The effects of grass pollen allergoid immunotherapy on clinical and immunological parameters in children with allergic rhinitis

Allergoid immunotherapy is a new form of allergen immunotherapy allowing safe administration of high allergen doses. There is limited information on the effects of allergoid immunotherapy in children with allergic rhinitis. To investigate the immunological and clinical effects of allergoid immunotherapy in children with allergic rhinitis due to grass pollen allergy. Children with allergic rhinitis were assigned to allergoid immunotherapy (n = 27) or control (n = 26, no immunotherapy) groups. Children in the immunotherapy group received seven injections of grass pollen allergoid immunotherapy before grass pollen season and continued to receive maintenance immunotherapy for 27 months. All patients were offered a pharmacotherapy regimen to be used on demand during the pollen seasons. Clinical and laboratory parameters were compared between the immunotherapy and control groups. The rhinoconjunctivitis symptom-medication score and asthma symptom score were lower in the immunotherapy group after 1 yr of maintenance immunotherapy (p < 0.01 for both). Skin test reactivity and nasal reactivity as determined by nasal provocation testing for grass pollen were significantly decreased after 1 yr of immunotherapy (p < 0.001 for both). The seasonal increase in bronchial reactivity and nasal lavage eosinophil cationic protein levels were prevented after the first year of immunotherapy (p < 0.05 for both). The seasonal increase in immunoglobulin (Ig)E decreased (p < 0.05) and grass-specific IgG, IgG(1) and IgG(4) increased significantly already at the end of the seven-injection build-up therapy (p < 0.001, for all). Interleukin (IL)-4 levels in the culture supernatants showed a steady decline from baseline at first and second year of immunotherapy (p < 0.001) but remained unchanged in the control group. Allergoid immunotherapy is an effective method in the treatment of grass pollen-induced allergic rhinitis in children and prevents the seasonal increase in bronchial hyper-reactivity. Changes in specific IgE and IgG levels and decreased IL-4 production in peripheral blood mononuclear cell culture supernatants may account for the observed clinical effects.     

The role of stem cells in suppurative environments

Purpose:  To evaluate all consecutive patients treated with infliximab for hidradenitis suppurativa (HS).
Patients and methods:  Within 1 year, all consecutive patients seen in our department for HS (1) resistant to usual medical therapies (2) which could not be easily cured by surgery (3) not treated with new medication within 2 months before inclusion were treated intravenously with infliximab (5 mg/kg) without corticosteroids premedication. Four infusions were planned (week 0, week 2, week 6 and week 10) before the interruption of therapy and follow-up. Clinical activity of HS and quality of life of the patients were assessed immediately before the first, the third and the fourth infusions of infliximab.
Results:  Seven patients were included. Five completed the four infusions. Two patients received only three infusions because of severe side effects. The Sartorius score moderately improved with infliximab (mean score at week 0: 94 ± 39, at week 6: 71 ± 38 and at week 10: 83 ± 48). At week 6, patients judged the efficacy of therapy as marked ( n  = 1), moderate ( n  = 4) or null ( n  = 2). At week 10, five patients were evaluated and judged this efficacy as marked ( n  = 2), moderate ( n  = 2) or null ( n  = 1). The mean Skindex-29 score varied from 22 ± 11 (E: 25 ± 9, S: 13 ± 5, F: 28 ± 12) at week 0 to 18 ± 10 (E: 22 ± 8, S: 12 ± 8, F: 22 ± 12) at week 10.
Conclusion:  The efficacy of infliximab in severe HS is partial. More experience is needed before finding a place for infliximab in the therapeutic armamentarium for HS.     

Altered apoptosis in bronchoalveolar lavage lymphocytes after allergen exposure of atopic asthmatic subjects.

The increased number of lymphocytes in airways during an asthmatic response is believed to be the result of increased recruitment of these cells. However, it is possible that a decreased apoptotic rate could also contribute to the increased number. The aim of the present study was to investigate whether allergen airway provocation influences the apoptotic phenotype of lung and peripheral blood lymphocytes (PBL) in subjects with atopic asthma. Bronchoalveolar lavage (BAL) lymphocytes and PBL from 12 asthmatic subjects previously challenged with allergen (n = 7) or saline (n = 5) were exposed to the apoptotic stimulus tributyltin (TBT) in vitro and assayed for apoptosis. Airway allergen provocation resulted in decreased sensitivity of BAL lymphocytes to TBT-induced apoptosis, with 42.2% (range 33.9-62.5%) apoptotic cells before challenge versus 23.5% (range 15.3-42.4%) after challenge, while PBL were unaffected. The increased apoptosis resistance correlated with higher numbers of Bcl-2-expressing lymphocytes. Interestingly, baseline caspase-3-like activity was significantly elevated in viable BAL lymphocytes compared with viable PBL, and was unaltered by allergen exposure. In conclusion, allergen inhalation renders bronchoalveolar lavage lymphocytes more resistant to apoptosis while peripheral blood lymphocytes were not influenced at all, indicating that the apoptotic phenotype of airway lymphocytes may play a role in asthmatic inflammation.     

Lipid peroxidation, occupational stress and aging in workers of a prehospital emergency service.

BACKGROUND: Stressful conditions lead to formation of excessive free radicals, and lipid peroxidation is one of the major outcomes of free radical-mediated injury that directly damages membranes and generates a number of secondary products. OBJECTIVES: To determine the levels of malondialdehyde, an end product of lipid peroxidation, according to demographic and occupational variables in workers of a prehospital emergency service and to analyse the relationship between malondialdehyde levels and burnout. MATERIAL AND METHODS: One hundred and eleven healthy workers of a prehospital emergency service and eighty aged-matched healthy individuals of both sexes as a control group were surveyed. Malondialdehyde levels were measured by the Bull and Marnett method. To measure burnout, the Maslach Burnout Inventory was used. RESULTS: Professional category is associated with lipid peroxidation and burnout levels (Malondialdehyde levels were: physicians 338.10+/-14.47, nurses 329.17+/-12.62 and technicians 296.74+/-14.28; burnout levels were: physicians 41.29+/-3.59, nurses 37.38+/-6.05 and technicians 35.33+/-5.87). Working at night and in the evening increased malondialdehyde and burnout levels. Malondialdehyde levels increase with age. No significant variations with respect to sex were detected. Significant variations in malondialdehyde levels were detected between singles (303.13+/-12.74) and married people (344.43+/-13.43) but not with respect to divorcees (326.44+/-11.74). Significant differences were detected in erythrocyte malondialdehyde levels between smokers (341.37+/-17.09) and nonsmokers (302.21+/-12.38), but not for alcohol consumption. CONCLUSIONS: These findings suggest a positive correlation between malondialdehyde, a biomarker of lipid peroxidation and occupational stress, as estimated by elements of the Maslach Burnout Inventory, and oxidative stress.     

Statins are associated with a reduced infrarenal abdominal aortic aneurysm growth.

OBJECTIVE: To evaluate the effect of statins on aneurysm growth in a group of consecutive patients under surveillance for infrarenal aortic aneurysms (AAA). MATERIALS AND METHODS: All patients (59 statin users, 91 non-users) under surveillance between January 2002 and August 2005 with a follow-up for aneurysm growth of at least 12 months and a minimum of three diameter evaluations were retrospectively included in the analysis. Multiple regression analysis, weighted with the number of observations, was performed to test the influence of statins on AAA growth rate. RESULTS: During a median period of 3.1 (1.1-13.1) years the overall mean aneurysm growth rate was 2.95+/-2.8 mm/year. Statin users had a 1.16 mm/year lower AAA growth rate compared to non-users (95% CI 0.33-1.99 mm/year). Increased age was associated with a slower growth (-0.09 mm/year per year, p = 0.003). Female gender (+1.82 mm/year, p = 0.008) and aneurysm diameter (+0.06 mm/year per mm, p = 0.049) were associated with increased AAA growth. The use of non-steroidal anti-inflammatory drugs, chronic lung disease, or other cardiovascular risk factors were not independently associated with AAA growth. CONCLUSIONS: Statins appear to be associated with attenuation of AAA growth, irrespective of other known factors influencing aneurysm growth.     

Pharmacokinetics of Moxifloxacin in Rabbits After Intravenous,Subcutaneous and a Long‐acting Poloxamer 407 Gel Formulation Administration

The pharmacokinetics (PK) of moxifloxacin in healthy white New Zealand rabbits was studied following intravenous (IV) and subcutaneous (SC) administration routes as well as a SC long‐acting poloxamer 407 gel formulation (SC‐P407). Moxifloxacin concentrations were determined by high‐performance liquid chromatography assay with fluorescence detection. Mean half‐life for IV, SC and SC‐P407 routes was 2.15, 5.41 and 11.09 h. Clearance value after IV dosing was 0.78 l/kg/h. After SC administration, the mean absolute bioavailability was 117% and the C_max was 1.61 ± 0.49 mg/l. After SC‐P407 administration, the bioavailability was 44% and the C_max 1.83 was ±0.62 mg/l. No adverse effects were observed in any of the rabbits following IV, SC and SC‐P407 administration of moxifloxacin. Minimal inhibitory concentrations of moxifloxacin against different strains of Staphylococcus aureus from different european countries were used to compute the main pharmacodynamic (PD) surrogate markers of efficacy. The high tolerability of this SC‐P407 formulation and the favourable PK behaviour such as the long half‐life, acceptable bioavailability and excellent PK–PD ratios achieved indicate that it is likely to be effective in rabbits.     

Safety considerations for operating room personnel during hyperthermic intraoperative intraperitoneal chemotherapy perfusion.

The new treatment strategy for Peritoneal Surface Malignancy combines a cytoreductive surgery and perioperative intraperitoneal chemotherapy. Cytoreduction removes all macroscopic tumor. Intraperitoneal chemotherapy avoids implantation of microscopic residual tumor cells on intra-abdominal surfaces when it is administered intraoperatively and/or early in the postoperative period. Delivering cytotoxic drugs directly into the peritoneal cavity maximizes dose intensity and minimizes systemic toxicity. Hyperthermia is selectively cytotoxic for malignant cells and potentiates the effect of chemotherapy. Implementation of this procedure makes the perioperative personnel to face a risk of exposure to cytotoxic agents. Furthermore, peritonectomies and electro-evaporation of tumor nodules are performed with high voltage electrocautery, generating a large amount of surgical smoke during several hours. Inhalation of these fumes may be also a risk for healthcare workers. In this article, we analyse in depth these new risks of the operating room personnel, we review the literature, and we give guidelines for secure performance of cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy, as well as for early postoperative intraperitoneal chemotherapy administration. These new procedures are safe techniques for patients and healthcare workers provided adequate policies are adopted to avoid occupational exposure.