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Biomedical subjects

I Morin

Publications and source records attributed to I Morin.

8 recordsLinked to original sources

Comparative bioavailability of a generic capsule formulation of the reverse transcriptase inhibitor efavirenz and the innovator product.

OBJECTIVE: Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that has been used successfully for more than a decade to treat human immunodeficiency virus (HIV) infection. The objective of the current study was to determine the bioequivalence between a generic capsule formulation of efavirenz and the innovator product. MATERIAL AND METHODS: A total of 41 healthy subjects (34 males and 8 females) received a single 200 mg oral dose of efavirenz as the generic (Ranbaxy-Efavirenz, Ranbaxy Laboratories Ltd.) and innovator (Sustiva, Bristol-Myers Squibb) capsule formulations under fasting conditions in a randomized, 2-way crossover study. Multiple blood samples were collected over 72 hours and plasma concentrations of efavirenz were assayed using an LC/MS/MS method. Pharmacokinetic (PK) parameters were calculated using non-compartmental methods. RESULTS: Plasma concentrations of efavirenz peaked within 2.5 hours and then declined in a multi-exponential manner for both formulations. At 72 hours post dose, all plasma concentrations of efavirenz were above the LOQ of the assay (10 ng/ml). Mean area under the curve from 0 - 72 hours (AUC0-72) and maximum plasma concentrations (Cmax) of efavirenz for the generic capsule formulation were 22,840 ng x h/ml and 1,199 ng/ml, respectively. Ratios and 90% confidence intervals of PK parameters between the two formulations were within 80.0 - 125.0%, suggesting that the two capsule formulations resulted in similar rate and extent of bioavailability under fasting conditions. Adverse events were similar in nature and frequency for the two formulations. CONCLUSIONS: Based on the above results, the generic capsule formulation of efavirenz developed by Ranbaxy should be as effective as the innovator product.

Administration, Oral↗

Three year injury crash records of new licensees with suspensions or invalidity periods lasting 90 days or more.

A subset of new licensees, namely the ones with suspensions or invalidity periods of at least 90 days are studied. This subpopulation is comprised of 3,550 men and 1,295 women for whom the study file contains age, gender, licensing exam performance, and the dates all police reported crashes for the first three years after licensing. This group is compared with the complementary subpopulation of 53,069 men and 58,464 women. The average injury crash rate per year, not prorated, is 0.057 for men and 0.033 for women, about twice the rate for those without lengthy suspensions. These licensees are older, have lower success rates at licensing exams, and have a longer learning period than the others. Separate logistic-normal regression models for men and for women are estimated for the probability of a collision in a year using the available explanatory variables.

Accidents, Traffic↗

Induction of stromelysin gene expression by tumor necrosis factor alpha is inhibited by dexamethasone, salicylate, and N-acetylcysteine in synovial fibroblasts.

Proinflammatory cytokines, altered connective tissue metabolism, and overexpression of matrix metalloproteinases (MMPs) such as stromelysin compared to tissue inhibitors of metalloproteinases (TIMPs) result in synovial inflammation and erosion of arthritic cartilage. Tumor necrosis factor alpha (TNF-alpha) is a major synovial inflammatory mediator responsible for inhibiting extracellular matrix (ECM) synthesis and stimulating degradation of cartilage ECM by activated MMPs in arthritic joints. To suppress these effects and to gain insight into the mechanism of TNF-alpha action, we identified the inhibitors of TNF-alpha stimulation of stromelysin gene expression. In bovine synovial fibroblasts, TNF-alpha did not affect a recently identified inhibitor, TIMP-3, but induced stromelysin mRNA expression in a dose- and time-dependent fashion (3- to 5-fold) which required de novo protein synthesis. Stimulation by TNF-alpha was potently inhibited (99-100%) by the synthetic glucocorticoid, dexamethasone. Sodium salicylate dose-dependently inhibited (100%) the TNF-alpha action. Indomethacin and ibuprofen were partially inhibitory. Free radical scavenger antioxidant, N-acetylcysteine (but not other antioxidants) also suppressed the TNF-alpha induction (36-100%) of stromelysin suggesting involvement of reactive oxygen species in the induction process. TNF-alpha induction of stromelysin gene expression can therefore be inhibited at the gene expression level by several pharmacological agents which are likely to function via arachidonic acid metabolites, free radical scavenging or interference with the activator protein 1, polyoma virus enhancer A-binding protein 3, and nuclear factor kappaB classes of transcription factors. Our results may help to elucidate the mechanism of TNF-alpha action and explain the beneficial role of these agents in the treatment of inflammatory diseases.

Acetylcysteine↗

A comparative study of the chemical stability of various mitomycin C solutions used in glaucoma filtering surgery.

OBJECTIVE: To determine the chemical stability of various mitomycin C (MMC) solutions used in glaucoma filtering surgery. METHODS: A survey of the MMC solutions currently in use in 21 hospitals (11 in Canada, 10 in the United States) was conducted. A comparative study of the chemical stability of five different representative solutions was performed. The effects of buffer and storage variables on the chemical breakdown of MMC in the solutions were studied by means of high-performance liquid chromatography (HPLC). RESULTS: The survey revealed 33 different variations (including recipes and storage conditions) in the preparation of MMC solutions. Although the majority of the hospitals (15 of 21; 72%) were preparing stable solutions, six of the hospitals (28%) were preparing potentially unstable solutions. The stability of the solutions varied in a nonuniform manner when stored at different temperatures in different buffers. CONCLUSION: The lack of standardization and quality control of MMC solutions used in filtering surgery allows for the possibility of hospitals preparing unstable solutions.

Buffers↗

[Multimodal or multisensorial agnosia?].

A 75 year-old right handed woman had persistent right homonymous hemianopia and alexia without agraphia caused by a haemorrhagic stroke of the left occipito-temporal region. Six months later she suffered sudden onset visual and auditory agnosia, following a second haematoma, contralateral to the first one, in the right occipito-temporal region including the lingual and fusiform gyri. None of the disorders concerned semantic representation, so that an asemantic agnosia was excluded. Her performance in naming and recognition tests, in both visual and auditory modalities, demonstrated a wide range of responses and errors. The pattern of visual symptoms suggested "associative visual agnosia narrow sense" (Farah, 1990); auditory agnosia concerned only the non verbal stimuli. These findings were discussed in terms of anatomical mechanisms subserving perceptual, semantical, visuo and auditory-verbal representation. In this case, visual and auditory, agnosia appears to be independent.

Aged↗

Right motor neglect associated with dynamic aphasia, loss of drive and amnesia: case report and cerebral blood flow study.

A 30-year-old right-handed man had right motor neglect, amnesia, aphasia and loss of drive following bilateral thalamic and subthalamic infarctions. Serial resting cerebral blood flow (CBF) measurements with either Xenon 133 inhalation or positron emission tomography at 1, 8 and 10 months post-onset showed a widespread and long-lasting low CBF in the cortex. An additional CBF measurement, during motor tasks, showed a marked interhemispheric asymmetry in the pattern of activation: whereas left hand movement resulted in a CBF increase in contralateral superior rolandic and prerolandic areas, no significant regional CBF changes were seen during right hand movement, despite recovery from motor neglect. This loss of CBF increase in cortical motor and premotor areas during voluntary movement of the previously neglected side points to a disruption of cortico-subcortical pathways subserving motor activation. The pathophysiology of aphasia, loss of drive and amnesia as well as their relationships to motor neglect, may also be discussed on the basis of thalamo-cortical disconnections.

Adult↗

[Severe amblyopia and Alzheimer' disease].

A 69-year-old woman developed a rapid and severe visual loss and became nearly blind in a few weeks. As she also presented with memory loss and other disturbances of cognitive functions, with progressive deterioration over one year, a probable Alzheimer's disease was diagnosed. Cerebral CT scan and magnetic resonance imaging were normal. However, clinical and electrophysiological (visual evoked potentials) data indicated an impairment of the primary visual pathways rather than a degeneration of the secondary visual cortex. This case is compared with and discussed in relation to recent reports concerning retinal and optic nerve damage in Alzheimer's disease.

Aged↗

[Crying provoked by sound stimuli in a case of probable dementia of Alzheimer's type].

A case of pathological crying elicited only by non-verbal auditory stimulations in a woman with probable dementia of the Alzheimer type is reported. As neuropsychological data available in this case have suggested a greater involvement of left than right temporal cortex, the authors propose that the crying phenomenon could have been explained by a similar inter-hemispheric asymmetry in pathological involvement of the limbic structures.

Acoustic Stimulation↗