Randomized open comparison of montelukast and sublingual immunotherapy as add-on treatment in moderate persistent asthma due to birch pollen.

BACKGROUND: No studies have directly compared the effects of immunotherapy and antileukotrienes due to the long time required to appreciate the clinical effects of immunotherapy. We compared the effect of montelukast (MK) and SLIT added to standard therapy in moderate asthma over 5 years. METHODS: Open randomized controlled trial. Patients with moderate asthma (and rhinitis) solely due to birch pollen were randomized to receive either MK (10 mg/d) or birch sublingual immunotherapy (SLIT) in the pollen seasons, in addition to formoterol/fluticasone. All the patients also received salbutamol and cetirizine as rescue medications. Asthma and rhinitis symptoms were recorded on diary cards from February to May at baseline and after 3 and 5 years of study. In-season nasal eosinophils and bronchial hyperresponsiveness were also evaluated. RESULTS: Thirty-three adult patients were enrolled and 29 completed the study. The groups were homogeneous at baseline. Bronchial and nasal symptom scores were lower at 3 and 5 years compared to baseline in the SLIT group. Bronchial hyperresponsiveness and bronchodilator use decreased significantly in both groups at 5 years, but only in the SLIT group at 3 years. In the SLIT group there was a significant decrease in nasal eosinophils compared to baseline and to the MK group. CONCLUSION: In patients with birch pollen-induced moderate asthma and rhinitis, the addition of SLIT provides a greater clinical benefit than that of MK.

The type of sensitizing allergen can affect the evolution of respiratory allergy.

BACKGROUND: Numerous factors affect the evolution of respiratory allergy, in children, but little is known in adults. We assessed in a prospective study the influence of the type of allergen on the progression of disease. METHODS: Outpatients, with respiratory allergy underwent skin tests and pulmonary function/methacholine challenge at baseline and after 3 years. Patients were subdivided in pure rhinitis or rhinitis + bronchial hyperreactivity (BHR). In polysensitized subjects a single relevant allergen (mites, grasses, birch, Parietaria) was identified based on symptom distribution and when needed on nasal challenge. RESULTS: 6750 patients (age range 12-46) were studied. Of them, 17.8% were monosensitized but this percentage decreased to 10.4% after 3 years (P < 0.05). Subjects with pure rhinitis were 81% at the beginning and 48% at the end. After 3 years, the patients with bronchial responsiveness increased from 18% to 58% for mites, 22% to 49% for birch, 18% to 44% for grasses, 17% to 32% for Parietaria, with a significant difference among allergens (P < 0.05). Almost the same was seen in monosensitized subjects, being mites most likely to cause a worsening. All patients with BHR at baseline received immunotherapy. In these patients the onset of new sensitizations was significantly lower than in the group (pure rhinitis) receiving drugs only and lower airways symptoms disappeared more frequently. CONCLUSION: The different type of allergen influences the course of the disease, as well as the use of immunotherapy.

Allergy to ragweed in northern Italy and prevention strategies.

Ragweed is spreading in Europe and in northern Italy, particularly in the Lombardia and Friuli areas. It constitutes a cause of significant morbidity for asthma and rhinoconjuntivitis involving as much as 12% of the general population in those countries most at risk. The public campaign to fight ragweed promoted in 1999 by the Lombardia Region failed to achieve significant results since the count of ragweed pollen in the subsequent years is similar to the previous and reached peaks of 700 pollens per m3.

Subacute combined degeneration in the spinal cords of totally gastrectomized rats. Ornithine decarboxylase induction, cobalamin status, and astroglial reaction.

BACKGROUND: The totally gastrectomized (TGX) rat is a new experimental model with which to produce widespread spongy vacuolation in spinal cord (SC) white matter, strongly reminiscent of that observed in subacute combined degeneration (SCD) of human SC. EXPERIMENTAL DESIGN: We did in long-term experiments combined biochemical and histologic studies on SCs from both TGX-rats and rats fed a cobalamin-deficient (Cbl-D) diet. We also investigated the effects of single in vivo administration of some neurotrophic growth factors on the activity of L-ornithine decarboxylase (ODC) (the key-point in the polyamine biosynthetic pathway) in rat SC. RESULTS: Biochemically, ODC activity was still induced 3 and 6 months after total gastrectomy (TG), while it did not change significantly even after 9 months of feeding a Cbl-D diet. Both TG and feeding the Cbl-D diet greatly decreased the cobalamin level in both serum and SC, although these decreases occurred more slowly in rats fed a Cbl-D diet. Nerve growth factor did not induce ODC in either Cbl-D myeloneuropathy; epidermal growth factor induced ODC in both Cbl-D myeloneuropathies. Basic fibroblast growth factor induced SC ODC only in TGX-rats. Histologically, spongy vacuolation was still widespread 3 and 6 months after TG, while it was spotty even after 9 months of feeding a Cbl-D diet. There was massively increased staining of astrocytes positive for glial fibrillary acidic protein, mainly in the gray matter, in both Cbl-D myeloneuropathies. Finally, repeated in vivo injections of cobalamin to TGX rats only partially reduced ODC induction, the severity of spongy vacuolation, and the increase in glial fibrillary acidic protein-positive astrocytes. CONCLUSIONS: These results suggest: (a) ODC induction is a persistent and inherent feature in the TG-induced SCD of rat SC; (b) an increase in glial fibrillary acidic protein positive astrocytes in rat SC is not mandatorily connected with an increase in polyamine biosynthesis; (c) a mere deficiency of Cbl seems to be not the only key-point in the pathogenesis of the ODC induction and of the SCD-like lesions, both brought about in rat SC by TG.

Subacute combined degeneration and induction of ornithine decarboxylase in spinal cords of totally gastrectomized rats.

Totally gastrectomized rats have been used to induce a spongy demyelination in the white matter of the spinal cord (SC) which is strongly reminiscent of that observed in subacute combined degeneration of human SC. Totally gastrectomized rats are deprived of intrinsic factor and thereafter become deficient in cobalamin. Morphologically, the spongy demyelination of the white matter of the rat SC, was evident 2 months after total gastrectomy. Biochemically, we investigated the hypothesis that polyamine biosynthesis might be deranged in the rat SC with experimental subacute combined degeneration, since polyamines are well known to be bound to myelin in the mammalian central nervous system. We measured the levels of both the polyamine biosynthetic decarboxylases, L-ornithine decarboxylase (ODC) and S-adenosyl-L-methionine decarboxylase, the key points in the polyamine biosynthetic pathway, in these SC. There was a sharp increase in ODC activity in SC 2 months after total gastrectomy, without significant changes in S-adenosyl-L-methionine decarboxylase activity. The increase in ODC activity seems to be organ-specific and was not due to a proliferation of neuroglial cells. Interestingly enough, the same morphologic and biochemical features found in SC of 2-month-totally-gastrectomized rats were present also in SC of newborn rats, which indeed showed incomplete myelination, vacuolated appearance, and an ODC activity level higher than that of adult SC. Therefore, total gastrectomy seems to induce a type of regression in the SC of totally gastrectomized rats toward neonatal life, at least in terms of the degree of myelination and of ODC activity level. Biochemically, no changes in ODC activity were observed in SC of rats fed a cobalamin-deficient diet for 3 months. Morphologically, only a proliferation of neuroglial cells with a moderate demyelination was observed in SC of these rats maintained on a cobalamin-deficient diet for 3 months.

[Macrocytosis, megaloblastosis and folate status in chronic alcoholics]. / Macrocitosi, megaloblastosi e stato dei folati negli etilisti cronici.

The figures obtained in simultaneous radioimmunological assays of serum folate and vitamin B12 concentrations and erythrocyte folate concentration in 74 patients are presented. All these patients had a regular daily intake of over 80 g ethyl alcohol and presented an increase in mean blood cell volume. Most of the patients were males hospitalised with liver disease and/or anaemia. All were given bone narrow needle aspirations and liver biopsies. 46% of the patients presented a reduction in erythrocyte folates but vitamin B12 deficiency was rarely encountered. Megaloblastic transformation of the bone narrow was present in 56% of the alcoholics with reduced erythrocyte folates and in 10% of those with normal folate concentration. No correlation was found between serum and erythrocyte folate concentration and degree of liver damage. Serum vitamin B12 levels were higher in patients with cirrhosis. Inadequate diet was frequently found in the alcoholics with reduced folate concentrations. Due to variations in patient selection it is difficult to compare these data with those of other series but they do seem to confirm the hypothesis that the macrocytosis in most "healthy" alcoholics reflects a direct toxic action of the alcohol on erythropoiesis. In contrast folate deficiency is found among "derelict" chronic alcoholics in whom the vitamin deficiency has often not yet produced megaloblastosis of the bone marrow.

[Radioactive immunoassay of digoxin during digitalis therapy (author's transl)]. / Valutazione radioimmunologica della digossinemia in corso di terapia digitalica

Measurements of plasma-digoxin concentrations (radioactive immunoassay) after single oral administration of different doses of beta-methyldigoxin, given by tablets or drops, were made. Their behaviour after more prolonged treatment with the same cardiac glycoside was also evaluated. The utility of radioimmunoassay of serum digoxin levels during digitalis therapy is confirmed.