Pyrrolo[2,3-d]pyrimidines and pyrido[2,3-d]pyrimidines as conformationally restricted analogues of the antibacterial agent trimethoprim.

Conformationally restricted analogues of the antibacterial agent trimethoprim (TMP) were designed to mimic the conformation of drug observed in its complex with bacterial dihydrofolate reductase (DHFR). This conformation of TMP was achieved by linking the 4-amino function to the methylene group by one- and two-carbon bridges. A pyrrolo[2,3-d]pyrimidine, a dihydro analogue, and a tetrahydropyrido[2,3-d]pyrimidine were synthesized and tested as inhibitors of DHFR. One analogue showed activity equivalent to that of TMP against DHFR from three species of bacteria. An X-ray crystal structure of this inhibitor bound to Escherichia coli DHFR was determined to evaluate the structural consequences of the conformational restriction.

Surveillance for postoperative infections in outpatient gynecologic surgery.

Postoperative infection rates were determined for gynecologic outpatient surgical procedures performed in a traditional operating room environment and a separate, recently opened, surgicenter within the same hospital. Infections were self-reported by attending surgeons responding to computer-generated line listings of their recent surgical procedures. Responses were obtained on 97.9% (612/625) of women having surgery in the operating room and 99.5% (629/632) of women with surgicenter procedures. The overall infection rate for reported women was 0.9% (11/1,241). The difference between operating room and surgicenter rates was not statistically significant. Postoperative infections occurred in 2.5% (3/118) of diagnostic laparoscopies with tubal lavage and 1.4% (3/214) of voluntary abortions by dilatation and evacuation and curettage (D&E&C). The five other infections were scattered among the remaining 25 procedure categories. Ten of the 11 infections were limited to the "clean-contaminated" wounds. No serious or life-threatening infections were encountered. The computer-assisted surveillance system worked well and was easily incorporated into the existing infection surveillance system. The degree of ascertainment of postoperative wound infections is unknown due to reliance on physician self-reporting. However, no patients requiring readmission for infection went unreported by the attending surgeons.

Evidence for multiple muscarinic receptor subtypes in human brain.

Pirenzepine, a compound with selective antimuscarinic activity, was used to distinguish muscarinic acetylcholine receptor subtypes in normal human brain. Hill coefficients and IC50 values derived from the inhibition of specific [3H]L-quinuclidinyl benzilate receptor binding suggest the presence of two muscarinic binding sites, differing both in affinity for pirenzepine and in tissue distribution.

Biliary tract operations: a personal series.

A personal series of 600 consecutive operations on the gallbladder and bile ducts is reported, along with the clinical and radiographic findings, complications, and mortality. It can be concluded that surgical treatment of gallstone disease can be carried out with a high degree of preoperative accuracy in the diagnosis and with relative safety. Death can occur in longstanding, neglected, or complex disease in the elderly or diabetic patient.