A new sclerosing agent in the treatment of venous malformations. Study on 23 cases.

SUMMARY: Absolute ethanol is the most effective agent in the treatment of venous malformation (VM) although it is quite risky to use because of the danger of diffusion beyond the target. To reduce this risk, we have developed an alcoholic sclerosing solution that is less diffusible. The viscosity of absolute ethanol was enhanced with monographic ethyl-cellulose at a concentration of 5.88% ie 0.75 g in 15 ml of absolute ethanol 95%. 23 patients with VM located on the buttock (1), hand (2), leg (1) and face (19) were treated. A mean volume of 1.99 ml of the solution was injected directly into the VM. Each patient had an average of 2.8 procedures. Sixteen patients were done under general anaesthesia and seven with local anaesthesia. Evaluation was performed by the patient, the dermatologist of the treating multidisciplinary team and a dermatological group not involved in the treatment of the patients. Patients were evaluated after a mean delay of 24.52 months. Evaluation of the cosmetic result was made with a five point scale and the global result with a three point scale. VM pain was evaluated by the patients with a Visual Analogue Scale. The aesthetic results were graded as satisfactory (> 3) for the patient and the dermatologist of the multidisciplinary team. However the results were not as good with the independent dermatological group evaluation. The pain was significantly less important after the treatment (p << 0.001). Among the 23 patients, the local adverse events were nine necrosis with or without ethylcellulose fistula followed by only two surgical procedures. There were no systemic adverse events. Sclerotherapy of VM is usually performed with absolute ethanol or ethibloc. The main advantage of our sclerosing mixture is that it expands like a balloon when injected slowly in a aqueous media. Because of the important increase in viscosity the volume of injected solution is much lower than ethanol alone and the risk of systemic reactions is lower. Contrary to ethibloc, post-sclerosing surgery is not necessary because sub-cutaneous ethylcellulose disappears secondarily.

Randomized multi-centre trial of the effects of a catheter coated with hydrogel and silver salts on the incidence of hospital-acquired urinary tract infections.

Catheters coated with hydrogel and silver salts have been proposed to prevent hospital-acquired urinary tract infections (UTI). We carried out a randomized, prospective, double-blind multi-centre trial to compare those catheters with classical urinary tract catheters. We included in the study 199 patients requiring urethral catheterization for more than three days: 109 in group 1 (classical catheter) and 90 in group 2 (catheter coated with hydrogel and silver salts). Urine from the patients was tested for 10 days after the insertion of the catheter (reactive dipsticks each day and diagnostic urinalysis every two days). The UTI associated with catheterization was defined on the basis of bacterial and cytological criteria (>10(5)cfu bacteria per mL and >10 leucocytes per mm(3)). Twenty-two UTIs were recorded: 13 in group 1 and nine in group 2. The cumulative incidence of UTI associated with catheterization was 11.1% overall, 11.9% for group 1 and 10% for group 2; the odds ratio was 0.82 (95% confidence interval: 0.30 to 2. 20); the cumulative incidence for UTI, calculated by the Kaplan-Meier method was 36.3 overall, 35.2 in group 1 and 36.0 in group 2; the overall incidence density was 19 per thousand days of catheterization, 21 in group 1 and 18 in group 2. The differences between the two groups were not significant. Overall, we feel that there is not enough evidence to conclude that catheters coated with silver salts and hydrogel give greater protection than classical catheters and to recommend widespread use.

Benzodiazepines: toxic serum concentrations in positive enzyme immunoassay responses.

A total of 588 blood specimens collected in an emergency unit were screened for benzodiazepines (BZDs) using enzyme-multiplied immunoassay and gas chromatography. Two-hundred eighty-five samples were positive for BZDs, and 303 samples that were negative by EMIT included 20 samples with BZDs detectable by gas-liquid chromatography. A total of 15 BZDs were identified, and the most frequently occurring were nordiazepam, bromazepam, diazepam, and alprazolam. Individual BZDs were found in 74% of cases, but some samples contained two, three, or even four BZDs. There is a risk of missing intoxication by BZDs with low therapeutic range and/or low cross-reactivity (alprazolam, bromazepam, flunitrazepam). There is a risk of misinterpreting a positive result for some BZDs with high therapeutic range and/or high cross-reactivity (nordiazepam), which may reflect a pharmacologically ineffective concentration. A semiquantitative analysis is inappropriate even when the identity of BZD is known. Immunoassays are the only methods presently available for use in emergencies, but physicians must be clearly informed of their limitations and interpret results with caution.

Food-dependent Cushing's syndrome mediated by aberrant adrenal sensitivity to gastric inhibitory polypeptide.

BACKGROUND: Some patients with Cushing's syndrome have nodular adrenal hyperplasia. In most the disease is corticotropin-dependent, but in others it is corticotropin-independent. The cause of the adrenal hyperplasia in the latter patients is not known. METHODS: We studied a 49-year-old woman with Cushing's syndrome and nodular adrenal hyperplasia in whom food stimulated cortisol secretion. Plasma cortisol concentrations were measured in response to the ingestion of mixed meals, glucose, protein, and fat and after the administration of various gastrointestinal and other types of hormones. We also studied the ability of the long-acting somatostatin analogue octreotide to prevent the food-induced increase in plasma cortisol concentrations and to ameliorate the clinical manifestations of Cushing's syndrome in this patient. RESULTS: The patient's fasting plasma cortisol concentrations were subnormal, ranging from 3.0 to 7.5 micrograms per deciliter (83 to 207 nmol per liter), and they increased to as high as 16.5 micrograms per deciliter (455 nmol per liter) after a mixed meal. Her urinary cortisol excretion ranged from 164 to 250 micrograms per day (453 to 690 nmol per day) and could not be suppressed by a large dose of dexamethasone. Plasma corticotropin concentrations were virtually undetectable at all times. The ingestion of glucose, protein, and fat increased plasma cortisol concentrations to 3.6, 2.2, and 4 times the base-line value, respectively; the meal-induced and glucose-induced increases were inhibited by octreotide. The infusion of gastric inhibitory polypeptide (GIP) increased the patient's plasma cortisol concentration to 3.7 times the base-line value, but had no effect in normal subjects. The patient's fasting plasma GIP concentrations were normal both before and after a meal, and there was a close correlation between her plasma cortisol and GIP concentrations. Treatment with octreotide decreased urinary cortisol excretion and ameliorated the clinical manifestations of Cushing's syndrome. CONCLUSIONS: The development of aberrant adrenal sensitivity to GIP can result in food-dependent adrenal hyperplasia and therefore in Cushing's syndrome.

Quinidine oxidative metabolism. Identification and biosynthesis of quinidine 10,11-dihydrodiol stereoisomers.

The isocratic reversed phase high performance liquid chromatographic method proposed for quinidine metabolic studies facilitates particularly the separation of 10(R) and (S) isomers of quinidine 10,11-dihydrodiols. The finding of each of these forms following a new synthetic pathway allows us to identify and quantify them in biological fluids. These two isomers have especially been observed in rat bile and hepatocyte secretions. The metabolic inducing effect of phenobarbital on the oxidative metabolism of quinidine is verified in rat isolated hepatocytes. Simultaneous secretion of the two dihydrodiols is also verified in human urine by a gas chromatography/mass spectrometry procedure.

Clinical pharmacology of hydroxy-3(S)-dihydroquinidine in healthy volunteers following oral administration.

Pharmacokinetics and effects of oral hydroxy-3(S)-dihydroquinidine (3-OH-HQ) on heart rate (HR), blood pressure (BP), and ECG intervals were studied in 12 healthy volunteers. Three oral single doses of 3-OH-HQ (225, 450, and 900 mg) and placebo were randomly administered to each subject at one week intervals. Pharmacokinetics of 3-OH-HQ was linear in the range of administered doses, with rapid absorption (tmax 0.5-2.5 h) and distribution (t1/2 alpha 0.8-1.2 h) phases. Elimination half-lives did not significantly change with the three doses (15 +/- 4.3, 13.7 +/- 3.9, and 13 +/- 2.2 h). Unchanged 3-OH-HQ was partially eliminated by urine (mean renal clearance 0.24 +/- 0.02 L h-1 kg-1). 3-OH-HQ significantly increased HR after the three doses as compared to placebo. PR interval was not significantly modified but QRS duration significantly increased from 91 +/- 7 to 108 +/- 11 ms (p less than 0.001) 2 h after the 900 mg dose. QTc interval was significantly prolonged from 0.5 to 8 h after the highest dose (14.4 +/- 8.7% 1 h after dosing). Heart rate QRS, and QTc variations were significantly correlated to 3-OH-HQ plasma levels.

Reverse-phase liquid chromatography and pharmacokinetic study of two hydroxylated analogues of quinidine in dogs.

Two hydroxylated analogues of quinidine with antiarrhythmic properties, 3S-hydroxyquinidine and 3R-hydroxydihydroquinidine were assayed by reverse-phase high-performance liquid chromatography. The analytical technique uses plasma protein precipitation and direct injection on a C18 column, with an isocratic mobile phase and spectrofluorometric detection. 3R-Hydroxyquinidine is employed as the internal standard. Linearity is verified up to 5 mg/L for the two drugs; concentrations between 0.5 and 2.5 mg/L were measured with a CV of 0.5-2.07% for a given day and a sensitivity limit of 50 micrograms/L. Plasma concentration-time profiles and pharmacokinetic parameters in three dogs are presented after intravenous or oral administration. A significant difference is observed in terminal half-life, terminal rate constant, and total clearance of the two polar analogues of quinidine.