Early bladder outlet obstruction in fetal lambs induces renal dysplasia and the prune-belly syndrome

A model of posterior urethral valves in fetal lambs was developed in order to evaluate the effect of intrauterine urinary obstruction on the developing kidney. Complete urethral obstruction was induced in five fetal lambs at 43 to 45 days of gestation. Two control fetal lambs underwent sham operations. At full term (140 days), two of the five experimental lambs and both control lambs were available for postmortem examination. Results of gross and histological examination of the control lambs were normal. In contrast, the kidneys of the experimental lambs were markedly asymmetrical in size. Histological examination of the kidneys in experimental lambs showed cystic dilatation of the collecting ducts and occasional cystic dilatation of Bowman's spaces, features compatible with obstruction. Also noted were peripheral cortical cysts and primitive tubules lined with cuboidal epithelium and surrounded by fibromuscular collarettes, characteristic of renal dysplasia. One of the infant lambs had many characteristics of the prune-belly syndrome, including a wrinkled, markedly distended abdomen, deficient abdominal wall musculature, flared chest wall, limb deformities, and undescended testes. These results suggest that early in utero urethral obstruction (at the beginning of the second third of gestation) causes renal dysplasia. The results also support the hypothesis that the prune-belly syndrome results from abdominal distention that occurs early in gestation.     

Carcinoma of the prostate with atypical immunohistological features. Clinical and histologic correlates

In seven patients with undifferentiated carcinoma of the prostate, the immunohistochemical stain for prostate-specific antigen was negative. The stain for prostatic acid phosphatase done on the same tissue samples was diffusely positive in three, focally positive in three, and negative in one. Only the three with diffusely positive immunostaining had elevated serum acid phosphatase levels, although five had evidence of metastatic disease. All seven neoplasms were histologically similar, being composed of large cells with large nuclei, a moderate amount of cytoplasm, and indistinct cell borders. All tumors grew as broad sheets within the prostatic stroma as well as in the prostatic urethra; in six cases. Thus, prostatic carcinoma with this histologic pattern frequently loses prostate-specific antigen immunoreactivity. Awareness of this occurrence should prevent a misdiagnosis of urothelial carcinoma in such cases. The prostatic origin of these neoplasms can usually be verified by prostatic acid phosphatase immunostaining, which proves to be more sensitive in this particular setting.     

Evaluation of renal transplant dysfunction by duplex Doppler sonography: a prospective study and review of the literature

A disconcertingly wide variation exists in the literature as to the accuracy of duplex Doppler sonography in the detection of acute renal transplant rejection. Sensitivities range from 9% to 76%. In an attempt to explain the disparity of results, we undertook a double-blind prospective study of the accuracy of duplex Doppler ultrasound in the detection of acute rejection in renal transplants. We scanned 49 consecutive patients with a total of 65 biopsies; 46 biopsies in 33 consecutive patients were included in our study. In our population, the prevalence of acute rejection was 61% (28/46). Using a resistive index (RI) cutoff of greater than 0.90 based on the main renal artery flow pattern, the sensitivity of our test was 43%, with a 67% specificity. The positive predictive value was 67%. Our results are contrasted and compared with the published data from other groups in a critical survey of the literature. We conclude that duplex Doppler sonography alone is inadequate to evaluate acute rejection in renal transplants.     

A patient with hyperkalemia and metabolic acidosis

Uptake of potassium by extrarenal tissues, primarily muscle and liver, represents a major defense mechanism in the maintenance of normokalemia following an acute elevation in the serum potassium concentration. Insulin, epinephrine, and aldosterone all play major roles in maintaining the normal distribution of potassium between the intracellular and extracellular environment. In addition to hormonal regulation, changes in blood pH and tonicity also exert a strong influence on extrarenal potassium metabolism. Last, the serum potassium concentration per se directly influences its own cellular uptake and this transport mechanism appears to be inhibited by uremia.     

Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1.

Six human cytochrome P450s expressed in HepG2 cells using vaccinia virus cDNA-directed expression, were used to study the biotransformation of caffeine and its metabolites. CYP1A2 alone was responsible for caffeine 3-demethylation and paraxanthine 7-demethylation; in addition, 1A2 catalysed virtually all reactions related to caffeine and its metabolites. The metabolic profile of caffeine biotransformation by CYP1A2 averaged 81.5% for paraxanthine, 10.8% for theobromine and 5.4% for theophylline formation. It remained quite uniform when caffeine concentrations were varied. The most striking finding was that CYP2E1 (the ethanol-inducible form) had major influences upon caffeine metabolism: in particular, it catalysed the formation of theophylline and theobromine from caffeine. Thus, the in vivo metabolite profiling of caffeine may reveal CYP2E1 activities in addition to the previously documented activities of CYP1A2, polymorphic N-acetyltransferase and xanthine oxidase.     

Improved intracranial lesion characterization by tissue segmentation based on a 3D feature map

Our aim was to develop an accurate multispectral tissue segmentation method based on 3D feature maps. We utilized proton density (PD), T₂-weighted fast spin-echo (FSE), and T₁-weighted spin-echo images as inputs for segmentation. Phantom constructs, cadaver brains, an animal brain tumor model and both normal human brains and those from patients with either multiple sclerosis (MS) or primary brain tumors were analyzed with this technique. Initially, misregistration, RF inhomogeneity and image noise problems were addressed. Next, a qualified observer identified samples representing the tissues of interest. Finally, k-nearest neighbor algorithm (k-NN) was utilized to create a stack of color-coded segmented images. The inclusion of T₁ based images, as a third input, produced significant improvement in the delineation of tissues. In MS, our 3D technique was found to be far superior to that based on any combination of 2D feature maps (P < 0.001). We identified at least two distinctly different classes of lesions within the same MS plaque, representing different stages of the disease process. Further, we obtained the regional distribution of MS lesion burden and followed its changes over time. Neuropsychological aberrations were the clinical counterpart of the structural changes detected in segmentation. We could also delineate the margins of benign brain tumors. In malignant tumors, up to four abnormal tissues were identified: 1) a solid tumor core, 2) a cystic component, 3) edema in the white matter, and 4) areas of necrosis and hemorrhage. Subsequent neurosurgical exploration confirmed the distribution of tissues as predicted by this analysis.     

Mass and in situ molar activity of tyrosine hydroxylase in the median eminence. Effect of thyroidectomy and thyroid hormone replacement

The effects of thyroidectomy and thyroid hormone replacement on the mass and in situ molar activity of tyrosine hydroxylase (TH) in the median eminence (ME) and superior cervical ganglia (SCG) of male rats were investigated. The tissue specificity of these effects were evaluated by comparing the ME with the superior cervical ganglion (SCG). All animals were thyroparathyroidectomized (Tx) or sham Tx. Tx rats were treated daily for 3 weeks with 0.15 M NaCl (solvent vehicle) or L-thyroxine (T4). Two doses of T4, 10 and 100 micrograms/day/kg BW, were used. Sham Tx rats were treated with 0.15 M NaCl. All animals were studied on the day following the last treatment. The mass of TH was determined using an immunoblot assay, and the in situ activity of TH was calculated from the rate of intracellular accumulation of L-dihydroxyphenylalanine (DOPA) after administration of an inhibitor of DOPA decarboxylase activity. In the ME, thyro-parathyroidectomy resulted in a 40% increase in the mass and a 100% increase in the in situ molar activity of TH over that of sham Tx rats. Compared to Tx animals given 0.15 M NaCl, Tx rats treated with a low dose of T4 (10 micrograms/day/kg BW) had a reduced quantity of TH in the ME, but the molar activity of the enzyme was increased. Treatment of Tx rats with a high dose of T4 (100 micrograms/day/kg BW) restored TH mass but not the in situ activity of TH in the ME to the level seen in sham Tx rats.(ABSTRACT TRUNCATED AT 250 WORDS)