THE SIGNIFICANCE OF CORONARY DEATH FOR THE EXCESS MORTALITY IN ALCOHOL-DEPENDENT MEN

General and validated cause-specific mortality, especially regardingcoronary disease, was studied in a population-based cohort of1049 alcohol-dependent (DSM-III-R) men, who were dischargedfrom a detoxification ward. The observed and expected numbersof deaths were 140 and 23.2. respectively (P<0.001). Theestimated risk quotient of death was 6.0 (95% confidence interval5.1–7.1). The concordance between revised and officialcauses of death was {small tilde}50%, but the resulting variationof risk quotients of cause-specific deaths generally remainedwithin the statistical uncertainty. Coronary disease contributedto 19% of the total excess mortality in cases with a validateddefinite death diagnosis. The risk of coronary death tendedto be augmented during the first 2 years of discharge (P%0.05).Thus, coronary death contributed significantly to the excessmortality in alcohol-dependent men, and an increased vulnerabilityfor sudden coronary death seemed to persist for a considerabletime after discharge from detoxification.     

Myotonic Dystrophy Treated with Selenium and Vitamin E

ABSTRACT. We have previously reported the successful treatment of a patient with myotonic dystrophy with selenium and vitamin E. This paper deals with the treatment of a further five patients with myotonic dystrophy in different stages. All five patients improved subjectively and objectively in two or more respects. All improved their grip strength according to vigorimeter measurements (Martin), two normalized their gait, another two can now sit down on their heels and stand up, one patient can now walk on his toes, one can now get up from lying on the floor without using a chair and two patients have improved their physical capacity. Patients in early stages of the disease improved faster and more markedly than those in late stages. Electromyographical measurements also showed improvements, in that the myotonic discharges had diminished. The daily dose was 4 mg of Na₂SeO₃ and 600 mg of vitamin E. Serum concentration of selenium increased in all patients at the beginning of the treatment, but stabilized at a level slightly above the normal. No side-effects were observed.     

Chronic 5-HT2-Receptor Blockade by Ritanserin Does Not Reduce Blood Pressure in Patients with Essential Hypertension

ABSTRACT The selective 5-HT₂-receptor-blocking agent ritanserin is an analogue of the antihypertensive agent ketanserin. By evaluating the antihypertensive effects of ritanserin the aim of this investigation was to indirectly elucidate the mechanism of action of ketanserin. Thirteen patients with essential hypertension were treated with placebo and ritanserin, 10 mg bid., in a double-blind, cross-over design (4-week periods). At the end of the treatment periods blood pressure as well as plasma concentrations of ritanserin were evaluated for 24 hours. Despite high steady state and peak plasma concentrations of ritanserin the compound did not lower the blood pressure compared with placebo. Since chronic selective 5-HT₂-receptor blockade by means of ritanserin did not lower the blood pressure, it is concluded that the 5-HT₂ blocking properties of ketanserin cannot alone be responsible for the antihypertensive effects of ketanserin.     

Synthesis and bioassay of LHRH-antagonists with N-Ac-d-O-phenyltyrosine and N-Ac-d-3-(2-dibenzofuranyl)alanine in position 1

N-Ac-d -O-phenyltyrosine was synthesized via the corresponding azlactone. Resolution of the dl methyl esters was achieved by Subtilisin Carlsberg. Treatment with palladium(II) acetate in trifluoroacetic acid converted N-Ac-d -O-phenyltyrosine into N-Ac-d -3-(2-dibenzofuranyl)alanine. These two amino acids were incorporated instead of N-Ac-d -2-Nal into position 1 of the LHRH-antagonist (N-Ac-d -2-Nal¹, d -pClPhe², d -3-Pal³, c-PzACAla⁵, d -PiCLyS⁶, ILys⁸,d -Ala¹⁰)-LHRH. The more rigid N-Ac-d -3-(2-dibenzofuranyl)alanine was structurally more effective than N-Ac-d -O-phenyltyrosine; the AOAs for the corresponding analogs were 82 and 38%, respectively, at 0.5 μg. Replacement of c-PzACAla in position 5 by O-phenyltyrosine significantly decreased potency.     

Design of protecting groups for the β-carboxylic group of aspartic acid that minimize base-catalyzed aspartimide formation

With the objectives of developing new protecting groups for the β-carboxyl group of aspartic acid that are resistant to base-catalyzed aspartimide formation and of evaluating the importance of sterical factors in the design of such protecting groups, four new alkyl ester derivatives of aspartic acid were synthesized. The β-3-pentyl, β-4-heptyl, β-2,6-dimethyl-4-heptyl and the recently described β-2,4-dimethyl-3-pentyl esters of Boc-aspartic acid were incorporated into model peptides, and the resin-bound protected peptides were treated with 20% pipetidine for 10 h. The levels of aspartimide-related side products were compared with the previously reported β-cyclohexyl, β-menthyl and β-2-adamantyl esters of aspartic acid. The results show that bulky, acyclic, aliphatic protecting groups (in particular the 2,4-dimethyl-3-pentyl ester) are significantly more resistant to base-catalyzed aspartimide formation than comparably rigid cyclic alkyl esters that under the same reaction conditions form several-fold more aspartimide-related side products. Using elevated temperatures to overcome difficult couplings leads to the formation of significant amounts of aspartimide when aspartic acid is protected with the cyclohexyl group, but the 2,4-dimethyl-3-pentyl protecting group offers excellent protection under these conditions. The use of the 2,4-dimethyl-3-pentyl protecting group will allow the use of orthogonally removable base-labile protecting groups in Boc chemistry and suggests a design of protecting groups for other nucleophile-sensitive trifunctional amino acids in both Boc and Fmoc chemistry. © Munksgaard 1996.     

Bacteriologic evaluation of the efficacy of mechanical root canal instrumentation in endodontic therapy

Abstract – The presence of bacteria in 15 single-rooted teeth, with periapical lesions, was studied throughout a whole period of treatment. The root canals were irrigated with physiologic saline solution during instrumentation. No antibacterial solutions or dressigs were used. Bacteria were found in all irnitial specimens form the teeth (median numver of bacterial cell 4x10⁵; range 10²-10⁷) and the number of strains in the specimens ranged from 1 to 10.88% of the strains were anaerobic. The most commonly isolated species were: Peptostreptococcus micros, Peptostrcptococcus anacrobius, Fusobacterium nucleatum, Bacteroides oralis, Bacteroides melaninogenicus subsp. intermedius and Eubacterium alactolyticum. Mechanical instrumentation reduced the number of bacteria considerably. Specimens taken at the beginning of each appointment usually contained 10⁴-10⁶ bacterial cells and at the end 10²-10³fewer. Bacteria were eliminated from the root canals of eight teeth during the treatment. In seven root canals bacteria presisted despite treatment on five successive occasions. There was no evidence that specific microorganisms were implicated in these persistent infections. Teeth where the infection persisted despite being treated five times were those with a hig number of bacteria in the initial sample.