Small bowel injury in gastroschisis: relation to fetal presentation

The study presented here attempts to assess the cost savings attributable to having an on-site corporate medical clinic. For a period of 4 months, employees using the clinic were surveyed regarding: (1) whether they would have used an outside doctor if the corporate medical department clinic were not available, and (2) how many days per year they estimated that they came to work because there was an on-site medical center when they would otherwise have stayed at home. The results indicated that, on average, employees who used the facility saved 3.3 days of absenteeism. That total cost savings was calculated to be $499,212 per year. In addition, 69% of employees indicated that they would have sought attention elsewhere, suggesting that the presence of an on-site medical center does not induce demand. The findings concerning the hidden savings brought about by an on-site medical center are also discussed.     

Human papillomavirus infection in squamous cell carcinoma of the vulva, in various synchronous epithelial changes and in normal vulvar skin

In patients with inferior vena cava (IVC) injuries, predictors of survival are investigated. From 1987 to 1995, 27 IVC injuries were identified among 514 patients with vascular trauma. The ability of clinical determinants to predict survival were retrospectively assessed. IVC injuries occurred in 7 females and 20 males (mean age, 27.7 +/- 2.5 years) from both blunt (n = 14) and penetrating (n = 13) trauma. The mean revised trauma score was 10.2 +/- 0.6. Injuries were treated by primary repair (n = 22), ligation (n = 4), or prosthetic grafting (n = 1). Thirteen patients died (48%), 10 within 12 hours of admission. Suprahepatic (n = 2), retrohepatic (n = 12), suprarenal (n = 1), and infrarenal (n = 12) injuries were associated with 100, 67, 100, and 20 per cent mortality, respectively. Blood transfusions (16 +/- 4 vs 23 +/- 4 units), coagulation factor replacement (7 +/- 2 vs 7 +/- 2 units), and electrolyte solution use (8.6 +/- 1.4 vs 9.6 +/- 1.4 L) were similar among survivors and nonsurvivors. Four complications [venous hypertension (n = 2), IVC thrombosis (n = 1), and pulmonary embolus (n = 1)] occurred in the 14 survivors (28.6%). Blunt injury, revised trauma score, free perforation, injury location, intraoperative hypotension, and blood loss were predictive of mortality. IVC injuries remain extremely lethal, and improved survival is associated with infrarenal penetrating injuries and a contained hematoma.     

High resolution footprinting of a type I methyltransferase reveals a large structural distortion within the DNA recognition site

The type I DNA methyltransferase M.EcoR124I is a multi-subunit enzyme that binds to the sequence GAAN6RTCG, transferring a methyl group from S-adenosyl methionine to a specific adenine on each DNA strand. We have investigated the protein-DNA interactions in the complex by DNase I and hydroxyl radical footprinting. The DNase I footprint is unusually large: the protein protects the DNA on both strands for at least two complete turns of the helix, indicating that the enzyme completely encloses the DNA in the complex. The higher resolution hydroxyl radical probe shows a smaller, but still extensive, 18 bp footprint encompassing the recognition site. Within this region, however, there is a remarkably hyper-reactive site on each strand. The two sites of enhanced cleavage are co-incident with the two adenines that are the target bases for methylation, showing that the DNA is both accessible and highly distorted at these sites. The hydroxyl radical footprint is unaffected by the presence of the cofactor S-adenosyl methionine, showing that the distorted DNA structure induced by M.EcoR124I is formed during the initial DNA binding reaction and not as a transient intermediate in the reaction pathway.     

Phase I study of a five-day dose schedule of 4-Ipomeanol in patients with non-small cell lung cancer

The mammalian pulmonary toxin 4-ipomeanol (IPO) is activated by the cytochrome P450 system in bronchial Clara cells in animals. The resulting metabolites bind rapidly to macromolecules, producing localized cytotoxicity. IPO has in vitro and in vivo antitumor activity in non-small cell lung cancer (NSCLC) and thus was proposed as a lung cancer-specific antitumor agent. We have completed a directed Phase I trial in patients with NSCLC. Forty-four patients (34 men and 10 women) with NSCLC were treated with IPO. All but two patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. They received 91 courses of therapy with i.v. IPO; 82 courses were administered daily for five days, and 9 were single bolus doses. The dose-limiting toxicity of elevated serum transaminases was observed in three of seven patients at 922 mg/m2/day. The maximum tolerated dose was 693 mg/m2/day on 5 consecutive days every 3 weeks. One patient developed grade 4 pulmonary toxicity at 167 mg/m2/day. There was no significant hematological or renal toxicity. No objective antitumor responses were observed. Pharmacokinetic analysis of 39 patients from day 1 of IPO administration showed biexponential elimination with mean half-lives of 8.6 (alpha half-life) and 76 min (beta half-life). There was a linear relationship between the area under the plasma drug concentration-time curve and the dose of IPO. There was no significant difference between the pharmacokinetic parameters measured on day 1 and day 5. Using a 4-day in vitro cytotoxicity assay, two tumor cell lines established from patients treated at 693 mg/m2/day had IC50s of approximately 6 mM, a concentration more than 75-fold higher than the plasma levels measured in these patients. Thus, although the total amount of drug administered per cycle on a daily times five dose schedule is more than 2.5-fold higher than the recommended single daily dose, IPO is unlikely to be a useful drug for patients with lung cancer.     

Transport of paraquat by a renal epithelial cell line, MDCK

Transport of paraquat (PQ), a herbicidal cation, was previously investigated in a proximal (LLC-PK1), renal epithelial cell line using permeable collagen-coated filters. PQ was actively transported from the basolateral side via a cation transport system by the LLC-PK1 cells. In the present study, the transport of PQ was investigated in a distal renal epithelial cell line, MDCK. PQ was predominantly transported from the basolateral to apical (B to A) side. The basolateral transport of PQ in MDCK cells was not saturable with increasing concentrations and not energy dependent. The flux and uptake of PQ was much lower in the MDCK than LLC-PK1 cells. It is concluded that MDCK, a distal renal tubular cell line, does not have an active transport system for PQ.     

Sex differences in corticosteroids in man

The serum concentrations of progesterone (P), 17-OH-progesterone (17-OHP), 11-deoxycorticosterone (DOC), corticosterone (B), 11-deoxycortisol (S), 18-OH-11-deoxycorticosterone (18-OH-DOC), aldosterone (Aldo) and cortisol (F) were measured in 18 normal men (M), 14 normal women in the folicular phase (FF) and 14 normal women in the luteal phase (FL) of menstrual cycle from blood samples obtained between 0800 and 0900 h. Steroids were estimated by a sensitive and specific radioimmunoassay allowing the simultaneous determination of all steroids studied from one 3 ml serum sample. The mean steroid concentrations (ng/1dl) in FF were found to be as follows: P, 20.3; 17-OHP, 58; DOC, 3.8; B, 241; S, 20.7; 18-OH-DOC, 12.3; Aldo, 8.8; F, 9860. Apart from P, steroid concentrations in FF were significantly lower than in M. Serum 17-OHP, DOC, B and Aldo in FF were significantly lower than in FL. With the exception of P, there were no significant differences of mean steroid concentrations between M and FL.     

Protection by cyclosporine A against normothermic liver ischemia-reperfusion in pigs

BACKGROUND: Cyclosporine A (CYA) is primarily utilized as an immunosuppressant, but its mechanisms of action (including decreased neutrophilic free radical production and stabilization of mitochondrial and lysosomal membranes) may have beneficial effects in ischemia and reperfusion (IR) injury. This study was undertaken to examine the effect of CYA pretreatment on porcine liver histopathologic changes and enzymatic release caused by ischemia and reperfusion. MATERIALS AND METHODS: CYA was administered orally for 4 days prior to surgery in two doses (10 or 20 mg/kg) while controls received only the control vehicle. Pigs were then exposed to 4 h of hepatic ischemia followed by 2 h of reperfusion. RESULTS: Significant decreases in AST levels compared to controls were seen in high dose CYA pigs at the end of ischemia and at 30-min intervals during the reperfusion period. Controls exhibited necrotic hepatocytes and severe inflammatory cell infiltration, while high dose CYA animals demonstrated mild inflammatory cell infiltrates. Controls had decreased survival--20% did not survive reperfusion. CONCLUSIONS: This study indicates that CYA may be useful in decreasing initial damage resulting from warm hepatic IR injury.     

Rationale and design of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study that evaluates atorvastatin in unstable angina pectoris and in non-Q-wave acute myocardial infarction

Pediococcus sp. is a nonpathogenic heat-resistant spoilage organism that has been used as a test organism in milk pasteurization studies. These characteristics make this bacterium an attractive test organism to study the mode of bacterial thermal inactivation in a food pilot plant. We report here the effect of growth medium on the thermal D value of this organism in skim milk, whole liquid egg, 10% glucose solution, pineapple juice, apple juice, tomato juice, and water at 60 degrees C. Thermal inactivation was done in a submerged coil; D values were calculated from the linear portion of the survival curves by linear regression analysis. The range of D values of stationary-phase cells grown at 28 degrees C in tryptone glucose yeast extract (TGY) or tryptic soy broth (TSB) was 0.14 to 12.05 min in all heating menstrua tested. The TSB-grown cells exhibited the highest thermal resistance with skim milk and 10% glucose solution as the heating menstrua. Survival curves of the TGY-grown cells indicated the presence of a cell population heterogeneous in thermal resistance. The TSB-grown cells exhibited a cell population uniform in thermal resistance and with a lag time for thermal inactivation. When compared to TGY-grown cells, Pediococcus sp. grown in TSB showed a significant (P < 0.05) increase in D values by up to eightfold in all heating menstrua. Results from this study suggested that thermal inactivation of Pediococcus sp. was dependent on the growth medium and on the heating menstruum with respect to both pH and composition.