The in vivo and in vitro effects of rhG-CSF on allergic, haematological and biochemical variables.

UNLABELLED: The objective was to evaluate the influence of treatment with rhG-CSF on allergic indexes. This was done by open trial of 5 days' treatment with rhG-CSF (5 microg/kg/day s. c.). 10 patients (6 men), aged 28 to 54 years, with rhinoconjunctivitis due to grass pollen allergy, participated in the investigation. Main measures were blood count, basophil histamine release, skin test and conjunctival provocation test. RESULTS: The treatment resulted in significant increases in numbers of neutrophils (590%), basophils (280%), eosinophils (250%) and lymphocytes (71%). Total blood histamine was increased, but basophil histamine releasability was decreased. Serum alkaline phosphatase increased 92% and serum lactate dehydrogenase increased 35% (both significant). There were no significant changes in the skin tests and the conjunctival provocation tests. Two months after the treatment all tests had returned to baseline levels. Five of the patients (50%) reported side effects, one withdrew. In conclusion treatment with rhG-CSF increases the number of circulating blood cells other than neutrophils without causing changes in indexes of allergic reactivity.

[Diagnostic reliability of the CLA test and RAST in IgE-mediated allergy compared with anamnesis and the prick test]. / Diagnostisk sikkerhed af CLA-allergitest og RAST ved IgE-medieret allergi sammenlignet med anamnese og priktest.

The principle and mode of conduction of a non-isotope method, the DHS-CLA-allergy test, for in vitro diagnosis of allergic disease is described. The method has been tested and found easy to carry out without special laboratory facilities. Thirty-nine patients all of whom were suspected of allergy were tested for nine typical allergens with the prick test, Al-RAST (ALK) and the DHS-CLA-allergy test. Definite allergy was defined on the basis of definite history of allergy and the positive prick test and, from this, the nosological sensitivity was calculated. No history of allergy and negative prick test results were defined as no allergy, and the nosological specificity was calculated from this. The nosological sensitivity for all nine allergens: Al-RAST: 46.8%, DHS-CLA: 85.5%. Nosological specificity for all nine allergens: Al-RAST: 85.7%, DHS-CLA: 80.3%. The results for the individual allergens are apparent from the text.

[Foot zone therapy and bronchial asthma--a controlled clinical trial]. / Fodzoneterapi og asthma bronchiale--en klinisk kontrolleret undersøgelse.

Thirty patients with proved bronchial asthma receiving treatment with inhaled steroid in dosages of less than 1,000 micrograms daily were subdivided at random into two groups of 15 patients. One group received foot zone therapy and the other merely uniform clinical care but without "placebo foot zone therapy". The "active" group received a total of ten foot zone therapy sessions of one hour at intervals of one week. The asthmatic symptoms, consumption of medicine and the objective pulmonary function parameters were followed-up during the subsequent six months. Decrease in consumption of beta-2-agonists and increase in peak-flow levels were observed in the group which had received foot zone therapy, but the same changes were observed in the control group. The authors do not find that this investigation demonstrates that foot zone therapy is of effect on the disease bronchial asthma. They conclude, however, that the favourable effect in both of the groups are due to increased care and control which occurred in both patient groups.

[Primary lung cancer in patients under 40 years of age]. / Primaer lungekraeft hos patienter under 40 år.

There seems to be a resistance of patients and physicians towards aggressive diagnostic evaluation of the symptoms of lung cancer in young people. We here review nine series of young patients with primary lung cancer. Patients below 40 years of age represent between 1.2 and 5% of the total lung cancer population. The distribution of sex and histopathologic findings is different, there being more women, fewer cases of squamous cell and more cases of small anaplastic and adenocarcinoma in the young group. Between 87 and 96% are smokers. There is a delay from the debut of symptoms to the first contact with a general physician of 2.4 to 10.8 months. There is a wide variation concerning tendency to operate with a frequency of curative resection of between 15 and 57%. Based on the survival of young patients who are treated by curative surgical resection, the outcome of surgical treatment for young patients does not differ from the general experience concerning resection in patients of all ages. Young patients who are found inoperable have worse survival than the older patients. Seventy to 90%, more than in the group of patients of all ages, have stadium II or III at the time of diagnosis. In conclusion, physicians should be aggressive with respect to the diagnostic evaluation even of young patients with symptoms suggestive of lung cancer.

[Adrenaline for self treatment of anaphylactic reactions. Indications, available preparations and prescription rules]. / Adrenalin til selvbehandling af anafylaktiske reaktioner. Indikationer, tilgoengelige praeparater og udleveringsregler.

Adrenaline is the drug of choice for the treatment of anaphylaxis. The indications, available formulations, and rules for prescribing adrenaline for self treatment of anaphylactic reactions in allergic subjects are summarized in this paper. Emergency kits containing adrenaline must be prescribed only to patients with a definite history of anaphylactic reactions or laryngeal oedema. A kit containing Adrenaline DAK 1 mg/ml in a traditional glass ampoule together with a 1 ml syringe and an i.m. cannula is the cheapest solution, and a usable alternative in the patient who after sufficient training feels safe to prepare his own injection. Ana-guard injector is recommended for the allergic adult due to its easy handling and the fact that it contains two doses of adrenaline 0.3 mg. For both children and adults with a low bodyweight, the Epi-Pen automatic injector is recommended. It contains one dose of adrenaline (0.15 or 0.30 mg) and requires no preparation before use. The Adrenalin Medihaler is recommended for the treatment of laryngeal oedema and threatened airway obstruction. Due to the low and unpredictable absorption after inhalation, adrenaline injection is recommended for the treatment of systemic symptoms. Prescribing adrenaline in semi-or automatic injectors requires special permission from the Danish Health Authorities.

[Disseminated primary bronchogenic carcinoma in 3 young patients]. / Dissemineret primaert bronkogent karcinom hos tre unge patienter.

Primary lung cancer in young patients is rare, patients under 40 years of age constituting between 1.2 and five percent of all cases. Three cases of primary lung cancer in young patients are presented, and the typical manifestations of primary lung cancer in young patients are discussed.

[Ion generators and bronchial asthma. A double-blind placebo controlled study]. / Iongeneratorer og asthma bronchiale. En dobbeltblind placebokontrolleret undersøgelse.

In this double blind, placebo-controlled study we examined the value of using a device for ionizing the air in the immediate environment as a therapy for asthma bronchiale. Nineteen adult patients with stable, reversible asthma were randomised to blind treatment with either an active device or an inactive placebo-device. After four weeks treatment the patients were given the alternative device for another period of four weeks. We measured daily peak-flow, symptomscore, use of medicine and spirometry and found no differences between the two periods. Therapy with ionization of the environmental air in patients with bronchial asthma should not be recommended.

The allergen specific B-cell response during immunotherapy.

The paper examines the allergen specific B-cell response in peripheral blood from patients undergoing immunotherapy with house dust mite extract. The 12 patients were part of a double blind placebo controlled study, and they were treated with either Dermatophagoides pteronyssinus (n = 4), Dermatophagoides farinae extract (n = 3) (Alutard SQ, ALK, Denmark) or placebo (n = 5). Blood was taken every fortnight on day seven after hyposensitization and tested for IgM, IgG, IgA and IgE antibody secreting cells (AbSC) to D. pteronyssinus and D. farinae allergens and for the total number of immunoglobulin secreting cells (IgSC). The data showed a maximum of approximately 120 Der f I+II specific AbSC/10(6) mononuclear cells (MNC). A comparison of specific AbSC to the major allergens of the two house dust mites demonstrated that there was no measurable species specificity in the B-cell response that could be correlated to immunotherapy with either of the two extracts. The specific IgM, IgG, and IgA response to Der f I+II was examined in the placebo (39 measurements) and the actively treated (56 measurements) groups, and the results demonstrated a significant rise in specific IgM and IgA AbSC following immunotherapy. The number of specific IgG AbSC did not change. There was a mean of less than one specific IgE AbSC/10(6) MNC, and no detectable change following the treatment. It is speculated that immunotherapy to inhalant allergens causes the induction of specific IgA AbSC. It would then be these partly differentiated plasma cells that are detected on their way to the bronchial or gut mucosa to exert their protective function mediated by allergen specific secretory IgA.

A 1-year, placebo-controlled, double-blind house-dust-mite immunotherapy study in asthmatic adults.

Thirty-one adult patients with asthma caused by house-dust mites (HDM) were included in this placebo-controlled, double-blind study to evaluate the efficacy and safety of specific immunotherapy (SIT) with biologically standardized extracts of HDM. The specific diagnosis was confirmed by skin prick tests, specific IgE, and bronchial provocation tests with HDM allergens. The patients were randomized to receive active treatment with extracts of either Dermatophagoides pteronyssinus (Dpt) or D. farinae (Dfa) (Alutard SQ, ALK, Denmark) or placebo injections. Twenty-three patients completed the study. After 1 year of treatment, we found a clinically important and significant reduction in both asthma medicine consumption (inhaled steroids 38% and beta 2-agonists 46%) and symptom score (57%) in the actively treated group, but not the placebo group. These findings were confirmed by a significant decrease in skin and bronchial sensitivity to HDM in the active group. Additionally, there was a significant difference in the patients' scores for effect in favor of the actively treated group. Total IgE and specific IgE to HDM showed no significant changes before and after treatment for either group. Spirometric lung-function measurements showed a significant increase in forced expiratory volume in 1 s (FEV1) from 85% before to 89% of predicted values after treatment for the actively treated group. Peak-flow measurements at home showed no significant changes during the study. It is concluded that allergen SIT is an effective treatment in adult patients suffering from asthma due to HDM.

Seasonal variations in T-lymphocyte response to grass pollen allergens from pollen-allergic patients and healthy controls.

Previous studies have demonstrated the presence of grass pollen-specific T cells in grass pollen-allergic patients (GPA) as well as nonallergic subjects (NA). In order to elucidate a possible seasonal variation in proliferation and cytokine production of peripheral blood mononuclear cells (PBMC), PBMC from 13 GPA and 11 NA were stimulated with extracts of Phleum pratense and tetanus toxoid before and during two grass pollen seasons. IL-4, IL-5 and interferon-gamma were determined by ELISAs. PBMC from GPA demonstrated a decreased proliferative response to grass pollen allergens during the pollen season as compared to NA (p < 0.05), but no difference was found in the response to tetanus toxoid. Cells from GPA produced higher amounts of IL-4 and IL-5 than NA (p < 0.05) and the seasonal variation in GPA proliferation was paralleled by the grass pollen-induced production of both IL-4 and IL-5 (p < 0.05). We conclude that during the grass pollen season PBMC from GPA have a reduced ability to proliferate and to produce Th2-type cytokines. This may be due to seasonal migration of the grass pollen-specific T cells from the blood to the tissues of primary allergen exposure.

A double-blind, randomized study investigating the efficacy and specificity of immunotherapy with Artemisia vulgaris or Phleum pratense/betula verrucosa.

This study investigated the specificity and efficacy of immunotherapy with Artemisia vulgaris (Artemisia) extract. We studied 25 patients with a more than two year lasting history of seasonal rhinoconjunctivitis and who had only two clinically important allergies, either to Artemisia and Betula verrucosa (Betula) or to Artemisia and Phleum pratense (Phleum). Patient selection was randomized and evaluation of results was conducted in double blind fashion. Twenty patients completed two years of specific immunotherapy. Nine patients were treated with extracts of Artemisia and 11 with extracts of either Betula (n = 3) or Phleum (n = 8). Treatment with Artemisia was followed by a significant decrease in skin sensitivity (p < 0.05) and eye sensitivity (p < 0.01) to Artemisia but not to Betula/phleum. No significant decrease was observed in medicine consumption or symptom scores. Patients treated with Betula or Phleum experienced a significant decrease in skin sensitivity to Betula or Phleum (p < 0.001), and eye sensitivity to Betula or Phleum (p < 0.05), but not to Artemisia and had significant decreases in medicine and symptom scores (p < 0.05) in Betula/phleum seasons but not in the Artemisia season. The treatment was both effective and specific with the one unexplained exception that both patient groups (Artemisia and Betula/Phleum) decreased their skin sensitivity to Artemisia.

Comparison of loratadine and terfenadine in allergic seasonal rhinoconjunctivitis with emphasis on nasal stuffiness and peak flow.

Non-sedating antihistamines have been used in the treatment of allergic rhinoconjunctivitis. Recommended dosage of loratadine (CAS 79794-75-5) is 10 mg once daily, whereas terfenadine (CAS 50679-08-8) until recently has been recommended as 60 mg twice daily. 105 patients took part in this double-blind 3-week controlled study comparing loratadine 10 mg once daily to terfenadine 120 mg once daily. Patient's daily symptom score and physician's assessment of symptoms, treatment effect and anterior rhinoscopy were evaluated as well as an objective parameter, nasal peak flow. In addition nasal peak flow was compared to patient's symptom score of stuffiness. A significant treatment effect in both treatment groups was found but there was no statistically significant difference between the two groups. Correlation between patient's feeling of stuffiness and nasal peak flow was significant. It is concluded that loratadine 10 mg once daily is as effective as terfenadine 120 mg once daily in controlling allergic rhinoconjunctivitis, and that patients' feeling of stuffiness correlates well to nasal peak flow.

Increased numbers of circulating basophils with decreased releasability after administration of rhG-CSF to allergic patients.

Preliminary studies in hematological patients have indicated that treatment with rhG-CSF reduces basophil releasability ex vivo. We examined this phenomenon further, in allergic patients. Ten patients with grass pollen rhinoconjunctivitis were given rhG-CSF (5 micrograms/kg/day s.c.) for 5 days, and examined before and after treatment. Basophil counts increased from 5 to 19 x 10(9)/l (P < 0.01). Total blood histamine increased from 80 to 160 micrograms/l (P < 0.01), corresponding to a decrease in average basophil histamine content from 1.5 to 0.81 pg/cell (P < 0.01). Isolated mononuclear cells showed a significantly decreased histamine release (HR) when stimulated with A23187 and grass. Whole blood experiments showed a similar decreased HR to grass and anti-IgE (P < 0.01). However, we found an increase in total blood histamine. We conclude that treatment with rhG-CSF (1) increases the number of circulating blood basophils, (2) reduces the average histamine content per basophil, and (3) reduces the basophil releasability. These findings could be due to the mobilization of immature basophils from the bone marrow.