Ifosfamide-induced encephalopathy precipitated by aprepitant: A rarely manifested side effect of drug interaction p. 38
Pritam Sureshchandra Kataria, Pradip Piraji Kendre, Apurva A Patel
DOI:10.4103/jpp.JPP_182_16  
Central nervous system (CNS) toxicity has been reported in approximately 10%–30% of patients receiving intravenous infusions of ifosfamide. Encephalopathy is a rare but serious CNS adverse reaction in these patients, and although usually transient and reversible, may cause persistent neurological dysfunction or death. Clinical features range from fatigue and confusion to coma and death. Ifosfamide forms backbone of various treatment regimens including curative treatment and palliative chemotherapy regimen. Precipitation of ifosfamide-induced encephalopathy (IIE) by aprepitant has been reported in the literature rarely. Ifosfamide is moderately emetogenic; hence, aprepitant is used to prevent emesis induced by ifosfamide. We here report a case where a patient of recurrent B-cell Philadelphia-negative acute lymphoblastic lymphoma was given aprepitant to prevent ifosfamide-induced emesis. After 24 h of ifosfamide infusion, the patient developed symptoms of encephalopathy, i.e., headache, vomiting, and one episode of seizure which was followed by disoriented behavior. After doing all routine investigations and neuroimaging, the diagnosis of IIE was kept on clinical grounds, and after looking for the various factors, we came across injection fosaprepitant as the precipitating factor. On the clinical grounds, the patient was treated with hydration and injection methylene blue for above complaints, and the patient recovered without any residual deficit within 48–72 h. Hence, in the presence of causative agent, i.e., ifosfamide and precipitating agent injection fosaprepitant with negative imaging and normal laboratory parameters as well as the early and good response to methylene blue, the diagnosis of IIE precipitated by aprepitant was confirmed.
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Pleural tuberculosis following infliximab therapy for ankylosing spondylitis p. 41
Vs Gokul Krishnan, Sharath Madhyastha, Kusugodlu Ramamoorthi, Raviraj V Acharya, Vinaya Gopalaswamy
DOI:10.4103/jpp.JPP_174_16  
We present a case of pleural tuberculosis (TB) in a patient on infliximab for ankylosing spondylitis. A 36-year-old male presented to our hospital with low back ache of inflammatory type along with multiple symmetric inflammatory type of joint pain. Further clinical examination, laboratory and radiological investigations were suggestive of ankylosing spondylitis. He was initially treated with nonsteroidal anti-inflammatory drugs but citing poor response it was decided to initiate biologic therapy using infliximab (antitumor necrosis factor-alpha). Mantoux test and chest radiograph were done before the therapy to rule out TB. Following three doses of infliximab, patient came with complaints of fever and cough for 1 week. On investigation, it was found to be a case of pulmonary TB. This shows the importance of close monitoring of patient for TB among patients on infliximab even though the screening test has come out to be negative.
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