Small heat shock proteins associated with cerebral amyloid angiopathy of hereditary cerebral hemorrhage with amyloidosis (Dutch type) induce interleukin-6 secretion

In hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D), severe cerebral amyloid angiopathy (CAA) is associated with an inflammatory reaction. Small heat shock proteins (sHsps) are molecular chaperones and association of HspB8 with CAA in HCHWA-D has been observed. The aims of this study were to investigate (1) if other sHsps are associated with the pathological lesions in HCHWA-D brains, (2) if the amyloid-beta protein (A beta) increases production of sHsps in cultured cerebral cells and (3) if sHsps are involved in the cerebral inflammatory processes in both Alzheimer's disease (AD) and HCHWA-D. We conclude that Hsp20, HspB8 and HspB2 are present in CAA in HCHWA-D, and that A beta did not affect cellular sHsps expression in cultured human brain pericytes and astrocytes. In addition, we demonstrated that Hsp20, HspB2 and HspB8 induced interleukin-6 production in cultured pericytes and astrocytes, which could be antagonized by dexamethasone, whereas other sHsps and A beta were inactive, suggesting that sHsps may be among the key mediators of the local inflammatory response associated with HCHWA-D and AD lesions.     

High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy

Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was administered over 29 to 69 hours by continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2. Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days total 150 to 200 mg/kg ideal body weight). At all dose levels myelosuppression was severe but reversible. Mucosal toxicity was dose-limiting with the maximum tolerated dose level combining etoposide 4.2 g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion produced stable plasma levels that were lower than would be achieved after administration by short intravenous infusion, and this could explain our ability to escalate etoposide above the previously reported maximum tolerated dose. There were 28 complete (35%) and 12 partial (16%) responses. Median duration of complete response (CR) was 3.5 months (range 1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia (AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine arabinoside resistance. We conclude that bone marrow transplantation is not required after maximum tolerated doses of etoposide and cyclophosphamide. This regimen is active in resistant hematologic neoplasms, and the occurrence of CR in patients with high-dose cytosine arabinoside-resistant AML indicates a lack of complete cross-resistance between these regimens.     

Distribution of tyrosine hydroxylase and dopamine immunoreactivities in the brain of the South African clawed frog Xenopus laevis

Summary The distribution of dopamine (DA) and the biosynthetic enzyme tyrosine hydroxylase (TH) has been studied immunohistochemically in the brain of the adult South African clawed frog, Xenopus laevis. The goals of the present study are, firstly, to provide detailed information on the DA system of the brain of a species which is commonly used in laboratories as an experimental model and, secondly, to enhance our insight into primitive and derived characters of this catecholaminergic system in amphibians. Dopamine-immunoreactive cell bodies are present in the olfactory bulb, the preoptic area, the suprachiasmatic nucleus, the nucleus of the periventricular organ and its accompanying cells, the nucleus of the posterior tubercle, the posterior thalamic nucleus, the midbrain tegmentum, around the solitary tract, in the ependymal layer along the midline of the caudal rhombencephalon, and along the central canal of the spinal cord. In contrast to the DA antiserum, the TH antiserum fails to stain the liquor-contacting cells in the periventricular organ. On the contrary, the latter antiserum reveals additional immunoreactive cell bodies in the olfactory bulb, the isthmic region and the caudal brainstem. Both antisera yield an almost identical distribution of fibers. Distinct fiber plexuses are observed in the olfactory bulb, the basal forebrain, the hypothalamus and the intermediate lobe of the hypophysis. Features that Xenopus shares with other anurans are the larger number of DAi cells, which are generally smaller in size than those observed in urodeles, and the lack of DAi fibers in pallial structures. On the other hand, the paired midbrain DA cell group and the innervation of the tectum of Xenopus resemble those found in the newt rather than those in frogs. Despite the existence of these species differences, the brain of Xenopus offers an excellent model for studying general aspects of neurotransmitter interactions and the development of catecholamine systems in this class of vertebrates.     

Bile duct stones: percutaneous transhepatic removal

Percutaneous transhepatic intervention for transduodenal removal of biliary stones was performed 38 times in 34 patients with obstructive jaundice, biliary colic, and cholangitis. The technique entailed the percutaneous transhepatic placement of a modified Dormia basket in the common duct with the flexible tip in the duodenum. The stones were passed into the duodenum and were crushed, or were crushed in the common duct and passed as fragments into the duodenum. In addition to the snare procedure, monooctanoin was used 18 times to dissolve remaining fragments of stone and sludge that could not be snared and passed into the duodenum. The average time for completion of the procedure was 10 days. There were no deaths from the procedure. The complication rate was 21%--probably no greater than would occur with surgery in a similar patient population. The procedure can be performed when endoscopic retrograde cholangiopancreatography and sphincterotomy with stone removal is technically impossible or refused, and in patients who have previously undergone choledochojejunostomy.     

Growth in children with steroid sensitive nephrotic syndrome

Background: Nephrotic syndrome in children usually has an onset between 2–8 years of age and steroids form the mainstay of management. Therapy may affect growth in children with relapsing nephrotic syndrome. This study was carried out to correlate growth with the cumulative dose of steroids in children with steroid sensitive nephrotic syndrome (SSNS).     

MR shoulder arthrography in patients younger than 40 years of age: Frequency of rotator cuff tear versus labroligamentous pathology

The purpose of this study was to compare the frequency of rotator cuff pathology versus labroligamentous pathology in patients younger than 40 years and to determine whether routine MR arthrography is justified in all patients in this age group, regardless of the clinical symptoms. The MR arthrography was carried out on 332 patients 40 years of age and younger. Two hundred and forty‐three patients had clinical history of instability and possible labroligamentous pathology. Eighty‐nine patients had no history or physical signs of instability and were referred for reasons other than instability, such as assessment for rotator cuff tear. In the 243 patients younger than 40 years with clinical history of potential labral pathology, 39% (95/243) showed a labral tear and 2.1% (5/243) had a full‐thickness rotator cuff tendon tear. In the 89 patients with no history suggesting labral pathology, 19% (17/89) showed an unsuspected labral tear and 4.5% (4/89) had a full‐thickness rotator cuff tear. These findings suggest that, regardless of the clinical indication for referral, patients aged 40 and less referred for shoulder MRI should be imaged using MR arthrography because of the significant risk that symptoms are related to unsuspected labral pathology.