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Incidence of postpartum endomyometritis following single-dose antibiotic prophylaxis with either ampicillin/sulbactam, cefazolin, or cefotetan in high-risk cesarean section patients.

OBJECTIVE: To assess the efficacy of single-dose antibiotic prophylaxis against postpartum endomyometritis in high-risk cesarean section patients. DESIGN: Patients were administered one of three single-dose antibiotic regimens following umbilical cord clamping after cesarean section delivery. SETTING: Prospective randomized trial at a university-based hospital. PATIENTS: The study evaluated 293 consenting women undergoing cesarean section who had either experienced labor for a duration of > or = 6 hr or rupture of amniotic membranes. MAIN OUTCOME MEASURES: Development of postpartum endomyometritis. RESULTS: The incidence of postpartum endomyometritis was 7/95 (7.4%) following the ampicillin/sulbactam regimen, 14/98 (14.3%) after the cefazolin regimen, and 11/99 (11.1%) after the cefotetan regimen. There was no significant difference in postpartum infection among the three study arms. In addition, the incidence of endomyometritis in the three single-dose study arms was not higher than previously noted in studies where three doses of antibiotic were administered. CONCLUSION: Single-dose antibiotic prophylaxis should replace the standard triple-dose therapy for uninfected women undergoing cesarean section who are at risk for postoperative endomyometritis. Ampicillin/sulbactam, cefazolin, and cefotetan are all reasonable antibiotic choices for single-dose therapy.

Adult↗

A proportional mortality ratio study of workers in a construction equipment and diesel engine manufacturing plant.

The mortality of 461 workers who were employed 10 or more years in a Midwest engine and construction equipment plant was examined, using the method of proportional mortality ratios. Both state and national deaths were used as the standard population. Major exposures in this plant included solvents, cutting oils, and metal fumes and dusts. However, precise exposure data were not available. Among white males, no significant deviations from expected deaths were found. Among black males, significant excess deaths were found for all malignant neoplasms combined, for cancer of the pancreas, and for non-Hodgkin's lymphomas. Proportional cancer mortality ratios produced similar results, although the excess of pancreatic cancer in blacks was only significant among those with 20 or more years of service. Although complete occupational histories were not available, these results may provide hypotheses for future studies of workers in heavy machinery production.

Cross-Sectional Studies↗

An evaluation of pelvic lymphoscintigraphy in the staging of colorectal carcinoma.

Lymphoscintigraphy was used to delineate the lymphatic drainage of the rectum and distal colon in 18 patients with carcinoma of the rectum or sigmoid colon, in four with inflammatory disease of the large bowel and in 20 controls without colorectal pathology. Abdominal imaging was performed after submucosal injection of either 4 mCi 99mTc-antimony sulphide colloid or 0.5 mCi 99mTc-dextran into the rectum through a proctoscope. In nine patients with colorectal carcinoma, abdominal imaging was performed immediately pre-operatively and the excised specimen of large bowel was also imaged in vitro immediately postoperatively. The presence or absence of nodal uptake of radionuclide on abdominal scanning did not discriminate between normal and diseased large bowel, and the extent of nodal uptake demonstrated either by abdominal scans or by in vitro scans of excised specimens bore no relationship to the presence or absence of nodal metastases demonstrated histologically in the cancer patients. Pelvic lymphoscintigraphy as performed in this study has no demonstrable value in the diagnosis or staging of colorectal cancer.

Aged↗

Double-prodrugs of L-cysteine: differential protection against acetaminophen-induced hepatotoxicity in mice.

A series of double-prodrugs of L-cysteine, designed to release L-cysteine in vivo and stimulate the biosynthesis of glutathione (GSH), were synthesized. To evaluate the hepatoprotective effectiveness of these double-prodrugs, male Swiss-Webster mice were administered acetaminophen (ACP) (2.45 mmol/kg (360 mg/kg), intraperitoneally (i.p.)). Prodrug (2.50 mmol/kg, i.p. or 1.25 mmol/kg, i.p., depending on the protocol) was administered 1 h before ACP as a priming dose. A supplementary dose of prodrug (2.5 mmol/kg, i.p. or 1.25 mmol/kg, i.p. depending on the protocol) was administered 0.5 h after ACP. The plasma alanine amino transferase (ALT) values, 24 h after ACP administration were transformed to logs and the 95% and 99% confidence intervals of the log values were plotted and compared for each group. Hepatoprotection was assessed by the degree of attenuation of plasma ALT levels. With these multiple dose schedules, the use of 2% carboxymethylcellulose as vehicle for the prodrugs was found to be detrimental; therefore, the prodrugs were dissolved in dilute aqueous base and the pH adjusted for administration. When a priming dose was given 1 h before ACP followed by a supplementary dose 0.5 h after ACP, only N,S-bis-acetyl-L-cysteine, where both the sulfhydryl and amino groups of L-cysteine were functionalized with the acetyl group, was found to be effective in protecting mice against the hepatotoxic effects of ACP. This suggests that these acetyl groups were rapidly hydrolyzed in vivo to liberate L-cysteine. In contrast, N-acetylation of 2(R,S)-methylthiazolidine-4(R)-carboxylic acid (MTCA) and its 2-n-propyl analog (PTCA), or N-acetylation of 2-oxothiazolidine-4-carboxylic acid (OTCA), reduced the hepatoprotective effects relative to the parent MTCA, PTCA, and OTCA, indicating that the release of L-cysteine in vivo from these N-acetylated thiazolidine prodrugs was metabolically unfavorable. The carbethoxy group, whether functionalized on the sulfhydryl or on the amino group of L-cysteine, or on the secondary amino group of MTCA, appears to be a poor "pro-moiety," since these carbethoxylated double-prodrugs of L-cysteine did not protect mice from ACP-induced hepatotoxicity.

Acetaminophen↗

M1 muscarinic acetylcholine receptors activate extracellular signal-regulated kinase in CA1 pyramidal neurons in mouse hippocampal slices.

Activation of extracellular signal-regulated kinases (ERK) is crucial for many neural functions, including learning, memory, and synaptic plasticity. As muscarinic acetylcholine receptors (mAChR) modulate many of the same higher brain functions as ERK, we examined mAChR-mediated ERK activation in mouse hippocampal slices. The cholinergic agonist carbachol caused an atropine-sensitive ERK activation in the dendrites and somata CA1 pyramidal neurons. To determine the responsible mAChR subtype, we combined pharmacologic and genetic approaches. Pretreatment with M1 antagonists inhibited ERK activation. Furthermore, mAChR-induced ERK activation was absent in slices from M1 knockout mice. ERK activation was normal in slices derived from other mAChR subtype knockouts (M2, M3, and M4), although these other subtypes are expressed in many of the same neurons. Thus, we demonstrate divergent functions for the different mAChR subtypes. We conclude that M1 is responsible for mAChR-mediated ERK activation, providing a mechanism by which M1 may modulate learning and memory.

Animals↗