Toxic epidermal necrolysis following Yersinia enterocolitica infection.
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Adult↗
Biomedical subjects
M Cazzola
Publications and source records attributed to M Cazzola.
Theophylline in the inhibition of angiotensin-converting enzyme inhibitor-induced cough.
Preliminary reports suggest that some pharmacologic agents may be effective in ameliorating angiotensin-converting enzyme (ACE) inhibitor-induced cough and, perhaps, allowing continuing use of ACE inhibitors in patients for whom this class of medication is important. We examined the effect of a once-a-day theophylline formulation on ACE inhibitor-induced cough and on the sensitivity of the cough reflex to capsaicin in 10 hypertensive patients who had developed cough during treatment with an ACE inhibitor. Theophylline did not induce bronchodilation but induced complete remission of clinical symptoms in 8 and attenuated the capsaicin-induced cough number in 7 subjects when compared with placebo. Theophylline may thus be effective in preventing ACE inhibitor-induced cough.
Adult↗
Erythrophagocytosis increases the expression of erythroid potentiating activity mRNA in human monocyte-macrophages.
The aim of the present study was to evaluate whether the erythropoietic response to hemolysis can be mediated by other regulatory peptides in addition to erythropoietin. For this purpose, we have investigated the influence of erythrophagocytosis by human monocytes and macrophages on the mRNA expression of several growth factor genes, including interleukin-3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM-CSF) and erythroid potentiating activity (EPA), which are supposed to influence erythropoiesis. Immunologically mediated erythrophagocytosis increased the expression of EPA mRNA (2 to 3 times). Such increase appeared to be specifically associated with phagocytosis of erythrocytes, since phagocytosis of yeast microorganisms or antibody-coated latex particles had no effect on EPA gene expression. Yeast, however, powerfully stimulated the expression of GM-CSF, granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) mRNAs which, with the exception of G-CSF, were not influenced by erythrophagocytosis. Erythropoietin and IL-3 mRNAs were never detected in cultured monocytes, either in control or in treated samples. Our findings may suggest that phagocytosis of erythrocytes by monocytes/macrophages increases the expression, and possibly the production, of EPA. This could in turn potentiate the erythropoietic response to extravascular hemolysis by increasing the number of cells responsive to erythropoietin. Thus, EPA might be a mediator of an end-product positive feedback on the rate of red cell production.
Cells, Cultured↗
Clinical trial of the efficacy and safety of moguisteine in patients with cough associated with chronic respiratory diseases.
This completely randomised, double-blind, placebo-controlled, multicentre trial was carried out to evaluate the antitussive activity and safety of a 200 mg t.i.d. regimen of moguisteine (20 mg/ml ready-to-use suspension) during four days in patients with cough associated to chronic respiratory disorders. A total of 87 patients were enrolled, 42 on moguisteine and 45 on placebo. All had persistent dry or slightly productive coughs associated with chronic respiratory disorders. Seventy three were submitted to per protocol efficacy analyses, and eighty-three to intention-to-treat efficacy analyses. All the patients who were administered the study drug were analysed for safety. The underlying disorders reported as being associated with the target symptom were chronic obstructive pulmonary disease, cough of unknown aetiology, respiratory tract malignant neoplasms and pulmonary fibrosis. The treatment groups appeared to have been homogeneous on admission. The number of coughs in the interval 8-10 a.m. on day four vs day one was reduced by 42% on moguisteine against 14% on placebo; the difference between treatments was statistically significant (p = 0.028). The mean percent reduction of ladder scale scores of cough frequency vs baseline was greater on moguisteine than on placebo both in the day-time (especially on days one and two), and at night. The antitussive activity of moguisteine did not show remarkable variations either by diagnosis or by type of cough (dry/slightly productive). No serious adverse events were reported. No changes/trends were identified in laboratory tests that might indicate functional or toxic effects of moguisteine on specific organs.
Adult↗
Inhibitors of tyrosine phosphorylation induce apoptosis in human leukemic cell lines.
Experimental evidence suggests that hematopoietic growth factors promote cell survival by suppressing apoptosis or programmed cell death. Since interleukin 3 (IL-3) and granulocyte-macrophage colony stimulating factor (GM-CSF) induce tyrosine phosphorylation of a common set of proteins in the factor-dependent cell line M07e, we have investigated whether growth-factor-induced tyrosine phosphorylation is involved in the promotion of cell survival and suppression of apoptosis. Experiments were carried out with the leukemic cell lines HL-60 and M07e and the tyrosine kinase inhibitors genistein and tyrphostin AG82. Both the tyrosine kinase inhibitors induced apoptosis of HL-60 and M07e cells. This was indicated by the appearance of DNA degradation and morphologic evidence of nuclear condensation and fragmentation. It was also confirmed by flow cytometry of DNA, which showed apoptotic cells as a fraction of cells characterized by a diminished DNA stainability, represented on the DNA frequency histograms as a distinct peak below the G0/G1 population. Kinase inhibitors also reduced the fraction of cells in the S phase of the cell cycle. That tyrphostin specifically inhibited tyrosine kinases was further suggested by the prevention of its effects by the tyrosine phosphatase inhibitor sodium orthovanadate (vanadate), at least during the first 18-24 h of treatment. The incomplete prevention of genistein effects by vanadate suggests that genistein is a less specific inhibitor of tyrosine kinases than tyrphostin, and may also act as an inhibitor of topoisomerase II. Vanadate also prevented apoptosis and reduction of the S phase in M07e cells cultured for 24 h in the absence of growth factors. These results suggest that tyrosine phosphorylation is an essential step in IL-3 and GM-CSF signal transduction. Since in our experimental model the effects of tyrosine kinase inhibition and growth factor deprivation could be reversed by concomitant inhibition of tyrosine phosphatases, it is suggested that a balance between tyrosine kinases and tyrosine phosphatases establishes whether a cell will survive or undergo apoptosis.
Apoptosis↗
Role of M1 muscarinic receptor subtypes in mediating airway smooth muscle contraction.
Muscarinic receptor subtypes have been identified on airways of several mammalian species, including humans. They are distributed in the lung over submucosal glands, airway ganglia and over the nerves; M1-receptors are found in airway ganglia, M2-receptors (autoreceptors) are present in cholinergic postganglionic nerves at the prejunctional level, whereas the muscarinic receptor subtypes found in airway smooth muscle are of the M3-receptor subtype. We had previously reported the presence of M1-receptors on the smooth muscle of large and small airways of patients suffering from chronic bronchitis, but only is the peripheral airways of healthy subjects; one possible explanation of these results is that the bronchial epithelium may play a role in bronchial responsiveness to relaxant muscarinic antagonists. To clarify this hypothesis we have studied in vitro the responses to acetylcholine (ACh), and some muscarinic selective (pirenzepine, PZ; p-fluorohexahydrosiladyphenidol, pFHHSiD) and non-selective (atropine, ATR) antagonists, on human bronchial smooth muscle in the presence and in the absence of epithelium. The absence of epithelium did not modify the responsiveness to ACh to any great extent and did not change the responsiveness to relaxant antagonists. Our results show that the M1-receptors may play a role in mediating contraction of airway smooth muscle; research is in progress regarding their function in disease.
Acetylcholine↗
Effects of some cephalosporins and teicoplanin on platelet aggregation.
Antibiotics may interfere with platelet (PLT) function, and beta-lactam antibiotics may interact with PLT aggregation, by inhibiting the binding of agonists of this aggregation (such as ADP and collagen) to specific receptor sites. In this study we have evaluated the relative in-vitro antiplatelet effects of some old and new cephalosporins (cefonicid, ceftazidime, ceftriaxone, cefotaxime, cefuroxime and flomoxef) and of teicoplanin, a new glycopeptide antibiotic. All the cephalosporins tested, and also teicoplanin, were found to have the potential to adversely affect human platelet aggregation only at high concentrations which are not achieved in vivo.
Adenosine Diphosphate↗
Flomoxef, a new oxacephem antibiotic, does not cause hemostatic defects.
Antibiotics of the beta-lactam class may cause coagulation defects and bleeding. It has been suggested that N-methyltetrazolethiol (NMTT), a common side chain group at the 3'-position of the cephem or 1-oxacephem frame, could be responsible for the hypoprothrombinemic effect of the antibiotics and that it could inhibit the liver vitamin K-epoxide reductase activity. Flomoxef (6315-S) is a new oxacephem antibiotic which differs from latamoxef because it has [1-(2-hydroxethyl)-1H-tetrazol-5-yl] thiomethyl (HTT) as a side chain at the 3'-position of cephem group instead of NMTT and an extensive modification of 7 beta-acylamino side chain. The present study was carried out to study its effects on vitamin K-dependent blood coagulation parameters in human volunteers. Ten adult patients (6 men and 4 women), suffering from chronic bronchitis, entered into the study. Each patient received ten 1 g i.m. injections of flomoxef at 12-hourly intervals. Apparently, the treatment with this oxacephem antibiotic had no significant effect. PT, PTT and fibrinogen remained in the normal range in all patients and factors II+VII+X, protein C, protein S and AT III were not depleted. The trend was similar both in men and women. Based on the results of the present study, we conclude that flomoxef is an antibiotic that does not exhibit an effect on blood coagulation, even in males.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Subcutaneous erythropoietin for treatment of refractory anemia in hematologic disorders. Results of a phase I/II clinical trial.
We have used recombinant human erythropoietin (rHuEPO) in a phase I/II clinical trial to evaluate its ability to reverse refractory anemia in hematologic disorders. rHuEPO was administered subcutaneously 5 days per week at escalating doses (50 to 150 U/kg per day). The aim of treatment was a hemoglobin (Hb) level greater than or equal to 10 g/dL without blood transfusion. Of 25 patients treated, 17 were evaluable, most of them with a regular need for transfusion. Eight of these had lymphoproliferative disorders (three cases of malignant lymphoma and five of monoclonal gammopathy) and were exposed to cytotoxic therapy. The other nine patients had hematopoietic stem cell disorders (four cases of myelodysplastic syndrome, three of idiopathic myelofibrosis, and two of chronic myelogenous leukemia). All patients with lymphoproliferative disorder had serum EPO levels inappropriately low for the degree of anemia, while patients with stem cell disorder showed variable values. Erythroid marrow activity was inadequate in all cases. Seven of eight patients with lymphoproliferative disorder responded to treatment maintaining Hb above 10 g/dL without transfusion. The median dose of rHuEPO required for correction of anemia was 75 U/kg. In four cases response was maintained with 50 U/kg, three times per week. There was no complete response among patients with hematopoietic stem cell disorder, although transfusion requirement was eliminated or reduced in four cases. Four patients developed functional iron deficiency during rHuEPO treatment and required iron supplementation to obtain response. Aggravation of splenomegaly was observed in two cases of myeloproliferative disorder. We conclude that: (1) subcutaneous administration of rHuEPO can be effective and safe in patients with lymphoproliferative disorder exposed to chemotherapy and showing inappropriate EPO response to anemia; (2) this is less likely in hematopoietic stem cell disorders, although favorable responses may be observed in occasional patients; and (3) functional iron deficiency as a cause of nonresponse to rHuEPO is frequent also in nonrenal anemia.
Adult↗
Role of 5-HT2 receptor subtypes in mediating adenosine-induced airway contraction.
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Acetylcholine↗
Effects of teicoplanin on human platelet aggregation in vitro and ex vivo.
The effects of teicoplanin on adenosine-diphosphate (ADP)-induced human platelet aggregation in vitro and on both ADP- and ristocetin-induced human platelet aggregation ex vivo were investigated. In the in vitro study carried out on platelets from 7 healthy volunteers, teicoplanin had no effect on platelet function even at a concentration (1 mg/ml) 10 times higher than the peak level found in the in vivo state, but at the highest concentration (10 mg/ml), which is 100 times higher than that reached in vivo, it inhibited ADP-induced platelet aggregation. In the ex vivo studies carried out in 10 healthy volunteers, teicoplanin, following single intravenous doses of 400 mg and 800 mg, did not produce any effect on platelet function up to 6 hours after administration. After 12 hours, teicoplanin, when given at 800 mg i.v., reduced ADP-induced platelet aggregation.
Adult↗
Recombinant human erythropoietin is effective in correcting erythropoietin-deficient anaemia after allogeneic bone marrow transplantation.
Two children affected by severe aplastic anaemia (SAA) underwent allogeneic bone marrow transplantation (BMT) using partially matched family donors. In both cases there was a successful engraftment of donor haemopoietic stem cells. However, after an initial erythropoietic recovery, 5 months following BMT both children became severely anaemic. Although multiple factors were responsible for anaemia, in both cases there was a markedly impaired erythropoietin response to anaemia, as indicated by the inappropriately low levels of serum erythropoietin (EPO). Treatment with recombinant human erythropoietin (rHuEPO) induced a sustained erythropoietic response with complete correction of anaemia. This pilot study suggests that rHuEPO can be effective in correcting long-lasting anaemia after marrow transplantation, characterized by inadequate erythropoietin production.
Anemia↗
New tools for clinical evaluation of erythron function in man.
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Anemia↗
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↗
Responsiveness and sensitivity to cholinergic agonists and antagonists in bovine isolated bronchial muscle.
1. Airways derived from different levels of the lung exhibit a difference in the reactivity and sensitivity to agonists. We have evaluated the effect of acetylcholine and cholinergic selective (pirenzepine, gallamine and 4-dipherylacetoxymethyl piperidine [4-DAMP]) and non-selective (atropine) antagonists on bovine proximal and distal smooth muscle preparations. 2. The distal preparations are more sensitive to acetylcholine than proximal bronchi. The relaxant effect of three selective antagonists on the distal and proximal tissues was the same when the results for each drug were compared. 3. Atropine and 4-DAMP were more potent than pirenzepine and gallamine in relaxing both proximal and distal bovine smooth muscle preparations. 4. These data suggest that the muscarinic sites on the smooth muscle of bovine airways are of the M3 subtype.
Acetylcholine↗
Multiple intra-articular treatment of rheumatoid arthritis: a randomized prospective study comparing rifamycin SV with pefloxacin.
In a randomized, prospective study the efficacy and tolerability of extensive multiple intra-articular administrations of two antibiotics, rifamycin SV and pefloxacin, were evaluated in 40 patients with classical or definite rheumatoid arthritis. Total weekly doses of 525 mg rifamycin or 560 mg pefloxacin were given for 10 weeks, and 12 months after treatment all clinical indices, erythrocyte sedimentation rate and C-reactive protein improved significantly in the rifamycin group. Some of the treatment indices (morning stiffness, severity of pain by visual analogue scale, grip strength and Ritchie's index) were already improved when the treatment ended, whereas others (erythrocyte sedimentation rate, C-reactive protein, number of painful and swollen joints) improved progressively during the follow-up. In the pefloxacin treatment group all indices except C-reactive protein and severity of pain determined using a visual analogue scale were significantly improved 12 months after treatment. Comparison of the two treatments showed a significant difference in erythrocyte sedimentation rate (P less than 0.047), Ritchie's index (P less than 0.036) and C-reactive protein (P less than 0.028) in favour of rifamycin.
Aged↗
Prevention of appearance of radiological lesions in early rheumatoid arthritis: a randomized, single-blind study comparing intra-articular rifamycin with auranofin.
In a prospective, randomized, single-blind study of 116 patients with early rheumatoid arthritis (mean disease duration 7 months), therapeutic activity of intra-articular rifamycin SV (525 mg/week) infiltration into each peripheral joint over 10 weeks was compared with that of 3 mg auranofin given orally twice daily. The incidence of side-effects was lower in rifamycin-treated patients. At the end of follow-up, the clinical variables and erythrocyte sedimentation rate showed a significant and persistent improvement both in 16 patients who continued the auranofin treatment regularly and in 55 treated with rifamycin who had completed the therapeutic cycle 62.5 months before; the latex test decreased only in the rifamycin group. In patients treated with auranofin or who changed to other commonly used antirheumatic agents, 57% of those with an initially negative radiological picture developed new radiological lesions in at least one of the small joints compared with 9% in the rifamycin group. Although the number of patients treated with rifamycin was small and the follow-up relatively short, the results of the study indicated that treatment with intra-articular rifamycin SV may prevent the appearance of radiological lesions in patients with early rheumatoid arthritis and normal radiographs initially.
Administration, Oral↗
Clinical improvement in ankylosing spondylitis with rifamycin SV infiltrations of peripheral joints.
In an open study, a new treatment modality was evaluated in 22 patients with active ankylosing spondylitis and compared with oral treatment. Patients were given a 10-week course of rifamycin SV infiltrations to all large peripheral joints, whether or not affected, and were followed for up to 12 months after the end of treatment. Clinical improvements observed at the end of the 10-week treatment cycle persisted for 12 months: morning stiffness (P less than 0.02); subjective pain (P less than 0.0001); Schober's test (P less than 0.006); hand-ground distance (P less than 0.001); erythrocyte sedimentation rate (P less than 0.001); and C-reactive protein (P less than 0.04). The number of painful joints became significantly lower at 6 (P less than 0.01) and 12 months (P less than 0.02) of the follow-up period. Oral administration of rifampin at three times the intra-articular dosage was devoid of any therapeutic activity. It is not known how treatment of peripheral joints influenced the inflammatory process at the level of the axial skeleton. These results must be considered preliminary due to the small number of patients and the short follow-up period, and because it was an open study.
Administration, Oral↗