[Comparison of tacrine hepatotoxicity in patients with Alzheimer disease or AIDS]. / Comparaison de l'hépatoxicité de la tacrine chez des patients atteints de la maladie d'Alzheimer ou du SIDA.

Previously used in Alzheimer disease Tacrine (THA): tetrahydroaminoacridine has shown a rise of hepatic transaminase enzyme activity (TEA) in 18% of patients for Summers and 19% for Ames. Although studies using THA from USA or Canada have noticed a rise of TEA in 30% of the patients, after a treatment course with French THA we also have noted a rise of TEA in 12% of the Alzheimer patients. However, these secondary effects yielded to the end of treatment. These studies have been done with THA from different origins and different associations. Summers, the Canadian group and the French one have used THA in association with lecithin, when american group study has been made with no additional product. Therefore we have initiated a trial with oral THA in AIDS patients. 52 patients with HIV infection (26 in the IVC1 group and 26 in IVC2 group) have been treated with the same THA as the one used for Alzheimer french group. The common dosage was 150 to 200 mg (3 to 4 of 50 mg dosing capsules per day). The THA has been synthetized such as having an over 99% pureness product. After a period of 260 months/patient no elevation of TEA has been noted in any patients of our group. These results observed in HIV advanced patients with this THA are discordant with the one observed in Alzheimer's study. The dosage used in AIDS is twice higher than the one used for Alzheimer which gives us credit to the lack of hepatic toxicity in HIV advanced patient after 7 months of treatment.

Factors influencing precipitation of pH-adjusted bupivacaine solutions.

Solutions of bupivacaine precipitate when bicarbonate is added. This limits the clinical use of pH-adjustment in optimizing bupivacaine activity. In this study four different bupivacaine solutions were studied with the addition of sodium bicarbonate at 4 degrees C or 20 degrees C. Bupivacaine concentrations remained unchanged after pH-adjustment. Least crystallization was observed with bupivacaine solutions containing a small amount of sodium bicarbonate and stored at 4 degrees C.

Direct measurement of the capsular bag.

Direct measurement of the capsular bag was performed after extracapsular cataract extraction on 49 cadaver eyes. These lenses had a collapsed bag size of 10.32 +/- 0.42 mm.

Alkalinization of epidural 0.5% bupivacaine for cesarean section.

Controversial results have been published in the literature concerning the efficacy of alkalinization of solutions of local anesthetics to shorten the time to onset of sensory block. Fifty-two parturients scheduled for cesarean section at term under epidural anesthesia were randomly allocated to one of four groups: group 1, 0.5% plain bupivacaine (pH = 5.38 +/- 0.05); group 2, 0.5% bupivacaine pH-adjusted with 1.4% sodium bicarbonate (pH = 6.87 +/- 0.01); group 3, 0.5% bupivacaine with 1:200,000 epinephrine (pH = 4.80 +/- 0.04); and group 4, 0.5% bupivacaine pH-adjusted with 1:200,000 epinephrine (pH = 6.68 +/- 0.01). The time to onset of the sensory block was evaluated using a nerve stimulator technique. Motor blockade was assessed using Bromage's scale. No differences in the characteristics of the onset of the sensory block were observed with epinephrine-containing solutions nor with pH-adjusted local anesthetics. The maximal degree of motor blockade was not significantly different in the four groups. We conclude that alkalinization of a 0.5% bupivacaine solution is not an effective way to shorten the latency of epidural block for cesarean section.

[Increase in nuclear aluminum concentration during hepatic regeneration: study by analytical ionic microscopy]. / Augmentation de la concentration d'aluminium nucléaire pendant la régénération hépatique: étude par microscopie ionique analytique.

20 hrs. after partial hepatectomy, a significant increase in the aluminum concentration of liver cell nuclei has been measured by analytical ion microscopy. These results indicate a possible role of aluminium in an in vivo induced proliferative response.

Stability of epinephrine in alkalinized solutions.

STUDY OBJECTIVE: Increasing the pH of an epinephrine solution favors its oxidation and may result in a decrease in its biological activity. It is therefore generally assumed that epinephrine and sodium bicarbonate should not be infused in the same IV line during CPR. The aim of this study was to determine the validity of this widely accepted proposition. DESIGN AND SETTING: Two different commercial solutions of epinephrine differing only in the concentration of sodium metabisulfite (0.46% and 0.02%) were studied. Two dosages of each solution type (1 mg/1 mL and 10 mg/10 mL) were diluted in 250 mL of 8.4% sodium bicarbonate. MEASUREMENTS AND MAIN RESULTS: The concentration of epinephrine was measured at different times for two weeks. It was found that the concentration of epinephrine decreased slowly to zero after two weeks, and was approximately at 70% and 100% of control values at 30 minutes after alkalinization. CONCLUSION: It was concluded that epinephrine in an alkaline solution is effectively oxidized but has a slow reaction that may not be clinically relevant over short periods of time.

Chemical stability of lignocaine (lidocaine) and adrenalin (epinephrine) in pH-adjusted parenteral solutions.

Recent clinical studies have shown that alkalinizing lignocaine (lidocaine) solutions is an effective way of shortening the time of onset and increasing the duration of anaesthesia. However, alkalinizing lignocaine solutions raises the problem of the stability of these preparations. Moreover, the adrenalin usually associated with it is unstable in alkalinized solutions designed for peridural injection. This study was performed to define the range of pH over which lignocaine and adrenalin in commercial solution is stable. The results indicate that it is possible to alkalinize lignocaine solutions and that the solutions prepared are stable for at least 6 h.

Chemical stability of bupivacaine in pH-adjusted solutions.

Recent clinical studies have suggested that alkalinization of bupivacaine may shorten the time to onset and lengthen its duration of action. However, addition of sodium bicarbonate to commercially manufactured bupivacaine can rapidly produce precipitation. This study was performed to study the stability and precipitation of bupivacaine solutions 0.25% and 0.50% with and without epinephrine 1:200,000 after alkalinization. The results indicate that alkalinization does not increase precipitation above recommended limits and that the concentration of bupivacaine in solutions is maintained at least 6 h after alkalinization.

Alkalinization of 0.5% lidocaine for intravenous regional anesthesia.

Although remaining a controversial issue, alkalinization of lidocaine or bupivacaine may shorten the time to onset and increase the duration of the sensory block. The aim of this study was to evaluate the effect of pH adjustment on the sensory and motor blocks during intravenous regional anesthesia (IVRA) with lidocaine. Thirty-one patients scheduled for minor hand surgery performed under IVRA were randomized into two groups: Group 1 (n = 14): 1% lidocaine, 3 mg/kg, diluted with the same volume of physiological saline solution (pH = 6.63 +/- 0.05), and Group 2 (n = 17): 1% lidocaine, 3 mg/kg, diluted with the same volume of 1.4% sodium bicarbonate (pH = 7.34 +/- 0.05). final concentration of lidocaine was thus 0.5% in both groups. Sensory block was assessed by pinprick every 2 minutes in areas corresponding to six terminal nerves: ulnar, median, radial, musculocutaneous, medial cutaneous nerve of arm and intercostobrachial, and medial cutaneous nerve of forearm. The time between release of tourniquet (at the end of surgery) and appearance of pain was recorded. Motor blockade was evaluated by asking the patient to squeeze strongly a blood pressure cuff previously inflated to 40 mmHg. This maneuver was performed before and every 2 minutes after injection. No statistical differences were found between the two groups whatever the parameter studied. In conclusion, there is no advantage (over plain solutions) to using pH-adjusted lidocaine during IVRA for hand surgery.

Intratumor treatment of C3H mouse mammary carcinoma with 5-fluorouracil adsorbed on activated charcoal particles.

A dosage form comprising 5-fluorouracil (5-FU, 25 mg/ml) adsorbed on a suspension of micronized charcoal (100 mg/ml) 2-5 microns in diameter, adsorbing 5-FU in aqueous solution was studied for intratumor treatment of mammary carcinoma in animal experiments. An in vitro desorption method is described to determine the amount of 5-FU adsorbed on activated charcoal particles which would be released once the drug concentration decreased around the charcoal. In vivo results indicate that an intratumor injection of 5-FU adsorbed on activated charcoal particles is a highly effective method for achieving tumor regression without increasing toxicity.