Infection and antibiotics in the aetiology, prediction and prevention of preterm birth.

Spontaneous preterm labour and delivery is a syndrome comprising diverse pathological pathways that result in labour and delivery before term. It is recognised that multiple pathological processes are involved, and infection has been well studied and firmly established as a cause. Although the molecular mechanisms responsible for this process have been identified, there is a lack of consensus about effective antibiotic intervention. Systematic reviews of the few well conducted studies suggest that antibiotics active against bacterial vaginosis or related organisms (clindamycin) given to appropriate women (those with objective evidence of abnormal genital tract flora), and used early in pregnancy (< 22 completed weeks of gestation) before irreversible inflammatory damage occurs, can reduce the rate of preterm birth. There is a need for well constructed trials to understand the vaginal microbiome and how the different types of maternal immune response influences outcome.

Direct alpha-oxytosylation of carbonyl compounds: one-pot synthesis of heterocycles.

N-Methyl-O-tosylhydroxylamine is an effective reagent for the direct alpha-oxytosylation of carbonyl compounds. The reactions proceed smoothly at room temperature in the presence of both moisture and air and functional group tolerance in the substrate is good. With nonsymmetrical substrates regioselectivity for primary over secondary centers is observed and complete regiospecificity for primary over tertiary centers is obtained. Addition of a bis-heteronucleophile directly to the crude reaction mixture in a one-pot process leads to the corresponding heterocyclic product.

Laparoscopic pelvic lymph node dissection.

Traditionally, cancer of the prostate has been staged by digital exam, ultrasound, CT scan, bone scan, prostatic acid phosphatase (PAP), and prostate specific antigen (PSA) determinations. These methods commonly lead to understaging, resulting in surgical or radiation therapy of questionable benefit. Pathologic staging, even though reliable and accurate, requires laparotomy with its associated morbidity and lengthy hospitalization/recovery period. Following national trends, we have recently introduced the technique of Laparoscopic Pelvic Lymph Node Dissection (LPND) at our institution. In July 1990 we performed the first LPND at CAMC (Memorial Division). This report details our experience with the first three patients treated in this manner and suggest that the procedure can be performed safely, effectively, and with a significant reduction in morbidity, thus allowing the surgeon to obtain an adequate specimen for pathologic staging. Possible cost containment, minimal discomfort, and little scarring are other advantages that appeal to both patients and surgeons alike.

Studies on the biosynthesis of clavulanic acid. III. Incorporation of DL-[3,4-13C2]glutamic acid.

The role of glutamate in clavulanic acid biosynthesis was investigated by feeding DL-[3,4-13C2]glutamate to a Streptomyces clavuligerus fermentation. The DL-[3,4-13C2]glutamate was synthesised by reacting [2-13C]diethylmalonate with O-tosyl-N-benzoyl-[3-13C]dehydroserine ethyl ester, which in turn was synthesised by condensing [13C]ethylformate with N-benzoylglycine ethyl ester. 13C NMR examination of the benzyl clavulanate derived from the fermentation revealed the predicted labelling of carbons 2 and 8 with accompanying 13C-13C spin-spin coupling. Other enrichments and couplings were observed which could be explained by metabolism of the labelled glutamate via the tricarboxylic acid cycle to give further clavulanic acid precursors. These results confirm that glutamate provides the oxazolidine carbon skeleton as predicted by previous experiments.

Studies on the biosynthesis of clavulanic acid. I. Incorporation of 13C-labelled precursors.

The biosynthesis of clavulanic acid was investigated by feeding 13C-labelled precursors to Streptomyces clavuligerus fermentations. The resulting samples of clavulanic acid were isolated as the benzyl ester and were examined by 13C NMR spectroscopy for 13C-enrichment. The results showed that the carbon skeleton of 1,3-13C2-glycerol was incorporated intact into the three beta-lactam carbons of clavulanic acid. Studies with 1-13C-acetate, 2-13C-acetate and 1,2-13C2-acetate indicated that the remaining five carbons of clavulanic acid were probably derived from alpha-ketoglutarate. 1-13C-Propionate and 3-13C-propionate were not metabolised via the same route as glycerol, but were probably converted to succinate, via methylmalonyl CoA, and hence via the tricarboxylic acid cycle to the clavulanic acid precursors.