Antiserum against chlorpromazine (CPZ) was produced in rabbits immunized with CPZ hapten conjugated to bovine serum albumin. The antiserum was used to develop a radioimmunoassay for CPZ. As little as 10 pg of CPZ can be detected with this radioimmunoassay. Major metabolites, CPZ sulfoxide, Nor1 -CPZ and Nor2 -CPZ are not bound significantly by the antibody unless the concentrations are very high. Although the antibody can bind 7-HO-CPZ, 8-HO-CPZ and promazine, the concentrations required to produce a 50% inhibition of 3H-CPZ-antibody binding are 5-10 times greater than CPZ. The plasma levels of CPZ and some minor metabolites in rats following administration of 10 mg/kg i.v. were determined by radioimmunoassay and showed a biphasic decay curve. Brain levels revealed that following i.v. administration CPZ traverses the blood-brain barrier rapidly and achieves peak concentration within 5 min. Plasma and brain levels can be detected for at least 24 hr.

Animals↗

PubMedDate not supplied

Role of central cholinergic neurons in experimental hypertension.

Intravenous injection of the cholinesterase inhibitor physostigimine evoked a hypertensive response in the unanesthetized 12- to 14-week-old spontaneously hypertensive rat (SHR). These responses were greatly enhanced in magnitude when compared to similar injections in normotensive Wistar-Kyoto (WKY) control rats. Stimulation of autonomic ganglia with dimethylphenylpiperazinium (DMPP) also evoked a pressor response in SHR; however, the magnitude of these responses was not different from those obtained in WKY. In unanesthetized, freely moving SHR, the intracerebroventricular (icv) injection of hemicholinium-3 (HC-3) to block the synthesis of brain acetylcholine (ACh) produced a marked hypotensive response. No reduction in arterial pressure was observed following similar injections of HC-3 in WKY. The decline in arterial pressure following icv HC-3 was correlated with the initial decline in brain ACh levels, particularly in the hypothalamus. These results indicate that enhanced sympathetic nerve activity and the resultant hypertensive state present in young SHR is dependent on increased central cholinergic activity.

Acetylcholine↗

PubMedDate not supplied

Multidimensional analysis of the subjective symptomatology of asthma.

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Adult↗

PubMedDate not supplied

Obervations on subjective symptomatology, coping behavior, and medical decisions is asthma.

The Asthma Symptom Checklist (ASC), describing the subjective symptoms reported to occur during asthmatic attacks, has been developed previously. In the present study, the ASC key cluster solution was replicated and refined within a sample of 374 asthmatic inpatients. All of the original symptom categories were reporduced, including two mood categories, Panic-Fear and Irritability, a Fatigue category, and two somatic categories. Hyperventilation-Hypocapnia and Airway Obstruction. Two refinements were notable: (1) The Airway Obstruction category was empirically divided into two conceptually clear components, Dyspnea anc Congestion, and (2) three secondary mood categories, Worry, Loneliness, and Anger, were identified, which describe a continuum of mood between the polar extremes of panic and irritability. Of the symptom categories, only Panic-Fear was related to the intensity of the discharge drug regimens recommended 2 to 6 mouths after ASC administration. Panic-Fear scores were independent of pulmonary function measurements. A combined index based on pulmonary functions and panic-fear yielded the best prediction of discharge steroid regiments. Finally, those physicians rated highest in "sensitivity" to their patients by their supervisors prescribed less steroids overall, but most frequently prescribed discharge steriod regimens in relation to their patients' Panic-Fear scores. In contrast, physicians rated lower on sensitivity prescribed higher steroid regimens overall, but based these drug recommendations more cleary on objective pulmonary functioning, and not in relation to their patients' Panic-Fear scores. The results strongly suggest that the ASC Panic-Fear scale is associated with coping behaviors that importantly affect the patient's overall clinical picture by increasing the apparent severity of the asthma, thereby leading to intensified treatment. The findings stress the need to evaluate independently the objective medical condition and subjective symptomatology with its related coping behavior, in order to direct appropriate modes of therapy to each.

Adaptation, Psychological↗

PubMedDate not supplied

Catechol-O-methyltransferase activity in erythrocytes of children with autism.

1. The activity of the enzyme catechol-O-methyltransferase (COMT) was determined in the erythrocytes of normal and autistic children. 2. There was no difference in enzyme activity between the two groups, although in both the normal and autistic females the erythrocyte COMT activity showed considerable within-group variation. 3. When the erythrocyte homogenates were divided into particulate and soluble fractions, some differences were observed. The COMT activity in the soluble fraction was less in erythrocytes from autistic males than in those from control males, whereas that in autistic females was higher than in those from control females.

Autistic Disorder↗

PubMedDate not supplied

Synthesis of collagen in cardiac and vascular walls.

Collagen synthesis and content have been shown to be elevated in the arterial wall and heart of hypertensive animals. These increases in collagen synthesis and content have been implicated in the maintenance of raised blood pressure. Inhibitors of collagen synthesis, beta APN and 3,4-dihydroproline, were shown to delay the onset of hypertension and reverse established hypertension. Therapeutic intervention with antihypertensive drugs resulted in a decrease in arterial collagen synthesis and a reversal of cardiac hypertrophy. In some instances (i.e., DOCA-salt), chronic administration of antihypertensive drugs caused a restructuring of the arterial wall and resulted in an apparent remission of the hypertensive disease.

Antihypertensive Agents↗

PubMedDate not supplied

Ipratropium bromide nasal spray 0.03% provides additional relief from rhinorrhea when combined with terfenadine in perennial rhinitis patients; a randomized, double-blind, active-controlled trial.

Medical treatment of perennial rhinitis is aimed at providing symptomatic relief of individual symptoms. Multiple agents are administered when no single agent provides complete relief. Studies assessing the benefit/risk of combined therapy are important, especially for newly available agents such as ipratropium bromide nasal spray, a topical anticholinergic agent approved for the treatment of rhinorrhea in allergic and nonallergic perennial rhinitis. The objective was to determine whether the combined use of ipratropium bromide nasal spray 0.03% (42 mcg per nostril) administered three times daily with a nonsedating antihistamine (terfenadine, 60 mg administered twice daily) is safe and provides greater clinical benefit than use of the placebo nasal spray plus terfenadine. Our method was a multicenter, 6-week, double-blind, randomized, active-controlled, crossover trial of 205 patients with perennial rhinitis (114 allergic and 91 nonallergic), 18 to 75 years of age, who had clinically significant rhinorrhea. After a 1-week run-in period, patients were treated for 2 weeks with one of the two treatment regimens, followed by a 1-week washout period, and then were treated for another 2 weeks with the other treatment regimen. Daily diary symptoms scores of rhinorrhea, congestion, and sneezing were obtained, as well as biweekly patient and physician global assessments of treatment effectiveness of each of the nasal symptoms. Ipratropium bromide nasal spray plus terfenadine was more effective than vehicle plus terfenadine in reducing the average severity (38% versus 28%) and duration (46% versus 30%) of rhinorrhea during the 2 weeks of treatment from baseline (p < 0.05). The advantage of ipratropium bromide nasal spray plus terfenadine was evident by the second day of treatment and continued throughout the 2-week treatment period. Of patients who responded more to one treatment than another, 69% responded to ipratropium bromide nasal spray plus terfenadine, compared to 31% to vehicle plus terfenadine (p < 0.05). Both physicians and patients rated control of rhinorrhea and sneezing by ipratropium bromide nasal spray plus terfenadine as superior to vehicle plus terfenadine (p < 0.05). The symptom of congestion was controlled equally well by both treatments. Combined active therapy was well tolerated with no increase in adverse events over that seen previously with ipratropium bromide nasal spray alone. The combination of ipratropium bromide nasal spray with terfenadine is more effective than vehicle plus terfenadine for the treatment of rhinorrhea, and does not result in a potentiation of adverse drug reactions.

Administration, Intranasal↗

PubMedDate not supplied

Skilled nursing. Can't we go smoke-free?

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Data Collection↗