Coinfection with hepatitis C virus (HCV) and HIV is not uncommon and therapies for both infections are currently available. A major drawback, however, could be a potentially higher risk for ...mitochondrial toxicity (MT), defined as the elevation of pancreatic enzymes or lactate levels due to the nucleoside analogue reverse transcriptase inhibitors contained in both therapies.
Prospective analyses of clinical and laboratory data, including plasma lactate levels and pancreatic enzymes, of 113 consecutive HIV/HCV-coinfected patients were assigned to receive ribavirin (RBV) plus interferon (IFN)-alpha.
Fourteen patients (12%) showed increased levels of amylase/lipase and/or hyperlactataemia. No patient developed clinical pancreatitis. Four patients with hyperlactataemia had clinical symptoms of lactic acidosis and recovered uneventfully by 2 weeks after treatment withdrawal. The variables significantly associated with MT in the univariate analysis were: therapy with didanosine (ddl), ddl plus stavudine (d4T), previous history of diabetes and the baseline lactate level. However, ddl use was the only independent risk factor for MT identified in the multivariate analysis. MT was not associated with gender, age, alcohol consumption, type of IFN, degree of steatosis and fibrosis in liver biopsy, presence of lipodystrophy, CD4+ cell count, HCV or HIV viral load, mitochondrial DNA and COXII-expression in liver tissue, or antiretroviral therapy containing d4T or protease inhibitors.
12% of HIV/HCV-coinfected patients receiving IFN plus RBV concomitantly with highly active antiretroviral therapy developed laboratory markers of MT. Although most of cases were asymptomatic, our study suggests that concomitant use of RBV plus ddl should be avoided, and that routine monitoring of lactate and pancreatic enzymes may be recommended.
Bleeding and thrombosis in myeloproliferative disorders (MPD) are common events, sometimes both are present in the same patient during the course of the disease. Platelet activation in patients with ...MPD is often suggested. The present study analyses the presence of circulating activated platelets, using simultaneously flow cytometry and aggregometric studies in MPD. We studied 28 patients: 13 with polycythaemia vera, seven with essential thrombocythaemia, and eight chronic myeloid leukaemia. We performed functional tests, aggregation and adenosine triphosphate (ATP) release and flow cytometric assays (mepacrine staining and platelet activation markers CD62, CD63 and fibrinogen binding (B-FG)). Twenty-one MPD samples (75%) had reduced aggregation and ATP release. Acquired delta-SPD was detected in 11 of 28 MPD patients (39%), and we found no association between reduced mepacrine labelling and abnormal ATP release. High levels of activation markers were obtained: CD62 in 19 of 28 patients (68%), CD63 in 13 of 28 patients (46%) and B-FG in 19 of 28 patients (68%). The most prevalent abnormality was a reduced aggregation and ATP release. The lack of association between ATP release and mepacrine labelling suggests that other mechanisms, besides the deficit of intraplatelet ATP/adenosine diphosphate, might occur. High levels of activation markers were also observed. We conclude that both tests are complementary and necessary to understand the functional status of platelets in MPD.
Abstract
Background
Glutaraldehyde fixation does not guarantee complete tissue biocompatibility in current clinical bioprosthetic heart valves (
BHV
s). Particularly, circulating anti‐α
G
al human ...antibodies increase significantly from just 10 days after a
BHV
implantation. The inactivation of such epitope should be mandatory to meet the requirements for a perspectively safe clinical application; nevertheless, its quantitative assessment in commercially available
BHV
s has never been carried out.
Methods
In this investigation, seven different models of
BHV
s were tested. The number of epitopes was determined with reference to a standard α
G
al source by an
ELISA
test. The presence of xenoantigen was subsequently confirmed by immunofluorescence analysis. Porcine tissue, knockout for the α
G
al epitopes, was used as negative control.
Results
E
pic™ valve was the only model among those tested, in which the α
G
al antigen appeared to be completely shielded. Composite
T
rifecta™ valve exhibited conflicting results: cusps of bovine pericardial tissue were devoid of reactive α
G
al epitopes, while the stent cover strip of porcine pericardium still maintained 30% of active antigens originally present in native tissue. All other tested
BHV
s express an α
G
al amount not significantly different from that exhibited by porcine
M
osaic
®
valve (5.2 ± 0.6 × 10
10
each 10 mg of tissue).
Conclusions
For the first time, the quantitative evaluation of the α
G
al epitope in heart valve bioprostheses, already in clinical practice for about 40 yrs, was finally determined. Such quantification might provide indications of biocompatibility relevant for the selection of bioprosthetic devices and an increase in the confidence of the patient. It might become a major quality control tool in the production and redirection of future investigation in the quest for α
G
al‐free long‐lasting substitutes.
Bovine herpesvirus 4 (BoHV-4) is a gamma herpesvirus with no clear disease association. Previous studies have demonstrated that macrophages can harbour persistent BoHV-4. Since mesenchymal stem cells ...in bone marrow regulate the differentiation and proliferation of adjacent haematopoietic precursors, such as macrophages, the interaction between BoHV-4 and mesenchymal stem cells was investigated. Primary bovine mesenchymal stem cells were highly permissive to support full replication of BoHV-4. This finding could be considered a new important step in studies on the potential pathogenesis related to BoHV-4.
This study evaluated the role of pulsed dose-rate (PDR) brachytherapy (BRT), delivered alone or as a boost to external beam radiotherapy, as adjuvant therapy for the local control of soft tissue ...sarcomas of the extremities and skeletal muscles of the trunk that have undergone surgical treatment.
Between July 1998 and January 2002, 42 patients were treated with a combination of surgery and BRT alone (18 patients) or BRT/external beam radiotherapy (24 patients) for the treatment of primary (n = 32) and recurrent (n = 10) soft tissue sarcomas located in the proximal extremity (n = 17), distal extremity (n = 17), and trunk (n = 8). Tumor size was <5 cm in 20 cases and >5 cm in 22 cases, with histological grading of 1 (n = 7), 2 (n = 18), or 3 (n = 17). The median BRT dose delivered was 15 Gy, and the median external beam irradiation dose was 50 Gy.
With a median follow-up of 34 months, the 36-month survival was 83.9% (SE, 6.1%), and the local control was 89%.
PDR interstitial BRT for soft tissue sarcoma is an effective, well-tolerated adjuvant radiation treatment that offers several practical advantages, among which are low acute and late toxicity with maximum normal tissue and critical structure sparing and overall shorter radiotherapy and hospital stay.
Introduction: The lupus anticoagulant (LA) and the anticardiolipin antibodies (ACA) are the antiphospholipid antibodies more relevant clinically. Their clinical manifestations are diverse with most ...patients being asymptomatic while others present venous or arterial thrombosis, and more rarely, bleeding. Our objectives were to evaluate clinical presentation of LA in children and to correlate it to LA behavior.
Patients and methods: A retrospective cohort of patients (under 18 years old) who had a positive determination of LA followed by at least another determination of LA at a variable period was evaluated. Personal and family history, including infectious diseases temporally related to the event, were recorded. The screening of other coagulation disorders was performed according to symptoms, family history or laboratory results.
Results: Thirty-six patients were evaluated, median age was 10.8 years old, and 52.8% were female. Asymptomatic patients were 19.4% (7/36) of study population. Bleeding and thrombosis were found in 52.8% and 27.8%, respectively. Median LA determinations per patient were 3. von Willebrand disease was diagnosed in 66.7% of patients consulting for bleeding. A concomitant hemostatic defect was found in 8/10 patients with thrombosis (
p=0.003). LA behavior was not uniform and not correlated to symptoms.
Conclusions: Most LA found in children is incidental and asymptomatic. In children with bleeding, LA might be a fortuitous finding associated with VWD. The persistence of LA does not imply a higher risk of thrombosis.
PDF
