Effect of warfarin on formation and growth of pre-neoplastic lesions in chemically induced colorectal cancer in the rat

Anticoagulant drugs are known to have an effect on tumour growth. However, the mechanisms by which they act are poorly understood, and have therefore been investigated in this study. Wistar rats were given eight weekly subcutaneous injections of azoxymethane, at a dose of 10 mg kg-1 week-1. Following this they were randomized into two groups: a control group, which received no further treatment, and a warfarin treated group, which received warfarin at 'non-therapeutic' doses in their drinking water, for a further 8 weeks. Pairs of rats from each group were killed at 5-weekly intervals from 10 to 35 weeks after the first azoxymethane injection. At 40 weeks all remaining rats were killed. Samples of colonic mucosa from the descending colon and rectum were taken for scanning electron microscopy. The number of microadenomas per low power field was determined in both groups at each time interval. Tumour incidence and distribution were noted in animals killed at 40 weeks. The median number of microadenomas was significantly lower in warfarin treated animals than in controls at all time intervals. Tumour number was also significantly decreased by warfarin treatment (27 in azoxymethane treated animals, 10 in animals receiving azoxymethane and warfarin, P less than 0.05). The distribution of tumours along the colon was similar to that seen previously, following 12 weeks of azoxymethane. These effects occurred despite the non-concurrent administration of azoxymethane and warfarin.     

Cryptococcal meningoencephalitis. Case report and review of Italian literature

A case of cryptococcal meningoencephalitis, as presented by a hypertensive hydrocephalus, is described. To our knowledge, this is the 24th case described in Italy since 1953. The diagnosis was made with ventricular fluid examination: the patient was successfully treated with amphotericin B and 5-fluorocytosine, thus avoiding the risks of surgical treatment of hydrocephalus. Early diagnosis and proper therapy are necessary in order to decrease the high lethality of cryptococcosis.     

Myectomy versus myotomy as an adjunct to membranectomy in the surgical repair of discrete and tunnel subaortic stenosis

The results of membranectomy and deep myectomy in the left ventricular outflow tract were compared to those of membranectomy and myotomy in 42 patients who underwent surgical repair of discrete and tunnel subaortic stenosis. Fifteen consecutive patients (Group A) underwent membranectomy and myotomy, and 27 consecutive patients (Group B) underwent membranectomy and myectomy. Two patients of Group A and nine of Group B had tunnel subaortic stenosis. The preoperative mean (+/- standard deviation) peak systolic gradients across the left ventricular outflow tract in patients with discrete subaortic stenosis types I and II were 64 +/- 29 mm Hg in Group A and 52 +/- 3 mm Hg in Group B (p = not significant). In the patients with tunnel subaortic stenosis the preoperative mean gradients were 97 +/- 74 mm Hg in Group A and 73 +/- 26 mm Hg in Group B (p = not significant). In patients with discrete subaortic stenosis types I and II, postoperative catheterization at a mean follow-up of 21 months revealed residual mean gradients of 29 +/- 24 mm Hg in Group A and 10 +/- 13 mm Hg in Group B (p less than 0.01). In the patients with tunnel subaortic stenosis, the postoperative mean gradients were 25 +/- 7 and 30 +/- 30 mm Hg in Groups A and B, respectively (p = not significant). We conclude that in the surgical management of discrete subaortic stenosis types I and II, deep myectomy (in addition to membranectomy) produces better relief of the left ventricular outflow obstruction than do membranectomy and myotomy. In patients with tunnel subaortic stenosis myectomy is less effective than in the non-tunnel type but still produces acceptable results and may delay radical procedures to a later age.     

Focal vulnerability of developing brain: CT studies on disproportionally dilated lateral ventricles

Summary Cranial computed tomography (CT) of 108 cases with dilated lateral ventricles was reviewed to elucidate the relationship between focal vulnerability of developing brain and disproportional dilatation of lateral ventricles. CT findings of 108 cases with symmetrical dilatation of lateral ventricles were classified into three types by morphometry of lateral ventricles: anterior horn predominant type (31 cases), diffuse type (36 cases), posterior horn predominant type (41 cases). Posterior horn predominant type has a tendency to occur in congenital anomalies and premature brain damage, and anterior horn predominant type in infantile brain damage. This disproportional dilatation of anterior or posterior horns suggests a vulnerability of periventricular structure in developing brain.     

Interactions in the solid state. II: Interaction of sodium bicarbonate with substituted benzoic acids in the presence of moisture

The interaction of an organic acid with sodium bicarbonate in water produces an effervescent reaction. The reaction products are carbon dioxide, water, and the sodium salt of the acid. The kinetic rate-determining step for this reaction is the dehydration of carbonic acid. The solid-solid interaction with known amounts of moisture was followed by quantitatively determining carbon dioxide evolution as a function of time. The aqueous solubilities, diffusion coefficients, dissociation constants, and solid-solid interaction rates of six different substituted benzoic acids were determined. Using a model based on diffusion of the organic acid through the aqueous layer coupled with chemical reaction, predicted rates and levels of carbon dioxide production were compared with experimental results. Included in the model were the effects of the reaction products on the solution properties of the reactants. It was found that high concentrations of substituted sodium benzoate were generated very quickly and affected the solubility of the reactants, diffusion coefficient of the acid, and the carbonic acid dehydration rate constant. Moisture content was found to have a profound influence on the interaction rate. Water provides a medium for diffusion of the reacting species as well as the reaction solvent.     

In vitro metabolism and toxicity assessment of toxin T-514 (Peroxisomicine A1) of Karwinskia humboldtiana in microsomes and primary cultured hepatocytes.

T-514 (Peroxisomicine A(1)) from Karwinskia humboldtiana is a dimeric hydroxyanthracenone with a highly selective cytotoxic effect on tumor cells. We evaluated the metabolism of this compound in two in vitro systems (liver microsomes and hepatocytes) and assessed the cytotoxicity of its metabolites on normal and tumor cells. Microsomes (12.5, 125 and 250 microg of protein/ml) and hepatocytes (1 x 10(6) cells/ml) were incubated with the toxin (25 microM) for 0.5, 1, 3, 6, 9, 12 and 24 h and the samples were examined using chromatographic analysis and UV spectra. Two metabolites (M1 and M2) were detected in the rat microsomes and one (M1) in the monkey microsomes. The retention times and UV spectra of the peaks were very similar to those of the toxin T-514. M1 was isolated and identified as a mixture of two isomers. The cytotoxicity of the metabolites was evaluated in Chang liver and Hep G2 cells but they did not show the selective cytotoxic effect on tumor cells seen in the original compound.