[Slipped capital femoral epiphysis in children]. / Epifysiolyse van de heupkop bij kinderen.

BACKGROUND: Slipped capital femoral epiphysis (SCFE) is among the most common causes of hip problems in childhood and adolescence. Its incidence is increasing due to rising childhood obesity. There are three different types of SCFE, the rarest of which is the acute traumatic slip. Early identification and urgent surgical treatment are necessary to minimise the risk of complications such as avascular necrosis. CASE DESCRIPTION: An overweight 12-year-old boy visited the emergency department complaining of pain in the left hip after falling from his scooter. The patient was unable to bear weight on his left leg and kept the hip in slight exorotation. An X-ray showed a slip of the femoral epiphysis, which was treated by emergency surgery. During short term follow-up there were no signs of complications such as avascular necrosis of the femoral head. CONCLUSION: Acute traumatic slip of the femoral epiphysis is rare. Patients with this condition require urgent surgical treatment to minimise the risk of complications.

Perceived health after kidney transplantation: a cross-sectional comparison of long-term and short-term cohorts.

Although increased longevity of grafts has led to a growing number of long-term kidney transplant recipients, knowledge about the perceived health of these patients remains limited. A cross-sectional sample of 609 patients (60% response) was stratified into a short-term (≤1 year), midterm (>1 and ≤8 years), and long-term cohort (>8 and ≤15 years posttransplantation). Cohorts were compared for perceived health (Visual Analogue Scale of the EQ-5D), number of symptoms, and number of comorbidities by analysis of variance/covariance and multivariate regression analyses. Long-term patients reported more symptoms, (F[2, 606] = 3.09, P = .046) and more comorbidities, (F[2, 588] = 4.75, P = .009) but similar levels of perceived health, (F[2, 550] = 2.37, P > .05). Furthermore, symptoms were less influential for perceived health among long- versus short-term (z = -2.08, P = .038) or midterm cohorts (z = -2.60, P = .009). Previously identified predictors of perceived health accounted for less variance in the long-term as opposed to short-term (z = 4.30, P < .001) and midterm cohort (z = 2.07, P = .039). Despite more symptoms and comorbidities, the perceived health of long-term kidney transplant recipients was comparable to the short- and midterm, possibly due to selective survival or patient adjustment. Because kidney function and symptoms were predominantly associated with short-term perceived health, there is an urgent need to identify variables associated with long-term perceived health.

Management of encapsulating peritoneal sclerosis: a guideline on optimal and uniform treatment.

Encapsulating peritoneal sclerosis (EPS) represents a rare complication of long-term peritoneal dialysis (PD). It is characterised by diffuse peritoneal membrane fibrosis, progressive intestinal encapsulation and the clinical spectrum of intestinal obstruction. The pathogenesis is as yet not well understood but includes inflammation, angiogenesis and fibrosis. The current diagnosis of EPS lacks specificity and relies on clinical, radiographic or macroscopic evaluation. There is no general agreement on managing EPS although accumulating clinical data suggest drug treatment (steroids, tamoxifen), surgery (enterolysis) or a combination of both. Here, we provide a short overview on the current knowledge of EPS, with a focus on treatment. Moreover, we present a diagnostic and a therapeutic algorithm for EPS based on the best available published data and our combined experience.

Use of bone morphogenetic proteins in traumatology.

An estimated 5-10% of all fractures show impaired healing, leading to delayed union, or non-union. Chemical, or physical methods to accelerate bone healing are of great interest to the orthopaedic and trauma community. Research over the last 20 years has established that successful fracture healing is steered by specific growth factors. Of these, the bone morphogenetic proteins (BMPs) are probably the most important. The signalling pathway of these proteins is tightly regulated, overseeing a finely orchestrated cascade of events that occur after a fracture. The promising results of BMPs in preclinical studies have recently cleared the way for their use in specific fractures, or non-unions in clinical practice. The purpose of this work is to give a brief overview of BMPs and to review the clinical data currently available on the use of BMPs in fracture healing.

[Hypokalemic paralysis with thyrotoxicosis]. / Hypokaliämische Lähmung bei Hyperthyreose.

Hypokalemic periodic paralysis as a complication of thyrotoxicosis (thyrotoxic periodic paralysis) most often occurs in east Asian men. It is characterised by recurrent episodes of flaccid paralysis, hypokalemia, and underlying hyperthyroidism. It needs to be distinguished from sporadic and familial forms of periodic hypokalemic paralysis. No disturbances in the acid-base state and no extracorporal potassium loss are present. We report on the typical case of a young Chinese man presenting with hypokalemic periodic paralysis associated with yet unknown Graves' disease. Intravenous substitution of potassium and oral propranolol were administered. Complete remission was achieved after 10 hours. After medical therapy had normalised thyroid hormone levels, no further hypokalemic paralytic attacks occurred.

Human mesangial cells in culture and in kidney sections fail to express Fc alpha receptor (CD89).

The mechanism of deposition of IgA in the renal mesangium in primary IgA-nephropathy is poorly understood. It has been suggested that membrane receptors for IgA on mesangial cells (MC) of the kidney may be involved. To obtain more insight in the occurrence of the myeloid receptor for IgA (CD89) on MC, both in situ and in culture, rabbit and goat polyclonal antibodies and mouse monoclonal antibody against recombinant CD89 were raised. Kidney sections from five control subjects and five patients with primary IgA-nephropathy failed to be positive for CD89 in the mesangium, using our polyclonal and monoclonal antibodies. Also, five primary human MC cultures assessed for CD89 expression showed no protein expression of CD89. Furthermore, reverse transcription-PCR failed to detect mRNA expression of CD89 in the cultured MC. It was demonstrated that all five human primary MC bound human IgA in a dose-dependent manner, which was not inhibitable by blocking monoclonal anti-CD89 antibody (My43). In contrast, binding of IgA to U937 cells was blocked efficiently by My43. Finally, incubation of human MC with either human or rat IgA led to increased interleukin-6 production, whereas only human IgA, but not rat IgA, was able to bind to human CD89. Therefore, it is concluded that human MC do not express CD89 (to a significant extent). These results strongly suggest that binding of IgA to human MC occurs via an IgA receptor distinct from CD89.

Role of interleukin-6 in mediating mesangial cell proliferation and matrix production in vivo.

Mesangial cell proliferation and matrix overproduction characterize many progressive glomerular diseases. Based on currently available data, the role of interleukin-6 (IL-6) in mediating mesangial cell proliferation and matrix production is controversial. The present study attempts to clarify this issue by showing that: (1) IL-6 knock out mice develop a normal glomerular architecture and in particular a normal mesangium. (2) Mesangioproliferative glomerulonephritis induced by Habu snake venom is equally severe in IL-6 knock out mice as in control mice. (3) A continuous seven-day intraperitoneal infusion of 50 micrograms recombinant human IL-6 into rats with a prior minimal (subnephritogenic) injury to mesangial cells does not induce glomerular cell activation, cell proliferation, matrix production, leukocyte influx, platelet influx or proteinuria. (4) A continuous seven-day IL-6 infusion into rats with mesangioproliferative nephritis (anti-Thy 1.1 nephritis) increases matrix protein transcription in the absence of detectable effects on matrix protein accumulation and otherwise has no effect on the natural course of the disease. We conclude from these findings that IL-6 is not an important mediator of mesangial cell proliferation and matrix overproduction in vivo, and that currently little rationale exists to advocate anti-IL-6 therapy in mesangioproliferative disease states.

Distinctive roles of neutrophils and monocytes in anti-thy-1 nephritis.

Anti-Thy-1.1 glomerulonephritis as an experimental model for mesangial proliferative glomerulonephritis was induced in Wistar rats by a single injection of monoclonal IgG2a-anti-Thy-1.1 antibody (ER4G). This transient model is complement-mediated and leads to mesangial-cell (MC) lysis followed by MC proliferation, glomerular microaneurysm formation, glomerular influx of polymorphonuclear leukocytes (PMNs) and macrophages, proteinuria, and hematuria. In this study we investigated the distinctive roles of infiltrating PMNs or monocytes/macrophages by treating rats with an antibody against rat integrin CD11b/CD18 (ED7) or by depletion of monocytes with multilamellar clodronate liposomes, respectively. ED7 administration resulted in reduction of the influx of PMNs in glomeruli during the first 6 days after induction of Thy-1.1 nephritis, whereas treatment with an isotype-matched irrelevant antibody (PEN9) or with phosphate-buffered saline had no effect on macrophage influx. Increased glomerular C3 and C6 deposition on days 1 and 3 was seen in the ED7-treated rats but not seen in the control groups. In addition, the ED7-treated group showed an increased number of aneurysmatic glomeruli and more severe hematuria. Monocyte/macrophage depletion led to a significant reduction of mesangial matrix expansion, although mesangial proliferation, proteinuria, and hematuria remained unaltered. These results, together with the known effects of PMN-derived enzymes on C3 cleavage, suggest that a reduction in the influx of PMNs results in sparing of C3 and consequently of more complement activation in the glomerulus with increased complement-mediated damage. Our data indicate that infiltrating PMNs and monocytes/macrophages play distinctive roles during inflammation in this model of MC glomerulonephritis.

Crosslinking of the human Fc receptor for IgA (FcalphaRI/CD89) triggers FcR gamma-chain-dependent shedding of soluble CD89.

CD89/FcalphaRI is a 55- to 75-kDa type I receptor glycoprotein, expressed on myeloid cells, with important immune effector functions. At present, no information is available on the existence of soluble forms of this receptor. We developed an ELISA for the detection of soluble CD89 (sCD89) forms and investigated the regulation of sCD89 production. PMA/ionomycin stimulation of monocytic cell lines (U937, THP-1, and MM6), but not of neutrophils, resulted in release of sCD89. Crosslinking of CD89 either via its ligand IgA or with anti-CD89 mAbs similarly resulted in sCD89 release. Using CD89-transfected cells, we showed ligand-induced shedding to be dependent on coexpression of the FcR gamma-chain subunit. Shedding of sCD89 was dependent on signaling via the gamma-chain and prevented by addition of inhibitors of protein kinase C (staurosporine) or protein tyrosine kinases (genistein). Western blotting revealed sCD89 to have an apparent molecular mass of 30 kDa and to bind IgA in a dose-dependent fashion. In conclusion, the present data document a ligand-binding soluble form of CD89 that is released upon activation of CD89-expressing cells. Shedding of CD89 may play a role in fine-tuning CD89 immune effector functions.