Effect of nedocromil on bronchospasm induced by inhalation of substance P in asthmatic subjects

Several studies have demonstrated that neuropeptides are present in peptidergic fibres of bronchial tissue. The aim of the present study was to evaluate in vivo the effect of nedocromil sodium (2 x 2 mg) on bronchospasm induced by inhalation of substance P. Six moderate asthmatic patients, mean age 25.17 years, were studied. Airway response was measured as FEV1 and the dose of substance P (using a dose range of 23-736 nmol) producing a 20% decrease in FEV1 (PD20) was calculated from the individual semilogarithmic dose-response curves. Patients were studied on 3 separate days in a randomized, double-blind manner. On the first day a baseline PD20 value was determined. On subsequent days substance P challenge was performed after pretreatment (20 min before challenge) with either placebo or nedocromil sodium. Student's paired t-test and Wilcoxon's test were used for statistical analysis. The results of this study demonstrated that inhalation of substance P causes a dose-dependent bronchoconstriction and that the bronchoconstriction induced by substance P can be prevented by pre-treatment with nedocromil sodium.     

Human interleukin 4 regulates the phenotype of lymphocytes generated during mixed lymphocyte culture and inhibits the IL-2-induced development of LAK function in normal and leukaemic cells

This study examined the immunoregulatory role of recombinant interleukin 4 (IL-4), also known as B-cell stimulating factor 1, on the generation of cytotoxic effector cells from normal and leukaemic human blood mononuclear cells. When tested on cells from normal individuals, the addition of IL-4 to mixed lymphocyte cultures led to a dose-dependent proliferation of T-helper cells (CD3, 4 positive) with a concomitant decrease in phenotypic and functional cytotoxic T cells and natural killer (NK) cells. IL-4 also inhibited the interleukin-2 (IL-2)-induced generation of lymphokine-activated killer (LAK) activity when added at the beginning of mixed lymphocyte culture. When tested on mature leukaemic NK cells, IL-4 also inhibited the ability of IL-2 to induce LAK function using a short-term culture system. These results show that IL-4 acts on both normal and leukaemic cells and suggests that it acts at more than one level during the development of LAK function.     

Percutaneous Endovascular Treatment for Stenoses and Occlusions of Infrarenal Aorta and Aortoiliac Bifurcation: Midterm Results

OBJECTIVE: evaluation and comparison of the endovascular treatment of isolated aortic and aortoiliac atherosclerotic lesions (stenoses and occlusions). METHODS: a percutaneous endovascular procedure was performed in 52 patients (38 men and 14 women) with a mean age of 52 years (range, 25-85 years). The baseline angiogram showed 35 aortic lesions (31 stenoses, 4 occlusions) and 17 aortoiliac lesions (14 stenoses, 3 occlusions). Percutaneous techniques used in this series included variable combinations of transluminal angioplasty and stenting. All stents placements were performed over-the-wire using the transfemoral route (most often bilateral approach). Clinical examination and Duplex-scan were performed at discharge, 1 month, 6 months, 12 months, and then yearly. RESULTS: technical success was 100% for aortic and aortoiliac lesions. Angiographic success rates were comparable for aortic (91%) and aortoiliac (94%) lesions. No death occurred during or early after the endovascular intervention. Duplex-scan confirmed 100% patency rate at discharge. There was no significant difference between the aortic (94%) and aortoiliac (96%) groups regarding immediate clinical improvement. Mean follow-up was 34+/-31 months (range, 0-130 months). The cumulative primary patency rate at 36 months was 85% in the aortic group and 86% in the aortoiliac group. Clinical success, defined as a symptom-free status at the end of follow-up, was also similar in both groups. CONCLUSION: endovascular treatment of isolated aortic lesions of the infra-renal aorta has favorable outcomes comparable to those of aortoiliac lesions.     

Management of sphenoid sinus cerebrospinal fluid rhinorrhea: making use of an extended approach to the sphenoid sinus.

OBJECTIVES: Specific information addressing the management of cerebrospinal fluid (CSF) fistulas that originate from within the sphenoid sinus remains scant. The objective of this study was to review the cause and management of CSF rhinorrhea arising from the sphenoid sinus. STUDY DESIGN AND SETTING: This is a retrospective chart review of 12 cases of CSF rhinorrhea arising from the sphenoid sinus that occurred in 11 patients. All patients were treated at a single institution between 1994 and 1999. RESULTS: All patients were managed surgically with sphenoid sinus fat obliteration using an endoscopic sublabial, transseptal approach. This approach was successful for all 12 cases, with median duration of follow-up of 18 months. CONCLUSIONS: Endoscopically assisted transseptal repair of CSF fistulas that originate within the sphenoid sinus offers an alternate approach to previously described methods of repair in this region. Advantages include wide access to the entire sphenoid sinus, improved access to laterally pneumatized regions within the sphenoid sinus, and rostral mucosal closure over the repair within the sinus.     

Beeinflussung humaner Osteoblasten durch verschiedene Analgetika

In der Behandlung von Frakturen spielt die Analgesie eine wesentliche Rolle. Es stellt sich daher die Frage, ob in der Klinik h?ufig eingesetzte Analgetika wie Tramadol oder Diclofenac negative Wirkungen auf die Knochenbruchheilung haben.     

Anti-thyroid drugs decrease mucosal damage in a rat model of experimental colitis

Background : Methimazole, an anti-thyroid drug, was recently found to be useful in the treatment of systemic lupus erythematosus and other autoimmune diseases. Moreover, decreased thyroid hormone production is associated with a variety of immunological manifestations, such as reduced activation of CD4⁺ cells, increased CD8⁺ cell activity and reduced soluble IL-2 receptors. In the present study we examined the effects of methimazole and propylthiouracil on a rat model of experimental colitis.
Methods : Colitis was induced by intracolonic administration of 30 mg trinitrobenzene sulphonic acid (TNB). Two weeks prior to induction of colitis, rats were treated by either methimaziole (0.04%) or propylthiouracil (0.01%) in drinking water after a week of free access to water. Rats were sacrificed 48 h or 7 days after induction of colitis. The colon was isolated, rinsed with ice-cold water and weighed. Damage was assessed both macroscopically and microscopically and myeloperoxidase (MPO) activity determined.
Results : All treated rats were hypothyroid as manifested by a significant elevation of thyroid stimulating hormone (TSH), by comparison with the control groups (mean -1.82±0.40 versus 0.11±0.02 mmol/L, respectively). The inflammatory response elicited by TNB resulted in severe mucosal damage 48 h after damage induction, which persisted for 7 days. Pre-treatment with either methimazole 0.04% or propylthiouracil 0.01% significantly decreased mucosal damage macroscopically (lesion area, lesion score and segmental weight) microscopically and also significantly decreased MPO level at both time points ( P <0.01).
Conclusions : Methimazole and propylthiouracil significantly reduce mucosal damage and colonic weight in a rat model of colitis. The mode by which they do so remains to be studied.     

Erythropoietin production in healthy volunteers subjected to controlled hypobaric hypoxia: further evidence against a role for adenosine

Aims Objective of this study was to investigate whether adenosine modulates renal erythropoietin production.
Methods In the present study erythropoietin production was stimulated by hypobaric hypoxia by subjecting healthy volunteers to a simulated altitude of 4000  m in a low pressure chamber for 5.5  h. During exposure to hypoxia the subjects received i.v. in a randomized, single-blind, cross-over fashion the non-specific adenosine antagonist theophylline, the adenosine reuptake inhibitor dipyridamole and placebo.
Results Contrary to the working hypothesis, theophylline did not decrease and dipyridamole did not further boost erythropoietin concentrations.
Conclusions The results are in agreement with our earlier study using haemorrhage as a controlled physiological stimulus of erythropoietin production, and would question a major role for adenosine as a mediator of renal erythropoietin production.     

Isolation impairs place preference conditioning to morphine but not aversive learning in mice

Morphine (8–100 mg/kg IP) induces place preference conditioning in mice. The effect of two different periods of isolation (15 and 30 days) was examined. Mice isolated for 15 days but not 30 days exhibited place preference conditioning to morphine (8 mg/kg). After 30 days of isolation morphine could not induce place preference conditioning with the following doses (8, 16, 64, 100 mg/kg). Social regrouping of male mice previously isolated for 30 days with naive female mice for 15 or 30 days resulted in a reappearance of the conditioned place preference to morphine (16 mg/kg). The specificity of this associative deficit was examined by testing learning in isolated compared to non-isolated mice in two distinct settings: escape learning in the Morris water maze and passive avoidance acquisition and retention. On the Morris water maze isolated mice did not differ from non-isolated mice regarding place learning, the probe trial or extinction. Isolated mice were unimpaired in passive avoidance acquisition and retention. It was concluded that the deficits in place preference conditioning were not the result of a global learning impairment in isolated mice. Received: 10 April 1996 /Final version: 20 September 1996