Biomedical subjects

L Baldini

Publications and source records attributed to L Baldini.

At least 109 records · Page 6Linked to original sources

PubMed1988

Effect of ketotifen on adriamycin toxicity: role of histamine.

The effect of ketotifen, an antianaphylactic drug which acts in part similarly to sodium cromoglycate, was tested on adriamycin-induced histamine release and toxicity. The intraperitoneal injection of various concentrations of ketotifen induced an important histamine release from rat mast cells. Thirty minutes after the injection, however, no more histamine was present in the peritoneum. When i.p. administered to mice 30 min before adriamycin (15 mg/kg), ketotifen significantly ameliorated the survival time and reduced the cardiotoxicity. On the contrary, when given simultaneously, the antiallergic drug increased the toxic effect of adriamycin.

Animals↗

PubMed1987

Visual evoked potentials in patients with neuropathy and macroglobulinemia.

Visual evoked potentials were studied in 11 patients with neuropathy and macroglobulinemia. The P100 latency was increased bilaterally in 5 of the 6 patients whose IgM M-proteins reacted with myelin-associated glycoprotein (MAG) and in 1 of the other patients. In patients whose M-protein bound to MAG, abnormal visual evoked potentials correlated with the presence of the M-protein in the cerebrospinal fluid. Subclinical involvement of the central nervous system is frequent in patients with neuropathy and anti-MAG M-proteins and may be due to the binding of M-proteins to central nervous system myelin.

Aged↗

PubMed1987

VAD protocol for treatment of advanced refractory multiple myeloma.

Twenty-three patients with advanced refractory multiple myeloma were treated with a combination chemotherapeutic regimen consisting of four-day continuous infusion of vincristine and doxorubicin plus intermittent high-dose dexamethasone (VAD). All patients included in the study were heavily pretreated with cytostatics and radiotherapeutic measures, and generally presented in poor general condition. In 3 of the 16 evaluable patients (18%) a response, and in 7 patients (44%) an improvement as defined by a reduction in tumor mass by more than 50% was achieved. Six patients had progressive disease. Evaluation of survival for responders (15 mos) versus non-responders (2 mos) by the landmark method seems to confirm the relative therapeutic efficacy of the VAD protocol in refractory multiple myeloma. The somewhat inferior response rate as well as the occurrence of considerable toxicity in several cases (when compared to the recent M. D. Anderson trial) may be related to differences in clinical features and pretreatment status of the two studies' population.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1987

Dimethyl sulfoxide inhibits histamine release induced by various chemicals.

Dimethyl sulfoxide was found to inhibit histamine release induced by compound 48/80 at concentrations ranging from 0.6 to 10%. At higher concentrations (20 and 40%) the substance caused histamine release by itself. Heat inactivation at 50 degrees C of the mast cells did not prevent this release, suggesting a lytic mechanism for this action and this was further proved by the trypan blue dye exclusion test. Dimethyl sulfoxide was also active in inhibiting histamine release induced by other polyamines such as bradykinin, polymyxin B and protamine, by concanavalin A and dextran, by ionophore A23187 and by three anthracyclines, doxorubicin, daunomycin and epirubicin. In contrast, the substance did not inhibit histamine release induced by a monoamine, chlorpromazine and by the detergent Triton X-100.

Animals↗

PubMed1987

Peripheral neuropathy in macroglobulinemia: incidence and antigen-specificity of M proteins.

Peripheral neuropathy was found in 12 (46%) of 26 patients with macroglobulinemia. The neuropathy was subclinical in two. Anti-myelin-associated glycoprotein (MAG) activity was found in six (50%) patients with neuropathy. Sural nerve biopsies showed demyelination and IgM deposits on the myelin sheath. In one patient who had no anti-MAG activity, the serum IgM bound to peripheral myelin by indirect immunofluorescence and to several protein bands in peripheral nerve and other tissues by immunoblot. In the other five patients with neuropathy, we found no binding of M proteins to nerve components, but in three patients there were endoneurial IgM deposits in nerve biopsy. Peripheral neuropathy may be related to the antigen-specificity of M proteins.

Adult↗

PubMed1987

Effects of suprofen on renal function in patients with rheumatoid arthritis.

Suprofen is a new potent analgesic with antiinflammatory properties that appears to inhibit prostaglandin synthetase in a tissue-selective manner, having relatively little effect on the kidneys of experimental animals. The effects were studied of one week of treatment of rheumatoid arthritis patients with suprofen or ibuprofen on Na+ and K+ excretion, creatinine clearance, urinary enzymes that are markers for tubular damage, and urinary prostaglandins such as PGE2 and 6-keto PGF1 alpha (a stable metabolite of prostacyclin). Neither compound caused changes in renal function related to the week of treatment, but significant decreases in prostaglandins were observed: this change was fully reversible after discontinuation of the drug.

6-Ketoprostaglandin F1 alpha↗

PubMed1986

Characterization of histamine secretion induced by anthracyclines in rat peritoneal mast cells.

The histamine-releasing activity of three anthracyclines, adriamycin, daunomycin and epirubicin, has been tested on rat peritoneal mast cells. The three drugs induced a marked and dose-dependent histamine secretion, in a noncytotoxic manner. The release was not sustained by extracellular calcium but was largely dependent on intracellular stores of this cation. This function was blocked by extremes of temperature (0 and 45 degrees), was very rapid and virtually complete within 10 sec. Treatment of mast cells with theophylline or disodium cromoglycate significantly reduced the secretory response to anthracyclines. On the basis of these results it is clear that the stimulant effect of anthracyclines is a true exocytotic response and thus is very similar to that of the classic mast cell secretagogue, compound 48/80.

Animals↗

PubMed1986

Anticonvulsant activity of two polyethylene glycols in mice.

The anticonvulsant activity of two polyethylene glycols of different molecular weight (400 and 4000) was tested in mice. The two substances were inactive in the maximal electroshock test, but, when intraperitoneally administered, were efficacious in the pentetrazole and strychnine seizure tests. Polyethylene glycol 4000 showed the most potent anticonvulsant action. On the contrary, when polyethylene glycols were orally administered, they did not alter the time for seizure onset and for death.

Animals↗

PubMed1986

Effect of polyethylene glycol 400 on adriamycin induced histamine release.

The activity of polyethylene glycol 400, a widely used drug solvent, was tested on the release of histamine induced by adriamycin in vitro on peritoneal rat mast cells and in vivo in a mouse model. Preincubation of mast cells with high (10 and 5%) concentrations of polyethylene glycol 400 significantly inhibited the important histamine release induced by 100 micrograms/ml of adriamycin; furthermore, polyethylene glycol 400 (3.45 g/kg; 0.345 g/ml) pretreatment almost completely abolished the peritoneal and pericardial mast cell degranulation and the cardiac toxicity caused by an intraperitoneal injection of 15 mg/kg of adriamycin. This effect of polyethylene glycol 400 on adriamycin-induced histamine release could explain the protective action exhibited in vivo on adriamycin treated animals, therefore confirming that adriamycin cardiotoxicity could be related to the release of histamine and other vasoactive substances.

Animals↗

PubMed1986

Inhibitors of adriamycin-induced histamine release in vitro limit adriamycin cardiotoxicity in vivo.

The activity of theophylline and disodium cromoglycate was tested on adriamycin-induced histamine release in vitro and on adriamycin cardiotoxicity in vivo. Both substances significantly inhibited the release of histamine induced by 100 micrograms ml-1 of adriamycin on rat peritoneal cells and produced significant protection against adriamycin-mediated acute and chronic cardiotoxicity in mice. N-acetylcysteine, a free radical scavenger, successfully used in the prevention of the cardiomyopathy, was also found to be an inhibitor of histamine release induced by adriamycin and compound 48/80 on rat peritoneal cells. This study further supports the hypothesis that the release of histamine may be involved in the pathogenesis of anthracycline cardiotoxicity.

Acetylcysteine↗

PubMed1986

Human recombinant interferon alpha-2C enhances the expression of class II HLA antigens on hairy cells.

Isolated splenic hairy cells from three untreated patients were cultured in presence of recombinant human interferon alpha-2C (IFN alpha). Ultrastructural cytochemistry and immunophenotype analysis with a large panel of monoclonal antibodies were performed to study cellular modification induced by IFN alpha. Hairy cells showed a typical pheno-type: Smlg+, B1+, BA1+/-, anti-Tac+, OKDR+, Leu-M5+, HC2+, TRAP+, myeloperoxidase-. Under our experimental conditions, we found no direct cytotoxic effects or significant variations in morphology, cytochemistry, and percentage of reactivity with the tested monoclonal antibodies. After culturing in the presence of different doses of IFN alpha, we observed a significant enhancement of the expression of class II HLA antigens as demonstrated by increased fluorescence for OKDR, OKla, Leu-10 at fluorescence-activated cell sorting analysis. In agreement with this finding IFN alpha-treated hairy cells showed an increased stimulatory capacity v allogeneic T cells in one-way mixed lymphocyte reaction. To our knowledge this is the first report describing the induction of class II HLA antigens on hairy cells by IFN alpha.

Antibodies, Monoclonal↗

PubMed1986

Cyclosporin A antileukemic activity: mode of action on target cells.

Cyclosporin A (CyA) is a potent immunosuppressive agent which has been reported to inhibit proliferation of human T leukemic lymphoblasts. We used the permanent cell line 8402 to perform a detailed investigation of the CyA mode of action on such cells. CyA treatment resulted in a dose-dependent inhibition of the 8402 cells growth rate which was paralleled by a decrease of tritiated thymidine uptake. These findings were the consequence of redistribution of treated cells in the cell cycle phase. By means of intracellular DNA content measurements made by flow cytometry, it was shown that the primary effect of CyA was accumulation of treated cells at the G1 phase of the cell cycle. At the doses used, CyA activity was not spontaneously reversible, resulting in death of treated cells which was apparent at about 72 h after exposure to the drug.

Cell Cycle↗

PubMed1985

Assessment of thromboresistance of intravenous cannulae by 125I-fibrinogen scanning.

Assessment of potentially thromboresistant polymers and other materials has been impeded by the lack of a simple and safe test procedure in man. This report describes the use of a portable gamma radiation detector to assess accumulation of 125I-fibrinogen in thrombi related to intravenous cannulae. The method was first employed in 19 dogs and one sheep with FEP-Teflon forelimb intravenous cannulae which were scanned for up to 6 h after insertion. Results were compared with findings at post mortem examination. Eleven thrombi developed, nine of which emitted more than 3500 counts per minute; eight of these (89%) were detected by external scanning. The smallest thrombus detected weighed 0.7 mg. The method did not distinguish between thrombus and hematoma. Fifty FEP-Teflon cannulae were then studied in 39 patients after injection of 100 microCi 125I-fibrinogen. Cannulae and control sites were scanned twice daily and an independent blind clinical appraisal was performed by an experienced nurse. A rise in percentage uptake (count at a limb site/heart count X 100) of 20 or a difference of 40 between adjacent sites was regarded as a positive test. Scans became positive up to 30 h before clinical evidence of phlebitis was observed. The interval between insertion and thrombosis of both large and small cannulae detected by scanning was significantly shorter than that determined by clinical assessment (p less than 0.001). Physical signs of phlebitis were noted with 58% of large cannulae (16 or 18 gauge)and 33% of small cannulae (22 gauge) at the time of removal. Positive 125I-fibrinogen tests were obtained with 70% of large cannulae and 75% of small cannulae. 125I-fibrinogen scanning is a safe simple sensitive technique to detect thrombosis related to intravenous cannulae. The test should enable comparisons of different cannula materials in man.

Animals↗

PubMed1985

Multimarker phenotypic characterization of adult and childhood acute lymphoblastic leukaemia: an Italian multicentre study.

A multicentre phenotypic study was carried out in Italy combining conventional immunological techniques with monoclonal antibody (MoAb) analysis in 190 cases of adult and childhood acute lymphoblastic leukaemia (ALL), in an attempt to define better the lineage relationship of the neoplastic cells. Of the 140 children evaluated, 79.3% expressed the common ALL (cALL) antigen (all analyses performed by MoAb), 11.4% were T-ALL and 9.3% were non-T, non-B, non-common ('null') ALL. The proportion of adult cALL cases was slightly lower (64% of the 50 cases studied) than that of childhood ALL, whilst the incidence of T-ALL was significantly higher in adults than in children (26% v. 11.4%, P less than 0.05). Because of the high proportion of cALL cases, the incidence of 'null' ALL in adult patients was similar (10%) to that of children, and lower than previously reported. The recognition of early pre-T-ALL cases (T1+, RFT2+, T10+, T6-, T11-, E-) contributed to the overall low proportion of 'null' ALL; prior to the use of MoAb, such cases would probably have been classified as undifferentiated acute leukaemia or 'null' ALL. The search for B-cell-related markers showed that the incidence of pre-B-ALL cases (cytoplasmic immunoglobulin positive cases) was similar in adults and in children (25.6% and 32%, respectively). Furthermore, the great majority of cases studied expressed the BA-1 antigen (92.8% of adults and 79% of children), whilst the BA-2 antigen was found in 53% of cases (tested only in children), confirming a hierarchy in the expression of B-cell related markers in cALL: BA-1, BA-2, CyIg. Several of the 'null' cases also expressed the BA-1 antigen on a variable proportion of cells, pointing to a possible B-cell origin of the blasts. This multicentre study shows that both in adult and in childhood ALL the combined use of conventional immunological markers and of a panel of MoAb allows identification of the cell lineage of the great majority of cases, thus reducing the number of 'null' ALL. Furthermore, these findings suggest that practically all cases of ALL belong either to the T or to the B cell compartment and that the neoplastic cells appear blocked at different levels along the lymphoid differentiation pathway.

Acute Disease↗

PubMed1985

Functional and multimarker analysis of T-cell chronic lymphocytic leukaemia.

The morphology, immunophenotype, cytoenzymatic and functional activities of T lymphocytes from 4 patients with chronic lymphoproliferative disease of T-cell origin were studied. Clonal proliferation was demonstrated by distinctive chromosomal abnormalities involving chromosomes 2 and 14. Patients 1 and 2 were classifiable as OKT4+ T-cell chronic lymphocytic leukaemia (T-CLL) and patient 3 as OKT4+/OKT8+ T-CLL, with helper function in vitro only in patient 1. Patient 4 has low-grade lymphocytosis with benign clinical course, with cells showing morphology of large granular lymphocytes (LGL), and immunophenotype HNK-1+, ER+, Fc gamma receptor+, OKT3+, OKT11+ and OKT8+, as well as natural killer activity, radiosensitive suppressor activity on Ig secretion and responsiveness to PHA; this case was interpreted as LGL leukaemia. This study indicates that a large proportion of cases of true T-CLL may belong to the OKT4 subset, and that extensive investigations should be made of the lymphocytic OKT8+/T gamma forms to characterize them precisely.

Aged↗

PubMed1985

Variability in the intradermal and in vitro lymphocyte responses to PPD in patients receiving isoniazid chemoprophylaxis.

Much attention has been focused on problems related to the interpretation of the tuberculin (Tb) skin test in terms of the "booster" phenomenon observed with repeated skin testing. However, relatively little attention has been given to the problem of the interpretation of repeat Tb skin tests in patients who have been given isoniazid (INH) chemoprophylaxis. Sixteen female hospital workers who were receiving INH for asymptomatic recent conversion of their Tb skin test, and 1 male physician under treatment with INH and rifampin for active tuberculosis as a result of a patient exposure, were studied over a 1-yr period. Intradermal skin tests with 5 tuberculin units purified protein derivative (PPD) and assessment of in vitro lymphocyte proliferation and production of leukocyte inhibitory factor on exposure to PPD were performed on 4 occasions at 3-month intervals-3 during therapy and 1 after completion of therapy. Four of 10 patients tested on all occasions showed at least 1 negative Tb skin test. In 2 of 4, the reversions were not stable. Considerable variability was observed between results of skin tests and in vitro lymphocyte responses, and no one in vitro lymphocyte response to PPD was adequate to identify the presence of delayed hypersensitivity to PPD. On the basis of these data, it is concluded that the presence of a single negative PPD skin test during or shortly after the completion of INH chemoprophylaxis does not constitute sufficient evidence to conclude that a patient has had a stable skin test reversion. Confirmation of the loss of tuberculin reactivity requires the in vitro assessment of lymphocyte responses to PPD both in terms of proliferation and the production of a lymphokine(s).

Cross Infection↗

PubMed1985

Prognostic significance of immunoglobulin phenotype in B cell chronic lymphocytic leukemia.

Seventy-six consecutive untreated patients with B cell chronic lymphocytic leukemia (B-CLL) and classified according to Binet's staging system were studied at the clinical presentation. Several immunologic parameters (number of total and T circulating lymphocytes and their surface membrane immunoglobulin [Smlg] phenotypes and levels of serum Ig) were evaluated with the aim of identifying a biologic marker of prognostic relevance. In this series of persons, Binet staging confirmed its usefulness as a prognostic index (P less than .001). With regard to Smlg, they were mu-type in 41 cases (53.9%), mu-type plus delta-type in 29 cases (38.2%), alpha-type in one case, and not detectable in five cases. No correlations were found between clinical stage and immunoglobulin phenotype, although all but one patient in stage C showed mu-type Smlg alone. On analyzing the survival curves of our patients according to different Smlg phenotypes, we found that patients with only mu-type Smlg had a poorer prognosis (P less than .05) than those with mu-type plus delta-type; this difference was even more significant (P less than .01) in patients in stage A, whereas there were no statistical differences in those in stages B and C. Because the appearance of surface heavy chain of delta-type could be an expression of cell maturation, these results suggest that in B-CLL the presence of phenotypically more mature leukemic cells may correlate with better clinical prognosis, particularly in the early phase of the disease.

Actuarial Analysis↗

PubMed1984

Plasma and urine cyclic nucleotide levels in patients with neoplastic diseases.

Plasma and/or urine cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP) levels were measured in 67 normal subjects, 55 patients with nonneoplastic diseases, and 324 patients with ten different types of cancer. There were no significant differences in plasma and urine cyclic nucleotide levels between normal subjects and patients with non-neoplastic diseases. In untreated cancer patients, plasma and urine cAMP levels were similar to those of normal subjects, whereas plasma and urine cGMP levels were markedly higher. This pattern was common to all the cancer groups studied. Chemotherapy per se did not seem to influence cyclic nucleotide levels in cancer patients. However, plasma and urine cGMP levels normalized in all patients who attained complete remission. Moreover, in acute leukemia patients who relapsed, plasma cGMP levels increased significantly with respect to the complete remission values, thus suggesting that this parameter may be useful in monitoring the response of cancer patients to treatment.

Adolescent↗