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Current scientific findings indicate that environmental factors affect women's health. Specifically, evidence has accumulated on the effects of the environment on reproductive health, cancer, injury, respiratory problems, autoimmune diseases, and other health problems. To review the current state of the science and policies related to women's health and the environment, the Federal Interagency Working Group on Women's Health and the Environment of the Department of Health and Human Services and the Society for Women's Health Research jointly sponsored a conference in 1998 entitled Women's Health and the Environment: Innovations in Science and Policy. The aim of the conference was to provide a forum for scientists to share recent findings, promising avenues of research, methodological barriers, and data gaps about women's susceptibility to environmental agents. The conference generated 22 recommendations for policy, 17 recommendations for communication and training, and 48 recommendations for research to be considered by the federal government. The purpose of this review is to bring to the attention of the scientific community and policymakers the breadth of the women's health implications associated with environmental factors by highlighting key research findings presented at the conference. This review summarizes the current status of science in women's health, it describes relevant activities by the federal government, and it suggests recommendations for future research and policy initiatives in the context of women's health and the environment.

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BACKGROUND: Malfunction of peritoneal catheters due to mechanical outflow problems is an annoying complication in patients undergoing chronic peritoneal dialysis (PD). Correction often involves catheter replacement or revision via laparotomy. METHODS: Twenty-five patients undergoing PD who developed mechanical catheter flow restriction underwent 28 laparoscopic procedures. Preoperative diagnoses were made by contrast catheter radiography and were: catheter sequestration (36%), omental wrap (64%). Pneumoperitoneum was induced after general anesthesia and laparoscopy was performed using a Storz laparoscope. The catheter was then identified and manipulation was attempted using instruments placed percutaneously. RESULTS: In 26 cases (93%), the catheter was freed and function restored. In two cases (7%), adhesions were so numerous and dense that the distal catheter could not be visualized. Four episodes of peritonitis developed subcutaneous leakage of peritoneal fluid which responded to cessation of PD for 2 weeks. Four patients had recurrent occlusions; three of these were managed laparoscopically. Two patients developed late hernias at the site of insertion of the laparoscope. Catheter patency averaged 9.2 months postoperatively. CONCLUSIONS: Laparoscopic revision is a successful technique for salvage of occluded peritoneal catheters.

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Laparoscopic cholecystectomy has changed the treatment of symptomatic gallstones. We present an initial experience with this technique. From March 1990 to March 1991, there were 250 patients who were studied. There were 182 females and 68 males, with most classified as American Society of Anesthesiology Index Class I or II. All procedures were done using electrocautery. There was a definite learning curve for the procedure as evidenced by the duration of the operation. The mean time to perform the procedure was 112 minutes for the first 50 patients and 79 minutes for the last 50 patients. We converted 12 percent of the procedures to an open cholecystectomy for a variety of reasons, the most common being inflammation and adhesions in the triangle of Calot. However, we only had a 4 percent conversion rate in the last 50 patients. There were nine serious complications, with no deaths. The most frequent was a bile leak from the cystic duct stump. Other complications included a pneumothorax, requiring chest tube drainage and an unobserved carcinoma of the stomach. There were no injuries to the common bile duct. The results of our current experience confirm the safety and efficacy of laparoscopic cholecystectomy for the treatment of symptomatic gallstones. The use of electrocautery is safe during laparoscopy and the need for a laser is optional. Laparoscopic cholecystectomy will continue to evolve as more experience is gained and new instruments are introduced.

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The ability of the polymerase chain reaction (PCR) to quantitate expression of mRNA was examined in the present study. The model chosen was expression of the multidrug resistance gene mdr-1/Pgp in two colon carcinoma cell lines which express mdr-1/Pgp at levels comparable to those found in many clinical samples. PCR was utilized to evaluate differences in mdr-1/Pgp expression in the two cell lines after modulation by sodium butyrate. Thus, comparisons were made across a range of mdr-1/Pgp expression as well as comparisons of small differences. The PCR was found to be both sensitive and quantitative. Accurate quantitation requires demonstration of an exponential range which varies among samples. The exponential range can be determined by carrying out the PCR for a fixed number of cycles on serial dilutions of the RNA reverse transcription product, or by performing the reaction with a varying number of cycles on a fixed quantity of cDNA. By quantitation of the difference in PCR product derived from a given amount of RNA from the sodium butyrate treated and untreated cells, the difference in mRNA expression between samples can be determined. Normalization of the results can be achieved by independent amplification of a control gene, such as beta 2-microglobulin, when the latter is also evaluated in the exponential range. Simultaneous amplification of the control and target genes results in lower levels of PCR products due to competition, which varies from sample to sample. The PCR is thus a labor-intensive but sensitive method of quantitating gene expression in small samples of RNA.

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Expression of a multidrug resistance gene (mdr1) and its protein product, P-glycoprotein (Pgp), has been correlated with the onset of multidrug resistance in vitro in human cell lines selected for resistance to chemotherapeutic agents derived from natural products. Expression of this gene has also been observed in normal tissues and human tumors, including neuroblastoma. We therefore examined total RNA prepared from human neuroblastoma cell lines before and after differentiation with retinoic acid or sodium butyrate. An increase in the level of mdr1 mRNA was observed after retinoic acid treatment of four neuroblastoma cell lines, including the SK-N-SH cell line. Western blot (immunoblot) analysis demonstrated concomitant increases in Pgp. However, studies of 3H-vinblastine uptake failed to show a concomitant Pgp-mediated decrease in cytotoxic drug accumulation. To provide evidence that Pgp was localized on the cell surface, an immunotoxin conjugate directed against Pgp was added to cells before and after treatment with retinoic acid. Incorporation of [3H]leucine was decreased by the immunotoxin in the retinoic acid-treated cells compared with the undifferentiated cells. These results demonstrate that whereas expression of the mdr1 gene can be modulated by differentiating agents, increased levels of expression are not necessarily associated with increased cytotoxic drug accumulation.

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Preliminary in vitro studies have been performed to assess the effect of experimental lipid emulsions of varying fatty acid composition on human adipose tissue metabolism. Subcutaneous human adipose tissue was obtained during elective surgery and placed in tissue culture. Physical mixtures of long chain triglyceride (LCT) and/or medium chain triglyceride (MCT) were added to the tissue culture medium so that the final concentration was 400 mg/dl. After a 3-day incubation period the tissue was harvested, placed in buffer and used to determine in vitro production of the prostaglandins prostacyclin I2 (measured as its stable endproduct 6-keto PGF1 alpha), thromboxane A2 (measured as TXB2), and prostaglandin E2. Measurements of the fatty acid profile found in the neutral- and phospholipid fraction of the adipose tissue and fat cell size were also made. The results demonstrate that samples incubated in 100% MCT had the most significant increase in prostaglandin production whereas those incubated in 100% LCT had the most significant decrease in activity of the three prostaglandins assayed, when compared to controls. The addition of LCT to MCT caused a dose-related decrease in adipose tissue prostaglandin production. There were no significant changes in the profile of fatty acids found in the neutral- or phospholipid fraction of adipose tissue. The results indicate that the relative level of MCT/LCT incubated with human adipose tissue has a significant effect on prostaglandin production.

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Tetanus, which occurs usually as a complication of minor trauma, has also been reported following elective and emergency surgical procedures, particularly those involving the gastrointestinal tract. Early diagnosis of tetanus in the postoperative period is difficult, requiring a high index of suspicion. The possibility of tetanus should be considered in any nonimmunized postoperative patient who develops crampy abdominal pain, fever, and abdominal wall rigidity. Adequate tetanus immunoprophylaxis is essential for all patients undergoing gastrointestinal surgery.

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A case of inguinal hernia repair at the time of repeat cesarean section is described. The success of the repair and the patient's uneventful recovery suggest that these procedures can be combined conveniently and safely in select cases.

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Hypocalcemia is common in toxic-shock syndrome (TSS); however, the role of magnesium deficiency in TSS remains to be defined. A previously healthy nurse on no maintenance medication developed hypocalcemia and hypomagnesemia in association with characteristic TSS, presenting with fever, headache, mental confusion, erythroderma, watery diarrhea and abnormal liver functions tests. Coagulase-positive Staphylococcus aureus as well as staphylococcal toxin were isolated from the cervix. Calcitonin levels were normal. Serum magnesium and calcium levels were low at presentation and later intravenous magnesium loading demonstrated a marked rise in 1,25-(OH)2 vitamin D and parathormone (PTH), with high retention of the infused load consistent with functional hypoparathyroidism. Intracellular magnesium deficiency may be a significant factor in the pathogenesis of hypocalcemia in TSS and warrants routine clinical consideration.

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The observed homology between G-proteins which regulate adenylate cyclase and ras proteins and the suggested role of ras in the regulation of adenylate cyclase in yeast prompted us to examine the regulation of adenylate cyclase in three cell lines: (i) NIH 3T3 cells, (ii) NIH 3T3 cells transformed by high levels of the normal rasH gene product and (iii) NIH 3T3 cells transformed by a mutated rasH gene product. We found that the regulation of adenylate cyclase by G-proteins is identical in the three cell lines, although the response of the transformed NIH 3T3 cells to agonists is strongly attenuated. Our data suggest that mammalian ras products do not interact directly with adenylate cyclase, although their increased expression may indirectly inhibit the interaction of adenylate cyclase stimulatory receptors with G-proteins.

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We studied 96 patients subjected to elective proximal gastric vagotomy for intractable duodenal ulceration. Dysphagia was a frequent finding and occurred in 32 percent. It appeared in the immediate postoperative period and usually lasted for 1 to 2 months without any abnormalities in lower esophageal sphincter function. In five patients, dysphagia was severe and, although transient, was associated with changes in lower esophageal function simulating those observed in achalasia. The mechanism of these motor abnormalities is probably due to a reversible neuromuscular dysfunction of the lower esophageal sphincter.

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Binding sites having the properties of high-affinity receptors for activated alpha 2-macroglobulin (alpha 2M) have been purified over 100-fold from membranes of spontaneously transformed NIH-3T3 cells (J. A. Hanover, S.-y. Cheng, M. C. Willingham, and I. H. Pastan [1983] J. Biol. Chem. 258, 370-377). To identify the molecular species involved in high-affinity binding, the solubilized receptor has been purified 500-fold by conventional procedures and further purified by affinity chromatography. After radioiodination of the 500-fold-purified preparation, the detergent-solubilized extract was applied to alpha 2M-Sepharose and an 85,000 +/- 5000 Mr species was selectively retained by the column. Binding of the 85,000 +/- 5000 Mr species to the affinity resin was inhibited by EDTA and by excess alpha 2M. Elution from the affinity column could be accomplished with bacitracin, a competitive inhibitor of alpha 2M binding, or with EDTA. Consistent with the previously reported characteristics of the high-affinity alpha 2M receptor, the 85,000 Mr species bound much more efficiently to methylamine-activated alpha 2M-Affigel than to alpha 2M-Affigel which had not been amine-activated. The present data suggest that a protein with a subunit Mr of 85,000 +/- 5000 may represent a component of the high-affinity alpha 2M receptor present on cultured fibroblasts.

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Evaluation of pancreatic duct pressure may be a pathogenetic mechanism in the development of acute pancreatitis. In this investigation the effect of bilateral cervical vagisection as well as the introduction of alcohol into the stomach and duodenum on pancreatic pressures in the main duct were studied in the dog. Bilateral vagisection resulted in decrease in pancreatic duct pressure. Intragastric alcohol elevated and intraduodenal alcohol depressed pancreatic ductal pressures before but had no effect after vagisection. These studies suggest regulation of pancreatic duct pressures by short as well as long nerve reflexes.

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The physiologic characteristics of the biliary tract cannot be adequately evaluated without analyzing both the resistive and compliant characteristics of the common bile duct. We studied the compliance of the common bile duct in six anesthetized dogs. Saline was infused continuously while pressure was monitored with the sphincter of Oddi intact and tied off. The mean opening pressure of the sphincter was 8.45 cm H2O. In the obstructed duct, compliance was found to decrease with increasing pressure. The mean compliance for all five dogs at low pressures (below opening pressure) was 11.0 X 10(-2) microliter/cm H2O/mm2, and at high pressures was 1.7 X 10(-2) microliters/cm H2O/mm2. Changes in flow rate did not affect the compliance of the duct. Although the compliance of the duct was found to be nonlinear overall, it was nearly linear in both the high- and low-pressure ranges.

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