Receptor binding of N-(methyl-11C) clozapine in the brain of rhesus monkey studied by positron emission tomography (PET)

By means of positron emission tomography the uptake and kinetics of N-(methyl-¹¹C)clozapine in different brain regions have been studied in Rhesus monkeys. ¹¹C-clozapine rapidly entered the brain and maximum radioactive uptake was seen 5–12 min after administration. Highest uptake was measured in the striatum. Other regions with an uptake higher than in the cerebellum were thalamus and mesencephalon. The radioactivity from different brain regions decreased with an elimination half-life of about 5 h and parallelled the plasma kinetics of unlabelled clozapine. The striatum/cerebellum ratio of ¹¹C-clozapine-derived radioactivity remained constant during the period studied and did not change after pretreatment with atropine. In contrast, the striatum/cerebellum ratio was somewhat lower after pretreatment with N-methylspiperone (NMSP), indicating competition for the same binding sites in the striatum. After pretreatment with increasing doses of clozapine, a dose-dependent protection of binding sites in the striatum for ¹¹C-NMSP was seen. It is concluded that clozapine is more loosely bound to dopamine receptors in the striatum than N-methylspiperone and that the kinetics of clozapine in the brain parallel that in the plasma. The binding properties of clozapine within the brain may explain some of the clinical properties of the drug.     

The relationship of low-back pain, work history, work environment, and stress. A retrospective cross-sectional study of 38- to 64-year-old women

The association between low-back pain (LBP) and different work factors was investigated in a retrospective cross-sectional study of a random sample of 1,760 38- to 64-year-old women. The life-time incidence of LBP was 66% and the prevalence was 35%. In a univariate analysis, eight work variables correlated to LBP viz. more forward bending, more lifting, more standing, more monotonous work, dissatisfaction with the work tasks, dissatisfaction with the work environment, a higher degree of worry, and fatigue at the end of the work day. In a covariate analysis, however, only the three psychological variables remained directly associated to LBP viz. dissatisfaction with the work environment, a higher degree of worry, and fatigue at the end of the work day.     

Fibrosarcoma of the breast: mammographic findings in five cases.

The mammographic features of fibrosarcoma of the breast, a rare malignant tumor, have not been described. Accordingly, we reviewed the mammograms, pathology reports, and medical records of five women with this tumor. All cases had surgical biopsies and a diagnosis made by histologic evaluation. The age of the patients ranged from 48 to 79 years. Histologically, three of the five fibrosarcomas were thought to have arisen from phyllodes tumor, and four were palpable. On mammograms, the tumors were dense masses with largely indistinct margins, ranging from 1.5 to 7.0 cm in diameter. One contained calcified osseous elements suggesting osseous trabeculae. Although the osseous trabeculae in that tumor strongly suggested sarcoma, most of the tumors had a nonspecific appearance on mammograms. Fibrosarcomas of the breast have a nonspecific mammographic appearance. Surgical biopsy and histologic evaluation are necessary for definitive diagnosis.     

Resting and volume-stimulated circulating atrial natriuretic peptide in young normotensive men with positive family histories of hypertension.

Normotensive young men (36 +/- 5 years old) with positive family histories of hypertension (n = 11) and age-matched controls (n = 21) with negative family histories of hypertension were examined. The control group was divided into one group matched for body mass index with those subjects with positive family histories (n = 10) and one group with normal body mass index (n = 11). Blood pressure, central venous pressure (CVP), plasma atrial natriuretic peptide (ANP) and serum aldosterone were examined at a baseline and during an acute volume load with 1000 ml saline solution. Subjects with positive family histories and controls matched for body mass index had a higher blood pressure at baseline than controls with normal body mass index. CVP and serum aldosterone did not differ between the three groups, while sodium intake and plasma concentrations of ANP were significantly higher in subjects with positive family histories. During volume loading, CVP increased significantly more in subjects with positive family histories as compared with the two control groups. A blunted response to ANP was observed during volume loading in subjects with positive family histories, while subjects in the two control groups demonstrated comparable and significant increases in circulating ANP. Serum aldosterone, however, decreased during volume loading in all three groups, with no difference between the groups. We conclude that normotensive subjects with positive family histories are characterized by increased basal concentrations of ANP and exhibit a blunted response to an acute volume load.(ABSTRACT TRUNCATED AT 250 WORDS)     

Composition and surface properties of the bronchial lipids in adult patients with cystic fibrosis

Bronchial secretions from seven patients with cystic fibrosis (CF) were aspirated by fibreoptic bronchoscopy and analysed for lipid composition. The total lipid fraction was also used to measure dynamic surface tension. Pooled samples from 'normal' patients, healthy volunteers, patients with chronic bronchitis, and individual samples from two patients with bronchiectasis were used as controls. Increased bronchial inflammation and infection correlated with a decrease of the phospholipid fraction, and an increase of the cholesterol, diglyceride and triglyceride fractions. When individual phospholipids were analysed, patients with clinically severe CF showed a markedly decreased phosphatidylcholine fraction, whereas the phosphatidylinositol fraction was significantly higher in CF patients than in controls (p less than 0.05). Minimum surface tension was higher in CF patients compared to patients with chronic bronchitis (p less than 0.05). This might be related to earlier reported specific changes in the pattern of fatty acids of the CF bronchial phospholipids.     

Increased carbon monoxide levels in the nasal airways of subjects with a history of seasonal allergic rhinitis and in patients with upper respiratory tract infection

BACKGROUND: Carbon monoxide (CO) has emerged as an endogenously produced gaseous mediator known to be involved in bronchial smooth muscle regulation. Increased amounts of CO have been found in exhaled air during asthma and lower airway inflammation. Recently CO has been shown to be produced in the nasal airways, but there are no reports of altered CO levels in nasal airways during inflammation. OBJECTIVE: This study was designed to investigate if CO levels increase in the human nasal airways during inflammatory conditions, such as allergy and upper airway respiratory tract infection (URTI). METHODS: CO was sampled separately from the upper and lower airways of 13 healthy control subjects, six patients with a history of allergic rhinitis and six patients with URTI. RESULTS: Nasal CO levels were increased in subjects with allergic rhinitis, compared to healthy controls (2.07 +/- 0.15 ppm, n = 6 and 1.62 +/- 0.08 ppm, n = 13, respectively, P < 0.01). CO levels were also increased in patients with URTI, compared to the same controls (1.92 +/- 0.09 ppm, n = 6, P < 0.05). Normal levels of CO were found in air from the lower airways among subjects with allergic rhinitis, whereas corresponding levels in the URTI patients were increased. CONCLUSION: The present data demonstrates that upper airway CO levels increase in parallel with different inflammatory stimuli, such as allergy and infection, suggesting a role for CO as marker or mediator of nasal inflammation.     

Prevention for those who have freedom of choice – or among the choice-disabled: confronting equity in the AIDS epidemic

With the exception of post-exposure prophylaxis for reported rape, no preventive strategy addresses the choice disabled – those who might like to benefit from AIDS prevention but who are unable to do so because they do not have the power to make and to act on prevention decisions. In southern African countries, where one in every three has been forced to have sex by the age of 18 years, a very large proportion of the population is choice disabled. This group is at higher risk of HIV infection and unable to respond to AIDS prevention programmes; they represent a reservoir of infection. Reduction of sexual violence would probably decrease HIV transmission directly, but also indirectly as more people can respond to existing AIDS prevention programmes.     

Development of specific antibody patterns and clinical symptoms following Ockelbo virus infection

Summary Sixteen patients with symptoms typical for Ockelbo disease (rash, arthralgia, fever) were enrolled in a 2 1/2 year study, during which clinical symptoms were recorded and ELISA was employed to study specific IgM, IgG and IgG subclass development. Initially, all patients presented with rash and arthralgia, and five patients still suffered from joint symptoms at the end of the study period. Ockelbo virus specific IgM was detected during the first week post onset in 6 patients and in 15 patients by day 14. One patient failed to develop specific IgM and was later diagnosed with a human parvovirus B 19 infection. All patients were IgM-negative 2 1/2 years post onset. Seroconversions or significant titer rises for specific total IgG were seen in 15 patients. IgG titers generally peaked within one year but in two patients maximum titers were seen 2 1/2 years post onset. Development of IgG1 followed that of total IgG, while IgG3, after an initial increase in all Ockelbo disease patients, remained at peak levels for one year in four patients, three of whom still had detectable IgG3 at the end of the study period. Ockelbo virus specific IgG2 or IgG4 was not detected in any of the patients.     

Disposition and pharmacokinetics of [14C]finasteride after oral administration in humans.

The disposition of [14C]finasteride, a competitive inhibitor of steroid 5 alpha-reductase, was investigated after oral administration of 38.1 mg (18.4 microCi) of drug in six healthy volunteers. Plasma, urine, and feces were collected for 7 days and assayed for total radioactivity. Concentrations of finasteride and its neutral metabolite, omega-hydroxyfinasteride (monohydroxylated on the t-butyl side chain), in plasma and urine were determined by HPLC assay. Mean excretion of radioactivity equivalents in urine and feces equaled 39.1 +/- 4.7% and 56.8 +/- 5.0% of the dose, respectively. The mean peak plasma concentrations reached for total radioactivity (ng equivalents), finasteride, and omega-hydroxyfinasteride were 596.5 +/- 88.3, 313.8 +/- 99.4, and 73.7 +/- 11.8 ng/ml, respectively, at approximately 2 hr; the mean terminal half-life for drug and metabolite was 5.9 +/- 1.3 and 8.4 +/- 1.7 hr, respectively. Of the 24-hr plasma radioactivity, 40.9% was finasteride, 11.8% was the neutral metabolite, and 26.7% was characterized as an acidic fraction of radioactivity. Binding of [14C]finasteride to plasma protein was extensive (91.3 to 89.8%), with a trend suggesting concentration dependency (range 0.02 to 2 micrograms/ml). Little of the dose was excreted in urine as parent (0.04%) or omega-hydroxyfinasteride (0.4%). Urinary excretion of radioactivity was largely in the form of acidic metabolite(s)--18.4 +/- 1.7% of the dose was eliminated as the omega-monocarboxylic acid metabolite. Finasteride was scarcely excreted unchanged in feces. In humans, finasteride is extensively metabolized through oxidative pathways.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reproducibility of angiotensin converting enzyme inhibitor induced cough: A double-blind randomised study

1 The reproducibility of angiotensin converting enzyme inhibitor induced cough was examined in a double-blind cross over study in patients previously shown to have exhibited this side effect.

2 Ninety-seven patients who had experienced angiotensin converting enzyme inhibitor cough within the last 2 years were challenged with enalapril 20 mg daily for 4 weeks to establish eligibility. Eighty-eight of 97 (91%) patients experienced a repeat of their cough symptoms. Sixty-four patients entered the double-blind part of the study where they were treated with enalapril 20 mg and a renin inhibitor for up to 4 weeks in random order. These periods were separated by a minimum 4 week placebo wash out.

3 Of 59 evaluable patients who received enalapril a second time, 37 (62.7%) experienced cough again. Of 62 patients on the renin inhibitor 16 (25.8%) experienced cough, however as it was not equi-efficacious to enalapril no valid comparison could be made.

4 Angiotensin converting enzyme inhibitor cough is not reproducible within patients, as other factors are involved in the aetiology. Objective testing with blinded assessment together with symptom reporting, would give a more accurate measure of the incidence, and mechanism of this side effect.