Substrate inhibition of beta-lactamases, a method for predicting enzymatic stability of cephalosporins

Selected cephalosporins, including cefamandole, cephaloridine, cephaloglycin, and cefoxitin, were examined for their ability to inhibit the enzymatic activity of and act as substrates for beta-lactamases produced by Enterobacter cloacae and Staphylococcus aureus. Enzyme inhibition was determined by Michaelis-Menten kinetic measurements and by a spot plate assay using a chromogenic substrate (Glaxo compound 87/312). These two methods provide comparable estimates of kinetic parameters. Inhibition of beta-lactamase, as measured by these two methods, was generally found to correlate with resistance to hydrolysis and is proposed as a preliminary method of assessing susceptibility of cephalosporins to beta-lactamase hydrolysis. Four 7-alphaOCH(3), 7-alphaH cephalosporin analogue pairs were also examined. The presence of the 7-alphaOCH(3) substituent invariably resulted in reduced susceptibility to enzymatic hydrolysis, regardless of the other C7 substituent. The 7-alphaOCH(3) compounds were also better inhibitors than were their 7-alphaH analogues, with the exception that 7-alphaOCH(3) compounds having C7 adipic acid substituents were less inhibitory to the S. aureus enzyme than were the corresponding 7-alphaH analogues. Response of these two enzymes to 7-alphaOCH(3) and 7-alphaH cephalosporins suggests that beta-lactamase hydrolysis of these compounds involves attack at the alpha side of the betalactam ring.     

Identification of early glaucoma cases with the scanning laser ophthalmoscope

PURPOSE: This study aimed to define the confocal laser scanning ophthalmoscope (Heidelberg Retina Tomograph [HRT]) parameters that best separate patients with early glaucoma from normal subjects. STUDY DESIGN: A cross-sectional study. PARTICIPANTS: A total of 80 normal subjects and 51 patients with early glaucoma participated (average visual field mean deviation = -3.6 dB). INTERVENTION: Imaging of the optic nerve head with the HRT and analysis using software version 1.11 were performed. MAIN OUTCOME MEASURES: The relation between neuroretinal rim area and optic disc area, and cup-disc area ratio and optic disc area, was defined by linear regression of data derived from the normal subjects. The normal ranges for these two parameters were defined by the 99% prediction intervals of the linear regression between the parameter and optic disc area, for the whole disc, and for each of the predefined segments. Normal subjects and patients were labeled as abnormal if the parameter for either the whole disc or any of the predefined segments was outside the normal range. The sensitivity and specificity values of the method were calculated. RESULTS: The highest specificity (96.3%) and sensitivity (84.3%) values to separate normal subjects and those patients with early glaucoma were obtained using the 99% prediction interval from the linear regression between the optic disc area and the log of the neuroretinal rim area. Similar specificity (97.5%) and lower sensitivity (74.5%) values were obtained with the 99% prediction interval derived from regression between the disc area and cup-disc area ratios. Poor separation between groups was obtained with the other parameters. CONCLUSIONS: The HRT, using the technique of linear regression to account for the relationship between optic disc size and rim area or cup-disc area ratio, provides good separation between control subjects and patients with early glaucoma in this population.     

Persistent fetal circulation: an evolving clinical and radiographic concept of pulmonary hypertension of the newborn

The roentgenographic presentations of 11 newborn infants with hypoxemia secondary to pulmonary vasospasm and subsequent right-to-left shunting of blood through the foramen ovale and/or ductus arteriosus (persistent fetal circulation) are described (P. F. C. Syndrome). One infant had radiographically normal lungs, while ten had pulmonary parenchymal abnormalities including hyaline membrane disease [4], meconium aspiration syndrome [4], or an ill defined pattern of retained lung fluid [2]. The roentgenographic appearance of the lungs, however, was discordant with the severe hypoxemia observed in most. Heart size was variable but some degree of cardiomegaly was commonly present. Tolazoline, a potent vasodilator, was useful diagnostically and may have resulted in increased survival. An expanded clinical and roentgeonographic concept of the PFC syndrome is suggested.     

Ascorbic acid stimulates chloride transport in the amphibian cornea

The cornea of the toad, Bufo marinus, actively transports chloride from the endothelial to the epithelial surface. This transport process has been related to the maintenance of the normal transparency of the cornea. Ion transport, as evidenced by the short-circuit current (SCC), is markedly stimulated by physiologic concentrations of ascorbic acid. Measurement of the unidirectional fluxes of 36Cl and 22Na shows that the increase in SCC is due primarily to a stimulation of the active transport of chloride.