Structural studies on tazobactam.

Tazobactam (3, C10H12N4O5S) is an effective inhibitor of bacterial beta-lactamases. It crystallizes with unit cell dimensions a = 10.230 (2) A, b = 14.396 (2) A, and c = 17.291 (2) A in space group P2(1)2(1)2(1). Compared to the related inhibitor sulbactam (2), which lacks the triazole ring, crystalline tazobactam exhibits very similar beta-lactam geometry and the same S(1) envelope conformation of the thiazolidine ring. However, in both independent molecules of 3 a triazole ring nitrogen atom accepts an intermolecular hydrogen bond; similar interaction by this moiety of 3 with a hydrogen-bond donor on the enzyme, which is impossible for 2, could account for its enhanced inhibitory power. Semiempirical molecular orbital calculations show pronounced negative potential there. Molecular mechanics supports the hypothesis that the carboxyl group can rotate freely and the triazole ring can "flip".     

Studies on corneal penetration ofp-hydroxybenzoic acid esters

Corneal permeability of variousn-alkylp-hydroxybenzoates (parabens) was studiedin vitro using excised rabbit corneas, and the effect of lipophilicity of parabens on the corneal permeability was also investigated. Permeability coefficients were obtained from the least-square linear regression after the steady state had been reached. Lipophilicity of parabens was calculated by distribution coefficients determined in octanol-S \(12_\phi [\kern-0.15em[ \) rensen’s buffer solution (pH 5.0). The relationship between lipophilicity and corneal permeability of parabens was not linear, but the optimum lipophilicity for the maximum permeation was found. The influence of tween 80 on corneal permeability of methyl and butylparaben was not significant.     

Integrating providers into quality improvement: a pilot project at one hospital

Brigham and Women's Hospital initiated a study of the quality of care centering on self-reporting of potential medical injuries by providers. The goal of the study is to decrease the incidence of such injuries through a continuous quality methodology that integrates providers into the identification phase and incorporates all hospital employees in the development of new practices. This article provides an overview of the investigation methodology and discusses the conceptual relationships between clinical epidemiological analyses and industrial quality improvement.     

Decreased amniotic fluid index in term pregnancy. Clinical significance.

In a study of 331 term pregnancies a four-quadrant technique was used to obtain amniotic fluid index measurements, and the results were compared with the current widely used single-pocket measurement. In contrast to the "2-cm rule," the amniotic fluid index measurements consistently demonstrated higher sensitivity in predicting poor fetal outcome with no decrease in specificity. It was noted that pregnancies with an index of < or = 8 cm showed higher incidences of meconium staining, cesarean delivery for fetal distress, abnormal fetal heart rate monitoring and Apgar scores of < or = 7 or less at one minute.     

Doppler velocimetry of intraplacental fetal arteries

Doppler velocimetry of the umbilical and intraplacental fetal arteries was studied by color flow mapping in 39 normal pregnancies. The systolic-diastolic ratio (S/D) and pulsatility index of the intraplacental fetal artery downstream to the umbilical artery decreased significantly with advancing gestational age, and its S/Ds were persistently lower than those of the umbilical artery. The difference in the S/D between the umbilical artery and its intraplacental downstream branches decreased with advancing gestational age and approached zero as the pregnancy progressed to term. We conclude that intraplacental fetal arteries, possibly fetal arteries in main stem villi, can be imaged by color flow mapping and that there is a significant "resistance gradient" between the intraplacental fetal artery and the umbilical artery. Intraplacental fetal artery velocimetry using color flow mapping may give further insights into the umbilical-placental circulation.     

Comparison of mononuclear cell proteins and plasma proteins before and during parturition by two dimensional electrophoresis.

Two dimensional electrophoresis is a technique whereby protein sources are organized by molecular weight and electrical charge on a polyacrylamide gel. To detect changes that may be associated with the onset of parturition, we compared electrophoresis patterns of mononuclear cell proteins and plasma proteins before and during active labor. Mononuclear cells and plasma were obtained from 5 pregnant volunteers. It appears that A-1 apolipoprotein, identified by Western Blot analysis, is increased in mononuclear cells during active labor. Conversely, a decrease in the concentration of A-1 apolipoprotein was seen in plasma during parturition. These "normal" protein patterns can now be compared with those observed in pathologic conditions including preterm labor and may allow early detection of disease by protein abnormalities before clinical signs and symptoms develop.     

Medical and dental implications of cocaine abuse

With the ever-increasing supply of cocaine and use of "crack," the potent and smokeable form of cocaine, the dangers of cocaine abuse, with its high morbidity and mortality, have become recognized. Oral and maxillofacial surgeons may frequently and unknowingly be treating patients who use cocaine, and, therefore, they must be educated about cocaine-related problems and be prepared to deal with the complications. This article discusses the nature of cocaine, its pharmacology, systemic affects, the oral manifestations of cocaine abuse, and recommended clinical management of the patient.