3,5-Diphenyl-1H-pyrazole derivatives. II--N-substituted 1-(2-aminoethyl)-3,5-diphenyl-1H-pyrazoles and their 4-bromo derivatives with analgesic and other activities

The synthesis of N-substituted 1-(2-aminoethyl)-3,5-diphenyl-1H-pyrazoles and their 4-bromo derivatives (V) by reaction of primary and secondary amines with the tosylates of 1-(2-hydroxyethyl)-3,5-diphenyl-1H-pyrazole and its 4-bromo derivative is described. Some of compounds (V) showed a remarkable analgesic activity in mice. Moreover, the above compounds usually exhibited moderate hypotensive, bradycardiac and antiinflammatory activities in rats, infiltration anesthesia in mice, as well as a weak platelet antiaggregating activity in vitro.     

Histochemical detection of glycoproteins in the intestinal epithelium of Columba livia

A histochemical investigation was carried out to detect glycoproteins in the epithelium of the small and large intestine, ceca and cloaca (coprodeum) of Columba livia. The results showed that the goblet cells of both crypts and villi of the various segments studied presented neutral and acid glycoproteins. Acid glycoproteins include sulphoglycoproteins and sialoglycoproteins with predominance of the sulphated components, particularly in the large intestine, ceca and coprodeum. In the striated border neutral glycoproteins were the predominant components in an inner wide band and the acid in a superficial pellicle.     

A rare case of hemangiomatous tumor of the posterior urethra

The authors report a rare case of a vascular neoplasm of the posterior urethra in an adult. They emphasize the histological and etiopathogenic features of the disease, and discuss the prognostic and therapeutical aspects of its management.     

Biotransformation of cibenzoline to 2-(2,2-diphenylcyclopropyl)-1H-imidazole

A microsomal metabolite of cibenzoline, 4,5-dihydro-2-(2,2-diphenylcyclopropyl)-1H-imidazole butanedioate, was identified by n.m.r. as the 4,5-dehydro analogue, 2-(2,2-diphenylcyclopropyl)-1H-imidazole. Three dogs dosed orally with 13.8 mg/kg 14C-cibenzoline base excreted 1.8-3.5% of the dose as this metabolite in the urine. Mean plasma concentrations of cibenzoline reached a peak of 1.5 micrograms/ml at 2 h while mean concentrations of the metabolite of 0.4-0.5 micrograms/ml were found between 2 and 7 h. The metabolite was synthesized and found to decrease the frequency of ventricular premature depolarizations in conscious dogs having a two-stage occlusion of the left anterior descending coronary artery performed 48 h before. It did not inhibit ventricular arrhythmia in rats induced by i.v. infusion of aconitine. Thus, in contrast to cibenzoline, the metabolite does not appear to be a true antiarrhythmic agent.     

The effect of distance to provider on employee response to changes in mental health benefits

We assess whether distance to provider moderates the effect of a change in mental health benefits on treatment initiation of employees of a large US-based company for psychiatric disorders. Mental health treatment administrative claims data plus eligibility information provided by a Fortune 50 company for the years 1995-1998 are used for the analysis. The effect of distance is measured using the relative effect of the initiative on residents living far from providers compared to those living close to providers. We model the probability of treatment initiation using a random effects logit specification. We find that the effect of distance to provider has the potential to over-shadow other incentives to initiate treatment, especially at distances greater than 4 miles. These results lend further support to the notion that geographic dispersion of providers should be an important consideration when forming a selective contracting network.     

Antioxidant potential of thymol determined by chemiluminescence inhibition in human neutrophils and cell-free systems

Thyme essential oil and thymol have antimicrobial, antifungal and antioxidant activities. Their antioxidant activity has been studied almost exclusively by means of chemical testing in order to be able to use it for food preservation purposes. The aim of this luminol amplified chemiluminescence (LACL) study was to investigate whether thymol can interfere with the production of reactive oxygen species, nitric oxide and the nitric oxide-derived peroxynitrite released by human neutrophils after activation by fMLP and PMA with and without the addition of the L-arginine (L-Arg) nitric oxide donor to the medium. The lowest thymol concentration that was still active in reducing LACL was 2.73 microg/ml, and there was a progressive linear inhibition of LACL from this concentration to 21.87 microg/ml, the highest thymol concentration investigated. This was also observed in the case of both fMLP and PMA stimulation with or without L-Arg. In cell-free systems using H(2)O(2)/HOCl(-) and SIN-1 as radical producers, a significant scavenging activity of thymol was present already at 0.08 and 0.68 microg/ml respectively, and these are very low concentrations. These findings can be related to the phenolic structure of thymol, because phenolic compounds have redox properties and play an important role in adsorbing and neutralizing free radicals and peroxynitrite, and in decomposing peroxides. Our findings in human neutrophils are pharmacologically relevant as they imply that thymol is a potential antioxidant and anti-inflammatory agent in human cells.     

Transbronchial lung biopsy in the diagnosis of lymphangitic carcinomatosis.

The clinical diagnosis of lymphangitic carcinomatosis of the lung has generally been confirmed by open lung or transthoracic needle biopsy, precedures with significant morbidity and mortality, particularly in patients with respiratory insufficiency. We present six cases of lymphangitic carcinomatosis diagnosed by transbronchial biopsy. Autopsy confirmation was obtained in 4 patients and ultrastructural confirmation of intralymphatic location of tumor in one. The diffuse bronchial and peribronchial lymphatic involvement demonstrated here suggests that this relatively noninvasive technique should be the procedure of choice in the diagnosis of lymphangitic carcinomatosis of the lung.     

Hypertension in early alcohol withdrawal in chronic alcoholics

AIMS: Hypertension is an established risk factor in chronic alcoholics, but little is known about the relationship between blood pressure (BP), severity of their alcohol abuse, and severity of alcohol withdrawal syndrome (AWS). METHOD: BP was assessed daily for 18 days in a series of chronic alcoholics on early alcohol withdrawal (AW), while also assessing the severity of their AWS on the CIWA-Ar scale. RESULTS: A sharp and sustained decrease in BP was observed after AW; at T0, BP had increased in 55% of patients, and at T18 in 21%. The variation of BP is partially explained by years of at-risk drinking and AWS severity, but other factors may play a role in hypertension in alcoholics, as a large amount of BP variation was not explained by the alcohol-abuse-related parameters that we studied. BP values were not correlated with cigarette smoking, anxiety, or depression. Hypertension found in 'detoxified' alcoholics (approximately 20%) may be related to alcohol-independent hypertension or to a long-lasting alcohol-induced derangement of the BP regulating mechanisms. Further research is needed in these patients to elucidate the mechanisms of persistent hypertension and to set up a treatment protocol. At present, careful monitoring is advisable, as well as pharmacological treatment for moderate or severe hypertension; often a modification of life-style is needed which includes physical activity and possibly sodium (Na) restriction, since hypertension in detoxified alcoholics seems to be Na sensitive. CONCLUSION: Complete alcohol abstinence must be recommended to all hypertensive alcoholics, as AW-induced transient hypertension was found to be harmless in all our subjects, and abstinence leads to a complete recovery from hypertension in most cases.     

The surgical treatment of discrete subaortic stenosis (author's transl)

The AA. examine their experience concerning 23 patients operated on for a discrete subaortic stenosis since 1969. Immediate results are satisfactory, even if there have been postoperative complications in 26% of the patients. Late results are less satisfactory, above all because of the progression of aortic insufficiency far from the operation. Date of literature are nor allowing valuable indications about the natural history of the patient after surgical treatment, because of the scarcity of postoperative hemodynamic controls and, especially, of serial examinations. The AA. believe, on the ground of considered data and personal experience, that it is prudent, awaiting for further critical evaluation of late results, to limit surgical indications, in asymptomatic patients, to cases with left ventricular-aortic gradient superior to 70 mmHg.