[Pathophysiology and prevention of contrast-induced acute renal failure]. / Fisiopatologia e prevenzione della insufficienza renale acuta da mezzo di contrasto.

Although the infusion of iodinated contrast media in diagnostic and interventional procedures may cause acute renal failure (ARF) especially in older or diabetic patients with preexisting nephropathy, these procedures are often unavoidable. Contrast medium-induced ARF is defined as an increase in serum creatinine of 0.5 mg/dL or a 25% or greater relative increase from baseline within 72 hours of iodinated contrast medium infusion. Because it is often very difficult to employ alternative diagnostic procedures, it is mandatory to adopt prophylactic protocols to prevent radiocontrast nephropathy. Renal hemodynamic lesions leading to medullary hypoxia, oxygen free radicals inducing tubular cell alterations, and parenchymal vasoconstriction are the main factors in the pathogenesis of contrast-induced ARF. Among the many proposed protocols to prevent contrast-induced renal toxicity, the most effective procedure is hydration with 1 mL/kg/h of isotonic saline solution in the 12 hours before and after contrast medium infusion. Promising results in terms of cardiac and renal protection have been reported in a recent trial with the use of high-dose N-acetylcysteine acting as an oxygen free radical scavenger: an intravenous bolus of 1200 mg N-acetylcysteine was given before coronary angiography followed by 1200 mg orally twice a day for 48 hours after the procedure. The protective effect seemed to involve not only the kidney: the drug was found to induce a significant reduction of the necrotic area in myocardial infarction.

Evaluation of the oxidative stress in growing pigs by microplate assays.

The ability of pigs to neutralize the reactive oxygen species (ROS) plays a key role in their welfare. Two micromethods were developed to evaluate the oxidative stress and the anti-oxidative response in sera. We tested these methods for linearity, repeatability and reproducibility. A hydroxyl radicals (HR) test, based on the Fenton reaction, showed a linearity between 0.26 and 4.5 mM H2O2 (r = 0.997), with a coefficient of repeatability (CVr) of 1.9 and a coefficient of reproducibility (CVR) of 2.9. An anti-oxidant power (AOP) test, based on the capability of sera to neutralize a titred hypochlorous acid solution (HClO), showed a linearity between 55 and 880 microM HClO neutralized (r = 0.984), with CVr = 3.1 and CVR = 4.9. We assessed the applicability of such tests in field conditions on three different farms. Farm A recorded a positive anamnesis of Mulberry heart disease. Dietary Vitamin E supplementation was given at 50 p.p.m. in farms A and B and at 150 p.p.m. in farm C, respectively. The group from farm A showed HR sera levels higher than those of farm B and farm C (farm A, mean = 31.61 +/- 2.87 mM H2O2, n = 10; farm B, 28.53 +/- 2.30, n = 10; and farm C, 25.63 +/- 1.03, n = 10; P < 0.01). The AOP test was not able to discriminate between farms. The AOP levels found (mean = 472.50 microM HClO neutralized: n = 30) probably represent the maximum response of the organism to compensate the oxidative stress. HR and AOP are stable in sera stored at +4 degrees C. We discuss the application of such methods for the assessment of farmed animals' welfare.

[Survival of 184 patients with hepatocellular carcinoma in cirrhotic liver treated with chemoembolization. A multicenter study]. / La sopravvivenza di 184 pazienti con carcinoma epatocellulare nel fegato cirrotico trattati con chemioembolizzazione. Studio multicentrico.

INTRODUCTION: We report the results of a multicenter study of 184 cirrhotic patients with hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization (TACE) and compare our results with those reported in the literature. MATERIAL AND METHODS: We treated 184 cirrhotic FNB-proved HCC patients with TACE in a 2 years' period; 159 were men and 25 women and their mean age was 59 years (range: 46-75 years). TACE was performed with selective or superselective injection of Doxorubicin chlorhydrate (20-50 mg) mixed with Lipiodol Ultrafluid before embolization with Spongostan. This procedure was repeated after 4-6 weeks for at least 3 cycles. Follow-up was performed by means of periodic US, CT and MR scans and by assessment of the clinical status and serum biochemical tests--alpha-fetoprotein, platelet and blood cell counts, protein electrophoresis, bilirubin and other standard liver and renal function tests. TACE results were assessed comparing site, size and local spread of tumor and TACE technique (lobar or segmental, number of performed procedures) with survival in each patient. The lesion was single in 85 (46.2%) and multiple in 99 (53.8%) patients. It exceeded 5 cm in 128 patients (69.5%) and was < 5 cm in 57 (30.5%). RESULTS: Angiography, CT and MRI showed complete necrosis in 148 patients (80.4%) and an unchanged pattern in 36 (19.6%). Overall survival rates were 95.7% at 6 months, 78.3% at 1 year, 46.0% at 2 years, 40.0% at 3 years. The best responses were obtained with lesions < 5 cm--with 100% survival at 6 months, 94.8% at 12 months, 71.4% at 18 months, 54.7% at 24 months and 50.0% at 36 months. Other factors affecting treatment response were singleness of lesion (96.4% at 6 months, 93.9% at 12 months, 71.4% at 18 months, 58.9% at 24 months, and 50.0% at 36 months) and at least 3 cycles of TACE (100% at 6 months, 87.8% at 12 months, 70.1% at 18 months, 48.7% at 24 months and 37.5% at 36 months). Abdominal pain and fever were the most frequent complications, particularly in the first TACE procedure, but both were mild and transient. Lipiodol cholecystitis was found in 3 patients but they were asymptomatic. No patients had evidence of cardiac toxicity or experienced significant leukopenia or thrombocytopenia as a result of systemic toxicity from Doxorubicin. CONCLUSIONS: We can conclude that TACE proves to be an efficacious treatment in the HCC patients who cannot undergo surgery.

Change in major amputation rate in a center dedicated to diabetic foot care during the 1980s: prognostic determinants for major amputation.

From 1990 to 1993, 115 diabetic patients were consecutively hospitalized in our diabetologic unit for foot ulcer and 27 (23.5%) major amputations were carried out. The major amputation rate of this series of cases was compared with that occurring in diabetic subjects taken into our hospital for foot ulcer in two previous periods: 1979-1981 (17 major amputations in 42 inpatients or 40.5%) and 1986-1989 (26 major amputations in 78 inpatients or 33.3%). The comparison shows a progressive reduction in major amputation rate [Odds ratio 0.66, 95% confidence interval (CI) 0.46-0.96]. Univariate and multivariate analysis, carried out in the population of the 1990-1993 period, in order to detect the independent factors associated with major amputation show the following prognostic determinants of major amputation: Wagner grade (odds ratio 7.69, CI 1.58-37.53), prior stroke (odds ratio 35.05, CI 3.14-390.53), prior major amputation (odds ratio 3.49, CI 1.26-9.38), transcutaneous oxygen level (odds ratio 1.06, CI 1.01-1.12), and ankle-brachial blood pressure index (odds ratio 4.35, CI 1.58-12.05), while an independent protective role was attributed to hyperbaric oxygen treatment (odds ratio 0.15, CI 0.03-0.64). In accordance with other studies, we, therefore, conclude that a comprehensive protocol as well as a multidisciplinary approach in a dedicated center can assure a decrease in major amputation rate. The parameters of limb perfusion were the modifiable prognostic determinants most strongly predictive for amputation.

Evaluation of the potential carcinogenic activity of Senna and Cascara glycosides for the rat colon.

Anthraquinone glycosides of Senna and Cascara were investigated for their ability to induce aberrant crypt foci (ACF) in the rat colon mucosa, which are considered putative preneoplastic lesions. Dietary exposure to high doses of these glycosides for 56 successive days did not cause the appearance of ACF or increase in incidence of ACF induced by 1,2-dimethyl-hydrazine (DMH). However, in rats treated with both DMH and the highest dose of glycosides, the average number of aberrant crypts per focus, considered a consistent predictor of tumor outcome, was higher than in rats given DMH alone. These findings suggest that Senna and Cascara glycoside might behave as weak promoters in rat colon carcinogenesis.

Transarterial oily chemoembolization for the treatment of hepatocellular carcinoma: a multivariate analysis of prognostic factors.

A total of 84 patients with hepatocellular carcinoma and cirrhosis were analyzed retrospectively to investigate prognostic factors. All patients received transarterial oily chemoembolization as the only anticancer therapy. The follow-up range was 1 to 39 mo (median, 9.5 mo). The overall actuarial survival rates at 12, 24 and 30 mo were 62%, 31% and 24%, respectively. According to univariate analysis, variables significantly associated with survival were age, Child-Pugh grade, total serum bilirubin, Okuda stage, tumor size, degree of labeling of the tumor with Lipiodol, gelatin foam use, changes with treatment in tumor size and changes with treatment in alpha-fetoprotein concentration. Two multivariate analyses were performed. When pretreatment and treatment variables were considered, parameters with independent prognostic value were age, Child-Pugh grade, total serum bilirubin, tumor size and degree of Lipiodol labeling of the tumor. When follow-up variables were also considered, we (a) confirmed the prognostic significance of all these parameters (age, Child-Pugh grade, total serum bilirubin, tumor size) and (b) found the independent prognostic value of the change in tumor size (or change in alpha-fetoprotein concentration). Both models yielded different risk coefficients for each class of each variable. Two simple prognostic indexes, based on these coefficients, are proposed: an "initial" index (including pretreatment and treatment variables) and a "follow-up" index (also including follow-up variables). According to the two indexes, the patients were classified into three groups with different prognoses: good (93% and 100% actuarial survival at 1 yr for the initial and follow-up indexes, respectively), intermediate (65% and 53%, respectively) and poor (27% for both indexes).

Human hepatocyte primary cultures in toxicity assessment.

Forty-two compounds of various chemical families were tested for their cytotoxicity and for their ability to induce DNA fragmentation and DNA repair synthesis in primary cultures of hepatocytes obtained from 74 human donors, and a comparison was carried out with data provided in the same experimental conditions by rat hepatocytes. The results indicate that for the majority of chemicals the intraspecies variability was greater than the average interspecies difference. Some chemicals, however, produced quite different effects in the hepatocytes of the two species, and this suggests that rat hepatocytes might be sometimes inappropriate predictor of the human response.

[Informatics in cardiology: proposal for standardized terminology in clinical records and in permanent cardiac electrostimulation]. / Informatica en cardiología: propuesta para una terminología estandarizada para el expediente clínico y la electroestimulación cardíaca permanente.

To make operative two medical computerized programs, one dedicated to the cardiological clinical record (PAC) and the other to permanent cardiac stimulation (PGP), we codified about 4000 terms concerning the general medical field and particularly the cardiological area. The importance of standardization of the medico-cardiological language is emphasized, specially in relation to the systematization of the information, necessary to work with computerized systems.

Formation of DNA-damaging nitroso compounds by interaction of drugs with nitrite. A preliminary screening for detecting potentially hazardous drugs.

Fifty-seven theoretically nitrosatable widely used drugs that are commonly administered orally have been screened to determine the formation of nitroso compounds by drug-nitrite interaction and to evaluate the genotoxicity of their nitrosation products against Chinese hamster ovary (CHO) cells, measured as DNA-damaging potency by the alkaline elution technique. The drug (0.1 mmol) was reacted with NaNO2 (0.4 mmol) at pH 3-3.5 for 1 h. Nitroso compounds were present in varying yield in the nitrosation mixture of 47 drugs. Twenty-two drugs formed direct-acting nitroso compounds capable of producing DNA fragmentation, i.e., a statistically significant (p less than 0.01) increase in the elution rate of CHO cell DNA. On a molar basis, their DNA-damaging potency varied over a 570-fold range, with 12 exhibiting greater potency than that of N-nitroso-N-methylurea.

[Threatening arrhythmia by uncommon digitalic toxicosis (author's transl)]. / Aritmia minacciosa da non comune intossicazione alimentare.

The authors describe the case of a 38 year old woman who ate some buds of "Helleborus viridis" collected in the mountains mistaken for wild asparagus. The clinical patterns were like in the digitalic toxicosis: the woman presented both ventricular and supraventricular threatening arrhythmias, gastro-enteric troubles, systemic hypotension. The patient improved with the glucose, potassium chloride and magnesium sulphate infusion and intravenous xylocaine. The authors conclude that in case of patient with threatening arrhythmias of unknown genesis it is useful to pay attention to the wild vegetables ingestion.

DNA repair synthesis in primary cultures of kidneys from BALB/c and C3H mice treated with dimethylnitrosamine.

A combined 'in vivo--in vitro' autoradiographic method was employed to examine the DNA repair induced in the kidney by a single dose of dimethylnitrosamine (DMNA). Unscheduled DNA synthesis was found to be dose-dependent in primary kidney cultures of DMNA-treated mice, and practically not detectable in controls. Its amount was positively correlated with the different susceptibility of C3H and BALB/c mice to kidney tumor induction by DMNA. This experimental model appears sensitive and able to provide repeatable results. It may be useful to detect the organotropic activity of a carcinogen toward the kidney.

A practical procedure for testing DNA damage in vivo, proposed for a pre-screening of chemical carcinogens.

The alkaline elution method was adapted to the evaluation of DNA damage induced in vivo through a practical and reliable microfluorometric procedure, without any need for tissue pre-labeling. The DNA damage induced in vivo by treatment with a single dose of N-nitrosodimethylamine (DMNA), N-methyl-N-nitroso-urea (MNU), 1,2-dimethylhydrazine (DMH) or cycasin has been detected in different organs of mice or rats. The results obtained are rather consistent with the organotropism of these carcinogens, and show a satisfactory dose dependent of DNA damage. DMH and cycasin, both negative in the Ames' Salmonella/microsome mutagenicity test, are clearly positive with in vivo DNA damage/alkaline elution assay. This latter method, complemented with other short-term tests, may play a useful role in the pre-screening of chemical carcinogens.