[Multivessel coronary disease: complete revascularization].
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Coronary Disease↗
Biomedical subjects
A Castiglioni
Publications and source records attributed to A Castiglioni.
The PTH-calcium relationship curve in secondary hyperparathyroidism, an index of sensitivity and suppressibility of parathyroid glands.
A sigmoidal relationship, fitting a four-parameter model, has been demonstrated in in vivo and in vitro studies to link the parathyroid hormone (PTH) secretion rate and calcium concentration changes. In uraemic patients different patterns of calcium-mediated PTH secretion were reported in different types of renal bone diseases and a shift to the right and a steeper slope has been observed in secondary hyperparathyroidism. To gain more information that could predict indexes for successful medical therapy we investigated the calcium-PTH sigmoidal relationship in 42 hyperparathyroid patients with different degrees of secondary hyperparathyroidism; we classified as moderate those patients presenting basal PTH (PTHbas) < 600 pg/ml and bone alkaline phosphatase (AP) < 500 U/l, and severe those with a PTHbas > or = 600 pg/ml and bone AP > or = 500 U/l. Changes in ionized calcium (iCa) were induced by calcium-free dialysis on the first day, to induce hypocalcaemia up to serum iCa 3.5 mEq/l, and calcium 8 mEq/l dialysis on the third day, to induce hypercalcaemia. The moderate hyperparathyroidism patients had PTHmax, PTHmin and slope, calculated in absolute values and relative values, lower than severe hyperparathyroidism patients but they did not differ in the minimal to maximal PTH ratio. In the moderate group the PTHbas correlated with all the curve parameters except PTHmin, calculated both in absolute and percentage values, while in the severe group PTHmin was the only parameter correlating to the PTHbas. In conclusion, by performing the dynamic test, we found that some glands were not suppressible among moderate hyperparathyroidism patients.
Adult↗
Minimal change nephrotic syndrome with cecum adenocarcinoma.
Membranous glomerulonephritis is the most common glomerular disease associated with malignancy, the association of minimal change glomerulopathy with solid tumor is still uncommon. We report a 72-year-old man with nephrotic syndrome due to minimal change glomerular disease; an accurate seek of underlying malignancy revealed a cecum adenocarcinoma. We had a complete remission of nephrotic syndrome after surgery of carcinoma.
Adenocarcinoma↗
Thrombospondin and transforming growth factor-beta 1 increase expression of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in human MDA-MB-231 breast cancer cells.
BACKGROUND: Thrombospondin is a high molecular weight adhesive glycoprotein that has been shown to function in mechanisms of tumor progression. The authors' previous studies have shown that thrombospondin promotes human lung carcinoma invasion by up-regulation of the plasminogen activator system through a mechanism involving the activation of transforming growth factor-beta 1 (TGF-beta 1). In this study, a similar thrombospondin-mediated mechanism operative in breast carcinoma cells is described. METHODS: The effect of thrombospondin and TGF-beta 1 on the capacity of a line of breast carcinoma cells to activate plasminogen was measured as well as the physiologic consequences of these activities on cell adhesion and proliferation. Plasminogen activation was assessed by measuring the plasmin activity and plasminogen activator inhibitor-1 (PAI-1) levels in cell-conditioned media and the cell-associated urokinase-type plasminogen activator (uPA) levels. RESULTS: Treatment of MDA-MB-231 breast carcinoma cells with either thrombospondin or TGF-beta 1 caused increased secretion of PAI-1 with a concomitant decrease in plasmin activity, whereas cell-associated uPA expression was increased with respect to controls. Thrombospondin (40 micrograms/ml) or TGF-beta 1 (5 ng/ml) stimulated the cells to secrete 5.5- and 6.7-fold more PAI-1 than controls, respectively, and caused decreased plasmin activity in the cell culture medium. Conversely, either thrombospondin (40 micrograms/ml) or TGF-beta 1 (5 ng/ml) caused the cells to express 4.55- and 5.38-fold more uPA than controls, respectively. Thrombospondin and TGF-beta 1 induced a more flattened and spread appearance in the cells with no effect on proliferation. These effects could be reversed with antibodies to either thrombospondin or TGF-beta 1 and were not due to contamination of thrombospondin with active TGF-beta 1. CONCLUSIONS: Thrombospondin and TGF-beta 1 function similarly to increase cell-associated uPA and cell-secreted PAI-1. These data suggest that thrombospondin may not only function as an adhesive molecule, but through a mechanism involving the activation of TGF-beta 1, may modulate cell surface protease expression. In addition, these observations suggest that thrombospondin and TGF-beta 1 could promote metastasis by increasing uPA-mediated cell invasion, whereas through the action of PAI-1, also protect blood-born tumor emboli from destruction by host fibrinolytic enzymes.
Breast Neoplasms↗
Thrombospondin (TSP) and transforming growth factor beta 1 (TGF-beta) promote human A549 lung carcinoma cell plasminogen activator inhibitor type 1 (PAI-1) production and stimulate tumor cell attachment in vitro.
A growing body of evidence has recently implicated TSP and TGF-beta in the process of malignancy, such as tumor cell proliferation, tumor angiogenesis, and metastasis. The purpose of the present study was to evaluate potential mechanisms of TSP and TGF-beta in tumor cell attachment and invasion. Our results indicate that both TSP and TGF-beta promoted tumor cell attachment and spreading in the presence of plasminogen. The mechanism for these effects appeared to be due, in part, to the capacity of TSP and TGF-beta to induce tumor cell production of (PAI-1). PAI-1, which is a natural inhibitor of tumor-cell associated urokinase-type plasminogen activator (uPA) activity, inhibited activation of plasminogen to plasmin in the growth media, thereby preventing plasmin-induced detachment of cells. The TSP-promoted production of PAI-1 could be inhibited not only by anti-TSP antibodies but also by a neutralizing antibody against TGF-beta. These results suggest that TSP by a mechanism involving TGF-beta can promote cell adhesion through stimulation of tumor cell secretion of PAI-1. These data provide evidence that TSP not only has the capacity of functioning as a matrix protein to directly promote cell-substratum adhesion but that TSP can also stimulate cell adhesion and spreading by modulating cell surface protease expression through stimulation of tumor-associated production of PAI-1.
Adenocarcinoma↗
Myocardial revascularization with bilateral internal thoracic artery in patients with left main disease: an incremental risk?
Although the long-term patency of the internal thoracic artery (ITA) has been well proved, there is still some concern about its preoperative performance. We considered 80 patients with left main disease (mean age 60.2 years) who underwent coronary artery bypass grafting in our institute from March 1988 to September 1992. Patients with left main disease were divided into 2 groups: group I-38 patients receiving only ITA grafts on the left coronary system and group II-42 patients having a single ITA graft together with saphenous vein grafts on the left coronary system. No patients in group I received a saphenous graft on the left coronary system and three patients with right coronary artery involvement received total arterial myocardial revascularization with the use of the inferior epigastric artery. Perioperative complications in group I and group II patients were, respectively: myocardial necrosis in 2 (6.9%) and 3 (8.8%), use of intraaortic balloon pump in 2 (6.9%) and 2 (5.9%). No death occurred in either group. In our experience, the use of bilateral ITA grafts in patients with left main stenosis was not related to an incremental risk. We conclude that left main disease should not be considered as counterindication to the extensive use of arterial conduits.
Aged↗
Chemical parathyroidectomy for recurrence of secondary hyperparathyroidism.
To avoid the risks of reoperation, we treated 15 uremic patients on regular extracorporeal dialysis and affected by hyperparathyroidism recurring after subtotal parathyroidectomy with ultrasound-guided ethanol injection. Follow-up was extended to 12 months after the last injection and for 11 patients to 24 months. Plasma parathyroid hormone concentration, as measured with a carboxyterminal parathyroid hormone (c-PTH) radioimmunoassay (normal, 0.2 to 2 ng/mL), significantly decreased from a basal value of 19.29 +/- 14.73 ng/mL to 11.19 +/- 9.54 ng/mL at 1 month, 7.45 +/- 4.99 ng/mL at 6 months, 6.91 +/- 4.71 ng/mL at 12 months, and 6.51 +/- 3.89 ng/mL at 24 months. Total and bone alkaline phosphatase decreased in parallel. The only remarkable side effect was transient dysphonia, which occurred in two cases. These data suggest that the technique of ultrasound-guided fine-needle ethanol injection might be a valuable alternative to surgery for recurrent hyperparathyroidism after subtotal parathyroidectomy in selected patients. This should be confirmed in larger series of patients and with a more prolonged follow-up.
Adult↗
Rest and exercise hemodynamics of stentless porcine bioprostheses in aortic position.
Mechanical and conventional stented bioprostheses, because of need for anticoagulants, hemodynamic characteristics and long-term durability, do not represent the optimal heart valve replacement device. In this study we compared the hemodynamic function of a stented aortic bioprosthesis (St Jude Bioimplant), implanted in 10 patients, with a stentless porcine aortic bioprosthesis (Biocor) implanted in 7 patients, by means of Doppler echocardiography early postoperative at rest (T1) and 6 months later at rest (T2a) and during exercise (T2b). Mean and peak systolic gradients across stentless porcine prostheses were significantly lower than across stented bioprostheses (T1 p = 0.008 and p = 0.004; T2a p < 0.0001 and p < 0.0001; T2b p < 0.0001 and p < 0.0001, respectively). Our results show that systolic and diastolic mechanical stress on biological components of a glutaraldehyde-fixed stentless porcine aortic bioprosthesis is much lesser than on stented bioprostheses. This feature has appeared evident at rest and much more after exercise testing. The reduction of systolic and diastolic stress is expected to determine lower calcification degree and longer durability of stentless porcine aortic bioprostheses. Moreover, aortic valve replacement by means of stentless bioprostheses allows the implantation of a 1 size (2 mm) larger device, appearing favourable especially in small aortic annulus. On the basis of these promising results we suggest that stentless bioprostheses are a valid alternative to stented bioprostheses for aortic valve replacement. However, patient population is too small and the follow-up is too short to draw a definite statement about long-term hemodynamic performance of this device.
Aged↗
[The treatment of arterial hypertension in diabetes mellitus. Choices and problems].
Recent studies indicate that arterial hypertension in diabetes mellitus is a paramount pathogenetic step in the evolution and acceleration of diabetic macro- and microangiopathy and in particular in the development of nephropathy and uremia. This paper deals with the clinical problems of antihypertensive treatment in diabetic patients and discusses the antihypertensive repertory with the aim at determining the best drug choice in the individual case. In the light of our present pathophysiologic knowledges of the intrarenal effects of the various classes of antihypertensive drugs the possibility of preventing diabetic nephropathy is discussed.
Antihypertensive Agents↗
Ultrasound-guided percutaneous fine-needle ethanol injection into parathyroid glands in secondary hyperparathyroidism.
To reduce parathyroid hormone concentrations in uraemic patients refractory or hyporesponsive to calcium supplements and active metabolites of vitamin D, we developed in 1982 a new parathyroid ablative technique consisting of percutaneous fine-needle ethanol injection (PFNEI) into enlarged parathyroid glands under ultrasonic guidance. Fifty uraemic patients have been treated. Decreases in carboxy terminal parathyroid hormone (PTH) were 50% or more in 13 of 50 patients followed up (26%) at 1 month, in 13 of 48 (27%) at 6 months, and in 9 of 25 (36%) at 12 months. Decreases of 30% or more in PTH were obtained in 21 of 50 (42%), in 25 of 48 (52%), and in 15 of 25 (60%). In 'responsive' patients, serum total alkaline phosphatase was significantly reduced [from 579 +/- 645 U/l to 360 +/- 354 U/l (P less than 0.01) at 6 months, and to 273 +/- 311 U/l (P less than 0.01) at 12 months] and bone isoenzyme decreased similarly [from 482 +/- 608 U/l to 256 +/- 344 U/l (P less than 0.005), and to 225 +/- 354 U/l (P less than 0.01)]. The best results were in seven patients who had relapsed after subtotal parathyroidectomy. Declines in PTH of 30% or more were observed in four of seven patients at 1 month, in six of the seven (85%) at 6 months, and in all four patients seen after 12 months. The treatment corrected hypercalcaemia, making it possible to start or to increase daily vitamin D treatment. Side-effects were mild, rare, and transient.
Adult↗
Bone mineral and aluminum concentrations in patients undergoing CAPD.
CAPD results in continuous peritoneal transfer of hormones and minerals involved in the pathogenesis of renal osteodystrophy (RO). Moreover, although CAPD patients seem to have better control of serum phosphate concentration than hemodialysis patients, the need for aluminum-containing phosphate binders (ACPB) may still be present. In a prospective study meant to investigate the evolution of RO, we obtained 79 bone biopsies in 29 uremic patients (20 male, 9 female; age 25-59, mean 46). Of these, 22 were obtained at the beginning of treatment, 24 after 24 months, 23 after 36 months and 10 after 60 months. All patients were treated with CAPD (Viaflex, Baxter 2-2.5 L x 4-5 bags/day; Ca(++) + 3.5, Mg(++) 1.5 mEq/L) as the first modality of therapy and received oral calcitriol, aluminum hydroxyde and/or calcium carbonate and magnesium hydroxyde in order to maintain serum calcium (Ca) and phosphorus within the normal range. Qualitative bone histology, bone Ca and magnesium (Mg) (Flame atomic absorption spectroscopy) and aluminum (Al) concentration (Graphite furnace atomic absorption spectrometry) were determined. CAPD achieves a good control of RO as indicated by the tendency toward a decreased incidence of mixed osteodystrophy and predominant hyperparathyroid bone disease and improvement of osteoid lesions. A defective Ca content of bone is persistent in the observed period and positively correlated to bone Mg concentration. An increased level of Al was shown in the serum and bone. The highest bone Al content was found among patients with predominant osteoid bone disease. Also in CAPD, patients consuming ACPB are at risk of bone Al accumulation despite the low Al levels in the dialysate.
Adult↗
[Clinical significance of consumption of polyunsaturated n-3 fatty acids of marine origin].
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Blood Glucose↗
[The pathogenesis of arterial hypertension in diabetes mellitus and its role in nephropathy].
This paper synthesizes the pathogenic steps of arterial hypertension in diabetes mellitus: hyperosmolarity due to the hyperglycemia and increased sodic tubular reabsorption accounting for the expansion of the extracellular volume with hypervolemia; abnormalities of the ionic membrane pumps leading to abnormal intracellular calcium distribution, thereby inducing an increased vascular tone; atypical vasomotor reactivity to cathecolamines; modifications of the renin-angiotension-aldosterone system. The pathophysiological derangements by which hypertension could induce nephropathy are examined: the vasodilatation which can be detected from the onset of diabetes, may be a determinant in the transmission of systemic hypertension to the glomerular microcirculation with resulting enhancement of the hydrostatic transglomerular pressure gradient (i.c. the major factor producing glomerular injury), glomerular plasmatic flow and filtration rate. The nephron hyperfiltration increases the movement of plasmatic proteins across the glomerular capillary wall with subsequent mesangial hyperactivity and sclerosis. Antihypertensive treatment in diabetes follows general guidelines and it should be instituted even in the case of microhypertension being facilitated in this setting the appearance of microalbuminuria i.e. the starting point of nephropathy. Even if experimental studies are to favor ACE inhibitors as the first-line drugs for abating glomerular hypertension by mitigation of the direct effect of angiotensin II on the efferent arteriolar tone, clinical observations suggest that, regardless of type of treatment, the normalization of systemic arterial pressure, by reversing glomerular hypertension may be effective in preventing diabetic nephropathy.
Diabetes Complications↗
[Current approach in the prevention and treatment of diabetic nephropathy].
Diabetic renal microangiopathy accounts for enormous morbidity and mortality, particularly in patients who develop diabetes in childhood or early youth; in the last few years its pathogenesis has been therefore extensively studied, aiming to prevent renal complications or at least of slowing down its progression toward uremia. Though not always in accordance with theoretical expectations, the results of clinical trials have nevertheless widened our therapeutic possibilities; in fact, besides the attainment of an optimal metabolic control, other possible interventions include a careful correction of albeit minimal elevations in arterial pressure; the interference with intrarenal hemodynamic parameters; the correction of insulin-independent metabolic pathways, abnormally activated in the diabetic, such as non enzymatic glycation and polyol pathway; the treatment of endothelial and platelet alterations; the improvement of the rheologic properties of blood.
Blood Coagulation Disorders↗
Physiopathology and clinical aspects of diabetic nephropathy.
End-stage renal failure is a severe and relatively frequent complication of insulin-dependent diabetes, also representing the only growing cause of uremia requiring replacement therapy in Western countries. Five principal pathogenic factors are to be considered: genetic, immunologic, hemorheologic, biochemic, and hemodynamic; of these, nonenzymatic glycosylation of proteins and glomerular hyperfiltration appear to be most important. In the last few years, a better understanding of the natural history of type I diabetes has been gained, with particular significance attributed to the stage of the disease defined as incipient diabetic nephropathy which is characterized by microalbuminuria. However, advances in pathophysiologic notions have not always been followed by corresponding results in the prevention and therapy of diabetic nephropathy; possible reasons for this are briefly discussed. In spite of these uncertainties, the importance of achieving the best possible correction of glycemic homeostasis and of albeit initial elevations in the arterial pressure appears to be well established.
Animals↗
Particle migration from haemodialysis circuit: electron microscopy and microprobe analysis.
It has been recognized that storage inflammation in organs of uraemic patients is due to silicone particle migration from tubing segments of the haemodialysis circuit to blood. Nevertheless, iatrogenic storage of foreign material containing Si has been also observed in long-term dialysis patients which, in our Unit, used only PVC or PU-PVC tubings. The origin and the nature of the particulate has been investigated in vivo and in vitro on bioptical samples as well as on cuprophan dialyser and PVC tubing eluates. This study carried out by means of TEM, SEM and microprobe EDS revealed the presence of variously shaped material and particles containing Si in bioptical samples and in eluates. Si containing contaminants were not demonstrated in eluates filtered in absence of the dialyser. This result suggests that leachable products can result from the dialyser and that such release can be an additional risk for uraemic patients.
Electron Probe Microanalysis↗
[Physiopathological bases of diabetic nephropathy].
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Basement Membrane↗
Different dialytic modalities in the management of hypertension in uremic patients.
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Antihypertensive Agents↗