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Biomedical subjects

G Rossi

Publications and source records attributed to G Rossi.

At least 289 records · Page 16Linked to original sources

alpha 1-Antitrypsin (AAT) deficiency and ANCA-positive systemic vasculitis: genetic and clinical implications.

A high incidence of alpha 1-antitrypsin (AAT) deficiency has been reported in patients with C-ANCA systemic vasculitis in association with antibodies against proteinase-3 (PR3). To clarify the role of AAT deficiency in the acute vasculitic process as well as in progression of the disease, we studied 84 patients with either C-ANCA or P-ANCA vasculitis with special reference to: (a) the AAT gene, (b) the phenotypic (Pi) variants and (c) the serum levels during both acute illness and remission. The PiZ gene was found in six patients (8% vs. 1.5% controls) irrespective of the type of autoantibodies (C-ANCA vs. P-ANCA). All PiZ patients displayed the ability to raise their AAT serum levels up to the normal range during acute illness. In contrast, 24 patients with the PiM phenotype presented low AAT serum levels during acute illness. In all these patients, the AAT levels returned to normal values during the remission. Low AAT levels were associated with low levels of C-reactive protein (PCR) (P < 0.001), with a less severe renal involvement or a minor risk of death, and, in one tested patient, with a novel point mutation (TCGA-->TCAA) at the enhancer-promoter region of the AAT gene. Low AAT serum levels did not correlate with either type/titre of autoantibody or distribution/severity of the vasculitis process. In the case-control study, high AAT levels emerged as a major determinant of progression towards end-stage renal failure [odds ratio 3 (95% CI 1.1-8.4)]. These results indicate: (a) a high incidence of the PiZ gene of AAT in systemic vasculitis irrespective of the type of autoantibodies; (b) a novel form of AAT deficiency associated with the normal PiM phenotype becoming manifest only during acute illness; (c) dysregulation of the acute-phase response affecting selectively AAT or both AAT and PCR; (d) correlation between low plasma levels of AAT and less severe renal involvement or risk of death.

Adult↗

Histopathological changes in bone marrow biopsies from patients with chronic myeloid leukaemia after treatment with recombinant alpha-interferon.

AIMS: Recombinant alpha-interferon (r-IFN) is an effective therapy for chronic myeloid leukaemia (CML), inducing haematological and major cytogenetic response in 70% and 30% of patients, respectively. In this study we have evaluated the significance of bone marrow (BM) histology on the subsequent response to r-IFN therapy, as well as the morphological changes induced by r-IFN within BM. METHODS AND RESULTS: 73 BM biopsies were studied from 21 patients with Ph1-positive CML in chronic phase at diagnosis and at different times during r-IFN treatment. At diagnosis the probability of achieving a major or complete cytogenetic response was significantly higher in patients with a total marrow cellularity lower than 90% (P = 0.02). During therapy with r-IFN, significant BM changes included disappearance of the CML pattern (P = 0.0002), reduction of M:E ratio (P = 0.0009) and total cellularity (P = 0.0027), and increase in number of terminal megakaryocytes (P = 0.0009) and of fatty tissue regeneration (P = 0.037); only after long-term therapy (mean 20 months), did reticulin fibrosis increase significantly (P = 0.032). CONCLUSIONS: The overall BM morphology in response to treatment displayed different pictures, ranging from persistence of CML (25 biopsies out of 51), to reversion to normal histology (14 out of 51). Persistence of diffuse morphological abnormalities was associated with lack of cytogenetic responsiveness (P = 0.025).

Adolescent↗

Resolution of pulmonary embolism: effect of therapy and putative age of emboli.

The purpose of this study was to evaluate functional and scintigraphic improvement in patients with pulmonary embolism (PE) according to the kind of treatment and the putative age of the emboli. The study includes 20 patients with both scintigraphic and angiographic diagnosis of PE enrolled in Pisa as a part of two previous multicenter trials: PAIMS 2 and BAPE. All patients were admitted to the Pulmonary Unit of the University of Pisa and treated with recombinant tissue-type plasminogen activator (rt-PA) plus heparin (H) (n = 10) or with H alone (n = 10). Results confirmed previous data, namely that perfusion damage decreases significantly from embolization to 7 days later in both patients treated with rt-PA + H and H alone (p < 0.001), although patients treated with rt-PA + H have a significantly higher perfusion restoration (p < 0.001) and a standard PaO2 increase (p < 0.01). Interestingly, our data also showed that the putative age of the emboli does not influence the efficacy of rt-PA + H treatment, while it does influence that of H treatment alone; in other words, rt-PA + H therapy may act efficaciously not only in fresh, but also in old pulmonary emboli.

Analysis of Variance↗

Comparative effect of the calcium antagonist verapamil and the synthetic steroids gestrinone and danazol on human monocyte phagocytosis in vitro.

Recent evidence suggested that periovulatory treatment with an immunomodulatory agent such as verapamil might be an effective alternative to conventional treatment for endometriosis-associated subfertility. In particular, it has been reported that the drug might reduce the accentuated macrophage peritoneal activation demonstrated in patients with endometriosis. In this study, we compared the effect of the calcium antagonist verapamil with those of gestrinone, danazol and testosterone on human monocyte phagocytosis in an attempt to evaluate any significant differences in their ability to influence a parameter of cell inflammatory activation. Peripheral blood monocytes were isolated from 37 healthy women. Monocyte function was determined by phagocytosis of fluorescent microspheres after an overnight incubation in the presence or absence of the various agents. This study indicates that verapamil at the pharmacological concentration of 0.4 micrograms/ml, the systemic level in patients taking 40-80 mg/8 h p.o., significantly inhibits monocyte function. A lower immunosuppressive but still significant effect was achieved in this assay system with gestrinone at a concentration of 3 x 10(-8) M). The pharmacological concentration of danazol (10(-6) M) and the physiologic concentration of testosterone (10(-8) M) did not significantly affect this immunologic test system. These results provide evidence that verapamil is able to exert a slightly greater immunosuppressive effect than steroidal drugs on monocyte phagocytosis. However, due to the small differences observed, further studies on the biological mechanism of the drug seem to be necessary to completely elucidate its potential role in endometriosis-associated subfertility.

Adult↗

Air pollution and daily admissions for chronic obstructive pulmonary disease in 6 European cities: results from the APHEA project.

We investigated the short-term effects of air pollution on hospital admissions for chronic obstructive pulmonary disease (COPD) in Europe. As part of a European project (Air Pollution and Health, a European Approach (APHEA)), we analysed data from the cities of Amsterdam, Barcelona, London, Milan, Paris and Rotterdam, using a standardized approach to data eligibility and statistical analysis. Relative risks for daily COPD admissions were obtained using Poisson regression, controlling for: seasonal and other cycles; influenza epidemics; day of the week; temperature; humidity and autocorrelation. Summary effects for each pollutant were estimated as the mean of each city's regression coefficients weighted by the inverse of the variance, allowing for additional between-cities variance, as necessary. For all ages, the relative risks (95% confidence limits (95% CL)) for a 50 microg x m(-3) increase in daily mean level of pollutant (lagged 1-3 days) were (95% CL): sulphur dioxide 1.02 (0.98, 1.06); black smoke 1.04 (1.01, 1.06); total suspended particulates 1.02 (1.00, 1.05), nitrogen dioxide 1.02 (1.00, 1.05) and ozone (8 h) 1.04 (1.02, 1.07). The results confirm that air pollution is associated with daily admissions for chronic obstructive pulmonary disease in European cities with widely varying climates. The results for particles and ozone are broadly consistent with those from North America, though the coefficients for particles are substantially smaller. Overall, the evidence points to a causal relationship but the mechanisms of action, exposure response relationships and pollutant interactions remain unclear.

Air Pollution↗

Integrin binding to immobilized collagen and fibronectin stimulates the proliferation of human thyroid cells in culture.

The expression of integrins of the beta1 family and their possible biological effects were investigated in normal human thyroid cells in monolayer culture. The expression of beta1 and alpha(1-6) integrin subunits was determined by flow cytofluorometry with specific antibodies. Follicular cells of subconfluent monolayer cultures expressed alpha2beta1 and alpha3beta1 at high levels, while alpha1beta1 was only slightly expressed, and alpha4beta1, alpha5beta1, and alpha6beta1 were never detected. Cell attachment assays were performed in fibronectin-, type I collagen-, and laminin-coated microtiter plates. Thyroid cells, while adherent to collagen and fibronectin, showed poor attachment to laminin despite the abundance of their putative receptors alpha2beta1 and alpha3beta1. In serum-free medium, collagen and fibronectin induced cytoskeletal organization, change of cell shape from round to flat, and cell spreading. [3H]Thymidine incorporation and proliferation assays were used to evaluate the effects of collagen and fibronectin on DNA synthesis and cell growth in the absence of a change in spreading or cell shape. Both substrates, in low serum-containing medium, induced a concentration-dependent increase in [3H]thymidine incorporation partially inhibited by RGD-containing peptides that blocked the cell attachment. Thyrocytes cultured in low serum-containing medium on immobilized fibronectin or collagen showed a dose-dependent stimulation of proliferation. These data indicate that fibronectin and collagen can regulate the cytoskeletal organization and cell shape and stimulate the proliferation of normal human thyroid cells in culture and that integrins mediate these effects of extracellular matrix proteins.

Cell Adhesion↗

Clozapine in Parkinson's disease tremor. Effects of acute and chronic administration.

The effects of the acute administration of clozapine on parkinsonian mixed tremor (i.e., resting and postural tremors) were evaluated to establish clozapine's predictive value for long-term response and to determine if there is a difference in the pharmacologic responses of the two tremors. We also investigated the correlation between reduction of tremor and induction of sedation after acute and chronic administration of clozapine. Clozapine (12.5 mg) or placebo were administered po in a double-blind manner to 17 PD patients with mixed L-dopa-resistant tremors. Two patients did not reach 50% improvement and were considered nonresponders. The remaining 15 patients reported moderate to marked reduction of tremor. Responsive patients in the acute test moved on to a long-term, open clozapine add-on study receiving an average daily dose +/- SD of 45 +/- 9.6 mg for a period of 15.5 +/- 8.3 months. A significant reduction of both resting (p < 0.05) and postural (p < 0.05) tremors was observed under clozapine from the first week of treatment through the entire period of the study. There was no statistically significantly difference between the degree of improvement for resting and postural tremors after either single or chronic clozapine administration. Sedation was the only side effect reported after clozapine; however, the time courses of sedation and tremor reduction did not coincide in the acute or in the chronic experimental paradigm, where it decreased considerably in a few weeks in all patients. During long-term clozapine treatment, neither systemic side effects nor worsening of motor disability scores were noted. Thus we wish to propose an acute test or a therapeutic attempt, or both, with clozapine before defining a case of mixed parkinsonian tremor as resistant tremor and therefore resorting to a neurosurgical approach.

Aged↗

Massive enterolithiasis associated with ileal dysgenesis.

A 20-year-old man with massive ileal enterolithiasis was investigated with plain radiography, ultrasound, computed tomography, barium follow through and double contrast barium enema. Ileocecal valve agenesis was found at surgery. The enteroliths were located in the distal ileum, which communicated with the large intestine via an ileotransverse fistula.

Adult↗

Granulocyte colony-stimulating factor (G-CSF, filgrastim) after or during an intensive remission induction therapy for adult acute lymphoblastic leukaemia: effects, role of patient pretreatment characteristics, and costs.

An early intensive anthracycline therapy can improve therapeutic outcome in adult acute lymphoblastic leukaemia (ALL) but is usually associated with marked myelosuppressive effects and significant morbidity by infections. To reduce this risk, we employed granulocyte colony-stimulating factor (G-CSF, filgrastim 5 microg/kg/d) as an adjunct to a myelotoxic, 14-day long induction regimen with idarubicin-vincristine-L-asparaginase-prednisone (IVAP). Owing to changes in study design, patients received 'late' (n = 28) or 'early' (n = 37) G-CSF from days 15 or 4 of IVAP, respectively, until resolution of severe neutropenia. Study endpoints included time to recovery from neutropenic nadir, duration of neutropenia <0.5 x 10(9)/l, incidence of infectious complications, assessment of variables affecting G-CSF response, clinical outcome and costs. Sixty-five consecutive cases were evaluable. Patients in early G-CSF group recovered significantly faster from the neutropenic nadir (p < 0.002), contracted less infectious complications (p = 0.007), and required less intravenous antibiotic (p = 0.008) and antifungal (p = 0.002) medications. Although these reductions did not compensate for the increased G-CSF treatment cost, the overall supportive care cost was not significantly increased by early G-CSF. Interestingly, T-ALL phenotype (p = 0.02) and higher neutrophil presentation count (p = 0.03) were associated with a shorter neutropenic course even with late G-CSF. Early G-CSF may be a valid approach to mitigate chemotherapy-induced neutropenia of IVAP and other similarly myelosuppressive adult ALL regimens.

Adolescent↗

Mortality in black siskins (Carduelis atrata) with systemic coccidiosis.

Ninety-five (97%) of 98 black siskins (Carduelis atrata) died within 2 months of arrival in Italy from South America with the following clinical sings: rapid weight loss, breast muscle atrophy, congested and distended abdomen, diarrhea, and lethargy. Macroscopically we observed hepato-splenomegaly, pulmonary congestion, and thickening of the interstinal wall. Histologically, lymphomonocytic transmural enteritis, interstitial mononuclear cell infiltrates in the lungs and in the liver, as well as activation of splenic follicles were common features. Large numbers of protozoa belonging to Isospora sp. were observed in various stages of their life-cycle in the intestinal epithelium, and some zoites were found in the extra-intestinal cellular infiltrate as well. No viral or bacterial pathogens were found.

Animals↗

[Anti-HAV screening patients with chronic hepatitis].

Following the decrease in HAV endemic levels in the last decades, nowadays in Italy most people aged less than 30 years are susceptible to the infection. We have tested for serum anti HAV IgG 194 chronic hepatitis patients from Naples to evaluate the level of protection against HAV in a category of patients in whom an acute necrosis due to HAV might induce liver failure. The study shows that 90.7% of Neapolitan chronic hepatitis patients has serologic evidence of prior HAV infection. Specifically, 98.1% of the patients over 40 years of age, but only 54.6% of those under 40 tested positive for anti HAV IgG. 102 patients had cirrhosis and only one tested negative. The data suggest that HAV vaccination in susceptible chronic hepatitis patients should be judged by the physicians in care on the basis of the severity of disease, patient's age, real risk of exposure to the infection, and level of education.

English Abstract↗

[Insulinoma. Clinical and surgical considerations concerning a case].

Insulinoma is the most common endocrine tumor of the pancreas. It arises from the beta-islet cells of Langerhans. Insulinomas synthesize and secrete insulin autonomously in the presence of low blood glucose levels, causing spontaneous hypoglycemia and characteristic clinical symptoms. The authors examined data the from the most important international research projects on this topic during the past 20 years. Insulinomas are rare, with an annual incidence of 0.5 per million population. Up to 90% patients have benign solitary pancreatic insulinomas. People of all ages can be affected with this neoplasm. The authors reported a case of a large insulinoma of the body and tail of the pancreas, with atypical psychic symptoms. A distal pancreatectomy with splenectomy was performed. No surgical complications occurred in the postoperative course. The psychic symptoms were emphasized with refusal of food. The patient underwent Parenteral Nutrition and was discharged 24 days after the operation. The surgical removal of the tumor permitted the patient to recover completely, with glucose and insulin blood levels in normal range.

Diagnosis, Differential↗

[Antiblastic locoregional perfusion with control of the aorto-caval flow: technique of percutaneous access].

The authors introduce a new technique for performing aortic stop-flow infusion (ASI) or hypoxic abdominal perfusion (HAP) to treat advanced thoracoabdominal tumors, via an angiographic percutaneous approach. To date, the maneuver has always been performed with surgical exposure of vascular sites in the groins. The materials available on the market were initially used and then dedicated materials have been developed, such as 11-F vascular sheaths, 8-F catheters, latex balloons with maximum phi's of 4 cm and maximum capacity of 70 ml. We performed 72 maneuvers in 56 patients during 22 months. No technical or instrumental complications occurred and all treatments were successful. Three patients (6%) died within 12 hours, two because of ARDS following thoracic perfusion and one for acute renal failure and disseminated intravascular coagulation following abdominal perfusion. The percutaneous approach provides the same mechanical-occlusive efficacy for aortocaval occlusion and therefore the same therapeutic results as surgery, but it has fewer risks of technical complications and no technical failures. Moreover, this technique is more repeatable and less expensive than surgery and its hospital stay and recovery time are shorter. To conclude, the ASI/HAP procedure is an interesting therapeutic chance in otherwise untreatable advanced cancer patients offering several prospects of technical and pharmacologic development to further increase its efficacy.

Aorta↗

[Antiblastic hypoxic stop-flow perfusion in the treatment of liver metastasis: preliminary results].

PATIENTS AND METHODS: 27 patients (14 men and 13 women aged 35 to 71 years; average: 59 years), with 3-11 months' follow-up (average: 5 months) were treated for hepatic metastases (17/22 from colorectal, 10/22 from other primary tumors) with hypoxic locoregional hepatic perfusion. Sixteen of 22 patients had been pretreated with resection, systemic chemotherapy or freeflow locoregional infusion. Our protocol consists in blocking arterial flow with an occlusion balloon catheter inflated in the hepatic artery; the main catheter channel is connected with a pump system and 250-300 ml saline with 30-40 mg Mitomycin C are perfused in the arterial hepatic system. Embolization with a gelatin sponge is performed after the end of perfusion. RESULTS: 19/27 patients are still alive, and 8/27 are dead but death was caused by the progression of intrahepatic disease in only 2/27 (7%). Iatrogenic lesions of the arterial wall were shown at follow-up DSA in 15/22 patients (56%). Thirteen CR (48%) and 9 PR (33%) were demonstrated at CT follow-up, amounting to 81% of objective responses. Follow-up showed a clinical CR in 12/18 symptomatic patients (66%). No case of hematologic toxicity was observed. Mean CEA values changed from 129 to 10.60. Twelve of 27 patients exhibited mild posttreatment sequels, none of them lasting longer than three days; ischemic cholecystitis was seen in 3/15 cases (14%). CONCLUSIONS: The occlusion catheters on the market are not optimal for this procedure; the axillary percutaneous approach is advantageous. CR rate was very high in our series but the objective response rate doses do not differ from those in the series with free-flow procedures. The highest CR rate was observed in untreated patients and in hypervascularized lesions; the rate of clinical sequels was low, clinical CR rates were high and there was no hematologic toxicity. This well-tolerated procedure provides good local disease control, but the high rate of deaths from extrahepatic progression suggests that systemic chemotherapy and long-step intraarterial perfusion be combined.

Adult↗