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Biomedical subjects

E Gallo

Publications and source records attributed to E Gallo.

At least 37 records · Page 2Linked to original sources

Size fractionation of bacterial capsular polysaccharides for their use in conjugate vaccines.

We have developed a chromatographic method suitable for the fractionation of polysaccharides having a negatively charged group. The method permits the removal of all those polysaccharide fragments having a short sequence and which are likely unsuitable for conjugate vaccine construction. The selected polysaccharide fragments can be used to produce glycoconjugate vaccines containing a restricted saccharide polydispersion. We have applied this chromatographic method to three different antigens, Haemophilus influenzae type b and Neisseria meningitidis group A and group C polysaccharides. The method is easily adapted for manufacturing purposes.

Antigens, Bacterial↗

Determination of azithromycin in gastric biopsy samples.

OBJECTIVES: To measure the concentration of azithromycin in gastric biopsy samples of gastritis patients undergoing Heliobacter pylori eradication treatment with azithromycin as one antibiotic constituent of the medication. PATIENTS: Seven male outpatients, non-smokers, non-alcoholics, aged 25-40 years (mean 32 years), suffering from gastritis with involvement of H. pylori. METHODS: The patients received a 5-day treatment with azithromycin (1 x 500 mg on day 1 and 1 x 250 mg on days 2-5), 40 mg pantoprazole once daily and 2 x 400 mg metronidazole once daily. Samples of gastric tissue were obtained from 5 patients and of gastric juice from 2 patients, at the occasion of gastroscopic interventions. The gastric samples were subject to analysis of azithromycin, using a highly sensitive and specific HPLC method with electrochemical detection. RESULTS: The median concentrations of azithromycin in gastric tissue amounted to 7.5 microg/g on day 2 and to 9.7 microg/g on day 5 of the treatment. Four days after the end of treatment, median concentrations were still at 3.9 microg/g. In all tissue samples, azithromycin concentrations were well above the MIC for H. pylori (0.25 microg/ml). The well-known tissue affinity of azithromycin was underlined by the lack of detectable levels in gastricjuice. CONCLUSION: The high concentrations of azithromycin observed in gastric tissue of patients with gastritis on a 5-day dosage regimen point to a favorable pharmacokinetic basis for a role of azithromycin as a component of the eradication therapy of Heliobacter pylori.

Adult↗

Bactericidal monoclonal antibodies that define unique meningococcal B polysaccharide epitopes that do not cross-react with human polysialic acid.

The poor immunogenicity of the Neisseria meningitidis group B polysaccharide capsule, a homopolymer of alpha(2-->8) sialic acid, has been attributed to immunologic tolerance induced by prenatal exposure to host polysialyated glycoproteins. Substitution of N-propionyl (N-Pr) for N-acetyl groups on the meningococcal B polysaccharide, and conjugation of the resulting polysaccharide to a protein carrier, have been reported to yield a conjugate vaccine that elicits protective Abs with minimal autoantibody activity. To characterize the protective epitopes on the derivatized polysaccharide, we isolated 30 anti-N-Pr meningococcal B polysaccharide mAbs. These Abs were heterogeneous with respect to complement-mediated bactericidal activity, fine antigenic specificity, and autoantibody activity as defined by binding to the neuroblastoma cell line, CHP-134, which expresses long-chain a(2-->8)-linked polysialic acid. Eighteen of the Abs could activate complement-mediated bacteriolysis. Seven of these 18 Abs cross-reacted with N-acetyl meningococcal B polysaccharide by ELISA and had strong autoantibody activity. Thus, N-Pr meningococcal B polysaccharide conjugate vaccine has the potential to elicit autoantibodies. However, 7 of the 18 bactericidal mAbs had no detectable autoantibody activity. These Abs may be useful for the identification of molecular mimetics capable of eliciting protective Abs specific to the bacteria, without the risk of evoking autoimmune disease.

Animals↗

Radiofrequency resection of bronchial tumours in combination with cryotherapy: evaluation of a new technique.

BACKGROUND: A number of treatments, including Nd-YAG laser therapy, brachytherapy, cryotherapy, electrocautery, and photodynamic therapy, can re-open the obstructed bronchial lumen in patients with inoperable obstructive bronchial tumours. None of these is considered to be a "gold standard". METHODS: The results of a retrospective study of 98 patients treated by radiofrequency tissue ablation and subsequent cryotherapy between January 1994 and June 1995 are reported. The patients were divided in two groups according to whether they were treated either after (group 1, n = 50) or before (group 2, n = 48) radiotherapy and/or chemotherapy. Bronchoscopic follow up was performed. The intervention was considered successful if the lumen was opened by > 80% and partially successful if it was opened by > 50%. RESULTS: In group 1 treatment was successful in 60%, partially successful in 32%, and unsuccessful in 8%. The median survival time was five months from the time of bronchoscopic surgery. In group 2 treatment was successful in 66%, partially successful in 21.5%, and unsuccessful in 12.5%, with a median survival time of 14 months from the time of bronchoscopic treatment. Forty patients (24 in group 1 and 16 in group 2) received a Dumon stent. CONCLUSIONS: Radiofrequency bronchoscopic surgery with cryotherapy appears to be a useful technique in the treatment of tracheobronchial obstruction.

Aged↗

[Percutaneous positioning of port catheter in the hepatic artery for chemotherapy of metastases using the Arai technique].

INTRODUCTION: Liver metastases from colorectal, gastric and breast cancers are a very frequent event; these metastases are treated with cycles of intraarterial chemotherapy with a permanent catheter positioned in the hepatic artery or with surgical or interventional radiology techniques. We tested Arai's technique and its feasibility and evaluated the efficacy of this chemotherapy schedule. MATERIAL AND METHODS: Four patients with liver metastases from colorectal carcinoma were treated with combined systemic and locoregional chemotherapy with a permanent catheter placed in the hepatic artery according to Arai's technique. Arai's technique consists in studying the hepatic vascularization and then redistributing hepatic flow in case of multiple hepatic arteries; the vessels in which the infusion of chemotherapies could cause toxicity are then occluded and finally a catheter is positioned in the hepatic artery with subclavian artery catheterization and the connection with a subcutaneous reservoir for injection--the port-a-cath system. We planned CT examinations to study liver morphology and radiographs of the abdomen and chest to depict the catheter position and patency, respectively. RESULTS: The catheter was positioned correctly without any complications in all patients, as planned. We administered 37 cycles of combined systemic and locoregional chemotherapy in all. Two patients died of disease progression after 6 months but the other 2 are still alive and CT showed partial disease remission. We observed no catheter dislocation or occlusion at chest radiography and transport angiography, respectively. CONCLUSIONS: Infusion chemotherapy in the hepatic artery from permanent catheters is widely accepted in our country and we believe that Arai's technique could be an alternative to the more classic and established surgery. The small number of our patients and the short follow-up do not permit definitive conclusions to be drawn on the clinical efficacy of this combined systemic and intra-arterial treatment.

Adult↗

[The use of allografts in the surgical treatment of patients with infected vascular prostheses].

The article is devoted to analysis of surgical treatment of patients with such a dangerous complication as infection of the vascular prosthesis. The authors have performed 25 operations for substituting the infected prostheses for allografts. In 18 patients the infected prostheses were located in the aorto-iliac segment, in 5 patients in the femoro-popliteal segment, 1 patient had it in the aorta, and 1 in the subclavian segment. The prostheses were removed and a simultaneous revascularization was made. The authors make a conclusion that it is very expedient to use alloprostheses as a protective measure against persistent or recidivating infections. The allografts have both early and long-term resistance to infection.

Aged↗

Revisiting the prognostic role of gallium scintigraphy in low-grade non-Hodgkin's lymphoma.

The purpose of this study was threefold: to evaluate the role of gallium-67 scintigraphy in the staging of low-grade non-Hodgkin's lymphomas (LGNHL), to assess the relationship between the expression of CD71 on the surface of the neoplastic cells and the 67Ga uptake by the tumour, and to establish the contribution of 67Ga scan in defining the prognosis of LGNHL. Forty-eight patients with untreated LGNHL diagnosed in a single institution over a decade were reviewed. The end point of the study was survival of the patients according to the scintigraphic 67Ga score at diagnosis. In addition to 67Ga scan, other prognostic variables were studied, relating to the neoplastic burden, the biology of the tumour and the host. Univariate and multivariate analyses were used. 67Ga scan identified only 116/286 (41%) nodes involved by lymphoma that were detected by clinical examination or computed tomography scan. A scintigraphic scoring system with an arbitrary cut-off value of 3 (high scan score) was able to predict patients with a dismal prognosis: with a mean follow-up of 47 months (range: 1-146 months) the median survival time was 28 months in patients with a high scan score and 74 months in patients with a low scan score (P=0.002). CD71 values were 27. 4%+/-14.9% (mean +/-SD) in the former and 8.9%+/-7.2% in the latter (P=0.0001). Only performance status and extranodal sites were significant variables for prognosis in multivariate analysis. It is concluded that 67Ga scan is inaccurate in staging but might be very important in defining the prognosis in LGNHL, in association with other prognostic variables.

Antigens, CD↗

Suppression of in vitro maintenance of non-promyelocytic myeloid leukemia clonogenic cells by all-trans retinoic acid: modulating effects of dihydroxylated vitamin D3, alpha interferon and 'stem cell factor'.

In a liquid culture system, all-trans retinoic acid (ATRA), alone and in combination with dihydroxylated vitamin D3 (D3) or alpha interferon (alphaIFN) at concentrations achievable in vivo, could significantly suppress the maintenance of non-promyelocytic myeloid leukemia clonogenic cells (CFU-L) in 9/20, 9/18 and 7/11 cases, respectively. That suppression was counteracted only slightly by the addition of 'stem cell factor', a cytokine which promotes CFU-L expansion in vitro. Differentiated cells slightly increased in 5/17 cases only, suggesting the prevalence of anti-proliferative rather than differentiating mechanisms. The present results extend our previous ones and suggest the possible therapeutical value of ATRA+D3 or alphaIFN, even in cases of non-promyelocytic myeloid leukemia.

Acute Disease↗

[Measurement of cardiac output with continuous thermodilution. b1 Clinical experience with the Intellicath-Vigilans system].

BACKGROUND: Thermodilution cardiac output measurements are commonly obtained by a manual bolus technique with a pulmonary artery catheter. METHODS: A new thermodilution catheter has been developed which utilizes an integral thermal filament and provides semicontinuous online cardiac output. The response of this new device in 25 patients undergoing coronary artery bypass grafting was examined. A total of 250 data pairs was obtained; the cardiac outputs ranged from 2.2 to 11.9 lts.min. RESULTS: The linear regression is represented by the following equation: continuous thermodilution = 0.7196 bolus thermodilution +1.038. The correlation coefficient was 0.75; the mean bias was 0.493 +/- 1.034. CONCLUSIONS: The new technique provides acceptable accuracy in many clinical situations except when sudden haemodynamic changes occur.

Cardiac Output↗

Combined differentiating therapy for myelodysplastic syndromes: a phase II study.

An in vitro synergism between different inducers of AML cell differentiation has been previously observed. Therefore, we treated 53 myelodysplastic (MDS) patients with a low dose combination of cis-retinoic acid (cRA, 20-40 mg/day) and 1,25 alpha (OH)2 cholecalciferol [(OH)2D3, 1-1.5 micrograms/day] +/- intermittent 6-thioguanine (30 mg/m2/day). The latter was reserved for patients with bone marrow (BM) blast excess (> or = 5%). The treatment was well tolerated, without major toxicity. Among 25 patients with BM blasts less than 5%, we observed one complete, eight partial and four minor responses (response rate 52%) with a median response duration of 8 months (2 +/- 24). Median survival, which did not correlate with response, is projected at 76 months. Thirty-one patients with BM blast excess (> or = 5%), including three of the previous group who progressed to refractory anemia with excess of blasts (RAEB), were treated with the three-drug protocol. One complete, 12 partial and six minor responses were obtained (response rate 61%) with a median response duration of 6 months (2-29+). A significant difference in survival (P < 0.005) was observed between the 19 responders (median 25 months) and the 12 non-responders (median 9 months). A reduction in the transfusion need was observed in 41% of the transfusion-dependent patients with blast excess and in 53% of those without blast excess. Therefore, combined differentiating therapy seems more effective than previously reported single agent treatments and should be considered for a larger randomized study to assess its actual impact on survival of MDS patients.

Aged↗

Robot-assisted microscope for neurosurgery.

We describe the implementation of a robotic arm connected to a neurosurgical operative microscope. A force feedback sensor drives the motors of the arm in response to the positioning of the microscope by the surgeon. Computer graphic techniques allow tracking of the current position of the microscope within the volumetric reconstruction of the brain. The integration of the prototype into the neurosurgical operating room is currently being evaluated. Preliminary comments on this experimental phase are offered.

Angiography, Digital Subtraction↗

Haematological support of high-dose sequential chemotherapy: clinical evidence for reduction of toxicity and high response rates in poor risk lymphomas.

The toxicity and feasibility of a high-dose sequential (HDS) chemotherapy programme delivered with growth factor support were evaluated in patients with intermediate and high-grade non-Hodgkin's lymphoma (NHL) or with progressive Hodgkin's disease. The scheme includes the sequential administration of single cytotoxic drugs at very high doses followed by intensified treatment with circulating progenitor autograft. In some instances, the original HDS scheme, initially designed at the Milan Cancer Center, was partially modified and intensified with a preliminary debulking phase. The use of G-CSF (filgrastim) made toxicity in the high-dose phase acceptable and allowed good harvests of peripheral blood progenitor cells (PBPC); the use of PBPC in the final autografting phase resulted in low haematological toxicity. Of 71 patients with NHL treated at our institution with either the original or the intensified HDS version, the overall toxicity-related mortality was 5.6%, thus comparable to lethal toxicity commonly associated with conventional chemotherapy. Adequate PBPC harvests are crucial for good tolerability of the programme. Optimal harvests are generally obtained in patients without neoplastic marrow infiltration while patients with marrow disease often have a poorer mobilisation. However, an optimally time-spaced chemotherapy debulking might also restore sufficient mobilisation in these latter patients. In terms of therapeutic efficacy, HDS had produced promising results since the initial experience in relapsed patients. More recently, HDS was evaluated as first-line treatment in a series of 22 consecutive patients, presenting with advanced-stage, intermediate-grade NHL other than diffuse large cell subtype. A CR rate of 82% was obtained following HDS, with a projected survival of 86% at five years. Thus, delivery of an intensive high-dose chemotherapy programme with haematopoietic growth factor support was found to be feasible and reasonably safe. The high anti-tumour efficacy of such a scheme makes it suitable for wider applicability in all those chemosensitive tumours where a dose increase might enhance the chance of cure.

Antineoplastic Combined Chemotherapy Protocols↗

Generation of anti-tumour activity by OKT3-stimulation in multiple myeloma: in vitro inhibition of autologous haemopoiesis.

T cells in multiple myeloma (MM) patients are highly susceptible to activation with the anti-CD3 monoclonal antibody (mAb) OKT3. When short-term OKT3 stimulation is carried out on bone marrow mononuclear cells (BMMC), large numbers of CD3+ CD25+ HLA-DR+ cells are rapidly generated and autologous malignant plasma cells are killed. OKT3 may thus be exploited in autologous bone marrow transplantation (ABMT) to purge residual plasma cells and simultaneously activate T cells to induce graft-versus-leukemia-like (GVL-like) activity upon reinfusion. However, the possible impact of ex-vivo short-term OKT3 stimulation on haematological recovery is unknown. The aim of this work was to investigate the effect of OKT3 stimulation in vitro on autologous haemopoietic progenitor cells (HPC) of MM patients. Colony formation by granulocyte-macrophage progenitor cells (granulocyte-macrophage colony-forming units, CFU-GM) was highly suppressed, although supernatants of OKT3-activated T cells contained up to 2,500 pg/ml of granulocyte-macrophage colony-stimulating factor (GM-CSF). T cell depletion completely prevented this suppression. Neutralizing antibodies against TNF-alpha, TNF-beta and IFN-gamma (which are also produced by OKT3-activated MM T cells) did not prevent it, and Transwell cultures showed that cell-to-cell contact was the main mechanism involved. OKT3-activated T cells also suppressed erythroid burst-forming units (BFU-E) and CFU-GM generation from HPC responsible for long-term maintenance of in vitro myelopoiesis. When tested on normal allogeneic BM, MM supernatants of OKT3-stimulated BMMC partially suppressed the generation of day 7 CFU-GM, but had no effect on day 14 CFU-GM. These data indicate that short-term stimulation of BMMC with OKT3 can be used to generate anti-tumour effector T cells for autologous adoptive immunotherapy. It is not a feasable approach for ex-vivo purging and activation procedures in ABMT because of its potent inhibition of autologous haemopoiesis.

Bone Marrow Cells↗

Stem cell factor improvement of proliferation and maintenance of hemopoietic progenitors in myelodysplastic syndromes.

Human recombinant stem cell factor (rSCF) was tested for its capability of improving the defective growth of hemopoietic progenitors in 28 cases of myelodysplastic syndromes (MDS). In vitro growth and response to rSCF were quite variable. However, in most cases, rSCF stimulated CFU-GM growth induced by rG-CSF, rGM-CSF, rIL-3, 5637 conditioned medium (50-1400% enhancement). rSCF effect was slightly more evident on day 14 CFU-GM and in the presence of rIL-3. BFU-E growth induced by rEPO or rIL-3 + rEPO was enhanced by rSCF in about 50% of cases, in linear correlation with the levels of patients' hemoglobin. rSCF did not increase CFU-E growth, whereas it slightly stimulated CFU-Mk in 33% of the cases. EPO, SCF and, particularly, their combination, enhanced the recovery of normal CFU-E and BFU-E after 7 days of liquid culture. This was less evident in cultures of MDS patients. Conversely, CFU-GM generation in long term liquid cultures, although highly variable, was stimulated by rSCF and, above all, by rSCF + rG-CSF, similarly to what was observed with normal bone marrow samples. SCF seems to enhance in vitro erythropoiesis only in MDS cases presenting without severe anemia. It has little effect on megakaryocytopoiesis, while it seems to be more active on CFU-GM growth and maintenance.

Cell Division↗

[Clinical considerations in Raynaud's phenomenon. How many and which patients are treated?].

Among the multiple aspects about which little is still known about Raynaud's phenomenon (RP), is that, in the author's opinion, regarding the question: how many and which patients are sufficiently troubled by this pathology to seek medical treatment from their own GP or specialist, and what are the results of any treatment commenced. The following questions were put to a group of 180 patients affected by RP attending the out-patient clinic for the first time: 1) how many had already received treatment; 2) which patients were receiving pharmacological treatment and/or had undergone surgery. In this context, the authors assessed the influence of the following parameters on the fact that they had or had not been treated: a) the age of patients; b) the duration of disease; c) the presence of stenosing or obliterating arterial lesions (RP on an organic basis); d) the co-presence of pathologies considered to be the possible etiological cause of RP in literature; e) the severity of symptoms; 3) what results were obtained by medical and/or surgical treatment; 4) what was the course of RP which failed to respond to therapeutic measures. The study examined a series of 180 subjects including 139 (77.22%) females (mean age 47.6% years) and 41 (22.78) males (mean age 42.4 years). Symptoms had been present for a period ranging between 2 and 44 years (mean 10.01). In order to ascertain the possible presence of associated diseases considered by many authors to be causal factors, all patients underwent hemotochemical and instrumental test.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Fibrinolytic imbalance in essential thrombocythemia: role of platelets.

Thrombotic and hemorrhagic complications are frequent in patients with essential thrombocythemia (ET), a myeloproliferative syndrome with an increased number of circulating platelets. Since platelets are a physiological reservoir for the plasminogen activator inhibitor (PAI-1) contained in plasma, we evaluated plasma and platelet tissue plasminogen activator (tPA) and PAI-1 in 20 ET patients with and without thrombotic complications and in 13 control subjects. In ET patients with thrombotic complications there was a significantly greater platelet PAI-1 functional activity than in ET patients without thrombotic complications and in the control group (p < 0.05 and p < 0.025, respectively). Moreover, platelet tPA activity was significantly low in all ET patients (p < 0.001). This fibrinolytic imbalance (increased plasminogen inhibitor and lowered activator) might be a critical cofactor in the thrombotic complications in ET patients.

Adult↗

Cryosurgery in bronchoscopic treatment of tracheobronchial stenosis. Indications, limits, personal experience.

Cryosurgery is one of the techniques available for bronchoscopic treatment of malignant and nonmalignant tracheobronchial stenosis; other techniques are electrosurgery, laser therapy, and endobronchial brachytherapy. Our experience began in 1976 and includes more than 300 patients treated with bronchoscopic cryosurgery either for malignant (the majority) or for nonmalignant tracheobronchial lesions. This study was performed on 234 patients treated in the years 1979 to 1988 subdivided as follows: 183 malignant tumors, 44 benign tumors, and 7 tumors of uncertain prognosis (adeno). The study demonstrated satisfying results in both (palliative in the first case, almost radical in the second one). The aim of our work was to report our personal data and to compare advantages and limits of this technique to others.

Bronchial Diseases↗

High-dose sequential (HDS) chemotherapy with blood and marrow cell autograft as salvage treatment in very poor prognosis, relapsed non-Hodgkin's lymphoma.

We tested the feasibility and efficacy of a novel high-dose sequential chemoradiotherapy programme (HDS) in 14 relapsed or refractory non-Hodgkin's lymphoma patients with very poor prognostic features, i.e. transformed histology, marrow invasion, low performance status. This regimen included the sequential administration of high-dose cyclophosphamide (CY) 7 g/m2 followed by high-dose methotrexate (MTX) 8 g/m2 and high-dose VP16 2 g/m2 and finally by total body irradiation (TBI)-melphalan and autograft of bone marrow and peripheral blood progenitor cells. No hemopoietic growth factor support was employed in any phase. There was one treatment-related death during the high-dose phase; three other patients did not complete the programme. All 10 patients concluding the programme achieved complete remission, with four patients in complete clinical remission at a median follow up of 34 months. Median overall survival was 27 months and median failure-free survival (FFS) was 12 months. Twenty-six well comparable patients received conventional salvage therapy during the same period. Their projected median overall survival (8 months) and median FFS (4 months) were shorter than in the HDS group (p = 0.06 for overall survival and p = 0.03 for FFS). Thus, HDS is a feasible programme and may offer superior results than conventional therapy in poor-prognosis NHL patients.

Adult↗