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.     

KTP Laser and Neutral Red Phototherapy of Human Squamous Cell Carcinoma

Neutral red (NR) is a cationic, nontoxic vital dye employed as a histologic stain for proliferating cells; it has been used clinically for photodynamic treatment of herpes simplex virus lesions. NR is selectively taken up and concentrated by mitotic cells, an important characteristic for more effective antineoplastic agents. In the present study, UCLA-SO-P3 human squamous carcinoma cells displayed minimal toxicity when incubated with up to 50 μg/ml NR in the absence of light. However, cells incubated with greater than 0.5μg/ml NR followed by exposure to KTP laser light at 532 nm exhibited nearly 100% tumor cell death. The degree of cell toxicity was proportional to NR dose and laser light fluence. This study demonstrates that NR is an excellent cancer cell photosensitizer in vitro, and, after adding additional in vivo preclinical testing, may prove to be a useful agent in photodynamic destruction of head and neck tumors.