An antecedent diagnosis of refractory anemia with excess blasts has no prognostic relevance in acute myeloid leukemia of older adult patients.

BACKGROUND: Conflicting results have been reported about the prognostic relevance of antecedent myelodysplastic syndrome (MDS) in acute myeloid leukemia (AML) of older adults. PATIENTS AND METHODS: Data from 87 intensively treated AML patients (median age 69 years) were analyzed, with the aim of comparing therapeutic results and toxicity between de novo and AML secondary to a previous MDS (s-AML). Rate of CD34+ cells mobilization and feasibility of autologous stem cell transplantation (ASCT) were also compared. RESULTS: Complete remission rate, death in induction and primary resistance were not statistically different between the two groups. Median time for neutrophil recovery was similar, while s-AML patients required a longer time for platelet recovery (P = 0.04). There was no difference as to eligibility for consolidation as well as for mobilization and feasibility of ASCT. S-AML had negligible impact on overall survival (OS) and disease-free survival (DFS). In the multivariate analysis the only parameter significantly related to either OS or DFS duration was adverse karyotype (P = 0.02 and 0.04, respectively). CONCLUSIONS: A diagnosis of s-AML does not represent a clinically relevant prognostic factor in elderly AML patients treated with aggressive therapy. Furthermore, s-AML patients can be mobilized and autografted with comparable results as opposed to de novo cases.

Continuous infusion idarubicin and oral busulfan as conditioning for patients with acute myeloid leukemia aged over 60 years undergoing autologous stem cell transplantation.

There is growing interest in autologous stem cell transplantation (ASCT) for elderly patients with acute myeloid leukemia (AML). While mortality and toxicity from ASCT have been reduced, relapse rate is still high. In a prospective study, we investigated the feasibility of a new conditioning regimen consisting of high-dose idarubicin plus busulfan in AML patients aged over 60 years undergoing ASCT. A total of 14 patients (median age: 64 years) received 2 days continuous infusion of idarubicin at 20 mg/m2/day, followed by 3 days of oral busulfan (4 mg/kg/day) as conditioning. No case of transplant-related mortality occurred. The median number of days to neutrophil ( > 0.5 x 10(9)/l) and platelet ( > 20 x 10(9)/l) recovery was 11 and 12, respectively. Cardiac toxicity was absent, while 12 patients (86%) had grade 3-4 mucositis. After a median follow-up of 9 months from ASCT, nine of 14 patients are alive in continuous complete remission (CR), four have relapsed at 3, 6, 8 and 9 months, and one died in CR1 from gastric cancer. Our data demonstrate the feasibility of a conditioning regimen based on high-dose idarubicin plus busulfan in elderly AML patients. Results concerning reduction of relapse rate need confirmation in a larger series with longer follow-up.

Neutrophil and monocyte adhesion molecules in bronchopulmonary dysplasia, and effects of corticosteroids.

AIMS: To study a longitudinal change in the expression of adhesion molecules CD11b, CD18, and CD62L on neutrophils and monocytes in very low birth weight babies who develop respiratory distress syndrome, to compare these levels between bronchopulmonary dysplasia (BPD) and non-BPD infants, and to assess the effect of corticosteroid treatment on these adhesion molecules. METHODS: Of 40 eligible neonates, 11 neonates were oxygen dependent at 36 weeks (BPD 36 weeks), 16 infants were oxygen dependent at 28 days, but not at 36 weeks (BPD d28), and 13 infants did not develop BPD. Seventeen neonates received a six day course of steroid treatment. Expression of CD11b, CD18, and CD62L was measured on neutrophils and monocytes in arterial blood on days 1, 3, 7, 14, 21, and 28, and before and 2-3 days after initiation of dexamethasone treatment by flow cytometry. RESULTS: CD18 expression on neutrophils and monocytes and CD62L on neutrophils, measured as mean fluorescent intensity, was significantly decreased in BPD neonates compared to non-BPD neonates on days 1-28. Dexamethasone treatment significantly decreased CD11b, CD18, and CD62L expression on neutrophils, and CD11b and CD18L expression on monocytes. CONCLUSIONS: Decreased CD18 expression on neutrophils and monocytes, and decreased CD62L expression on neutrophils, measured as mean fluorescent intensity during the first four weeks of life in micropremies may be risk factors and early predictors of BPD. Dexamethasone use was associated with decreased expression of CD11b, CD18, and CD62L.

Respiratory burst activity in bronchopulmonary dysplasia and changes with dexamethasone.

The first objective of this study was to evaluate longitudinal changes in respiratory burst activity in circulating neutrophils and monocytes in infants of less than 30 weeks of gestation with respiratory distress syndrome (RDS), and to examine differences in neonates who subsequently developed bronchopulmonary dysplasia (BPD) compared with those neonates who did not. The second objective was to investigate the effects of dexamethasone on respiratory burst activity in neutrophils and monocytes. We measured burst activity on neutrophils and monocytes in fresh heparinized blood in response to E. coli, N-formyl-met-leu-phe (fMLP), and phorbol 12-myristate 13-acetate stimulation on days 3, 7, 14, and 21 of life, before and 2-3 days after initiating a 6-day course of dexamethasone treatment. Infants with RDS participating in the study were followed until discharge, and were classified as non-BPD and either 1) BPD d28, reflecting their oxygen requirement at day of life 28, or 2) BPD 36 weeks, reflecting oxygen dependence at 36 weeks' corrected gestational age. The diagnosis of BPD was supported by radiological changes of BPD. The percentage of activated neutrophils producing a respiratory burst increased in all premature infants with increasing postnatal days during the first 28 days of life, when the physiological stimulus E. coli was used as an activator (P < 0.02). There was no significant difference in respiratory burst activity measured either as percent activation or as mean fluorescence intensity between non-BPD and BPD infants after adjusting for the difference in weight and gestational age between the two groups. The treatment of premature infants with dexamethasone was associated with decreased activation of neutrophils (P < 0.005) when E. coli was used as a stimulus. In conclusion, a significant increase in neutrophil respiratory burst activity occurs during the first month of life in very low birth weight infants. Greater pulmonary damage in BPD cannot be attributed to reduced burst activity in either neutrophils or monocytes. Dexamethasone treatment was associated with decreased neutrophil respiratory burst activity.

Acute effects of higher than customary doses of salmeterol and salbutamol in patients with acute exacerbation of COPD.

Worsening of underlying bronchospasm may be associated with acute exacerbations of chronic obstructive pulmonary disease (COPD). As airway obstruction becomes more severe, the therapeutic option is to add salbutamol, but not salmeterol, as needed to cause rapid relief of bronchospasm. Unfortunately the most effective dosage of beta2-agonists may increase above that recommended during acute exacerbations. In this study, we compared the acute effects of higher than customary doses of salmeterol and salbutamol in 20 patients with acute exacerbation of COPD. A dose-response curve to salmeterol pMDI, 25 microg/puff or salbutamol pMDI, 100 microg/puff, was constructed using 1, 1, and 2 puff' i.e., a total cumulative dose of 100 microg salmeterol or 400 microg salbutamol on 2 consecutive days. After baseline measurements, dose increments were given at 30-min intervals with measurements being made 25 min after each dose. Hear rate (HR) and pulse-oximetry (SpO2) measurements were then taken. Both salmeterol and salbutamol induced a larg and significant (P < 0.05) dose-dependent increase in FEV1 [mean differences from baseline (L) = after 100 microg salmeterol 0.174 (95% CI: 0.112 to 0.237); after 400 microg salbutamol: 0.165 (95% CI: 0.080 to 0.249)], in IC [mean differences from baseline (L) = after 100 microg salmeterol: 0.332 (95% CI: 0.165 to 0.499); after 400 microg salbutamol: 0.281 (95% CI: 0.107 to 0.456)] (Fig. 2), and in FVC mean differences from baseline (L) = after 100 microg salmeterol: 0.224 (95% CI: 0.117 to 0.331); after 400 microg salbutamol: 0.242 (95% CI: 0.090 to 0.395)]. There was no significant difference between the FEV1 values (P=0.418), the ICvalues (P=0.585), and the FVCvalue (P=0.610) after 100 microg salmeterol and 400 microg salbutamol. HR [mean differences from baseline (beats/min) = after 100 microg salmeterol: 3.15 (95% CI: -0.65 to 6.96); after 400 microg salbutamol: 2.30 (95% CI: -0.91 to 5.51)] and SpO2 [mean differences from baseline (%) = after 100 microg salmeterol: -0.20 (95% CI: -1.00 to 0.60); after 400 microg salbutamol: -0.11 (95% CI: -1.00 to 0.79)] did not change significantly from baseline (P > 0.05). These data indicate that salmeterol is effective and safe in the treatment of acute exacerbation of COPD and support its use in this clinical condition.

Formoterol as dry powder oral inhalation compared with salbutamol metered-dose inhaler in acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are managed with increased doses or frequency of the patient's existing bronchodilator therapy. The use of formoterol in the treatment of mild acute exacerbations of COPD has been suggested; however, a comparison of cumulative doses of formoterol with salbutamol, the gold standard bronchodilator agent for this pathologic condition, is still lacking. OBJECTIVE: The aim of the study was to compare the inhaled beta2-agonists salbutamol (rapid onset, short duration of action) and formoterol (rapid onset, long duration of action), both used as needed in patients attending outpatient clinics because of mild acute exacerbations of COPD (Anthonisen exacerbation type I or II). METHODS: A dose-response curve to formoterol via Turbuhaler or salbutamol via pressurized metered-dose inhaler (pMDI) was constructed. On 2 consecutive days, the patients received, in randomized order, both of the following active dose regimens: A = 12 + 12 + 24 microg formoterol via Turbuhaler (48-microg cumulative metered dose); B = 200 + 200 + 400 microg salbutamol via pMDI (800-microg cumulative metered dose). Dose increments were given at 30-minute intervals, with measurements made 25 minutes after each dose. The maximum forced expiratory volume in 1 second (FEV1) value during the dose-response curve to formoterol or salbutamol was chosen as the primary outcome variable to compare the 2 treatments. Oxygen saturation by pulse oximetry (SpO2) and pulse rate were also measured at each assessment period. Every adverse event, either reported spontaneously by the patients or observed by the investigators, was recorded. RESULTS: Sixteen patients (2 women, 14 men) aged 51 to 77 years (most older than 65 years) participated in the study. Both formoterol and salbutamol induced a large, significant, dose-dependent increase in FEV1, inspiratory capacity (IC), and forced vital ca- pacity (FVC). There was no significant difference between FEV1, IC, and FVC values after 48 microg formoterol and 800 microg salbutamol. There was no significant difference in FEV1 after 24 microg formoterol and 800 microg salbutamol; however, the difference in FEV1 after 24 and 48 microg formoterol was significant. Neither heart rate (mean differences from baseline after 48 microg formoterol, 1.9 beats/min [95% CI, -3.4, 7.2] and 800 microg salbutamol, 3.7 beats/min [95% CI, -1.1, 8.5]) nor SpO2 (mean percentage differences from baseline after 48 microg formoterol, -0.37% [95% CI, -1.22, 0.47] and 800 microg salbutamol, -0.75% [95% CI, -1.73, 0.23]) changed significantly. However, SpO2 decreased below 90% in 2 patients after the highest dose of formoterol and in 1 patient after the highest dose of salbutamol. CONCLUSIONS: In this small, selected group of patients with mild acute exacerbations of COPD, formoterol via Turbuhaler induced a fast bronchodilation that was dose dependent and not significantly different from that caused by salbutamol. Furthermore, formoterol appeared to be as well tolerated as salbutamol.

Formoterol Turbuhaler for as-needed therapy in patients with mild acute exacerbations of COPD.

Worsening of underlying bronchospasm may be associated with acute exacerbations of chronic obstructive pulmonary disease (COPD). As airway obstruction becomes more severe, the therapeutic option is to add a short-acting inhaled beta2-agonist as needed to cause rapid relief of bronchospasm. Unfortunately however, the most effective dosage may increase above that recommended during acute exacerbations. Formoterol (Oxis) Turbuhaler has a rapid onset of action (within minutes) and demonstrates a maintained effect on a rway function. In this study, we examined the effects of formoterol used as needed in 20 patients with acute exacerbations of COPD. A dose response curve to inhaled formoterol (9 microg per inhalation) or placebo was constructed using three separate inhalations, i.e. a total cumulative dose of 27 microg. Dose increments were given at 20-min intervals, with measurements being made 15 min after each dose. Formoterol, but not placebo, induced a large and significant (P<0.001) dose-dependent increase in forced expiratory volume in 1 sec (FEV1) [mean differences from baseline = 0.1311 after 9 microg formoterol (95% CI: 0.096-0.167)] 0.1811 after 18 microg formoterol (95% CI: 0.140-0.2221) and 0.2081 after 27 microg formoterol (95% CI: 0.153-0.2631). However, 27 microg formoterol did not induce further benefit [0.0271 (95% CI: -0.008-0.0621); P=0.121] when compared wth 18 microg formoterol. Results of this study suggest the use of higher than customary dose of formoterol for as-needed therapy to provide rapid relief of bronchospasm in patients suffering from acute exacerbations of partially reversible COPD.

Predictive value of technetium-99m sestamibi in patients with multiple myeloma and potential role in the follow-up.

Technetium-99m 2-methoxyisobutylisonitrile (99mTc-MIBI or setamibi) has recently been proposed for use in the evaluation of multiple myeloma (MM). The aims of this study were to investigate its potential predictive value in patients with MM and its possible role in the follow-up. Thirty patients with MM who had undergone two 99mTc-MIBI scintigraphic studies at least 2 months apart constituted the study group; 22 of them received chemotherapy in the interval between the two scans. The scans were classified as showing pattern N when only physiological uptake was present, pattern D when diffuse bone marrow uptake was observed, pattern F when areas of focal uptake of the tracer were evident, and pattern F + D when both D and F patterns were observed. Comparative 99mTc-MIBI scintigraphy was considered indicative of disease progression when there was a worsening of the pattern (i.e. from N to D, or from N or D to F or to F + D) or an increase in the pattern D semiquantitative score. It was considered indicative of disease improvement when the opposite trend was observed; otherwise, it was considered to document a stable condition. A significant association was observed between the baseline scintigraphic pattern and clinical status at follow-up in the group of patients evaluated after chemotherapy (chi 2 = 16.7, P < 0.05). A negative baseline 99mTc-MIBI scintigram showed a high predictive accuracy (100%) for remission, while the presence of pattern F or F + D was often associated with a less favourable outcome. A multivariate analysis showed that 99mTc-MIBI uptake pattern has an added value in relation to known prognostic variables such as C-reactive protein. 99mTc-MIBI scintigraphy patterns at follow-up were significantly associated with the clinical status evaluated after chemotherapy (chi 2 = 32.6, P < 0.0001). Considering pattern N as indicating remission, pattern D stable condition, and pattern F or F + D progressive disease, a high concordance between scintigraphic findings and clinical status was found in the 22 patients undergoing chemotherapy (91%). Variation in 99mTc-MIBI findings comparing baseline and follow-up evaluations was significantly associated with clinical status both in patients undergoing chemotherapy (chi 2 = 26.5, P < 0.0005) and in those not undergoing chemotherapy (chi 2 = 8.0, P < 0.005). In conclusion, the results of this study suggest a prognostic value of 99mTc-MIBI scintigraphy in patients with MM and a potential role during the follow-up.

Bone marrow uptake of 99mTc-MIBI in patients with multiple myeloma.

In a previous study, we showed the ability of technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) scan to identify active disease in patients with multiple myeloma (Eur J Nucl Med 1998; 25: 714-720). In particular, a semiquantitative score of the extension and intensity of bone marrow uptake was derived and correlated with both the clinical status of the disease and plasma cell bone marrow infiltration. In order to estimate quantitatively 99mTc-MIBI bone marrow uptake and to verify the intracellular localization of the tracer, bone marrow samples obtained from 24 multiple myeloma patients, three patients with monoclonal gammopathy of undetermined significance (MGUS) and two healthy donors were studied for in vitro uptake. After centrifugation over Ficoll-Hypaque gradient, cell suspensions were incubated with 99mTc-MIBI and the uptake was expressed as the percentage of radioactivity specifically retained within the cells. The cellular localization of the tracer was assessed by micro-autoradiography. Twenty-two out of 27 patients underwent 99mTc-MIBI scan within a week of bone marrow sampling. Whole-body images were obtained 10 min after intravenous injection of 555 MBq of the tracer; the extension and intensity of 99mTc-MIBI uptake were graded using the semiquantitative score. A statistically significant correlation was found between in vitro uptake of 99mTc-MIBI and both plasma cell infiltration (Pearson's coefficient of correlation r=0.69, P<0.0001) and in vivo score (Spearman rank correlation coefficient r=0.60, P<0.01). No specific tracer uptake was found in bone marrow samples obtained from the two healthy donors. Micro-autoradiography showed localization of 99mTc-MIBI inside the plasma cells infiltrating the bone marrow. Therefore, our findings show that the degree of tracer uptake both in vitro and in vivo is related to the percentage of infiltrating plasma cells which accumulate the tracer in their inner compartments.

Cat allergen sampling by a new personal collector (Partrap FA 52).

Recent studies carried out by us and others have demonstrated that Fel d 1, the main cat allergen, may be passively transferred by human clothing in cat-free environments. Consequently, the monitoring of the Fel d 1 levels either in indoor environments or on allergen-contaminated clothes of sensitized cat owners should be considered an important tool in prevention strategies. The aim of this study was to evaluate the efficacy of a personal air sampler (Partrap FA 52) in capturing cat allergen from wool fabrics. Seven identical wool webs (80 x 100 cm) were put in the baskets of seven male cats for 1 week. In our laboratory each web was divided into two parts (80 x 50 cm), the first of which was then divided in two parts (40 x 50 cm) and each was vacuumed directly by one collector. The second part was dry-cleaned at a professional cleaners, divided in two parts and then vacuumed. For the dust collection from wool webs we used a fixed high volume air sampler (CF/20 Gelaire Flow Labs, Milan, Italy) and a personal collector (Partrap FA 52, Coppa Biella, Italy). Fel d 1 content was determined using a two site ELISA (ALK-Abelló Group, Madrid, Spain). Both air samplers collected cat allergens from cat-exposed wool fabrics before and after dry cleaning. There were significant differences between the levels of Fel d 1 before and after dry cleaning by using either CF/20 or Partrap FA52 and between the levels of Fel d 1 before dry cleaning using CF/20 and Partrap FA 52. The results of our study suggest that Partrap FA 52, although its air flow is half that of the CF/20, is able to collect even residual amounts of cat allergen from wool webs after dry cleaning and consequently may constitute a simple and effective means of monitoring the levels of Fel d 1 on the clothes of cat owners.

Effect of transfusional iron overload on immune response.

Increased susceptibility to infectious disease is observed in persons with transfusion-dependent thalassemia and iron overload who experience increased exposure to pathogens and chronic immune stimulation. An abnormal low CD8(+) T (LT8) immune phenotype defines a subgroup of patients. The CD8(+) T cell immunophenotype is stable despite continued blood transfusion and is independent of age. CD8(+) T cells, but not CD4(+) T cells, were modulated during intravenous chelation with deferoxamine. Return to characteristic pretreatment levels of CD8 was observed in both the low and the normal groups, suggesting the possibility of a set point. Proliferative response to mitogens and antigens was increased by chelation. Because CD8(+) T cells are important in immune response to infectious disease, these studies suggest that intrinsic CD8(+) T cell subset differences may be a critical factor in determining susceptibility to infection independent of transfusional iron overload or alloantigen exposure.

Prolonged response to cyclosporin-A in hypoplastic refractory anemia and correlation with in vitro studies.

BACKGROUND AND OBJECTIVE: Lymphocyte abnormalities in myelodysplastic syndromes (MDS) have been widely described, but the role of the immune system in the pathogenesis of these clonal disorders remains controversial. An active role of lymphocytes in suppressing normal hematopoiesis may be implicated in MDS with hypoplastic marrow. We have studied in vitro and in vivo activity of cyclosporin-A (CSA) on hematopoiesis in patients affected by hypoplastic MDS without blast excess. DESIGN AND METHODS: Nine consecutive patients with hypoplastic refractory anemia (RA), followed up in our out-patient unit, were treated with CSA at daily doses of 1-3 mg/kg for at least three months. Low dose steroids or danazol were transiently added in 7/9 patients. Differences between pre- and post-treatment parameters were studied by the Student's t-test. In vitro effect of CSA on circulating hematopoietic progenitors was studied by the methylcellulose colony assay. RESULTS: Before treatment, fewer circulating hematopoietic progenitors were found in all patients as compared to normal subjects. The number of CD34+ cells was about halved, while circulating erythroid and myeloid colony-forming cells (CFC) were reduced to one-fifth. After a mean period of 22 months of CSA treatment (median: 14.5 months), hemoglobin was significantly and persistently increased in two patients, platelets in one, platelets and hemoglobin in two. Two patients showed transient responses, one patient did not tolerate the treatment and one patient is close to a significant response. At in vitro CSA concentrations similar to those achieved in vivo after oral administration the drug significantly increased cell colony growth in hypoplastic RA. This test correctly predicted a positive clinical response to CSA in 3/5 cases and treatment failure in 4/4 cases. INTERPRETATION AND CONCLUSIONS: About one half of hypoplastic RA patients benefited from CSA treatment. A larger study could verify whether in vitro culture of hematopoietic progenitors in the presence of CSA can predict the clinical response and whether this treatment could prolong patients' survival.

Probiotics and immune response.

Current evidence supports the concept that oral administration of probiotic lactobacilli may be therapeutic in preventing antibiotic-associated diarrhea in children and in reestablishing normal flora in the gastrointestinal tract. Children with human immunodeficiency virus (HIV) infections may have episodes of diarrhea and frequently experience malabsorption associated with possible bacterial overgrowth; together these may interact to produce the growth abnormalities characteristic of this group. The overall objective of this investigation has been to determine whether oral administration of the probiotic Lactobacillus plantarum 299v could improve nutrient status and promote growth in children congenitally exposed to HIV. In addition, the possible beneficial effect of Lactobacillus plantarum 299v in modulating immune response was evaluated. In preliminary results described here, we report on the ability of Lactobacillus plantarum 299v to colonize children with HIV and to elicit specific systemic immune response after oral supplementation.

Acute effect of pretreatment with single conventional dose of salmeterol on dose-response curve to oxitropium bromide in chronic obstructive pulmonary disease.

BACKGROUND: An earlier study documented that, in patients with chronic obstructive pulmonary disease (COPD), addition of ipratropium bromide at the clinically recommended dose (40 microg) does not produce any further bronchodilation than that achieved with salmeterol 50 microg alone. However, the dose of ipratropium bromide needed to produce near maximal bronchodilation is several times higher than the customary dosage. The full therapeutic potential of combined salmeterol plus an anticholinergic drug can therefore only be established using doses higher than those currently recommended in the marketing of these agents. A study was undertaken to examine the possible acute effects of higher than conventional doses of an anticholinergic agent on the single dose salmeterol induced bronchodilation in patients with stable and partially reversible COPD. METHODS: Thirty two outpatients received 50 microg salmeterol or placebo. Two hours after inhalation a dose-response curve to inhaled oxitropium bromide (100 microg/puff) or placebo was constructed using one puff, one puff, two puffs, and two puffs-that is, a total cumulative dose of 600 microg oxitropium bromide. Dose increments were given at 20 minute intervals with measurements being made 15 minutes after each dose. On four separate days all patients received one of the following: (1) 50 microg salmeterol + 600 microg oxitropium bromide; (2) 50 microg salmeterol + placebo; (3) placebo + 600 microg oxitropium bromide; (4) placebo + placebo. RESULTS: Salmeterol induced a good bronchodilation (mean increase 0.272 l; 95% CI 0.207 to 0.337) two hours after its inhalation. Oxitropium bromide elicited an evident dose-dependent increase in forced expiratory volume in one second (FEV(1)) and this occurred also after pretreatment with salmeterol with a further mean maximum increase of 0.152 l (95% CI of differences 0.124 to 0.180). CONCLUSIONS: This study shows that acute pretreatment with 50 microg salmeterol does not block the possibility of inducing more bronchodilation with an anticholinergic agent when a higher than normal dosage of the muscarinic antagonist is used.

Incremental benefit of adding oxitropium bromide to formoterol in patients with stable COPD.

The effects of the long-acting beta(2)-agonist formoterol, the anticholinergic drug oxitropium bromide, and their combination were compared in 16 patients with partially reversible stable COPD. On each of 4 study days patients inhaled both drugs separated by 180 min in alternate sequence, with formoterol being administered in two doses (formoterol 12 microg + oxitropium bromide 200 microg; oxitropium bromide 200 microg + formoterol 12 microg; formoterol 24 microg + oxitropium bromide 200 microg; oxitropium bromide 200 microg + formoterol 24 microg). FEV(1)and FVC were measured baseline and after 30, 60, 120, 180, 210, 240, 300 and 360 min. In terms of onset of action, formoterol performed better than oxitropium bromide. Within the first 180 min after inhalation formoterol 24 microg was the most effective drug (maximal change in FEV(1): formoterol 24 microg = 25.6%, formoterol 12 microg = 21.1%, oxitropium bromide = 18.2%). Increased bronchodilation was obtained when the second drug was added, the sequence formoterol 24 microg + oxitropium bromide being the most effective (maximal change in FEV(1)over baseline: formoterol 24 microg + oxitropium bromide 28.8%, oxitropium bromide + formoterol 24 microg 20.9%, formoterol 12 microg + oxitropium bromide 26.6%, oxitropium bromide + formoterol 12 microg 22.5%). Significant improvement in pulmonary function may be achieved by giving two different bronchodilators in stable COPD patients. The sequence formoterol 24 microg + oxitropium bromide 200 microg seems to be the most effective.

AlphaIFN-induced hematologic and cytogenetic remission in chronic eosinophilic leukemia with t(1;5).

Chronic eosinophilic leukemia (CEL) is a myeloproliferative disease characterized by excessive eosinophilic proliferation with clonal cytogenetic abnormalities. The most frequent cytogenetic abnormality is a break in the q 31-35 region of chromosome 5, where genes encoding for IL-3, IL-5 and GM-CSF (all cytokines involved in eosinophilopoiesis) are located. We report the case of a patient with CEL with t(1;5) (q23;q31), who obtained complete hematologic and major cytogenetic response after two years of alpha-interferon (alpha-IFN) therapy. Two other cases of complete response to alpha-IFN are reported in the literature. A trial with alpha-IFN could be considered as front line treatment in this rare disease.

Comparative study of dirithromycin and azithromycin in the treatment of acute bacterial exacerbations of chronic bronchitis.

We compared the clinical and microbiological efficacy of dirithromycin with that of azithromycin in outpatients with acute bacterial exacerbations of chronic bronchitis who could be graded into stage III according to Ball's system of stratification. A total of 80 patients was studied. Of these, 40 were treated with dirithromycin as a once-daily dose of 500 mg for 5 days, and 40 with azithromycin as a once-daily dose of 500 mg for 3 days. At post-therapy, treatment success (cure or improvement) was achieved in 36 out of 40 (90%) patients receiving dirithromycin compared with 37 out of 40 (92.5%) in the azithromycin group. At the late post-therapy visit, 34 out of 36 (94.4%) dirithromycin-treated patients were cured as were 33 of 37 (89.2%) azithromycin-treated patients. A small proportion of patients treated with dirithromycin (10%) or with azithromycin (12.5%) suffered mild side effects. Gastrointestinal disorders, including abdominal cramps, nausea, or diarrhea, were common adverse effects. The main pathogens isolated before treatment were Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Eradication rates at the end of treatment were 90% (36 out of 40) for the dirithromycin group and 92.5% (37 out of 40) for the azithromycin group. Persistence of H. influenzae isolates was found in 3 out of 11 (27.3%) patients treated with dirithromycin and in 2 out of 9 (22.2%) who had received azithromycin. At the late post-therapy visit, eradication occurred in 34 out of 36 (94.4%) strains in the dirithromycin group and in 33 out of 37 (89.2%) in the azithromycin group. We conclude that dirithromycin and azithromycin appear to be equally effective in the treatment of acute bacterial exacerbations of chronic bronchitis.