Cabergoline compared to levodopa in the treatment of patients with severe restless legs syndrome: results from a multi-center, randomized, active controlled trial.

We report the first large-scale double-blind, randomly assigned study to compare two active dopaminergic therapies for Restless Legs Syndrome (RLS), the dopamine agonist cabergoline (CAB) and levodopa/benserazide (levodopa). Patients with idiopathic RLS were treated with fixed daily doses of 2 or 3 mg CAB or 200 or 300 mg levodopa for 30 weeks. Efficacy was assessed by changes in the IRLS (International RLS Severity Scale) and by time to discontinuation of treatment due to loss of efficacy or augmentation. 361 of 418 screened patients (age 58 +/- 12 years, 71% females) were randomly assigned and treated (CAB: n = 178; levodopa: n = 183) in 51 centers of four European countries. Baseline IRLS total score was 25.7 +/- 6.8. The baseline-adjusted mean change from baseline to week 6 in IRLS sum score was d = -16.1 in the CAB group and d = -9.5 in the levodopa group (d = -6.6, P < 0.0001). More patients in the levodopa group (24.0%) than in the CAB group (11.9%, P = 0.0029, log-rank test) discontinued because of loss of efficacy (14.2% vs. 7.9%, P = 0.0290) or augmentation (9.8% vs. 4.0%, P = 0.0412). Adverse events (AEs) occurred in 83.1% of the CAB group and in 77.6% of the levodopa group. In both groups, most frequent AEs were gastrointestinal symptoms (CAB: 55.6%, levodopa: 30.6%, P < 0.0001). This first large-scale active controlled study in RLS showed superior efficacy of cabergoline versus levodopa after a 30-week long-term therapy. Tolerability was found more favorable with levodopa than with cabergoline.     

133Granulation Tissue Induction by Lassar Ointment vs. Collagen‐Polyvynilpyrrolidone in Venous Ulcers

Venous leg ulcers derived from tissue destruction is the consequence of a chronic inflammatory process that produces pain and physical disability, diminishing quality of life in patients. In this work, Lassar ointment and lyophilized collagen‐polyvinylpyrrolidone were administered separated each on one half in the same ulcer to 9 patients at the beginning and every 4 days. On day 16, all patients were auto‐grafted with partial thickness skin. Granulation tissue and graft integration were assessed clinically during 3 months. Inflammatory infiltrate, type I and III collagens, elastic fibers, alkaline phosphatase as well as blood vessels were evaluated histologically or histochemically in biopsies taken at the beginning and 16 days after the local treatment. Clinically and morphologically, both treatments demonstrated appropriate granulation tissue promotion and optimal graft integration since the beginning. Nevertheless, in Lassar ointment treated group regionalization of alkaline phosphatase activity was observed, as well as the presence of granuloma in 2 of the 9 patients. In conclusion, Lassar ointment or lyophilized collagen‐polyvinylpyrrolidone are two different promoters of granulation tissue in venous leg ulcers, however Lassar ointment has the capability to produce granuloma and an exacerbated immune response; in consequence, ulcer recidivism could be present, may be due to mineral deposits in the wound.     

Reduced expression of CD69 and adhesion molecules of T lymphocytes in asthmatic children receiving immunotherapy

T lymphocytes play a fundamental role in the initiation and regulation of chronic inflammatory responses in patients with asthma. CD69 is an early marker of T‐cell activation. The levels of intercellular adhesion molecule‐1 (ICAM‐1, CD54) and L ‐selectin have been reported to increase in patients with allergic diseases and asthma. The present study was therefore undertaken to investigate the expression of CD69, CD54, and L ‐selectin by T lymphocytes of children with asthma, before and after immunotherapy. Eighteen children newly diagnosed with asthma, 11 good and nine poor responders to immunotherapy, and 16 normal subjects, were enrolled in this study. The percentages of CD69⁺, CD54⁺, and CD62L⁺ cells in T lymphocytes were measured by using flow cytometry. The levels of CD69, CD54, and CD62L in serum and culture supernatants were determined by using enzyme‐linked immunosorbent assay (ELISA). The expression of CD69 and CD54 on CD3⁺ T lymphocytes was significantly higher in children with asthma than in control patients. All the patient groups expressed (spontaneously and following stimulation with phorbol myristate acetate and ionomycin together with mite‐extract proteins) greater amounts of CD69 and CD54 than did control subjects. With long‐term immunotherapy, the percentages of CD69⁺ and CD54⁺ T lymphocytes were significantly lower in patients with a good response to immunotherapy. Our results also showed significantly lower serum L ‐selectin levels following immunotherapy. In conclusion, successful immunotherapy resulted in decreased expression and production of CD69 and CD54. These results may explain, in part, the clinical efficacy of immunotherapy.     

Same-day surgery preparation: reduction of pediatric patient arousal and distress through participant modeling

Twenty-six children (mean age = 5.5 years) were exposed to one of three surgery preparatory conditions: participant modeling alone (n = 9), participant modeling with mother (n = 8), and standard procedure control (n = 9). Children exposed to the modeling slide-tape without their mothers had significant reductions in physiological arousal after the slide-tape presentation, unlike children viewing the tape with their mothers and children exposed to the control condition. Both participant modeling groups exhibited significantly fewer distressful behaviors during recovery (postsurgery) than did control group children. Results are discussed with respect to previous medical preparation research. Implications of these findings concerning clinical application and future research are addressed.     

Antiviral immune responses modulate the nature of central nervous system (CNS) disease in a murine model of multiple sclerosis

Summary: In animals and in humans, T-cell therapy can cure advanced disseminated leukemia that would otherwise be fatal. The therapeutic effect of immune T cells is quantitative. As the dose of effector T cells is increased, survival is proportionately increased. Therefore, effective T-cell therapy is predicated on the ability to procure large numbers of immune effector T cells. By using cultured T cells, the number of immune T cells can be increased in vivo substantially above che level achievable by vaccination. The survival of cultured T ceils in vivo is dependent upon both the culture conditions used and the therapeutic regimens employed. Under appropriate conditions, cultured T ceils can proliferate in vivo in response to stimulation by antigen, distribute widely and survive long term to provide effector function and immunologic memory. Given that T cells recognize peptides. the need for immunization with tumor can be circumvented by immunization with peptide. Peptide-specific T cells and the progeny of single T-cell clones can provide the necessary cellular functions to eradicate disseminated murine leukemia. The ability of cloned T cells to similarly provide substantial measurable immunity in humans has been validated in clinical trials. By priming with peptides and by using established culture conditions, T-cell therapy can now be directed against virtually any antigen within the host T-cell repertoire. The major remaining question to be answered is which proteins and which peptides are the most suitable targets for T-cell therapy trials.     

Digestive cancer in relation to diet in Spain.

Dietary factors are widely considered to be largely responsible for the different cancer incidences observed in different populations. In the present study we investigated the possible influence of dietary habits on the incidence of digestive cancer in the provinces of Spain. Data on specific mortality due to digestive cancer corresponding to the period 1975 to 1985 were obtained from the Instituto Nacional de Estadística. Nutritional data on the different provinces were in turn gathered from the Instituto de Nutrición del Consejo Superior de Investigaciones Científicas. The information was processed by the SPSS statistical software package. Lifestyle and socio-cultural factors are found to influence dietary risk factors in digestive cancer, particularly among women. The most significant correlations with the different cancers studied corresponded to total energy intake (responsible for 27.4% of variance), animal fats, and smoked fish and coffee. The latter is related to oral and esophageal cancer in particular (responsible for 15.4% of variance). Consumption of carrots and frozen vegetables is responsible for 6.5% of variance, vs. 4.4% of variance for alcoholic beverages, sugar, and Vitamin D. Differences are noted between both the sexes and their relationship to the different cancers studied.     

Efficacy of short‐term oral cobalamin therapy for the treatment of cobalamin deficiencies related to food‐cobalamin malabsorption: A study of 30 patients

Background: It has been suggested that oral cobalamin (vitamin B₁₂) therapy may be an effective therapy for treating cobalamin deficiencies related to food‐cobalamin malabsorption. However, the duration of this treatment was not determined. Patients and method: In an open‐label, nonplacebo study, we studied 30 patients with established cobalamin deficiency related to food‐cobalamin malabsorption, who received between 250 and 1000 μg of oral crystalline cyanocobalamin per day for at least 1 month. Endpoints: Blood counts, serum cobalamin and homocysteine levels were determined at baseline and during the first month of treatment. Results: During the first month of treatment, 87% of the patients normalized their serum cobalamin levels; 100% increased their serum cobalamin levels (mean increase, +167 pg/dl; P < 0.001 compared with baseline); 100% had evidence of medullary regeneration; 100% corrected their initial macrocytosis; and 54% corrected their anemia. All patients had increased hemoglobin levels (mean increase, +0.6 g/dl) and reticulocyte counts (mean increase, +35 × 10⁶/l) and decreased erythrocyte cell volume (mean decrease, 3 fl; all P < 0.05). Conclusion: Our findings suggest that crystalline cyanocobalamin, 250–1000 μg /day, given orally for 1 month, may be an effective treatment for cobalamin deficiencies not related to pernicious anemia.