Public opinion on smoke-free policies among Egyptians.

SETTING: A smoke-free law was passed in Egypt in 2007. In 2010 a bylaw was issued, leading to a drive by the Ministry of Health and Population (MOHP) to launch a smoke-free initiative in Alexandria, the second largest city. OBJECTIVE: To assess public opinion with regard to 100% smoke-free legislation and its implementation in the Alexandria governorate. DESIGN: The Union Middle-East Office, in collaboration with the Central Agency for Public Mobilization and Statistics and the MOHP, conducted a cross-sectional survey among 427 randomly selected adults (206 males and 221 females), covering the seven major districts of the Alexandria governorate. RESULTS: The majority of the interviewed subjects (98%) expressed support of the government in enacting 100% smoke-free indoor legislation in all public places and public transport. Respondents endorsed the government plan to implement legislation imposing 100% smoke-free public places. More than one third (33.5%) of all respondents indicated that they would increase visits to restaurants if they were smoke-free, and 63% indicated no impact at all. CONCLUSION: The results of the poll clearly support results from different countries worldwide that smoke-free policies are popular and supported by the public.

The Pharmacokinetics of the THC in fat and brain: Resulting functional responses to marihuana smoking: G. Nahas, Volume 16 Issue 3, April 2001, pages 247-255.

The original article to which this Erratum refers was published in Human Psychopharmacology: Clinical and Experimental 16 (3) 2001, 247-255.

Cognitive dysfunction in obsessive-compulsive disorder.

OBJECTIVE: Assessment of cognitive functions among obsessive-compulsive disorder (OCD) patients would help in understanding the neurobiology and brain areas involved in that disorder. The objective of this work was to study the cognitive dysfunction in OCD patients and to identify its correlation with both the clinical picture and the severity of the disorder. METHOD: Neuropsychological and electrophysiological event-related potentials were tested in 30 OCD patients and compared with 30 normal volunteers of a matched gender, age and education. RESULTS: Results showed a defective visuospatial recognition, which worsens with chronicity, deteriorated set-shifting abilities, overfocused attention to irrelevant stimuli and delayed selective attention to relevant tasks. Mild cases showed better selective attention than severe cases. Obsessive cases had a defective visual memory, while compulsive cases had delayed perception of task relevant stimuli. Mixed cases showed disturbed information-processing both early and late. CONCLUSION: OCD patients have a characteristic pattern of cognitive dysfunction that differs among patients of varied severity, chronicity and symptom type. We suggest a striatofrontoparietal neural pathophysiology. OCD seems to be a heterogeneous disorder, both clinically and pathophysiologically.

Guidelines for the treatment of acidaemia with THAM.

THAM (trometamol; tris-hydroxymethyl aminomethane) is a biologically inert amino alcohol of low toxicity, which buffers carbon dioxide and acids in vitro and in vivo. At 37 degrees C, the pK (the pH at which the weak conjugate acid or base in the solution is 50% ionised) of THAM is 7.8, making it a more effective buffer than bicarbonate in the physiological range of blood pH. THAM is a proton acceptor with a stoichiometric equivalence of titrating 1 proton per molecule. In vivo, THAM supplements the buffering capacity of the blood bicarbonate system, accepting a proton, generating bicarbonate and decreasing the partial pressure of carbon dioxide in arterial blood (paCO2). It rapidly distributes through the extracellular space and slowly penetrates the intracellular space, except for erythrocytes and hepatocytes, and it is excreted by the kidney in its protonated form at a rate that slightly exceeds creatinine clearance. Unlike bicarbonate, which requires an open system for carbon dioxide elimination in order to exert its buffering effect, THAM is effective in a closed or semiclosed system, and maintains its buffering power in the presence of hypothermia. THAM rapidly restores pH and acid-base regulation in acidaemia caused by carbon dioxide retention or metabolic acid accumulation, which have the potential to impair organ function. Tissue irritation and venous thrombosis at the site of administration occurs with THAM base (pH 10.4) administered through a peripheral or umbilical vein: THAM acetate 0.3 mol/L (pH 8.6) is well tolerated, does not cause tissue or venous irritation and is the only formulation available in the US. In large doses, THAM may induce respiratory depression and hypoglycaemia, which will require ventilatory assistance and glucose administration. The initial loading dose of THAM acetate 0.3 mol/L in the treatment of acidaemia may be estimated as follows: THAM (ml of 0.3 mol/L solution) = lean body-weight (kg) x base deficit (mmol/L). The maximum daily dose is 15 mmol/kg for an adult (3.5L of a 0.3 mol/L solution in a 70kg patient). When disturbances result in severe hypercapnic or metabolic acidaemia, which overwhelms the capacity of normal pH homeostatic mechanisms (pH < or = 7.20), the use of THAM within a 'therapeutic window' is an effective therapy. It may restore the pH of the internal milieu, thus permitting the homeostatic mechanisms of acid-base regulation to assume their normal function. In the treatment of respiratory failure, THAM has been used in conjunction with hypothermia and controlled hypercapnia. Other indications are diabetic or renal acidosis, salicylate or barbiturate intoxication, and increased intracranial pressure associated with cerebral trauma. THAM is also used in cardioplegic solutions, during liver transplantation and for chemolysis of renal calculi. THAM administration must follow established guidelines, along with concurrent monitoring of acid-base status (blood gas analysis), ventilation, and plasma electrolytes and glucose.

Molecular characteristics of cocaine-induced cardiomyopathy in rats.

Cocaine abuse induces severe cardiomyopathy. To investigate the molecular effects of acute and prolonged administration of cocaine, mRNAs encoding markers of either mechanical overload, as atrial natriuretic factor (ANF) and alpha- and beta-myosin heavy chains, or fibrosis as type I and III procollagens, were quantitated in the left ventricle of rats 4 h after one injection of cocaine (40 mg/kg, n = 7), or 14 (n = 15) and 28 days (n = 10) after chronic infusion of cocaine (40 mg/kg per day). Plasma cocaine and benzylecgonine concentrations were both significantly augmented during the infusion while plasma levels of triiodothyronine and thyroxine were lowered. Acute injection of cocaine induced ANF gene expression. Cocaine treatment during 28 days resulted in left ventricular hypertrophy (+ 20% after 24 days, P < 0.05) with normal blood pressure, associated with an accumulation of mRNAs encoding ANF and type I and III collagens (+66% and +55%, P < 0.05). Such a chronic treatment also induced a shift from the alpha- to the beta-myosin heavy chain gene expression (-40% and +50%, P < 0.05). In conclusion, cocaine activates markers of both hemodynamic overload and fibrosis. Such an activation may result from direct and/or indirect effects of the drug such as myocardial ischemia, mechanical overload and/or hypothyroidism.

Effects of antidotes to cocaine on the deregulation of the baroreflex by the alkaloid.

Cocaine exerts in the rat an inhibitory effect on the baroreflex induced by bilateral clamping of the carotid arteries. The present series of experiments were designed to test the effectiveness of cocaine antidotes on this deregulation of the baroreflex. Sprague-Dawley rats were fitted under pentobarbital anesthesia with a catheter in the caudal artery, and their carotid arteries were exposed. The pressure signal from the caudal artery was treated on line by a microcomputer for continuous display of blood pressure and heart rate measurements. The animals were administered intraperitoneally either 50 mg cocaine or an equal volume of saline. Five minutes later, they were administered either saline or proven antidotes to cocaine (diltiazem, nicardipine, enzyme converting inhibitor [ECI], enalaprilat associated with diazepam). After 2 min, stimulation of the baroreceptor was performed by bilateral clamping of the two carotids for a period of 2 min. The measures of the maximal variation in systolic pressure before and after clamping indicated a significant difference between saline and cocaine treated animals (P < 0.05), with the former displaying a much greater increment in blood pressure after clamping. The cocaine-treated animals, administered diltiazem, nicardipine, and ECI associated with diazepam, presented after clamping of the carotid arteries a normal baroreflex with increments in blood pressure not significantly different from those occurring in the animals receiving saline, but significantly different from those administered cocaine only (P < 0.05). Baroreflex deregulation by cocaine may also be restored by an angiotensin II receptor antagonist. The possible role of this peptide in mediating in part baroreflex activity is discussed.

Inhibition by cocaine of the baroreflex in the rat.

Sprague-Dawley rats were fitted under pentobarbital anesthesia with a catheter in the caudal artery and their carotid arteries were exposed. The pressure signal from the caudal artery was treated on line by a microcomputer for continuous display of blood pressure and heart rate measurements. The animals were administered intraperitoneally either 50 mg/kg of cocaine or an equal volume of saline. Five minutes later, stimulation of the baroreflex was performed by bilateral clamping of the two carotids for a period of 2 min. The same maneuver was repeated at 12, 24, and 31 min. Analysis of variance for repeated measures indicated that before carotid artery clamping, there was no significant difference between blood pressure measurements of the saline- and cocaine-treated groups. A two-factor analysis of variance of the repeated measures of the maximal variation in systolic pressure after each clamping showed a significant difference between control and cocaine-administered groups (P < 0.001), with the former displaying a much greater increment in blood pressure after carotid clamping. Cocaine exerts an inhibitory effect on the baroreflex that may be mediated through the increased angiotension II caused by the alkaloid.

The human toxicity of marijuana.

The pathophysiological effects of marijuana smoke and its constituent cannabinoids were reported first from in-vitro and in-vivo experimental studies. Marijuana smoke is mutagenic in the Ames test and in tissue culture and cannabinoids inhibit biosynthesis of macromolecules. In animals, marijuana or delta 9-tetrahydrocannabinol (THC), the intoxicating material it contains, produces symptoms of neurobehavioural toxicity, disrupts all phases of gonadal or reproductive function, and is fetotoxic. Smoking marijuana can lead to symptoms of airway obstruction as well as squamous metaplasia. Clinical manifestations of pathophysiology due to marijuana smoking are now being reported. These include: long-term impairment of memory in adolescents; prolonged impairment of psychomotor performance; a sixfold increase in the incidence of schizophrenia; cancer of mouth, jaw, tongue and lung in 19-30 year olds; fetotoxicity; and non-lymphoblastic leukemia in children of marijuana-smoking mothers.

[Potentiation of the acute toxic effects of cocaine by ethyl alcohol]. / Potentialisation des effets toxiques aigus de la cocaïne par l'alcool éthylique.

Ethyl alcohol increases significantly the lethality of cocaine intoxication in the rat. This lethality is not modified by nicardipine or flunarizine, antidotes to cocaine, and might be due to the formation of a newly identified active metabolite cocaethylene. In addition alcohol like cocaine inhibits the baro receptor reflex.

Catecholamines, cocaine toxicity, and their antidotes in the rat.

Acute lethal cocaine intoxication in the rat induces significant increases of plasma dopamine, norepinephrine, and epinephrine concentrations associated with cardiac functional and morphologic changes. Nitrendipine (a calcium channel antagonist) administered 5 min following cocaine administration lowers catecholamine concentration and restores cardiovascular function to normal, while preventing lethality, and so does enalaprilat (an enzyme-converting inhibitor) administration with diazepam. Cocaine cardiac toxicity in the rat appears to be associated with a significant stimulation of the sympathoadrenal and a sustained elevated plasma concentration of epinephrine. The renin angiotensin system also appears to be activated.

Antidotes to lethal cocaine toxicity in the rat.

Cocaine, like catecholamines or angiotensin II, may induce lethal cardiac or cerebral damage. Restrained rats were fitted with a caudal arterial catheter for on-line cardiovascular monitoring and antidote administration. They were given 60 mg/kg of cocaine i.p., a dose which produces behavioral and cardiovascular effects, convulsions and death in an average time of 10 min. Selected antidotes were administered 5 min after the lethal dose of cocaine. Incidence of lethality was not changed by propranolol, prazosin, labetalol, diazepam or enalaprilat, a converting enzyme inhibitor. Animals treated with any one of the following agents, alpha- or beta-blockers, diazepam or competitive inhibitors of angiotensin II [Sar-1-ile-8] and [Sar-1-thr-8] angiotensin II, presented myocardial infarction. All animals treated with calcium channel antagonists or enalaprilat, whether they survived or not, did not present myocardial infarction. Treatment with nitrendipine, flunarizine or diltiazem, resulted in survival of the animals with no observable aftereffects. Similar results were observed when enalaprilat was administered, with diazepam as an antidote, to a lethal dose of cocaine. Antagonists to the sympatho-adrenal system and to the renin angiotensin system appear to be effective antidotes to cocaine toxicity in the present experimental model.

Interactions of nimodipine and cocaine on endogenous catecholamines in the squirrel monkey.

The effects of nimodipine on the cocaine-induced alterations in blood pressure, heart rate, and plasma catecholamines were studied in the squirrel monkey. Cocaine in intravenously administered doses of 0.5, 1, and 2 mg/kg produced significant increases in blood pressure and significant decreases in heart rate. These cardiovascular changes were associated with transient episodes of arrhythmias and with significant increases in plasma concentrations of dopamine, epinephrine, and norepinephrine. Nimodipine, 1 micrograms/kg/min for 5 min administered intravenously 5 min after cocaine, corrects the cardiovascular and plasma catecholamine concentration changes induced by this alkaloid. The same dose of nimodipine administered 5 min before cocaine prevents elevations of blood pressure. Plasma catecholamine increments are also prevented except for the highest dose of cocaine. Cardiovascular changes induced by cocaine administration in the squirrel monkey are temporally associated with significant increments in plasma catecholamines. Administration of nimodipine prevents or minimizes these endocrine and physiologic changes.