Sarcoidosis presenting as isolated giant splenomegaly.
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Biomedical subjects
Publications and source records attributed to A Perna.
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Glucocorticoids have a major role in the treatment of glomerular diseases. Despite recent advances in understanding of their mechanism of action, very few studies have addressed the relative advantage of the wide range of different dose regimens employed in clinical practice. We studied the effects of methylprednisolone given intravenously for three consecutive days at the doses of 1 mg/kg (group 1, N = 7; group 2, N = 5), 5 mg/kg (group 3, N = 5) or 15 mg/kg (group 4, N = 6) on total blood peripheral leukocytes and on lymphocyte subsets in patients with glomerular diseases, and investigated whether such effects were a function of the drug concentration in the blood. Since glucocorticoids have an inhibitory effect on the formation of eicosanoids in different cells, we also investigated in the same patients the effect of 1 and 15 mg/kg methylprednisolone on systemic and renal eicosanoid synthesis. Results of pharmacokinetic study showed that the three different doses of methylprednisolone we used resulted in major differences in patient's exposure to the drug, and within the same dose there was a great individual variability. By contrast the three different doses of methylprednisolone induced a comparable drop in the absolute number of lymphocytes six hours after the first injection of methylprednisolone, while 24 hours later blood lymphocyte counts returned to the pre-injection values in all patients. Analysis of lymphocyte subsets showed a selective decrease in the number of circulating CD4+ and CD8+ cells six hours after methylprednisolone which was comparable in the four groups of patients studied. As for the effect of methylprednisolone on systemic and renal eicosanoid synthesis in patients with glomerular diseases, 1 and 15 mg/kg were equally unable to reduce thromboxane A2 (TxA2) and prostaglandin E2 (PGE2) release by circulating polimorphonuclear cells (PMNs). By contrast, methylprednisolone partially inhibited eicosanoid synthesis by PMNs in vitro. Consistent with the data on PMNs, urinary excretion of TxA2 and prostacyclin (PGI2) metabolites were unaltered by the different doses of methylprednisolone. By contrast urinary PGE2 was markedly and significantly reduced in patients given 15 but not 1 mg/kg. We conclude that 1 mg/kg methylprednisolone given to patients with glomerular diseases has the same effect on peripheral total blood leukocyte count and lymphocyte subsets than 5 and 15 mg/kg. The same is true for eicosanoid synthesis by PMNs. Renal synthesis of PGE2 is inhibited by 15 mg/kg but not by 1 mg/kg.(ABSTRACT TRUNCATED AT 400 WORDS)
A case is reported of an accidental laboratory infection with a strain of Spotted Fever-Group Rickettsiae freshly isolated from a tick collected in Western Sicily. Inoculation into the left thumb of cell-cultured organisms (10(5)/ml) gave rise to clinical signs and symptoms of Boutonneuse Fever after six days, i.e., a lesion at the point of inoculation, fever, headache, conjunctivitis and myalgias. Rickettsiae were isolated from acute-phase blood samples collected from the infected individual and IgM and IgG response was detected in the patient's serum by indirect immunofluorescence. Complete recovery was obtained after antibiotic treatment. Serologic analysis of the strain, together with analyses of the proteins of the isolate, documented that the isolate was Rickettsia conorii and was identical to prototype strain. The relationship of this infection to ongoing studies on the epidemiology of Boutonneuse Fever in Western Sicily is discussed.
The effect of an acute protein load (2 g kg-1 bodyweight [BW]) was studied in nine type 1 diabetic children. Patients were maintained on two different dietary regimens. In study one, patients were on a high protein diet providing from 2.7 to 1.8 g of protein/kg of BW per day. In study two, patients were reevaluated after three weeks of a diet providing from 1.0 to 1.2 g kg-1 of BW per day of protein. In study one (High Protein Diet), we failed to observe any rise in GFR and RPF following the protein meal (137 +/- 21 basal vs. 110 +/- 14 and 472 +/- 93 basal vs. 494 +/- 93 ml/1.73 m2 of SA min-1 at 60 min. This is in contrast with results from seven age matched controls consuming a free diet, which showed a significant rise in both GFR and RPF. In study two (low protein diet), basal GFR was significantly reduced. However after the protein load, both GFR (92 +/- 11 vs. 126 +/- 18 ml/1.73 m2 of SA min-1) and RPF (467 +/- 83 vs. 705 +/- 102 ml/1.73 m2 min-1) rose significantly (P less than 0.05 vs. basal). The data indicate that: 1. short term protein restriction reduces significantly GFR in type 1 diabetic children; 2. diabetic children maintained on an high protein intake show an altered haemodynamic response to protein ingestion; 3. a normal response to protein ingestion can be restored by short term dietary protein restriction.
Hepatorenal bypass can successfully accomplish revascularization of the right renal artery when the aorta or the iliac vessels cannot be used for a standard renal bypass or renal autotransplantation. The use of the hepatic circulation can be increased by the gastroduodenal to renal artery bypass procedure. Herein we report a clinical case of severe hypertension in a patient with a solitary functional kidney and an extensive atheromatous alteration of the aortoiliac segment. It has been corrected by means of a gastroduodenal end-to-side renal saphenous vein bypass graft.
The effect of plasma amino acid and hormone (insulin, glucagon, and growth hormone) levels on renal hemodynamics was studied in 18 healthy subjects. The following four protocols were employed: study 1, a balanced amino acid solution was infused for 3 h to increase plasma amino acid concentrations two to three times base line; study 2, the same amino acid solution was infused with somatostatin (SRIF) and infusions of insulin, glucagon, and growth hormone were concomitantly administered to replace the time sequence of increase in peripheral concentrations of these hormones as observed during study 1; study 3, the same amino acid infusion was administered with SRIF plus infusions of insulin, glucagon, and growth hormone to maintain plasma hormone concentrations constant at the basal level; study 4, SRIF was infused with insulin, glucagon, and growth hormone to reproduce the time sequence of increase of these hormones as observed in study 1; amino acids were not infused in this study. During study 1, glomerular filtration rate (GFR) and renal plasma flow (RPF) rose by 19 and 21%, respectively. During study 2 both the time sequence of and magnitude of rise in GFR and in RPF were similar to the changes observed during study 1. In studies 3 and 4 neither RPF nor GFR changed significantly from base line. These results indicate that 1) hyperaminoacidemia stimulates insulin/glucagon/growth hormone secretion and causes a modest rise in GFR and RPF; and 2) if hyperaminoacidemia is created while maintaining basal hormone levels constant or if plasma insulin/glucagon/growth hormone levels are increased while maintaining the plasma amino acid concentration at basal levels, neither RPF nor GFR rise.(ABSTRACT TRUNCATED AT 250 WORDS)
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The results of an approximately 14-day treatment with 500 mg broncaspin capsules in 25 patients with recrudescent chronic bronchitis are presented. There was a marked, constant improvement in the subjective and objective symptomatology, and in respiratory function indices. The expectoration cell parameters displayed changes consonant with the therapeutic effect. Local and general tolerance were good overall.
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Notch signaling is an evolutionarily conserved mechanism used by invertebrates and vertebrates to control cell fates through close-range cell interactions. Four Notch receptors have been identified in vertebrates and different ligands, divided into Delta-like and Serrate-like (Jagged). Several studies have demonstrated that Notch signaling is involved in different branches of the cell fate decision tree: differentiation, proliferation and apoptosis. These three processes are finely regulated in human placenta in order to allow a successful pregnancy and a correct fetal growth. Moreover, Notch and its ligands participate in the vascular remodelling and stabilization, other two processes much important and ticklish in human placenta. So, we decided to investigate the pattern of expression of Notch-1, Notch-4 and Jagged-1, together with two members related to Notch pathway and involved in angiogenesis: VEGF and p21, in human placenta during gestation by immunoblotting and immunohistochemistry. We showed a modulation of Notch proteins throughout the pregnancy; in particular we showed a slight decrease of Notch-1 throughout pregnancy, with a decreased cytoplasmic staining from the first to the third trimester of gestation in cytotrophoblast and syncytiotrophoblast. In contrast Jagged-1 showed an increase throughout pregnancy especially in syncytiotrophoblast and stroma during the third trimester of gestation. In addition, we found by immunoblotting an increase of VEGF expression from the first to the third trimester and an intense VEGF expression inside endothelial cells throughout the gestation as also confirmed by immunohistochemistry. We also showed a decrease of p21 expression during the pregnancy both through immunoblotting and immunohistochemistry assays. Moreover, we observed Notch localization in extravillous trophoblast cells that are able to invade the decidualized endometrium. Our results suggest an involvement of Notch signaling in regulation of placental cell fate decision and in angiogenesis that are dramatically important to maintain a normal physiology of this organ during pregnancy.
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