Ritodrine hydrochloride infusion in pregnant baboons. I. Biophysical effects

Pulmonary edema is a potentially fatal complication of beta-sympathomimetic therapy for premature labor. Isolated case reports have supported either primary pulmonary capillary membrane injury or left ventricular failure as the cause of pulmonary edema. By simultaneously monitoring cardiac function and extravascular lung water in six control and six ritodrine hydrochloride-treated pregnant baboons, we attempted to define this pathophysiology. The pulmonary capillary wedge pressure increased in treated animals, reaching significance at 16 hours of ritodrine treatment (p less than 0.0001) concurrent with the maximum increase in cardiac index (p = 0.02). Treated animals also retained 61% of intravenously administered fluids compared with 23% in untreated control animals (p less than 0.002). There were, however, no significant differences between groups in extravascular lung water, central venous pressure, or pulmonary artery pressure. Chest radiographs and arterial blood gas analysis were also comparable between ritodrine-treated and control animals. Fluid retention and elevated hydrostatic pressure are postulated as the etiology of beta-sympathomimetic-induced pulmonary edema. There was no evidence to support a primary pulmonary capillary membrane injury by ritodrine.     

Uterine contraction pressures with oxytocin induction/augmentation

Uterine contraction pressures were quantified (in Montetevideo units) in 109 women at term gestation who received oxytocin for induction or augmentation of labor and whose labor resulted in a spontaneous vaginal delivery. Newborn five-minute Apgar scores were greater than or equal to 8 in 108 of the 109 neonates, and no immediate neonatal morbidity was attributable to the oxytocin stimulation of labor. Women undergoing oxytocin induction had significantly greater uterine contraction pressures than those with oxytocin augmentation. During oxytocin induction 91% of women achieved at least 200 to 224 Montevideo Units and 40% at least 300 Montevideo units versus 77 and 7.7%, respectively, during augmentation of labor. With concurrent fetal monitoring these levels of uterine activity should be sought before consideration of a cesarean delivery because of presumed cephalopelvic disproportion or failure to progress.     

Early repair of an external sphincter ani muscle and rectal mucosal dehiscence

Little information is available to assist in the management of a dehiscence subsequent to a fourth degree episiotomy repair. Delayed repair of the external sphincter ani muscle and rectal mucosa may result in weeks or months of disability and inconvenience for these women. A series of eight women is presented whose fourth degree episiotomy repair dehiscence was managed by early puerperal repair. The details of wound and bowel preparation, the operative technique, and postoperative care are described. Because all eight women had a successful repair, the authors believe that early surgical correction is an acceptable treatment for this puerperal complication.     

Development of esophageal metaplasia and adenocarcinoma in a rat surgical model without the use of a carcinogen

In order to establish an animal model for studying the cause and prevention of esophageal adenocarcinoma (EAC) and its frequent precursor, Barrett's esophagus (BE), factors affecting the pathogenic processes were investigated in an esophagoduodenal anastomosis model with rats. Experiments by us and others have shown that surgical treatment produced reflux esophagitis with cell hyperproliferation, but not EAC. Additional treatment with a carcinogen has been shown to be necessary for the development of EAC, squamous cell carcinomas (SCC) or EAC/SCC mixtures. We found that the surgically treated animals developed anemia due possibly to reduced iron absorption. When the operated animals were supplemented with iron, EAC occurred at a high rate (73%) after 30 weeks, and treatment with N'-nitrosonornicotine did not enhance the rate of tumorigenesis. Treatment with carcinogen, however, induced SCC in the group of rats killed after 22 weeks. The results suggest that iron overload, which is known to cause oxidative damage, is an enhancing factor for adenocarcinogenesis. The pathogenesis of EAC in the iron-supplemented, non-carcinogen treated group resembles human esophageal adenocarcinogenesis in many features. All the BE was the specialized type with goblet cells (containing sialomucin or sulfomucin) and columnar cells (containing acid or neutral mucin) as well as an incompletely developed brush border. Almost all of the BE was located at the bottom of the esophagus and was continuous with the duodenal mucosa; dysplasia became more frequent at later time points. All of the cancers were well-differentiated mucinous EAC, and most of the EAC had an adjacent area of BE with dysplasia. The results are consistent with the proposed human sequence for pathogenic events of BE progression to 'BE with dysplasia' and then to EAC. Esophagoduodenal anastomosis and iron treatment in rats produces a high rate of BE and EAC which are morphologically similar to human BE and EAC; this may be a useful animal model to study the development and prevention of EAC in humans.      

Effects of the carcinogen, acrylonitrile, on forestomach cell proliferation and apoptosis in the rat: comparison with methacrylonitrile

Acrylonitrile (AN) and methacrylonitrile (MAN) are two major industrial nitriles used in the production of plastics and acrylic fibers. Whereas AN is a potent acute toxin and carcinogenic in rats, little is known regarding MAN. Current work is part of an overall effort designed to assess the potential toxicity/carcinogenicity of MAN. The present study compares the ability of the two chemicals to induce epithelial proliferation and apoptosis in the forestomach (FS; a target of AN carcinogenicity), liver and glandular stomach (non-targets of AN carcinogenicity) of male F344 rats. AN was administered to rats daily, by gavage, for 6 weeks, at 0.43 and 0.22 mmol/kg. MAN was administered at 0.87 and 0.43 mmol/kg. Both AN and MAN induced a dose-dependent increase in epithelial cell proliferation in the FS of male F344 rats as determined by bromodeoxyuridine (BrdU) incorporation into DNA. In contrast, AN, but not MAN caused a dose-dependent increase in the thickness of the forestomach squamous mucosa. This increased thickness (hyperplasia) was reflected by an increase in the number of total epithelial cells per unit length of mucosa. At doses of AN and MAN which induced a 2.3-fold increase in BrdU incorporation, apoptosis was 5- and 18-fold greater than controls, respectively. Although both MAN and AN caused a similar increase in cell proliferation, the relatively more prominent increase in the apoptotic index of the squamous epithelium of rats exposed to MAN may explain the lack of a detectable increase in the thickness of the mucosa compared to that seen with AN. The disruption of the balance between FS mucosal cell proliferation and apoptosis in favor of a net increase in the number of FS epithelial cells per unit length may contribute to the carcinogenicity of AN. In conclusion, present work demonstrated that AN selectively induced a net enhancement in FS cell proliferation, a site of its carcinogenicity. On the other hand, MAN-induced FS cell proliferation was associated with a parallel increase in apoptosis. The relatively greater increase in apoptosis by MAN may have compensated for the increase in FS mucosal cell proliferation and the lack of observable change in the FS thickness.      

Human tubal fluid: production, nutrient composition and response to adrenergic agents

Vascularly perfused Fallopian tubes have been used to study the formation and composition of human tubal fluid and the response to adrenergic agents. An artery serving the tube was cannulated and perfused with Medium 199 supplemented with bovine serum albumin (BSA) and antibiotics. A second cannula was attached to the fimbriated end for native tubal fluid collection. The preparation was viable for up to 2 h. Tubal fluid was only obtained in tubes removed in the proliferative and early secretory phases of the ovarian cycle. Isoproterenol (1 mM) added to the perfusate stimulated fluid production, whereas dibutyryl cyclic AMP (1 mM) reduced fluid formation by 66%. Glucose, pyruvate and lactate concentrations in tubal fluid, measured by microfluorescence assays, were 1.11, 0.14 and 5.4 mM respectively. The concentrations of 17 amino acids in tubal fluid were measured by high performance liquid chromatography following fluorescence derivatization. Arginine (0.19 mM) > alanine (0.11 mM) > glutamate (0.09 mM) were present in highest concentration in all phases of the cycle. All 17 amino acid concentrations in tubal fluid were below those in the vascular perfusate. These data provides the basis for a culture medium whose composition mimics the physiological environment to which early human embryos are exposed.      

Use of PGMY primers in L1 consensus PCR improves detection of human papillomavirus DNA in genital samples

The novel PGMY L1 consensus primer pair is more sensitive than the MY09 and MY11 primer mix for detection and typing with PCR of human papillomavirus (HPV) DNA in genital specimens. We assessed the diagnostic yield of PGMY primers for the detection and typing of HPV by comparing the results obtained with PGMY09/PGMY11 and MY09/MY11/HMB01 on 299 genital samples. Amplicons generated with PGMY primers were typed with the line blot assay (PGMY-line blot), while HPV amplicons obtained with the degenerate primer pool MY09/MY11/HMB01 were detected with type-specific radiolabeled probes in a dot blot assay (standard consensus PCR test). Cervicovaginal lavage samples (N = 272) and cervical scrape samples (N = 27) were tested in parallel with both PCR tests. The PGMY-line blot test detected the presence of HPV DNA more frequently than the standard consensus PCR assay. The concordance for HPV typing between the two assays was 84.3% (214 of 255 samples), for a good kappa value of 0.69. Of the 177 samples containing HPV DNA by at least one method, 40 samples contained at least one HPV type detected only with PGMY-line blot, whereas positivity exclusively with the standard consensus PCR test was found for only 7 samples (P < 0.001). HPV types 45 and 52 were especially more frequently detected with PGMY than MY primers. However, most HPV types were better amplified with PGMY primers, including HPV-16. Samples with discordant results between the two PCR assays more frequently contained multiple HPV types. Studies using PGMY instead of MY primers have the potential to report higher detection rates of HPV infection not only for newer HPV types but also for well-known genital types.     

Re: Frisch & Simonson. Non-therapeutic male circumcision in infancy or childhood and risk of human immunodeficiency virus and other sexually transmitted infections: national cohort study in Denmark

European Journal of Epidemiology -     

Pancreatic neoplasms: how useful is evaluation with US?

The usefulness of ultrasonography (US) in the evaluation of pancreatic neoplasms was assessed in 51 patients. Indications for US included jaundice (n = 19), pain (n = 16), weight loss and anorexia (n = 4), clinically palpable mass (n = 3), bleeding in the upper gastrointestinal tract (n = 1), and gastric outlet obstruction (n = 1). Three patients were investigated because of a previous abnormal US examination; in four the mass was an incidental observation. Sonograms were interpreted without knowledge of results from other procedures. Pancreatic masses were detected in 50 patients. Biliary and pancreatic duct obstructions were seen in 29 and 27 patients, respectively. Liver metastases were identified in 16 patients and missed in three that were not detected with either US or computed tomography. Vascular involvement was predicted in 12 patients and missed in four, while lymphadenopathy was seen in 16 and missed in five. Thirty-one cases of unresectable disease were correctly predicted with US. Resectability was not as accurately determined; only seven of 19 "resectable" lesions were successfully removed. US is an effective tool in the detection and preoperative evaluation of pancreatic malignancy.