Optical penalization can improve vision after occlusion treatment

BACKGROUND: Optical penalization (OP) has previously been shown to successfully maintain vision in amblyopic eyes of older children when patching compliance is poor and when vision decreases once patching is discontinued. This study shows that the final vision in optically penalized eyes is often better than the vision obtained after patching alone. SUBJECTS AND METHODS: During the 5-year period from January 1992 to February 1997, 28 children aged between 3.7 and 8.2 years (average age, 6.5+/-1.1 years) were optically penalized for an average of 1.5+/-0.75 years. The maximum length of penalization was 3.3 years, whereas the minimum time was 6 months. There were 21 children with strabismic amblyopia and 7 children with anisometropic amblyopia. All 28 children had worn a patch to achieve their best visual levels and then had shown a loss of best vision when occlusion was stopped. Patching was usually resumed and continued until the previous best vision was obtained; at this point OP was started to "maintain" vision. Eighteen of the 28 children have discontinued penalization and have been followed up an average of 1(1/2) years. RESULTS: Twenty-six (93%) of the 28 patients showed an increase in best vision from that found at the conclusion of patching, and 2 patients maintained their vision at the initial level. The average visual acuity at the start of penalization was 20/50 (0.42+/-0.11 logarithm of the minimum angle of resolution [log MAR]). Final average visual acuity was 20/27 (0.15+/-0.12 log MAR). The average increase in vision was nearly 3 lines or 0.27+/-0.12 log MAR. CONCLUSION: OP alone (without the use of pharmacologic agents such as atropine) not only maintains vision after patching therapy, but also appears to improve the final visual outcome.     

Discriminative stimulus effects of flumazenil in untreated and in diazepam-treated rhesus monkeys

Rationale: Long-term use of benzodiazepine agonists can have adverse effects (e.g., development of dependence), thereby limiting their clinical usefulness. Objectives: The goal of the current study was to examine the discriminative stimulus effects of flumazenil in untreated and diazepam-treated monkeys to determine whether this type of procedure could be used to examine benzodiazepine dependence. Methods: Flumazenil (0.32 mg/kg s.c.) was established as a discriminative stimulus in eight monkeys receiving 5.6 mg/kg/day of diazepam (p.o.); four responded under a fixed ratio (FR)5 schedule of stimulus-shock termination (SST) and four responded under a FR5 schedule of food presentation. For comparison, 1.0 mg/kg flumazenil (s.c.) was established as a discriminative stimulus in four untreated monkeys responding under a FR5 schedule of SST. Results: Flumazenil dose-dependently increased responding on the flumazenil-appropriate lever in all monkeys. In diazepam-treated monkeys, Ro 15-4513, ethyl beta-carboline-3-carboxylate and bretazenil substituted for flumazenil with pentylenetetrazole substituting in some monkeys; other drugs failed to substitute for flumazenil. Acute administration of 10.0 mg/kg diazepam (s.c.) shifted the flumazenil dose–effect curve threefold to the right of the control dose–effect curve. Temporary suspension of diazepam treatment produced a time-related increase in flumazenil-lever responding that was reversed by diazepam. In untreated monkeys, midazolam substituted for flumazenil, with other drugs, including those with primary mechanisms of action at non-γ-aminobutyric acid_A receptors, substituting in some monkeys. Ro 15-4513 did not substitute in any untreated monkey. Conclusions: The flumazenil discriminative stimulus appears to be pharmacologically selective in treated monkeys with only negative and low efficacy positive modulators substituting for flumazenil; in contrast, a variety of drugs substitute for flumazenil in untreated monkeys. This apparent difference in selectivity suggests that diazepam treatment modifies the flumazenil discriminative stimulus perhaps due to the development of dependence. Received: 30 November 1998 / Final version: 25 May 1999     

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). Received: 15 July 1998 / Final version: 21 December 1998     

The discriminative stimulus effects of MK-801 in pigeons

The discriminative stimulus effects of MK-801 [(+)-5-methyl-10, 11-dihydroxy-5H-dibenzo (a,d) cyclohepten-5, 10-imine], a proposed noncompetitive N-methyl-D-aspartate (NMDA) antagonist, were studied in pigeons discriminating MK-801 from saline, responding being maintained by food. Compounds with noncompetitive NMDA antagonist effects in other preparations (PCP [0.18-5.6mg/kg], dextrorphan [1-32mg/kg], ketamine [1-32mg/kg] and dexoxadrol [1-10mg/kg]) produced MK-801-appropriate responding dose-dependently. The potency order for this effect, and for response rate decreasing effects, closely mirrored the potency order for these compounds in causing catalepsy, an effect believed to be mediated by antagonism at the NMDA receptor complex. NMDA (0.32-5.6mg/kg), morphine (1-10mg/kg) and pentobarbital (1-17.8mg/kg) produced almost no MK-801-appropriate responding. There were no consistent potency differences among the (+)-isomer (1-32mg/kg), the (-)-isomer (1-17.8mg/kg) and the racemate (1-17.8mg/kg) of SKF 10,047 in producing MK-801-appropriate responding. The competitive NMDA antagonist CGS 19755 (1-10mg/kg) produced partial MK-801-appropriate responding (maximum value = 77.8%) up to 8h after administration. The homogeneity of the discriminative stimulus effects among compounds with noncompetitive NMDA antagonist effects in vitro, as well as the partial substitution for MK-801 by CGS 19755, suggest that the MK-801 discriminative stimulus in pigeons is due to noncompetitive NMDA antagonism.     

Residual curarization in the neonate after Caesarean section

The transplacental transfer and the neonatal effects of atracurium 0.3 mg.kg-1 (ED95) were compared with those of d-tubocurarine at the usual clinical dose of 0.3 mg.kg-1 (ED90) in 46 patients undergoing elective Caesarean section. The atracurium group (25 patients) was similar to the d-tubocurarine group (21 patients) as far as age, parity and time intervals between precurarization, induction, skin incision, muscle relaxant administration, hysterotomy and birth. The transplacental transfer of atracurium was lower than that of d-tubocurarine, with a feto-maternal ratio of 9 +/- 3% for atracurium and 12 +/- 5% for d-tubocurarine (P less than 0.05). The transplacental transfer of laudanosine was low at 14 +/- 5%, with blood levels of 0.101 +/- 0.032 microM.L-1 in the umbilical vein. Newborns in the two groups were comparable in terms of Apgar scores at one, five and ten minutes, as well as for NACS scores (neurological and adaptive capacity scoring test) at two and 24 hours after birth. However, at 15 min after birth, only 55% of newborns in whom the mothers received atracurium had a normal NACS score (greater than or equal to 35/40) compared with 83% of newborns in whom the mothers received d-tubocurarine (P less than 0.05). Further analysis of the five variables related to active muscle tone revealed that the modal score for active extension of the neck of newborns from the atracurium group was lower than for newborns from the d-tubocurarine group (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hospital comparisons using a Euro Health Data Base for resource management and strategic planning

A European approach for resource management and strategic planning has been implemented in the HOSCOM project of AIM by defining information standards needed across countries, as well as a methodology to measure resources and costs at the institutional and interinstitutional level. A Euro Health Data Base (EHDB) has been obtained in order to test data availability and comparability as well as to validate models through macrocomparisons using case-mix (DRG's, refined grouping, disease staging) and microcomparisons based on three diseases (cardiac valve replacement, diabetes mellitus and hip fracture). The EHDB's presently based on 274 164 medical record summaries sampled from 7 countries allowed us to build prototypes (using Clipper, Prolog and SQL) in order to export uniform aggregates in the different countries, with standard software tools for statistical comparisons. It showed the present feasibility of using case-mix based on the European Minimum Basic Data Set (MBDS) and the difficulty of obtaining uniform data on resources and costs other than length of stay across countries. Medical data confidentiality was assured but not yet population-based representativity. Given the present state of the EHDB, problems have been clearly identified in order to be solved by international research and development projects in the near future.