Pulmonary amyloidosis in hematological disorders

Amyloidosis is defined by tissue deposits of amyloid, a proteic substance with a characteristic spatial structure of beta-sheet fibrils assembled into bundles. This structure results in specific staining with Congo red dye, with green birefringence under polarized light microscope. AL amyloid forms from amyloidogenic immunoglobulins produced by clonal plasma cells. Pulmonary amyloidosis may be either part of systemic amyloidosis (primary amyloidosis or associated with myeloma) or organ-limited. Pulmonary interstitial amyloidosis in systemic amyloidosis is rarely symptomatic unless amyloid deposits severely affect gas exchange alveolar structures, thus resulting in serious respiratory impairment. Localized parenchymal involvement may present as nodular amyloidosis or as amyloid deposits in the vicinity of pulmonary lymphomas. Tracheobronchial amyloidosis, which is not associated with evident clonal proliferation, results in airway stenoses necessitating iterative laser treatment. Treatment of systemic amyloidosis aims at reducing the clonal cell populations producing amyloidogenic immunoglobulins, using high-dose chemotherapy followed by autologous stem cell transplantation in carefully selected patients. Its efficiency in treating diffuse pulmonary amyloidosis has not been established.     

Evaluation of thrombotic children with malignancy

The purpose of this study was to evaluate inherited and acquired prothrombotic risk factors among children with malignancies who have thrombosis and emphasize the importance of inherited prothrombotic risk factors. Thirty-seven consecutive children with thrombosis and malignancy were included in this study. The patients were evaluated separately for time of development of thrombosis, insertion of a central venous line (CVL), history of l-asparaginase usage, and recent infections. Prothrombotic risk factors such as factor V G1691A and prothrombin G20210A mutation, protein C, protein S, antithrombin III deficiencies, factor VIII and lipoprotein(a) elevation, and antiphospholipid antibodies were analyzed for all patients. Of 387 children with thrombosis, 37 (9.5%) had a malignancy. Thrombosis was detected in 9 patients at the time of diagnosis, during maintenance therapy in 25 patients, and after the discontinuation of treatment in 3 patients. One or two additional prothrombotic risk factors other than l-asparaginase therapy and insertion of central venous lines were present in 20 of these patients (54%). It was found that eight patients had the factor V G1691A mutation in the heterozygote state. One of them had the factor V G1691A mutation associated with a history of infection and one patient had the factor V G1691A mutation associated with factor VIII elevation. One had the the prothrombin G20210A mutation in the heterozygote state, four had lipoprotein(a) elevation, two had factor VIII elevation, one had a decreased protein S level, one had a decreased protein C level, one had antiphospholipid positivity, and two had histories of infection. Malignancy is an important risk factor for the development of childhood thrombosis. However, the risk of thrombosis increases when accompanied by additional prothrombotic risk factors. For this reason, especially children with malignancy and at high risk for the development of thrombosis, such as those who have received l-asparaginase or a replaced CVL during their therapy, might be screened for additional prothrombotic risk factors and appropriate measures might be taken to prevent the development of thrombosis.     

The prevalence of symptomatic knee and distal interphalangeal joint osteoarthritis in the urban population of Antalya, Turkey

The aim of this cross-sectional study was to estimate the prevalence and risk factors of symptomatic knee and distal interphalangeal (DIP) joint osteoarthritis (OA) in the elderly (50 years of age) urban population of Antalya, Turkey. According to the 1997 national census, Antalyas population was 508,840. By random cluster sampling, 655 individuals aged 50 years or more were interviewed face-to-face and subjected to structured interviews regarding knee pain, worsening pain on exertion, and the gelling phenomenon. They were also asked about performing namaz (a fundamental act of worship in Islam performed five times a day), smoking, type of residence, type of toilet, work style, and duration of walking per day. They were also questioned about swelling in DIP joints. In the case of suspicion of knee OA, the individuals were invited to the hospital for further evaluation by physical examination and direct roentgenogram. The diagnosis of knee OA was based on clinical or clinical and radiographic findings. The prevalence of symptomatic knee OA was determined as 14.8% in the population aged 50 years or over. Advanced age, female sex, namaz, and type of residence were found to be associated with knee OA. The rate of symptomatic knee OA was significantly lower in smokers and those walking more than 2 h per day. Female sex was also strongly associated with OA DIP joints. OA of DIP joints was found significantly associated with symptomatic knee OA. The latter is a major health problem in the elderly population, especially in about one fourth of women aged 50 years or over. These data suggest that advanced age, female sex, and type of residence are risk factors.     

Dipeptidyl peptidase IV in mammalian lungs

Endothelial cells of the pulmonary circulation are equipped with an ectoenzyme protease system on their luminal surface. The membrane-bound proteases act on the circulating polypeptides and cleave certain peptide bonds in their structure, thus modifying their biological properties. We studied the enzyme dipeptidyl peptidase IV (DP-IV) in mammalian lungs in order to elucidate its contribution to the aforementioned proteolytic processing. We have found that lungs of mammalian species posses DP-IV with different levels of specific activity. In rat lungs the specific activity of DP-IV progressively increased during development between the 18th fetal and the 70th postnatal days. Human embryonal and fetal lungs had significantly higher specific activity of DP-IV compared with the lungs of adult individuals. The enzyme in lungs was mainly membrane bound and was solubilized by some detergents, but not with papain and trypsin. The Triton X-100-solubilized DP-IV from rat lung lysosomal-microsomal membranes migrated during electrophoresis on continuous 4–30% gradient polyacrylamide gel at native apparent M_r values of 260 000 and 490 000. Using a histochemical technique we found the enzyme activity of DP-IV in the capillary bed of the lung alveolar septa only. Four aminoacyl-L-proline-4-nitroanilide substrates for DP-IV were cleaved rapidly during one passage through isolated perfused blood-free rat lungs. The perfusion profiles of cleavage of these substrates were largely coincident with that of Blue Dextran 2 000, a compound, which is unlikely to leave the intravascular space. Taken together, the data suggest that DP-IV operates in vivo as a membrane-bound ectoenzyme on the luminal surface of pulmonary endothelial cells and that it may cleave certain circulating polypeptides.     

Flt3-ligand induces adhesion of haematopoietic progenitor cells via a very late antigen (VLA)-4- and VLA-5-dependent mechanism

The adhesion of haematopoietic progenitor cells (HPC) to the bone marrow microenvironment is a process regulated by cytokines. In this study, we have shown that flt3-ligand (FL), a growth factor that controls early haematopoiesis, regulated the function and expression of the beta-1 integrins, very late antigen (VLA)-4 and VLA-5 on HPC. The modulation of the adhesiveness of HPC by FL was studied by adhesion assays on umbilical vein endothelial cells (HUVEC). Stimulation by FL induced two peaks of increased adhesiveness of HPC. The first peak was at around 30 min and was mechanistically related to an activation of the beta-1 integrins, mainly VLA-4 and VLA-5. The second peak was at around 12 h and was related to increased expression of VLA-4 and VLA-5. The control of HPC adhesiveness by FL is a previously unreported property of FL that may be important for the homing and the retention of flt3-expressing HPC within the bone marrow microenvironment.     

Measuring pressure-derived fractional flow reserve through four French diagnostic catheters

Measurement of fractional flow reserve (FFR) with a pressure wire is used to discriminate between patients with and without functionally significant lesions. FFR can be assessed through a conventional 4Fr diagnostic catheter, which is a more convenient method of assessment. The aim of this study was to assess the feasibility, safety, repeatability, and reliability of routine FFR measurements through 4Fr diagnostic catheters. From a single-center prospective registry, results of FFR assessment through a 4Fr catheter were used to determine: (1) feasibility and safety, by the procedural success rate and immediate and 30-day clinical outcome; (2) repeatability, by the intraclass correlation coefficient and comparison of the difference (means +/- 2 SDs); and (3) reliability, by comparison of results obtained using 4Fr versus 7Fr guiding catheters. During the study period, FFR was measured in 190 patients, in 122 using a diagnostic 4Fr catheter (study population) and in 68 using a 7Fr guiding catheter. Measurement of FFR wa successful in 115 of 122 patients (94%). No complications related to the use of the 4Fr catheter occurred. Repeatability was determined from 108 repeated measurements: the intraclass correlation coefficient was 0.942 and the mean difference between repeated FFR measurements was -0.001 +/- 0.038. Reliability was determined from 15 unselected patients; there was no systematic error and only 1 value was out of the range of 2 SDs of the mean difference. Using a threshold value of 0.75, the Kappa coefficient for the qualitative agreement was 0.84. Thus, pressure-derived FFR assessment can safely be performed through 4Fr diagnostic catheters, with similar repeatability and reliability as 7Fr guiding catheters, resulting in a simplification of the measurement procedure.     

Investigation of megakaryocyte apoptosis in children with acute and chronic idiopathic thrombocytopenic purpura

OBJECTIVE: Although the platelet destruction shows a primary role in the thrombocytopenia of idiopathic thrombocytopenic purpura (ITP), it has been demonstrated that impaired platelet production may also contribute to the severity of thrombocytopenia in ITP. The present study examined megakaryocyte apoptosis in bone marrow aspirates of children with acute and chronic ITP and investigated the role of megakaryocyte apoptosis in ITP pathophysiology. METHODS: Thirteen children diagnosed with acute ITP and eight children diagnosed with chronic ITP comprised the study group. Ten children, who were hospitalized for scoliosis operation but healthy otherwise, comprised the control group. In all children, megakaryocytes were isolated from the same amount of bone marrow aspirate samples using MACS CD61 MicroBeads (Miltenyl Biotec, Auburn, CA, USA). Megakaryocyte apoptosis was studied with transferase-mediated d-UTP-bitin nick end-labeling method. RESULTS: Isolated megakaryocyte counts did not differ significantly between acute ITP, chronic ITP and control groups. The percentage of apoptotic megakaryocytes did not differ significantly between acute ITP group and control group and between chronic ITP group and control group. The percentage of apoptotic megakaryocytes in patients with chronic ITP was significantly lower than the patients with acute ITP. There was no correlation between the percentage of apoptotic megakaryocytes and platelet counts of the cases. CONCLUSIONS: Increased megakaryocytic apoptosis does not play a role in the pathogenesis of dysmegakaryopoiesis and impaired platelet production in children with ITP. Decreased megakaryocyte apoptosis in cases with chronic ITP may be due to suppression of megakaryocyte maturation, as the terminal phase of the megakaryocyte lifespan is characterized by the onset of apoptosis.     

Occurrence, productivity and spatial distribution of key-premises in two dengue-endemic areas of Rio de Janeiro and their role in adult Aedes aegypti spatial infestation pattern

Objectives To evaluate: (1) the occurrence, maintenance, productivity, spatial distribution and premise condition index score of Adese aegypti‐infested houses and key‐premises in a suburban district (Tubiacanga) and a slum (Favela do Amorim) of Rio de Janeiro and (2) the role of these factors in adult Ae. aegypti female spatial distribution. Methods and Results A total of 2456 premises were inspected for immature and 1100 for adult collection. Key‐premises corresponded to 16.08% and 17.86% of infested houses in Tubiacanga, and 13.5% and 11.1% in Favela do Amorim, during the dry and wet seasons, respectively. Key‐premises held significantly more immature Ae. aegypti, pupae and larvae than infested houses in Favela do Amorim and Tubiacanga during the dry and wet seasons. In Favela do Amorim, key‐premises had a significantly higher PCI score than infested but non‐key houses. Conclusion The spatial distribution of key‐premises and adult Ae. aegypti females was often congruent, indicating that key‐premises influence the infestation pattern observed in the study areas.     

Melatonin ameliorates oxidative organ damage induced by acute intra-abdominal compartment syndrome in rats

Acutely increased intra-abdominal pressure (IAP) can lead to multiple organ failure. As blood flow to intra-abdominal organs is reduced by high venous resistance, ischemia-reperfusion (I/R) injury plays an important role in the pathogenesis of abdominal compartment syndrome (ACS) following IAP. Melatonin, a secretory product of the pineal gland, is known to have free radical scavenging and antioxidative properties in several oxidative processes. The objective of this study was to examine the potential protective properties of melatonin on the oxidative organ damage in a rat model of ACS. Under ketamine anesthesia, an arterial catheter was inserted intraperioneally (i.p.) and using an aneroid manometer connected to the catheter, IAP was kept at 20 mmHg (ischemia group; I) for 1 hr. In the ischemia/reperfusion (I/R) group, pressure applied for an hour was decompressed and a 1-hr reperfusion period was allowed. In another IR group, melatonin was administered (10 mg/kg, i.p.) immediately before the decompression of IAP. The results demonstrate that tissue levels of malondialdehyde (MDA) and myeloperoxidase activity (MPO; index of tissue neutrophil infiltration) were elevated, while glutathione (GSH; a key to antioxidant) levels were reduced in both I and I/R groups (P < 0.05-0.001). Melatonin treatment in I/R rats reversed these changes (P < 0.01-0.001). Moreover, melatonin given to the I/R group reduced the elevations in serum aspartate aminotransferase, alanine aminotransferase and blood urea nitrogen levels and abolished the increase in serum creatinine levels. Our results indicate that melatonin, because of antioxidant and free radical scavenging properties, ameliorates reperfusion-induced oxidative organ damage. In conclusion, the results of the present study suggest that the therapeutic value of melatonin as a 'reperfusion injury-limiting' agent must be considered in ACS.