[Communication on smoking in community pharmacy. Results of a survey in Belgium]. / La communication sur le tabagisme en officine. Résultats d'une enquête menée des pharmaciens flamands et bruxellois.

For several reasons the community pharmacist plays an important role in smoking cessation. In order to know how he is fulfilling this role, a survey was conducted among Belgian community pharmacists on smoking cessation communication in their pharmacy. The pharmacists and the pharmacy personnel were invited to answer an online questionnaire. In community pharmacy the patient is quite often asked if he smokes, however there still remain some obstacles to talk with the patient about smoking behaviour. The major obstacles are lack of time and the fear of a conflict with the patient. The results of the survey reveal that pharmacists and their assistants have a good knowledge of smoking cessation, but there is still some room to improve. In order to improve the smoking cessation support by pharmacists and their assistants, some efforts are necessary to overcome the obstacles. It would also be useful to organise more courses of tabacology at the faculties of pharmacy of the universities and in the continuing education programs for pharmacists.

Etiologic discussion and clinical relevance of thyroid ultrasonography in subclinical hypothyroidism. A retrospective study in 1845 patients.

BACKGROUND: Acquired subclinical hypothyroidism in adulthood is mainly due to autoimmune thyroiditis. In the absence of a goiter or a palpable firm thyroid, measurement of thyroid antibodies can improve the diagnosis. Whether thyroid antibodies are detected or not, what might be the clinical relevance of ultrasonography in this setting? METHODS: We studied 1845 cases of subclinical hypothyroidism in adults recruited for symptoms indicative of hypothyroidism or thyroid pathology. All patients were screened for thyroid antibodies and underwent an ultrasonographic thyroid examination. LOCALISATION: Multicentric retrospective study. RESULTS: Chronic autoimmune thyroiditis was confirmed in 70% of patients. Thyroid antibodies were undetectable in 30% of patients. In all patients, thyroid ultrasound facilitated measurement of the thyroid volume and detection of non-palpable nodules and therefore allowed biopsy. In patients negative for thyroid antibodies, ultrasonography suggested autoimmune thyroiditis in 31% of cases. Ultrasonography did not contribute to diagnosis in a large number of patients without nodules and in case of normal echostructure. The strategy of thyroid hormone replacement therapy was not influenced by ultrasonographic data. Thyroid biopsies detected smears suspected to be cancerous in 10 patients (4%). Cancer was confirmed in nine patients after surgery. Ultrasonography displayed suspicious aspects in six patients. CONCLUSION: In subclinical hypothyroidism, thyroid ultrasonography is not required for the diagnosis of autoimmune thyroiditis but is useful for patients with abnormal thyroid palpation and allows detection of non-palpable thyroid nodules. For patients that were negative for thyroid antibodies, thyroid ultrasonography can improve diagnosis for some patients, allowing detection of autoimmune thyroiditis.

[Adrenal enzymatic block with late-onset caused by 11-hydroxylase deficiency. Apropos of 29 cases]. / Blocs enzymatiques surrénaliens à révélation tardive par déficit de la 11-hydroxylase. A propos de 29 observations.

Late-onset congenital adrenal hyperplasia is a cause of a spectrum of clinical manifestations of postnatal androgen excess. In these cases, ACTH stimulation test with measurement of 17-Hydroxyprogesterone (17OHP) is usually done to assess 21-hydroxylase (21-OH) deficiency. Determination of the 11-deoxycortisol (S) and the S to cortisol ratio is rarely done, so that 11 beta-hydroxylase (11-OH) deficiency seems unusual. We systematically investigated this biosynthetic defect among women complaining of hyperandrogenism (n = 519) and, comparing the patient's hormonal responses to ACTH with those of 31 normal women, found 29 11-OH deficiency (5.6%): this is the largest group ever reported. S was elevated only 9 times, so that using this single determination, diagnosis of 20 enzymatic defects would not have been made. Only three of the patients (10%) had hypertension, even though the pathway of aldosterone was involved in 33% of cases (criteria: elevation of the ratio desoxycorticosterone to corticosterone). We also described one new patient with both 11-OH and 3-beta-hydroxysteroid dehydrogenase deficiencies. The patho-physiology is particularly interesting in these cases. It is concluded that the single research for 21-OH deficiency is inadequate among women complaining of hyperandrogenism: the screening for 11-OH deficiency should be made, even if blood pressure is normal.

[Results of ultrasonographic and cytologic follow-up of 311 initially non-suspicious thyroid nodules]. / Résultats de la surveillance échographique et cytologique de 311 nodules thyroïdiens initialement non suspects.

The follow-up of initially non suspect thyroid nodules after fine needle biopsy is not completely worked out. Since 1985, we have entered upon a prospective study concerning the followup of thyroid nodules supposed to be benign after initial evaluation. What are the nature and the frequency of means to be used for their follow-up? Three hundred and eleven nodules are followed up on a mean duration of 2.44 years. The follow-up of 65 of them is 4 years or more. The follow-up of 120 others is 3 to 4 years; 197 nodules are followed up during 2 to 3 years. A physical examination, an ultrasonography completed with a fine needle biopsy or an ultrasonically guided fine needle biopsy are worked out every year. Twenty-three per cent of initial biopsies are non significant and 90% of them are ultrasonically guided biopsies. At the end of the study, the repeating biopsies reduce to 6% the non significant biopsies ratio. Four histological thyroid cancers are detected in three female patients 1 year, 2 years and 5 years after the initial evaluation. Ultrasound alterations of nodules are observed in case of very suspect biopsies. Ninety-six per cent of the followed up thyroid nodules remain not cytologically suspect. These findings allow us to propose the following guidelines for the assessment of a non suspect thyroid nodule: half-yearly or yearly physical examination, yearly or biennial ultrasonography, repeat biopsy after 2 or 3 years when clinical or ultrasound suspect modification is wanting.

[Nodular or pseudo-nodular Hashimoto thyroiditis. Value of cytologic examination]. / Thyroïdites de hashimoto à aspect nodulaire ou pseudo-nodulaire. Intérêt de l'examen cytologique.

OBJECTIVES: Nodular or pseudo-nodular aspects of Hashimoto's thyroiditis raise the problem of the association with a differentiated carcinoma or a non Hodgkin's lymphoma. METHODS: We looked for patients needing surgery in 165 cases of Hashimoto's thyroiditis. For this purpose, we used fine needle aspiration cytology. RESULTS: We found a differentiated carcinoma in 4% of cases and a non Hodgkin's lymphoma in 1% of cases. CONCLUSION: In nodular or pseudo-nodular aspects of Hashimoto's thyroiditis, fine needle aspiration cytology is helpful for the nodule diagnosis and for the selection of suspicious nodules only to be referred to surgery.

[Novel beta-lactam structures: design problems]. / Novye betalaktamnye struktury. Problemy konstruirovaniia.

The methology of the development of new biologically active betalactams is proposed. One of the two ways proposed is specific modification which is peculiar to certain betalactam structure and involves introduction of substitutes changing particular physico-chemical properties of the natural or synthetic analogous. General guidelines for modification of the biologically active compounds are given. The space and depth of the necessary physico-chemical investigation are determined. The alternative way of the new biologically active compounds development is the principle of similarity. The distinctive feature of this approach is the use as building blocks of the substitutes already used in the well-known betalactam antibiotics and "implantation" of this substitutes into other (new) betalactam structures. The ways of the new betalactams synthesis including the methods of enzyme engineering are considered. The possibility to use enzyme engineering processes for production of not only new individual betalactams--hits, but also for synthesis of the groups of betalactams--leads, is shown. More than 6000 new betalactam structures were constructed on the base of the principle of similarity. At least 700 of this compounds demonstrates not only antimicrobial activity but other types of biological activity due to the implementation of additional pharmaceutical units other than betalactams. The constructed compounds are summarized in the tables, the request for the electronic version of the tables can be sent by the address: valan@orc.ru.

[Enzymatic synthesis of beta-lactam antibiotics. II. Aminocephalosporins]. / Fermentativnyi sintez betalaktamnykh antibiotikov. II. Aminotsefalosporiny.

Enzymatic synthesis of cephalexin and cefaclor with the use of immobilized aminocephalosporin synthetase from Xanthomonas sp. as a biocatalyst was studied. The employment of a mathematical model based on the acyl-enzyme mechanism of the biocatalyst action was shown possible for the quantitative description of the antibiotic syntheses. A relationship providing determination of the complex of the physico-chemical investigations required for the enzymatic synthesis design was suggested. Kinetic and thermodynamic parameters of the processes were evaluated and the ratios of the maximum conversion of the key amino acids and the initial concentrations of the substrate and nucleophile were calculated. The regions of the model fit to the experimental data within a wide range of the substrate and nucleophile concentrations were defined. The technology for the enzymatic synthesis of aminocephalosporins exemplified by cephalexin and cefaclor was designed.

[Enzymatic synthesis of beta-lactam antibiotics. I. Cefazolin]. / Fermentativnyi sintez betalaktamnykh antibiotikov. I. Tsefazolin.

Production of cefazolin by acyl transfer enzymatic synthesis with immobilised cefazolin synthetase from Escherichia coli as a biocatalyst acting in accordance with the mechanism including formation of the acyl-enzyme complex was shown possible. The process kinetic parameters and the ratio of the maximum conversion of the key amino acid and the initial concentrations of the substrate and nucleophile were determined. Correlation of the calculated and experimental data on the cefazolin yield in the enzymatic synthesis was good. The main physico-chemical properties of the substrates and the reaction products i.e. dissociation constants and solubility were investigated. The complex of the physico-chemical studies makes it possible to design a highly efficient technological process for production of cefazolin including not only the stage of the enzymatic synthesis but also the stage of separation of the reaction mixture components.

[Role of biocatalysis in the creation and improvement of production of beta-lactam antibiotics in Russia]. / Rol' biokataliza v sozdanii i sovershenstvovanii proizvodstva betalaktamnykh antibiotikov v Rossii.

The paper presents the results of the studies carried out by the authors within 20 years on development of processes for production of beta-lactam antibiotics with using biocatalysis. The proposed general principles for the development of efficient biocatalytic technologies are discussed in regard to production of the key compounds and synthesis of beta-lactams. The paper includes 4 parts concerned with comparison of the biocatalytic and chemical processes for production of beta-lactam antibiotics, requirements to the quality of the biocatalysts used and criteria for estimation of the efficiency of the stage of the technological biocatalyst production. The criteria provided determination of the optimal biocatalyst for production of the key compounds in the synthesis of beta-lactams. A retrospective analysis of the biocatalytic processes for production of 6-amino-penicillanic acid is presented and the impact of the activity and the form of the biocatalyst on the process efficiency is substantiated. Various schemes of the enzymatic synthesis of beta-lactam antibiotics and the approaches to the improvement of the technological processes including those with the use of immobilized microbial cultures at the stage of the production of the initial biosynthetic antibiotics are described. The prospects for the improvement of the processes for production of drugs with the use of biocatalysis are indicated and the main trends of the research required for the large scale use of the immobilized enzymes, microbial cells, oligo-enzymatic and poly-enzymatic systems in transformation and synthesis of organic compounds are defined.

[Stability of various cephalosporins in solutions. Cefazolin, cefazedone, cefaclor]. / Ob ustoichivosti nekotorykh tsefalosporinov v rastvorakh. Tsefazolin, tsefazedon, tsefaklor.

The kinetics of splitting out the substitute at C3 in the molecule of beta-lactam antibiotics such as cefazolin, cefaclor, cefazedone and others as well as that of splitting out the chlorine atom in the side radical of the cefazedone molecule was studied within wide ranges of pH and temperature. The destruction processes for all the investigated compounds were shown to be described by the 1st order equations. The values of the activation energy, pre-exponential factors and reaction order by the hydrogen ions were measured. This provided the mathematical description of the destruction processes within wide ranges of pH and temperature. An unusual mechanism of synchronous splitting out the substitute at C3 and one of the chlorine atoms in the side radical of the cefazedone molecule was observed.

[Kinetics of 7-aminocephalosporanic acid in aqueous solutions]. / Kinetika prevrashchennii 7-aminotsefalosporanovoi kisloty v vodnykh rastvorakh.

Stability of 7-aminocephalosporanic acid (7-ACA) and desacetyl-7-ACA in aqueous solutions at the pH value higher than 6 and wide ranges of the temperature was studied. The kinetic parameters of the hydrolysis of the ester link in the molecule of 7-ACA and the openings of the betalactam link in the molecules of 7-ACA and desacetyl-7-ACA were estimated. It was shown that all the destruction processes were describable by the 1st order equations. A procedure for the calculation of the velocity constants of the above mentioned three processes by changes in the concentration of 7-ACA and desacetyl-7-ACA in the solutions is described.

[Ways of developing the first and second generation biocatalysts for antibiotic production]. / Puti sozdaniia biokatalizatorov pervogo i vtorogo pokoleniia dlia protsessov polucheniia antibiotikov.

Methods for development of bioengineering systems of different types useful in synthesis and transformation of antibiotics are discussed. It was shown that in development of monoenzymatic biocatalysts on the basis of immobilized cells and in preparation of immobilized cultures producing secondary metabolites with enzymological engineering directed action on the cells could be provided which made it possible to establish highly efficient bioengineering systems. Various means for providing the directed action and method for estimation of the carrier-culture interation are proposed. The prospects of using the second generation biocatalysts in improvement of the processes for production of antibiotics are described.

[An evaluation of completely ceramic crowns]. / Een evaluatie van volledig porseleinen kronen.

All-ceramic crowns (Cerestore by Johnson & Johnson) were made on premolars and molars following two procedures: the finishing line was a straight shoulder or a hollow chamber. In vivo replicas were made of the marginal zone on the buccal and on the lingual side. The replicas were studied with scanning electron microscopy. Results showed a relatively large variability in marginal discrepancy in the same crown margin ranging from 12.2 mm to 134.3 mm. In a second series of crowns even discrepancies up to 232.7 mm have been measured. The discrepancy slightly increased after cementation. Several crowns fractured during the try-on session. No crowns fractured after cementation in a six months' interval. The gingiva surrounding the crowns remained healthy. The esthetic results were sometimes poor due to the whitish core not covered by porcelain. This study suggests that the Cerestore crowns are acceptable as a solitary restoration in premolar and molar region but that both esthetics and marginal fit can be improved.

Intraoperative laryngeal nerve monitoring during thyroidectomy and parathyroidectomy: A prospective study.

OBJECTIVES: The aim of this study was to stimulate the recurrent laryngeal nerve during thyroidectomy or parathyroidectomy and to record the muscle responses in an attempt to predict postoperative vocal fold mobility. PATIENTS AND METHODS: Intraoperative recurrent laryngeal nerve monitoring during general anaesthesia was performed by using an electrode-bearing endotracheal tube (nerve integrity monitor EMG endotracheal tube [Medtronic Xomed, Jacksonville, Flo, USA]). Two hundred and fifteen recurrent laryngeal nerves from 141 patients undergoing total thyroidectomy (n=74), hemithyroidectomy (n=63), or parathyroidectomy (n=4) were prospectively monitored. In each case, the muscle potential was recorded after stimulation of the recurrent laryngeal nerve by a monopolar probe. RESULTS: The nerve stimulation threshold before and after dissection that induced a muscle response of at least 100 µV ranged from 0.1 to 0.85 mA (mean 0.4 mA). The supramaximal stimulation intensity was defined as 1 mA. The amplitude of muscle response varied considerably from one patient to another, but the similarity of the muscle response at supramaximal intensity between pre- and postdissection and between postdissection at the proximal and distal exposed portions of the nerve was correlated with normal postoperative vocal fold function. Inversely, alteration of the muscle response indicated a considerable risk of recurrent laryngeal nerve palsy, but was not predictive of whether or not this lesion would be permanent. CONCLUSIONS: Recurrent laryngeal nerve monitoring with a system using surface electrodes is a simple, non-invasive technique that is just as sensitive as monitoring by intramuscular electrodes. Monitoring is helpful for initial nerve identification and is useful to determine nerve function during and after surgery, and to adapt the surgical strategy accordingly.

[Integral criteria of the effectiveness of an enzyme immobilization process]. / Integral'nye kriterii éffektivnosti protsessa immobilizatsii fermentov.

It was found that estimation of the samples of immobilized enzymes and cells by particular characteristics often produces contradictory results. This makes difficult the choice of the best biocatalyst. Integral criteria equally taking into account both the quality of the biocatalysts and the amounts of the native enzyme required for their production are described. Example confirming the advantages of the integral criteria in estimation of large lots of the samples of the biocatalysts are cited.

[Initial indices for calculating the integral criteria of the effectiveness of the enzyme immobilization procedure]. / K voprosu ob iskhodnykh pokazateliakh dlia rascheta integral'nykh kriteriev éffektivnosti protsessa immobilizatsii fermentov.

The possibility of using a simplified model of the kinetics of the enzymatic process catalyzed by the immobilized enzyme for definition of the integral criteria for the efficacy of the immobilization process is theoretically validated. The means for determination of the initial characteristics for these criteria, i.e. the constants of the inactivation rate of the immobilized enzyme and the critical value of the catalyst activity are discussed. The use of the catalyst under the manufacturing conditions at the value lower than the critical one is not advisable.