SUMMARY. Thc most widely used methods for the assay of total bilirubin in serum are based on a coupling reaction with various diazo dyes in the presence of an accelerating agent. The 'direct' reaction, without accelerator, gives a good estimate of the conjugated and protein bound ( 5 ) species of bilirubin only if carefully standardized reaction conditions are used. Enzymatic methods based on bilirubin oxidase appear to give similar results, for both total and direct bilirubin. and through difficult to calibrate, spectrophotometric methods can also give reliable results for total bilirubin at the higher concentrations seen in neonates. More sophisticated HPLC or dry-slide techniques are required for the specific assay of the various conjugated and protein-bound species of bilirubin in serum.

During the clinical trials 8,861 patients have been treated with ciprofloxacin worldwide. 3,822 of the therapeutic courses were valid for analysis of efficacy according to FDA standards. The following dosages were usually administered: UTI: 100 to 500 mg twice daily orally or 100 mg twice daily intravenously; RTI: 250 to 1000 mg twice daily orally or 200 mg twice daily intravenously; septicemia: 200 mg intravenously twice daily; gonorrhea: 250 to 500 mg single tablet orally; all other infections: 500 to 1000 mg twice daily orally or 200 mg twice daily intravenously. Ciprofloxacin was administered to 762 courses of lower RTI, 88 courses of upper RTI, 108 courses of bacteremia, 766 courses of skin structure infection, 142 courses of bone and joint infections, 149 courses of intra-abdominal infections, 33 courses of gastrointestinal infections, 1,633 courses of UTI, 49 courses of pelvic infections, 279 courses of STD, mainly gonorrhea, and three courses of meningitis. The clinical response was resolution in 76%, improvement in 18% and failure in only 6%. Bacteriologic response by all sites evaluable: pathogens were eradicated from 74%, markedly reduced in 2%, persisted in 10%. Relapse occurred in 4% and reinfection was observed in another 6%. The overall response was favourable for 90% of the patients. Drug safety was established on a data base of 8,861 courses worldwide. The following side-effects according to COSTART terminology were observed: digestive 5%, metabolic nutritional 4.6%, central nervous 1.6%, skin 1.4%, hemic and lymphatic 1%, cardiovascular 0.4%, body as a whole 0.4%, urogenital 0.3%, special senses 0.3%, musculo-skeletal 0.1%, respiratory 0.08%. Several courses had more than one reaction. Thus the total incidence of side-effects for the treated patient population was 10.2%. Ciprofloxacin is a highly effective drug and a breakthrough in several areas of medical interest. It is relatively safe and side-effects are usually mild or moderate in intensity and transient.

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By using the continuous culture technique, the transition from aerobiosis to anaerobiosis and its effect on a number of enzymes has been investigated in Escherichia coli K-12. A decrease in the oxygen partial pressure below 28.0 mm of Hg resulted firstly in an increase of the respiratory enzymes (reduced nicotinamide adenine dinucleotide [NADHI oxidase, 2.53-fold; succinic dehydrogenase, 1.4-fold; cytochrome b1, 3.91-fold; and cytochrome a2, 2.45-fold) before the electron transport system gradually collapsed as cytochrome a2, followed by cytochrome b,, succinic dehydrogenase, and finally NADH oxidase dephate aldolase (FDP-aldolase) (6), 0.1 M tris(hydroxymethyl)aminomethane (Tris)-hydrochloride (pH 7.0), 3 mm mercaptoethanol, and 0.45 mm fructose 6-1099 on August 2, 2020 by guest http://jb.asm.org/ Downloaded from 1104

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