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Biomedical subjects

R Bakshi

Publications and source records attributed to R Bakshi.

At least 73 records · Page 4Linked to original sources

Acute transverse myelitis after influenza vaccination: magnetic resonance imaging findings.

Descriptions in the literature of magnetic resonance imaging (MRI) findings in post-vaccination myelitis are scarce. Described here is a case of acute transverse myelitis that occurred after administration of an influenza vaccination. T1-weighted MRIs showed diffuse, fusiform spinal cord enlargement, extending from C-3 to rostral thoracic levels. Intramedullary lesions containing increased T2 signal were found in the areas of cord enlargement. The involvement on MRI was profound, extending far rostral to the level of the discrete clinical myelopathy. The lesions did not enhance after contrast administration. The patient had a complete long-term recovery of neurological function. This represents the first report of MRI findings in acute transverse myelitis after influenza vaccination.

Acute Disease↗

Comparative efficacy and tolerability of two diclofenac formulations in the treatment of painful osteoarthritis.

The efficacy and tolerability of a new resinate formulation of diclofenac 75mg taken once or twice daily were compared with that of conventional enteric-coated diclofenac sodium 50mg tablets given two or three times daily in a double-blind, randomised, between-patient, 12-week trial in 216 adult patients suffering from painful osteoarthritis of the hip and/or knee. Similar and clinically significant reductions in the mean intensity scores of pain at rest or on activity were observed after treatment with either formulation. Global evaluations showed the overall response rate to range between 60% and 75%. A significant analgesic effect was obtained within two weeks of treatment with 150mg diclofenac daily; this improvement was maintained on reduction of the dosage to 75-100mg over the next ten weeks. One or more drug-related adverse events, predominantly gastrointestinal adverse events, were reported by 40% and 38% of patients in the diclofenac resinate and diclofenac sodium groups, respectively.

Adolescent↗

Comparative efficacy of diclofenac dispersible 50 mg and ibuprofen 400 mg in patients with primary dysmenorrhea. A randomized, double-blind, within-patient, placebo-controlled study.

Sixty female out-patients suffering from moderate to severe primary dysmenorrhea, aged 14-40 years (mean 27 years), entered this randomized, double-blind, 3-period, within-patient study, evaluating the efficacy and tolerability of diclofenac dispersible 46.5 mg (equivalent to 50 mg of diclofenac sodium), ibuprofen 400 mg and placebo taken up to 4 times daily for a maximum of 3 days. Pain relief was evaluated on a verbal rating scale (0 = none, 1 = slight, 2 = moderate, 3 = considerable, 4 = complete) at 0.5, 1,2,3,4,5 and 6 hours after the first dose; the weighted sum of pain relief scores over the 6-hour observation period was also investigated (TOTPAR-6). Pain intensity was assessed on a verbal rating scale (0 = nil, 1 = mild, 2 = moderate, 3 = severe) at baseline and at the above mentioned time points; the weighted sum of pain intensity differences at each time point was also analyzed (SPID-6). A rescue medication was permitted 1 hour or more after the intake of the test drug: in such cases the last value of pain intensity/relief scores was carried forward and used for the analysis. A global evaluation of efficacy and of trial medication as compared to her usual medication was performed by the patient at the end of each treatment period. Finally, adverse experiences were recorded throughout the study period. Analysis of covariance and Koch's adaptation of the Wilcoxon-Mann-Whitney rank sum test were used, where appropriate, for statistical analysis. Mean TOTPAR-6 values for diclofenac dispersible, ibuprofen and placebo were 16.5, 17.8 and 14.7, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A placebo-controlled comparative evaluation of diclofenac dispersible versus ibuprofen in postoperative pain after third molar surgery.

The analgesic efficacy of single oral doses of drinkable diclofenac dispersible 50 mg was compared with that of ibuprofen 400 mg and placebo in a randomized, double-blind, parallel-group trial in 257 adult patients (245 valid for efficacy) with severe postoperative pain after extraction of an impacted lower third molar. In this study, pain intensity (on a 100-mm visual analog scale) and pain relief from baseline (using a five-point verbal rating scale) were assessed serially during an observation period of 6 hours. Intake of rescue analgesic was permitted in case of insufficient therapeutic effect; however at least 1 hour should have elapsed after test drug consumption. On the main efficacy variable, namely, reduction in the pain intensity score, both diclofenac dispersible (n = 83) and ibuprofen (n = 80) were statistically significantly (P < .01) superior to placebo (n = 82) starting at 20 and 40 minutes, respectively, after drug intake. The active medications were also significantly (P < .01) better than placebo for the secondary efficacy parameters viz. summed pain relief scores over 6 hours (TOTPAR-6); frequency of remedication with a rescue analgesic in the three treatment groups (diclofenac, 24%; ibuprofen, 28%; placebo, 65%); mean time to remedication; and global evaluation. All the treatments were well tolerated. Thus assay sensitivity of this trial (ibuprofen significantly better than placebo) has been demonstrated; in addition, diclofenac as a dispersible formulation has been shown to be an effective analgesic for the treatment of post-surgical dental pain.

Administration, Oral↗

Efficacy and tolerability of diclofenac dispersible in painful osteoarthrosis.

A multicentre, twelve-week, double-blind, randomized trial was conducted to evaluate the efficacy and tolerability of diclofenac dispersible in patients suffering from osteoarthrosis of the knee and/or hip. Symptomatic adult patients (N = 129) of either sex were treated with diclofenac dispersible or the conventional enteric-coated tablet of diclofenac sodium 50 mg orally, thrice daily. Both formulations of diclofenac led to comparable and clinically significant reductions in the intensities of pain at rest and during activity within 1 week of therapy initiation. More than 70% of patients in both treatment groups had no or mild pain on full passive movement by the end of the study with the Lequesne Index showing a reduction of around 50% from initial values. Overall assessments of efficacy by the patient and the investigator indicated a positive response rate for both diclofenac formulations ranging between 71% and 82%. The proportion of patients reporting adverse effects, predominantly gastro-intestinal, was slightly higher in the dispersible group, 40.3%, compared to 37.3% with enteric-coated diclofenac sodium.

Diclofenac↗

The analgesic efficacy of diclofenac dispersible and ibuprofen in postoperative pain after dental extraction.

We have compared single oral doses of drinkable diclofenac dispersible (50 mg) with ibuprofen (400 mg) and placebo in a randomized, double-blind, parallel-group trial in 127 adults complaining of at least moderately severe pain after removal of an impacted third molar. Within 40 min both diclofenac and ibuprofen produced significant pain relief that persisted for 6 h. There were no differences between diclofenac and ibuprofen in analgesic efficacy.

Administration, Oral↗

N-methyl-D-aspartate (NMDA) and opioid receptors mediate dynorphin-induced spinal cord injury: behavioral and histological studies.

Both N-methyl-D-aspartate (NMDA) and opioid receptors have been implicated in the pathophysiology of traumatic spinal cord injury and dynorphin-induced paralysis. The present studies compared the effects of the non-competitive NMDA antagonist dextrorphan (Dex) and the kappa-selective opioid antagonist nor-binaltorphimine (nor-BNI) on the acute motor deficits and chronic neuropathological alterations caused by intrathecally administered dynorphin A-(1-17) (Dyn A). Infusion of Dyn A into the rat lower thoracic spinal subarachnoid space produced acute, reversible hindlimb paresis. Histological evaluations of spinal cord sections from these animals at 2 weeks post-infusion revealed ventral grey matter necrosis, neuronal loss and gliosis as well as axonal loss in adjacent white matter; however, there was minimal alteration in serotonin immunocytochemistry caudal to the injury zone. Dex or non-BNI pretreatment each significantly (P less than 0.05) reduced, and to a similar degree, the acute motor deficits and certain histological changes associated with Dyn A administration. These findings further support the hypothesis that dynorphin-induced spinal cord injury involves both NMDA receptors and opioid receptors.

Animals↗

Efficacy and tolerability of diclofenac dispersible in elderly patients with osteoarthritis.

The efficacy and tolerability of a new dispersible formulation of diclofenac were evaluated in a randomized, double-blind, placebo-controlled, multi-centre study in patients aged 60 to 80 years suffering from osteoarthritis. A total of 314 elderly patients with a mean age of 68.9 years received either 50 mg diclofenac dispersible or placebo 3-times daily for a period of 4 weeks, with paracetamol being allowed as rescue analgesic for both treatment groups. The study consisted of a baseline evaluation and two follow-up visits after 14 and 28 days of treatment. The following clinical parameters were assessed: pain at rest, on movement and on local pressure; global severity of pain; effect of pain on daily activity; duration of stiffness after immobility; rescue analgesic consumption; overall opinion of the investigator on efficacy; and occurrence of adverse events. At either one or both post-treatment assessments, diclofenac dispersible was found to be significantly superior to placebo for almost all measures of efficacy (p less than or equal to 0.05). Thirty (14.4%) patients out of 208 assessed in the diclofenac group reported adverse events compared to 18 (17%) out of 106 who received placebo; therapy was discontinued prematurely due to poor tolerability in 4.8% and 5.7% of patients, respectively. The adverse events were predominantly related to the gastro-intestinal system and were mostly mild to moderate in severity. The results of this 4-week study thus demonstrate that diclofenac dispersible is not only effective in treating osteoarthritis in the elderly but also has an acceptable tolerability profile in a patient population which is especially vulnerable to adverse effects induced by non-steroidal anti-inflammatory drugs.

Administration, Oral↗

The effects of task preference on performance during purposeful and nonpurposeful activities.

This study examined the number of repetitions, increase in heart rate, increase in blood pressure, and rating of perceived exertion of subjects performing the most-preferred and least-preferred tasks from a predetermined list under purposeful and nonpurposeful conditions. Twenty healthy women completed the four experimental tests in random order for a period of 10 min each. The results indicated that there was no significant interaction (p greater than .05) between task choice and condition, thus implying that the subjects' performance was not influenced by task preference regardless of whether the activity was purposeful or nonpurposeful. Comparisons between the purposeful and nonpurposeful conditions revealed that the increase in heart rate and rating of perceived exertion were significantly higher (p less than .05) during nonpurposeful activity for both the most-preferred and the least-preferred tasks. On the basis of these results, it is recommended that therapists use purposeful, or goal-directed, activities in their practice, even if they are unable to provide their patients with a choice of therapeutic tasks.

Adult↗

Comparative bioavailability of slow release diclofenac (Voveran SR) with enteric coated tablet and internationally used Voltaren Retard.

The objective of the study was to compare the enteric coated diclofenac sodium (Voveran), the slow release formulation developed in India (Voveran SR) and the internationally marketed formulation Voltaren Retard. Ten healthy volunteers were administered 100 mg each of the three formulations in a three-way crossover fashion. Blood samples were collected over 24 hours following administration of the drug; plasma levels of unchanged drug were determined by gas chromatography. Pharmacokinetic parameters for the three formulations were compared. The extent of the drug available from the three formulations was the same as the mean AUC values were not significantly different. Cmax and MRT values for the two slow release formulations were comparable but were significantly different from the values obtained with the enteric coated formulation. Tmax values for the two slow release formulations were similar while the enteric coated tablet had faster time to peak. Voveran SR is comparable to Voltaren Retard and has the distinct advantage of a slow release formulation in that its Cmax is much lower and levels are maintained over 12 hours and detectable upto 24 hours. This slow release formulation will offer clinical advantages of better compliance, relief of early morning symptoms and better tolerability over long term usage.

Adult↗

Blockade of the glycine modulatory site of NMDA receptors modifies dynorphin-induced behavioral effects.

Intrathecal (i.t.) administration of the opioid dynorphin causes neurological dysfunction and tissue damage. It has been suggested that these effects of dynorphin may be mediated, in part, by N-methyl-D-aspartate (NMDA) receptors. In the present studies, recently developed compounds that block the glycine potentiation site of the NMDA receptor (Gly-NMDA site), including the competitive antagonist 5-fluoro-indole-2-carboxylic acid and the non-competitive antagonist 7-chlorokynurenic acid, prevented the neurologic deficits and mortality caused by i.t. dynorphin A(1-17). These findings are consistent with the hypothesis that dynorphin-induced neurological dysfunction involves activation of NMDA receptors. Moreover, blockade of the Gly-NMDA site may provide an alternative to blockade of the glutamate binding site or NMDA receptor ion channel as an in vivo pharmacological strategy to treat conditions previously associated with excitotoxin mediated tissue injury.

Animals↗

Competitive and non-competitive NMDA antagonists limit dynorphin A-induced rat hindlimb paralysis.

It has been proposed that the endogenous opioid dynorphin A (Dyn A) contributes to the pathogenesis of posttraumatic spinal cord injury (SCI). Dyn A-related peptides given intrathecally (i.t.) produce hindlimb paralysis. These include Dyn A(1-17), Dyn A(1-13), Dyn A(2-17), and Dyn A(3-13). Because Dyn A(2-17) and Dyn A(3-13) are inactive at opiate receptors, Dyn A-induced paralysis may include a non-opioid component. Recently, it has been reported that competitive N-methyl-D-aspartate (NMDA) antagonists block the loss of tail-flick reflex caused by i.t. administration of Dyn A(1-13). In the present studies we examined whether competitive [(4-[3-phosphonopropyl]-2-piperazine-carboxylic acid (CPP)] or non-competitive (dextrorphan) NMDA antagonists could attenuate paralysis induced by Dyn A(1-17) or Dyn A(2-17). CPP or dextrorphan each significantly attenuated the neurologic dysfunction and mortality associated with Dyn A(1-17) administration. In addition, CPP and dextrorphan significantly reduced the neurologic dysfunction caused by Dyn A(2-17)(all P less than 0.05). From these data we suggest that the non-opioid component of Dyn A-induced paralysis is mediated in part by the NMDA receptor.

Animals↗

Dynorphin A-(1-17) induces alterations in free fatty acids, excitatory amino acids, and motor function through an opiate-receptor-mediated mechanism.

The endogenous opioid dynorphin A-(1-17) (Dyn A) has been implicated as a mediator of tissue damage after traumatic spinal cord injury (TSCI) and causes hindlimb paralysis when administered intrathecally. Motor impairment following intrathecal Dyn A is attenuated by antagonists of excitatory amino acids (EAAs); whether opioid receptors mediate such injury has been questioned. TSCI causes various biochemical changes associated with secondary tissue damage, including alterations in tissue amio acids, phospholipids, and fatty acids. Such changes reflect injury severity and correlate with motor dysfunction. The present studies examined whether dynorphin administration causes similar biochemical alterations and whether effects of Dyn A can be modified by treatment with opioid-receptor antagonists. At 24 hr after intrathecal Dyn A, there were significant declines in tissue levels of glutamate, aspartate, and glycine. Increases in total free fatty acids were found at 2 and 24 hr, reflecting changes in both saturated and unsaturated components, which were associated with significant decreases in tissue cholesterol and phospholipid phosphorus at the earlier time point. Each of these neurochemical changes, as well as corresponding motor deficits, were limited by pretreatment with the opioid antagonist nalmefene. In separate experiments, both nalmefene and the selective kappa-opioid antagonist nor-binaltorphimine (nor-BNI) limited dynorphin-induced motor dysfunction; effects of nor-BNI were dose related, and those of nalmefene were stereospecific. Therefore, behavioral and neurochemical consequences of Dyn A administration are mediated in part through opiate receptors, most likely kappa-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Double-blind, multicenter evaluation of the efficacy and tolerability of diclofenac dispersible in the treatment of acute soft-tissue injuries.

In a randomized, double-blind, parallel-group, multicenter study, the efficacy and tolerability of diclofenac dispersible were compared with placebo in the treatment of acute soft-tissue injuries. Patients seen within 48 hours of a soft-tissue injury received either diclofenac dispersible 50 mg or placebo three times daily for 3 to 7 days, with paracetamol allowed as a rescue analgesic. Of a total of 253 recruited patients. 247 patients (122 in the diclofenac dispersible group and 125 in the placebo group) were eligible for tolerability assessment and 229 patients (115 diclofenac dispersible and 114 placebo) were eligible for efficacy analysis. In general, median reductions in the intensities of pain at rest, on movement, and on local pressure (as measured on 100-mm analog chromatic continuous scales) were greater with diclofenac dispersible than with placebo after treatment (differences did not reach statistical significance). At the center that recruited the largest number of patients, the initial median levels of pain at rest and on movement were considerably lower than those at the other centers. On reanalysis of the pain data without this center, a significant difference favoring diclofenac dispersible over placebo was noted for pain on movement and on local pressure (P < or = 0.044). With respect to daily assessment of pain severity, more patients in the diclofenac dispersible group had none or mild pain while fewer had moderate or severe pain during the early posttreatment days; this treatment difference versus placebo reached statistical significance on days 3 and 4 (P < or = 0.045).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗