High concentrations of antibiotic obtained for a short time excel more long-standing lower levels in the therapy of gonorrhoea. Implications of an in vitro model

During recent decades there has been a controversial discussion if comparable plasma level profiles which are rather constant or those which show a high peak are more efficient for the cure of gonorrhoea. So far, investigations in this field were not based on the Grasso apparatus. Although the findings with cefotiam and ceftizoxime do not allow to formulate a general hypothesis without any restriction, it can be stated that on the basis of an identical area under the antibiotic level time curve, 'peak concentration' profiles are more favourable.     

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     

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.