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Biomedical subjects

D Miotto

Publications and source records attributed to D Miotto.

At least 37 records · Page 2Linked to original sources

Eotaxin and monocyte chemotactic protein-4 mRNA expression in small airways of asthmatic and nonasthmatic individuals.

BACKGROUND: Although an eosinophilic infiltrate has been observed in the small airways of asthmatic individuals, the mechanisms responsible for cellular recruitment in the lung periphery remain to be clarified. Eotaxin and monocyte chemotactic protein (MCP)-4 are 2 eosinophil-associated chemokines shown to be upregulated at sites of allergic inflammation. However, their expression within the small airways of asthmatic individuals remains to be elucidated. OBJECTIVE: We sought to determine the expression of eotaxin and MCP-4 in the peripheral airways and parenchyma of lungs of subjects with asthma and to assess their relationship to the numbers of resident eosinophils. METHODS: We examined surgically resected lung tissue from 6 asthmatic and 10 nonasthmatic subjects for the presence of eotaxin and MCP-4 mRNA by in situ hybridization. Chemokine mRNA expression was examined with respect to the numbers of eosinophils within the airways, as detected by immunocytochemistry for major basic protein. RESULTS: Numbers of chemokine mRNA-positive cells were significantly increased in the large and small airways of asthmatic subjects compared with nonasthmatic subjects. Although eotaxin and MCP-4 mRNA were widely expressed in the lungs of subjects with asthma, their expression was particularly evident within the bronchial epithelium and inflammatory cells. In the airways of the asthmatic individuals, the expression of eotaxin mRNA was significantly correlated to the numbers of eosinophils present. CONCLUSION: There is an increased expression of eotaxin and MCP-4 mRNA within the peripheral airways of lungs of asthmatic subjects, suggesting that these chemokines contribute to the small airways and peripheral lung inflammation in asthma.

Asthma↗

Mechanisms of occupational asthma.

BACKGROUND: The pathogenesis and the pathologic alterations of occupational asthma are similar to those of nonoccupational asthma. Occupational asthma may therefore represent a useful model of "human asthma" to investigate mechanisms and pathophysiology of asthma in general. In an occupational setting the cause and onset of asthma may be easily identified, and the natural history may be examined in follow-up studies. The mechanisms involved in occupational asthma include genetic predisposition, immunologically mediated responses, as well as nonspecific airway inflammation. In particular, high molecular weight (eg, grain dust, flour) and some low molecular weight sensitizers (eg, acid anhydrides and platinum halide salts) have been shown to induce occupational asthma through an immunoglobulin E (IgE)-dependent mechanism, while cell-dependent immunologic mechanisms are likely to be more relevant for occupational asthma induced by other low molecular weight sensitizers (eg, toluene diisocyanate and plicatic acid contained in western red cedar). The pathology of the airway mucosa of occupational asthma is remarkably similar to the pathology of nonoccupational asthma, ie, characterized by infiltration and accumulation of eosinophils, mast cells, and activated lymphocytes along with subepithelial fibrosis. In this article, the most relevant mechanisms are discussed with particular reference to the similarities and discrepancies between occupational and nonoccupational asthma.

Asthma↗

Transcatheter arterial chemoembolization for hepatocellular carcinoma in patients with Child's grade A or B cirrhosis: a multivariate analysis of prognostic factors.

We evaluated factors affecting long-term survival after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) complicating cirrhosis. One hundred eighty-two patients with Child's class A or B cirrhosis and an HCC, not amenable to surgery or percutaneous ethanol injection, underwent 346 TACEs (mean 1.9) with epirubicin, iodized oil, and gelatin sponge. Many prognostic factors were subjected to univariate analysis and thereafter, when significant, to the Cox's hazard proportional model. Finally, the significant indices in the Cox's model were used to estimate the accuracy of the probability of death with computation of the area under the receiving operative characteristic (ROC) curve. The cumulative survival rates at 1, 2, 3, and 5 years were 0.83, 0.52, 0.40, and 0.16, respectively. According to Cox's model, the factors associated with significantly worse survival were the presence of ascites (p = 0.0027), elevated bilirubin levels (p = 0.0163), elevated alpha-fetoprotein (alphaFP) values (p = 0.0067), a tumor greater than 5 cm in diameter (p = 0.0001), and the absence of a tumor capsule-like rim (p = 0.0278). According to these parameters, the accuracy of the probability of death estimated with ROC analysis was 0.63. Minor and major complications occurred in 82 patients (45%) and caused death in 2 patients. Long-term prognosis after TACE for HCCs in patients with Child's class A or B cirrhosis depends on the presence of ascites, the bilirubin level, the alphaFP value, the diameter of the tumor, and the presence of a tumor capsule-like rim. However, when considered altogether, these variables are poor predictors to evaluate survival, and other factors should be investigated to identify subjects more responsive to TACE. Complications occur in a high percentage of patients, but they do not affect long-term prognosis.

Adult↗

Immunization and challenge with toluene diisocyanate decrease tachykinin and calcitonin gene-related peptide immunoreactivity in guinea pig central airways.

Toluene diisocyanate (TDI) is a potent sensitizer that causes occupational asthma in a significant proportion of subjects exposed. We used an animal model to investigate whether neuropeptide changes occur in the airways of immunized and TDI-challenged guinea pigs. Animals were immunized by weekly intradermal injections, challenged with TDI (5 to 20 ppb) after the third injection, and killed 6 h after exposure. Control guinea pigs received injections of saline. Lung tissue was processed immediately and analyzed for nerves using the streptavidin-biotin complex peroxidase method with antisera to the neural marker protein gene product 9.5 (PGP 9.5), substance P (SP), and calcitonin gene- related peptide (CGRP). We also quantified the inflammatory infiltrate in the submucosa of central airways, and we measured the serum level of specific IgG and IgG1. Specific antibodies against TDI were present only in immunized animals. Immunized as compared with nonimmunized animals had a significant increase in eosinophils in the submucosa of central airways, and a further increase was observed 6 h after TDI challenge. Immunization and TDI challenge did not modify the number of mononuclear cells in the submucosa of central airways in both nonimmunized and immunized animals. TDI exposure did not change the overall innervation in both nonimmunized and immunized animals, but the density of PGP 9.5-positive nerves was significantly different between nonimmunized and immunized TDI-challenged animals. The density of SP-, and CGRP-immunostained nerves was significantly lower in immunized TDI-challenged than in nonimmunized animals. TDI exposure significantly decreased the density of SP-positive nerves in nonimmunized animals. A negative relationship was found between the presence of airway inflammation, as indexed by eosinophil cell infiltration, and the density of PGP 9.5-, SP-, and CGRP-immunostained nerves. In conclusion, TDI produces airway inflammation and neuropeptides changes in the central airways of immunized guinea pigs 6 h after TDI challenge. These findings support an interaction between tachykinins, inflammatory (i.e., eosinophils) and possibly immune cells.

Animals↗

Monocyte chemotactic protein expression in allergy and non-allergy-associated chronic sinusitis.

OBJECTIVE: Chronic sinusitis (CS) is characterized by inflammatory mucosal thickening and polyp formation with a predominantly eosinophilic infiltrate. Chemokines are a novel group of inflammatory mediators capable of attracting specific inflammatory cell populations. Monocyte chemotactic proteins (MCP) are a subfamily of chemokines (MCP-1, MCP-2, MCP-3, and MCP-4) that share a number of functional properties including chemotactic activity for eosinophils. The purpose of this study was to investigate the expression of the MCP family of chemokines in allergy and non-allergy-associated chronic sinusitis using the technique of immunocytochemistry. METHOD: We examined the expression of MCP-1, MCP-3, and MCP-4 in biopsies from the ethmoid sinuses of patients with CS and normal controls. RESULTS: MCPs were localized to the epithelial cells and a subset of inflammatory cells within the mucosa. The expression of both MCP-3 and MCP-4 immunoreactivity were significantly increased in patients with both allergy and non-allergy-associated CS compared to normal controls (p < .001). There was no significant difference in the expression of MCP-1 in nasal biopsies from individuals with CS and normals. The level of expression of MCP-3 and MCP-4 correlated with eosinophil (p < .001) and CD4-positive T-cell infiltrate (p < .001) but not with CD8-positive T-cell infiltration. CONCLUSIONS: Our data suggest biologic redundancy in the expression of eosinophil chemoattractants in CS and a potential role for MCP-3 and MCP-4, but not MCP-1, in the pathophysiology of this disorder. Further, chemokines may be a common link between the eosinophilia of allergy-associated and non-allergy-associated CS, a finding that may have therapeutic implications.

Adult↗

Folliculo-stellate cells of human pituitary adenomas: immunohistochemical study of the monocyte/macrophage phenotype expression.

Folliculo-stellate cells (FS) represent a small percentage of anterior pituitary elements of still undetermined embryological origin. They are sparse among endocrine pituitary cells and are characterized by the lack of secretory granules and by the presence of few branching processes inserted between hormone-secreting cells. Although FS cell role is still under discussion, recent reports showed that they produce monocyte-derived cytokines able to influence the hormone production and modulate the immunoendocrine connections. In this study we applied three monocyte-macrophage markers (HAM56, KP1, HLA-DR) to 15 pituitary adenomas in order to ascertain whether FS cells belong to the macrophage lineage. In this case FS cells could be considered the resident macrophages of the pituitary. FS cells were identified according to the reactivity to S-100, GFAP and vimentin. We confirm that S-100 represents the most useful marker for these cells that were detected scattered between tumor cells in more than half of the adenomas. GFAP stained only a percentage of FS cells, while vimentin recognized in addition to stellate cells endothelia, perivascular and infiltrating macrophages. We were unable to detect the expression of the macrophage markers on S-100 and GFAP reactive cells. Indeed, HAM56, KP1 and HLA-DR-positive cells were mostly round, small size and located in the perivascular and septal positions where FS cells were never detected. Lack of expression of monocyte-macrophage lineage markers by FS cells in pituitary adenomas suggests their preferential neuroectodermal origin. However, further studies on normal human pituitary will be needed before ruling out a possible role for FS cells as resident pituitary macrophages.

Adenoma↗

Anti-gabaergic neuron autoantibodies in a patient with stiff-man syndrome and ataxia.

We describe a patient with autoimmune insulin-dependent diabetes whose original symptoms of trunk stiffness and rigidity of the abdomen were followed three years later by a pancerebellar syndrome. An autoantibody (autoAb) against GABAergic neurons was found in the patient's serum and cerebrospinal fluid (CSF); on Western blot, this autoAb recognized a 64-kDa antigen of cerebellar protein. The detection of this antibody in a case with ataxia suggests that a spectrum of different neurological diseases may be observed in patients harbouring anti-GABAergic neuron autoAb and supports the concept that factors other than autoAb contribute to the clinical presentation of these disorders.

Animals↗

Short-term effects of transcatheter arterial chemoembolisation on metabolic activity of the liver of cirrhotic patients with hepatocellular carcinoma.

BACKGROUND: Transcatheter arterial chemoembolisation, a procedure for the treatment of hepatocellular carcinoma, provokes a pronounced but transient increase in hepatic cytolysis parameters. A definite evaluation of the impairment of liver function after this treatment, performed by adequate techniques, is still lacking. AIMS: To assess and quantify the impairment of liver metabolic activity after arterial chemoembolisation in patients with cirrhosis. The variations of hepatic vein pressure gradient provoked by this procedure were evaluated. PATIENTS: 15 patients with cirrhosis (Child's class A and B) and hepatocellular carcinoma. METHODS: 17 transcatheter arterial chemoembolisations with epirubicin, iodised oil, and gelfoam were performed; liver function was assessed before, the following day, and after seven days measuring galactose elimination capacity; aminopyrine breath test was also performed in six patients before the procedure and seven days after. In 10 patients intrinsic hepatic clearance of indocyanine green and hepatic vein pressure gradient were measured by hepatic vein catheterisation before and 30 minutes after chemoembolisation. RESULTS: Intrinsic hepatic clearance of indocyanine green decreased significantly from (mean (SEM)) 355 (140) ml/min to 277 (98) ml/min after the procedure (p = 0.0007). Galactose elimination capacity did not show significant changes, being 4.00 (0.90) mg/min/kg body weight at baseline, 4.20 (0.90) mg/min/kg body weight after one day, and 3.95 (0.87) mg/min/kg body weight seven days after chemoembolisation. Aminopyrine breath test was 2.31 (1.09)% and remained unchanged after treatment, being 2.39 (2.04)% at day 7. Baseline hepatic vein pressure gradient was 17.0 (5.5) mm Hg, and 14.4 (3.7) mm Hg 30 minutes after chemoembolisation (p = 0.09). CONCLUSIONS: A single transcatheter chemoembolisation in cirrhotic patients was detected by galactose elimination capacity and aminopyrine breath test one and seven days after the procedure. Therefore it can be considered a safe therapeutic tool for hepatocellular carcinoma in Child's class A and B cirrhotic patients.

Adult↗

Intravascular ultrasound evaluation for assessment and therapeutic decisions in aortic diseases.

Intravascular sonography (IVS) was employed in several aortic pathologies. Acute dissecting aneurysm, chronic or recurrent dissection in previously repaired aneurysm, iatrogenic (postcatheterism) dissection, noncommunicating dissection (mural hematoma), chronic and acute partial thrombosis, and mural fibrosis following aspecific aortitis were studied. The stationary and dynamic observations combined with angiographic findings provided useful information for characterization of the lesions and for therapeutic decisions. In all 14 patients studied, supplemental data achieved from IVS suggest that a combination of angiography and IVS is the most nearly complete examination for concomitant and fast diagnostic workup.

Adult↗

Erythropoietin stimulates testosterone production in man.

Human recombinant erythropoietin (rHuEPO) treatment improves sexual function in end-stage renal failure patients with a still-debated mechanism. Experimental data suggested that rHuEPO was able to stimulate rat Leydig steroidogenesis; therefore, it has been suggested that rHuEPO may induce its effects in humans by acting on gonadal steroid production. Thirteen young adult males (age range, 16-28 yr) catheterized at peripheral and left internal spermatic venous levels during a contrast study for varicocele, were studied. In five subjects, rHuEPO (60 IU/kg, up to a maximum of 4000 IU total) was injected over 1 min in the cubital vein. Similarly, in other five patients, 50 micrograms GnRH were infused. In three subjects, 2 mL saline were injected, as controls. Plasma LH, FSH, and testosterone (T) levels were then determined at -15, 0, 15, 30, 45, 60, 90, and 120 min simultaneously in peripheral and spermatic venous blood. rHuEPO infusion did not have any effect on plasma LH and FSH levels in peripheral or spermatic veins. Similarly, rHuEPO infusion did not affect peripheral T concentration, but increased (approximately 400% vs. controls; P < 0.05) spermatic T levels. GnRH infusion induced an increase in plasma LH and FSH levels in both peripheral and spermatic veins. After GnRH infusion, an increase of approximately 12-fold (P = 0.05-0.001) in T was observed only at the spermatic venous level, without any peripheral T variation. These findings show that rHuEPO was able to influence testicular steroidogenesis by stimulating T production in man, whereas the absence of any effect on gonadotropin secretion suggests that rHuEPO might act directly on human Leydig cell function.

Adolescent↗

[The preoperative chemoembolization of hepatocarcinoma due to cirrhosis].

PURPOSE: To investigate clinical value and tumor response of preoperative transcatheter arterial chemoembolization for hepatocellular carcinoma (HCC) secondary to cirrhosis. MATERIALS AND METHODS: The clinical, radiologic and histologic findings were reviewed relative to 13 cirrhotic patients operated on for HCC after chemoembolization with an emulsion of Lipiodol UF and epirubucin; additional gel-foam embolization was performed in 12 cases. RESULTS: The mean survival was 24 months. Three patients died within 1 month after surgery; 2 other patients died 10 and 32 months after surgery, respectively. The 2-year recurrence rate was 40%. Tumor size, the grade of iodized oil retention and the embolization technique affected primary tumor necrosis ratio: most of satellite nodules and capsular invasions were persistently viable at histology. CONCLUSIONS: Preoperative chemoembolization neither facilitates, nor contraindicates, HCC surgery. Nevertheless, chemoembolization should always be performed before surgery first to stage the patients with Lipiodol CT and second to administer the first palliation whenever the patient is ineligible for surgery.

Aged↗

Arterial complications of pancreatitis: diagnostic and therapeutic role of radiology.

Hemorrhage from pseudoaneurysm complicating pancreatitis is an infrequent but very severe condition. In most cases, acute, massive gastrointestinal bleeding is typical at onset, and prognosis of these cases is usually poor. Nine cases of arterial lesions secondary to pancreatic inflammation are presented, eight related to chronic pancreatitis and one to acute postoperative pancreatitis. Five patients were evaluated during emergency episodes because of acutely gastrointestinal bleeding (four cases), and pseudocyst acute bleeding (one case). Four patients were selectively evaluated: three had a history of self-limiting gastrointestinal hemorrhage, whereas one had experienced no episodes of gastrointestinal hemorrhage. Angiography was performed in all cases and was always diagnostic, even in the two cases of very small pseudoaneurysms. Transcatheter arterial blockade was attempted in five patients and failed to control the hemorrhage in one acutely bleeding patient because of irreversible shock. Two cases of pancreatic hemorrhage not related to a pseudocyst were effectively and permanently treated by embolization. A case of a pseudoaneurysm associated with a pseudocyst required surgery in addition to embolization for a definite treatment. Nevertheless, when a pseudoaneurysm or a pseudocyst hemorrhages acutely, transcatheter arterial blockade can control the hemorrhage and improve the hemodynamic status of the patient before surgery.

Acute Disease↗

Palliative treatment of hepatocellular carcinoma with transcatheter arterial embolization.

Thirty-three consecutive patients with previously untreated hepatocellular carcinoma (HCC) and 6 patients with recurrent HCC were treated with transcatheter arterial embolization (TAE). The patients were not eligible for surgical resection or percutaneous ethanol injection. TAE was performed with Lipiodol Ultra-Fluid, epidoxorubicin and Gelfoam, with a mean of 1.7 treatments per patient. CT was performed 15 days after TAE. The mean cumulative survival was 14.2 months in patients with previously untreated HCC. The survival of patients stages Okuda I and II did not differ significantly (p > 0.05); tumor size did not affect survival (p > 0.05). Two patients with recurrent HCC died 7.0 and 9.3 months after the diagnosis of tumor recurrence; the remaining 4 patients are still alive with a maximum follow-up of 22.5 months from the diagnosis of HCC recurrence. Ten complications occurred in 8 patients, and were controlled by medical therapy. Eleven patients died during the study; no death was related to TAE. The series was not randomized, but comparison with the natural history of HCC suggests that TAE is effective as palliative treatment of advanced or recurrent HCC.

Aged↗

Spontaneous idiopathic subclavian arteriovenous fistula: a case report.

Systemic arteriovenous (AV) fistulas are a rare but correctable cause of hyperkinetic circulation and congestive heart failure. They are generally due to catheterization procedures, surgery, trauma, or aneurysms. A case of truly spontaneous AV fistula between left subclavian artery and left innominate vein is described. This patient presented with symptoms that might clinically be mistaken for a carpal tunnel syndrome. The discovery of a continuous to-and-fro murmur on her left upper sternal border led to the correct diagnosis. Surgical ligature of the fistula provided complete relief of the woman's symptoms.

Angiography↗