[Right ventricular hypertension caused by hypothalamic stimulation in the curare-treated cat. 3. Simultaneous recording of left atrial pressure].
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Biomedical subjects
Publications and source records attributed to A Grossi.
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A significant percentage of patients undergoing myocardial revascularization suffer from extracranial cerebrovascular disease; recognition of such combined lesions identifies patients at risk for cerebrovascular accidents during the cardiac procedure. Simultaneous or staged coronary artery bypass graft (CABG) and carotid endarterectomy operations have been performed for the last 20 years, however, the clinical indications and the timing of the procedures remain controversial issues. Between November 1988 and January 1994, 1122 patients underwent myocardial revascularization at our Institute and in 35 cases (3.7%) carotid endarterectomy was simultaneously performed; 502 isolated carotid endarterectomies were performed in the same period. Trivascular coronary artery disease was found in 27 cases and low ejection fraction in six. Each patient received an average of 3.7 coronary grafts. Hospital mortality was 5.7% and major neurologic morbidity 2.8%. We believe that a simultaneous approach is recommended in patients with unstable angina and symptomatic carotid artery disease; in patients with a critical but asymptomatic carotid artery stenosis the indication for operation is subject to individual clinical judgment.
Release of vascular endothelial growth factor (VEGF) and other candidate angiogenic factors such as basic fibroblast growth factor and transforming growth factor beta, may play a role in sustaining neoplastic cell proliferation and tumor growth. We evaluated VEGF expression and synthesis in the two erythromegakaryocytic cell lines B1647, HEL and one megakaryocytic cell line MO7 expressing erythroid markers. In this study RT-PCR was performed to evaluate VEGF expression and that of its receptor KDR; VEGF production was assayed by Elisa test and western blot analysis; sensitivity to VEGF was tested by thymidine incorporation. VEGF and its receptor KDR were expressed in B1647 and HEL, both as mRNAs and as proteins, while only KDR transcript was found in MO7 cells. Only B1647 and HEL cells showed a strong spontaneous proliferating activity. In fact, measurable amounts of VEGF were present in the unstimulated cell medium, thus suggesting an autocrine production of VEGF by B1647 and HEL cells, but not by MO7, which was inhibited in mRNA-silencing conditions. This production could not be further boosted by other growth factors, whereas it was inhibited by TGF-beta1. Finally, analysis of Shc signal transduction proteins following stimulation with VEGF indicated that only p46 was tyrosine phosphorylated. These data indicate that leukemic cells may be capable of autocrine production of VEGF which, in turn, maintains cell proliferation, possibly mediated by Shc p46 phosphorylation.
BACKGROUND: There is some evidence that the erythropoietin (Epo) feedback mechanism in response to anemia can be altered in the period immediately following allogeneic bone marrow transplantation (BMT). METHODS: By using a RIA, serum erythropoietin (sEpo) levels were serially measured in 10 BMT patients, from day -10 up to day +30, and the results correlated with the concurrent hemoglobin (Hb) value. Thirty healthy subjects and 15 iron-deficiency anemic patients were used in order to construct our own reference sEpo vs Hb curve. A sEpo value recorded in BMT patients was considered to be inappropriate for any given Hb value when falling below the lower 95% confidence limit of the control curve. RESULTS: Basal sEpo levels were significantly higher than in healthy subjects, and increased further during the BMT procedure, being still higher than controls on day +30. However, Epo production resulted inappropriate for each given Hb value, when compared with the control curve, in 60 out of 67 sEpo determinations performed following graft infusion. The inadequate Epo production was not associated with the development of clinically manifest signs of kidney toxicity. CONCLUSION: These data indicate that Epo production is impaired in the period immediately following BMT and suggest a role for the administration of recombinant human Epo in the short-term management of the anemia associated with BMT.
BACKGROUND AND METHODS: Twenty-five thrombocytopenic patients underwent quantitative in vivo platelet kinetic studies using a scintillation camera and a computer-assisted imaging system. They fulfilled the criteria for chronic immune thrombocytopenia, and the object of the study was to evaluate platelet sequestration and destruction in the spleen. In this sense, the differences in the distribution of the radiolabelled platelets in the spleen and the liver, as well as the differences in the platelet mean life span (MLS) as computed by different methods were assessed. Serial images of the spleen pool, liver and heart were taken after reinjection of In-111-oxine labelled autologous platelets. RESULTS AND CONCLUSIONS: The spleen/liver ratio proved to be a more reliable index in indicating the splenectomy outcome that the Z index (see text). Platelet survival curves were analyzed using four mathematical models, and it was found that MLS estimation is model dependent. Thus, it seem advisable to apply at least two different methods when analyzing experimental data.
As it's well known from the clinic, human syndromes depending on pituitary GH, ACTH and PRL secreting tumors are associated with alteration of glucose homeostasis. There is an hypothetical but convincing explanation for this, based on a number of concrete observations and experiments. The main mechanism for glucose intolerance or overt diabetes is related to insulin-resistance. The increased concentration of the three hormones would alter the action of insulin on its target cells at binding and (mainly) post-binding level. Besides recent researches indicate that the hypothalamus may play an important role in the pathogenesis of at least some cases of pituitary adenomas and, directly or indirectly, of the glucose homeostasis derangement.
Erythroid precursors were obtained from the spleen of mice made anemic with phenylhydrazine and used to study the binding of bioactive 125I-rEp to membrane receptors. Kinetic analysis, using splenic cells obtained at different times following the induction of anemia, showed that the maximum binding was reached at day 3, and decreased thereafter; minimal amounts of 125I-rEp were bound to the splenic cells of normal mice. Splenic cells of day 3 anemic mice were fractionated using continuous Percoll density gradients, resulting in a fraction enriched in CFU-E (delta = 1.065-1072 g/ml) which showed the highest 125I-Ep binding on a per cell basis. The amount of 125I-rEp bound was greatly reduced in the densest fractions, which were comprised of maturing erythroblasts. The binding was time- and temperature-dependent, and a significant correlation was found with cell concentration up to 12 X 10(6). The amount of radioactivity specifically bound rose with increasing concentrations of 125I-rEp until a plateau was reached (2.5 nM), whereas non specific binding increased slightly and linearly. The binding of 125I-rEp was susceptible to competitive inhibition by unlabeled rEp, while other hematopoietic growth factors were ineffective. The calculated receptor density on these purified immature erythroid progenitors was 570 molecules with a Kd = 0.5 nM. Overall, these results suggest that the expression of the Ep receptor is reduced with increasing maturation.
Early diagnosis of total or partial GH (GHD) deficiency permits immediate treatment with biosynthetic GH and the achievement of a final stature close to the target one. However we frequently observe a progressive reduction in rate of growth ("vaning") during this therapy which delays attainment of adult stature compared to normal subjects. Subacute administration of GH on alternating days results in fair comparability of GH and Sm-C levels with physiological levels and it is therefore preferable to the i.m. route. Treatment should be interrupted when the growth rate is L2 cm/year or upon attainment of puberal stage P4 (female)-P5 (male). Rare side effects are the appearance of hypothyroidism, anti-GH antibodies (treatment with Met-Gh) and Creutzfeldt-Jakob disease (extractive GH).
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Fourteen patients with pituitary lesions and 6 normal subjects underwent the following tests: a) LHRH (100 mcg) + TRH (200 mcg) + Human Insulin (0.1 UI/kg) i.v. (Politest "A"); b) LHRH (100 mcg) + TRH (200 mcg) + GHRH 1-29NH2 (100 mcg) i.v. (Politest "B"); c) GHRH 1-29NH2 (100 mcg) i.v. (GHRH-TEST). FSH, LH and PRL, as assayed in patients and controls in response to Politest "A" and "B", revealed no significant differences between the tests. Plasma TSH values were significantly higher after Politest "B" in both patients and normals. The GH response after Politest "A" and "B" was similar in magnitude and concordant in 88.8% of cases.
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BACKGROUND: Stem cell factor (SCF) has already been shown to participate in the regulation of erythro- and granulopoiesis. The aim of this study was to define the possible role of SCF in the regulation of megakaryocytopoiesis. METHODS: Stem cell factor activity has been assessed in an in vivo murine model, in which different doses of the factor were either given alone or in association with recombinant human erythropoietin (rhEpo). Mice were sacrificed after a six-day treatment to evaluate the effect of SCF on the number of bone marrow and spleen colony-forming units-megakaryocyte (CFU-Mk), and after a two-day treatment for evaluation of thrombopoietin-like activity. RESULTS: We found that SCF induces a dose-related increase in the number of CFU-Mk in both the bone marrow and spleen of the treated mice, and that in the range of the doses used (from 25 to 200 mg/kg/day) the greatest activity was observed when a dose of 200 mg/kg/day was injected. The effect was enhanced by adding rhEpo to optimal SCF concentrations. SCF also stimulated megakaryocyte maturation as assessed by the megakaryocyte number, the size of acetylcholinesterase-positive cells, 35Sulphur (35S) incorporation into the newly formed platelets. All these parameters were only minimally affected by the addition of rhEpo. CONCLUSIONS: These data suggest that SCF participates in the regulation of megakaryocytopoiesis and that its administration might have a role in the treatment of disorders of platelet production.
BACKGROUND: The occurrence of coagulation system alterations after bone marrow transplantation (BMT) and their possible role in the pathogenesis of thrombotic complications such as veno-occlusive disease of the liver (VOD) are still a matter of debate. The aim of this study was to evaluate prospectively the alterations in hemostatic balance developing during the early period after BMT (up to day +21) and their relationships (if any) with VOD. PATIENTS AND RESULTS: Twenty-nine patients (15 autologous and 14 allogeneic BMT) entered the study. No patient suffered from thrombotic and/or major hemorrhagic events. Since there were no differences between the two groups of patients with regard to modifications of coagulation parameters, they were considered together for the purposes of the study. We observed a progressive increase from baseline levels of fibrinogen, factor VIII activity (fVIII:C) and von Willebrand factor antigen (vWf), while factor VII antigen (fVIIAg), protein C and plasminogen significantly decreased. The alterations in these test values were maximal on day +14, with a trend towards normal levels one week later. There was no modification of PT, PTT, prothrombin fragment 1 + 2 (F 1 + 2), fXIIC, tPA, PAI-1, D dimer or protein S levels; serum levels of tumor necrosis factor-alpha were also unchanged. CONCLUSIONS: These results suggest that some alterations of the hemostatic system, probably a consequence of endothelial damage, can be detected early after BMT, but their clinical significance remains uncertain due to the lack of a correlation between hemostatic test alterations and the occurrence of thrombotic complications.
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