Search PubMed⌕ Search

Biomedical subjects

R Invernizzi

Publications and source records attributed to R Invernizzi.

At least 55 records · Page 3Linked to original sources

Long term results of interferon treatment in hairy cell leukemia. Italian Cooperative Group of Hairy Cell Leukemia (ICGHCL).

Eighty nine of 104 patients with hairy cell leukemia (HCL), enrolled between 1985 and 1987 in a multicenter prospective study on human lymphoblastoid IFN alpha-n1, were evaluable for long-term follow-up. The induction treatment, 3 MU/mq daily for a median of 5.7 months, produced a response of 93%, complete+partial response (CR+PR) = 80%, minor (MR) = 13%. Neither prior splenectomy nor pre-treatment variables were associated with the rate of response to IFN. However maintenance treatment of 3 MU/mq weekly given randomly had a slightly significant effect on failure free survival (FFS). Of the 43 patients who relapsed, 31/36 (86%) obtained a new response with IFN. No differences in FFS were recorded between first and second response. At the third induction 7/11 patients were treated again with IFN, 4/7 obtaining some response, but the FFS was significantly worse. The overall survival is still 85%. We conclude that (1) IFN should be used as chronic uninterrupted treatment for HCL, (2) reduced dosage is sufficient to prolong the disease free status and (3) continuous lymphoblastoid IFN administration seems not to be associated with the development of resistance to retreatment.

Aged↗

[Kaposi's sarcoma--classic form. A rare familial case].

Although Kaposi's sarcoma became very well-known with the outbreak of AIDS, this pathology in the classic Mediterranean form is still unusual and obscure. Nowadays we identify four types of Kaposi's sarcoma: 1) the classic Mediterranean form, 2) the endemic African one, 3) the therapeutical in immunosuppressed patients, 4) the epidemic AIDS-related one. We report a very rare case of familial Kaposi's sarcoma: the father (72 y.o.) manifested Kaposi's sarcoma in 1989 with several angiomatoid nodules on the penis and hands; the son (31 y.o.) presented in 1991 only one little nodule on the penis. The right therapy in these cases (patients with a small number of localizations) was to remove all the tumors and to wait: whereas in other cases it's preferable to use radio- or chemo-therapy or immunomodulator agents. We studied the patients and identified their form of Kaposi like the classic one not completely related (the son) to the HLA DR5, which is the HLA-phenotype most frequent in this sarcoma. Moreover we stress the rarity of genital localization in the classic form, instead it is very common (20%) in the AIDS-related one.

Adult↗

Application of monoclonal anti-idiotypes in the study of AL amyloidosis: therapeutic implications.

A monoclonal anti-idiotyped antibody (IgG1k MAb 3B11D4) has been raised against the lambda-chain dimers isolated from the urine of a patient (DEP) with AL amyloidosis. This antibody binds a conformational idiotope present on the monoclonal DEP IgA, but does not recognize the reduced and alkylated lambda-chain monomers, nor the 15- to 17-kDa light chain fragments obtained from the amyloid fibrils, which have the same N-terminal sequence as the urinary light chains. The nonreactivity of this MAb with amyloid fibrils was confirmed by immunohistochemical examination of cryostatic sections of an amyloidoma surgically removed from the patient's subcutaneous tissue. Our data demonstrate that the deletion of about 70 amino acid residues of the C-terminus of the lambda chain prevents the formation of the self-limiting dimer and may facilitate the deposition of fragments into amyloid fibrils. With regard to the amyloidogenic clone, MAb 3B11D4 recognizes the plasma cell clone in bone marrow and 9% of circulating B lymphocytes. Panning and cytotoxicity experiments demonstrate that this antibody has the capability of selectively eliminating the idiotype-positive cells from peripheral blood. Antibodies with these properties could find application in a new therapeutic strategy which provides high-dose chemotherapy, total body irradiation, and rescue with circulating stem cells. These antibodies could be used in two distinct phases: first, in the purging of the stem cells to be infused from the amyloidogenic clone and, secondly, in an attempt to eliminate residual disease by intravenous infusion.

Amyloid↗

[The use of piperacillin in the preoperative prophylaxis of colorectal surgery].

The authors present a prospective trial in 34 patients undergoing elective colo-rectal surgery. Seventeen patients received 2 g of piperacillin; intravenously, 30' min before surgery, and again 5 times, postoperatively, every 6 hours. The other 17 patients received 2 g of the same drug, intravenously, every 12 hours, immediately after surgery, at least for 5 days. The first group showed postoperative wound infections, with a rate of 11.75%. In the second group 5 patients showed postoperative infection, with a rate of 29.41%. There were 3 wound infections, one urinary tract infection and two pleuropolmonitis (a patient had two infections simultaneously). No side effects were registered. The better results registered in the first group, suggest the use of piperacillin in shortterm prophylaxis. This choice is attractive because of the comparison with other antibiotics, used in a similar way, shows similar results.

Adult↗

Graft-versus-leukemia effects after allogeneic bone marrow transplantation are active also in the presence of clones with chromosomal anomalies in addition to the Ph chromosome.

Two male patients with Philadelphia-chromosome (Ph+) chronic myelogenous leukemia (CML) underwent allogeneic bone marrow transplantation (ABMT) in the first chronic phase after busulfan treatment. In both cases, the donor was a sister, and engrafting was demonstrated by chromosome analyses which showed only donor cells in the BM. Cytogenetic relapse occurred 29 and 30 months after ABMT, respectively, when host cells reappeared: in both cases, the Ph and additional anomalies typical of the blastic phase of CML were evident. We then monitored the chromosome picture for 52 and 39 months, respectively: no striking evolution occurred, and cells with the Ph and additional anomalies persisted together with donor cells, which were a minority in the first patient and a great majority in the second throughout the observation period. A clinical relapse was observed in the first patient, but the disease never progressed to a blastic phase, whereas the second patient has not relapsed 7 years after ABMT. We reviewed data from the literature on cytogenetic relapse after ABMT in CML without clinical relapse, especially the 12 patients in whom cytogenetic relapse included chromosome anomalies in addition to the Ph, as in our patients. We suggest that graft-versus-leukemia (GVL) reactions in such patients are able to arrest progression of the leukemic blastic clone and prevent a possible relapse in blastic phase.

Bone Marrow Transplantation↗

Citalopram's ability to increase the extracellular concentrations of serotonin in the dorsal raphe prevents the drug's effect in the frontal cortex.

Administered intraperitoneally to rats at 1 mg/kg, citalopram, a potent and selective inhibitor of serotonin uptake, significantly increased dialysate serotonin in the dorsal raphe, but not in the frontal cortex. At 10 mg/kg citalopram had a greater effect on raphe serotonin and a moderate and short-lasting increase in the dialysate serotonin in the frontal cortex. Citalopram 1 mg/kg i.p. significantly increased the extracellular concentration of serotonin in the frontal cortex of rats which had received a continuous infusion of 1 microM methiothepine in the dorsal raphe, a condition which by itself did not change cortical serotonin concentrations. The results suggest that the ability of serotonin uptake inhibitors to enhance the extracellular concentrations of serotonin in the dorsal raphe attenuates the drug's effect in the frontal cortex.

Animals↗

Nodular sclerosing Hodgkin's disease and large cell lymphoma. Immunophenotypic characterization of a composite case.

Composite lymphomas have rarely been reported in Hodgkin's disease (HD), except in the lymphocyte predominance sub-type, and immunohistochemical investigations have been performed in only few cases. We describe the histological and immunophenotypical findings in a case of composite nodular sclerosing HD and high-grade, large cell non-Hodgkin's lymphoma (NHL). In our case HD and NHL cells displayed striking morphological and immunophenotypical divergence, suggesting a lack of correlation between the two neoplasms.

Adult↗

Tianeptine increases the extracellular concentrations of dopamine in the nucleus accumbens by a serotonin-independent mechanism.

The effect of various doses of tianeptine on the extracellular concentrations of dopamine was studied in the striatum and nucleus accumbens of the rat. At 5 (but not 2.5) mg/kg intraperitoneally, tianeptine increased the extracellular dopamine only in the nucleus accumbens. At 10 mg/kg, the effect was also seen in the striatum but it was less marked and shorter-lasting. At 10 mg/kg (i.p.), tianeptine significantly raised the extracellular concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in both regions. The effect of 10 mg/kg tianeptine on dopamine and its metabolites was not significantly changed in animals which had received this dose twice daily for 15 days. Intracerebroventricular administration of 150 micrograms/20 microliters 5,7-dihydroxytryptamine, which markedly depleted serotonin in the brain, did not modify the effect of 10 mg/kg tianeptine on the extracellular concentrations of dopamine and HVA in the nucleus accumbens but reduced the effect on DOPAC. Various doses of tianeptine (1, 3 and 10 mg/kg i.p.) did not change the synthesis of serotonin and dopamine in the striatum and nucleus accumbens. The results show that tianeptine increased the extracellular concentrations of dopamine more in the nucleus accumbens than in striatum. The effect on the output of DA in the nucleus accumbens could be involved in the antidepressant activity of tianeptine.

3,4-Dihydroxyphenylacetic Acid↗

Immunocytochemical detection of factor XIII A--subunit in acute leukemia.

Factor XIII (FXIII) is a plasma pro-transglutaminase consisting of A and B subunits in a tetrameric structure. A cellular form of FXIII consisting exclusively of A subunits exists in platelets and monocytes: monocyte FXIII may be involved in connective tissue organization. To evaluate the expression and diagnostic significance of FXIII A subunit (FXIIIA) in acute leukemia, we performed an immunocytochemical study (PAP technique) with rabbit antiserum against FXIIIA on leukemic blasts of 48 cases. FXIIIA was detected only in myelomonocytic (M4), monocytic (M5) and megakaryocytic (M7) cases: in M4 and M5 samples the amount of blast cytoplasmic FXIIIA was closely correlated with the expression of monocyte-specific antigenic and cytochemical markers. Our data show immunocytochemical detection of FXIIIA to be useful for acute leukemia characterization.

Acute Disease↗

Antibodies for denatured human H-ferritin stain only reticuloendothelial cells within the bone marrow.

Human H-ferritin homopolymer was denatured in sodium dodecyl sulphate and injected in mice to obtain antibodies for dissociated H-subunit. The antisera and Moabs obtained were specific for the denatured H-chain with no cross-reactivity with assembled ferritins in immunoblotting experiments. In contrast the Moabs for native recombinant H-ferritin are specific for the assembled ferritin molecules with weak cross-reactivity with the denatured H-subunits. The epitope recognized by one of the anti-denatured H-chain Moabs was mapped on the C-terminal helix of ferritin. The antibodies were used to study H-ferritin conformation in cells. In immunocytochemistry experiments the antibodies for denatured H-ferritin stained HeLa and K562 cells weakly, with a different intensity and pattern to those obtained with anti-native H-ferritin antibody. In human bone marrow smears the anti-denatured ferritin antibodies stained only reticuloendothelial cells, and did not recognize the H-ferritin rich immature erythroblasts. It is concluded that assembled and denatured H-ferritins are immunogenically distinct, and that erythroid and reticuloendothelial cells within the bone marrow contain H-ferritin in different conformations.

Antibodies, Monoclonal↗

Use of an anti-idiotypic monoclonal antibody in studying amyloidogenic light chains in cells, urine and fibrils: pathophysiology and clinical implications.

A monoclonal anti-idiotype antibody (IgG1k MoAb 3B11D4) raised against the amyloidogenic DEP lambda chain dimer binds a conformational idiotope also present on the monoclonal DEP IgA immunoglobulin. MoAb 3B11D4 does not recognize the reduced and alkylated lambda chain monomers, nor the 15-17-kDa fibrillar light chain fragments which have the same N-terminal sequence of the urinary light chains. The lack of about 70 amino acid residues of the C terminal of the protein prevents the formation of the self-limiting dimer and may facilitate the deposition of the fragments into amyloid fibrils. MoAb 3B11D4 recognizes the plasma cell clone in bone marrow and 9% of circulating B lymphocytes. Panning experiments demonstrate that this antibody has the capability to selectively eliminate the idiotype positive cells from peripheral blood. Antibodies with these characteristics could become a useful tool for better understanding the pathogenesis of the disease and for new therapeutic options.

Amino Acid Sequence↗

Effect of amineptine on regional extracellular concentrations of dopamine and noradrenaline in the rat brain.

The effect of amineptine (1.25-20 mg/kg i.p.), an antidepressant inhibiting dopamine uptake, on extracellular concentrations of dopamine was studied in the rat striatum and nucleus accumbens by using the microdialysis technique and two Ca++ concentrations (1.26 and 3.4 mM) in the perfusion medium. In one experiment the effect of amineptine was studied on extracellular concentrations of dopamine and noradrenaline in the frontal cortex perfused with a medium containing 1.26 mM Ca++. Basal extracellular concentrations of dopamine in the striatum and nucleus accumbens were significantly higher at 3.4 mM Ca++. At 5 to 20 mg/kg, amineptine dose-dependently increased extracellular dopamine in the striatum and nucleus accumbens. No differences were found in the effect of amineptine in the two brain regions at the two calcium concentrations. When extracellular dopamine was expressed as a percentage of basal values, amineptine (20 mg/kg) caused greater increases in rats perfused with 1.26 mM Ca++ than in rats perfused with 3.4 mM Ca++ in both brain regions. A similar effect was found when 10 microM amineptine was infused through the dialysis fiber. The effect of 10 mg/kg i.p. of amineptine on dopamine output in the two brain regions was prevented by infusing 1 microM tetrodotoxin in the dialysis fiber. In the frontal cortex, 10 and 20 mg/kg of amineptine significantly raised dopamine and noradrenaline concentrations, whereas 5 mg/kg only increased noradrenaline output significantly. At 10 mg/kg i.p., amineptine also increased extracellular noradrenaline in the dorsal hippocampus. Amineptine had no consistent effects on the concentrations of dihydroxyphenylacetic acid and homovanillic acid in the various brain regions.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

Hyperosmolar hyperglycemic nonketotic coma in Waldenström's macroglobulinemia associated with type II diabetes and complicated by pulmonary tuberculosis.

In this paper we describe a successfully treated case of hyperosmolar hyperglycemic non ketotic coma (HHNC). The HHNC was observed in a patient affected by Waldenström's macroglobulinemia, associated with type II diabetes and complicated by pulmonary tuberculosis. Hyperosmolar hyperglycemic nonketotic coma is a clinical condition with a high mortality rate associated with a severe increase in blood viscosity. This increase in blood viscosity justifies several clinical manifestations of the HHNC. We believe that an increase in the blood viscosity produced by the simultaneous presence of the single diseases mentioned above may have encouraged the development of hyperosmolar coma in the case reported.

Aged↗

Release of dopamine is reduced by diazepam more in the nucleus accumbens than in the caudate nucleus of conscious rats.

The effects of 1-20 mg/kg diazepam were studied on the extracellular concentrations of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens and striatum of conscious rats, using intracerebral microdialysis. Five, but not 1 mg/kg diazepam significantly reduced extracellular DA, DOPAC and HVA in the nucleus accumbens. Twenty mg/kg diazepam significantly reduced extracellular DA, DOPAC and HVA in the striatum. A significant effect on striatal DOPAC, but not on DA and HVA, was seen with 10 mg/kg diazepam, while no changes were found with 5 mg/kg diazepam. The results suggest that diazepam reduces the release and metabolism of DA in the nucleus accumbens more than in the striatum.

3,4-Dihydroxyphenylacetic Acid↗

Effects of intracerebroventricular administration of d-fenfluramine and d-norfenfluramine, as a single injection or 2-hr infusion, on serotonin in brain: relationship to concentrations of drugs in brain.

The effects of d-fenfluramine (DF) and d-norfenfluramine (DNF), administered intracerebroventricularly (i.c.v.) on levels of serotonin (5-HT) in the brain, was assessed in relation to levels of drugs in brain. d-Fenfluramine, as a single injection (500 micrograms/20 microliters), caused no significant changes in 5-HT in whole brain from 15 to 480 min after injection. When infused intraventricularly for 2 hr, DF and DNF at 500 but not at 125 250 micrograms/hr, markedly reduced concentrations of 5-HT in brain 4 hr after the end of the infusion. At this time levels of DNF in brain were similar (between 4 and 5 micrograms/g) with both compounds, whereas levels of DNF after single intraventricular injections of DF were below 2 micrograms/g at all times after injection. Infusion of 500 micrograms/hr of DNF for 2-hr reduced concentrations of 5-HT in various regions of the brain, with the exception of the brainstem, whereas 250 micrograms/hr of DNF significantly lowered levels of 5-HT only in the cortex. The effect of infusion of 500 micrograms/hr of DNF was specific for 5-HT (no effect on dopamine and norepinephrine) and lasted for at least 168 hr. The results suggest that the effect on 5-HT in brain of intraventricular infusion of DF, but not a single injection, was due to the fact that, only in the former condition were adequate levels of DNF, the active metabolite of DF, reached in the brain. These results are relevant to the interpretation of studies in which biochemical changes in the brain after intraventricular administration, are reported without any measurement of the drug or its active metabolites, in plasma and brain.

Animals↗

Postremission chemotherapy in adult acute non-lymphoblastic leukaemia including intensive or non-intensive consolidation therapy.

From October 1983 to December 1988, 84 consecutive adult patients with acute non-lymphoblastic leukaemia (ANLL; median age = 51 yr) were uniformly treated to induce remission (CR) with intravenous vincristine and cytarabine sequentially followed by daunomycin and infusion cytarabine. From October 1983 to December 1985 consolidation was non-intensive (2 courses with the same drugs used for induction) (protocol ANLL83: 27 patients, median age = 45). From January 1986 to December 1988 consolidation was intensive (4 courses of vincristine and cytarabine sequentially followed by etoposide plus thioguanine or amsacrine) (protocol ANLL86: 57 patients, median age = 57). Excluding early deaths, the CR rate was 71.6%. Median CR, responsive patient survival and overall survival were 11.1, 15.3 and 8.5 mo, respectively. For protocol ANLL83 and ANLL86, median CR was 8.7 and 13.2 mo (P less than 0.05) and median survival was 13.1 and 16.9 mo (P less than 0.05) for responders and 8.0 and 9.2 mo (P not significant) for all patients. Intensive consolidation including drugs not previously used for induction seems to prolong CR duration and responder survival in adult ANLL.

Adolescent↗