Risedronate Reduces the Risk of First Vertebral Fracture in Osteoporotic Women

Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined. We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score =–3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg (n= 328) or placebo (n= 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4% in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval 37% to 90%; P= 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of 70%, 95% CI 8% to 90%; P= 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P= 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women with osteoporosis, with a similar magnitude of effect early and late after the menopause. Received: 12 September 2001 / Accepted: 11 December 2001     

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.     

Verz?gerte Radialisparese nach Monteggia-Fraktur – Ein Fallbericht

Nervensch?digungen als Begleitverletzungen bei Monteggia-Frakturen sind selten und betreffen meistens den N. radialis. üblicherweise kommt es bei frischen Frakturen zu einer spontanen neurologischen Remission, nachdem der Radiuskopf wieder reponiert wurde. Im vorliegenden Fall erlitt ein heute 33-j?hriger Mann eine Parese des N. interosseus posterior 27 Jahre nach einer Monteggia-Fraktur, wobei der Radiuskopf in luxierter Stellung verblieb. Nach einem Bagatelltrauma am Handgelenk beim Federballspielen kam es zu einer L?hmung der Handgelenk- und Fingerstreckmuskulatur. Eine konservative Behandlung mittels intensiver Physiotherapie blieb auch nach 4 Monaten erfolglos. Daraufhin wurde der Nerv exploriert. Der Profundusast zeigte sich dabei narbig adh?rent im Bereich einer beengenden und verdickten Frohse-Arkade. Anschlie?end erfolgte eine Narbenl?sung sowie Spaltung der Arkade, der Radiuskopf wurde im ursprünglichen verrenkten Zustand belassen. Eine v?llige Erholung des l?dierten Nerven war 9 Monate postoperativ erreicht.     

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.     

Responses of CDKs and p53 in Delayed Ischemic Neuronal Death

Stroke is a debilitating disease that affects millions each year.While in many cases cerebral ischemic in jury can be limited by effectivw resuscitation or thrombolytic treatment,the injured neurons wither in a process known as delayed neuronal death(DND).Mounting evidence indicates that DND is not simply necrosis played out in slow motion but apoptosis is triggered.Of particular interest are two groups of signal proteins that participate in apoptosis-cyclin dependent kinases(CDKs) and p53-among a myriad of signaling events after an ischemic insult.Recent investigations have shown that CDKs,a family of enzymes initially known for their role in cell cycle regulation,are activated in injured neurons in DND.As for p53,new reports suggest that its up-regulation may represent a failed attempt to rescue in jured neurons,although its up-regulation was previously considered an indication of apoptosis.These observations thus rekindle an old quest to identify new neuroprotective targets to minimize the stroke damage.In this review,the author will examine the evidence that indicates the participation of CDKs and p53 in DND and then introduce pre-clinical data to explore CDK inhibition as a potential neuroprotective target.Finally,using CDK inhibition as an example,this paper will discuss the pertinent criteria for a viable neuroprotective strategy for ischemic in jury.     

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.     

Effects of acute administration of d-amphetamine and haloperidol on procedural learning in man

The effects of an indirect dopamine-agonist, d-amphetamine, and a non-selective dopamine receptor antagonist, haloperidol, were investigated in normal male volunteers using a between-subjects double-blind design in a procedural learning task, thought mainly to involve unconscious/automatic learning. The results showed: (1) d-amphetamine facilitated response speed, whereas haloperidol inhibited it, in comparison to placebo; (2) the linear increase in procedural learning corresponded with pharmacological manipulation of degree of dopaminergic activity, i.e. subjects given haloperidol showed the least, and subjects given d-amphetamine the greatest, procedural learning. The implications of these findings are discussed in relation to investigation of abnormalities of procedural learning processes in schizophrenia. Received: 28 June 1996/Final version: 2 October 1996     

Experience of expandable metallic stents for central airway obstruction

The aim of this study was to investigate retrospectively the efficacy of expandable metallic stents (EMSs) for severe respiratory distress in patients with central airway obstruction. Twenty patients with central airway obstructions were treated with an EMS. An intraluminal stricture was present in 15 and an extraluminal stricture in 5 patients. Of the 15 patients with intraluminal stenosis, 11 exhibited symptomatic improvement. All 11 patients had tumor infiltration occupying less than 50% of the endoluminal diameter. The other four patients with intraluminal stenosis had tumor infiltration occupying > 50% of the endoluminal diameter and demonstrated no improvement. All five patients with extraluminal stenosis were improved. EMS is useful for an extraluminal stricture in the central airway and the effect of EMS for intraluminal stenosis is related to the degree of infiltration and of tumor progression itself.