Is Achieving High Flexion Necessary for Satisfaction after Total Knee Arthroplasty in Indian Patients?

BACKGROUND: Total knee arthroplasty (TKA) is a very successful operation for the treatment of end-stage arthritis of the knee joint. In spite of improvement in surgical technique, implant design, postoperative pain management, and rehabilitation, some patients are not satisfied with the outcome of the surgery. It is believed that high-flexion (H-F) activities such as cross-legged sitting and squatting are necessary for satisfaction after TKA in Indian patients due to cultural and social reasons. This has led to the development and marketing of implant designs allowing H-F after TKA without strong evidence in the literature. MATERIALS AND METHODS: We carried out a retrospective study to determine the level of satisfaction in 74 patients operated for 120 TKA over a 5 year period. This was determined on the basis of a satisfaction questionnaire which included questions to assess satisfaction regarding pain relief and ability to perform routine daily activities and high knee flexion activities such as squatting and cross-legged sitting. RESULTS: Out of a total of 74 patients, 69 patients were overall satisfied with their TKA. Out of these, only 5 patients could squat or sit in a cross-legged position. Majority of the patients were satisfied with the pain relief and improvement in their capacity to work provided by TKA. CONCLUSIONS: Ability to perform H-F activities after TKA is not a necessary prerequisite for satisfaction in Indian patients. Implant designs allowing H-F should be used in a selected group of patients with good preoperative knee flexion and specific requirements.

Estimation of carvedilol in human plasma by using HPLC-fluorescence detector and its application to pharmacokinetic study.

A simple, precise and sensitive high performance liquid chromatography procedure has been developed for determination of carvedilol in human plasma. The method was developed on Lichrosphere R CN column using a mobile phase of acetonitrile/20 mM ammonium acetate buffer with 0.1% triethylamine (pH adjusted to 4.5) (40/60, v/v). The peaks were detected by using fluorescence detector (excitation wavelength 282 nm and emission wavelength 340 nm). Carvedilol and domperidone (internal standard) were extracted by liquid-liquid extraction procedure using dichloromethane. This method was specific and had a linearity range of 1-128 ng/ml with intra- and inter-day precision (%C.V.) less than 15%. The accuracy ranges from 87.3 to 100.88% and the recovery of carvedilol was 69.90%. The stability studies showed that carvedilol in human plasma was stable during short-term period for sample preparation and analysis. This method was used to assay the carvedilol in human plasma samples obtained from subjects who had been given an oral tablet of 12.5 mg carvedilol.

A new high performance liquid chromatographic method for quantification of atomoxetine in human plasma and its application for pharmacokinetic study.

Atomoxetine is the first, non-stimulant alternative to other stimulant medications used for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). Reported methods for the determination of atomoxetine include expensive liquid chromatography tandem mass spectrometry (LCMS) and high performance liquid chromatography (HPLC) with liquid scintillation counting (LSC) detection. Till date, no method has been reported in literature to determine atomoxetine using HPLC with UV detection. In this paper, we describe a new HPLC method for the determination of atomoxetine using liquid-liquid extraction with tertiary butyl methyl ether and UV detector. This method was found to be linear over the concentration range of 0.05-3.0 microg/ml. The limit of quantification was 0.05 microg/ml. Intra- and inter-day precision was <15% and accuracy was in the range of 95.67-108.80%. Stability studies showed that atomoxetine was stable in human plasma for short- and long-term period for sample preparation and analysis. This method was used for sample analysis in a pharmacokinetic study of atomoxetine (25mg) in five healthy adult female volunteers. The observed mean+/-S.D. pharmacokinetic parameters Cmax, Tmax and AUC(0-t) were 0.40+/-0.06 microg/ml, 3.40+/-0.42 h and 1.34+/-0.52 microg h/ml, respectively.

Analytical method development and validation of mianserin hydrochloride and its metabolite in human plasma by LC-MS.

Mianserin is a tetracyclic antidepressant drug and administered as racemate of R (-) and S (+) mianserin hydrochloride in a dose of 30-90 mg/day in divided doses. Liquid chromatography-mass spectroscopy (LC-MS) is a tool, which is widely used for determination of drug and their metabolites in biological fluids because of its high sensitivity and precision. Here we describe a liquid chromatography mass spectroscopy method for simultaneous determination of mianserin and its metabolite, N-desmethylmianserin, from human plasma using a liquid-liquid extraction with hexane:isoamylalcohol (98:2) and back extraction with 0.005 M formic acid solution. This method is specific and linear over the concentration range of 1.00-60.00 ng/ml for mianserin and 0.50-14.00 ng/ml for N-desmethylmianserin in human plasma. The lowest limits of quantification (LLQ) is 1.00 ng/ml for mianserin and 0.50 ng/ml for N-desmethylmianserin. Intraday and interday precision (%C.V.) is <10% for both mianserin and N-desmethylmianserin. The accuracy ranges from 94.44 to 112.33% for mianserin and 91.85-100.13% for N-desmethylmianserin. The stability studies showed that mianserin and N-desmethylmianserin in human plasma are stable during short-term period for sample preparation and analysis. The method was used to assay mianserin and its metabolite, N-desmethylmianserin, in human plasma samples obtained from subjects who had been given an oral tablet of 30 mg of mianserin.

Routine chemoprophylaxis for deep venous thrombosis in Indian patients: Is it really justified?

BACKGROUND: Venous thromboembolism (VTE), which consists of deep vein thrombosis (DVT) and pulmonary embolism, is a potentially fatal disease. According to the Western literature, DVT of lower limb veins is one of the most common complications following total hip and knee arthroplasty and surgeries for lower limb fractures. Very few studies have been published from India on the subject and very little is known about the true incidence of the condition. The issue has acquired greater significance in Indian subjects in recent times as there is a manifold increase in the number of joint replacement surgeries and surgeries for lower limb fractures. There are no clear guidelines regarding the prophylaxis for VTE for Indian patients. MATERIALS AND METHODS: We carried out a prospective study to determine the incidence of DVT. Present study included 125 patients undergoing total knee and hip joint arthroplasty and surgeries for fractures of the lower limb over a three-year period. All the patients underwent duplex ultrasonography between the seventh and 14(th) postoperative day. No mechanical or chemical form of DVT prophylaxis was used. RESULTS: Only nine patients (7.2%) showed sonographic evidence of DVT and the majority of them resolved without treatment. There was no case of pulmonary embolism. CONCLUSION: DVT following total joint arthroplasty and surgery for lower limb fractures in Indian patients is not as common as reported in the Western literature. A high level of suspicion and close clinical monitoring is mandatory, routine chemoprophylaxis is perhaps not justified in every patient undergoing lower limb surgery in our opinion. More trials involving a larger number of patients and at multi centers, in future, would be required to confirm the findings of our study.

QSAR studies on some thiophene analogs as anti-inflammatory agents: enhancement of activity by electronic parameters and its utilization for chemical lead optimization.

Small molecule heterocycle is an integral part of new drug discovery in anti-inflammatory research. In our previous papers we reported the synthesis of thiophene analogs substituted at the fifth position with alpha-oximino propionic ester moiety and the fact that such new chemical entities exhibit anti-inflammatory activity in male/female Sprague-Dawley rats. In this paper we report the quantitative structure activity relationship (QSAR) studies of a series of 43 thiophene analogs. The analogs when subjected to cluster analysis technique led to the formation of four homogeneous groups. The cluster analysis technique grouped the 2-anilino-5-substituted-4-methyl-thiophene-3-carboxylic acid methyl esters as one homogeneous group. The clusters were individually taken up for a Hansch type of QSAR study with 10 molecular descriptors. The QSAR equations generated were cross validated by the leave out one method. The studies gave an insight into the dominant role played by electronic properties like energy of the lowest unoccupied molecular orbital (ELUMO) and dipole moment (dipole) in modulating the anti-inflammatory activity. From the QSAR studies a three point pharmacophore has been established for designing novel anti-inflammatory molecules.

Safety and antiretroviral effectiveness of concomitant use of rifampicin and efavirenz for antiretroviral-naive patients in India who are coinfected with tuberculosis and HIV-1.

OBJECTIVE: To study the safety and antiretroviral effectiveness of concomitant use of rifampicin and efavirenz for antiretroviral-naïve patients in India who are coinfected with tuberculosis (TB) and HIV-1. DESIGN AND METHODS: The study was an observational longitudinal cohort investigation. HIV-1-infected patients with CD4 cell counts of < or = 200/microL who attended the Infectious Disease Clinic of Sterling Hospital (Ahmedabad, India) from June 2001 to December 2002 were recruited for the study. Patients were divided in 2 groups: group A, patients with active TB (n = 126); and group B, patients without TB (n = 129). Group A patients were given efavirenz with 2 nucleoside reverse transcriptase inhibitors along with rifampicin-containing anti-TB treatment. Group B patients were treated for presenting opportunistic infections and started therapy with efavirenz plus 2 nucleoside reverse transcriptase inhibitors. The nucleoside reverse transcriptase inhibitors were either zidovudine and lamivudine (n = 30) or stavudine and lamivudine (n = 225). Patients self-funded their investigations and medications (antiretroviral, anti-TB, and other opportunistic infection-related agents). Indian generic medications were used. RESULTS: Efavirenz-based highly active antiretroviral therapy with rifampicin for HIV/TB-coinfected patients resulted in an immunologic response that was comparable with that of the group not receiving rifampicin. Median CD4 cell counts at baseline, 3 months, 6 months, and 9 months in group A were 84/microL (range, 5-200/microL), 225/microL (range, 26-528/microL), 251/microL (range, 65-775/microL), and 275/microL (range, 61-611/microL), respectively, and in group B, these values were 118/microL (range, 2-200/microL), 244/microL (range, 38-881/microL), 294/microL (range, 23-1322/microL), and 295/microL (range, 26-991/microL), respectively. The overall increase in CD4 cell count was greater in group A than in group B at 9 months (190 vs. 176/microL, respectively). Patients in both groups tolerated the therapy well; the adverse effects profile was comparable except that group A patients had a higher incidence of hepatitis than group B patients (13.49% vs. 0, respectively; P < 0.0001). CONCLUSION: Clinical and immunologic benefits are comparable for patients receiving efavirenz-based antiretroviral therapy with or without rifampicin.

Comparative study of plateletpheresis using Baxter CS 3000 plus and Haemonetics MCS 3P.

Platelet concentrates made from cell separators are used more frequently due to less donor exposure and leucodepletion. This retrospective study was done to compare plateletpheresis done on two cell separators: Baxter CS 3000 plus and Haemonetics MCS 3p. Plateletpheresis procedures, done from January 1997 to April 2002, were included in the study. One hundred and seven procedures were done on Haemonetics MCS 3p using SDP protocol, 49 procedures were done on Haemonetics MCS 3p using PLP protocol, and 107 were done on Baxter CS 3000 plus. Pre-procedure donor's platelet count and haemoglobin were comparable in all the groups. Platelet yield was comparable in PLP (6.44 x 10(11) platelets) and SDP (5.27 x 10(11)) protocols, but significantly less in Baxter (4.05 x 10(11) platelets, P < 0.001 for PLP and P < 0.05 for SDP). Efficiency of platelet removal was statistically significantly different in all the groups (P < 0.0001), however it was more in PLP (PLP-55.02%, SDP-47.38%, Baxter 38.98%). A significant number of products (19.51%) of Baxter failed to comply platelet count of product < or = 2,435 x 10(9)/l compared to 5.13% in PLP and 1.23% in SDP group; 36.96% of units from PLP and 28% from SDP qualified for split products compared to 1.18% of Baxter. PLP protocol of Haemonetics MCS 3p gives better platelet yield compared to Baxter CS 3000 plus and SDP protocol of Haemonetics MCS 3p.