Reference intervals for thyrotropin in an area of Northern Italy: the Pordenone thyroid study (TRIPP).

PURPOSE: Thyrotropin (TSH) is the most accurate marker of thyroid dysfunction in the absence of pituitary or hypothalamic disease. Studies on TSH reference intervals (RIs) showed wide inter-individual variability and prompted an intense debate about the best estimation of TSH RIs. DESIGN: We performed a population study on TSH RIs, using current data stored in the laboratory information system (LIS), at the Hospital Department of Laboratory Medicine, Pordenone (Italy), historically an area of mild-moderate iodine deficiency with a relatively high goiter prevalence. METHODS: 136,650 individuals constituted the final sample. A TSH immunoassay was performed on fasting serum samples with the Dimension Vista 1500 analyzer (Siemens Healthineers). We adopted the Kairisto's procedure to analyze TSH data downloaded by the LIS, applying the indirect strategy for deriving RIs. RESULTS: TSH RIs of the entire population were 0.32-3.36 mIU/L with a distribution skewed towards higher values. RIs were 0.26-3.61 mIU/L for females, and 0.32-3.01 mIU/L for males. Unlike other studies, TSH median levels progressively decreased from 0-4 to 85-104 years in the overall population, both in male and in female subgroups, showing an inverse correlation between TSH and age in all groups. CONCLUSIONS: This study is the first to analyze a high percentage (40%) of individuals from an ethnically homogenous Caucasian population. The results obtained emphasize the opportunity to define the TSH RIs according to age, gender and race, in addition to assay methods, and provide further insight about the possible role of iodine status.

Identification of a novel agrin-dependent pathway in cell signaling and adhesion within the erythroid niche.

Establishment of cell-cell adhesion is crucial in embryonic development as well as within the stem cell niches of an adult. Adhesion between macrophages and erythroblasts is required for the formation of erythroblastic islands, specialized niches where erythroblasts proliferate and differentiate to produce red blood cells throughout life. The Eph family is the largest known family of receptor tyrosine kinases (RTKs) and controls cell adhesion, migration, invasion and morphology by modulating integrin and adhesion molecule activity and by modifying the actin cytoskeleton. Here, we identify the proteoglycan agrin as a novel regulator of Eph receptor signaling and characterize a novel mechanism controlling cell-cell adhesion and red cell development within the erythroid niche. We demonstrate that agrin induces clustering and activation of EphB1 receptors on developing erythroblasts, leading to the activation of α5ß1 integrins. In agreement, agrin knockout mice display severe anemia owing to defective adhesion to macrophages and impaired maturation of erythroid cells. These results position agrin-EphB1 as a novel key signaling couple regulating cell adhesion and erythropoiesis.

Enhanced responsiveness of blood pressure to sodium intake and to angiotensin II is associated with insulin resistance in IDDM patients with microalbuminuria.

We assessed blood pressure (BP), body weight, renal hemodynamics, and insulin sensitivity (by euglycemic-hyperinsulinemic clamp) in nine normoalbuminuric and seven microalbuminuric IDDM patients after 6 days on a low-sodium diet (20 mEq) and after 6 days on a high-sodium diet (250 mEq). In microalbuminuric but not in normoalbuminuric IDDM patients, switching from a low to a high-sodium diet was associated with a significant increase in mean BP (from 92 +/- 3 to 101 +/- 4 mmHg; P < 0.001) and in body weight (2.91 +/- 0.63 vs. 1.47 +/- 0.26 kg; P < 0.05). Moreover, under high-sodium conditions, angiotensin II infusion (3 ng x kg(-1) x min(-1)) caused a greater increase in mean BP (14 +/- 2 vs. 7.4 +/- 1 mmHg; P < 0.05) and a smaller reduction in renal plasma flow (-122 +/- 29 vs. -274 +/- 41 ml x min(-1) x 1.73 m2; P < 0.05) in microalbuminuric than in normoalbuminuric IDDM patients. Under low sodium conditions, aldosterone increments after angiotensin II infusion were lower (P < 0.05) in microalbuminuric than in normoalbuminuric IDDM patients. Insulin-mediated glucose disposal was not affected by sodium dietary content, but it was lower in microalbuminuric (P < 0.05) than in normoalbuminuric IDDM patients. The salt-induced changes in mean BP were related to insulin sensitivity (r = -0.78; P < 0.001). In conclusion, in IDDM patients, microalbuminuria is associated with 1) an increased responsiveness of BP to salt intake and angiotensin II, 2) impaired modulation of renal blood flow, and 3) insulin resistance. Therefore, salt sensitivity in IDDM patients clusters with other factors that are likely to play an important role in the pathogenesis of diabetic nephropathy and its cardiovascular complications.

A "primitive" catastrophic antiphospholipid syndrome.

A female patient affected by a thrombotic syndrome due to non SLE-related antiphospholipid antibodies (APA), developed a serious, non inflammatory, thrombotic macroangiopathy and uremic-hemolytic syndrome during oral anticoagulant therapy. She was treated with aspirin, dipyridamole i.v. and with a total of 14 fresh frozen plasma exchange (PEX), but the thrombotic syndrome only showed a partial response with the APA titre dropping considerably. Renal failure did not improve because of acute cortical necrosis. The patient died from infective complications.

Plateletpheresis during plasma collection.

New systems for collection of platelet concentrate (PC) and platelet poor plasma (PPP) are presently available. The aim of our work was to test the possibility of preparing PC routinely from normal plasma donors in a minimum amount of time and, at the same time, providing a second product that can be used as source-plasma or fresh-frozen plasma. Over a 3 year period (from 1990 to 1992) we performed 3503 procedures using 2 Haemonetics PCS machines (1236 procedures) and 3 Autopheresis-C (2267 procedures). With the PC produced we were able to satisfy all the requests coming from the hospitals of our region. The platelet yield was 1.95 x 10(11) with PCS and 3.2 x 10(11) with Auto-C in a PC volume of 150 and 200 ml respectively; collection times were quite similar (56 and 63 min). The results show that plasma-plateletpheresis is an efficient and competitive system. Regarding platelet yield, the best results were obtained with the Auto-C.

A hemorrhagic syndrome of the elderly patient caused by anti-factor VIII antibodies.

We report here 2 cases of elderly patients who were admitted to our Department of Geriatrics for a hemorrhagic syndrome. The patients were found to be affected by a coagulopathy with prolonged activated partial thromboplastin time (aPTT), caused by the presence of an acquired inhibitor of Factor VIII. This syndrome, due to anti-Factor VIII antibodies, is surely an important clinical entity that is not easy to diagnosed, but in concomitance with a hemorrhagic syndrome and prolonged aPPT it should always be suspected. In fact, a quick diagnosis is very important in order to apply specific treatment as soon as possible.

Prolymphocytic leukemia: a very satisfactory response to treatment with recombinant interferon alpha.

We report the case of a patient with prolymphocytic leukemia in whom a lengthy survival of 5 years was observed after treatment with splenic irradiation and chemotherapy. The patient obtained a surprising improvement with a significant reduction in the absolute count of the prolymphocytes and considerable reduction in splenomegaly after 3 months' therapy with interferon alpha.

[Burkitt's lymphoma with leukemic evolution]. / Linfoma di Burkitt ad evoluzione leucemica.

An account of the clinical, histopathological and aetiopathogenetic aspects of Burkitt's lymphoma is followed by the presentation of a personal case, in which the typical clinical picture of the African form progressed to terminal leukaemia. The aetiological and pathogenetic rôle of the Epstein-Barr virus is also briefly discussed.