Vascular alpha-adrenergic blocking properties of quinidine

The specificity of the alpha-adrenergic vascular blockade by quinidine was tested in the intact dog, in rabbit isolated aortic strips, and in rats under ganglionic blockade. Quinidine did not affect the pressor response of angiotensin II in dogs, the contractile response of histamine nor angiotensin II in aortic strips, nor the dose-pressor response curve of the alpha-agonist, B-HT 933 in the rat. However, the pressor effect of adrenaline and noradrenaline (NA) were significantly reduced in dogs, and the dose-response curves to NA in aortic strips and to the alpha-agonist, phenylephrine in rats was shifted to the right in a parallel manner by quinidine. In the rat, quinidine is at least 14 times more potent in antagonizing the vasopressor effect of an alpha 1-vs. and alpha 2-adrenoceptor agonist.     

Pseudoaneurysms complicating organ transplantation: roles of CT, duplex sonography, and angiography

In a retrospective study of proved pseudoaneurysms (PAs) in 15 patients with transplanted organs (11 liver, three kidney, one pancreas), the results of computed tomography (CT), duplex sonography, and angiography were reviewed. Of the 15 cases of PA, eight occurred at the arterial anastomosis and seven were nonanastomotic. Three of the eight anastomotic PAs were caused by infection. Of the seven nonanastomotic PAs, four were caused by percutaneous biopsy, two were caused by infection, and one was of undetermined cause. In nine (60%) of the 15 patients the PAs were incidentally detected at imaging studies performed for other reasons. Diagnosis requires a high degree of suspicion. CT was performed in nine cases and duplex sonography in ten. The diagnosis of PA was made with CT in six (67%) patients and with duplex sonography in five (50%). CT and duplex sonography could not enable diagnosis when the PA was small, when the arterial anastomosis was not included in the field of study, or when enhancement with intravenously administered contract material was suboptimal. Angiography depicted the PAs in all 15 patients. In three liver transplant recipients with gastrointestinal tract bleeding, the causative PAs were detected only with angiography.     

Study of color perception using a new color test and desaturated panel D 15 in normal subjects and diabetics

The authors used two tests (the Lanthony's New Color Test and the desaturated Panel D 15 test) to evaluate color vision in 235 subjects (235 eyes) of which 80 normal and 155 diabetic (85 with background retinopathy and 70 without retinopathy, as demonstrated by fluorescein angiography). The diabetic patients with maculopathy or macular oedema, with mixed or proliferative retinopathy, or with any form of advanced degenerative retinopathy were excluded from this study. The New Color Test was performed in accordance with Lanthony's standardized method, applying only the separation phase (to quantifying the color perception defect, if any) in photopic illuminance conditions at 250 lux. The desaturated Panel D 15 (qualitative classification test) has been performed at illuminance of 500 lux. Both normal and diabetic subjects were divided into two age groups (below and above 45 years) and the discriminatory value of two tests has been assessed in relation to age, diabetes and background retinopathy. The New Color Test showed a highly significant difference between normal subjects and diabetics of comparable age with background retinopathy. There was also a highly significant difference between diabetics with and without retinopathy. On the other hand, the difference between normal subjects and diabetics without retinopathy proved significant in the below-45 age group and no-significant in the above-45 age group. The results obtained in the desaturated Panel D 15 test have been similar: below the 45 years of age all differences among the three subject groups proved significant, whereas in the above-45 age group no significant differences were observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Toxic side effects of drugs used to treat Chagas' disease (American trypanosomiasis)

Chagas' disease (American trypanosomiasis) is an endemic parasitic disease in some areas of Latin America. About 16-18 million persons are infected with the aetiological agent of the disease, Trypanosoma cruzi, and more than 100 million are living at risk of infection. There are different modes of infection: (1) via blood sucking vector insects infected with T. cruzi, accounting for 80-90% of transmission of the disease; (2) via blood transfusion or congenital transmission, accounting for 0.5-8% of transmission; (3) other less common forms of infection, eg, from infected food or drinks or via infected organs used in transplants. The acute phase of the disease can last from weeks to months and typically is asymptomatic or associated with fever and other mild nonspecific manifestations. However, life-threatening myocarditis or meningoencephalitis can occur during the acute phase. The death rate for persons in this phase is about 10%. Approximately 10-50% of the survivors develop chronic Chagas' disease, which is characterized by potentially lethal cardiopathy and megacolon or megaoesophagus. There are two drugs available for the aetiological treatment of Chagas' disease: nifurtimox (Nfx) and benznidazole (Bz). Nfx is a nitrofurane and Bz is a nitroimidazole compound. The use of these drugs to treat the acute phase of the disease is widely accepted. However, their use in the treatment of the chronic phase is controversial. The undesirable side effects of both drugs are a major drawback in their use, frequently forcing the physician to stop treatment. The most frequent adverse effects observed in the use of Nfx are: anorexia, loss of weight, psychic alterations, excitability, sleepiness, digestive manifestations such as nausea or vomiting, and occasionally intestinal colic and diarrhoea. In the case of Bz, skin manifestations are the most notorious (e.g., hypersensitivity, dermatitis with cutaneous eruptions, generalized oedema, fever, lymphoadenopathy, articular and muscular pain), with depression of bone marrow, thrombocytopenic purpura and agranulocytosis being the more severe manifestations. Experimental toxicity studies with Nfx evidenced neurotoxicity, testicular damage, ovarian toxicity, and deleterious effects in adrenal, colon, oesophageal and mammary tissue. In the case of Bz, deleterious effects were observed in adrenals, colon and oesophagus. Bz also inhibits the metabolism of several xenobiotics biotransformed by the cytochrome P450 system and its reactive metabolites react with fetal components in vivo. Both drugs exhibited significant mutagenic effects and were shown to be tumorigenic or carcinogenic in some studies. The toxic side effects of both nitroheterocyclic derivatives require enzymatic reduction of their nitro group. Those processes are fundamentally mediated by cytochrome P450 reductase and cytochrome P450. Other enzymes such as xanthine oxidoreductase or aldehyde oxidase may also be involved.