Biomedical subjects
C A Gauthier
Publications and source records attributed to C A Gauthier.
Reproductive parameters and paracallosal skin color changes in captive female guinea baboons, Papio papio.
Reproductive data are presented for female Papio papio housed in the Zoological Park of Paris and are compared with previously published data from free-ranging populations of other baboon species. The results indicate similar intermenstrual intervals and durations of sexual swelling. Sexual swelling and pregnancy are accelerated in captivity, while postpartum amenorrhea and interbirth interval are reduced. Interbirth intervals in P. papio were short, approximately 13 months in the case of viable, surviving infants and approximately 11 months in the case of stillbirth or neonatal mortality. The shorter interval may represent the lower physiological limit, and the generally shorter interbirth interval reported here may be explained by lower stress and reduced maternal investment costs in the captive environment. Paracallosal skin color variations during the menstrual cycle were influenced by parity, but sexual swelling patterns were not. The paracallosal skin changes might be used by males as a cue to females' reproductive status.
The discriminative stimulus effects of naloxone and naltrexone in morphine-treated rhesus monkeys: comparison of oral and subcutaneous administration.
RATIONALE: Opioid antagonists are used to reverse the toxic effects of opioids, to diagnose opioid dependence and to treat opioid and other (alcohol) drug abuse. OBJECTIVES: This study compared the discriminative stimulus effects of two opioid antagonists (naloxone and naltrexone), after parenteral and oral administration. METHODS: The discriminative stimulus effects of naloxone and naltrexone were evaluated every 15 min over a 2-h period in four morphine-treated (3.2 mg/kg per day) rhesus monkeys discriminating between subcutaneous (SC) injections of naltrexone (0.01 or 0.032 mg/kg) and saline, while responding under a fixed-ratio 5 schedule of stimulus shock termination. RESULTS: Within 15 min of SC administration, naloxone and naltrexone produced greater than 90% drug-appropriate responding at doses of 0.032 and 0.01 mg/kg, respectively. The largest dose of naloxone (3.2 mg/kg) administered orally produced 82% drug-appropriate responding within 90 min; the same dose of naltrexone administered orally produced greater than 90% drug-appropriate responding within 30 min. Although both drugs were at least 100-fold more potent when administered SC, as compared to orally, there was little difference (3-fold) between the potency of naloxone and naltrexone by either route. CONCLUSIONS: These results fail to support the view that naloxone has reduced bioavailability after oral administration, as compared to naltrexone, or that its pharmacokinetic profile is particularly advantageous for some therapeutic settings (e.g. Talwin Nx).
Daily mirfentanil induces (cross-) tolerance to the rate-decreasing effects of morphine and not mirfentanil.
The fentanyl derivative mirfentanil has a novel set of behavioral effects in non-humans including low-efficacy opioid actions and non-opioid antinociceptive actions. This study evaluated the rate-decreasing effects of mirfentanil, morphine, naltrexone and ketamine in pigeons both prior to and during a period of chronic treatment with mirfentanil (3.2-17.8 mg/kg/day). Daily treatment with mirfentanil did not modify the rate-decreasing effects of mirfentanil or ketamine; however, daily treatment decreased sensitivity to the rate-decreasing effects of morphine and increased sensitivity to naltrexone. These results demonstrate a lack of tolerance to an apparently non-opioid action (rate-decreasing effect) of mirfentanil, which might predict a lack of tolerance to the non-opioid antinociceptive actions of this compound. These results further indicate that cross-tolerance (to morphine) and dependence (increased sensitivity to naltrexone) can occur in the absence of tolerance (to mirfentanil).
The rate-decreasing effects of fentanyl derivatives in pigeons before, during and after chronic morphine treatment.
Mirfentanil is a fentanyl derivative with non-opioid actions, including non-opioid antinociceptive effects in rhesus monkeys. The current study examined the rate-altering effects of mirfentanil and several other compounds in pigeons to assess: 1) the opioid and non-opioid actions of acutely-administered fentanyl derivatives; and 2) the development of cross-tolerance between each of these compounds and morphine. Seven pigeons responded under a fixed-ratio 20 (FR20) schedule of food delivery. In untreated pigeons, fentanyl, morphine, naltrexone, ketamine and three fentanyl derivatives (mirfentanil, OHM3463 and OHM3295) decreased rates of key pecking in a dose-related manner. Naltrexone (0.1-1.0 mg/kg) attenuated the effects of OHM3463 and not mirfentanil or OHM3295, suggesting non-opioid mediation of the rate-decreasing effects for the latter two fentanyl derivatives. Subjects were treated daily with morphine for 9 weeks, up to a dose of 100 mg/kg per day, during which time the dose-effect curves for morphine, fentanyl and OHM3463 shifted rightward 6-, 10- and 2-fold, respectively, indicating the development of tolerance to morphine and cross-tolerance to fentanyl and OHM3463. Dose-effect curves for ketamine, OHM3295 and mirfentanil were not shifted to the right during morphine treatment, and the dose-effect curve for naltrexone was shifted leftward 180-fold. To the extent that rate-decreasing effects are predictive of antinociceptive effects, these data suggest that some fentanyl derivatives might be useful therapeutics under conditions where tolerance develops to morphine-like opioids.
Assessment of high and low contrast visual acuity after photorefractive keratectomy for myopia.
BACKGROUND: Our aim was to assess visual acuity using standardized charts and illumination conditions after photorefractive keratectomy. METHODS: High and low contrast visual acuity were measured on Bailey-Lovie logarithm of the minimum angle of resolution (LogMAR) charts under high and low illumination conditions on 105 photorefractive keratectomy patients who had been treated with the Summit (N = 60) or the VISX (N = 45) excimer laser. RESULTS: Best corrected visual acuity was reduced in the treated eye compared with the untreated control eye under all test conditions, with the greatest differences under conditions of low contrast and low illumination. Reduction of acuity under low contrast and low illumination was related to small optic zone sizes and steep ablation edge profiles found in Summit-treated eyes. In the VISX-treated eyes, high contrast acuity was reduced in the presence of central topographical irregularities, subepithelial haze, and higher myopic corrections. CONCLUSIONS: Testing conditions such as those described here may be useful in quantifying vision degradation in suboptimal viewing conditions and among patients with vague complaints.
The effects of postmortem delay on mu, delta and kappa opioid receptor subtypes in rat brain and guinea pig cerebellum evaluated by radioligand receptor binding.
Studies of human and animal central nervous system receptor degradation and measurement postmortem are important as human tissue can rarely be collected under ideal experimental conditions. Correlating the change in binding of opioid receptor subtypes over time will help define the conditions under which human studies may be valid. The present study was designed to investigate the rate at which opioid receptor subtypes degrade postmortem. Brains from rats or cerebelli from guinea pigs were kept at 22 degrees C or 4 degrees C at times from zero to 24 hours to simulate two common human collection techniques; room temperature and morgue refrigeration. Tissue homogenates from these brains were analysed for mu1, mu2, delta, kappa1 and kappa3 opioid receptor binding using standard radioligand binding techniques. At room temperature mu1, mu2 and delta opioid receptor binding was reduced between 6 and 12 hours, whereas kappa1 and kappa3 binding was reduced after 24 hours. At 4 degrees C mu1, mu2, delta, kappa1 and kappa3 binding remained constant over the 24 hour period.
Factors affecting epithelial hyperplasia after photorefractive keratectomy.
PURPOSE: To determine the effect of patient age, postoperative time, ablation zone diameter and depth, attempted correction, and corneal topography on postoperative corneal epithelial thickness after photorefractive keratectomy (PRK). SETTING: Private clinic and university hospital, Stockholm, Sweden. METHODS: This retrospective, unmasked study comprised 136 myopic patients treated unilaterally with PRK. Seventy eyes had been treated with the Summit excimer laser 27 months +/- 7 (SD) earlier using ablation zone diameters of 4.1 to 5.0 mm. Sixty-six eyes had been treated with the VISX excimer laser 6 +/- 3 months earlier using a 6.0 mm zone diameter. The untreated fellow eyes served as controls. Epithelial thickness was measured at a standardized central corneal area with a modified optical pachymeter, and corneal topography was determined using computerized videokeratoscopy. RESULTS: In the Summit group, the epithelial layer in the PRK eyes was 12.0 microns (21%) thicker than in the control eyes (P < .001; 95% confidence interval [CI] 9.35 to 14.3 microns). This thickness differential correlated significantly with increased ablation depth and attempted correction. In the VISX group, the epithelium in the treated eyes was 7.0 microns (7%) thinner (P = .0009; 95% CI -1.9 to -6.7 microns) and thickness did not correlate with ablation depth or attempted correction. There was no correlation between epithelial hyperplasia and patient age or postoperative follow-up. With the laser groups combined, epithelial hyperplasia was greater with smaller zone sizes and a greater rate of change in power at the edge of the ablation zone. CONCLUSION: The factors associated with an increase in epithelial thickness were small ablation zones, greater attempted corrections, and deeper ablations. Larger, smoother ablation profiles may result in less epithelial hyperplasia.
A comparative study of epithelial hyperplasia after PRK: Summit versus VISX in the same patient.
Epithelial hyperplasia has been found to occur after photorefractive keratectomy in eyes treated with small (5 mm or less) ablation zone diameters with the Summit laser, but not with large zones (6 mm) with the VISX laser (Gauthier et al. 1995a). The aim of this study was to further investigate the effect of surgical parameters on epithelial hyperplasia by comparing eyes treated with the same zone diameter but two different lasers. We examined 11 subjects who had photorefractive keratectomy for myopia performed with 5 mm ablation zones with the Summit excimer laser in one eye and the VISX 20/20 laser in the fellow eye an average of 21 months previously. Epithelial thickness and corneal topography were measured. The mean epithelial thickness was not statistically different (p = 0.083) between the eyes treated with the Summit (66 +/- 12 microns) and VISX (60 +/- 14 microns) lasers. Postoperative corneal dioptric power showed a similar profile between the two eyes at the edge of the zone, with the VISX-treated corneas being more shallow centrally. There was a trend towards greater epithelial thickness with deeper ablations. This study supports the hypothesis that epithelial hyperplasia is dependent on ablation zone diameter and ablation depth.
Role of epithelial hyperplasia in regression following photorefractive keratectomy.
AIM: To determine the relation between epithelial hyperplasia and regression of effect after photorefractive keratectomy (PRK). METHODS: Seventy unilaterally treated patients with PRK were examined. All eyes had been treated with the Summit excimer laser 27 (SD 7) months previously with zone diameters of 4.1 to 5.0 mm. The untreated fellow eyes served as controls. Epithelial thickness was measured centrally with a thin slit optical pachometer and manifest subjective refraction was performed. RESULTS: The epithelium was 21% thicker in the treated eye (p < 0.0001). The relation between refractive regression and epithelial hyperplasia was significant (r = 0.41; p < 0.001). CONCLUSIONS: Epithelial hyperplasia after PRK correlated with the myopic shift (including hyperopia reduction) after treatment with the Summit laser. A model is proposed suggesting that both subepithelial and epithelial layers contribute to regression in the Summit treated eyes with 18 microns of epithelial hyperplasia contributing each dioptre of regression.
Tracker-assisted photorefractive keratectomy for myopia of -1 to -6 diopters.
BACKGROUND: The Autonomous Technologies T-PRK (Tracker-assisted Photorefractive Keratectomy) excimer laser system uses a small beam scanner that allows flexibility in the ablation pattern that is applied to the cornea and incorporates a sophisticated LADARVision eye tracker that is capable of following saccadic movements. This paper describes the first clinical results on sighted eyes for the correction of low myopia. METHODS: Forty-two normal sighted eyes of 42 patients were treated for spherical myopia between -1.00 diopters (D) and -6.00 D with 6 mm ablations. Visual acuity, refractive error, contrast sensitivity (with and without glare), corneal haze, endothelial cell density, and patient satisfaction were measured. RESULTS: Mean manifest refraction was -0.39 D +/- 0.68 D at 1 month with regression to -0.94 D at 3 months and -1.05 D at 6 months. At 6 months, 5 (20%) eyes were +/- 0.50 D and 14 (56%) eyes were +/- 1.00 D. Consistent with this undercorrection and regression, uncorrected visual acuity (UCVA) of 20/20 and 20/40 or better was achieved by 10 (40%) and 34 (85%) eyes at 3 months and 16 (40%) and 17 (68%) eyes at 6 months. None of the eyes lost 2 or more lines of spectacle corrected visual acuity. Corneal haze was graded as 1/2 trace or less in 89% to 100% of eyes at all intervals. There was no loss of endothelial cells (mean +/- SD cell density centrally: preop 3115 +/- 322 and 6 months 3220 +/- 333) and contrast sensitivity recovered to baseline levels at 3 months. CONCLUSIONS: The Autonomous Technologies T-PRK excimer laser system is safe and effective for the reduction or correction of myopia from -1.00 D or -6.00 D. The refractive results may be improved by adjusting the calibration to reduce the undercorrection and by instituting use of topical corticosteroids on an individual basis for those who regress.
Patient preferences and comparative ocular responses to rigid and soft contact lenses.
Patient preferences and ocular responses were compared between rigid and soft contact lenses by randomly fitting 32 neophyte subjects with a rigid lens in 1 eye and a soft lens in the contralateral eye. Twenty-seven of 32 subjects completed the 3-month study and 16 subjects were willing to continue for an additional 3-month extension. Subjects preferred the comfort and handling of the soft lens but preferred the vision provided by the rigid lens and initially its ease of maintenance. There was also a marked preference for the soft lens when all aspects of lens wear were compared. Objectively, the rigid lenses were responsible for more ocular changes than the soft lenses. Palpebral aperture sizes of the rigid gas permeable (RGP) wearing eyes decreased significantly (0.5 mm; p < 0.05) compared to the soft lens wearing eyes. The incidence of corneal staining was significantly greater in the rigid lens wearing eye (50% RGP vs. 22% soft) but limbal injection was greater in the soft lens wearing eye (18% soft vs. 6% RGP). Refractive sphere, cylinder, and corneal astigmatism decreased in the rigid lens wearing eye after 3 months. This daily wear clinical trial has shown a marked subjective preference for wearing soft lenses with fewer short-term ocular effects.
Interest of presbyopes in contact lens correction and their success with monovision.
The presbyopic population is seen as a large potential source of contact lens wearers. The aims of this study were: (1) to estimate the percentage of presbyopes interested in contact lenses, (2) to ascertain the success of interested presbyopes with monovision correction, and (3) to determine the percentage willing to continue wearing monovision lenses after 1 month's trial. Seven practitioners in Sydney surveyed consecutive presbyopes attending their practices about their interest in contact lenses. Of the 1133 presbyopes surveyed, 314 (28%) were interested in trying monovision lenses. A total of 72 patients were subsequently fitted with monovision in high water content hydrogel form. After 1 month, 46 of these patients (64%) were still wearing the lenses, and 39 (54%) expressed willingness to continue with monovision correction. The major reasons for discontinuation from lens wear during the 1-month trial were inadequate vision and difficulty in lens handling.
Clinical performance of two opaque, tinted soft contact lenses.
Comfort, visual acuity, visual fields, daytime corneal edema and corneal staining were evaluated on 22 subjects wearing opaque tinted and non-opaque control hydrogel lenses. CooperVision Permaflex Mystique (38% polymacon) and Wesley-Jessen Durasoft 3 Colors (55% phemfilcon A) opaque lenses were compared to non-opaque lenses from the same manufacturers (CooperVision CV Classic and Wesley-Jessen Durasoft 3). Subjects were randomly assigned one type of opaque lens and one clear lens on each of two days, and two opaque lenses on another day. All lenses yielded similar results in terms of comfort, visual acuity, visual fields and corneal staining. The only visual problem with the opaque lenses was the reporting of "haziness" (usually peripheral) in 72 percent of Mystique and 59 percent of Durasoft 3 Colors trials. The greatest daytime corneal edema, 4.7 percent, occurred with the Mystique lens compared with 2.7 percent with CV Classic and 1.8 percent and 1.7 percent with the opaque and clear Durasoft 3 lenses respectively. These levels of edema were associated with a 40 percent incidence of striae with Mystique (17/43), 14 percent with the CV Classic (3/21 eyes), 5 percent with Durasoft 3 clear (1/22 eyes) and 2 percent with Durasoft 3 opaque lenses (1/44 eyes). Corneal swelling correlated with the measured Dk/L of the lenses. The Durasoft 3 Colors lens was the opaque tinted lens of choice based primarily on corneal physiology.
Effect of phosphate buffer concentration on the heat resistance of Bacillus stearothermophilus spores suspended in parenteral solutions.
The effect of various quantities of Butterfield phosphate buffer added to four parenteral solutions on the survival of Bacillus stearothermophilus spores heated at 121 degrees C was determined. The effect of the addition of phosphate buffer on spore survival varied with the parenteral solution. Spore survival was increased or decreased, depending upon the composition of the parenteral solution and the buffer concentration. The results obtained in these experiments attest to the fact that environmental factors, including the type of ions present and ionic concentration, affect the heat destruction rate of B. stearothermophilus spores. Therefore, the sterilization requirements of a product such as a parenteral solution may be affected by small changes in formulation.
Epithelial alterations following photorefractive keratectomy for myopia.
BACKGROUND: A retrospective observational study was conducted to test the hypothesis that there is clinically measurable epithelial hyperplasia after photorefractive keratectomy (PRK), and to determine its effect on the epithelial oxygen uptake rate. METHODS: One hundred myopic eyes who had been previously treated unilaterally with PRK were examined. Fifty eyes were treated with the Summit excimer laser (Summit Technology, Waltham, Mass) 27 +/- 7 months previously with ablation zone diameters of 4.1, 4.3, 4.5, or 5.0 mm. Fifty eyes were treated with the VISX excimer laser (VISX Inc, Sunnyvale, Calif) 5 +/- 4 months previously with one ablation zone diameter of 6.0 mm. The untreated eyes served as controls. Epithelial thickness was measured at a standardized central area within the ablation zone with a modified optical pachometer. Oxygen uptake rate was measured in a subgroup of 30 eyes (20 Summit and 10 VISX). RESULTS: The epithelium after PRK was 24% thicker than in the control eye in the Summit group (mean difference 13 +/- 10 microns; p < .01) and 7% thinner in the VISX group (mean difference -4 +/- 10 microns; p < .01). A higher oxygen uptake rate correlated with a thicker epithelium (r = 0.42; p < .05). CONCLUSIONS: The epithelium was significantly thicker after PRK between 13 and 37 months after treatment with the Summit excimer laser using ablation zone diameters of 4.1 to 5.0 mm. The epithelium was thinner between 1 and 15 months after treatment with the VISX laser using an ablation zone diameter of 6.0 mm. An increase in oxygen uptake rate reflected the metabolic rate of a greater number of cells in the hyperplastic layer.
Failure of mechanical epithelial removal to reverse persistent hyperopia after photorefractive keratectomy.
BACKGROUND: Residual hyperopic overcorrection after photorefractive keratectomy (PRK) using early algorithms is a rare but serious complication. Anecdotal evidence suggests that epithelial removal can stimulate epithelial hyperplasia, thereby reducing overcorrection. The aim of this study was to determine if epithelial removal effectively reduced hyperopia after PRK for myopia and, concurrently, to correlate the healing response with the refractive outcome. METHODS: Enrolled were seven eyes of seven patients (mean age, 44 +/- 13 years) who had undergone PRK with a mean manifest refractive error of +2.21 +/- 0.74 diopters (D). All had undergone PRK an average of 24 +/- 9 months previously. Epithelial removal was performed over the excimer-treated zone with a surgical blade. Subjective refraction, epithelial thickness, corneal topography, and subepithelial haze were measured up to 1 year postoperatively. RESULTS: Reduction in hyperopia between the baseline and 1-year visit was not statistically significant (mean difference, 0.55 D reduction; p = .102). That epithelial removal did not stimulate a wound-healing response is further supported by the absence of change in epithelial thickness over the first month and the small amounts of subepithelial haze. Central corneal power was reduced by a mean of 0.64 D after 1 month (p < .05). CONCLUSIONS: Epithelial removal alone did not reduce the hyperopic overcorrection present after PRK, nor did it stimulate epithelial hyperplasia in the majority of these eyes. However, a trend toward improvement was noted with time was noted.