Comparative Assessment of Revascularization Versus Drug Management in Coronary Artery Disease (CAD) Associated with Left Ventricular Dysfunction (EF < 40%) - A 12 Month Study with FDG PET and SPECT MPI Analyses.

AIM OF THE STUDY: Left Ventricular (LV) function and myocardial viability is the key predictor of prognosis after myocardial infarction. Management of ischemic cardiomyopathy (revascularization and or drugs alone) is the objective of this study. METHODOLOGY: 72 patients were assigned to revascularization and medical management group based on the inclusion criteria Follow up was done upto 12 months with advanced imaging techniques (FDG PET and SPECT MPI analyses). RESULTS: Subjects with significant viable myocardium, revascularization resulted in significant improvement in heart failure symptoms. The mean NYHA functional class improved from 2.9 ± 0.3 to 2.3 ± 0.5(mean ± SD) after 6 months of revascularization (p < 0.01). This improvement in functional class was maintained after 12 months of revascularization (2.0 ± 0.4 (mean ± SD). Subjects on medical management with a baseline NYHA functional class 2.7 ± 0.5, at 6 months of follow, there was no significant change in functional class (2.8 ± 0.3) (p<0.24). However at 12 months follow up functional class had dropped to 3.0 + 0.3, which was significant as compared to baseline (p <0.03). CONCLUSION: coronary revascularization has a protective effect on patients with ischemic coronary who have viable myocardium and reversible myocardial ischemia as assessed by 18F-FDG PET and SPECT MPI Imaging.

Comparison of safety and analgesic efficacy of diclofenac sodium with etodolac after surgical extraction of third molars: a randomized, double-blind, double-dummy, parallel-group study.

BACKGROUND: Surgical extraction of third molars is associated with postoperative pain and swelling at the extraction site. Pain is commonly managed using non-steroidal anti-inflammatory drugs (NSAIDs). Postoperative pain is usually moderate to severe in the first 12 h postoperatively and lasts for 3-5 days. However, with NSAIDs, these symptoms usually subside within 24 h. Diclofenac sodium and etodolac are NSAIDs, more selectively cyclooxygenase-2 inhibitors, with good analgesic efficacies. METHODS: We compared the safety and analgesic efficacy of diclofenac sodium with etodolac peroral after surgical extraction of third molars in a double-blind, double-dummy, parallel-group study. The subjective pain improvement and pain relief after 2, 6, 24, 48, and 72 h using the visual analogue scale were measured as the study outcome. RESULTS: Etodolac was equivalent to diclofenac sodium in pain alleviation at all postoperative time periods. No significant differences were found between diclofenac sodium and etodolac groups (P > 0.05). Both study medications were well tolerated and safe with mild adverse effects in only a few participants. CONCLUSION: Diclofenac sodium and etodolac are comparable in terms of analgesic efficacy and safety after surgical removal of third molars.

Comparison of safety and analgesic efficacy of diclofenac sodium with etodolac after surgical extraction of third molars: a randomized, double-blind, double-dummy, parallel-group study

BACKGROUND@#Surgical extraction of third molars is associated with postoperative pain and swelling at the extraction site. Pain is commonly managed using non-steroidal anti-inflammatory drugs (NSAIDs). Postoperative pain is usually moderate to severe in the first 12 h postoperatively and lasts for 3–5 days. However, with NSAIDs, these symptoms usually subside within 24 h. Diclofenac sodium and etodolac are NSAIDs, more selectively cyclooxygenase-2 inhibitors, with good analgesic efficacies.@*METHODS@#We compared the safety and analgesic efficacy of diclofenac sodium with etodolac peroral after surgical extraction of third molars in a double-blind, double-dummy, parallel-group study. The subjective pain improvement and pain relief after 2, 6, 24, 48, and 72 h using the visual analogue scale were measured as the study outcome.@*RESULTS@#Etodolac was equivalent to diclofenac sodium in pain alleviation at all postoperative time periods. No significant differences were found between diclofenac sodium and etodolac groups (P > 0.05). Both study medications were well tolerated and safe with mild adverse effects in only a few participants.@*CONCLUSION@#Diclofenac sodium and etodolac are comparable in terms of analgesic efficacy and safety after surgical removal of third molars.

A Rare Case Report of Toxic Epidermal Necrolysis Due to Ofloxacin.

BACKGROUND: Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), also known as Lyell's syndrome, are rare and life-threatening conditions, for which etiopathogenesis, as well as pharmacotherapy, is yet unclear. CASE REPORT: A 45-year-old male patient by chance on re-exposure to Ofloxacin developed Severe Cutaneous Adverse Drug Reaction (SCADR), diagnosed with toxic epidermal necrolysis. His comorbid conditions and systemic complications of TEN lead him to death. In developing countries, where antibiotics especially fluoroquinolones are widely prescribed, a physician should be now vigilant for such kind of SCADRs because of increasing numbers of such kind of reports.

Novel bio analytical method development, validation and application for simultaneous determination of nebivolol and S-amlodipine in human plasma using ultra performance liquid chromatography-tandem mass spectrometry.

A sensitive and specific ultra-performance liquid chromatography tandem mass spectrometric (UPLC-MS/MS) method has been developed, validated and applied for the assay of Nebivolol and S-amlodipine in human plasma. Sample extraction was carried out through hybrid extraction method from 250 µL of human plasma sample. Linearity of the method was (r ≥ 0.9996) was found to be dynamic for both the analytes over concentration range of 25.0-4000 pg/mL. Chromatographic separation was achieved on UPLC column {Waters Acquity UPLC BEH C18 (50 mm × 2.1 mm, 1.7 micrometer)} with the mobile phase composition of 0.1% (v/v) formic acid in 5 mM Ammonium formate in water-acetonitrile (20:80, %v/v). Analytes Stability was assured under different requisite conditions in human plasma, reconstitution solution and diluents. Inter and intra-day assay precision and relative error (accuracy) were within ±5% for both analytes. The method was applied and reproduced to support a pharmacokinetic study of 5 mg Nebivolol (NEB) and 2.5 mg S-amlodipine (LAM) tablet on 9 healthy subjects.

Simultaneous determination of etonogestrel and ethinyl estradiol in human plasma by UPLC-MS/MS and its pharmacokinetic study.

A selective, sensitive and rapid ultra-performance liquid chromatography tandem mass spectrometry method was developed and validated for the simultaneous determination of etonogestrel (ENG) and ethinyl estradiol (EE) in human plasma. The analytes and their deuterated internal standards, ENG-d7 and EE-d4, were extracted from plasma samples by solid-phase extraction on HyperSep™ Retain PEP cartridges. The chromatographic analysis was performed on an Acquity UPLC HSS Cyano column, 100 Å (50 × 2.1 mm, 1.8 µm), column using gradient mobile phase, acetonitrile and 2.0 mm ammonium trifluoroacetate at 0-1.7 min (65:35, v/v) and 1.8-2.7 min (95:5, v/v) with 0.250 mL/min flow rate. Analytes and IS protonated precursor → product ion transitions (ENG, m/z 325.2 → 257.2; EE, m/z 530.2 → 171.2; ENG-d7, m/z 332.2 → 263.2; EE-d4, m/z 534.2 → 171.2) were monitored on a Triple Quadrupole Mass spectrometer (TQMS), operating in multiple reaction monitoring and positive ionization mode. The calibration curves were established at 10.00-2500 pg/mL for ENG and 1.500-150.0 pg/mL for EE with a correlation coefficient (r2 ) ≥0.9996 for both. The validated method was successfully applied to support a bioequivalence study of 0.15 mg ENG and EE 0.03 mg tablet formulation, administered in 24 healthy Indian females. Method reliability was assessed by reanalysis of 94 incurred study samples.

Evaluation of cardioprotective effect of aqueous extract of Allium cepa Linn. bulb on isoprenaline-induced myocardial injury in Wistar albino rats.

To investigate the cardioprotective potential of the aqueous extract of Allium cepa Linn. bulb in isoprenaline-induced myocardial injury in Wistar albino rats. In vitro total phenolic, total flavonoid content and 2, 2'-diphenyl-1-picrylhydrazyl hydrate radical scavenging activity was measured. Isoprenaline-induced myocardial injury model was used to evaluate in vivo effect of aqueous extract of A. cepa in Wistar albino rats. Seventy two rats were randomly divided in 6 groups. Rats were treated with A. cepa 400 mg/kg and 800 mg/kg doses for 30 days and myocardial injury was produced by subcutaneous injection of isoprenaline (ISO) 85 mg/kg on day 28 and 29. Carvedilol 1 mg/kg for 30 days served as active control. Electrocardiogram parameters, cardiac injury markers, oxidative stress markers and histopathological changes were evaluated in each group and compared using appropriate statistical tests. In vitro evaluation of aqueous extract of A. cepa showed significant antioxidant property. ISO produced significant myocardial injury as compared to normal control group (P < 0.05). Administration of A. cepa in the dose of 400 mg/kg significantly recovered the altered parameters (Troponin-I, Creatine kinase-MB, glutamate-pyruvate transaminase, HR, R-R interval, and oxidative stress markers) compared to disease control group (P < 0.05) while A. cepa in the dose 800 mg/kg recovered the altered parameters (HR, heart weight/body weight ratio, and superoxide dismutase level) compared to disease control group. Histopathological parameters did not recover in the doses of 400 and 800 mg/kg (P > 0.05). The aqueous extract of A. cepa 400 mg/kg was found to be cardioprotective against myocardial injury while A. cepa 800 mg/kg did not show significant cardioprotective activity. So, we presume that A. cepa might be effective within certain dose range only.

A novel, sensitive and selective method of UPLC/MS-MS for rapid simultaneous determination of midodrine and its active metabolite desglymidodrine in human plasma: Application to support bioequivalence study in healthy human volunteers.

A specific, rapid, sensitive and selective ultra-performance liquid chromatography - tandem mass spectrometry has been developed for the simultaneous determination of midodrine and desglymidodrine in human plasma. The analytes and its deuterated analogs were quantitatively extracted from 100µL of human plasma by solid phase extraction technique. Separation of analytes was achieved on the Waters Acquity UPLC BEH C18 (50×2.1mm, 1.7µm) column using acetonitrile-4.0mM ammonium formate, pH 2.5(90:10, v/v) as mobile phase. The protonated analytes were quantified by selected reaction monitoring in the positive ionization mode by triple quadrupole mass spectrometer. The calibration plots were linear over the concentration range of 0.050-50.0ng/mL. The intra-batch and inter-batch precision (%CV) across quality control levels was <4.0 and the% mean relative recovery was ≥96%. Various other parameters like stability in different conditions; matrix effect and reproducibility of the method were performed in accordance with the guidelines specified by the USFDA for bioanalytical method development and validation. The developed method was successfully administered to the pharmacokinetics study of 5 mg midodrine tablet in 12 healthy subjects. Reproducibility of assay was proved by reanalysis of 48 incurred samples.

Evaluation of cardioprotective effect of aqueous extract of Garcinia indica Linn. fruit rinds on isoprenaline-induced myocardial injury in Wistar albino rats.

In the present study, cardioprotective effect of aqueous extract of Garcinia indica Linn. fruit rinds in isoprenaline-induced myocardial infarction in Wistar albino rats was evaluated. In vitro total phenolic, total flavonoid content and 2, 2'-diphenyl-1-picrylhydrazyl hydrate radical scavenging activity was measured. In vivo effect of aqueous extract of G. indica was evaluated in Wistar albino rats by isoprenaline-induced myocardial injury model. Thirty six rats were randomly divided in 6 groups. Rats were treated with G. indica 250 mg/kg and 500 mg/kg doses for 21 days and myocardial injury was produced by subcutaneous injection of isoprenaline 85 mg/kg on day 20 and 21. Carvedilol 1 mg/kg for 21 days served as active control. Electrocardiogram parameters, cardiac injury markers (serum troponin-I, uric acid, lactate dehydrogenase, creatinine kinase-MB, aspartate aminotransferase and alanine aminotransferase), oxidative stress markers (superoxide dismutase, catalase and malondialdehyde level) and histopathological changes were evaluated in each group and compared using appropriate statistical tests. In vitro evaluation of aqueous extract showed significant antioxidant property. Isoprenaline produced significant myocardial ischemia as compared to normal control group (P<0.05). Administration of G. indica in both the doses did not significantly recover the altered electrocardiogram, cardiac injury markers, oxidative stress markers and histopathological myocardial damage as compared to disease control group (P>0.05). The aqueous extract of G. indica was not found to be cardioprotective against myocardial injury. Further study with more sample size and higher dose range may be required to evaluate its cardioprotective effect.

Analysis of 21-hydroxy deflazacort in human plasma by UPLC-MS/MS: application to a bioequivalence study in healthy volunteers.

A sensitive and rapid ultra performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method has been developed for the determination of 21-hydroxy deflazacort in human plasma using betamethasone as the internal standard (IS). After solid-phase extraction from 100 µL human plasma, the analyte and IS were analyzed on Waters Acquity UPLC BEH C18 (50 mm × 2.1 mm, 1.7 µm) column using acetonitrile-4.0mM ammonium formate, pH 3.5 (90:10, v/v) as the mobile phase. The protonated analyte was quantified by selected reaction monitoring in the positive ionization mode by triple quadrupole mass spectrometer. The calibration plots were linear over the concentration range 0.50-500 ng/mL. Intra-batch and inter-batch precision (% CV) and accuracy (%) for five quality control samples ranged within 1.40-4.82% and 98.0-102.0% respectively. The overall mean extraction recovery of 21-hydroxy deflazacort from plasma ranged from 95.3 to 97.3%. Matrix effect was assessed by post-column analyte infusion and the extraction recovery was >95.0% across four quality control levels for the analyte and IS. Stability was evaluated under different conditions like bench top, autosampler, processed sample (at room temperature and in cooling chamber), freeze-thaw and long term stability. The method was applied to support a bioequivalence study of 30 mg deflazacort tablet formulation in 28 healthy subjects. Assay reproducibility was demonstrated by reanalysis of 115 incurred samples.

Aggressive natural killer cell leukaemia: a rare and fatal disorder.

Natural killer (NK) cell neoplasms, which include extra-nodal NK/T-cell lymphoma (nasal and extra-nasal) and aggressive NK cell leukaemia, are generally rare, but they are more common in people of Oriental, Mexican and South American descent. These neoplasms are highly aggressive, and show a strong association with Epstein-Barr virus. Aggressive NK cell leukaemia affects younger patients, who present with poor general condition, fever, and disseminated disease; they often die within a short time from systemic disease or complications such as multi-organ failure. Aggressive NK cell leukaemia must be distinguished from T-cell large granular lymphocyte leukaemia and indolent NK cell lympho-proliferative disorder, both of which are indolent. We present a case of young Asian male with aggressive NK cell leukaemia who presented with a poor general condition and disseminated disease. The patient had a rapidly progressive disease and died within weeks of diagnosis.

Surgical bypass for subclavian vein occlusion in hemodialysis patients.

BACKGROUND: The majority of patients with end-stage renal disease are dependent on hemodialysis. Significant stenosis or occlusion of the subclavian vein is known to occur in 20% to 50% of patients who have had central venous catheters inserted into the subclavian vein or the internal jugular vein. Surgical bypass of the obstructed venous segment proximal to a functioning dialysis access site is an established treatment to relieve symptoms and salvage the functional dialysis access. STUDY DESIGN: A retrospective review of all subclavian venous bypass procedures performed at St Louis University Hospital from May 1987 to May 2000 was undertaken. Twelve procedures were performed during this time. The mean age of the patient was 55.5 years (range 17 to 72 years). There were 11 men and 1 woman. Before surgical bypass, all patients underwent bilateral venograms to evaluate their central venous systems. RESULTS: An extraanatomic surgical bypass was performed in all patients. Patients were followed for a mean of 16 months (range 1 to 79 months). At 1 month, 100% of hemodialysis access sites remained functional. At 1 year, 80%; 2 years, 60%; and 3 years, 25% of the salvaged arteriovenous hemodialysis access sites provided for functional dialysis. One patient required thrombectomy of the bypass graft at 14 months. CONCLUSIONS: Surgical bypass of an occluded or stenotic subclavian vein segment is successful in providing both symptomatic relief and salvage of a functioning dialysis access in the hemodialysis patient population. Study of the central venous system is essential in selecting an appropriate bypass procedure in individual patients.