[Management of Fabry disease]. / Fabry-betegség - terápiás útmutató

Fabry disease is a rare, X-linked lysosomal storage disorder that leads to accumulation of globotriaosylceramide in different tissues of the body. The disease is progressive and the first symptoms usually present in childhood. Consequences of the disease are disability and premature death. The disease in females could be as severe as in males although women may be asymptomatic. The possibility of enzyme replacement therapy has made it necessary to elaborate a comprehensive guideline for the diagnosis and treatment follow-up. The guideline has been summarized by a Hungarian multi-disciplinary working group consisting of physicians who are involved in diagnosis and care of Fabry patients. Previous clinical studies, published articles, and recently established international treatment guidelines were reviewed by the group.

[Fabry disease--diagnostic guideline]. / Fabry-betegség. Diagnosztikai útmutató.

Fabry disease is a rare, X-linked lysosomal storage disorder that leads to accumulation of globotriaosylceramide in different tissues of the body. The disease is progressive, first symptoms usually present in childhood. Consequencies of the diseases are disability and premature death. The disease in females could be as severe as in males although women may also be asymptomatic. The possibility of enzyme replacement therapy has made it necessary to elaborate a comprehensive guideline for the diagnosis and treatment follow-up. The guideline was established by a Hungarian multi-disciplinary working group, consisting of physicians who are involved in health care of Fabry patients. Previous clinical studies, published materials, and recently established international treatment guidelines were reviewed by the group.

Surface markers of lymphocyte activation in pregnant asthmatics.

PROBLEM: Pregnancy-associated immunologic alterations may improve the course of asthma. Severe maternal asthma with an exacerbation impairs fetal growth. METHOD OF STUDY: Lymphocyte activation was estimated by flow cytometry analysis of surface markers in non-pregnant healthy and mild or moderate persistent asthmatic women and healthy as well as mild or moderate persistent asthmatic, third trimester pregnant women. RESULTS: Compared with non-pregnant healthy subjects (n = 12) activated pools within CD4 and CD8 T cells were larger and the number of NK T cells were increased both in non-pregnant asthmatic (n = 12) and in healthy pregnant (n = 13) subjects (all p\0.05). No further lymphocyte activation was observed in pregnant asthmatics (n = 21) compared either with non-pregnant asthmatic, or pregnant healthy women. Average birth weight of newborns was lower (p\0.05) in the asthmatic than in the healthy pregnant group. CONCLUSION: Pregnancy is a state of wide-spread lymphocyte activation but it may blunt lymphocyte activation which characterizes bronchial asthma.

Cisplatin-vinorelbine chemotherapy in non-small cell lung cancer is safe and well tolerated: results of a retrospective Hungarian clinical data analysis.

OBJECTIVE: The efficacy of cisplatin-vinorelbine chemotherapy (CT) in NSCLC is well established. In this retrospective data analysis, haematological safety and tolerability, furthermore the effects of cisplatin-vinorelbine combination on patients' quality of life (QoL) are examined by reviewing the clinical data of NSCLC patients in a retrospective manner. RESEARCH DESIGN/METHODS: All patients (n = 25) received the following regimen: cisplatin (80 mg/m(2) on day 1 by i.v. infusion) and vinorelbine (30 mg/m(2) on days 1 and 8 by i.v. infusion; 21-day cycles; patients received four cycles of CT). Haematological laboratory and QoL data on day 1 of all cycles were collected. Quality of life was assessed by reviewing the data of patients' charts considering physical limitation, fatigue, nausea, vomiting, diarrhoea, constipation, social activities, fever, appetite and weight loss. The absence of problems was scored as 0, moderate complaints as 1 and serious deterioration as 2. RESULTS: The QoL data showed no significant deterioration in the analysed symptoms of patients during the four cycles of cisplatin-vinorelbine CT (total QoL score was 3.0 +/- 1.4 points before treatment versus 3.6 +/- 0.5 on day 1 of the last cycle, p > 0.05). Haemoglobin values were 118.4 +/- 12.3 g/l before CT and 109.0 +/- 11.3 g/l on day 1 of last cycle of CT (p > 0.05). The mean number of platelets in the beginning and in the end was 256 +/- 123(*)10(12)/l and 217 +/- 119(*)10(12)/l, respectively (p < 0.05). White blood cell count was 8.36 +/- 3.21(*)10(9)/l, absolute granulocyte count 5.95 +/- 5.81(*)10(9)/l before the treatment, and these data were 4.50 +/- 1.96(*)10(9)/l and 2.15 +/- 1.21(*)10(9)/l, respectively, on day 1 of last cycle of CT (both p < 0.005). CONCLUSIONS: Cisplatin-vinorelbine CT is a safe and well-tolerated chemotherapeutic option of NSCLC.

[Experience with aprepitant in the prevention of nausea and vomiting caused by highly emetic chemotherapy of lung cancer]. / Aprepitant a tüdorák kemoterápiája okozta hányinger és hányás megelozésében.

Approximately one half of cancer patients experience nausea or vomiting during chemotherapy containing high-dose cisplatin, despite the use of a corticosteroid and 5-hydroxytryptamine(3) (5-HT(3)) receptor antagonists. The addition of aprepitant, a neurokinin 1 receptor antagonist, improves control of emesis by a further 15-20%, and improves late phase symptoms (>24 h after chemotherapy). The cornerstone of standard first line lung cancer chemotherapy is high-dose cisplatin. Our experience with aprepitant in the chemotherapy of 10 lung cancer patients is described, who reported more than one episode of vomiting caused by chemotherapy despite the use of ondansetron previously. Aprepitant prevented acute and late phase oncoming vomiting in all 10 patients and acute and late phase nausea in 9 of the 10 patients. According to our experience on a limited number of patients, aprepitant may be of clinical benefit in the supportive treatment of lung cancer, in achieving better quality of life during chemotherapeutic cycles in these patients.

[Erythropoietic protein supportive treatment in small cell lung cancer]. / Kissejtes tüdorákban szenvedo betegek hatékony eritropoetikus protein kezelése--Saját tapasztalatok.

Anemia is common among patients with malignant tumors, due to the disease and chemotherapy. Anemia decreases patient's quality of life, and worsens the dose intensity of chemotherapy. The aim of this retrospective data-analysis was to determine the rate of transfusions and the maintenance of chemotherapeutic dose intensity in 9 small cell lung cancer patients receiving beta-erythropoietin, due to anemia observed after the first cycle of chemotherapy. The mean pre-treatment hemoglobin concentration of the patients was 116.67+/-8.17 g/L (mean+/-SD). The mean pre-erythropoietin hemoglobin concentration at baseline was 103.11+/-7.52 g/L. Six cycles of platinum compounds and etoposide were used. The post-treatment hemoglobin concentration of patients was 110.11+/-5.37 g/L (p = 0,028 vs. baseline). During these 54 chemotherapeutic cycles, only 2 patients needed transfusion, each of them once. According to our experience, the use of beta-erythropoietin in 9 anemic small cell lung cancer patients resulted in a low rate of transfusions and maintenance of cytotoxic treatment dose intensity. The adequate use of beta-erythropoietin is of great help to the physician in the management of small cell lung cancer patients.

[Erythropoietin is a novel therapeutic option in the treatment of anemia caused by small cell lung cancer]. / Az eritropoetin új lehetôség a kissejtes tüdodaganat okozta anémia kezelésében--Esetbemutatás.

Anemia is very common among patients with malignant tumors, due to the disease and chemotherapy. Anemia decreases the patient's quality of life. Erythropoietin therapy is accessible in Hungary for the treatment of chemotherapy-induced anemia in patients suffering from small cell lung cancer. In our case report we present the case of a 62-year-old female small cell lung cancer patient with severe anemia, treated by erythropoietin-beta. The erythropoietin treatment provided the possibility of effective chemo- and radiotherapy. The patient's quality of life greatly improved due to the lack of the symptoms of anemia. The adequate use of erythropoietin is of great help to the physician in the management of small cell lung cancer patients, by improving the quality of life.

Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study.

BACKGROUND: The contributions of as-needed inhaled corticosteroids and long-acting beta2 agonists (LABA) to asthma control have not been fully established. We compared the efficacy and safety of three reliever strategies: a traditional short-acting beta2 agonist; a rapid-onset LABA (formoterol); and a combination of LABA and an inhaled corticosteroid (budesonide-formoterol) in symptomatic patients receiving budesonide-formoterol maintenance therapy. METHODS: We did a 12-month, double-blind, parallel-group study in 3394 patients (aged 12 years or older), in 289 centres in 20 countries, who were using inhaled corticosteroids at study entry and symptomatic on budesonide-formoterol (160 microg and 4.5 microg, respectively), one inhalation twice daily, during a 2-week run-in. After run-in, patients were randomly assigned budesonide-formoterol maintenance therapy plus one of three alternative as-needed medications-terbutaline (0.4 mg), formoterol (4.5 microg), or budesonide-formoterol (160 microg and 4.5 microg). The primary outcome was time to first severe exacerbation, defined as an event resulting in hospitalisation, emergency room treatment, or both, or the need for oral steroids for 3 days or more. FINDINGS: Time to first severe exacerbation was longer with as-needed budesonide-formoterol versus formoterol (p=0.0048; log-rank test) and with as-needed formoterol versus terbutaline (p=0.0051). The rate of severe exacerbations was 37, 29, and 19 per 100 patients per year with as-needed terbutaline, formoterol, and budesonide-formoterol, respectively (rate ratios budesonide-formoterol versus formoterol 0.67 [95% CI 0.56-0.80; p<0.0001]; budesonide-formoterol versus terbutaline 0.52 [0.44-0.62; p<0.0001]; formoterol versus terbutaline 0.78 [0.67-0.91; p=0.0012]). Asthma control days increased to a similar extent in all treatment groups. As-needed formoterol did not significantly improve symptoms compared with as-needed terbutaline. All treatments were well tolerated. INTERPRETATION: Both monocomponents of budesonide-formoterol given as needed contribute to enhanced protection from severe exacerbations in patients receiving combination therapy for maintenance.

Efficacy and safety of roflumilast in the treatment of asthma.

BACKGROUND: The central role of chronic inflammation of the airways in asthma pathogenesis is supported by the efficacy of corticosteroids in controlling clinical symptoms. However, the search continues for potentially safer anti-inflammatory alternatives. Roflumilast is an oral, once-daily phosphodiesterase type 4 inhibitor with anti-inflammatory activity in preclinical models of asthma and chronic obstructive pulmonary disease. OBJECTIVE: To investigate the dose-ranging efficacy and safety of roflumilast in patients with mild-to-moderate asthma. METHODS: Patients (N = 693) were randomized in a double-blind, parallel-group, phase 2/3 study. After a 1- to 3-week placebo run-in period, patients (mean forced expiratory volume in 1 second [FEV1], 73% of predicted) were randomized to receive 100, 250, or 500 microg of roflumilast once daily for 12 weeks. The primary end point was change from baseline in FEV1; secondary end points included change from baseline in morning and evening peak expiratory flow. RESULTS: Roflumilast use significantly increased FEV1 (P < .001 vs baseline). Improvements from baseline in FEV1 at the last visit were 260, 320, and 400 mL for the 100-, 250-, and 500-microg dose groups, respectively. Roflumilast, 500 microg, was superior to roflumilast, 100 microg, by 140 mL in improving FEV1 (P = .002). There were also significant improvements from baseline in morning and evening peak expiratory flow in all the dose groups (P < or = .006). Roflumilast was well tolerated at all doses tested. Most adverse events were mild to moderate in intensity and transient. CONCLUSION: These results support the emerging role of roflumilast, 500 microg/d, in the treatment of asthma.

Comparable efficacy of ciclesonide once daily versus fluticasone propionate twice daily in asthma.

BACKGROUND: Inhaled corticosteroids are the mainstay of therapy in asthma, but local and systemic side effects and adherence remain a concern. Ciclesonide is an inhaled corticosteroid with on-site lung activation that provides potent anti-inflammatory activity and has been shown to have a good safety profile, even at high doses. OBJECTIVE: The aim of this study was to compare the efficacy and safety of once-daily ciclesonide versus twice-daily fluticasone propionate at comparable daily doses in patients with asthma. METHODS: In this multicenter, randomized, double-blind, double-dummy, parallel group study, 529 patients were randomized to ciclesonide 160 microg once daily or fluticasone propionate 88 microg twice daily for 12 weeks. The primary endpoint was change in lung function. RESULTS: Both ciclesonide and fluticasone propionate significantly improved forced expiratory volume in 1s, forced vital capacity, and morning peak expiratory flow compared with baseline (p<0.0001 for all variables). Both medications reduced asthma symptoms and rescue medication use within the first 24 h. At the tested dose, both medications were equally safe and well tolerated. CONCLUSION: Ciclesonide 160 microg once daily was as effective as fluticasone propionate 88 microg twice daily in improving lung function and asthma symptoms, and in reducing rescue medication use in patients with asthma.

[The management of bronchial asthma during pregnancy--Hungarian experiences]. / Az asthma bronchiale kezelése terhességben--hazai tapasztalatok.

INTRODUCTION: The prevalence of bronchial asthma is 4-8% among pregnant women. The complications, which threaten the asthmatic pregnancies according to the literature, are the following: spontaneous abortion, diabetes mellitus, caesarean delivery, pre-eclampsia, low gestational weight, neonatal icterus. OBJECTIVE: The aim of the study was a retrospective analysis of the data of asthmatic pregnant patients managed between 2000 and 2004, with a special consideration on the treatment and gynecologic complications. METHODS: The data of 53 persistent asthmatic patients--who had already undergone delivery--were collected. All of them were treated according to the guidelines issued in 2000 by the American College of Allergy, Asthma and Immunology and the American College of Obstetricians and Gynecologists: the inhalative corticosteroid budesonide, the long-acting beta-agonist formoterol or salmeterol and the short-acting beta-agonist terbutaline were used. RESULTS: The mean peak expiratory flow of the asthmatic pregnant patients was 71 +/- 16% of predicted, and the mean partial arterial oxygen tension 96 +/- 9 mmHg (means +/- SE). 10 of the 53 patients had cesarean delivery, 3 developed pre-eclampsia, 1 diabetes mellitus. The mean gestational age was 38.84 +/- 2.17 weeks and the weight of newborns 3132 +/- 604 g. The hospitalization was prolonged due to the infants' hyperbilirubinaemia in 3 cases. No congenital malformations or spontaneous abortions were detected. CONCLUSION: Based on the results of this retrospective study it can be concluded, that bronchial asthma slightly decreases the weight of newborns. The appropriate treatment of asthma during pregnancy resulted that the prevalence of gynecologic complications did not exceed the prevalence observed in the normal population--without increasing the risk of congenital malformations.

Efficacy of gemcitabine--cisplatin treatment in stage IIIA ("bulky"N2), IIIB and IV non-small cell lung cancer.

UNLABELLED: The objective of the study was to assess the efficacy of a gemcitabine and cisplatin combination for patients with stage IIIA"bulky"N2, IIIB or IV non-small cell lung cancer(NSCLC). PATIENTS AND METHODS: Patients with histological and/or cytological diagnosis of NSCLC were administered gemcitabine 1250 mg/m2 on days 1 and 8, and cisplatin 70 mg/m2 on day 1, every 3 weeks. RESULTS: One hundred and twenty patients with NSCLC, with median age of 53 years, and a WHO performance status of 0 (26%) or 1 (74%), were evaluated. The overall response rate was 40.0% with 37.5% partial response (PR) and 2.5% complete response (CR). Also, 38% of the patients had either minimal response (MR) or stable disease (SD). The median survival was 54.9 weeks. The time to progression was 28.1 weeks. There was no treatment-related death in this series. CTC grade 3/4 neutropenia occurred in 4.4% of the patients, while febrile neutropenia developed in 0,9% of the patients. CTC grade 4 thrombocytopenia occurred in 2.2%, and CTC grade 3/4 anemia developed in 3.3%. CONCLUSION: Our results support that gemcitabine and cisplatin administered as a 3-week cycle is an effective and safe regimen for the treatment of locally advanced or metastatic NSCLC.

Correlation between severity of endoscopic findings and apnea-hypopnea index in patients with gastroesophageal reflux disease and obstructive sleep apnea.

AIM: To assess the relationship between severity of gastroesophageal reflux disease and apnea-hypopnea index (AHI) as an indicator of the severity of obstructive sleep apnea. METHODS: Data of 57 patients with proven obstructive sleep apnea and gastroesophageal reflux disease were analyzed. Patients were divided into two groups according to severity of the sleep apnea: "mild-moderate" (A)-AHI >or=5-30, n = 27, "severe" (B)-AHI >30, n = 30. All patients underwent apnea monitoring during the night, upper panendoscopy and were asked about typical reflux symptoms. RESULTS: All examined patients in both groups showed a significant overweight and there was a positive correlation between body mass index and the degree of sleep apnea (P = 0.0002). The occurrence of erosive reflux disease was significantly higher in "severe" group (P = 0.0001). Using a logistic regression analysis a positive correlation was found between the endoscopic severity of reflux disease and the AHI (P = 0.016). Forty-nine point five percent of the patients experienced the typical symptoms of reflux disease at least three times a week and there was no significant difference between the two groups. CONCLUSION: A positive correlation can be found between the severity of gastroesophageal reflux disease and obstructive sleep apnea.

[Correlations between gastroesophageal reflux disease and obstructive sleep apnea]. / A gastro-oesophagealis refluxbetegség és az obstruktív alvási apnoe kapcsolatának vizsgálata.

INTRODUCTION: Several studies have reported an increased prevalence of gastroesophageal reflux disease in patients with obstructive sleep apnea. The increasingly negative intrathoracic and transdiaphragmatic pressure should facilitate of reflux-events during apnea. AIMS: The aim of the present study was to investigate whether there exists a link between endoscopic severity of reflux disease and the parameters of obstructive sleep apnea and the typical symptoms of reflux disease. METHODS: 57 patients with proven obstructive sleep apnea were divided into two groups according to the severity of the sleep apnea: "mild-moderate"--apnea-hypopnea index > or = 5-30, n = 27, "severe"--apnea-hypopnea index > 30, n = 30. All patients underwent upper panendoscopy, apnea monitoring during the night and were asked about existing and frequency of typical reflux symptoms. RESULTS: All examined patients in both groups showed significant overweight and there was a positive correlation between body mass index and the degree of sleep apnea (p = 0.0002). The occurrence of erosive reflux disease was significantly higher in "severe" group (p = 0.0001). Using a logistic regression analysis a positive correlation was found between endoscopic severity of reflux disease and apnea-hypopnea index (p = 0.016). 49.5% of all patients experienced the typical symptoms of reflux disease at least three times a week and there was not significant difference between groups. CONCLUSION: The study reveals that in patients with severe obstructive sleep apnea, erosive reflux disease is more frequent and a positive correlation can be found between severity of reflux disease and sleep apnea as well.

Severity of gastroesophageal reflux disease influences daytime somnolence: a clinical study of 134 patients underwent upper panendoscopy.

AIM: To asses the relationship between severity of gastroesophageal refluxe disease and Epworth sleepiness scale as an indicator of daytime somnolence. METHODS: One hundred and thirty-four patients underwent an upper panendoscopy as indicated by the typical reflux symptoms and were also investigated with regard to somnolence. Sleepiness was evaluated by Epworth Sleepiness Scale, which was compared to the severity of endoscopic findings (Savary-Miller/modified by Siewert). Patients with psychiatric disorders or being on sedato-hypnotics as well as shift workers were excluded from the study. The relationship between the severity of the reflux disease and daytime somnolence was analyzed with the help of multivariate regression analysis. RESULTS: A positive tendency was found between the severity of the reflux disease and the corresponding Epworth Sleepiness Scale. In the case of the more severe type - Savary-Miller III - at least a mild hypersomnia was found. For this group daytime somnolence was significantly higher than in the case of the non-erosive type of Gastroesophageal Reflux Disease representing the mildest stage of reflux disease. CONCLUSION: The severity of Gastroesophageal Reflux Disease influences daytime somnolence.

Lower prevalence of Helicobacter pylori infection in patients with inflammatory bowel disease but not with chronic obstructive pulmonary disease - antibiotic use in the history does not play a significant role.

BACKGROUND: Patients with inflammatory bowel disease have lower prevalence of Helicobacter pylori infection, but the exact reason for this is not yet clear. AIM: To examine whether the antibiotics frequently used in inflammatory bowel disease are responsible for the lower prevalence of H. pylori infection. Patients with chronic obstructive pulmonary disease on prolonged previous antibiotic therapy were used for comparison. METHODS: Presence/absence of H. pylori infection was detected by a (13)C-urea breath test in 133 patients with inflammatory bowel disease (82 ulcerative colitis, and 51 Crohn's disease) and compared with that of 135 patients with chronic obstructive pulmonary disease and with two age-matched control groups (200 patients each). Primary disease location, duration of disease and detailed analysis of previous and current medication (dose and duration of antibiotics, steroids, 5-aminosalicylic acid) were analysed in each cases. RESULTS: Seventeen of the 133 patients with inflammatory bowel disease [12.2% (10/82) of ulcerative colitis and 13.7% (7/51) of Crohn's disease] and 90/135 patients with chronic obstructive pulmonary disease (66.7%) were positive for H. pylori. A total of 78/200 (39%) for the inflammatory-bowel-disease-group-matched controls and 110/210 (55%) for the chronic-obstructive-pulmonary-disease-matched controls were positive for H. pylori. The history of any antibiotic or steroid therapy had no influence on H. pylori status of patients with inflammatory bowel disease. CONCLUSION: The prevalence of H. pylori compared to the age-matched controls is significantly lower in patients with inflammatory bowel disease but not in those with chronic obstructive pulmonary disease. Antibiotic use is not responsible for the lower prevalence of H. pylori infection in patients with inflammatory bowel disease.

Cost, morbidity, and control of asthma in Hungary: The Hunair Study.

OBJECTIVE: To assess asthma-related morbidity, symptom control, and societal cost of asthmatic patients in Hungary. Secondary objective was to assess the relationship between asthma symptom control and costs incurred. METHODS: Three hundred seventy-eight pediatric asthma patients (6-14 years of age) and 711 adult asthma patients (18-55 years of age) in 19 pulmonary clinics were interviewed by their physicians regarding asthma-related drug therapy and recent (past 2 weeks) asthma morbidity (daytime asthma symptoms, nocturnal symptoms, limitation in daily activities resulting from asthma and asthma exacerbation). Physicians estimated patients' level of asthma control based on the Global Initiative of Asthma guidelines. Direct and indirect costs for asthma-related resources were determined based on patient reported 6 months' data except for drug costs that were based on patient reported 2 weeks of data. All cost data were annualized. RESULTS: Patients in the study were mostly prescribed inhaled controller medications for asthma symptom management (76.2% pediatric and 92.3% adult) during the 2 weeks preceding the survey. Asthma-related morbidity was experienced by 15% of pediatric patients and 30% of the adult patients at least once during the 2 weeks preceding the survey. Physician classified 69% of pediatric patients as having good control, 27.5% as having moderate control, and 2.8% as having poor control of their asthma. In the adult population, 50.7% were classified as having good control, 36.6% as having moderate control, and 12.7% as having poor control. The average total annual costs (direct and indirect costs) per patient were 833 EUR (897 USD) for pediatric patients and 632 EUR (681 USD) for adult patients. In both pediatric and adult patients the total costs were highest for patients with poor asthma control. The total cost per patient increased in the ratios of 1 to 1.4 to 2.4 for pediatric patients and 1 to 1.5 to 2.9 for adult patients with good, moderate, and poor control of asthma, respectively. CONCLUSION: Inhaled corticosteroids was the most frequent treatment prescribed for asthma patients in the study. However, patients reported substantial asthma-related morbidity. Children used more resources than adults, despite being classified as having better control. Patients with poor control of asthma symptoms incurred the highest societal cost, improving patient control may reduce cost to society by 40% or more.

[Effectiveness of Gemzar-Cisplatin therapy in stage IIIA-N2, IIIB and IV non-small cell lung cancer]. / A Gemzar+Cisplatin kezelés hatékonysága a nem kissejtes tüdôrák IIIA-N2, IIIB és IV-es stádiumában.

UNLABELLED: 120 chemotherapy naive patients were treated with gemcitabine 1250 mg/m2 iv. days 1 and 8 and cisplatin 70 mg/m2 iv. on day 1 between May 1999 and June 2001. The treatments were administered in 21 cycles. The median age of the patients was 53.1 years, the male/female ratio 65%-35%. Performance status was: WHO 0: 26%, WHO 1: 74%. The staging of patients were: IIIA-N2 23%, IIIB 37%, IV 40%. By histology the tumors were: 53.3% adenocarcinoma, 40% squamous cell carcinoma, 2.5% adenosquamous carcinoma, 0.8% macrocellular carcinoma and 3% non-small cell carcinoma (not categorised). We evaluated 413 cycles of chemotherapy. The median number of cycles was 3.44. The primary endpoint of the study was the median survival and time to progression, and the response rate. The results are the following: RR 40% (PR 37.5%, CR 2.5%), MR 13.3%, SD 25%, PD 22%. The time to progression (TTP) in the SD+MR group: 29.8 weeks, in the RR group: 34.1 weeks, mean of all patients: 28.1 weeks. The survival time was estimated by Kaplan-Meier curves. The median survival (MS) of all treated patients was: 54.9 weeks, in the PD group: 34.4 weeks, in the SD+MR group: 59.1 weeks, in the PR+CR group: 62.1 weeks. CONCLUSION: gemcitabine and cisplatin combination is a very well tolerated therapeutic regimen in the 1st line treatment of NSCLC. Furthermore, this treatment improves the RR and the survival of the patients as well.

Histamine deficiency in gene-targeted mice strongly reduces antigen-induced airway hyper-responsiveness, eosinophilia and allergen-specific IgE.

Histamine is an important mediator released from activated mast cells provoked by allergen and has a substantial role in the pathophysiology of asthma. However, several lines of evidence indicate that histamine could also have important functions in the regulation of basic cell biological processes. We have used histidine decarboxylase gene-targeted (HDC-KO) mice, lacking histamine, to investigate the effect of histamine deficiency in an animal model of asthma. Our previous investigations revealed that HDC-KO mice had fewer mast cells with reduced granular content and defective degranulation characteristics. Ovalbumin (OVA)-sensitized and challenged HDC-KO mice had significantly reduced airway hyper-responsiveness, lung inflammation, bronchoalveolar lavage eosinophilia, and OVA-specific IgE compared with congenic wild-type littermates treated in the same way. Comparing the expression profiles of cytokines, the levels of IL-1alpha, IL-1beta, IL-4, IL-5, IL-6 and IFN-gamma were significantly lower in the HDC-KO mice in asthmatic late phase, indicating a significantly altered immune response to OVA provocation and challenge. Evaluation of chemokine gene expression revealed that OVA treatment caused elevation of both T(h)1- and T(h)2-type chemokines in wild-type mice, while the chemokine expression was polarized toward a T(h)1 response in HDC-KO mice. According to our results we can suggest that the possible causes of the reduced asthma symptoms in the HDC-KO mice may be the imperfect mast and eosinophil cell system, and an altered immune response to OVA provocation and challenge.