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.     

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.     

Decision-making after ultrasound diagnosis of fetal abnormality

During the last few decades, the use of ultrasonography for the detection of fetal abnormalities has become widespread in many industrialised countries. This resulted in a shift in timing of the diagnosis of congenital abnormalities in infants from the neonatal period to the prenatal period. This has major implications for both clinicians and the couples involved. In case of ultrasound diagnosis of fetal anomaly, there are several options for the obstetric management, ranging from standard care to non-aggressive care and termination of pregnancy. This essay explores the context of both clinical and parental decision making after ultrasound diagnosis of fetal abnormality, with emphasis on the Dutch situation. While normal findings at ultrasound examination have strong beneficial psychological effects on the pregnant woman and her partner, the couple is often ill prepared for bad news about the health of their unborn child in the case of abnormal findings. This is, in particular, true in settings where ultrasonography for the detection of fetal abnormalities is offered as an integral part of antenatal care without appropriate counselling. An important question is to what extent the couple should be supported in decision making when a fetal abnormality is diagnosed. In this context, the parental perception of having a choice varies markedly. When parents consider end-of-life decisions, they experience both ambivalent and emotional feelings. On the one hand, they are committed to their pregnancy, while on the other hand, they want to protect their child, themselves and the family from the burden of severe disability. These complex parental reactions have implications for the counselling strategy.

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.     

Traumatic giant aneurysms of the intracranial carotid artery presenting long after head injury

Three patients presented with giant aneurysms of the intracranial internal carotid artery that became symptomatic with expanding mass effects 4-10 years after severe head trauma accompanied by skull base injuries at the site of aneurysm formation. These aneurysms are therefore considered to be late manifestations of traumatic vessel disruption. Posttraumatic aneurysm growth was documented in one case of a supraclinoidal aneurysm. One intracavernous aneurysm was combined with a traumatic carotid-cavernous sinus fistula. Although the origin of intracranial aneurysms is usually considered to be traumatic only within a period of weeks or months after head injuries, giant aneurysms of the intracranial internal carotid may represent late complications of trauma in a number of cases.     

Life-threatening intrathoracic complications during treatment with extracorporeal membrane oxygenation

Extracorporeal membrane oxygenation (ECMO) has been successful (greater than 80% survival) in 35 centers in greater than 900 newborns with severe respiratory failure having an estimated mortality of greater than 80% on conventional management. During the last 3 years we have treated 79 newborns with 74 survivors (94%). Their diagnoses included meconium aspiration, persistent fetal circulation, respiratory distress syndrome, congenital diaphragmatic hernia, and sepsis. Seven patients (9%) had life-threatening intrathoracic complications requiring emergent intervention while on ECMO: tension hemothorax (3), tension pneumothorax (2), and pericardial tamponade (2). Pericardial tamponade and tension hemothorax and pneumothorax show a similar pathophysiology of increasing intrapericardial pressure and decreasing venous return. Perfusion is initially maintained by the nonpulsatile flow of the ECMO circuit before further decrease in venous return results in decreasing ECMO flow and progressive hemodynamic deterioration. Each of the seven patients demonstrated a clinical triad that includes increasing PaO2 and decreasing peripheral perfusion (as evidenced by decreasing pulse pressure and decreasing SvO2) followed by decreasing ECMO flow with progressive deterioration. The diagnoses were confirmed by transillumination, chest x-ray, or cardiac echocardiogram. Initial emergent placement of a percutaneous drainage catheter was temporizing in all seven cases. However, four patients required emergent thoracotomy for definitive treatment while still on ECMO. All seven patients were weaned from ECMO and are short-term survivors (6 months to 3.5 years). As use of ECMO for newborn severe respiratory failure increases, responsible physicians must be familiar with life-threatening intrathoracic complications and appropriate treatment strategies.     

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.