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Biomedical subjects

J Mendelson

Publications and source records attributed to J Mendelson.

At least 19 recordsLinked to original sources

Malaria deaths in visitors to Canada and in Canadian travellers: a case series.

Over the last decade there has been a marked increase in case of drug-resistant and severe malaria in Canadian travellers. We report 7 deaths due to falciparum malaria that occurred in Canada or in Canadian travellers. Risks for malaria infection include inappropriate recommendations for malaria prevention by health care providers and lack of knowledge about or adherence to appropriate recommendations by the travelling public. Risks for death include delays in seeking medical attention, delays in diagnosis and inadequate care by Canadian physicians and hospitals, and lack of access to parenteral therapy for severe malaria. Malaria infections and deaths are preventable. Better education of health care providers and travellers about the risks of malaria and appropriate prevention and treatment measures may decrease this unnecessary burden on the Canadian health care system.

Adult↗

Mycotic aneurysm of the carotid bifurcation in the neck: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Mycotic aneurysms of the extracranial carotid artery are rare and difficult to diagnose. A search of the world literature published since 1966 reveals at least six cases of mycotic carotid aneurysms due to a Salmonella septicemia. We present an exceptional case of mycotic pseudoaneurysm of the bifurcation of the carotid artery due to Salmonella septicemia and discuss the pathogenesis as well as various aspects of the diagnosis and surgical management. CLINICAL PRESENTATION: A 68-year-old man presented in Poland with Salmonella sepsis; 1 month later, he was admitted to the emergency department of the Sir Mortimer B. Davis-Jewish General Hospital in Montreal with a bulky and pulsatile right cervical mass. An angiogram and a computed tomographic scan revealed a voluminous and partially thrombosed aneurysm the size of a tangerine originating from the posterior aspect of the carotid junction. INTERVENTION: Balloon trapping was attempted at the Montreal Neurological Hospital. Subsequently, the patient developed a significant neurological deficit, which was quickly reversed by the administration of hypertensive, hypervolemic, and hemodilution therapy. Thereafter, the pseudoaneurysm was resected surgically, and the internal and external carotid arteries were sacrificed. Pathological examination of the excised specimen of the carotid junction revealed a pseudoaneurysm. Bacterial culture of the lesion showed growth of Salmonella. CONCLUSION: The postoperative course was satisfactory except for laryngeal paralysis due to involvement of the vagus nerve. Four months later, a computed tomographic scan showed only small lacunae in both centra semiovale.

Aged↗

Buprenorphine and naloxone co-administration in opiate-dependent patients stabilized on sublingual buprenorphine.

Buprenorphine and naloxone sublingual (s.l.) dose formulations may decrease parenteral buprenorphine abuse. We evaluated pharmacologic interactions between 8 mg s.l. buprenorphine combined with 0, 4, or 8 mg of naloxone in nine opiate-dependent volunteers stabilized on 8 mg s.l. buprenorphine for 7 days. Combined naloxone and buprenorphine did not diminish buprenorphine's effects on opiate withdrawal nor alter buprenorphine bioavailability. Opiate addicts stabilized on buprenorphine showed no evidence of precipitated opiate withdrawal after s.l. buprenorphine-naloxone combinations. Buprenorphine and naloxone bioavailability was approximately 40 and 10%, respectively. Intravenous buprenorphine and naloxone produced subjective effects similar to those of s.l. buprenorphine and did not precipitate opiate withdrawal.

Administration, Sublingual↗

Cardiovascular effects of 3,4-methylenedioxymethamphetamine. A double-blind, placebo-controlled trial.

BACKGROUND: The psychoactive stimulant 3, 4-methylenedioxymethamphetamine (MDMA), also known as "ecstasy," is widely used in nonmedical settings. Little is known about its cardiovascular effects. OBJECTIVE: To evaluate the acute cardiovascular effects of MDMA by using transthoracic two-dimensional and Doppler echocardiography. DESIGN: Four-session, ascending-dose, double-blind, placebo-controlled trial. SETTING: Urban hospital. PATIENTS: Eight healthy adults who self-reported MDMA use. INTERVENTION: Echocardiographic effects of dobutamine (5, 20, and 40 microg/kg of body weight per minute) were measured in a preliminary session. Oral MDMA (0.5 and 1.5 mg/kg of body weight) or placebo was administered 1 hour before echocardiographic measurements in three weekly sessions. MEASUREMENTS: Heart rate and blood pressure were measured at regular intervals before and after MDMA administration. Echocardiographic measures of stroke volume, ejection fraction, cardiac output, and meridional wall stress were obtained 1 hour after MDMA administration and during dobutamine infusions. RESULTS: At a dose of 1.5 mg/kg, MDMA increased mean heart rate (by 28 beats/min), systolic blood pressure (by 25 mm Hg), diastolic blood pressure (by 7 mm Hg), and cardiac output (by 2 L/min). The effects of MDMA were similar to those of dobutamine, 20 and 40 microg/kg per minute. Inotropism, measured by using meridional wall stress corrected for ejection fraction, decreased after administration of dobutamine, 40 microg/kg per minute, but did not change after either dose of MDMA. CONCLUSIONS: Modest oral doses of MDMA increase heart rate, blood pressure, and myocardial oxygen consumption in a magnitude similar to dobutamine, 20 to 40 microg/kg per minute. In contrast to dobutamine, MDMA has no measurable inotropic effects.

Administration, Oral↗

Self-reported marijuana effects and characteristics of 100 San Francisco medical marijuana club members.

In order to assess the relationships between medical marijuana users' reasons for use, side effects, and drug use patterns, 100 participants were recruited from the San Francisco Cannabis Cultivator's Club. Users, averaging 14 years pre-illness use, perceived marijuana to be more effective than other treatments and to have less severe side effects. Urine drug assays showed recent use of other drugs, particularly stimulants. History of substance abuse or dependence and other psychiatric disorders was common. Those with greater past dependence on other drugs thought marijuana to be more effective but also reported worse side effects and quality of life. Quality of life was associated more with marijuana side effects rating than effectiveness. Patients reported potentially serious marijuana side effects on some questionnaires but not others. Inconsistencies in reporting made interpretation of results difficult. Physician supervision of medical marijuana use would allow more effective monitoring of therapeutic and unwanted effects, some unrecognized by patients.

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↗

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↗