A Homogeneity Test for Follow-up Studies

A statistical method is presented for detecting random variationin the transition probabilities of certain simple, discrete-timeMarkov chains that have been found useful for modelling follow-upstudies.     

Interprofessional education in medical school

The opinions of entering medical students regarding interprofessional education (IPE), and their reasons, are described in this article. More female than male students favour IPE, 49 as compared to 25%. Students who endorse IPE give different reasons for their position than students who oppose it. The former group refer to increased communication and respect among health professionals, increased knowledge about mutual roles and function, greater equality among members of the health team and improved patient care. The opposing group fear that IPE would lower the quality of education by increasing class size and slow the pace of instruction to accommodate students with limited scientific backgrounds. Students also protest against having to study irrelevant subjects and acquire irrelevant skills. The opposing group is concerned primarily with IPE's effect on medical students; the group in favour is concerned more with the effect on patients and interprofessional relations. It seems that opinions about IPE are part of a basic attitudinal structure that medical students bring with them when they enter medical school. The implications for IPE in medical school are discussed.     

Experiments on the protection of the thioether in methionine

The decrease in the solubility of peptides when their methionine residues are replaced by methionine sulfoxides prompted the exploration of an alternative approach to the protection of the thioether in methionine side chains. Alkylation of tert.-butyloxycarbonyl methionine p-nitrophenyl ester with methyl p-toluenesulfonate yielded the crystalline derivative of methionine S -methyl p-toluenesulfonate which could be incorporated into peptide chains. Alternatively, methionine S -methyl p-toluenesulfonate (Mmt) residues could be generated by the action of methyl p-toluenesulfonate on methionine containing peptides. The protecting group remained intact under the conditions of aminolysis and ammonolysis commonly used in peptide synthesis, and it was unchanged after the removal of other blocking groups with trifluoroacetic acid or diethylamine. On treatment with hydrobromic acid in acetic acid the toluenesulfonate anion was replaced by bromide ion, while hydrogenation resulted in the decomposition of the modified methionine side chain. In the process of deprotection Mmt residues could be smoothly converted to methionine residues by thiolysis. Thus, the protecting group functioned well in several respects but an increase in solubility (in dimethylformamide) on alkylation was observed only in a part of the peptide derivatives tested. Therefore, the value of the new approach for the protection of the methionine side chain in peptide synthesis remains to be established.     

Biliary antibody response in rats infected with rodent Giardia duodenalis isolates

Using a sensitive ELISA, specific serum and bile anti-Giardia IgM and IgA responses were studied in rats infected with two strains of Giardia duodenalis: a rat isolate which produces a chronic infection and a mouse isolate which produces a self-limiting infection. Paired samples of serum and bile were collected from groups of DA (RT1avl) rats at various times during primary and secondary infections. Antibody responses to both organisms were similar. Only IgA anti-Giardia antibodies were detected in bile whereas both IgM and IgA antibodies were detected in serum. Biliary IgA antibody titres increased throughout the course of the primary infection and remained at high levels for at least 10 weeks. Biliary IgA titres increased 16-fold during the secondary infection with both isolates. Serum IgA anti-Giardia titres also increased but more slowly than the titres in bile. Serum IgM antibody responses were observed against both organisms during the primary and secondary infections. Trophozoites harvested from the intestinal lumen during primary infections were examined for surface-bound IgA by immunofluorescence microscopy. IgA was detected on 3% of trophozoites on day 7 after infection but on over 70% of trophozoites by the 10th day. The data demonstrate the occurrence of a secretory IgA immune response in rats infected with both G. duodenalis isolates, some of which is directed against surface antigens of the trophozoites.     

Coupling in absence of tertiary amines:

Highly acid sensitive amine protecting groups, such as the triphenylmethyl or the biphenylylisopropyloxycarbonyl group, are cleaved by the N-protected carboxyl component particularly if deprotection is carried out in trifluoro-ethanol. It was also found possible to apply certain activated derivatives of the carboxyl component (symmetrical anhydrides and 2,4-dinitrophenyl esters) for deblocking and concurrent acylation in the same solvent.     

Comparison of two techniques used to collect normal and motile sperm

To improve the quality of sperm for intra-uterine insemination (IUI) or in-vitro fertilization (IVF) swim-up (SU) and migration-sedimentation (MS) methods were compared, for the selection of morphologically normal and motile sperm. In 74 patients consulting for couple infertility, it was shown that MS gave a better yield of motile sperm than did SU. An improvement in morphology and motility was achieved, especially in asthenospermia (motility less than 40%) and/or teratospermia (normal shape less than 40%). The percentage of midpiece and tail abnormalities was lowered by the MS technique. It is proposed that the MS method be used for IUI and IVF, adapting the number of tubes to the initial sperm concentration.     

Coupling in the absence of tertiary amines

In order to avoid base catalyzed side reactions during coupling, attempts were made to render superfluous the addition of tertiary amines to the reaction mixture. Weak acids were applied for the removal of acid labile protecting groups. Acetic acid and other carboxylic acids were considered unsuitable for this purpose because the resulting salts could be the cause of chain termination in the next coupling step. Pentachlorophenol and 2,4-dinitrophenol cleaved the Bpoc, Nps and Trt groups but more practical rates were reached with solutions of 1-hydroxybenzotriazole (HOBt) in trifluoroethanol, in acetic acid, or in a mixture of phenol and p-cresol. In addition to acidolysis, HOBt salts of amino components could also be obtained through hydrogenolysis of the Z group or thiolysis of the Nps group in the presence of HOBt, or by the displacement of acetic acid from acetate salts with HOBt. Acylation of HOBt salts of amino components with symmetrical or mixed anhydrides or with active esters did not require the addition of tertiary amine.