Transcranial high-intensity Doppler signals in patients with mechanical heart valve prostheses: their relationship with abnormal intracavitary echoes.

BACKGROUND AND AIMS OF THE STUDY: In preceding studies, we reported that abnormal Doppler signals of high intensity (HITS) were frequently found in the cerebral arteries of patients with prosthetic mechanical heart valves. These signals should be attributed either to air microbubbles, possibly due to cavitations or to solid emboli elements. On the other hand, the presence of abnormal intracardiac echoes has been reported in patients with mechanical valves. These echoes should be also attributed to air microbubbles or to formed elements. Although in vitro experiments are in favor of the first explanation, the discussion of their origin remains open. METHODS: Among patients subjected to a transesophageal echocardiography (TEE), we selected subjects with mechanical prosthetic heart valves, according to the following criteria: (i) normally functioning valves; (ii) bright echoes suggesting microbubbles, inside the prosthetic valve and/or upstream from it (left ventricular outflow tract or left atrium); (iii) no morphological lesions that could generate solid microemboli at the prosthetic level; (iv) normal carotid arteries, as investigated by color echo-Doppler. RESULTS: Twenty patients were selected: 11 men and nine women of age range 40-64 years. They were implanted with mechanical heart valves (24 Saint-Jude Medical, three Björk-Shiley and one CarboMedics) in the mitral position (10), aortic position (two), or mitral and aortic position (eight) for periods ranging from 10 days to 17 years. There was no major left ventricular dysfunction (mean end-diastolic diameter 51.8 mm; mean ejection fraction 59%). The mean diameter of the left atrium was 46.1 mm. All but three patients were in sinus rhythm; seven had presented with a transient ischemic attack or amaurosis within the six months preceding the investigation. Immediately after TEE, Doppler signals were recorded on the middle cerebral arteries (MCA) during 10 minutes on each side, and the abnormal Doppler signals were counted. Seventeen subjects (85%) exhibited HITS repetition rate from 0.2 to 5.5 per min. CONCLUSION: The percentage of patients with HITS in a non-selected group with mechanical heart valves was about 50%, as observed in previous studies. It appears that in a selected group of patients the percentage with HITS is consistently higher. Therefore, HITS and abnormal intracardiac echoes could have a common origin.

Determination of sodium diethyldithiocarbamate (Imuthiol) and its S-methyl metabolite by gas chromatography-mass spectrometry. Use of deuteromethyl iodide derivatization.

A gas-chromatographic-mass spectrometric method is described to measure the plasma concentration of sodium diethyldithiocarbamate (ditiocarb sodium, DEDTC-Na), the active ingredient of Imuthiol, a drug found to be active in the opportunistic infections occurring in AIDS, and its S-methyl metabolite. Plasma samples are treated with deuteromethyl iodide and DEDTC-Na is transformed into its deuteromethyl ester, which is then co-extracted with the S-methyl metabolite. Gas chromatography-mass spectrometry and selected-ion monitoring allow the specific determination of both compounds. Linear calibration curves were obtained up to 4000 ng/ml. This method has been successfully applied for pharmacokinetic studies after Imuthiol and disulfiram, the dimer of DEDTC, were administered to humans.

Intravenous immunoglobulins: can the blood pressure response in laboratory animals be considered a predictive criterion for good clinical tolerance?

Having noted that the only physico-chemical and biological test recommended cannot ensure good tolerance of i.v. IgG in man, we studied a physiological test consisting of evaluating blood pressure during infusion in conscious dogs (10 mg/kg/min) or after i.v. injection in rats (250 mg/kg in 12 sec.). The data were obtained on more than 100 dogs and 500 rats. For preparations known to be well tolerated in man or inducing a few clinical intolerances, the correlation with hypotension in rats and dogs seems good. Therefore, we think this test has its place in the battery of i.v. IgG qualification tests carried out before passage to man. Institut Mérieux has developed a new intact i.v. IgG equilibrated in sub-classes, without PKA, low in IgA and not hypotensive in these two species.

Sub-acute toxicity of xylitol in rats; absence of hepatotoxicity.

Some workers have suggested that 6 days xylitol administration to rats results in hepatic dysfunction. In our study xylitol was administered to rats by daily gastric intubation for a period of 14 days. Dose levels were 1.25, 2.5, 5 and 10 g/kg. During treatment (2, 5 and 14 days), animals were submitted to careful clinical examinations and to blood serum analysis related to hepatic functions. They were sacrificed after 2, 5, and 14 days treatment. In the 2 and 5 days treatment groups, main organs were submitted to histological study. This examination was only performed on liver in the 14 days treatment group. No evidence of hepatotoxicity was recorded. Serum levels of all parameters measured were within normal limits (including bilirubin and serum alkaline phosphatase (SAP). No anomalies were shown histologically.

[Toxicologic evaluation of irradiated corn starch by long term experimentation with rats]. / Evaluation toxicologique de l'amidon de maïs irradié par expérimentation à long terme chez le rat

Maize starch pasteurized by irradiation was fed to OFA rats (Sprague Dawley derived) in an uncooked form (irradiated at 300 krad.) and in a cooked form (irradiated at 300 and 600 krad.) at dietary level of 62%. A six month toxicity trial was performed with uncooked starch and a 24 month trial with cooked starch. At the same time a reproduction study was conducted, over 3 generations with 2 litters per generation, using both uncooked and cooked irradiated starch. The parent generation (Fo) was randomly selected from animals in the feeding study and after the production of the F1a and F1b generations they were returned to that study. Control groups corresponding to each form of starch were established. They were fed the same diet except that the starch was not irradiated. The results of the various investigations conducted during the study (behavior, growth, mortality, haematology, serum biochemistry, histopathology) did not reveal any toxicological effect due to treatment, nor any effect on reproduction. No significant differences were shown between treated and control group.