Molecular heterogeneity of somatostatin analogue BIM-23014C receptors in human breast carcinoma cells using the chemical cross-linking assay.

Distinct proteins complexed with somatostatin and the somatostatin analogue BIM-23014C were revealed in human breast cancer cells using the cross-linking assay. One BIM-23014C-specific complex (Mr 57,000) was observed in MCF-7 (monolayer, nodule, and tumor) and T47D. Growth inhibition of MCF-7 tumor xenografts by BIM-23014C was dose related in the 6-day subrenal capsule assay. Three complexes (Mr 27,000, 42,000, and 57,000) were detected in MDA-MB-231, and no complex was visible in HBL-100. No correlation was found between receptors for BIM-23014C and epidermal growth factor in these lines. Twenty-seven of 30 human breast tumors (90%) had at least one BIM-23014C receptor. Sixteen had three complexes (Mr 27,000, 42,000, and 57,000). Six had the two complexes (Mr 27,000 and 57,000), two had Mr 42,000 and 57,000 complexes, two had just the Mr 27,000 complex, and one had just the Mr 42,000 complex. The presence of the three BIM-23014C receptors was positively correlated (P less than 0.05) to the low amount of sex steroid receptors (less than 20 fmol/mg) [seven of eight (estrogen receptor negative, progesterone receptor negative) versus four of 14 (estrogen receptor positive, progesterone receptor positive)]. Another positive correlation was established between the absence of progesterone receptors and the presence of these three complexes [12 of 16 (progesterone receptor negative) versus four of 14 (progesterone receptor positive)]. This high percentage of BIM-23014C receptor-positive biopsies and its inhibitory activity would support its clinical potential for the treatment of breast cancer.     

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)     

Amikacin alone and in combination with trimethoprim-sulfamethoxazole in the treatment of actinomycotic mycetoma

We report the excellent therapeutic response obtained with amikacin alone and in combination with trimethoprim-sulfamethoxazole in the treatment of 15 patients with actinomycotic mycetoma who had a poor response to the traditional pharmacologic agents and/or in whom important organs such as lungs, spinal cord, and bone were involved. We evaluated the results by clinical, radiologic, and laboratory tests. No important side effects were detected during or after the therapy.     

Examination of spinal cord in diseases of the craniocervical junction and high cervical spine.

A simple necropsy technique for the removal of the craniocervical junction was devised: a relatively small specimen comprising part of the clivus, the foramen magnum, and cervical vertebral canal is removed in one piece with the medulla and spinal cord inside, and examined systematically after fixation. This method, used in a series of patients with chronic craniocervical instability, allows both good clinicopathological correlations to be made and histological changes in the lower medulla or upper cervical cord segments to be related to sites of extrinsic compression.     

Complications of intravesical bacillus Calmette-Guerin: a case report.

Bacillus Calmette-Guerin (BCG) is the most effective agent currently available to treat superficial bladder cancer. However, this form of therapy is not without potential serious or fatal complications. In addition to the potentially toxic systemic side effects attributed to hematogenous absorption of the bacillus, direct upper tract seeding may occur in patients with vesicoureteral reflux. We report on a patient treated with intravesical BCG for bladder cancer in whom unilateral necrotizing granulomatous pyelonephritis developed. Although severe, this complication is rare and we conclude that reflux is not a contraindication for intravesical BCG therapy.