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Biomedical subjects

S Garelli

Publications and source records attributed to S Garelli.

At least 19 recordsLinked to original sources

Adjuvant androgen deprivation impacts late rectal toxicity after conformal radiotherapy of prostate carcinoma.

To evaluate whether androgen deprivation impacts late rectal toxicity in patients with localised prostate carcinoma treated with three-dimensional conformal radiotherapy. One hundred and eighty-two consecutive patients treated with 3DCRT between 1995 and 1999 at our Institution and with at least 12 months follow-up were analysed. three-dimensional conformal radiotherapy consisted in 70-76 Gy delivered with a conformal 3-field arrangement to the prostate+/-seminal vesicles. As part of treatment, 117 patients (64%) received neo-adjuvant and concomitant androgen deprivation while 88 (48.4%) patients were continued on androgen deprivation at the end of three-dimensional conformal radiotherapy as well. Late rectal toxicity was graded according to the RTOG morbidity scoring scale. Median follow up is 25.8 (range: 12-70.2 months). The 2-year actuarial likelihood of grade 2-4 rectal toxicity was 21.8+/-3.2%. A multivariate analysis identified the use of adjuvant androgen deprivation (P=0.0196) along with the dose to the posterior wall of the rectum on the central axis (P=0.0055) and the grade of acute rectal toxicity (P=0.0172) as independent predictors of grade 2-4 late rectal toxicity. The 2-year estimates of grade 2-4 late rectal toxicity for patients receiving or not adjuvant hormonal treatment were 30.3+/-5.2% and 14.1+/-3.8%, respectively. Rectal tolerance is reduced in presence of adjuvant androgen deprivation.

Aged↗

The determination of dose characteristics of ruthenium ophthalmic applicators using radiochromic film.

Ruthenium ophthalmic applicators are energetic beta ray sources, supplied in several shapes and dimensions, and used in intraocular tumor therapy. Because of their small dimensions, the determination of dosimetric characteristics represents a technical challenge. We developed a semiautomatic method to define surface dose, dose distribution, and percentage depth dose of such applicators using radiochromic dosimetric media. These detectors consist of a thin (7 microns) radiation sensitive layer on polyester base (100 microns total thickness) changing color as a function of radiation exposure. Transmission images of exposed films were then grabbed with a TV-digitizer system to obtain a gray-level image from which dosimetric characteristics such as isodose distribution, dose values, and homogeneity of nuclide distribution were derived. Good agreement between experimental results and Monte Carlo simulation performed using the GEANT 3 code, appear to be a confirmation of the validity of the method. Moreover while manufacturer specifications of absolute and relative dose rates present a standard deviation error of +/- 30% on dose rate and +/- 6% on accuracy of relative dose values, the proposed method reduces the errors to +/- 10% and +/- 4%, respectively.

Beta Particles↗

In vitro immunoglobulin synthesis: T-cell requirement in pokeweed and staphylococcus aureus B-cell activation.

The T-cell requirement for the B-lymphocyte immunoglobulin synthesis induced by Pokeweed mitogen (PWM) and by Staphylococcus aureus Cowan I (SAC) was investigated. We found that the PWM induced B-cell activation was controlled by an absolute Mitomycin-C resistant T-cell helper activity and by a Mitomycin-C sensible T-cell suppressor activity. On the other hand the SAC induced B-cell activation was less thymus dependent and was not influenced by Mitomycin-C treated or irradiated T cells. The different T-cell requirement could be an expression of different responding B-cell subpopulations.

Adult↗

Neutrophil function during cyclic chemotherapy for cancer disease.

A study of some aspects of granulocyte function was carried out before, during, and after cyclic chemotherapy in 9 patients surgically treated for carcinoma and in 6 patients with very advanced and inoperable cancer. In most patients, total leukocyte mobilization, Candida-stimulated nitroblue tetrazolium dye reduction, and phagocytosis increased after chemotherapy. Furthermore, delayed hypersensitivity skin reactions to PPD and above all to Varidase increased in the same cases. A significant correlation between accumulation of polymorphonuclear leukocytes into skin chambers and skin tests was found in both groups of patients (p less than 0.001). In some instances, fluctuations in the levels of circulating immune complexes without a distinct correlation between these complexes and granulocyte function were found. The data support the hypothesis that depressed granulocyte function may contribute to an increased susceptibility to infections and may be considered an additional factor that favors tumor dissemination. Chemotherapy seems to restore polymorphonuclear function and delayed hypersensitivity skin reactions.

Adult↗

Plasma exchange in neurological diseases. A critical approach.

The rationale for and results of plasma exchange (PE) in the therapy of different immune-mediated neurological diseases such as myasthenia gravis, multiple sclerosis, acute and chronic-relapsing Guillain-Barré syndromes, polymyositis, dermatomyositis and amyotrophic lateral sclerosis are reviewed. Dialysis dementia and Refsum's disease, subacute sclerosing panencephalitis and schizophrenia are mentioned, too. If we exclude the treatment of acute Guillain-Barré syndrome, where PE alone appears to be sufficient to produce recovery or improvement, the combined use of immunosuppressive drugs and/or lymphocytapheresis is probably needed in the treatment of the other diseases. PE allows the disease to be controlled rapidly while long-term pharmacological control is established. An underlying theme in this review is the need of adequately controlled studies or at least of large case lists with exhaustive reports concerning both positive and negative results since a new perspective is needed for this topic. Nonetheless, a number of uncontrolled observations suggest that probably PE effectiveness in most immune-mediated neurological diseases could be proven if the requisite trials were performed.

Acute Disease↗

A simple and rapid test for the quantification of osmotic fragility of red blood cells.

We have developed a simple and rapid nephelometric test for the quantification of the osmotic fragility of red blood cells. 10 microliters of whole blood are mixed with hypotonic NaCl solutions under mechanical stirring while the hemolysis curve is continuously recorded for 1 min. In our preliminary studies, this test was reproducible, time-saving, easy to set up and to standardize. No false-positive or false-negative results have been recorded so far. Moreover, it seems that this test can differentiate heterozygous beta-thalassemic patients from patients with sideropenic anemia, which was hardly possible with previously proposed assays.

Adult↗

Plasma exchange combined with cytotoxic drugs and lymphocytapheresis for myasthenia gravis.

20 patients with myasthenia gravis (MG), refractory to anticholinesterase and steroid therapy, underwent plasma exchange therapy combined with immunosuppressive drugs and lymphocytapheresis. In all these patients an apparent clinical improvement was obtained since their first exchange session. During a follow-up of 8-18.5 months, a long-lasting benefit was achieved in 16 patients even though 6 of these had a single recurrence shortly after their first apheretic cycle. 3 patients who achieved substantial improvement of their symptoms during plasmapheresis showed recurrence of weakness after each apheretic course was stopped. However, their clinical response to therapy tended to improve with the following courses, which would be consistent with the effects of immunosuppression. This study strongly suggests that plasma exchange combined with immunosuppressive drugs and lymphocytapheresis can bring about dramatic and sustained improvement of MG and may alter its natural history.

Azathioprine↗

Plasma exchange and immune complex diseases: the predictability of immune complexes removal to clinical response.

58 patients were treated by discontinuous flow plasma exchange because of an immune complex (IC) disease. 41 patients who had a high level of circulating IC prior to plasmapheresis showed both clinical and immunochemical evidence of improvement with plasma exchange. Only 2 patients with a high level of IC did not improve after therapy: these patients suffered from multiple sclerosis and idiopathic thrombocytopenic purpura, respectively. Prior to PE therapy the level of circulating IC in 15 patients was within the normal range, when measured according to Manca et al. In this group none of the patients worsened after therapy, whereas 8 patients showed an objective improvement. The positive correlation between IC removal and clinical results suggests that patients with a high level of circulating IC are most likely to benefit from apheretic treatment.

Amyotrophic Lateral Sclerosis↗

Management of immune-mediated and paraproteinemic diseases by membrane plasma separation and cascade filtration.

Membrane plasma separation was utilized in the management of 19 patients with autoimmune, immune complex or paraproteinemic diseases. In these patients 34 procedures were carried out employing a new filter composed of polyvinyl alcohol hollow fibers with a nominal pore size of 0.4 micrometer. Cascade filtration was performed in 23 procedures using a second filter built up with ethylenevinylalcohol copolymer hollow fibers with a nominal pore size of 0.1-0.2 micrometer. Both filters employed showed a very good biocompatibility, and no untoward effect was observed. Using the differential sieving effect of cascade filtration it was possible to eliminate circulating immune complexes and immunoglobulin M without the loss of necessary plasma components.

Antigen-Antibody Complex↗

Defective function of granulocytes in patients with cancer.

Mobilization of granulocytes into a serum-filled chamber, histochemical nitroblue tetrazolium (NBT) reduction tests, and phagocytosis were performed in 11 patients with solid tumors treated with surgical excision and chemotherapy and in 22 untreated or surgically treated patients. The results revealed a decreased mobilization (p less than 0.001) and an impaired capability of neutrophils to reduce NBT after stimulation (p less than 0.05) in both groups of patients. The decrease in the values in the stimulated reduction of NBT was more pronounced in untreated patients than in treated ones. At the same time the phagocytic activity of neutrophils on Candida albicans, which was decreased (p less than 0.01) in untreated patients, was normal in those who had been treated with chemotherapy. There were no distinctive correlations between circulating immune complexes and granulocyte function. We propose that this newly demonstrated defect in neutrophil mobilization and low median C. albicans-stimulated NBT reduction contributes more in the evolution of the tumor than in the pathogenesis of infections and that chemotherapy seems to restore a better granulocyte function.

Adult↗

Plasma exchange in the management of patients with multiple sclerosis: preliminary observations.

Since humoral factors have been implicated in the pathogenesis of multiple sclerosis (MS) and previous attempts at therapeutic intervention have not met with uniform success, plasma exchange (PE) was recently proposed for the management of this disease. We are currently investigating the possible effectiveness of PE in the treatment of MS, and to date 6 patients have been entered into the study. At least 4 of our patients who did not respond to conventional therapy have shown unequivocal, moderate to marked improvement following the first session of PE. At the time of treatment, these patients had an acute exacerbation of their disease. We found no correlation between clinical improvement and the serum immune complex levels, suggesting that other poorly known mechanisms were operative. Based on our preliminary results, we feel that PE may be efficacious in treating exacerbations of MS. More evidence is needed on the effects of PE in the chronic stage of the disease.

Adult↗

Plasma exchange as a therapy for Guillain-Barré syndrome with immune complexes.

Small volume plasma exchange (PE) was evaluated in 6 patients with acute Guillain-Barré syndrome (GBS) and in 1 with its chronic relapsing type. Patients were treated during the onset or progression of their neurologic involvement and no other combined therapy was provided. 6 of our patients had clear benefit following the first session. Two procedures on alternate days were carried out in 4 patients while a third procedure was performed in 3 due to insufficient exchange or to equivocal improvement. After PE, patients showed moderate to marked improvement in motor strength, in their ventilatory function and in their sensory symptoms, which improved definitely but more slowly than motility. Each patient showed, prior to therapy, high levels of immune complexes; their level was clearly reduced by PE and clinical results correlated with this removal. No relapse was observed during 5-15 months of appropriate follow-up.

Adult↗

Patients with high titers of circulating immune complexes are most likely to benefit from plasmapheresis treatment.

Intermittent flow centrifugation system was utilized in the management of 17 patients with IC diseases. 14 out of 14 patients that had high levels of ICs prior to plasmapheresis showed both clinical and immunochemical evidence of improvement with plasmapheresis. 3 patients had no evidence of circulating ICs prior to plasmapheresis: in these cases no apparent result was achieved after the apheretic therapy. Although the striking correlation between IC removal and clinical result is not a formal proof of responsibility of CIC in the pathogenesis of the disease, it is suggested that quantitative determination of CICs (utilizing several different recognition units) may be a useful parameter in the decision to apply plasmapheresis in the therapy of selected autoimmune diseases.

Adolescent↗

Plasmapheresis in the treatment of four cases of Guillain-Barré syndrome (acute form).

Four patients with GBs were treated by PE. In all cases the treatment was successful in that it halted the progression of the disease, induced regression of the signs of bulbar impairment, ventilatory failure and cranial nerve paralysis and improved motility. In all instances the response was quicker for the nerves affected last. Our results confirm that PE is probably the only pathogenetic therapy that can be offered to GBs patients, especially since it can halt the progression of the disease and dramatically shorten its course. It is noteworthy that clinical benefit correlates strongly with removal of large quantities of circulating immune complexes.

Acute Disease↗

Plasma exchange for a hemolytic crisis due to autoimmune hemolytic anemia of the IgG warm type.

A patient with a hyperacute hemolytic crisis due to AIHA of the IgG type was treated by combined plasmapheresis and exchange transfusion. A discontinuous flow centrifuge was used. Immediately after the exchange the hemoglobin level rose from 2.6 to 9.8 g/dl. The D. A. T. became weakly positive and the hemolytic crisis subsided. During the days following the exchange the autoantibodies responsible for the hemolytic crisis, switched from IgG1 and IgG3 to IgG2 and IgG4. The clinical and laboratory picture stabilized thereafter.

Adult↗