Bendamustine-120 plus rituximab therapy for relapsed or refractory follicular lymphoma: a multicenter phase II study.

The optimal dose, schedule, and other aspects of bendamustine plus rituximab treatment remain unclear for patients with relapsed or refractory follicular lymphoma (FL). Herein, we analyzed the efficacy of bendamustine combined with rituximab (RB-120) treatment for Japanese patients with relapsed or refractory FL. This phase II clinical trial included patients with relapsed or refractory FL who received 375 mg/m2 rituximab on day 1 and 120 mg/m2 bendamustine on days 2 and 3 every 28 days for up to 6 cycles. The primary endpoint was the overall response rate (ORR), and the secondary endpoints included the complete response (CR) rate, progression-free survival (PFS), overall survival (OS), and safety. Thirty-seven patients were enrolled in the trial (median age 62 years, range 42-75 years). All patients were previously treated with rituximab-containing chemotherapy, and 83.8% were previously treated with the R-CHOP regimen. A median of 5 cycles (range 1-6) and 48.6% of patients completed 6 cycles. The ORR was 91.9% (95% confidence interval [CI] 78.1-98.3%), with a CR rate of 86.5% (95% CI 71.2-95.5%). The 3-year PFS and OS were 70.9% (95% CI 52.3-83.3%) and 88.9% (95% CI 73.1-95.7%), respectively, with the median 39.5 months follow-up duration. The most-frequently observed grade 3/4 adverse events were hematologic: lymphopenia (95%) and neutropenia (70%). No treatment-related deaths were observed. RB-120 showed a good efficacy with equivalent toxicities, compared with the bendamustine 120 mg/m2 monotherapy. However, the problem of high drop-out incidences cannot be ignored.

Effectiveness and safety of Omalizumab in the treatment of chronic spontaneous urticaria: Systematic review and meta-analysis.

INTRODUCTION: Chronic spontaneous urticaria (CSU) affects approximately 1% of the population, affecting both children and adults. Omalizumab (Oma) is a therapeutic option for patients with refractory forms of CSU. OBJECTIVES: To determine the effectiveness and safety of Oma in the treatment of CSU. METHODS: Systematic review (Cochrane Collaboration methodology) of randomized clinical trials comparing Oma to placebo in refractory CSU treatment. The search is based on MEDLINE; EMBASE, Central Cochrane Library, and LILACS. The outcomes evaluated were: control of the illness, adverse events, and quality of life. RESULTS: Of the 848 identified studies 13 were selected for further review and six were included in the meta-analysis. For all outcomes, high-quality evidence has confirmed that Oma is effective in the treatment of CSU. The dosage of 300mg/month achieved better results; namely a significant reduction in pruritus, papules, and urticaria activity, as well as an increase in the number of patients with a controlled condition, improvement in the quality of life and no differences in adverse events compared to the placebo. CONCLUSIONS: High-quality evidence demonstrates that Oma is effective and safe in the treatment of CSU refractory to therapy with H1 antihistamines.

Doctors' awareness concerning primary immunodeficiencies in Brazil.

BACKGROUND: PIDs are a heterogeneous group of genetic illnesses, and delay in their diagnosis is thought to be caused by a lack of awareness among physicians concerning PIDs. The latter is what we aimed to evaluate in Brazil. METHODS: Physicians working at general hospitals all over the country were asked to complete a 14-item questionnaire. One of the questions described 25 clinical situations that could be associated with PIDs and a score was created based on percentages of appropriate answers. RESULTS: A total of 4026 physicians participated in the study: 1628 paediatricians (40.4%), 1436 clinicians (35.7%), and 962 surgeons (23.9%). About 67% of the physicians had learned about PIDs in medical school or residency training, 84.6% evaluated patients who frequently took antibiotics, but only 40.3% of them participated in the immunological evaluation of these patients. Seventy-seven percent of the participating physicians were not familiar with the warning signs for PIDs. The mean score of correct answers for the 25 clinical situations was 48.08% (±16.06). Only 18.3% of the paediatricians, 7.4% of the clinicians, and 5.8% of the surgeons answered at least 2/3 of these situations appropriately. CONCLUSIONS: There is a lack of medical awareness concerning PIDs, even among paediatricians, who have been targeted with PID educational programmes in recent years in Brazil. An increase in awareness with regard to these disorders within the medical community is an important step towards improving recognition and treatment of PIDs.

Ictal SPECT of thalamocortical coupling in a patient with frontal absence.

Petit mal absence has been reported with 3-Hz generalized spike-and-wave discharges induced by secondary bilateral synchrony. Absence seizure may be present in patients with frontal lobe epilepsy. The thalamic rhythmogenic mechanisms responsible for spike-and-wave discharges have been investigated, providing a better understanding of the underlying anatomico-physiological mechanisms. We report the thalamocortical coupling in a patient with frontal absence by performing synchronous ictal single photon emission computed tomography (SPECT) analysis. Ictal SPECT revealed thalamic hyperperfusion combined with ipsilateral frontal cortical hyperperfusion in the patient. Moreover, lateral indexes of cerebral blood flow in the frontal region and thalamus were higher than those from non-epileptic control subjects. Thalamocortical coupling was thus revealed by ictal SPECT. Frontal absences should be considered as a secondarily generalized epilepsy syndrome originating from the frontal regions. The thalamus may play a crucial role as a pacemaker of rhythmic electroencephalographic activities such as secondary bilateral synchronous discharges in patients with frontal absences.

Reduction of endoplasmic reticulum Ca2+ levels favors plasma membrane surface exposure of calreticulin.

Some chemotherapeutic agents can elicit apoptotic cancer cell death, thereby activating an anticancer immune response that influences therapeutic outcome. We previously reported that anthracyclins are particularly efficient in inducing immunogenic cell death, correlating with the pre-apoptotic exposure of calreticulin (CRT) on the plasma membrane surface of anthracyclin-treated tumor cells. Here, we investigated the role of cellular Ca(2+) homeostasis on CRT exposure. A neuroblastoma cell line (SH-SY5Y) failed to expose CRT in response to anthracyclin treatment. This defect in CRT exposure could be overcome by the overexpression of Reticulon-1C, a manipulation that led to a decrease in the Ca(2+) concentration within the endoplasmic reticulum lumen. The combination of Reticulon-1C expression and anthracyclin treatment yielded more pronounced endoplasmic reticulum Ca(2+) depletion than either of the two manipulations alone. Chelation of intracellular (and endoplasmic reticulum) Ca(2+), targeted expression of the ligand-binding domain of the IP(3) receptor and inhibition of the sarco-endoplasmic reticulum Ca(2+)-ATPase pump reduced endoplasmic reticulum Ca(2+) load and promoted pre-apoptotic CRT exposure on the cell surface, in SH-SY5Y and HeLa cells. These results provide evidence that endoplasmic reticulum Ca(2+) levels control the exposure of CRT.

Tissue transglutaminase-dependent posttranslational modification of the retinoblastoma gene product in promonocytic cells undergoing apoptosis.

The retinoblastoma gene product (pRB) plays an important role in controlling both cell release from the G1 phase and apoptosis. We show here that in the early phases of apoptosis, pRB is posttranslationally modified by a tissue transglutaminase (tTG)-catalyzed reaction. In fact, by employing a novel haptenized lysis synthetic substrate which allows the isolation of glutaminyl-tTG substrates in vivo, we identified pRB as a potential tTG substrate in U937 cells undergoing apoptosis. In keeping with this finding, we showed that apoptosis of U937 cells is characterized by the rapid disappearance of the 105,000- to 110,000-molecular-weight pRB forms concomitantly with the appearance of a smear of immunoreactive products with a molecular weight of greater than 250,000. The shift in pRB molecular weight was reproduced by adding exogenous purified tTG to extracts obtained from viable U937 cells and was prevented by dansylcadaverine, a potent enzyme inhibitor. The effect of the pRB posttranslational modification during apoptosis was investigated by determining the E2F-1 levels and by isolating and characterizing pRB-null clones from U937 cells. Notably, the lack of pRB in these U937-derived clones renders these p53-null cells highly resistant to apoptosis induced by serum withdrawal, calphostin C, and ceramide. Taken together, these data suggest that tTG, acting on the pRB protein, might play an important role in the cell progression through the death program.

Ceramide accumulation precedes caspase-dependent apoptosis in CHP-100 neuroepithelioma cells exposed to the protein phosphatase inhibitor okadaic acid.

The protein phosphatase inhibitor okadaic acid (OA) dose-dependently induced apoptosis in CHP-100 neuroepithelioma cells when administered for 24 h at concentrations ranging from 10 - 100 nM. Apoptosis was largely, albeit not completely, dependent on cystein protease (caspase) activation. CPP32 processing and poly(ADP-ribose) polymerase (PARP) cleavage started to be observed only at 20 nM OA; moreover, the caspase inhibitor Z-Val-Ala-DL-Asp-fluoromethylketone (Z-VAD.fmk) (100 microM) had negligible effect on apoptosis induced by 10 nM OA, but rescued from death an increasing cell fraction as OA concentration was raised from 20 - 100 nM. Cell treatment for 24 h with OA induced ceramide accumulation; the phenomenon started to be evident at 20 nM OA and reached its maximum at 50 - 100 nM OA. In cells exposed to 50 nM OA, ceramide was already elevated by 5 h; at this time, however, PARP cleavage and apoptosis were not yet observed. Z-VAD.fmk (100 microM) had no effect on ceramide elevation induced by 50 nM OA within 5 h, but markedly reduced ceramide accumulation as the incubation was prolonged to 24 h. The latter phenomenon was accompanied by elevation of glucosylceramide levels, thus suggesting that a caspase-dependent reduction of glucosylceramide synthesis might contribute to late ceramide accumulation. Short-chain ceramide (30 microM) induced apoptosis in CHP-100 cells and its effect was additive with that evoked by OA (10 - 20 nM). These results suggest that ceramide generation might be an important mechanism through which sustained protein phosphatase inhibition induces caspase activation and apoptosis in CHP-100 cells.

Prognostic significance of the RT-PCR assay of PML-RARA transcripts in acute promyelocytic leukemia. The Leukemia Study Group of the Ministry of Health and Welfare (Kouseisho).

Minimal residual disease (MRD) was prospectively monitored at the 10(-5) level by the reverse transcriptase-polymerase chain reaction (RT-PCR) of PML-retinoic acid receptor alpha (RARA) transcripts from 27 acute promyelocytic leukemia (APL) patients who achieved complete remission (CR) with all-trans retinoic acid and chemotherapy (previously untreated patients, 15; refractory to chemotherapy or relapsed, 12). The RNA quality from bone marrow cells was firstly assessed by gel electrophoresis to avoid false negativity because of the fragility of the APL cells and the PML-RARA transcripts. In 12 of 15 untreated patients, RT-PCR became negative during consolidation and intensification therapy 4-16 months after the initiation of therapy, whereas it remained positive in nine of 12 refractory patients. At the end of therapy, RT-PCR was negative in 14 patients and positive in 13 patients. The former patients remained in CR at median follow-up of 9 months after the end of therapy. In the latter, however, 10 patients relapsed at a median of 5 months after the end of therapy. These results suggest that the RT-PCR assay can evaluate the quality of CR in APL and predict subsequent relapse.

Superovulatory response in Japanese Black cows receiving a single subcutaneous porcine follicle-stimulating hormone treatment or six intramuscular treatments over three days.

To reduce labor for superovulation treatment by twice-daily intramuscular (im) administration of FSH for more than 3 to 4 days, we investigated the superovulatory responses of Japanese Black cows to porcine FSH (pFSH) used as a single subcutaneous (sc) administration at two different doses in two different volumes of saline. In experiment 1, 20 Armour units (AU) of pFSH dissolved in either 10 mL (treatment A; n = 14) or 50 mL (treatment B; n = 14) of saline was administered subcutaneously in the neck region. In experiment 2, 30 AU of pFSH dissolved in either 10 mL (treatment C; n = 15) or 50 mL (treatment D; n = 15) of saline was administered subcutaneously in the neck region. The control animals in experiment 1 (n = 14) and experiment 2 (n = 15) received 20 AU of pFSH administered intramuscularly twice daily in decreasing doses for more than 3 days. In experiment 1, mean (±SEM) numbers of CL (15.4 ± 2.5, 18.1 ± 3.4, and 17.2 ± 2.6), total number of ova and embryos (12.9 ± 1.4, 15.9 ± 3.5, and 16.2 ± 2.8), and transferable embryos (7.5 ± 2.0, 10.4 ± 2.8, and 8.0 ± 2.1) did not differ among treatments A, B, and control. In experiment 2, mean (±SEM) numbers of CL (20.5 ± 4.3, 20.4 ± 2.7, and 20.1 ± 3.4), total number of ova and embryos (21.7 ± 4.2, 17.3 ± 3.4, and 16.5 ± 3.2), and transferable embryos (8.1 ± 1.6, 9.3 ± 2.2, and 9.5 ± 1.9) did not differ among treatments C, D, and control. Although there were no differences in serum pFSH concentrations among the three treatments at each of the time points in experiment 1, in experiment 2, the serum pFSH concentration at 6 and 8 hours after pFSH administration in treatment C (3.1 ± 0.8, 2.7 ± 0.5 ng/mL, mean ± SEM) was significantly greater (P < 0.05) than in the control (0.7 ± 0.1, 1.1 ± 0.2 ng/mL). At 10 hours after administration, the pFSH concentration had decreased and there were no differences among the three treatments at subsequent time points. These results suggest that increasing the volume of saline or the dose of pFSH does not affect the absorption pattern of pFSH administered as a single sc administration. In conclusions, single sc administration of pFSH at a dose of 20 or 30 AU dissolved in 10 or 50 mL of saline is able to induce a superovulatory response comparable with that obtained by twice-daily im administration in Japanese Black cows.

Calpain involvement in calphostin C-induced apoptosis.

A major problem in assessing the role of calpains in apoptosis induction concerns the fact that calpain inhibitors can also impair the activity of the proteasome, also reported to be involved in apoptosis. Herein we showed that apoptosis induced by calphostin C in U937 human promonocytic leukemia cells was associated, at its onset, with enhanced protein (poly)ubiquitination. This observation prompted us to study whether protein degradation through the ubiquitin/proteasome pathway was involved in apoptosis induction. We found that N-acetyl-Leu-Leu-norleucinal (50 microM), a proteasome as well as a calpain inhibitor, was able to reduce calphostin C-induced apoptosis by approximately 60%, whereas lactacystin (10 microM), a specific proteasome inhibitor, was ineffective. These results suggest that calphostin C-induced apoptosis is partly calpain-mediated, but does not require protein degradation through the ubiquitin/proteasome pathway.

Trisomy 11 acute myeloid leukemia: 5 additional cases from the Japan Adult Leukemia Study Group AML-92 and AML-95 databases.

We searched for trisomy 11 in acute myelogenous leukemia (AML) patients using the Japan Adult Leukemia Study Group (JALSG) AML-92 and -95 databases to clarify the clinical and hematologic features of a rare numerical chromosome abnormality. Among the sequentially registered patients of JALSG AML-92 (655 patients) and JALSG AML-95 (531 patients), chromosome findings were obtained for 1074 patients (90.6%); we found 5 patients with trisomy 11 as the sole abnormality. The patients were 4 women and 1 man with trisomy 11 AML, all aged more than 45 years (median, 52 years), with 4 M1 morphologies and 1 M2. No patients manifested hepatosplenomegaly or lymph node enlargement, and no central nervous system leukemia or extramedullary lesions were detectable. All showed positivity for CD13 (5/5), CD33 (5/5), CD34 (3/3), CD38 (2/2), and HLA-DR (5/5). Except for 1 patient, all achieved complete remission after 1 course of induction chemotherapy, but 2 relapsed after discontinuation of chemotherapy. A third case of relapse occurred during intensification of chemotherapy, and the patient underwent allogenic bone marrow transplantation but died from interstitial pneumonia.

Liver resection using a water jet.

The water-jet method has been used during hepatic resection. The instrument cuts the hepatic tissue with the high pressure of the fine water flow, while the exposed elastic intrahepatic vessels are spared injury. A comparative study on the water-jet method with the previously employed conventional methods was undertaken. Hepatic resections were performed on 35 patients using the water-jet method. Cirrhosis of the liver was associated with 10 of the 24 patients with hepatocellular carcinoma. An ordinary saline solution was used as the jet, which was projected at a pressure of between 12 kg/cm2 and 20 kg/cm2 through a 0.15/mm-diameter nozzle. A higher jet pressure was needed to cut the fibrotic hepatic parenchyma. In the case of normal liver, the intrahepatic vessels of more than 0.2 mm were well preserved. In most of the cases, the loss of blood when cutting the hepatic parenchyma can be easily reduced with a jet pressure of 15-16 kg/cm2, thus preserving the fine vessels more than 0.2 mm in diameter without injury. When the same pressure was applied in the cutting of a cirrhotic liver, it took much longer time compared to that of a non-cirrhotic normal liver parenchyma. The cut surface was smooth compared to that after using CUSA, although its disadvantages lie in the formation of air bubbles, which obscure the operative field. The controlled projection of a jet of water under optimal pressure may ensure a safe hepatic resection of both normal and cirrhotic livers. Furthermore, because of its uncomplicated form, a wide range of applications can be expected, while the lower cost will also expedite its large-scale use for economic reasons.

Spontaneous regression of hepatocellular carcinoma.

A 62-year-old Japanese man with hepatitis B virus-related liver cirrhosis revealed alpha-fetoprotein (AFP) elevation. Dynamic computed tomography, taken at this time, showed a liver tumor in the anterior segment. As the patient refused any further medical treatment, he was observed in an outpatient clinic. The size of the tumor reduced and the serum level of AFP decreased gradually without any treatment. Twelve months after the initial diagnosis, the tumor could not be detected by computed tomography (CT) scan, and the level of AFP had declined to the normal range. Blood supply is essential for tumor growth and an arterioportal shunt near the tumor may change the dynamics of blood flow to the tumor. The shunt found in this patient was thought to be one of the causative factors leading to regression, but it could not be denied that immunological mechanisms may have played an important role in the spontaneous regression of hepatocellular carcinoma.

Body weight and longevity: insurance experience in Japan.

Adverse effects of obesity on health and longevity are widely known in clinical medicine. The author reports here the result of a study on the relationship of body weight and longevity based on the data obtained by the life insurance cohort study in which he participated. The result is summarized below: 1. Mortality by body weight assumed a U-shaped curve with the nadir near the average weight for both men and women. 2. Because the mortality for some causes went upward toward right or reverse with the shift from underweight to overweight, the curve for all-cause mortality became U-shaped. 3. The relationship between hospitalization ratio and body weight showed substantially the same trend although the cause for hospitalization varied. 4. The body weight showing the lowest mortality was slightly heavier than the average body weight in Japan, which was different from North America. 5. Based on Metropolitan Life's principle of lowest mortality, we published Meiji Life's height and weight tables in order to set the standard body weight for the Japanese today.

Pseudotumor cerebri in a patient with acute promyelocytic leukemia during treatment with all-trans retinoic acid.

We report a rare case of pseudotumor cerebri associated with all-trans retinoic acid (ATRA) treatment of acute promyelocytic leukemia (APL). An 18-year-old male was admitted to our hospital complaining of palpitations and shortness of breath; he was found to have APL. The administration of ATRA and chemotherapy was started. After 23 days, he complained of nausea, headache and double vision. Computed tomography and magnetic resonance imaging of the head showed no intracranial abnormalities. Bilateral papilledema, a symptom of increased intracranial pressure, was noted. A diagnosis of pseudotumor cerebri was made. Symptoms were improved by administration of glycerin and the discontinuation of ATRA. After 29 days, a complete remission was achieved.

Male reproductive toxicity of ethinylestradiol associated with 4 weeks daily dosing prior to mating in rats.

Parameters of male reproductive toxicity of ethinylestradiol were assessed by conducting a mating test, sperm assay, organ weight determination and histopathological examination. Male Sprague Dawley rats were orally administered 0.1, 0.3, 3 or 10 mg/kg/day ethinylestradiol for 4 weeks prior to mating. Body weight gain and food consumption were suppressed in all treated groups. Reproductive ability of the 3 and 10 mg/kg/day males disappeared. Slightly low copulation indices were observed in the 0.1 and 0.3 mg/kg/day groups, although fertility indices were not affected. Sperm could hardly be found in the epididymis of 3 and 10 mg/kg/day males. Sperm counts were also decreased in the other treated groups, but sperm motility was not affected. Decreased absolute and/or relative weights of testes, epididymides, prostate and seminal vesicles were observed in all treated groups along with testis, epididymis, seminal vesicle and prostate atrophy, and degenerative changes of spermatocytes, spermatids, Sertoli cells and Leydig cells. These results suggest that sperm quantification and histopathological assessment are more appropriate for assessing male reproductive toxicity of ethinylestradiol than performance of copulation and fertility tests.

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 25). Effects of 2- and 4- week repeated-dosing of dibromoacetic acid.

To assess the sensitivity of rats to a testicular toxicant, 2- and 4-week repeated-dose studies using dibromoacetic acid (DBAA) were performed. Four groups of 6- or 8-week old male SD rats were given DBAA at a daily dosage of 0, 5, 50 or 250 mg/kg. The highest dose was given for 2 weeks, and the others for 2 and 4 weeks. There were no effects on body or testicular weights in any of the DBAA-treated groups. However, the mean absolute epididymal weight in the 250 mg/kg group was significantly lower than that of the control group. Histopathologically, atypical residual bodies (ARBs) and retention of Step 19 spermatids were evident with this high dose. In the same group, ARBs in the epididymal ducts and narrowing of these lumina were also observed. Retention of Step 19 spermatids was similarly apparent in the testes of animals given 50 mg/kg for 2 or 4 weeks, and in one animal given 5 mg/kg for 4 weeks. Based on these data, DBAA testicular toxicity is histopathologically detectable within 2-weeks of repeated dosing at an appropriate dose.

Immunohistochemical characterization of hepatoblastomas in B6C3F1 mice treated with diethylnitrosamine and sodium phenobarbital.

Hepatoblastomas (HBs) were induced in B6C3F1 male mice by diethylnitrosamine (DEN) and sodium phenobarbital (PB). Six-week-old mice received a single intraperitoneal dose of DEN followed by a continuous treatment with PB in diet at a concentration of 0 (group 1) or 500 (group 2) ppm for 50 weeks. HBs were observed in 13 of 21 (62%) group 2 mice, with typical histologic features as reported previously, while no such tumors were observed in group 1. Seven of 13 (54%) HBs were found in and/or adjacent to hepatocellular adenomas (HCAs) or hepatocellular carcinomas (HCCs). Immunohistochemically, all HBs were positive for S-100 protein but negative for keratin, alpha-fetoprotein (AFP), albumin (ALB) and vimentin, while HCC cells occasionally reacted positively for AFP with a mosaic pattern. HCC and HCA cells were occasionally positive for ALB. Non-neoplastic hepatocytes and normal bile ducts were positively stained for ALB and keratin/S-100 protein, respectively. S-100 protein is known to be expressed in many mesenchymal tissues and neoplasms including neuroectodermal elements but negative in cells of the hepatic lineage. Thus, the present immunohistochemical results suggested that mesenchymal differentiation occurs in mouse HB cells as observed in human HBs, one of the most frequent infant liver tumors in humans. Although the susceptibility of mouse HBs to PB-promotion suggests a hepatocytic histogenesis, the present immunohistochemical results support the hypothesis that the mouse HB is derived from pluripotent endodermal stem-like cells.

[Augmentation of pirarubicin cytotoxicity by chlorpromazine in doxorubicin-resistant mouse P388 leukemia cells].

The intracellular uptake, retention and cytotoxicity of pirarubicin, an anthracycline derivative, combined with chlorpromazine were investigated in doxorubicin-resistant mouse P388 leukemia (P388/DXR) cells. The number of viable cells was determined by the dye exclusion method. Chlorpromazine increased the cytotoxicity of pirarubicin in a dose-related manner in P388/DXR cells. A similar dose-response relationship was observed for chlorpromazine in increasing net intracellular pirarubicin accumulation. The accumulation was based on block of enhanced pirarubicin efflux from resistant cells by chlorpromazine. However, chlorpromazine did not affect cytotoxicity or transport of pirarubicin in the drug-sensitive cell line. The possible mechanisms of the restoration of pirarubicin sensitivity in P388/DXR cells by chlorpromazine are discussed.

[Duration of bronchodilator effect of inhaled Salmeterol (dry powder x metered dose inhaler) in children with acute asthma attack]. / Duração do efeito broncodilatador do Salmeterol inalado (pó seco e aerossol dosificador) em crianças com asma aguda.

Patients during a mild to moderate acute attack of asthma (FEV1: 50 - 80% of predicted) were treated with Salmeterol MDI - 50mcg or Rotadisk - 50mcg or Salbutamol (MDI -200mcg). The children were followed by Spirometry, measuring FEV1 (basal) and after treatment: at 30 minutes, 60 minutes and thereafter every 60 minutes until 780 minutes, if the patients maintained the FEV1 above 80% of the predicted value and/or an increment of 20% in the VEF1 basal value. The Salmeterol group showed a significant bronchodilation at 60 minutes which was maintained in half of the patients up to 9 hours. This was not observed in the Salbutamol group: the peak bronchodilatation was observed at 30 minutes and the bronchodilation effect was observed in half of the patients up to 6 hours. There were no significant differences between both presentations of Salmeterol. This drug allowed a prolonged bronchodilator effect and is, according to the several consensus on management of asthma, an adequate option in the treatment of moderate to severe asthma.