Short-term application of ibuprofen before ovulation.

AIM OF THE STUDY: The aim was to analyse if ibuprofen, as a non-selective cyclooxygenase (COX) inhibitor, has any negative effect on oocyte competence and embryo quality. COX- inhibitors are popular over-the-counter analgesics. Whereas selective COX inhibitors have been shown to impair female fertility, data on non-selective COX inhibitors are poor. Hence, they have not been recommended for women trying to conceive. METHODS: This is an observational study comparing ibuprofen exposed and unexposed women from 18 to 42 years of age, using the model of natural cycle in vitro fertilisation (IVF) to determine oocyte and embryo quality. Follicular growth was monitored and if the follicle was mature (≥ 15mm size and estimated oestradiol level of ≥ 800pmol/l), ovulation was triggered. Women with luteinising hormone (LH) surge received 400mg ibuprofen every 8 hours to postpone ovulation, whereas women without LH surge received none (controls). Oocyte retrieval rate, oocyte maturity, fertilization rate, embryo development and embryo quality as well as implantation rate were analysed. RESULTS: Of the 111 women included, 63 received ibuprofen, and 48 did not. Rates of mature oocytes and implantation rate did not differ. Logistic regression showed no significant association of ibuprofen intake, LH- level or reason for infertility on embryo quality. CONCLUSION: Based on our results, we suggest that, particularly within natural cycle IVF, ibuprofen does no harm around ovulation as analgesic treatment.

A prospective study of mechanical physiotherapy for lumbar disk prolapse: five year follow-up and final report.

OBJECTIVES: To evaluate the long-term effect of a specific conservative treatment method for patients with lumbar disc prolapse. BACKGROUND DATA: Low back pain and symptoms of disc herniation have a good prognosis. Yet the rates of disability and sick-leave because of recurrences are high and cost-intensive. METHODS: Fifty consecutive patients with clinically and neuroradiologically confirmed lumbar disk prolapse, who responded to the first five daily physiotherapy sessions with pain centralization, were prospectively treated with mechanical physiotherapy with repeated end range spinal movements and leg movements. The results after one year of follow-up have been published previously (J Neurology 250 (2003), 746-749). RESULTS: From the initial cohort of 50 patients, 5 patients were operated within one year after discharge and one patient died. One patient had surgery for disc prolapse 13 months after discharge. Three patients were lost for follow-up. None of the 40 remaining patients has had surgery until the last follow-up. CONCLUSION: Pain centralization during the first 5 treatment sessions of mechanical physiotherapy is a useful diagnostic tool to predict a good longterm outcome. Mechanical physiotherapy with end range spinal movements and leg movements is an effective treatment strategy for many patients with lumbar disk disease.

Intensive coordinative training improves motor performance in degenerative cerebellar disease.

OBJECTIVES: The cerebellum is known to play a strong functional role in both motor control and motor learning. Hence, the benefit of physiotherapeutic training remains controversial for patients with cerebellar degeneration. In this study, we examined the effectiveness of a 4-week intensive coordinative training for 16 patients with progressive ataxia due to cerebellar degeneration (n = 10) or degeneration of afferent pathways (n = 6). METHODS: Effects were assessed by clinical ataxia rating scales, individual goal attainment scores, and quantitative movement analysis. Four assessments were performed: 8 weeks before, immediately before, directly after, and 8 weeks after training. To control for variability in disease progression, we used an intraindividual control design, where performance changes with and without training were compared. RESULTS: Significant improvements in motor performance and reduction of ataxia symptoms were observed in clinical scores after training and were sustained at follow-up assessment. Patients with predominant cerebellar ataxia revealed more distinct improvement than patients with afferent ataxia in several aspects of gait like velocity, lateral sway, and intralimb coordination. Consistently, in patients with cerebellar but without afferent ataxia, the regulation of balance in static and dynamic balance tasks improved significantly. CONCLUSION: In patients with cerebellar ataxia, coordinative training improves motor performance and reduces ataxia symptoms, enabling them to achieve personally meaningful goals in everyday life. Training effects were more distinct for patients whose afferent pathways were not affected. For both groups, continuous training seems crucial for stabilizing improvements and should become standard of care. LEVEL OF EVIDENCE: This study provides Class III evidence that coordinative training improves motor performance and reduces ataxia symptoms in patients with progressive cerebellar ataxia.

Compensation of muscarinic bronchial effects of talsaclidine by concomitant sympathetic activation in guinea pigs.

The aim of the present investigation was to determine the reasons why the muscarinic receptor agonist talsaclidine (WAL 2014 FU, 1-azabicyclo[2.2.2] octane,3-(2-propynyloxy)-, (R)-,(E)-2-butenedioate) is devoid of bronchospastic effects in anaesthetized guinea pigs but causes contracture in isolated tracheal muscle from this species. Effects on airway resistance were assessed with a modified Konzett-Rossler method in guinea pigs anaesthetized with urethane. Intravenous injection of 1-64 mg/kg talsaclidine did not cause substantial bronchospasm in control animals. After blockade of beta-adrenoceptors, the muscarinic receptor agonist induced dose-dependent bronchospasm which could be blocked by atropine. In despinalized animals and in animals with spinal transection, talsaclidine was bronchospastic but ED50 values were higher and maximal effects were smaller than in intact animals after beta-adrenoceptor blockade. In adrenalectomized guinea pigs, talsaclidine was nearly as bronchospastic as after blockade of beta-adrenoceptors. In contrast, the muscarinic ganglion stimulant McN-A-343, 4-(m-chlorophenylcarbamoyloxy)-2-butyn-trimethyl-ammonium chloride, (2-32 mg/kg i.v.), which has a muscarinic receptor profile similar to that of talsaclidine, i.e., full muscarinic agonism and highest affinity at muscarinic M1 receptors, partial agonism at muscarinic M3 receptors, but in contrast to talsaclidine does not penetrate the blood-brain barrier, caused dose-dependent bronchospasm in control animals. These results indicate that talsaclidine has bronchospastic potential which, however, does not become evident in vivo because of functional antagonism via beta-adrenoceptors resulting from concomitant activation of the sympathetic nervous system in general and the adrenals in particular. It can be concluded that the unique profile of action of talsaclidine is due to partial agonism at bronchial muscarinic M3 receptors, a prerequisite for susceptibility to functional antagonism, and to its ability to penetrate the blood-brain barrier readily and to induce sympathetic activation as a result of full agonism at peripheral ganglionic and adrenal as well as central muscarinic M1 receptors.

In vivo consequences of M1-receptor activation by talsaclidine.

The aim of this investigation in anaesthetized dogs was to provide direct evidence for an activation of the sympathetic nervous system by the muscarinic agonist talsaclidine (WAL 2014 FU). Intravenous infusion at a rate of 1 mg/kg/min increased plasma catecholamines and in particular epinephrine, thus indicating a predominant stimulation of the adrenals. Sympathetic activation was also indicated by increases in renal vascular resistance, an effect which was sensitive to alpha-adrenolysis. It is concluded that the sympathetic activation by talsaclidine is due to full agonism at the M1-receptor and the ability to cross the blood-brain barrier. As talsaclidine is less potent and only a partial agonist at M2- and M3-receptors many peripheral actions mediated by these receptor subtypes are functionally antagonized by the concomitant sympathetic activation.

Validity of western immunoblot band patterns in the serodiagnosis of Lyme borreliosis.

Serodiagnosis of Lyme disease is hampered by low specificity of the standard assays currently used. The Western immunoblot has therefore been proposed as a potential confirmatory test. For the present report, the method was evaluated by testing sera from patients with clinically defined early- and late-stage borreliosis. In early-stage borreliosis, the 41,000-molecular-weight flagellin protein (41K) of Borrelia burgdorferi was the major antigen detected by antibodies in sera, but the specificity of the reaction pattern was dependent on the intensity of the band. The evaluation of different interpretation rules based on a semiquantitative record of band intensities showed the highest specificity (96%) and a corresponding sensitivity of 78% if there was at least one distinct (optical density range, 0.2 to 0.4) immunoglobulin G and immunoglobulin M reaction with the 41K band. Blots of B. burgdorferi proteins were also probed with sera from patients who were diagnosed by clinical criteria as having stage III Lyme borreliosis and with a control group of sera from asymptomatic persons with positive antibody titers against B. burgdorferi in the standard assays. Reaction patterns were recorded densitometrically. Statistical analysis and graphical marker analysis revealed significant discriminating capacities and relatively high specificities, respectively, for the 94K, 30K, and 21K bands, whereas the 41K and 60K bands were not discriminative between the symptomatic and asymptomatic groups and were specific only at high intensity values. Different multiple-band rules were evaluated, revealing a low specificity for positivity definitions of the type "four or five bands present" if the rules were not confined to known major bands.