Levocetirizine as treatment for symptoms of seasonal allergic rhinitis.

OBJECTIVES: The aim of this study was to assess the effectiveness and safety of levocetirizine in the treatment of the symptoms of seasonal allergic rhinitis (SAR) in patients consulting their primary care doctor. METHODS: Open-label uncontrolled and non-randomised multi-centre study including patients presenting symptoms of SAR and treated with levocetirizine tablets, 5 mg OD, for 4 weeks. INCLUSION CRITERIA: patients with nasal symptoms who were not on treatment or not responsive to treatment, or affected by excessive adverse events due to the antihistamines used previously. There were two visits (initial and after four weeks). Primary end point: efficacy as measured by T4SS (combined score of sneezing, rhinorrhoea, nasal and ocular pruritus, ranging from 0 to 12 recorded by the patient); change in Clinical Global Impression (CGI-c) as rated by the general practitioner, subjective satisfaction with and preference for levocetirizine. Secondary end points: treatment-related adverse events. RESULTS: 1290 patients were evaluated. Before the start of the study, 61.2% did not use any medication, 36.4% took anti-histamines which were not effective, and 27.0% of those previously treated patients experienced excessive adverse events. Statistically significant decreases (p < 0.01) compared to baseline were observed for each individual symptom of the itemised T4SS as well as for the global T4SS. The CGI-c improved in 91.1% of the patients who had received treatment previously and 96.8% of those who had not. Of the patients who had received treatment previously, 91.7% (p < 0.01) were satisfied with the study treatment and 84.5% of these patients reported they would prefer levocetirizine in future. All adverse events (somnolence, fatigue, headache, dry mouth) decreased by comparison with previous treatments after levocetirizine was used. CONCLUSION: Levocetirizine showed an improvement in symptom control for SAR and was preferred by patients compared to the antihistamines they had taken previously. Levocetirizine was well tolerated.

Synthesis and evaluation of a 99mTechnetium labeled chitin-binding protein as potential specific radioligand for the detection of fungal infections in mice.

AIM: Radiopharmaceuticals can be used to exploit differences between microorganisms in order to distinguish fungal from bacterial infection. Chitin, abundant in the cell wall of fungi, is not present in mammalian or bacterial cells and therefore represents a highly specific target to localize fungal infection. In this study, we have examined the potential of chitin-binding protein (CBP21) from Serratia marcescens as a specific radiotracer for the detection of invasive fungal infections. METHODS: CBP21 was labeled with 99mTc via hydrazinonicotinamide (HYNIC) and its characteristics were analyzed. In vitro binding studies with polymorphic chitin forms and microorganisms (fungi as well as bacteria) were performed. In vivo biodistribution of the compound was studied in immunocompromised mice with bacterial and fungal infections in the left and right thigh muscle, respectively, using 99mTc-HYNIC-myoglobin as size-matched control and 67Ga-citrate as positive control. Scintigraphic images were acquired at 1 and 7 h postinjection of the tracer. RESULTS: 99mTc-HYNIC-CBP21 was labeled with a radiochemical yield of 61% and a specific activity of 22.3 MBq/nmol. Highest in vitro binding percentages were found with beta-chitin (86.8+/-2.4%). Binding interactions to fungi were higher than to bacteria (P<0.05). In vivo, best ratios of fungal infection versus bacterial infection were seen at 5 and 7 h (3.6+/-1.2 and 2.9+/-1.4, respectively) postinjection of the tracer. Maximum uptake of the tracer in fungal infections (0.63+/-0.11%ID/g) at 7 h was significantly (P<0.05) higher than uptake seen in bacterial infections (0.34+/-0.11%ID/g) or the uptake of 99mTc-HYNIC-myoglobin (P<0.05) in the same infections (0.35+/-0.11%ID/g, respectively, 0.3+/-0.01%ID/g). CONCLUSIONS: This study shows that 99mTc-HYNIC-CBP21 is able to specifically interact with chitin in vitro. Scintigraphy and postmortem in vivo data indicate that 99mTc-HYNIC-CBP21 is able to distinguish fungal infection from bacterial infection probably due to a specific interaction of the protein with the chitin in the fungal cell wall.

The use of IL-2 cultures to measure chromosomal radiosensitivity in breast cancer patients.

Enhanced chromosomal radiosensitivity in breast cancer patients has been demonstrated in several studies. To investigate the chromosomal radiosensitivity of lymphocytes in breast cancer patients the G2 and micronucleus (MN) assays are often used. In these assays blood samples are exposed to ionizing radiation and the number of radiation-induced micronuclei or chromatid breaks are scored. In most studies investigating the in vitro chromosomal radiosensitivity of breast cancer patients the G2 and MN assays were performed on freshly drawn blood. The disadvantage of working with fresh blood samples is that in most cases only one blood sample can be obtained and that the assay cannot be easily repeated without further blood sampling. To allow repeated testing we propose the use of long-term cultures of T lymphocytes (IL-2 cultures). In this study we therefore investigated whether the radiation-induced MN response in IL-2 cultures was the same as in concordant whole blood cultures. For this study the MN assay (2 Gy) was performed on IL-2 cultures of 11 sensitive breast cancer patients and 20 healthy women. The results demonstrate that the enhanced chromosomal radiosensitivity observed in whole blood cultures of breast cancer patients is not present in IL-2 cultures derived from the same blood samples. Therefore, care has to be taken when IL-2 cultures are used to assess chromosomal radiosensitivity in breast cancer patients.

The use of EBV-transformed cell lines of breast cancer patients to measure chromosomal radiosensitivity.

To investigate the chromosomal radiosensitivity of lymphocytes in cancer patients the micronucleus (MN) assay is often used and performed on freshly drawn peripheral blood lymphocytes. The use of Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines may have a lot of advantages (e.g. large pool of cells) compared with fresh blood samples. In this study we have investigated whether the response of EBV-transformed lymphoblastoid cell lines to irradiation in the G1/S/G2 phases of the cell cycle is the same as in concordant whole blood cultures where primary lymphocytes were irradiated in the G0 phase of the cell cycle. For this study the MN assay (2 Gy) was performed on EBV-transformed cell lines of breast cancer patients and a group of healthy women. Those breast cancer patients were selected who showed an elevated chromosomal radiosensitivity in fresh blood samples in a previous study. The results demonstrated that the enhanced chromosomal radiosensitivity observed in fresh blood cultures of breast cancer patients is not present in EBV-transformed cell lines derived from the same blood samples. Therefore, care must be taken when EBV cell lines are used to assess chromosomal radiosensitivity in breast cancer patients.