Sublingual immunotherapy with a standardised grass pollen extract; a double-blind placebo-controlled study

Congenital dislocation of the knee is a uncommon malformation. Frequently there is an association with other congenital deformities including congenital dislocation of the hip. The classification of Leveuf and Pais into three separate groups (Type A, Type B, Type C) is now widely accepted. Between October 1989 and April 1995 we evaluated ten children (five girls and five boys) with twelve dislocated knees. Clinical, radiographic and different ultrasonography examinations were carried out on both knees. The sonographic classification showed Type A in 3, Type B in 5 and Type C in 4 cases. The sonographic examination revealed the essential anatomic structures and their pathomorphology. The anterior and the posterior cruciate ligament could be demonstrated in the majority of the cases. Three dislocated knees showed an obliteration of the recessus suprapatellaris and fibrotic changes in the m. quadriceps. These cases required operative treatment. With conservative treatment we achieved a satisfactory result in eight children with nine disease knees. There was a good functional result with an average flexion of 106 degrees. Early conservative treatment recommend as the therapy of choice. Ultrasonography imaging offers the possibility of reliable differentiation into one of the three groups of the classification of Leveuf and Pais. Radiographic documentation during the therapy has become the exception. Ultrasonography imaging helped substantially in the decision making and the timing of operative treatment.     

Double-blind, placebo-controlled evaluation of sublingual immunotherapy with standardized olive pollen extract in pediatric patients with allergic rhinoconjunctivitis and mild asthma due to olive pollen sensitization

For evaluation of the efficacy and the safety of specific sublingual immunotherapy with high allergen dose, 66 children with seasonal asthma, rhinitis, and conjunctivitis due to sensitization to olive pollen were enrolled in a double-blind, randomized, placebo-controlled study between October 1994 and October 1996 in Greece. Thirty-four patients were randomly allocated to the active group, and 32 received placebo. Immunotherapy consisted of olive-allergen extracts (Stallergènes SA) administered sublingually pre- and coseasonally from January to July for 2 consecutive years. Serial concentrations from 1 to 300 IR. were used up to the maintenance dose of 20 drops of 300 IR daily. The cumulative dose for each patient was 300 times higher than in parenteral immunotherapy, and the cumulative dose of the major allergen Ole e 1 was 8.1 mg/2 years. The patients were assessed by clinical parameters (symptom and medication scores from patients' daily diaries) and immunologic measurements (specific IgE, IgG4, eosinophil cationic protein [ECP]) were performed. The actively treated patients had a significantly lower score for dyspnea (P<0.04 during the first season; P<0.03 during the second season). At the pollinic peak during the second year, a lower score of conjunctivitis was recorded (P<0.05) in the actively treated patients. The analysis of intragroup evolution showed that the total score of rhinitis increased significantly during the pollinic peak in the group under placebo, whereas there was no symptomatic peak for the same period in the group under active treatment. However, the difference between the groups was not significant. The medication score did not differ significantly between the groups. Oral steroids were the only variables with a P value near the significance level (P=0.06) in favor of the actively treated group. A significant decrease in skin reactivity was recorded in the active group after 2 years of treatment. No significant variation in specific IgE and IgG4 was detected. A significantly lower level of serum ECP was observed at the pollinic peak in the actively treated patients during the first pollen season (P=0.01), but this was not confirmed the second year when the ECP levels doubled in both groups without correlation to the clinical findings. Tolerance was excellent with only a few minor side-effects reported. In conclusion, high-dose specific sublingual immunotherapy appears to be safe and effective in improving mild seasonal asthma and conjunctivitis linked to olive-pollen sensitization.     

Results of specific immunotherapy with Allergovit in patients with pollen allergy

The immunotherapy among patients with pollen allergy was performed by individuals composed Allergovit. The effects of this treatment was compared to patients with pollenosis who don't have desensitization because they would'nt it. This results indicated that is need to do the nasal provocation test before the choice of antigens for the specific immunotherapy because the prick skin test was very often positive but patients don't have the symptoms. Precise composition of the vaccine improved the course in first season in 77.9 per cent, in second season in 87.5 per cent and in third season in 91.6 per cent.     

Activation of B-lymphocytes during pollen season. Effect of immunotherapy

BACKGROUND: B-lymphocytes play an important part in the allergic reaction as producers of IgE antibodies. OBJECTIVE: To investigate the cell surface expression of the activation antigens CD23, CD40 and HLA-DR on B-lymphocytes in birch pollen allergic patients before and during birch pollen season and to study the effect of immunotherapy. METHODS: The study included 24 birch pollen allergic patients half of whom were treated with immunotherapy against birch pollen before the start of the season. Eleven of the 24 patients had asthma. Blood samples were taken and lung function was registered before the season began and before the immunotherapy treatment in January to February and during the season in May. The relative number of B-lymphocytes (CD19+) of the lymphocyte population and the cell surface expression of CD23, CD40 and HLA-DR on B-lymphocytes was measured by the use of flow cytometry. RESULTS: In the control group of patients the relative number and concentration of B-lymphocytes, the cell surface expression of CD23, CD40 and HLA-DR on B cells, and the serum concentration of IgE increased during season compared with before season. In contrast, in the immunotherapy treated patients no changes in the number of B cells or cell surface expression of CD23, CD40 and HLA-DR were demonstrated. CONCLUSION: The elevated expression of CD23, CD40 and HLA-DR on B cells, combined with increased levels of IgE in allergic patients during season could be explained by the effect of cytokines produced by activated TH2 cells. A shift from TH2 to TH1 cells might be the mechanism after the absence of signs of B-cell activation in immunotherapy treated patients. The prevention of increased cell surface expression on B cells by immunotherapy may constitute a significant mechanism behind the beneficial effects of immunotherapy in the treatment of pollen atopy.     

Identification of a prostate inhibitory substance in a pollen extract

Recently, much attention has focused on the treatment of BPH with the pollen extract, Cernilton. The present investigation was designed to identify the active component in this agent which might be responsible for the symptomatic relief of BPH as previously reported. Sequential purification of the active component present in the pollen extract was carried out by a combination of dialysis, gel filtration, and reverse phase chromatography. To monitor the biological activity of each of the purified fractions, a biological assay employing the human prostate cancer cell line DU145 was undertaken. While we have identified a number of constituent components in the pollen extract, only one fraction designated V-7 (FV-7) maintained a strong inhibitory effect on the growth of DU145 cells. The inhibition was time- and dose-dependent, and the concentrations of FV-7 required to reduce the cell numbers by 50% (IC50) after 2 days of exposure was 5 micrograms/ml. FV-7 was also inhibitory towards the primary culture of prostate stroma and epithelial cells, with the stroma/fibroblast showing greater sensitivity towards the HPLC-purified component. However, it should be noted that this inhibitory activity measured in the primary culture cells was only achieved at higher concentrations of FV-7. Preliminary characterization of the active ingredient identified FV-7 as DIBOA which is a cyclic hydroxamic acid. FV-7 and DIBOA induce similar inhibitory effects on the growth of DU145 cells.     

Histopathological and lipid changes in experimental colon cancer: effect of coconut kernal (Cocos nucifera Linn.) and (Capsicum annum Linn.) red chilli powder

Influence of coconut kernal and red chilli on the metabolism of lipids was studied in animals given 1,2-dimethylhydrazine (DMH). The average weight gain by the animals in the coconut kernal group was more than DMH and chilli treated groups. The concentration of cholesterol showed a decrease and phospholipids an increase in most of the tissues studied, of the kernal groups. The cholesterol-phospholipid ratio was found to be increased in most of the tissues of all experimental groups, when compared to control animals. HMG CoA reductase activity decreased in the high fat and most of the tissues of the kernal + DMH, kernal + chilli and kernal + chilli + DMH groups, while it increased in the DMH, chilli and chilli + DMH groups. Histopathological studies showed that coconut kernal supplemented animals had fewer papillae, lesser infiltration into the submucosa and lesser changes in the cytoplasm with decreased mitotic figures. Coconut kernal, thus reduced the mutagenic and carcinogenic effect of chilli and DMH respectively.     

The hepatoprotective and hyoplipidemic effect of flower pollen lipid extract in androgenized rats

Hepatoprotective, hypolipidemic and hypocholesterolemic effects of the lipid flower pollen extract in subchronically testosterone-androgenized rats were shown. Normalization of AspAT, A1AT and alkaline phosphatase--biochemical indicators of necrotic changes in the hepatic cell--substantially testifies to the hepatoprotective effect of the investigated lipid flower pollen extract on the hepatic cell, and constitutes a premise for further clinical studies.     

Induction of allergy to new aeroallergens during specific immunotherapy (SIT) in grass pollen sensitive patients

In the group of 50 patients suffering from grass pollen allergy and successfully treated with SIT for three consecutive years, we observed in 5 persons after the end of this treatment the induction of allergy to new allergens (to weeds, mites or tree) manifested by the change of the symptoms season. The induction of the new kind of allergy was confirmed by revealing of the positive skin prick tests to new allergens and by an increase of the specific IgE serum level to them. Despite disappearance of the symptoms of the illness during grass pollen season in all 5 patients we noted the higher total IgE as well as specific to grasses IgE serum level, in comparison to the value at the start of SIT. In the paper the possible mechanisms of this phenomenon are discussed, which seems to be not connected with the natural development of allergy and which confirms once more that during SIT individual changes in humoral and cellular immunity of the patient take place, sometimes very difficult to be predicted. They may among others switch clinical profile of allergy, what indicates that patient during SIT should be under the careful immunological supervision.     

Effect of bee pollen extract on glutathione system activity in mice liver under X-ray irradiation

It has been established that small x-irradiation dozes activate the lipid peroxidation and antioxidant system enzymes in mice liver. The introduction of bee pollen extract to animals normalized the activity of only several glutathione system enzymes in mice liver.     

Treatment of septic shock with immunotherapy

Sepsis is the thirteenth leading cause of death in the United States. Despite increased knowledge about its pathophysiology, availability of powerful antibiotics, and advanced diagnostic and monitoring techniques, mortality rates have not changed significantly over the past 30 years. Immunotherapy may improve outcome in the critically ill with sepsis, although trial results have been disappointing to date.     

Changes in allergic inflammation associated with successful immunotherapy

Allergen injection immunotherapy in selected patients is effective and has wide ranging anti-inflammatory effects. These include modulation of serum (and presumably local) IgE and IgG antibody responses, a reduction in mast cell numbers in the target organ and inhibition of mast cell mediator release. Tissue eosinophilia and eosinophil activation are also reduced. We have compared and contrasted the effects of immunotherapy and topical corticosteroids on allergen-induced late nasal responses. Both treatments inhibit allergen-induced late nasal symptoms and associated CD4+ T cell and eosinophil recruitment, possibly by distinct mechanisms. Whereas topical corticosteroids may act by suppressing cytokine mRNA expression for Th2-type cytokines, particularly interleukin-4, immunotherapy induces a local Th1 response with an increase in interferon-gamma.     

Successful treatment of disseminated facial verrucae with contact immunotherapy

A 29-year-old woman presented with multiple rheumatoid nodules in both hands. Clinical features and supportive laboratory investigations revealed antiphospholipid syndrome. A review of rheumatoid nodules and cutaneous manifestations of antiphospholipid syndrome is presented.     

Adjuvant immunotherapy for patients with cancer of corpus uteri

A randomized study was carried out of the efficacy of a new procedure of adjuvant immunotherapy for cancer of corpus uteri in conjunction with anticoagulant treatment. Ninety-seven patients (76-stage I-II and 21-stage III-IV) were inoculated tularemia booster (TB) and received fibrinolysin, pelentan and aspirin 15-20 days before combined treatment including uterine extirpation or extirpation with adnexa followed by telegammatherapy. Two groups of identical numbers of patients with an identical distribution of tumor progression stage were used as controls. No vaccination was carried out in one of them while TB inoculation was performed without anticoagulants in the other. A higher effectiveness of immunostimulation accompanied by anticoagulant administration was registered on the basis of the short-term (wound healing) and end results (relapse and metastasis frequency, duration of relapse-free survival and 2-, 3- and 5-year survival).     

Immunological changes during specific immunotherapy of grass pollen allergy: reduced lymphoproliferative responses to allergen and shift from TH2 to TH1 in T-cell clones specific for Phl p 1, a major grass pollen allergen

BACKGROUND AND OBJECTIVE: The mechanisms operative in specific immunotherapy (SIT) of Type I allergy are not completely understood. In the present study we evaluated immunological changes during SIT in pollinosis. METHOD: Eight patients suffering from pollinosis (monosensitized to grass pollen) were treated with conventional SIT. All subjects had IgE specific for Phl p 1, a major allergen of timothy grass. In vitro changes in the immunological reactivity to grass pollen extract and to recombinant Phl p 1 were evaluated. Subjects were examined at three occasions: before, after 3 months and after 1 year of SIT. RESULTS: Serological analysis revealed a marked increase of grass pollen- and Phl p 1-specific IgG, titres of specific IgE did not change significantly. Lymphoproliferative responses to grass pollen extract and rPhl p 1 were reduced already after 3 months of treatment. Accordingly, the cloning efficiency for Phl p 1-specific T-cell clones (TCC) dropped markedly in all patients. The majority of allergen-specific TCC raised before SIT revealed a TH2-like pattern of cytokine production, TCC established after SIT revealed TH1 characteristics. This shift was due to a decrease in IL-4 rather than an increase in IFN-production by T cells. Investigations of the epitopes recognized by T cells before and after SIT did not reveal the outgrowth of new ('protecting') specificities. We could not observe induction of allergen-specific CD8+ lymphocytes (supressor cells). CONCLUSION: Our data indicate that -- on the level of TH lymphocytes -- SIT induces tolerance to the allergen and a modulation of the cytokine pattern produced in response to allergen stimulation.     

Active immunotherapy with allogeneic tumor cell vaccines: present status

This review will concentrate on allogeneic vaccines for melanoma The important principles of melanoma vaccine effectiveness are discussed in detail, followed by a review of the progress of several clinical trials investigating allogeneic vaccines. No therapeutic cancer vaccine has yet been approved for general use by the US Food and Drug Administration. However, much progress has been made in the field of vaccine immunotherapy, especially for the treatment of melanoma. Active immunotherapy with tumor vaccines is progressing rapidly as an emerging option for cancer therapy.     

Skeletal and soft tissue sarcomas. Treatment with adjuvant immunotherapy

Because there is evidence for an active immunologic response against sarcoma, a clinical trial of adjuvant immunotherapy using bacillus Calmette-Guérin (BCG) and tumor cell vaccine was begun. Eleven of 18 patients with localized soft tissue sarcoma who received immunotherapy are free of disease, compared to only 5 of 15 treated by operation alone who are free of disease. Furthermore, immunotherapy also prolonged the median disease-free interval from 7.3 months to 15 months in the patients who experienced recurrence of their disease.     

Active specific immunotherapy of malignant melanoma with anti-idiotypic monoclonal antibodies

In this study, we have utilized the human high molecular weight-melanoma associated antigen (HMW-MAA) as a target for active specific immunotherapy with mouse anti-idiotypic (anti-id) monoclonal antibodies (mAb) in patients with malignant melanoma. After having summarized the characteristics of HMW-MAA which account for its selection as a target for immunotherapy, we describe the development and characterization of mouse anti-id mAb MK2-23 which bears the internal image of HMW-MAA. Furthermore, we describe the results of the first clinical trial performed with mouse anti-id mAb MK2-23 in patients with malignant melanoma.     

A prospective safety-monitoring study of immunotherapy with biologically standardized extracts

We evaluated the safety of immunotherapy in 419 patients who attended our allergy department for treatment. They were suffering from rhinitis and asthma caused by sensitization to grass pollen or Dermatophagoides pteronyssinus. Immunotherapy was given by biologically standardized aluminum hydroxide adsorbed extracts according to a conventional schedule. Local reactions were recorded in 10.5% of the patients and systemic reactions in 4.8%. Only 0.37% of the doses administered were associated with systemic side-effects. We found that 84% of the patients who showed systemic reactions were asthmatic subjects (P < 0.01), and most of them were sensitized to D. pteronyssinus (71%). Side-effects occurred more frequently during the dose-increase period (P < 0.05). After 9482 doses had been administered, no anaphylactic shock or life-threatening reactions were registered. We believe the risk associated with immunotherapy to be drastically reduced when treatment is carefully monitored by skilled personnel. In such conditions, as shown by our study, immunotherapy is safe.     

IgG antibodies to pollen allergens in children with rye-grass lung sensitivity

This study determined the changes in the amount (Abt) and relative avidity (Krel) of antibody to a purified rye-grass pollen extract during the rye-grass pollen season in 15 asthmatic children. For the group, there was a significant rise in Abt pre- to mid-season and fall mid- to post-season (p less than 0.05), but no consistent changes in Krel values during the study were seen. Asthmatic children with and without bronchial reactivity to rye-grass pollen extract showed similar Abt and Krel changes during the study.