Direct conversion from tramadol to tapentadol prolonged release for moderate to severe, chronic malignant tumour-related pain.

BACKGROUND: A recent randomized-withdrawal, active- and placebo-controlled, double-blind phase 3 study showed that tapentadol prolonged release (PR) was effective and well tolerated for managing moderate to severe, chronic malignant tumour-related pain in patients who were opioid naive or dissatisfied with current treatment (Pain Physician, 2014, 17, 329-343). This post hoc, subgroup analysis evaluated the efficacy and tolerability of tapentadol PR in patients who previously received and were dissatisfied with tramadol for any reason and who had a pain intensity ≥5 (11-point numerical rating scale) before converting directly to tapentadol PR. METHODS: In the original study, eligible patients had been randomized (2:1) and titrated to their optimal dose of tapentadol PR (100-250 mg bid) or morphine sulphate-controlled release (40-100 mg bid) over 2 weeks. The present report focuses on results during the titration period for a subgroup of patients randomized to tapentadol PR after having been on tramadol treatment prior to randomization in the study (n = 129). Results for this subgroup are compared with results for all 338 patients who received tapentadol PR during titration (overall tapentadol PR group). RESULTS: Responder rates (responders: completed titration, mean pain intensity <5 [0-10 scale] and ≤20 mg/day rescue medication during last 3 days) were slightly better for the tramadol/tapentadol PR subgroup (69.8% [90/129]) vs. the overall tapentadol PR group (63.9% [214/335]). Tolerability profiles were comparable for both groups. CONCLUSIONS: Results of this subgroup analysis indicate that patients with cancer pain could safely switch from prior treatment with the weak centrally acting analgesic tramadol directly to the strong centrally acting analgesic tapentadol PR, for an improved analgesic therapy for severe pain. WHAT DOES THIS STUDY ADD?: Results of this post hoc analysis show that patients who had received prior tramadol therapy could switch directly to tapentadol PR, with the majority (˜70%) experiencing improved efficacy.

Implant-supported anterior tooth restoration.

Various options are available for restoring anterior teeth. Their choice is dictated by the severity of infection of the teeth to be extracted and the pocket depth. Immediate single-stage implant placement proved to be the least traumatic option, which best preserved the soft tissue. A differential use of surgical and prosthodontic techniques is indispensable to account for conditions in the individual case. Given an adequate amount of hard tissue, soft tissue contours can be expected to return to normal. Immediate implants combined with a soft tissue support have been found to ensure that the depth of even larger pockets is stable for years.

Indoor environment and respiratory symptoms in children living in the Dutch-German borderland.

OBJECTIVE: To investigate the relation between indoor environmental risk factors and respiratory symptoms in 7-8-year-old children living in the Dutch-German borderland. METHODS: A nested case-control study was conducted among children participating in a large longitudinal study on respiratory health. Parents of all 781 children with respiratory complaints and an equal number of randomly selected controls were asked to complete a questionnaire, including questions on indoor environment. RESULTS: The parents of 1191 children (76.2%) participated. Past exposure to environmental (OR = 2.73, 95% CI 1.14-6.67) as well as in utero exposure (OR = 2.28, 95% CI 1.15-4.53) to tobacco smoke, use of an unvented geyser for water heating (OR = 3.01, 95% CI 1.21-7.56), long-term exposure to dampness (OR = 2.98, 95% CI 1.10-8.28) or pets (OR = 2.18, 95% CI 1.39-3.42) increased the risk of asthmatic symptoms in 7-8-year-old children. A middle or low socio-economic status also increased the risk of asthmatic symptoms. An inverse association with asthmatic symptoms was seen for wall-to-wall carpeting (OR = 0.57, 95% CI 0.33-0.95) and insulation measures (OR = 0.46, 95% CI 0.25-0.83). Except for the presence of an unvented geyser, these environmental risk factors also presented a risk for coughing symptoms in children. CONCLUSION: This study showed an increased risk of respiratory symptoms in children exposed to several indoor environmental risk factors.

[Interreg II--European regional study of chronic respiratory tract diseases in children in the Germany-Netherlands border zone]. / Interreg II--Euregionale Untersuchungen zu chronischen Atemwegserkrankungen bei Kindern im deutsch-niederländischen Grenzraum.

AIM OF THE STUDY: In Westelijke Mijnstreek (WM), Midden-Limburg (ML), both The Netherlands, and Kreis Heinsberg (HS), Germany, the relationship between quality of the indoor environment and respiratory symptoms in children was studied, finally resulting in proposals for prevention of respiratory symptoms in the three regions. This paper presents the results of the first part of the study, investigating prevalences of respiratory complaints. METHODS AND RESULTS: A brief questionnaire was used to document prevalences of respiratory complaints, physicians diagnoses and treatment in about 7,000 children 5-6 resp. 7-8 years of age from HS, ML and WM, in 1995 and 1997. Prevalences of respiratory symptoms differed slightly between the regions, but there were differences in physician-diagnosed asthma and bronchitis and treatment of the children. PERSPECTIVES: The brief questionnaire is a useful instrument to get an overview on respiratory symptoms. Since 1995, it is used by several German Municipal Health Services for Public Health Reports.

Value of acoustic rhinometry in environmental medicine.

It is a weak point of environmental medicine that health disturbances, e.g. functional affections of the upper respiratory tract, cannot be objectively judged by physicians resp. researchers. In this study, the validity of acoustic rhinometry, a method giving information on cross-sectional areas of the upper airways by means of ultrasound probing, was tested in 40 volunteers seven times during one year. Furthermore, using a simplified model of the nose the accuracy of this method to measure the minimal cross-sectional area (MCA) in the nose was tested. The measurements were extremely confounded by the mode of connection to the nose (e.g. selected adapter, direction of application) and by the MCA in the nasal cavity. Statistical analyses showed a good reproducibility of measurements repeated within minutes, but suggested an intrapersonal variability over the analyzed examination phases due to apparatus independent factors. However, this variability could not be explained by influencing and confounding factors obtained by questionnaire, medical history, and physical examination. The test model showed little to great errors (1.5 to 568.5%) between the actual and the measured MCA, depending on the diameter. It is concluded that the method of acoustic rhinometry has to be standardized before it's value for environmental medicine can finally be judged. Further studies are necessary that should focus among others on factors influencing the variability of MCA and the effect of MCA on the measurement of the area behind the MCA. So far, the use of acoustic rhinometry for the evaluation of nasal function cannot be recommended.

Sema3C and netrin-1 differentially affect axon growth in the hippocampal formation.

The interaction between outgrowing neurons and their targets is a central element in the development of the afferent and efferent connections of the hippocampal system. This requires that axonal growth cones recognize specific guidance cues in the appropriate target area. At present, little is known about the mechanisms that determine the lamina-specific termination of hippocampal afferents. In order to understand the role of different guidance factors, we analyzed the effects of Sema3C and Netrin-1 on explants from the entorhinal cortex, dentate gyrus, cornu ammonis regions CA1 and CA3 and medial septum in a collagen coculture assay. Our observations suggest that both semaphorins and netrin play important roles in the neuron-target interactions in the hippocampal system. Sema3C is involved in the control of the ingrowth of the septohippocampal projection. We also show that netrin-1 is involved in attracting commissural neurons from dentate gyrus/hilus and CA3 to their target area in the contralateral hippocampus.

Semaphorin D acts as a repulsive factor for entorhinal and hippocampal neurons.

We analysed the effects of semaphorin D on axons from the developing rat entorhinal-hippocampal formation. Explants from superficial layers of the entorhinal cortex and of the hippocampus anlage were obtained from various developmental stages and co-cultured with cell aggregates expressing semaphorin D. Neurites extending from entorhinal explants that had been isolated from early embryonic stages (E16 and E17) were not affected by semaphorin D, but were repelled at later stages (E20 and E21). Axons from hippocampal neurons explanted at E21 were also repelled by semaphorin D. In situ hybridization studies revealed expression of the semaphorin D receptor neuropilin-1 in the entorhinal cortex from stage E17 to stage P7, and in the dentate gyrus and CA1-3 regions between E17 and adulthood. These data suggest that semaphorin D is involved in the formation of the perforant pathway and acts, via the neuropilin-1 receptor, as a repulsive signal that prevents entorhinal fibres from growing into the granular layer of the dentate gyrus. These data also suggest a role for semaphorin D in the development of intrahippocampal connections.

Inner room-questionnaire for the German-speaking area.

The sick building syndrome (SBS) is well known in Germany, too. Because reliable objective data are missing questionnaires are essential in investigations of SBS. Internationally, different questionnaires are used which often lack thorough validation. Therefore, aim of this study was to combine the development of a questionnaire and the analysis of its sensitivity and reliability. For proofing sensitivity, 40 volunteers kept a Symptom Diary for one week and, for comparison, answered the questionnaire in the following week seven times during one year. For testing reliability, 60 volunteers filled in the questionnaire on Monday and on Friday of the same week. Agreement was tested by statistical measure kappa (kappa). The sensitivity test showed that details obtained by diary occurred less pronounced but similarly distributed in the questionnaire. The reliability test showed stable socio-demographic and work-related variables. Among the symptoms, eye troubles (kappa = 0.88), skin troubles in the face (kappa = 0.77) and on the hands (kappa = 0.75) were stable. Among the indoor complaints unpleasant odors (kappa = 0.68), sounds (kappa = 0.72), bright lighting (kappa = 0.85), and dust (kappa = 0.86) were stable. Our questionnaire recorded principally plausibly indoor complaints and well-being disturbances. A definite judgement of the questionnaire can only be made after its application to a SBS-affected group. Nevertheless, our questionnaire can be introduced into the process of developing a standardised international SBS-questionnaire. Moreover, our results indicate that events asked by questionnaire over a retrospective period of more than one week should be interpreted with caution.

Toe agnosia in Gerstmann syndrome.

The following case report presents a patient exhibiting Gerstmann syndrome accompanied by toe agnosia. A 72 year old right handed woman had a focal lesion in the angular gyrus of the left hemisphere which was caused by a glioblastoma multiforme. The first symptom she had complained of was severe headache. Standardised neuropsychological tests of intelligence, memory, attention, fluency, apraxia, and language functions as well as tests for the assessment of agraphia, acalculia, right-left disorientation, and digit agnosia were performed. The patient displayed all four symptoms of the Gerstmann syndrome--namely, agraphia, acalculia, right-left disorientation, and finger agnosia. The patient did not display aphasia, constructional apraxia, or any other neuropsychological impairment. In addition to the four symptoms of the Gerstmann syndrome an agnosia of the toes was found. Further studies should determine whether finger agnosia in Gerstmann syndrome is usually accompanied by toe agnosia. Finger agnosia in the context of this syndrome may be better named digit agnosia.

Subjective time estimation in Parkinson's disease.

Patients with idiopathic Parkinson's disease and control subjects were given two types of time estimation task. In the verbal estimation task subjects were required to judge the duration of time intervals of 10, 30 and 60 seconds, signalled by the examiner. Operative estimation required subjects to indicate when intervals of 10, 30 and 60 seconds had passed. Parkinsonian patients off L-Dopa medication were less accurate than control subjects in both tasks. They underestimated the time intervals determined by the examiner in the verbal estimation task, while in the operative estimation task parkinsonian subjects overestimated the required time intervals compared with controls. The administration of L-Dopa to the parkinsonian patients led to time judgements that were similar to those of control subjects. The present findings lend support to the hypothesis of the role of dopamine in the modulation of the internal clock.

[The effect of indomethacin and dexamethasone on the excretion of epinephrine, levarterenol and dopamine in the urine of rats with adjuvant arthritis]. / Einfluss von Indometacin bzw. Dexamethason auf die Ausscheidung von Epinephrin, Levarterenol und Dopamin im Urin von Ratten mit Adjuvansarthritis.

The repeated application of indometacine or dexamethasone on rats with adjuvant arthritis results in a most cases significant inhibition of the arthritis in the primary and secondary phase as well as in a normalisation of the increased urinary excretion of epinephrine and norepinephrine of untreated arthritis rats. The dopamine excretion of adjuvant arthritis rats was also higher then the prepared rats. We suppose, that the results show the regulative endogenous excretion of epinephrine and norepinephrine in inflammatory processes. Consequently these drugs have essentially antiinflammatory activities. The inhibition of the inflammation is than connected with the normalisation of the excretion of catecholamines.

Inhibition by vitamin D pretreatment of ATP-induced vasoconstriction in rats.

In the isolated perfused hind legs of rats, ATP-Na2 injections induce an increase of perfusion pressure. Maximum pressure increase, EAm, is comparable to maximum increase induced by norepinephrine or vasopressin. In vitamin D2-pretreated rats, ATP-Na2-induced pressure increase is strikingly decreased as it is the case when using norepinephrine or vasopressin as vasoconstrictors. Vasodepression seems to be due to unspecific impairment by vitamin D2 of contractile elements of the vessel wall.

[Fluorometric determination of levarterenol, epinephrine and dopamine in the urine of rats with carrageenan edema and adjuvant arthritis]. / Fluorimetrische Bestimmung von Levarterenol, Epinephrin und Dopamin im Urin von Ratten mit Carrageeninödem und Adjuvansarthritis.

After adsorption-chromatographic separation (using aluminium oxide) and chemical conversion to the corresponding trihydroxyindole derivatives, epinephrine, levarterenol and dopamine were determined fluorometrically in urine from rats. In case of carrageenin oedema, as well as during the secondary phase of adjuvant arthritis, the excretion of epinephrine and levarterenol was increased as compared to that in control animals. This difference was statistically significant. These findings can possibly be connected with an inhibitory activity of the catecholamines in inflammatory processes; as to dopamine, it seems to be of minor importance.