Inflamed fibronectin: an altered fibronectin enhances neutrophil adhesion

Recent investigations have emphasized the role of activated granulocytes in mediating vascular endothelial injury in the pathogenesis of shock lung. In vitro studies have indicated that tight adherence of the neutrophil to the endothelium is crucial for the development of cellular injury. Fibronectin is critical to cell-to- substratum and cell-to-cell interactions. Since fibronectin resides in plasma, on endothelial cell surfaces and is secreted into cell matrices, the adhesive properties of fibronectin must be modulated, lest universal cell agglomeration occur, yet be enhanced when cell attachment is appropriate. In these studies, treatment of fibronectin- coated surfaces with neutrophil release products increased the adhesion of activated neutrophils. Similarly, endothelial cells treated with neutrophil release products become a more adherent substrate for neutrophils. This enhanced adherence generated by treatment of fibronectin with neutrophil supernatants is inhibitable by heat and the lysosomal proteinase inhibitor, pepstatin-A. Neutrophil release products cause proteolytic fragmentation of fibronectin and enhanced fibronectin immunofluorescence on endothelial cells. In addition, neutrophils are more injurious to endothelial cells that have been pretreated with neutrophil release products. Neutrophils may enhance their own adherence to endothelial cells by altering fibronectin, and this altered, or "inflamed," fibronectin may serve as an amplifier of inflammation.     

Microbial O-carbamylation of novobiocin

Novobiocin was inactivated by Streptomyces niveus US 2094 in fermentation. The inactivation product was isolated and characterized by NMR and MS as 2"-O-carbamylnovobiocin. The MICs of novobiocin and 2"-O-carbamylnovobiocin were determined for S. niveus strains.     

Doppler velocimetry of intraplacental fetal arteries

Doppler velocimetry of the umbilical and intraplacental fetal arteries was studied by color flow mapping in 39 normal pregnancies. The systolic-diastolic ratio (S/D) and pulsatility index of the intraplacental fetal artery downstream to the umbilical artery decreased significantly with advancing gestational age, and its S/Ds were persistently lower than those of the umbilical artery. The difference in the S/D between the umbilical artery and its intraplacental downstream branches decreased with advancing gestational age and approached zero as the pregnancy progressed to term. We conclude that intraplacental fetal arteries, possibly fetal arteries in main stem villi, can be imaged by color flow mapping and that there is a significant "resistance gradient" between the intraplacental fetal artery and the umbilical artery. Intraplacental fetal artery velocimetry using color flow mapping may give further insights into the umbilical-placental circulation.     

Initial results of laser angioplasty under angioscopic guidance for salvage of an ischemic lower limb: preliminary report

From March to July 1989, nine patients at risk for peripheral artery disease underwent intraoperative Nd:YAG laser angioplasty using angioscopy at the Veterans General Hospital (Taipei, Taiwan, Republic of China). Following the laser angioplasty, balloon dilatation was performed in all cases. Eight men and one woman at an average age of 68 were included in the study (range: 58 to 78 years old). Ischemic symptoms included five patients with disabling claudication, four with pain at rest and one with gangrene on the toes. Eight of the nine patients had complete occlusions ranging from 2 to 19 cm in length. Two patients had high degree multiple segmental stenosis of the superficial femoral artery from 1 to 2 cm in length. Initial clinical success (indicated by relief of symptoms and increase in Doppler ankle pressure and index) and improvement in the angiographic luminal diameter was noted in 9 of 10 occluded vessels (90%) that underwent Nd:YAG laser treatment which was delivered at 10 to 12 watts through laser probes. Prelaser intraluminal diameter increased from 0.05 +/- 0.07 to 0.53 +/- 0.07 mm, Doppler ankle pressure index rose from 0.51 +/- 0.12 to 0.81 +/- 0.12, Doppler ankle pressure increased from 62.44 +/- 16.10 to 104 +/- 21.21 mmHg and the amplitude of pulse volume recorder at ankle level rose from 5.77 +/- 2.80 to 12.11 +/- 2.77 mm as compared with prelaser therapy (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Observation of nervous tissue in a Wilms' tumor: its histogenetic significance.

A case of Wilms' tumor occurring in a horseshoe kidney is reported in which bona fide nervous tissue containing ganglion cells was observed. This finding cannot be reconciled with the currently held "metanephrogenic blastema" theory of the histogenesis of this tumor. Masson's concept of "neuroepithelial origin" of the Wilms' tumor should be re-evaluated.     

The cholinergic deficit coincides with Abeta deposition at the earliest histopathologic stages of Alzheimer disease

Effective therapeutic intervention in Alzheimer disease (AD) will be most effective if it is directed at early events in the pathogenic sequence. The cholinergic deficit may be such an early event. In the present study, the brains of 26 subjects who had no history of cognitive loss and who were in early histopathologic stages of AD (average Braak stage less than II) were examined at autopsy to determine whether a cortical cholinergic decrement was associated with Abeta concentration or deposition. In the superior frontal and inferior temporal gyri, the choline acetyltransferase (ChAT) activity of plaque-containing cases was significantly decreased (p < 0.05, unpaired, two-tailed t-tests), measuring 70.9% and 79.5%, respectively, relative to plaque-free cases. In the inferior temporal gyrus, Spearman's rank correlation analysis showed that ChAT activity had a significant inverse correlation with Abeta concentration (p = 0.075; r = -0.3552). The results indicate that the cholinergic deficit is established at an early histopathologic stage of AD, before the onset of clinical symptoms.     

Disposition and metabolic fate of atomoxetine hydrochloride: pharmacokinetics, metabolism, and excretion in the Fischer 344 rat and beagle dog.

These studies were designed to characterize the disposition and metabolism of atomoxetine hydrochloride [(-)-N-methyl-gamma-(2-methylphenoxy)benzenepropanamine hydrochloride; formerly know as tomoxetine hydrochloride] in Fischer 344 rats and beagle dogs. Atomoxetine was well absorbed from the gastrointestinal tract and cleared primarily by metabolism with the majority of its metabolites being excreted into the urine, 66% of the total dose in the rat and 48% in the dog. Fecal excretion, 32% of the total dose in the rat and 42% in the dog, appears to be due to biliary elimination and not due to unabsorbed dose. Nearly the entire dose was excreted within 24 h in both species. In the rat, low oral bioavailability was observed (F = 4%) compared with the high oral bioavailability in dog (F = 74%). These differences appear to be almost purely mediated by the efficient first-pass hepatic clearance of atomoxetine in rat. The biotransformation of atomoxetine was similar in the rat and dog, undergoing aromatic ring hydroxylation, benzylic oxidation (rat only), and N-demethylation. The primary oxidative metabolite of atomoxetine was 4-hydroxyatomoxetine, which was subsequently conjugated forming O-glucuronide and O-sulfate (dog only) metabolites. Although subtle differences were observed in the excretion and biotransformation of atomoxetine in rats and dogs, the primary difference observed between these species was the extent of first-pass metabolism and the degree of systemic exposure to atomoxetine and its metabolites.     

Laparoscopic donor nephrectomy increases the supply of living donor kidneys: a center-specific microeconomic analysis

BACKGROUND: A tenet of microeconomics is that new technology will shift the supply curve to the right. Laparoscopic donor nephrectomy (LDN) is a new technique for removal of living donor kidneys. Centers performing this procedure have noted an increased number of patients presenting for donor evaluation. This has not been previously studied. METHODS: The records of all LDN performed from May 1998 to February 1999 were reviewed. The following variables were examined: sex, age, related vs. unrelated donation, estimated blood loss, i.v. analgesia, length of stay, and time out of work. Donors undergoing traditional open donor nephrectomy during January 1997 to May 1998 served as the control group. A composite cost index was constructed. RESULTS: LDN significantly decreased length of stay, pain, and time out of work; the supply function shifted to the right. Telephone interviews revealed that 47% donated solely because of the LDN procedure. CONCLUSIONS: LDN increases the supply of living donor kidneys.     

Pathophysiology of lower urinary tract symptoms in aged men without bladder outlet obstruction

OBJECTIVE: To assess the pathophysiology of lower urinary tract symptoms (LUTS) in aged men without bladder outlet obstruction in a videourodynamic study. METHODS: In a videourodynamic study of 324 consecutive men with moderate to severe LUTS suggestive for bladder outlet obstruction, 112 were found to be urodynamically nonobstructed. International prostatic symptom score (IPSS), uroflowmetry and transrectal sonography of the prostate were assessed before videourodynamic study. The pressure flow expression and the obstructive parameters were compared between the 212 obstructed and 112 nonobstructed men. RESULTS: Of the 112 nonobstructed men investigated, 25 had a normal bladder and urethral trace (22.3%), 5 had detrusor instability (4.5%), 17 had a hypersensitive bladder and a normal urethra (15.2%), 3 had detrusor underactivity and a normal urethra (2.7%), while 61 were found to have a poorly relaxed external sphincter and low detrusor contractility (54.5%). Most of the patients in the normal and hypersensitive groups had normal voiding pressure and high flow (NPHF) tracings, whereas men with detrusor underactivity or a poorly relaxed external sphincter had normal voiding pressure and low flow (NPLF) tracings. Only the maximal flow rate and voided volume were significantly higher in patients with NPHF than in patients with NPLF tracings. However, both groups showed a significantly lower IPSS, less residual urine, and a smaller transition zone index than the obstructive group. After medical treatment, 78 patients (69.6%) had satisfactorily improved, 31 patients (27.6%) remained stationary, while 3 (2.7%) worsened. CONCLUSION: Nonobstructed men with LUTS have various pathophysiologies other than benign prostatic obstruction. In this study 54.5% of these patients had poorly relaxed external sphincter on videourodynamic study. Identification of the underlying pathology can not only prevent unnecessary prostate surgery but can also enable proper medical treatment to be selected.