PGE1 abolishes the mitochondrial-independent cell death pathway induced by D-galactosamine in primary culture of rat hepatocytes

Background and Aim:  PGE₁ reduces in vivo and in vitro D-galactosamine (D-GalN)-induced cell death in hepatocytes. The present study was undertaken to elucidate the intracellular pathway by which D-GalN induces cell death in cultured hepatocytes. In addition, we evaluated if PGE₁ was able to modulate different parameters related to D-GalN-induced apoptosis in cultured rat hepatocytes.
Methods:  Hepatocytes were isolated from male Wistar rats (225–275 g) by the classical collagenase procedure. PGE₁ (1 µM) was administered 2 h before D-GalN (5 mM) in primary culture of rat hepatocytes. Apoptosis was determined by DNA fragmentation and caspase-3, -6, -8 and -9 activation in hepatocytes. Caspase activation was evaluated by the detection of the related cleaved product and its associated activity. Cell necrosis was determined by the measurement of lactate dehydrogenase (LDH) activity in culture medium. To elucidate the role of mitochondria, we measured neutral (nSMase) and acid (aSMase) sphingomyelinase, as well as the expression of cytochrome c in mitochondria and cytoplasm fractions from D-GalN treated hepatocytes.
Results:  D-GalN induced caspase-3 activation and DNA fragmentation in hepatocytes. This apoptotic response was not associated with the activation of caspase-6, -8 or -9. The use of specific inhibitors confirmed that only caspase-3 was involved in D-GalN-induced apoptosis. D-GalN did not modify nSMase and aSMase activities, nor mitochondrial cytochrome c release in hepatocytes.
Conclusions:  D-GalN induced apoptosis through caspase-3 activation but without modification of the activity of caspase-6, -8, -9, SMases or cytochrome c release. PGE₁ appears to prevent D-GalN-induced apoptosis by a mitochondria-independent mechanism.     

The whole leg radiograph

The whole leg radiograph (WLR), the standard technique for determining axial alignment, is usually taken in a standing position, although some prefer the supine position. To determine the difference between these two positions, we performed a standing and a supine WLR in 20 patients with a varus alignment. We found an average of 2 degrees more varus deviation in the standing position than in the supine position.     

Digital subtraction arthrography in preoperative evaluation of painful total hip arthroplasty

 Objective. The objective of this clinical study was to define the diagnostic value of plain radiography, digital subtraction arthrography and two-phase bone scintigraphy in patients with clinically loose or infected hip prostheses. Design. Digital subtraction arthrograms, scintigrams and plain radiographs of 70 consecutive patients who underwent revision hip arthroplasty were scored individually and in masked fashion for the presence or absence of features indicating loosening of femoral and/or acetabular components. The operative findings acted as the gold standard. Results. Digital subtraction arthrography was best (P<0.001) for predicting a loose acetabular component, while no significant additional predictive value was found for plain radiographs (P=0.24) and scintigraphy (P=0.27). Digital subtraction arthrography was also the most important modality for predicting a loose femoral component (P=0.001), while the plain radiograph was of significant (P=0.04) additional value and scintigraphy was of no additional value (P=0.13) on multivariate analysis. Conclusion. Digital subtraction arthrography gives the best results in the prediction of loosening of acetabular and femoral components. Plain radiographs give additional information on loosening of the femoral component, but scintigraphy offers no additional advantage.     

High sensitivity cardiac troponin T and interleukin‐6 predict adverse cardiovascular events and mortality in anticoagulated patients with atrial fibrillation

Summary. There are limited data on the prognostic role of biomarkers in anticoagulated patients with atrial fibrillation (AF). We evaluated the prognostic value of high sensitivity TnT (hsTnT) and high‐sensitivity interleukin‐6 (hsIL6) in a large cohort of AF patients taking oral anticoagulant therapy (OAC) as both biomarkers have been associated with adverse cardiovascular events. Methods: We studied 930 patients (51% male; median age 76) with permanent/ paroxysmal AF who were stabilized (for at least 6 months) on OAC (INRs 2.0–3.0). Plasma hsTnT and hsIL6 levels were quantified by electrochemiluminescense immunoassay at baseline. Patients were followed‐up for up to 2 years, and adverse events (thrombotic and vascular events, mortality and major bleeding) were recorded. Results: At follow‐up, 96 patients (3.97%/year) died whilst 107 had an adverse cardiovascular event (3.14%/year). On multivariate analysis, high hsTnT and high hsIL6 remained significantly associated with prognosis even after adjusting for CHADS₂ score: HR 2.21 (1.46–3.35, P < 0.001) for high hsTnT and 1.97 (1.29–3.02, P = 0.002) for high hsIL6, for adverse cardiovascular events. For all‐cause mortality, the HRs were 1.79 (1.13–2.83, P = 0.013) and 2.48 (1.60–3.85, P < 0.001), respectively. The integrated discrimination index (IDI) values of clinical scores (CHADS₂ and CHA₂DS₂‐VASc) were improved by the addition of hsTnT and/or hsIL6 (all P < 0.05). Conclusion: In a large ‘real world’ cohort of anticoagulated AF patients, both hsTnT and hsIL6 levels provided prognostic information that was complementary to clinical risk scores for prediction of long‐term cardiovascular events and death, suggesting that these biomarkers may potentially be used to refine clinical risk stratification in AF.     

A dermoid cyst fistulating with the transverse colon

We present a rare case of fistulation of a dermoid cyst with the transverse colon. We illustrate how an infected dermoid cyst can be diagnosed as an appendix abscess although the management of these is quite different. The general surgeon should be aware of this as a differential diagnosis for an appendix abscess.     

Joint space narrowing and relationship with symptoms and signs in adults consulting for hip pain in primary care

OBJECTIVE: To study whether clinical symptoms and signs can predict radiological osteoarthritis (OA) of the hip in primary care patients with hip pain. METHODS: Consecutive patients (n = 220) aged 50 years or older consulting the general practitioner for hip pain and referred for radiological investigation underwent a standardized history, radiological, laboratory, and physical examination. Radiological OA was confirmed with joint space < or = 2.5 mm. Additionally, a more stringent definition was used (< or = 1.5 mm). The relationship between radiological OA and possible clinical symptoms/signs of OA was tested. Combinations of clinical symptoms/signs that had shown an independent relationship with radiological OA in multivariate analyses were tested for their predictive value. RESULTS: Radiological OA (joint space < or = 2.5 mm) of the (more) symptomatic hip was present in 35.5% of the study population and more severe OA (joint space < or = 1.5 mm) in 11.4%. Presence of 4 specific symptoms/signs from history and examination showed a positive predictive value (PPV) of 73% (specificity 91%, sensitivity 45%) for radiological OA. When 5 specific symptoms/signs were present, the PPV for the more severe radiological OA was 82% (specificity 98%, sensitivity 72%), and when 6 or 7 specific symptoms/signs were present the PPV was 100% (specificity 100%, sensitivity 40% and 8%, respectively). Negative predictive values were high for almost all combinations. CONCLUSION: In primary care patients with hip pain, clinical symptoms and signs can to a moderate extent predict radiological OA and to a large extent more severe radiological OA.