The time course for the development of renal interstitial fibrosis (RIF) in rats between days 5 and 25 after unilateral ureteral obstruction (UUO) was studied. In kidneys with UUO under histological examination, an interstitial fibrosis was observed after more than 10 days with progression up to day 25. On day 5, collagen peptidase activity in homogenates of UUO kidneys was about 50% higher than in controls but gradually declined afterwards until reaching the level obtained from contralateral kidneys (CL) on day 25. 10 days after UUO, renal hydroxyproline content was elevated about twofold as compared to CL and sham-operated rats, and increased considerably by day 25 of UUO. In primary cultures of cells obtained from UUO kidneys, fibroblast proliferation increased regardless of the extent of fibrosis. This could be a result of an early inflammatory process. Renal fibroblasts from rats are heterogenous when studied in vitro. When fibroblasts of passage 1 obtained from kidneys 25 days after UUO were plated at low density, the number of mitotic type I clones was elevated 5.5-fold as compared with cultures from CL kidneys. The majority of type I clones in UUO cultures from fibrotic kidneys developed in an unusual fashion with formation of three-dimensional structures. The changes detectable under the unfavorable conditions of clonal culture suggest phenotypical differentiation of a small fraction of fibroblasts from kidneys with RIF. These cells are able to overgrow cell monolayers forming circular growing colonies. Obviously, one needs to distinguish between intensitive proliferation as a consequence of acute inflammation, and the changes in phenotype of a small fraction of renal fibroblasts which are resistant to normal physiologic regulative mechanisms in cell culture. The latter may contribute to matrix disorders and RIF.

The aims of this clinical study were to compare the maintenance doses for intravenous (i.v.) and subcutaneous (SC) administration of recombinant human erythropoietin (rhEPO) and to investigate whether there is any difference in the increase of the packed cellular volume (PCV) per week under i.v. and SC administration of rhEPO from two production sites (Genetics Institute, Cambridge, USA; and Boehringer Mannheim, Penzberg, Germany). A total of 90 patients suffering from end-stage renal disease were included in the study. All patients had already been treated for at least 6 months with chronic hemodialysis. The study was carried out as a randomized, multicenter parallel group comparison study with a 1-week pretreatment phase, a subsequent 8-week double-blind phase, and a final open phase. The final open phase consisted of a correction phase and a maintenance phase. The production site had no influence on the PCV increase per week, and there were no differences with respect to tolerability. The median rhEPO dose required to maintain the target PCV of 30 to 35 vol.% was 33 U/kg body weight three times a week in the i.v. group compared with 22 U/kg in the SC group (i.e., an average of 30% less with SC administration). Development or aggravation of hypertension under rhEPO therapy was observed, especially during the correction phase and more frequently in the SC group than in the i.v. group. During the maintenance phase, there was no essential difference between the two groups.

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Introduction:Hand held, colorimetric, end-tidal CO2 detector devices are being used to verify correct endotracheal tube (ETT) placement. The accuracy of these devices has been questioned in situations of cardiac arrest. The use of the esophageal detector device (EDD) is an easy alternative for detection of ETT placement, and may be more accurate in situations of cardiac arrest.Hypothesis:The use of the esophageal aspiration device in comparison with a colorimetric end-tidal CO2 detector is more accurate in detecting proper ETT placement and easier to use in the prehospital setting than is the colorimetric end-tidal CO2 detection device.Methods:This was a prospective alternating weeks, 6-month study in a prehospital setting. Participants included all patients older than 18 years who were intubated by the Portsmouth, Virginia Emergency Medical Services (EMS) personnel from 01 July 1993 through 31 December 1993. The aspiration device used, also known as an esophageal detector device (EDD), was a 60 ml, luer-lock syringe attached to a 15 mm ETT adapter. Its efficacy was compared with an already accepted method of ETT position detection, the colorimetric endtidal CO2 detector. Each device was used on alternating weeks, and correct ETT placement was determined by the receiving emergency department physician using standard techniques. Chi-square analysis and Fisher's Exact test were used to compare parameters, time of device use, and ease of use. Sensitivity and specificity were calculated, and provider preference was assessed using a survey instrument administered following completion of the study.Results:There were 49 patients who met the inclusion criteria, but six were excluded because of situational circumstances rendering use of the device a possible compromise of patient care. Twenty-five patients were in the EDD group, and 18 were in the endtidal CO2 detector group. There was no statistically significant difference detected between groups for the gender ratio, underlying condition, CPR in progress, perceived difficulty of intubation, or percentage of nasotracheal intubation. The EDD was significantly easier to use (p<0.005). There was no statistically significant difference in time required for use of end-tidal CO2 detector device versus the EDD. The sensitivity and specificity for correct tracheal placement using the EDD was 100%, and the sensitivity for correct tracheal placement using the end-tidal CO2 detector device was 78%. Use of the EDD was preferred over use of the end-tidal CO2 detector device by 75% of participating EMS providers. One case of nasotracheal intubation with an ETT placement above the cords raised the question of accuracy of this device in situations where direct visualization is not utilized.Conclusion:The EDD was accurate in all cases of orotracheal intubation, and was easier to use than was end-tidal CO2 detector device. It was preferred by 75% of participating EMS providers. In cases in which the ETT may be above the vocal cords, caution must be used with interpreting the results obtained by use of the EDD.