[Rare diseases in anesthesia : Knowledge mining and core points of perioperative anesthesiological care]. / Seltene Erkrankungen in der Anästhesie : Wissensbeschaffung und Kernpunkte der perioperativen anästhesiologischen Versorgung.

Due to refined and new diagnostic possibilities and improved medical care, in the future anesthesiologists will be more frequently confronted with patients suffering from rare diseases. As the physicians providing perioperative care often have little or no experience with the diseases of such patients, the access to high-quality specific literature is essential. In this respect they must be able to assess and classify the quality of the information which is predominantly available online, especially as when evidence-based knowledge is available, it is only available to a very limited extent. Patients with rare diseases mostly present with recurring problem constellations. A systematic assignment to the most important problem areas (airway, circulation, metabolism, etc.) as well as a structured and interdisciplinary approach are decisive for a successful perioperative treatment of these patients. Due to low prevalence, lack of personal experience and lack of evidence-based data, anesthesia in patients with SE is an absolute challenge, especially in time-critical situations.

[Anesthesia for patients suffering from neuromuscular diseases]. / Anästhesie bei neuromuskulären Erkrankungen.

Neuromuscular diseases (NMD) are a heterogeneous group of motor unit disorders. Common to all is the main clinical symptom of muscle weakness. Depending on entity and phenotype, a broad range of disorders of neuronal, junctional or myocytic structures occurs. In addition to a weakness of the skeletal musculature, NMD can also affect throat musculature, respiratory and heart muscles. The possible consequences are immobility, deformities, tendency to aspiration as well as respiratory and cardiac insufficiency. In the context of surgery and anesthesia, complications that can result from the underlying disease and its interaction with anesthesia must be anticipated and averted. This article describes along the treatment pathway how preoperative evaluation, choice of the anesthetic procedure and postoperative care can be effectively and safely tailored to the needs of patients with NMD. Concise and practical recommendations for carrying out anesthesia for the most important NMDs are presented as well as relevant external sources of practice recommendations.

Precision and accuracy of a new device (CNAPTM) for continuous non-invasive arterial pressure monitoring: assessment during general anaesthesia.

BACKGROUND: Continuous non-invasive arterial pressure measured with CNAP (CNAP) has been shown to be superior to intermittent oscillometric measurements during procedural sedation and spinal anaesthesia. We assessed the performance of CNAP during general anaesthesia by analysis of agreement with invasive measurements of arterial pressure (AP). METHODS: Eighty-eight patients undergoing elective abdominal surgery, cardio-, or neurosurgery were included in the study. Systolic, diastolic, and mean AP measured by an intra-arterial catheter in the radial artery (IAP) were compared with those obtained by CNAP from the same arm. Data were analysed to determine the precision (i.e. measurement error) and accuracy (i.e. systematic error) of beat-to-beat CNAP values with respect to IAP. Also, we compared the frequency of fast changes in AP (FCAP) and hypotension (IOH) by both methods. RESULTS: CNAP precision of 4.5, 3.1, and 3.2 mm Hg (systolic, diastolic, and mean AP, respectively) was not significantly different from IAP precision, and CNAP accuracy was +6.7, -5.6, and -1.6 mm Hg. The frequency of AP pairs having a difference within the calculated limits of agreement was 81%, 64%, and 76% for systolic, diastolic, and mean AP, respectively. The calculated limits of agreement were +/-17.6, +/-11.4, and +/-12.0 mm, Hg, respectively. CNAP and IAP detected simultaneously to 82.1% FCAP and to 84.6% IOH. CONCLUSIONS: CNAP provides real-time estimates of arterial pressure comparable with those generated by an invasive intra-arterial catheter system during general anaesthesia.

Isolation and characterization of new MIKC*-Type MADS-box genes from the moss Physcomitrella patens.

MADS-box genes encode for a large family of transcription-regulating proteins, which were isolated from all groups of eukaryotic organisms. The plant-specific MIKC-type MADS-box genes have been intensively analyzed for their roles in controlling developmental processes. Well-known are the MADS-box genes acting as homeotic selector genes in the differentiation of whorls of floral organs in seed plants. The MADS-box gene family has also been studied in non-flowering plants, such as lycophytes, pteridophytes, and bryophytes. The analysis of MADS-box genes in the moss Physcomitrella patens led to the identification of a new class of MIKC-type genes, designated as MIKC*-type genes. The MIKC*-type genes possess a number of structural features which clearly distinguish them from the already known MIKC-type genes. Recently, orthologues of the Physcomitrella MIKC*-type genes were found in Arabidopsis thaliana, demonstrating the conservation of these genes in tracheophytes. Here, we report the isolation of two new MIKC*-type MADS-box genes from Physcomitrella. Structural features and expression patterns of these genes were analyzed. The contribution of our findings to a better understanding of the evolution of MIKC*-type genes in land plants is discussed.

Rocuronium for muscle relaxation in two children with Friedreich's ataxia.

Friedreich's ataxia is a rare hereditary neurodegenerative disease caused by a defect in the gene that encodes a mitochondrial protein called frataxin. We report the use of rocuronium 0.6 mg kg(-1) in two adolescent girls with Friedreich's ataxia undergoing propofol-sufentanil-oxygen-air anaesthesia for spinal surgery. Neuromuscular transmission was monitored using acceleromyography, and onset and recovery times were recorded. The clinical duration of rocuronium was comparable to that of children without neuromuscular disease (25% recovery T(1)=44 and 24 min for patients 1 and 2 respectively).

Identification of the human P450 enzymes involved in the in vitro metabolism of the synthetic steroidal hormones Org 4060 and Org 30659.

1. The type of human P450 enzymes involved in the in vitro metabolism of Org 4060 and Org 30659, two synthetic steroidal hormones currently under clinical development by NV Organon for use in oral contraceptive and hormone replacement therapy, was investigated. 2. Both steroids were mainly hydroxylated at the 6beta-position in incubations with human liver microsomes. 3. The results from experiments with supersomes, correlation studies as well as inhibition studies with ketoconazole, a selective inhibitor of CYP3A, strongly suggest that the CYP3A family plays a significant role in the 6beta-hydroxylation of both steroids. 4. Measurements of kinetic parameters of P450 enzymes that could metabolize both steroids, combined with the fact that CYP3A4 is known to be the most abundant P450 enzyme in the human liver, indicate that CYP3A4 will be of major importance for the in vivo human metabolism of Org 4060 and Org 30659.

Characterization of three GLOBOSA-like MADS-box genes from maize: evidence for ancient paralogy in one class of floral homeotic B-function genes of grasses.

Floral homeotic B-function genes are involved in specifying the identity of petals and stamens during flower development in higher eudicotyledonous plants. Monocotyledonous plants belonging to the grass family (Poaceae) have very similar B-function genes, except that these genes specify lodicules rather than petals. All B-function genes known so far are members of the MADS-box gene family encoding transcription factors. In some eudicot model systems such as Arabidopsis and Antirrhinum, the B-function is provided by heterodimeric protein complexes encoded by one DEF- and one GLO-like gene. In several different lineages of flowering plant species, however, more than one DEF- or GLO-like gene is found. A known example is the monocot model system rice, which contains two GLO-like genes, termed OSMADS2 and OSMADS4. Duplications of floral homeotic genes may have played a critical role in the diversification of floral homeotic functions and thus the evolution of flowers. In order to date the gene duplication event that gave rise to these two genes, we cloned cDNAs of three different GLO-like genes from maize, a distant relative of rice within the Poaceae family. Phylogeny reconstructions and chromosomal mapping indicate that one of these genes, named ZMM16, is orthologous to OSMADS2, and that the other two, ZMM18 and ZMM29, are probably orthologous to OSMADS4. The gene duplication which gave rise to OSMADS2- and OSMADS4-like genes occurred probably after the split of the lineages that resulted in extant Liliaceae and Poaceae, but before the separation of the lineages that gave rise to extant maize and rice about 50 MYA. Northern and in situ hybridization studies demonstrated that the maize genes are expressed in lodicules, stamens and carpels throughout spikelet development in male and female inflorescences. The GLO-like genes from rice have very similar patterns of mRNA accumulation. In addition, ZMM16 shows also weak expression in vegetative organs. Conservation of the expression in lodicules and stamens is in perfect agreement with a floral homeotic B-function of the GLO-like genes in grasses. The conserved expression in carpels is discussed. Moreover, circumstantial evidence for a functional diversification of GLO-like genes in grasses is provided.

A short history of MADS-box genes in plants.

Evolutionary developmental genetics (evodevotics) is a novel scientific endeavor which assumes that changes in developmental control genes are a major aspect of evolutionary changes in morphology. Understanding the phylogeny of developmental control genes may thus help us to understand the evolution of plant and animal form. The principles of evodevotics are exemplified by outlining the role of MADS-box genes in the evolution of plant reproductive structures. In extant eudicotyledonous flowering plants, MADS-box genes act as homeotic selector genes determining floral organ identity and as floral meristem identity genes. By reviewing current knowledge about MADS-box genes in ferns, gymnosperms and different types of angiosperms, we demonstrate that the phylogeny of MADS-box genes was strongly correlated with the origin and evolution of plant reproductive structures such as ovules and flowers. It seems likely, therefore, that changes in MADS-box gene structure, expression and function have been a major cause for innovations in reproductive development during land plant evolution, such as seed, flower and fruit formation.

Postural dependency of the cerebral venous outflow.

We have shown that predominance of the jugular veins in cerebrovenous drainage is limited to the supine position. In the erect position, the vertebral venous system represents the major outflow pathway.

Pharmacotherapeutic strategies for disease-modifying antirheumatic drug (DMARD) combinations to treat rheumatoid arthritis (RA).

OBJECTIVE: To provide a rational model for the use of disease-modifying antirheumatic drug (DMARD) combinations in the treatment of rheumatoid arthritis. METHODS: The DMARDs used today were examined for their mechanisms of action, kinetics, and toxicity, and collected into tabular formats for easier comparison. From these tables, matrices of potential positive or negative interfaces among combinations were constructed. Finally, these matrices were used to examine the usefulness of DMARD combinations by comparing them with published data. RESULTS: When clearly overlapping cells were found with respect to mechanisms of action, kinetics, or toxicity (e.g., methotrexate [MTX] plus azathioprine or MTX plus auranofin) predictions were good. When knowledge in these areas of kinetics and/or mechanisms of action were inadequate, predictions and results were not always consonant (e.g. MTX plus sulfasalazine; D-penicillamine plus hydroxychloroquine). CONCLUSIONS: The approach demonstrated in this paper toward rational combination therapy is logical and can be successful, although its success is circumscribed by our knowledge about the drugs we use. The rational approach to combination therapy demonstrated in this article can: 1) help prevent the use of combinations unlikely to be effective; 2) can point toward directions for useful research; and 3) can even be used when physicians are faced with patients whose needs have exceeded our present scientific knowledge.

Blood flow velocities in the vertebral veins of healthy subjects: a duplex sonographic study.

Along with the jugular veins, the vertebral veins serve as an important pathway for venous blood returning from the brain. In this study, the authors report duplex sonographic findings in 138 healthy subjects without central nervous disease. Successful insonation was possible in 70.7% of all examined vessels. Bilateral insonation was achieved in 86 subjects (62.3%). Only 1 vertebral vein was detected in 23 persons (16.7%), whereas no vein was found in 29 persons (21%). The authors observed a marked variation of peak flow velocities ranged (5-81 cm/s, mean +/- standard deviation, 23.9 +/- 12.3 cm/s). No significant gender-related or side-to-side differences or age influences on flow velocities were detected. The authors' findings may be of relevance when discussing flow velocities in the vertebral veins in cases of cerebrovenous disorders (e.g., dural sinus thrombosis) or in patients after neck dissection.

MADS-box genes reveal that gnetophytes are more closely related to conifers than to flowering plants.

The evolutionary origin of the angiosperms (flowering plants sensu stricto) is still enigmatic. Answers to the question of angiosperm origins are intimately connected to the identification of their sister group among extinct and extant taxa. Most phylogenetic analyses based on morphological data agree that among the groups of extant seed plants, the gnetophytes are the sister group of the angiosperms. According to this view, angiosperms and gnetophytes are the only extant members of a clade called "anthophytes" to emphasize their shared possession of flower-like reproductive structures. However, most phylogeny reconstructions based on molecular data so far did not support an anthophyte clade, but also could not clarify the case because support for alternative groupings has been weak or controversial. We have isolated 13 different homologs of MADS-type floral homeotic genes from the gnetophyte Gnetum gnemon. Five of these genes fall into monophyletic gene clades also comprising putatively orthologous genes from flowering plants and conifers, among them orthologs of floral homeotic B and C function genes. Within these clades the Gnetum genes always form distinct subclades together with the respective conifer genes, to the exclusion of the angiosperm genes. This provides strong molecular evidence for a sister-group relationship between gnetophytes and conifers, which is in contradiction to widely accepted interpretations of morphological data for almost a century. Our phylogeny reconstructions and the outcome of expression studies suggest that complex features such as flower-like reproductive structures and double-fertilization arose independently in gnetophytes and angiosperms.

Modulation of transcription factor NF-kappaB by enantiomers of the nonsteroidal drug ibuprofen.

1. The nonsteroidal drug ibuprofen exists as an R(-)- and S(+)-enantiomer. Only the S(+)-enantiomer is an effective cyclo-oxygenase inhibitor, while the R(-)-enantiomer is inactive in this respect. Thus the molecular mechanism by which R(-)-ibuprofen exerts its anti-inflammatory and antinociceptive effects remains unknown. 2. In this study the effects of the enantiomers of ibuprofen on modulation of transcription factors have been examined with electrophoretic mobility-shift assay (EMSA), transient transfection experiments, confocal immunofluorescence and nuclear import experiments, to determine their selectivity and potency as inhibitors of the activation of transcription factor nuclear factor-kappaB (NF-kappaB). 3. R(-)-ibuprofen (IC50: 121.8 microM) as well as the S(+)-enantiomer (IC50: 61.7 microM) inhibited the activation of NF-kappaB in response to T-cell stimulation. The effect of ibuprofen was specific because, at concentrations up to 10 mM, ibuprofen did not affect the heat shock transcription factor (HSF) and the activation of NF-kappaB by prostaglandin E2 (PGE2). Very high concentrations of ibuprofen (20 mM) did not prevent NF-kappaB binding to DNA in vitro. Immunofluorescence and nuclear import experiments indicate that the site of ibuprofen action appeared to be upstream of the dissociation of the NF-kappaB-IkappaB-complex. 4. Our data raise the possibility that R(-)-ibuprofen exerts some of its effects by inhibition of NF-kappaB activation.

Floral homeotic genes were recruited from homologous MADS-box genes preexisting in the common ancestor of ferns and seed plants.

Flowers sensu lato are short, specialized axes bearing closely aggregated sporophylls. They are typical for seed plants (spermatophytes) and are prominent in flowering plants sensu stricto (angiosperms), where they often comprise an attractive perianth. There is evidence that spermatophytes evolved from gymnosperm-like plants with a fern-like mode of reproduction called progymnosperms. It seems plausible, therefore, that the stamens/carpels and pollen sacs/nucelli of spermatophytes are homologous to fern sporophylls and sporangia, respectively. However, the exact mode and molecular basis of early seed and flower evolution is not yet known. Comparing flower developmental control genes to their homologs from lower plants that do not flower may help to clarify the issue. We have isolated and characterized MADS-box genes expressed in gametophytes and sporophytes of the fern Ceratopteris. The data indicate that at least two different MADS-box genes homologous to floral homeotic genes existed in the last common ancestor of contemporary vascular plants, some descendants of which underwent multiple duplications and diversifications and were recruited into novel developmental networks during the evolution of floral organs.