Biomedical subjects
Publications and source records attributed to J C Henry.
Strokes have been rarely associated with immunoglobulin G (IVIg) therapy. A 70-year-old woman with stable polycythemia vera developed Guillain-Barré syndrome and received IVIg, 8 days following which she became comatose due to bilaterally symmetric cerebral infarcts. Autopsy showed intravascular aggregates of fibrin-IgG but also platelets and a necrotizing microangiopathy in the infarcts.
Velo-cardio-facial syndrome (VCFS) is associated with deletions on the long arm of chromosome 22, mild intellectual disability, poor social interaction and a high prevalence of psychosis. However, to date there have been no studies investigating the neuropsychological functioning of adults with VCFS. We compared 19 adults with VCFS with 19 age, gender and IQ matched controls using a comprehensive neuropsychological battery. Compared to controls, adults with VCFS had significant impairments in visuoperceptual ability (Visual Object and Space Perception Battery), problem solving and planning (Tower of London) and abstract and social thinking (Comprehension WAIS-R). It is likely that haploinsufficiency (reduced gene dosage) of a neurodevelopmental gene or genes mapping to chromosome 22q11 underlies the cognitive deficits observed in individuals with VCFS.
Female athletes who participate in jumping and cutting-type sports have a four- to six-fold higher incidence of serious knee injuries compared with male athletes in the same sports. Many of these injuries involve the anterior cruciate ligament, and occur by non-contact mechanisms. The susceptibility of the female athlete's knee to injury is likely multifactorial, although neuromuscular factors seem to have an important role. Recent studies have identified neuromuscular differences between male and female athletes. Specifically, female athletes have decreased stiffness and decreased potential for dynamic stabilization of the knee joint. Proprioception deficits involving the knee and side-to-side strength and coordination imbalances are more frequent in female athletes. Also, female athletes more commonly demonstrate imbalances in strength, timing of activation, and recruitment patterns of the lower extremity muscles. Based on these findings, neuromuscular training programs have been studied in an effort to correct lower extremity neuromuscular imbalances. Preliminary results from these programs have been encouraging in reducing peak landing imact forces in the knee, correcting strength and proprioception deficits, and ultimately in decreasing the incidence of serious knee injuries in female athletes.
PURPOSE: To compare the effect of four commercially available viscoelastic agents on postoperative intraocular pressure (IOP). SETTING: Four outpatient sites. METHODS: Sixty-nine patients having routine extracapsular cataract extraction were enrolled in the study; 54 were available for a 3 month follow-up examination. The four viscoelastic agents were Amvisc, Amvisc Plus, Healon, and Viscoat. Intraocular pressure was measured preoperatively and at 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours and 3 months postoperatively. Pachymetry and endothelial cell counts were performed preoperatively and 3 months postoperatively. RESULTS: Mean postoperative IOP and IOP changes from baseline did not differ among the four treatment groups at any time. However, when mean maximal IOP was compared, the Healon group demonstrated the highest IOP increases (P = .0033). There was also a significant difference (P = .0015) among the treatment groups in the mean maximum postoperative change from baseline; the Healon group exhibited the largest mean change in IOP. At 3 months postoperatively, IOP values and pachymetry were normal for all treatment groups and were not statistically different among groups, indicating the four agents provided similar degree of endothelial protection and IOP stability. CONCLUSION: These results suggest that IOP increases occur in varying degrees and at varying times in the early postoperative period after cataract surgery using a viscoelastic agent.
The aim of this study was to evaluate instrumented tank rowing for its ability to measure objectively the individual performance components of power output and rowing skill in a sample of collegiate rowers. The measuring system utilized strain gauges and a potentiometer to measure force on the oar and its angular position at each sampling interval. Power outputs were calculated for 13 collegiate rowers tested individually during a 30-s bout of maximal work. Results from this 'tank test' were compared with power measurements from both Concept II (CII) and Stanford rowing ergometers and from a Wingate test, using similar 30-s bouts of maximal work. Significant differences (P < 0.05) were found between the tank test and all other modes of testing except the Wingate test for average power. These differences can probably be attributed to the different methods of power measurement and to the different skill-dependence associated with the tests. For each subject, peak power and average power per stroke were measured from the rowing tests. The CII and Stanford test data for all subjects were correlated with their tank test data. Similar correlations were made between tank data and the peak and mean power from the Wingate test. The strongest correlation was in peak power measurements with the Wingate test (r = 0.92, P = 0.0001). Instrumented tank rowing provided objective information on individual power output unique from rowing and cycling ergometry. Of the various tests, the tank test appeared to provide better and more complete power data specific to rowing. This method also provided objective data for interpreting various aspects of rowing skill, including oar handling, technical efficiency, consistency, stroke frequency, stroke recovery ratio and stroke length. Instrumented tank rowing has substantial potential as a coaching tool or as a self-training device for improving rowing ability.
Investigation of the naturally occurring, nicotinic agonist anabaseine and novel derivatives has shown that these compounds have cytoprotective and memory-enhancing effects. The hypothesis that these arise at least in part through actions on brain nicotinic receptors was evaluated by examining the ability of these compounds to displace the binding of nicotinic ligands and to affect the function of the alpha 4 beta 2 and alpha 7 receptor subtypes expressed in Xenopus oocytes. The derivative 3-(4)-dimethylaminocinnamylidine anabaseine (DMAC) was found to be a selective alpha 7 receptor agonist; it was more potent than nicotine, acetylcholine, anabaseine, and other derivatives at activating the alpha 7 receptor subtype, while displaying little agonist activity at alpha 4 beta 2 and other receptor subtypes. Compared with anabaseine and the other derivatives, DMAC was the most potent at displacing 125I-alpha-bungarotoxin binding (putative alpha 7) and the least potent at displacing [3H]cytisine binding (putative alpha 4 beta 2) to brain membranes. Independently of agonist activities, all of the novel compounds displayed secondary inhibitory activity at both receptor subtypes. At the alpha 4 beta 2 receptor subtype, inhibition by the 3-(2,4)-dimethoxybenzylidene derivative was enhanced by coapplication of acetylcholine, suggesting a noncompetitive form of inhibition. Anabaseine and nicotine prolonged the time course of activation of alpha 4 beta 2 receptors, compared with acetylcholine, suggesting sequential channel-blocking activity. As selective agonists, anabaseine derivatives such as DMAC may be useful for elucidating the function of alpha 7 nicotinic receptors, including their potential role(s) in the cytoprotective and memory-enhancing effects of nicotinic agents.
Given the often reported relationships between sleep-wake regulation and the cerebral prostaglandins (PGs), the effect of chronic rapid eye movement (REM) sleep deprivation on brain PGE2 and PGD2 biosynthesis in mouse was evaluated, since they are known to have opposite actions as respectively wake- and sleep-inducing substances. Mice were subjected to 5 and 10 days of REM sleep deprivation by the flower pot technique. After sacrifice, PGE2 and PGD2 were determined in the pituitary, hypothalamus and hippocampus. Except in the pituitary where no changes were shown, the PGE2/PGD2 ratio was significantly enhanced after 5 and 10 days of REM sleep loss, when compared to control. These results showed an alteration of cerebral PGE2 and PGD2 biosynthesis, resulting in a shift from PGD2 toward PGE2. These results were not consistent with a role of PGD2 as a sleep-promoting substance as, if that was the case, it would be increased during the REM sleep deprivation. But they do not rule out its involvement as a facilitating substance.
OBJECTIVE: To evaluate the efficacy of 0.5% brimonidine tartrate, an alpha 2-adrenergic agonist, in preventing intraocular pressure (IOP) elevation following argon laser trabeculoplasty. DESIGN: In a multicenter, double-masked, randomized study, 248 patients (248 eyes) who underwent argon laser trabeculoplasty were allocated to four treatment groups: (1) brimonidine administered before and after the procedure; (2) brimonidine administered before the procedure; (3) brimonidine administered after the procedure; and (4) a vehicle administered before and after the procedure. RESULTS: In the first 3 hours after argon laser trabeculoplasty, only one (0.54%) of the 183 brimonidine-treated patients had a postlaser IOP increase of 10 mm Hg or more, while increases of this magnitude occurred in 13 (23%) of the 56 patients who received only the vehicle (P < .001). The three brimonidine-treatment groups demonstrated significant mean reductions in IOP from the pretrabeculoplasty level (-4 to -8 mm Hg), whereas the vehicle-treated group showed an increase in mean IOP (4 mm Hg). Side effects associated with brimonidine treatment included conjunctival blanching (40.9%), lid retraction (7.6%), and a slight lowering of the systolic blood pressure. CONCLUSIONS: One drop of 0.5% brimonidine administered either before or after surgery was found to be efficacious and safe in preventing posttrabeculoplasty elevations in IOP.
Devil's Claw (Harpagophytum procumbens), an herbal product being marketed in Canada and in Europe as a home remedy for the relief of arthritic disease, was investigated in healthy humans on eicosanoid production during spontaneously blood clotting. Volunteers took H. procumbens (daily 4 capsules of 500 mg powder containing 3% of total glucoiridoids) for a period of 21 days. The following are the results (mean (SEM)): before H. procumbens intake, prostaglandin (PG)E2 (ng/ml serum): 2.1 (0.4) (n = 25), thromboxane (TX)B2: 147 (27) (n = 25), 6-keto-PGF1 alpha: 4.4 (0.7) (n = 13), leukotriene (LT)B4: 3.4 (0.4) (n = 25); after intake: PGE2: 3.2 (0.6), TXB2: 143 (24), 6-keto-PGF1 alpha: 4.2 (0.9), LTB4: 3.8 (0.6). Each subject serving as her own control, no statistically significant differences were observed between before and after H. procumbens intake. These results indicate that Devil's Claw lacks, at least in healthy humans and under the selected conditions, the biochemical effects on arachidonic acid metabolism of antiarthritic drugs of the non-steroidal antiinflammatory type.
To investigate the blood pressure lowering effect of magnesium (Mg2+) in the hypertensive rat, we measured the prostacyclin release (PGI2, as immunoreactive 6-keto-PGF1 alpha) by isolated aortae from normotensive and deoxycorticosterone acetate (DOCA)-salt hypertensive rats fed a control or Mg(2+)-enriched diet. We also studied the in vitro effect of Mg2+ on aortic PGI2 release. The Mg(2+)-enriched diet significantly decreased by 10% blood pressure in DOCA-salt hypertensive rats but not in normotensive rats. The Mg(2+)-enriched diet significantly increased by 122% aortic PGI2 release in DOCA-salt hypertensive rats, but not in normotensive rats. Mg2+ supplementation in the incubation medium (4.8 mM) significantly increased aortic PGI2 release by 94% in DOCA-salt hypertensive rats, but not in normotensive rats. These data suggest that the Mg(2+)-induced attenuation of blood pressure in DOCA-salt hypertensive rats could be linked with the enhanced vascular PGI2 release.
Injection of diltiazem (40 mg/kg/d) to gentamicin (75 mg/kg/d = G 75 or 100 mg/kg/d = G 100) treated rats enhances aminoglycoside-induced nephrotoxicity. As a result of this combination, acute renal failure becomes systematic and is often irreversible. The lesion is of tubular origin and is characterized by a large increase in the urinary N-acetyl-beta-D-glucosaminidase (u-NAG) activity and its NAG-B isoenzyme level. The phenomenon is twice as marked with G 75 (u-NAG x 6.8, NAG-B x 2.2) as with G 100 (u-NAG x 3.1, NAG-B x 1.1). The effect seems to be attenuated if diltiazem is administered as a preventive treatment or in drinking water. As well as its diuretic properties, diltiazem may aggravate the renal toxicity of gentamicin by reducing the proximal tubular availability of calcium. Diltiazem inhibits reabsorption and behaves like a non-competitive inhibitor of calcium. This deficiency favours the proximal tubular binding and the non-specific penetration of gentamicin in the cytosol and cellular organelles (microsomes, mitochondria). The tubular toxic symptoms which ensure (inactivation of membranaceous enzyme, reduction of microsomal protein synthesis and ATP level, decreased of solute reabsorptive flux) lead in turn to proximal tubular necrosis and acute renal failure.
The renal toxicity of combined administration of cyclosporin and aminoglycosides was evaluated in rats. Increasing doses of amikacin (A) or gentamicin (G) were injected alone or in association with cyclosporin (CS). Creatinine clearance rate, urinary N-acetyl-Beta-D-glucosaminidase (NAG) activity and NAG-B isoenzyme level were determined to evaluate glomerular or tubular dysfunctions. When given alone, high doses of aminoglycosides (100 mg/kg/day of G and 375 mg/kg/day of A) induced transient inhibition of glomerular filtration rate. The concomitant administration of CS caused severe acute renal failures with 50 mg/kg/day of G and only with 375 mg/kg/day of A. With equal doses of G, urinary NAG excretion was seven times higher in association with CS than in monotherapy. In the same conditions, NAG activity was only doubled with A. A specific increased of NAG-B isoenzyme level occurred only during the most nephrotoxic association. This attest of a proximal tubular lesion, preliminary to glomerular dysfunction. The results of this study confirm the potent synergistic nephrotoxicity that CS exerts in combination with aminoglycosides. Nevertheless, the good tolerance of amikacin lead us to reconsider the principle of exclusion of such association in transplant recipients.
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Our study indicates that amikacin (AK) inhibited urinary N-acetyl-beta-D-glucosaminidase (NAG) activity. In vivo and in vitro experiments showed significant increase of Michaelis constant of urinary NAG, in human and in rat, treated by amikacin. Our data indicate that the inhibition of amikacin on NAG and its isoenzymes was "apparently competitive" rather than competitive as reported by others. In the "apparently competitive" inhibition the amikacin-enzyme binding would be irreversible, including combined action of many hydrogen bonds which could have a strength like covalent bond.
In order to investigate the contribution of eicosanoids to human oesophageal functions and disorders (gastrooesophageal reflux, GOR and reflux oesophagitis, RO), we have used a selected ion monitoring gas chromatographic/mass spectrometric methodology to quantify the cyclooxygenase and lipoxygenase products biosynthesized in vitro by endoscopic mucosal biopsy specimens. Prostaglandins (PGs) were quantified as MEMOTMS derivatives and HETEs, as hydrogenated methyl ester of tert-butyldimethylsilyl) ether derivatives. PGE2, PGF2 alpha appeared as the major prostanoids, whereas 12HETE seemed to be the major lipoxygenase product. In the case of GOR or RO, biosynthesis of PGE2 was dramatically increased, while no change could be detected for 12HETE. PGE2 increase seems to be related to inflammatory reaction, in which its exact role remains unclear. Moreover, it cannot be excluded that PGE2 is a side product which might be protective to the oesophageal mucosa.
In an attempt to elucidate the possible involvements of eicosanoids in esophageal functions and disorders, we have investigated the formation of both cyclooxygenase and lipoxygenase metabolites from 14C-arachidonic acid by rabbit esophageal tissues. Homogenates of rabbit esophageal mucosa and muscularis were incubated with 14C-arachidonic acid and after ether extraction eicosanoids were separated and quantified by reverse phase high performance liquid chromatography. The predominant cyclooxygenase products were 6-keto-PGF1 alpha, PGF2 alpha, and PGE2 for mucosa and 6-keto-PGF1 alpha, and PGE2 for muscularis. The formation of these products was inhibited both by indomethacin and the dual pathway inhibitor, nordihydrogualaretic acid (NDGA). In mucosa the major eicosanoid was 12-HETE (12-hydroxyeicosatetraenoic acid) which was inhibited by NDGA but not by indomethacin which on the contrary enhanced its formation. Additionally four polar products were synthesized which appeared to be lipoxygenase-dependent as their formation was inhibited by NDGA but not by indomethacin. Muscularis produced as a minor lipoxygenase product only 12-HETE, which was inhibited by NDGA but unchanged in the presence of indomethacin. In addition, both tissues, but mucosa more than muscularis, possessed large prostaglandin catabolizing capacity. The present findings indicate that rabbit esophageal tissues can convert 14C-arachidonic acid into lipoxygenase as well cyclo-oxygenase products which may have a role in esophageal physiology and pathophysiology.
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Lysosomal enzyme activities can be modified by aminoglycosides. In this study, we have investigated the "in vitro" effect of gentamicin (G), tobramycin (T), dibekacin (D), netilmicin (N) and amikacin (AK) on urinary N-acétyl-beta-D-glucosaminidase (NAG) and its isoenzymatic forms. G, D and N are activators of this enzyme, specifically of the B isoenzymatic form, while T inhibits slightly the A, I1 and I2 forms. At usual therapeutical urinary concentration of AK during antibiotherapy, NAG and its isoenzymes are very strongly inhibited (more than 65%). Dixon plot indicates that the nature of inhibition is "competitive apparent", without binding of inhibitor to the active site of the enzyme. This binding of aminoglycosides to NAG as to other lysosomal enzymes may represent one of the accumulation mechanisms of aminoglycosides in tubular cells. It can explain the specific alteration of lysosomes during nephrotoxic antibiotherapy. Consequently, when urinary NAG determination is used as indicator of nephrotoxicity during therapy, the activation or inhibition of the enzyme by aminoglycosides could lead to false assay results.