Focal segmental glomerulosclerosis

Over the last 2 decades, we have learnt that focal segmental glomerulosclerosis (FSGS) is a ubiquitous phenomenon underlying the progressive deterioration of many different types of renal diseases in both pediatric and adult populations. FSGS may also be the primary renal lesion, whether in new disease entities such as glycogen storage disease and human immunodeficiency virus infection, or in idiopathic FSGS. Although the mechanism which triggers the development of primary FSGS still remains unknown, laboratory and clinical studies have identified several key pathophysiological events leading to end-stage renal disease. While therapeutic modalities have not changed remarkably, a recent study, although uncontrolled, demonstrated an impressive efficacy of intravenous steroid pulse therapy in inducing remission. Nevertheless, it remains largely unknown whether such a forced remission decreases the overall risk of developing chronic renal failure. Studies have revealed an important pathophysiological role of angiotensin and the therapeutic efficacy of angiotensin converting enzyme inhibitors in progressive loss of renal function in diseases where glomerulosclerosis is secondary; however, it remains to be verified whether these results hold true in primary FSGS. As a result of the improvement in allograft survival rate, the benefit of renal transplant outweighs the risk of recurrence of FSGS, hence transplantation continues to be a vital therapy for FSGS patients who have reached renal failure. Thus, FSGS is not one disease, but rather a range of lesions seen in many settings. The type of lesions and the patient's unique genetic factors contribute to prognosis, and also may dictate choice of optimum therapy.     

α2-adrenoceptor blockade,pituitary-adrenal hormones,and agonistic interactions in rats

The effects of adrenergic activation on aggressiveness and the aggression induced endocrine changes were tested in rats. α₂ adrenoceptor blockers were used for enhancing activation of the adrenergic system, and changes in aggressiveness were tested in resident-intruder contests. Three experiments were conducted. In experiment 1, saline injected rats responded to the presence of an opponent by aggression and the increase in plasma ACTH and corticosterone. Intraperitoneal administration of 1 mg/kg CH-38083 (an α₂ adrenoceptor antagonist) produced a several fold increase in clinch fighting and mutual upright scores, and also further enhanced the plasma ACTH and corticosterone response. In experiment 2, the effect of three doses (0.5, 1 and 2 mg/kg) of three different α₂ adrenoceptor blockers CH-38083, idazoxan and yohimbine were tested. All the substances increased aggression at 0.5 and 1 mg/kg; at 2 mg/kg the effect of idazoxan and yohimbine disappeared, while with CH-38083 an additional increase was obtained. In yohimbine treated animals the enhancement of aggression was reduced already at 1 mg/kg. In experiment 3, indomethacin, a potent inhibitor of the catecholamine-induced ACTH release completely abolished the effects of the α₂ adrenoceptor antagonist CH-38083: the intensity of agonistic interactions, as well as ACTH and corticosterone plasma concentrations, returned to control levels. The possible role of catecholamines and the stress hormones in the activation of aggression is discussed.     

Verbal learning in Alzheimer's dementia.

Many recent findings in Western countries suggest that episodic recall is the most sensitive discriminator between patients with mild Alzheimer disease (AD) and the normal elderly, while semantic memory tends best to differentiate between moderate and severe AD patients. The present study is the first to examine in detail the episodic memory of Chinese AD patients in Hong Kong with a locally developed list learning test, comparing procedures that do or do not encourage the use of semantic organization. The performance of 28 AD patients was compared to that of 30 normal controls. AD patients did significantly worse in terms of acquisition and retention and also benefited significantly less from external organization cues. In the discriminant function analysis, the rate of forgetting in the random condition and the total retention score in the blocked condition were found to be the best predictors for differentiating between AD patients and controls. On the other hand, in the differentiation between mild and moderate AD, semantic clustering in the blocked condition was found to be the best predictor. Results of the present study were discussed in the light of the previous findings reported in the Western countries and the neuropathological changes of AD patients.     

Intraperitoneale hypertherme Chemoperfusion bei Ovarialkarzinom

Schlu?folgerungen Für die Peritonealkarzinose bei rezidivierendem Ovarialkarzinom sollte die IHCP als Konsolidierungstherapie nach neuerlicher zytoreduktiver Chirurgie in Erw?gung gezogen werden. Bei grobknotiger diffuser Carcinosis peritonei und massivem Aszites kann die IHCP über l?ngerer Zeit dessen Neubildung verhindern und damit zu einer Verbesserung der Lebensqualit?t und Verl?ngerung der überlebenszeit beitragen.     

Different proliferative activity of the glandular and myoepithelial lineages in benign proliferative and early malignant breast diseases.

The aim of the present study was to explore cell biological characteristics of normal breast, benign proliferative breast diseases and noninvasive breast malignancies based on the recently published adult progenitor cell concept from our group. Here, we investigated the proliferative activity of CK5/14(+), CK8/18/19(+) and alpha-smooth muscle actin(+) cellular phenotypes encountered in normal mammary gland, in a series of usual ductal hyperplasias and early malignant breast diseases, such as atypical ductal and lobular hyperplasias, as well as ductal and lobular in situ carcinomas. Immunohistochemical double labeling was performed on frozen sections from diagnostic breast biopsies by using antibodies to basal cytokeratins (CK5/14), glandular cytokeratins (CK8/18/19), smooth muscle actin and the Ki-67 antigen (MIB1). Normal breast tissues and usual ductal hyperplasias were characterized by a heterogeneous cellular composition of the growth fraction. The proliferative cell compartment consisted of CK8/18/19(+) glandular and, in a variable proportion, CK5/14(+) progenitor phenotypes. In contrast, noninvasive breast malignancies were composed of a monotonous proliferation of CK 8/18/19(+) neoplastic glandular cells. These findings indicate a significant role of progenitor cells in the development of benign proliferative breast diseases and lend support to the view that malignant transformation in the human breast usually occurs in a cell committed to the glandular lineage. Our results provide cell kinetic support to the functional progenitor cell hypothesis, and we propose this concept as an operative model for understanding benign proliferative and malignant breast diseases.     

Monocytes in active multiple sclerosis: intact regulation of HLA-DR density in vitro despite decreased HLA-DR density in vivo

HLA-DR expression on circulating monocytes varies as a function of disease activity in patients with multiple sclerosis (MS), a putative immunopathological demyelinating disorder. Specifically, monocytes isolated from subjects with active MS exhibit reduced HLA-DR antigen density, and immunoregulatory aberrations such as impaired T lymphocyte-mediated suppression correlate strongly with this quantitative defect. To address the mechanism underlying this phenomenon, we compared in vitro regulation of HLA-DR by interferon beta (IFN beta), interferon gamma (IFN gamma), and lipopolysaccharide (LPS) in monocytes from patients with stable and active MS and normal individuals. Interferon-gamma and LPS enhanced monocyte expression of HLA-DR equally in both MS patient groups, suggesting that underexpression of HLA-DR in active MS was not explained by impaired in vivo monocyte responsiveness. Furthermore, interferon regulation of HLA-DR in normals and stable MS subjects was indistinguishable, indicating that aberrant interferon-mediated regulation of class II major histocompatibility complex (MHC) on circulating monocytes does not appear to be a characteristic of the MS disease state.     

Femoral prosthesis implantation induces changes in bone stress that depend on the extent of porous coating

The objective of this study was to evaluate the effect of implantation of porous-coated anatomic medullary fitting prostheses on stress in the proximal femur. Three-dimensional finite element models of a cadaveric femur before and after implantation were used to evaluate the resulting changes in stress in the bone. Models of the femur were generated automatically from computed tomographic scan data with use of an innovative mesh-generation technique. The models were analyzed for three levels of porous coating (proximal, 5/8, and full), with the assumption of ideal ingrowth (perfect bonding) over porous areas and a frictionless, tension-free surface on smooth areas. All models were loaded and restrained to represent conditions of normal gait. The stresses predicted in the implanted femur are consistent with clinical observations of proximal cortical atrophy (normal stress reduced to 6-9% of normal at the calcar and 50–55% at mid-prosthesis) and of hypertrophy at the porous coating junctions (normal stress at the 5/8-coating junction, 123% of stress proximal to the junction) and hypertrophy near the distal tip of the prosthesis (anterior and posterior normal stresses 200–800% of normal). The fully coated prosthesis induced stresses in the bone near the tip of the prosthesis that were most like stresses in the normal femur (medial and lateral normal stress 105 and 102% of the stress in the normal femur). Below the collar, the normal stress associated with the proximally coated prosthesis was 6% greater than that produced with the other two levels of coating but still was only 2% of normal. The 5/8-coated prosthesis appeared to combine the worst features of the fully coated and proximally coated prostheses–greater stress-shielding at the calcar and higher stress near the tip of the prosthesis.