Effect of Armagnac fractions on human platelet aggregation in vitro and on rat arteriovenous shunt thrombosis in vivo probably not related only to polyphenols

Previous studies showed that alcohol-free extracts of Armagnac, an oak cask aged spirit rich in polyphenols, inhibit human platelet function in vitro and in vivo, in an experimental rat arteriovenous shunt thrombosis model and in human healthy volunteers. To identify active compounds, we fractionated a freeze-dried extract of a 10-year-old Armagnac using successively chloroform, diethyl ether and ethyl acetate. The 4 resulting fractions were tested on in vitro human platelet aggregation induced by ADP and in vivo on arteriovenous shunt thrombosis after 10 days oral treatment in rats. Active components were found mainly in fractions 1 and 3: at the highest concentration (2.4 10(-2) g/l), in vitro ADP-induced aggregation was inhibited by 62.7+/-2.1% and 51.2+/-3.8% for F1 and F3, respectively, vs 18.9+/-2.4% and 13.9+/-0.4% for fractions 2 and 4 and 33.6+/-1.5% for the crude extract. There was a significant decrease in thrombus weight with the crude extract and all fractions tested after 10 days treatment with 2.5 mg/kg/day orally, greatest with fraction 1. Characterisation of phenol content showed that fraction 1, the most biologically active, was essentially devoid of ellagic acid and ellagitannins, the polyphenols initially thought responsible for the effect, whereas fraction 2 which was mostly inactive, was the richest in polyphenols. CONCLUSION: The antiplatelet and antithrombotic activity of Armagnac seems mostly unrelated to polyphenols.     

Correlating the degree of needle trauma during prostate brachytherapy and the development of acute urinary toxicity

PURPOSE: To determine if there is an association between the degree of prostate trauma during prostate brachytherapy and development of acute urinary toxicity. METHODS AND MATERIALS: In a consecutive prospective cohort of permanent (125)I prostate brachytherapy patients, the number of times each needle was repositioned was tracked, and the dosimetry plans were used to determine the number of times needles within 1 cm of the urethra were manipulated. Additionally, prostate volume, total number of needles, number of needles/prostate volume, and the number of periurethral needle manipulations/prostate volume were determined. The need for catheterization beyond 24 hours and the Radiation Therapy Oncology Group (RTOG) urinary toxicity score at 4 weeks were recorded. The independent samples t test was used to search for a correlation between these parameters and the recorded toxicity scores. RESULTS: Twenty-eight consecutive implant patients were evaluated in the study. Median (range) values were as follows: prostate volume 35 cc ( range, 15-51 cc), number of needles per patient 32 (range, 21-41), number of needle manipulations per patient 94.5 ( range, 55-147), and number of periurethral needle manipulations 42 (range, 17-65). The only significant association between urinary toxicity and these variables was for the number of periurethral needle manipulations (p = 0.025). CONCLUSIONS: These data provide evidence that needle prostate trauma during brachytherapy contributes to acute urinary toxicity.     

Late neointimal tissue growth behind the stent after intravascular gamma-radiation

PURPOSE: To determine the nature of the changes of the vascular wall after intravascular brachytherapy in stented arteries leading to incomplete stent apposition. METHODS AND MATERIALS: Stents were implanted in the infrarenal aortas of rabbits, and gamma-intravascular brachytherapy (18 Gy) or a sham radiation procedure was immediately implemented. The arteries were harvested at 6 months for histologic analyses. RESULTS: The external elastic lamina area, as well as the vascular wall area behind the stent, were significantly greater in irradiated vs. control arteries (8.94 +/- 0.68 mm2 vs. 6.87 +/- 0.40 mm2 [p <0.001] and 1.56 +/- 0.13 mm2 vs. 0.72 +/- 0.07 mm2 [p <0.001], respectively). The ratio of the intimal area behind the stent related to the total intimal area was greater in the irradiated segments (control vs. irradiated: 9.0% +/- 5.9% vs. 55.3% +/- 15.5%, p <0.05). Neointimal growth of the irradiated vessels outside the stent was characterized by marked fibrin depositions and an inflammatory response around the stent struts. CONCLUSION: Our study revealed the presence of a neointimal layer specifically located behind the stent, which represented the result of an unhealed fibrin-rich tissue growth process 6 months after intravascular brachytherapy.     

Patient doses in gamma-intracoronary radiotherapy: the Radiation Burden Assessment Study

PURPOSE: To determine accurately the radiation burden of both patients and staff from intracoronary radiotherapy (IRT) with (192)Ir and to investigate the importance of IRT in the patient dose compared with interventional X-rays. METHODS AND MATERIALS: The Radiation Burden Assessment Study (RABAS) population consisted of 9 patients undergoing gamma-IRT after percutaneous transluminal coronary angioplasty and 14 patients undergoing percutaneous transluminal coronary angioplasty only as the control group. For each patient, the dose to the organs and tissues from the internal and external exposure was determined in detail by Monte Carlo N-particle simulations. Patient skin dose measurements with thermoluminescence dosimeters served as verification. Staff dosimetry was performed with electronic dosimeters, thermoluminescence dosimeters, and double film badge dosimetry. RESULTS: With respect to the patient dose from IRT, the critical organs are the thymus (58 mGy), lungs (31 mGy), and esophagus (27 mGy). The mean effective dose from IRT was 8 mSv. The effective dose values from interventional X-rays showed a broad range (2-28 mSv), with mean values of 8 mSv for the IRT patients and 13 mSv for the control group. The mean dose received by the radiotherapist from IRT was 4 microSv/treatment. The doses to the other staff members were completely negligible. CONCLUSION: Our results have shown that the patient and personnel doses in gamma-IRT remain at an acceptable level. The patient dose from IRT was within the variations in dose from the accompanying interventional X-rays.     

Urinary tract candidiasis: report of a case with bilateral ureteral obstruction

A brief review of the literature on urinary tract candidiasis is presented. The presence of Candida albicans in the urine is rather uncommon and most patients have candiduria without any apparent disease. Among the others, three different clinical types of infection are recognized: (1) pyelonephritis, (2) lower urinary tract infection and (3) ureteral obstruction. Of this last type only seven cases were found in the literature; four of the patients died. We add one case in which the patient did very well after the obstruction of the ureters was relieved by means of ureteral catheters and a large urinary output was maintained for several days.     

Kidney allograft tolerance in diabetic patients after total lymphoid irradiation (TLI)

The value of total lymphoid irradiation (TLI) combined with low dose prednisone as sole immunosuppressive regimen in renal allograft transplantation in humans has been investigated. Seventeen patients with end-stage diabetic nephropathy received TLI to a cumulative dose of 20-30 Gy in fractions of 1 Gy. Cadaver kidneys were grafted as soon as they were available after completion of TLI. Low dose prednisone was given after transplantation. Profound and long-term immunosuppression has been achieved in all patients. Six patients live already more than one year (greater than 2 years in 3 of them) and 7 for less than one year with a functioning kidney graft. Two out of these 13 patients had repeated rejection episodes necessitating a supplementary immunosuppressive treatment with cyclosporine A. One patient returned to chronic hemodialysis 11 months after transplantation and died of pericardial tamponade one month later. One patient had severe acute rejection for which cyclosporine A was administered; he died of septic shock as a consequence of immune deficiency a month later. The other two patients succumbed to other causes (myocardial infarction and hyperglycemia). The amount of steroids and azathioprine administered to these patients was substantially lower than in the case of conventional immunosuppression. The preliminary results are thus encouraging. However, the treatment schedule as used in the present study can not yet be considered as optimal since the majority of patients still had one or more rejection episodes. Further investigations are warranted. The optimal dose of radiation, the importance of the interval between TLI and organ transplantation, the influence of splenectomy on the immunity, etc., are still to be assessed.     

Occurrence of gastroesophageal reflux on induction of anaesthesia does not correlate with the volume of gastric contents

In an attempt to explain the discrepancy between the high number of patients said to be at risk of aspiration pneumonitis and the low reported incidence of this anaesthetic complication, 100 ASA physical status I-II elective surgical patients were studied. The volume of fluid present in the stomach at the time of induction of anaesthesia was correlated with gastroesophageal reflux (GER) detected by visual inspection of the pharynx and by continuous measurement of upper oesophageal pH. Mean gastric volume was 30 +/- 28 ml (range 0-210 ml). Gastric fluid volume greater than or equal to 0.4 ml.kg-1 at pH less than or equal to 2.5 was present in 46 patients. No GER was detected during induction of anaesthesia in our sample of 100 patients. Furthermore, patient age, duration of preoperative fasting, body mass index, cigarette smoking, alcohol consumption, preoperative anxiety, and a history of preoperative GER were not correlated with significant modifications of gastric volume or pH. We conclude that the low incidence of aspiration pneumonitis in elective surgical patients may be explained in part by the very low risk of GER, despite gastric fluid volumes of more than 0.4 ml.kg-1 in a high proportion of this patient population.     

Hepatocarcinogenesis in rats fed methyl-deficient, amino acid-defined diets

The ability of methyl-deficient, amino acid-defined diets toproduce liver tumors was studied in rats treated both with andwithout initiating doses of diethylnitrosamine (DENA). Male,weanling F344 rats were fed a complete, amino acid-defined dietfor one week. They were then injected once i.p. with one of3 doses of DENA (20, 70 or 200 mg/kg body weight) and fed thecomplete diet for an additional week. Thirty animals from eachdose group were then maintained for 76 weeks on the completediet (Diet 1) or one of 4 methyl-deficient diets: Diet 2, devoidof methionine and choline; Diet 3, devoid of methionine only;Diet 4, devoid of choline only and Diet 5, devoid of methionine,choline, folic acid and vitamin B₁₂. In Diets 2, 3 and 5 methioninewas replaced by equimolar amounts of its metabolic precursorDL-homocystine. Control rats were injected i.p. with the salinevehicle and maintained for the 76-week period on Diets 1 and2. Forty percent of the rats fed Diet 2, but receiving no DENA,developed hepato-cellular carcinomas or cholangiomas. A 90–100%incidence of hepatocellular carcinomas was seen in all groupsinitiated with DENA and fed Diet 2. No malignant liver tumorsdeveloped in Diet 1 rats that had received 0 or 20 mg/kg DENA;however, hepatocellular carcinomas were noted in one-half ofsuch animals receiving the 70 and 200 mg/kg doses. Liver metastasesgrew in the lungs of 60% of the tumor-bearing rats fed Diet2; none were seen in the Diet 1-fed rats. The singly deficientDiets 3 and 4 enhanced liver tumor formation to DENA-initiatedrats to a significantly lesser extent than did Diet 2. All DENA-initiatedrats fed the severely deficient Diet 5, died within 23 experimentalweeks with livers containing hepatocytes of atypical appearanceand, particularly at the 2 higher dosages, a cirrhotic pseudo-nodulararchitecture. No hepatocellular carcinomas or cholangiomas wereobserved in Diet 5-fed rats. None of the diets tested appearedto enhance tumor formation in extra-hepatic tissues. In fact,significant decreases were noted in the formation of spontaneoustesticular interstitial cell tumors in Diet 2-fed rats and ofpancreatic acinar tumors in rats fed Diets 2 and 3. Diet 2,devoid of both methionine and choline, also induced metaplasiaof pancreatic acinar cells to hepatocyte-like cells and wasasociated with moderate to severe hyperplasia of the transitionalepithelium lining the renal pelvis. Finally, DENA initiationgave weak but significant dose-dependent increases in the incidencesof kidney parenchymal tumors and lung bronchioalveolar celltumors that could not be directly correlated with the extentof methyl deprivation. The results indicate that dietary methyldeficiency markedly promotes liver carcinogenesis and exhibitscomplete carcinogenic activity in this organ in the rat.     

Synthèse et propriétés d'oligomères dièniques partiellement et totalement hydrogénés

Hydrogenations of several hydroxy-terminated low molecular weight polybutadienes (PB) or non functional PB and one polyisoprene by homogeneous catalysis were studied. Hydrogenation of 1,4-polybutadienes gave solid crystalline polymers. In the case of hydrogenated 1,2-polymers a decrease of the glass transition temperature was noted, the hydrogenation leading to amorphous polymers. The rheological behaviour of oligomers was found to be Newtonian at low shear rates (≤ 100 s^?1). The viscosity at T_g+100°C increased in every case with the hydrogenation rate. It was found that hydrogen bonding induced by hydroxyl groups has a great effect on the glass transition temperature but does not change the viscosity at T_g + 100°C.     

A pilot study of iron depletion as adjuvant therapy in chronic hepatitis C patients not responding to interferon

The aim of this study was to assess the efficacy of iron depletion obtained by phlebotomy to enhance interferon response in 11 patients who had failed to respond to a standard 3-month interferon treatment. Despite a significant effect on serum aminotransferase levels, there was no effect on viremia, and iron depletion was unable to trigger interferon response.