More about parkinsonism after taking ecstasy.
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Hallucinogens↗
Biomedical subjects
J Mendelson
Publications and source records attributed to J Mendelson.
Malaria deaths in Canadian travellers.
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Adult↗
Buprenorphine and naloxone combinations: the effects of three dose ratios in morphine-stabilized, opiate-dependent volunteers.
Sublingual buprenorphine is a promising new treatment for opiate dependence, but its opioid agonist effects pose a risk for parenteral abuse. A formulation combining buprenorphine with the opiate antagonist naloxone could discourage such abuse. The effects of three intravenous (IV) buprenorphine and naloxone combinations on agonist effects and withdrawal signs and symptoms were examined in 12 opiate-dependent subjects. Following stabilization on a daily dose of 60 mg morphine intramuscularly, subjects were challenged with IV doses of buprenorphine alone (2 mg) or in combination with naloxone in ratios of 2:1, 4:1, and 8:1 (1, 0.5, or 0.25 mg naloxone), morphine alone (15 mg) or placebo. Buprenorphine alone did not precipitate withdrawal and had agonist effects similar to morphine. A naloxone dose-dependent increase in opiate withdrawal signs and symptoms and a decrease in opioid agonist effects occurred after all drug combinations. Buprenorphine with naloxone in ratios of 2:1 and 4:1 produced moderate to high increases in global opiate withdrawal, bad drug effect, and sickness. These dose ratios also decreased the pleasurable effects and estimated street value of buprenorphine, thereby suggesting a low abuse liability. The dose ratio of 8:1 produced only mild withdrawal symptoms. Dose combinations at 2:1 and 4:1 ratios may be useful in treating opiate dependence.
Adult↗
Buprenorphine and naloxone interactions in methadone maintenance patients.
Buprenorphine is undergoing clinical trials for the treatment of opiate addiction. Although the abuse liability of sublingual buprenorphine is low, reports of intravenous abuse have appeared. This study describes the physiologic and subjective effects of intravenously administered buprenorphine and naloxone given alone and in combination to methadone-maintained patients (40-60 mg/day). On four separate occasions at least 1 day apart, 6 subjects were administered either 0.2 mg buprenorphine, 0.1 mg naloxone, 0.2 mg buprenorphine and 0.1 mg naloxone in combination, or placebo. One male subject quit the experiment after three sessions because of excessive opiate withdrawal. Buprenorphine produced no significant physiologic or subjective effects. Naloxone produced marked opiate withdrawal symptoms. Buprenorphine in combination with naloxone produced characteristic physiologic and subjective opiate antagonist-like symptoms and signs. The parenteral abuse potential of the buprenorphine and naloxone combination is discussed.
Adult↗
The generation and maintenance of schedule-induced polydipsia in normal male rats without weight reduction.
Experiment One demonstrated that two normal male Sprague-Dawley rats (approximately 60 days old) with free access to food and two control rats whose weights were held constant by dietary restriction acquired schedule-induced polydipsia (SIP) in daily 33-35 min sessions of fixed-time 60-s food delivery. Three of the rats showed rapid acquisition of SIP; the fourth acquired SIP more slowly and consumed less per session the other three rats. After a 36-40 day period without sessions, the constant-weight rats showed a 37% decrease in overall consumption due to reduced drinking bout length. The SIP of the free-feeding rats was not affected by the interruption. After 90-100 periodic food delivery sessions, all subjects consumed an average of 11.2-12.2 mL per session compared with 1.8-4.8 mL per session in baseline sessions with massed food presentations. Experiment Two replicated the acquisition phase of Experiment One using two non-weight-reduced rats of the age and size of those typically used in SIP studies (approximately 30 weeks old). Both acquired SIP, although one showed only a small average increase in consumption per session over baseline (2.8 mL/session under periodic food vs. 0.8 mL following massed-food presentations). Before weight reduction, the stronger drinker consumed approximately 8.8 mL per session compared with an average of 0.6 mL per session in baseline. After weight reduction, both exhibited strong SIP (18-19 mL per session in the final five sessions). This study demonstrates that weight reduction is not a necessary condition for the generation and maintenance of SIP in rats.
Animals↗
Topical undecylenic acid for herpes simplex labialis: a multicenter, placebo-controlled trial.
A multicenter, patient-initiated, double-blind, placebo-controlled trial of 15% undecylenic acid cream was conducted with 573 patients with recurrent herpes labialis. Treatment was applied 5 or 6 times daily until crusting and then thrice daily until healing. Patients were assessed daily until 48 h after crusting and then every other day until healing. Undecylenic acid significantly reduced the incidence and duration of viral shedding and the duration and severity of itching but did not increase abortive episodes or reduce times to healing, crusting, or progression of lesion size. When treatment was initiated during the prodrome, the time to crusting was reduced (P = .02) and the area under the symptom-time curve for pain and tenderness was reduced, approaching statistical significance (P = .06). Active treatment was well tolerated but caused dysgeusia and local irritation. Undecylenic acid 15% cream reduces viral shedding in recurrent herpes labialis, but clinical benefits are minimal and largely restricted to patients initiating therapy during the prodrome.
Administration, Topical↗
Streptococcal venereal edema of the penis.
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Adult↗
Bioavailability of sublingual buprenorphine.
Buprenorphine administered sublingually is a promising treatment for opiate dependence. Utilizing a new, sensitive, and specific gas chromatographic electron-capture detector assay, the absolute bioavailability of sublingual buprenorphine was determined in six healthy volunteers by comparing plasma concentrations after 3- and 5-minute exposures to 2 mg sublingual and 1 mg intravenous buprenorphine. The amount of unabsorbed buprenorphine in saliva was measured after 2-, 4-, and 10-minute exposures to 2 mg sublingual buprenorphine in 12 participants. Pharmacokinetic parameters were analyzed by analysis of variance; bioequivalence was evaluated by the Schuirmann two-sided test. The 3- and 5-minute sublingual exposures each allowed 29 +/- 10% bioavailability (area under the plasma concentration-time curve unextrapolated) and were bioequivalent. Buprenorphine recovered from saliva after 2-, 4-, and 10-minute exposures was, on average, 52% to 55% of dose. Increased saliva pH was correlated with decreased recovery from saliva. Study results indicate that bioavailability of sublingual buprenorphine is approximately 30%. Sublingual exposure times between 3 and 5 minutes produce equivalent results. Buprenorphine remaining in saliva causes an almost twofold overestimation of bioavailability.
Administration, Sublingual↗
Temporal processing in cat primary auditory cortex.
In this short review, we discuss several aspects of how temporal coding is reflected in the response of primary auditory cortical neurons. We attempt to establish a link between several different temporal response properties including onset latency, response strength to repetitive stimuli, and the recovery of a response from suppression by a preceding signal. The results suggest a relationship between temporal effects that are expressed at quite different time scales. The results are discussed in relation to spatial representational properties and to coding in other sensory cortices.
Animals↗
Subnanogram-concentration measurement of buprenorphine in human plasma by electron-capture capillary gas chromatography: application to pharmacokinetics of sublingual buprenorphine.
We describe a sensitive and specific method for the measurement of buprenorphine in human plasma. The method involves a structural analog as an internal calibrator, careful control of pH during sample extraction to maximize drug recovery, and back-extraction into acid followed by reextraction to eliminate endogenous interferences. After evaporation, sample residues are derivatized with heptafluorobutyric anhydride and analyzed by separation on a fused-silica polymethylsiloxane capillary column and electron-capture detection. Calibration curves were linear in the ranges 0.1-2.0 micrograms/L and 2.0-20 micrograms/L, with within-run CVs of 9.7% at 0.1 microgram/L to 5.0% at 20 micrograms/L, and total CVs of 15.9% at 0.1 microgram/L to 6.5% at 10 micrograms/L. The limit of quantification was 0.1 microgram/L. The method was utilized in studies to determine the absolute bioavailability of sublingual doses of 2 mg of buprenorphine in 1 mL of 300 mL/L ethanol and the bioequivalence of sublingual 8-mg tablet and 300 mL/L ethanol solution formulations.
Administration, Sublingual↗
Buprenorphine and naloxone interactions in opiate-dependent volunteers.
OBJECTIVE: Sublingual buprenorphine appears useful in the treatment of opiate dependence. A combination sublingual dose of buprenorphine and naloxone could have less potential for parenteral use by opiate-dependent individuals. To estimate the abuse potential of a combination formulation, we assessed the parenteral effects of a buprenorphine and naloxone combination in untreated heroin addicts. METHODS: Eight healthy, opiate-dependent daily users of heroin were given, under double-blind conditions on four separate occasions, either (1) 2 mg buprenorphine, (2) 2 mg naloxone, (3) 2 mg buprenorphine and 2 mg naloxone combined, or (4) placebo as a single intravenous infusion during a 30-second interval. Opiate agonist and antagonist physiologic and subjective effects were measured. Data were analyzed by analysis of variance. RESULTS: Buprenorphine increased opiate intoxication and relieved withdrawal. The buprenorphine and naloxone combination precipitated opiate withdrawal and was unpleasant and dysphoric in all subjects. Fifty percent of the subjects were unable to distinguish between naloxone alone and the combined medications during the first hour of testing. CONCLUSIONS: The buprenorphine and naloxone combination has a low abuse potential in opiate-dependent daily heroin users.
Adult↗
Development of mupirocin resistance among methicillin-resistant Staphylococcus aureus after widespread use of nasal mupirocin ointment.
All methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from colonized or infected patients in a 625-bed public teaching hospital during an epidemic, and for 3 years thereafter, underwent susceptibility testing to mupirocin. Mupirocin resistance among MRSA increased markedly over this period (1990, 2.7%; 1991, 8.0%; 1992, 61.5%; 1993, 65%) in association with increased use of mupirocin ointment as an adjunct to infection control measures.
Administration, Intranasal↗
Levodopa therapy improves motor function in HIV-infected children with extrapyramidal syndromes.
Five children with human immunodeficiency virus type-1 (HIV-1) infection, aged 4 to 13 years, manifested extrapyramidal dysfunction characterized by rigidity/stiffness, ambulation difficulties/shuffling gait, dysarthria/drooling/swallowing dysfunction, hypomimetic/inexpressive facies, and bradykinesia. Levodopa therapy caused an initial improvement in all symptoms, and the effect was sustained in most patients. Levodopa is a useful adjunctive therapy in HIV-1-infected children with extrapyramidal syndromes, by enhancing motor function and improving their quality of life.
Child, Preschool↗
Immediate effects of intravenous cocaine on the thoracic aorta and coronary arteries. A transesophageal echocardiographic study.
UNLABELLED: STUDY OBJECTIVES AND DESIGN: Arterial vasoconstriction is thought to play a role in the etiology of cocaine-induced cardiovascular complications, but little is known about the immediate effects of cocaine on the thoracic aorta and coronary arteries. To examine these effects, we used transesophageal echocardiography to examine the thoracic aorta and coronary arteries before and immediately after intravenous (i.v.) cocaine (1.2 mg/kg) in 15 subjects. MEASUREMENTS AND RESULTS: Immediately after cocaine infusion, average heart rate, systolic BP, and double product were increased compared with baseline (22%, 15%, 35%, respectively). There was no significant change in the diameters of the ascending aorta (27.5 vs 27.1 mm; p = 0.85), the descending aorta (19.8 vs 20.4 mm; p = 0.62), or the left main coronary artery (4.3 vs 4.7 mm; p = 0.15). However, there was a trend for an increase in coronary blood flow immediately after cocaine (226 vs 309 mL/min; p = 0.10). CONCLUSIONS: We conclude that in the 15 subjects studied, there was no evidence of thoracic aorta of coronary artery vasoconstriction immediately after i.v. cocaine. Instead, we found that the diameters of the thoracic aorta and the left main coronary artery were unchanged, and that there was a trend for augmentation of coronary artery blood flow.
Adult↗
Left ventricular morphologic features and function in nonhospitalized cocaine users: a quantitative two-dimensional echocardiographic study.
To determine whether left ventricular (LV) hypertrophy or dysfunction is present in nonhospitalized cocaine users, we performed quantitative two-dimensional echocardiography in 20 intravenous cocaine users and 20 age- and sex-matched controls. Cocaine users were normotensive, had begun taking cocaine an average of 14 years earlier, and had used cocaine an average of 8 times/mo during the preceding year. There were no significant differences between cocaine users and control subjects for LV mass index (79 vs 74 gm/m2, respectively), mean wall thickness (0.95 vs 0.91 cm), end-diastolic volume index (55 vs 56 ml/m2), end-systolic volume index (17 vs 19 ml/m2), or ejection fraction (70 vs 66%; p > or = 0.09 for all comparisons). Moreover, none of the cocaine users or control subjects had significant regional wall motion abnormalities, and none of the subjects or controls had ejection fractions < 55%. Thus we found little evidence that significant LV hypertrophy or dysfunction is present in nonhospitalized cocaine users. From these results we speculate that cocaine-associated LV hypertrophy and dysfunction may be restricted to certain high-risk groups of chronic cocaine users.
Adult↗
Methamphetamine and ethanol interactions in humans.
OBJECTIVE: Methamphetamine and ethanol are commonly used together. We examined the effects of intravenous methamphetamine (30 mg), oral ethanol (1 gm/kg), and the combination of methamphetamine (30 mg) and ethanol (1 gm/kg). METHODS: Eight methamphetamine and ethanol users were studied in a double-blind, double-placebo, within-subject, balanced Latin-square design. Ethanol was administered in six drinks over 30 minutes. Methamphetamine was injected 60 minutes after the first drink was begun. Cardiovascular, subjective, and neuropsychologic effects of the drug combinations were measured for 6 hours. Methamphetamine and amphetamine in plasma and urine were measured by capillary gas chromatography for 48 hours. Data were analyzed by repeated-measures ANOVA. RESULTS: Compared with methamphetamine alone, the combination increased heart rate but decreased systolic blood pressure. The net cardiovascular effect was an increase in rate pressure product, an index of cardiac work and myocardial oxygen consumption. The combination diminished the subjective effects of ethanol while not affecting the subjective effects of methamphetamine. Methamphetamine pharmacokinetics were not altered by the concurrent administration of ethanol, with the exception of lowering the apparent volume of distribution at steady state for methamphetamine. CONCLUSIONS: As a potent sympathomimetic drug with alpha-agonist-like effects, methamphetamine increased systolic blood pressure, with minimal change in heart rate. The concurrent administration of methamphetamine and ethanol increased cardiac work, which could produce more adverse cardiovascular effects than either drug taken alone. The increased perceived global intoxication may explain the popularity of this drug combination.
Administration, Oral↗
Anterior chamber contamination after uncomplicated phacoemulsification and intraocular lens implantation.
PURPOSE: To determine the frequency of anterior chamber contamination occurring during uncomplicated cataract surgery with intraocular lens implantation using phacoemulsification through a scleral tunnel incision. METHODS: In a prospective study, anterior chamber aspirates of one eye each of 103 consecutive ambulatory patients who underwent uncomplicated cataract surgery with lens implantation were cultured. The anterior chamber aspirate was withdrawn immediately upon the completion of surgery. Conjunctival cultures of the same eye were taken immediately before surgery, after the eye and periocular area had been prepared and draped. Multiple use topical medications used preoperatively on all patients were cultured at the end of the surgical day. RESULTS: Intraocular aspirates yielded positive cultures in five specimens (5%), four of which were identified as Staphylococcus epidermidis. Quantification disclosed colony counts ranging between 100 and 200 colony forming units per milliliter. Results of conjunctival cultures were positive in ten specimens (10%). Staphylococcus epidermidis was the most common isolate, identified in seven of the ten positive cultures. Positive intraocular and conjunctival culture results were not present concurrently in any patient. Microorganisms were recovered from the multiple use topical medications on nine of the 26 successive surgical days. Neisseria species was the most frequent isolate (7,44%), followed by S. epidermidis (5,31%). The frequency of contamination of the anterior chamber was independent of wound width (chi 2 = 0.869) and operative time (chi 2 = 4.77). CONCLUSION: Bacterial contamination of the anterior chamber was detected in five (5%) of the patients. This reduced incidence of contamination compared with that of previous studies may be related to the preoperative preparation, the surgical technique, or both. Contamination of the multiple use topical medications and bulbar conjunctiva define possible sources of pathogens that may enter the anterior chamber. The absence of any clinical ocular infection in all patients attests to the small inoculum sizes, as well as the ability of the anterior chamber to clear small bacterial loads.
Administration, Topical↗