Odorant responses of Xenopus laevis tadpole olfactory neurons: a comparison between preparations

We used a slice preparation of the olfactory epithelium of Xenopus laevis tadpoles to record odorant responses of olfactory receptor neurons (ORNs) and compared these to odorant responses recorded in isolated ORNs. The maximum recording time in the slice was considerably longer than in isolated ORNs, which is essential when many odorants are to be tested. No odorant-induced responses could be obtained from isolated ORNs recorded in the on-cell mode, while recordings in the slice (on-cell and whole-cell) as well as previously reported perforated-patch recordings in isolated ORNs of the same species () were successful, though qualitatively different. In the slice preparation, amino acids as well as an extract from Spirulina algae always induced excitatory responses, while, in a previous study on isolated ORNs, responses were either excitatory or inhibitory. The results of this study show that ORNs obtained using different preparation techniques can give markedly different responses upon the application of odorants. Our experiments indicate that the slice preparation combined with the on-cell configuration of the patch-clamp technique is the method of choice for testing many odorants on individual ORNs.     

Neurobiology of primate audio-vocal behavior

Audio-vocal behavior is an outstanding means of social communication among nonhuman primates and man. Neurobiological studies of this behavior contribute to a better understanding of communication processes in general and of the cerebral prerequisits for the evolution of language and speech in particular. In the first part of the review the cerebral system which generates, selects and controls species-specific vocal behavior is described in anatomical and physiological terms. Its structures and functions are organized in a hierarchical manner whereby the pericingular cortex and the periaqueductal gray are nodal areas in the system. In the second part auditory decoding mechanisms of vocal signals are discussed in terms of cortical ablation studies and response characteristics of single neurons along the auditory pathway. There are marked differences in the processing of natural calls at the collicular, medial geniculate and cortical levels. The cortex makes a necessary contribution to the decoding of complex sounds. References to the problem of lateralization of auditory function in non-human primates are made. A keystone for the understanding of communication processes in general lies in the question of how the signal producing motor system and the signal receiving decoding system is centrally tied together. One way to investigate such processes is to compare single unit responses along the auditory pathway during an animal's own phonation and during the playback of that vocalization. The results provide evidence for an internal feed-forward mechanism during phonation which influences parts of the auditory system.     

Beneficial effects of atorvastatin on myocardial regions with initially low vasodilatory capacity at various stages of coronary artery disease

Purpose The aim of this study was to analyse non-invasively the regional effect of therapy with an HMG-CoA reductase inhibitor on myocardial blood flow in patients with coronary artery disease (CAD) with special reference to segments with initially substantially impaired vasodilation.Methods The study included 26 patients with untreated hypercholesterolaemia. Coronary angiography revealed CAD in nine patients with stenosis >50% and wall irregularities or minimal stenosis <30% in 17 patients. Before and 4.6±1.8 months after atorvastatin therapy, ¹³N-ammonia positron emission tomography (PET) studies were performed at rest and under pharmacological stress. Minimum coronary vascular resistance (MCR) and coronary flow reserve (CFR) were determined. Segments were divided into those with normal or near-normal (MBF during adenosine 2.0 ml/min/g) and those with abnormal (MBF<2.0 ml/min/g) vasodilator flow response. In CAD patients, 156 segments were analysed, 85 of which had abnormal MBF; in the non-obstructive group, 59 of 297 segments had abnormal MBF.Results LDL cholesterol decreased after atorvastatin therapy from 186±43 mg/dl to 101±26 mg/dl (p<0.001). In normal segments no significant changes in MBF, CFR and MCR were found. However, initially abnormal segments showed significant improvements in MCR (15%, p<0.0001) and MBF during adenosine (30%, p<0.0001) after therapy.Conclusion The improvement in regional coronary vasodilator function after atorvastatin in patients with coronary atherosclerosis may be caused, at least in part, by increased flow-mediated (endothelium-dependent) dilation of the total arteriolar and arterial vascular system. These data further support the concept of non-invasive management of stable CAD by statin therapy and life-style modification guided by PET.P. Wielepp and D. Baller contributed equally to the study     

Overlapping induction of anesthesia: an analysis of benefits and costs

BACKGROUND: Overlapping induction (OI), i.e., induction of anesthesia with an additional team while the previous patient is still in the operating room (OR), was investigated. METHODS: The study period was 60 days in two followed by three ORs during surgical Block Time (7:30 am until 3:00 pm). Patients were admitted the day before surgery and were thus available and did not have surgery that day unless there was a time reduction. Facilities were already constructed. Number of cases, Nonsurgical Time (Skin Suture Finish until next Procedure Start Time), Turnover Time, and Anesthesia Control Time plus Turnover Time were studied. In addition, economic benefit was calculated. RESULTS: Three hundred thirty-five cases were studied. Using OI, the time of care of regularly scheduled cases was shortened, and the number of cases performed within OR Block Time increased (151 to 184 cases; P < 0.05). Nonsurgical Time (in h:min) decreased (1:08 +/- 0:26 to 0:57 +/- 0:18; P < 0.001), Turnover Time decreased (0:38 +/- 0:24 to 0:25 +/- 0:15; P < 0.05), and Anesthesia Control Time plus Turnover Time decreased (0:43 +/- 0:23 to 0:28 +/- 0:18; P < 0.001). Subgroup analysis showed a significant benefit of OI only in three ORs. In three ORs, economic benefit can be gained at a case mix index greater than 0.3 besides additional costs. CONCLUSIONS: Overlapping induction increased productivity and profit despite the expense of additional staff. Subgroup analysis emphasizes the importance of the number of ORs involved in OI.     

Current use of glucocorticoids in patients with rheumatoid arthritis in Germany

OBJECTIVE: To describe the current use of glucocorticoids in German patients with rheumatoid arthritis (RA). METHODS: We analyzed clinical and patient-derived data from 10,068 outpatients with RA from the national database of the German Collaborative Arthritis Centres for the year 2001 collected by more than 80 rheumatologists in hospitals and private practices. RESULTS: Systemic glucocorticoid therapy was prescribed for 60% of all patients with RA in rheumatologic care. The proportion of patients receiving systemic glucocorticoids in addition to disease-modifying antirheumatic drug (DMARD) therapy ranged from 53% to 81% of the patients for the various DMARDs. Glucocorticoid therapy was administered more often in combination with tumor necrosis factor inhibitors (81%), cyclosporin A (80%), or leflunomide (77%) than with more traditional DMARDs such as methotrexate (63%) or sulfasalazine (55%). Regarding the prevention and treatment of osteoporosis, 63% of patients taking systemic glucocorticoids were also receiving some type of osteoporosis therapy, as opposed to only 26% of those not taking glucocorticoids. CONCLUSION: Glucocorticoids play a pivotal role in the management of RA. This is reflected in the extensive use of low-dose glucocorticoids by German rheumatologists. Even if highly effective DMARDs are prescribed, they are accompanied by glucocorticoids, at least in the initial phase. High-dose glucocorticoids are prescribed for only a small proportion of the patients. There is increasing awareness of the risk of osteoporosis in long-term glucocorticoid treatment, demonstrated by the fact that osteoporosis medication is prescribed for a large proportion of patients taking glucocorticoids.     

The first missense alteration in the MCPH1 gene causes autosomal recessive microcephaly with an extremely mild cellular and clinical phenotype

Autosomal recessive primary microcephaly (MCPH) is a rare neurodevelopmental disorder characterized by mental retardation and congenital microcephaly with a head circumference at least 4 SD below age and sex means, in the absence of other significant malformations or neurological deficits. Truncating alterations in the MCPH1 gene have previously been shown to exhibit a distinct cellular phenotype, with a high proportion of prophase-like cells (>10%) due to premature chromosome condensation in early G2- and delayed decondensation in early G1-phase of the cell cycle. We report here the first patient with a homozygous substitution of a highly conserved threonine residue by an arginine (c.80C>G, Thr27Arg) localized in the N-terminal BRCT domain of MCPH1. The cellular and clinical phenotype of this patient is much less pronounced than that of previously described patients with truncating alterations in the MCPH1 gene. Firstly, the fraction of prophase-like cells accounts for just 3-4% of the cell population. Secondly, clinically, he has only a very mild mental retardation with predominantly delayed motor skills but normal verbal IQ attainment. Additionally, head circumference was less severely affected, being -2.4 SD at birth and -3 SD at the age of six years. This justifies reconsideration and widening of the clinical phenotype definition of MCPH1.     

Glucocorticoidtherapie im Wandel der Zeit

Ohne Zusammenfassung     

Suppression of kindled seizures by paracrine adenosine release from stem cell-derived brain implants

PURPOSE: Stem cells and their derivatives have emerged as a promising tool for cell-based drug delivery because of (a) their unique ability to differentiate into various somatic cell types, (b) the virtually unlimited donor source for transplantation, and (c) the advantage of being amenable to a wide spectrum of genetic manipulations. Previously, adenosine-releasing embryonic stem (ES) cells have been generated by disruption of both alleles of adenosine kinase (Adk-/-). Lack of ADK did not compromise the cells' differentiation potential into embryoid bodies or glial precursor cells. The aim of the present study was to investigate the potential of differentiated Adk-/- ES cell progeny for seizure suppression by paracrine adenosine release. METHODS: To isolate paracrine effects of stem cell-derived implants from effects caused by network integration, ES cell-derived embryoid bodies and glial precursor cells were encapsulated into semipermeable polymer membranes and grafted into the lateral brain ventricles of kindled rats. RESULTS: While seizure activity in kindled rats with wild-type Adk+/+ implants remained unaltered, rats with adenosine-releasing Adk-/- ES cell-derived implants displayed transient protection from convulsive seizures and a profound reduction of afterdischarge activity in EEG recordings. Long-term seizure suppression was precluded by limited viability of the encapsulated cells. CONCLUSIONS: We thereby provide a proof-of-principle that Adk-/- ES cell-derived brain implants can suppress seizure activity by a paracrine mode of action. Adk-deficient stem cells therefore represent a potential tool for the treatment of epileptic disorders.     

Fanconi anemia in a neonate with pancytopenia

We report the case of a newborn infant with Fanconi anemia with congenital thrombocytopenia and development of pancytopenia during the neonatal period. The boy showed no malformations characteristic for Fanconi anemia.