[Recurrent intracerebral haemorrhage in a 24-year-old female patient]. / Rezidivierende intrazerebrale Blutungen bei einer 24-jährigen Patientin.

A 24-year-old female patient from Sierra Leone was referred to the authors' hospital after several unclear intracerebral bleeding events and an echogenic structure on the aortic valve. The patient was receiving oral anticoagulation therapy due to paroxysmal atrial fibrillation and left ventricular noncompaction. Fluorescence in situ hybridization in combination with polymerase chain reaction and sequencing revealed infective endocarditis of the mitral and aortic valve caused by Bartonella quintana. In retrospect, the intracerebral bleeding events could be identified as septic emboli with secondary haemorrhagic transformation under anticoagulation therapy. The patient showed significant clinical improvement and no further bleeding events occurred after receiving biological mitral and aortic valve replacement and several weeks of doxycycline and gentamicin antibiotic therapy.

[Comparison of piezoelectric and conventional osteotomy in rhinoplasty : A systematic review]. / Vergleich von piezoelektrisch assistierter und konventioneller Osteotomie bei der Rhinoplastik : Ein systematisches Review.

BACKGROUND: Postoperative periorbital edema and ecchymosis after rhinoplasty are mainly caused by the osteotomy with hammer and chisel. The introduction of piezoelectric surgery could lead to a better early postoperative outcome due to improved preservation of soft tissues. The aim of this systematic review was to evaluate the methods and results of studies comparing conventional osteotomy to piezoelectric osteotomy. METHODS: A systematic literature search was conducted in the PubMed/MEDLINE and Google Scholar databases. In the primary selection, all studies on the comparison of conventional and piezoelectric osteotomies with regard to postoperative periorbital edema and/or ecchymosis were identified. Secondary selection included only study designs with a control group. RESULTS: Primary selection resulted in 15 thematically relevant publications with a notable increase in annual publications between 2007 and 2017. Six studies with control groups were selected secondarily. Qualitatively and methodologically, the studies were very heterogeneous. The results of five of the six studies indicated a significant advantage of piezo technology compared to conventional osteotomy. Only in one study was no significant difference found in the investigated postoperative outcome. CONCLUSION: Piezoelectric osteotomy resulted in a reduced propensity for postoperative edema and ecchymosis compared to the conventional osteotomy technique with a chisel. At this time, the results should be regarded as a trend. A definite recommendation favoring piezoelectric osteotomy cannot be made until more studies with higher patient numbers become available.

Substance P in the human brain.

The distribution of substance P immunoreactive sites was investigated by immunoenzymatic methods in a large series of paraffin embedded human brain sections from the collection assembled by Oscar and Cécile Vogt several decades ago, as well as from more recent post-mortem material. These studies demonstrated that substance P immunoreactivity was preserved in archival material permitting a detailed account of the localization of immunoreactive cell bodies, fibre networks and tracts in the human brain. Previous observations made on experimental animals and man were confirmed and extended. Additionally, substance P immunoreactive cell bodies were seen in most cortical areas and novel features were noted in the distribution of substance P-containing elements in the tuberal region, corpus striatum, substantia nigra (particularly in relationship to blood vessels) and in association with melanin-containing cells. Reconstruction of some substance P pathways was attempted by the analysis of semi-serial sections in more than one plane. Immunocytochemistry, in combination with image analysis, enabled some measurements of the differential concentrations of substance P immunoreactive material to be made and allowed a close correlation of this with defined anatomical landmarks or enkephalin immunoreactive sites.

Morphometric studies of the neuropathological changes in choreatic diseases.

The striatum, pallidum and subthalamic nucleus were studied by combined morphometric methods in serial sections of 13 brains of normal adults and of 15 patients with choreatic diseases. In addition the volume of the hemispheres and of the cortex were measured. All data obtained were corrected by the shrinkage factor to represent fresh brain values. In Huntington's chorea the pallidum was more severely affected than is commonly appreciated. The average volume reduction was of the same degree (lateral-57%, medial-50%) as that of the striatum (-56%). The absolute number of nerve cells of the pallidum decreased in both segments by about 40%. The reduction of the volume and of the number of nerve cells was not reduced in the three subcortical nuclei studied. For the first time it has been shown that there is no increase in the absolute number of glial cells in the striatum. The increased numerical density of glial cells is caused by shrinkage. The loss of nerve cells of the pallidum and subthalamic nucleus is caused mainly by a primary process. Huntington's chorea is a multifocal process. Morphometric data do not suggest that subchorea is a variant of Huntington's chorea. Chorea minor is regarded as a multifocal process with varying affliction of the striatum, pallidum and subthalamic nucleus. An increase in the number of glial cells and, as a rule, a moderate loss of nerve cells were found in this disease.

Studies on the distribution of 14C-sulpiride and its metabolites in the rat and guinea pig.

After ip. injection of 14C-labelled sulpiride in rats, about one third is metabolized while the other two thirds are excreted unchanged in feces and urine. The highest level of its metabolites was found in the liver (about 65% of total radioactivity). In the brain, 90% of the radioactivity consisted of unchanged sulpiride, which seems to be responsible for the central effects of the drug. The highest concentrations within the brain were found in the median eminence, circumventricular organs, plexus, and pineal body.

[Morphometrical-statistical structure analysis of human striatum, pallidus and subthalamic nucleus. II. Globus pallidus]. / Morphometrisch-statistische Strukturanalysen des Striatum, Pallidum und Nucleus Subthalamicus beim Menschen. II. Pallidum

1. The pallidum of 13 hemispheres of 11 human brains of normal adults was studied by morphometric-statistical methods. 2. The values obtained on paraffin-embedded frontal serial sections were corrected individually for shrinkage in order to get comparable fresh values. 3. The mean fresh volume of the pallidum laterale of males (1220 mm3) was 13% higher than that of females (1065 mm3). The corresponding mean values of the pallidum mediale were 520 mm3 (male) and 430 mm3 (female), the difference being 17%. The difference between sexes failed to be significant. The lateral segment accounted for about 70% of the total volume of the pallidum. 4. The pallidum occupied 0,32% or ca. 1 over 300 of the volume of the hemisphere. 5. The numeric cell densities showed no significant age or sex differences. The mean value of the lateral pallidum was 437 nerve cells/mm3 and of the medial part 327 nerve cells/mm3, the difference being highly significant (p less than 0,001). 6. The pallidum laterale showed a numerical density of 66000 glial cells/mm3, the medial segment had 62000 glial cells/mm3, the difference just reaching the 5% -- level of significance. 7. On the average the ratio of glial cells to nerve cells was 158:1 in the lateral pallidum, and 159:1 in the medial part. The difference was statistically significant (p less than 0,01). 8. The mean of the total number of nerve cells in the pallidum laterale amounted to 540000 for males and 465000 for females. The corresponding values of the medial part were 171000 (male) and 143000 (female). The total number of pallidal nerve cells is just about as high as the number of large striatal nerve cells (670000 (male) and 570000 (female). 9. In the pallidum laterale we calculated the total number of glial cells to be 82 million for males and 63 million for females. In the medial pallidum we found 32 million (male) and 26 million (female). 10. The total numbers of nerve and glial cells were well correlated in the lateral as well as in the medial segment (r = 0,636 and r = 0,734, respectively). 11. The volumetric nerve cell densities showed no significant differences between sexes. The values were 0,36 Vol.-% lateral and 0,31 Vol.-% medial. This difference failed to be significant. 12. The volumetric densities of the glial cell nuclei were equal in both segments, the value being 0,43 Vol.-%. They were strictly correlated (r = 0,830). 13. The mean volume of a nerve cell in the medial segment (9600 mum3) was 19% higher (p less than 0,05) than in the lateral segment (8100 mum). 14. The mean volume of a nucleus of a glial cell showed only insignificant differences, being lateral 65 mum3 and medial 70 mum3. 15. The various morphometric data indicated a closer correlation between striatum and pallidum laterale than between striatum and pallidum mediale. Within the striatum, the putamen showed a better correlation with the pallidum than the nucleus caudatus.

CDH: preliminary report on a new anterior spinal instrumentation.

CDH (Cotrel-Dubousset-Hopf) instrumentation was developed with the aim of improving stability in ventral operation procedure and facilitating treatment of all anterior spinal diseases. The implantation of anterior plates and drawers, the use of a double-rod fixation within the implant in nonparallel directions, which provide an automatic locking mechanism against displacement, the prevention of dislocation of the cancellous bone srews, and the crosslink principle are its main characteristics. The device can be applied to the spine in accordance with its three-dimensional anatomy by any kind of force (distraction, compression, and rotation). Additional posterior instrumentation and postoperative external support are unnecessary in most cases because of improved stability. No reoperation was necessary following the mono- and multisegmental application of this method in 60 patients (28 with scoliosis, 12 with spondylodiscitis, 8 with primary tumors or isolated metastasis, 6 with fractures, 3 with failed back syndrome, 1 with kyphotic deformity, 1 with spondylolisthesis on two levels, and 1 with loss of correction after the dislocation of another posterior spinal instrumentation). Average blood loss was 950 ml; the average operating time was 3 h. In all, 16 monosegmental and 44 multisegmental procedures were carried out. In 25 patients, in particular those with paralytic scoliosis, a double-stage anterior and posterior spondylodesis was done.

[Histological, electromicroscopical and histochemical studies on the central nervous system of rats after chronic treatment with imipramine (author's transl)]. / Histologische, elektronenmikroskopische und histochemische Untersuchungen am Zentralnervensystem der Ratte nach chronischer Gabe von Imipramin.

Rat brains have been studied after treatment with oral doses of 50 mg imipramine/day for 3 and 6 months. 20 brains have been studied histologically, 3 brains electronmicroscopically, 6 brains histochemically as well as 34 controll brains. On the light microscopic level no pathologic changes of intravital origin have been revealed. The hyperchromatic changes of neurons were of the same character and degree and showed the same topic distribution in the experimental and in the control group. They should be regarded as postmortem artifacts. The pyramidal cells of hippocampus field h3, the Purkinje cells and the Golgi epithelial cells have been examined by electron microscopy. Besides a possible slight induction of lysosomes no alterations could be found. The histochemical studies (succinate dehydrogenase, ATPase, AMPase, acid phosphatase, PAS, methylgreenpyronin) revealed no differences between the experimental and the control group.

[Morphometric-statistical structure analysis of human striatum, pallidum and nucleus su-thalamicus. III. Nucleus subthalamicus]. / Morphometrisch-statistische Strukturanalysen des Striatum, Pallidum und Nucleus subthalamicus beim Menschen III. Nucleus subthalamicus

1. A morphometric-statistical analysis of the subthalamic nucleus was carried out on 14 hemispheres of 12 normal human brains. 2. The values determined in paraffin embedded sections were corrected for shrinkage which showed considerable interindividual variation. 3. The mean fresh volume of the subthalamic nucleus amounted to 144 mm3 for males and 134 mm3 for females, the difference of 7% not being statistically significant. 4. In the medial part of the subthalamic nucleus the nerve cells were smaller and more closely grouped than in the lateral part which had larger nerve cells. The ratio of the volumes of the two parts was about 1:4 (medial: lateral). 5. The nucleus subthalamicus occupied 0,027% of the volume of the hemisphere. 6. The numerical nerve cell densities -- corrected for shrinkage -- were 1970 +/- 145 nerve cells/mm3 for the lateral part and 2910 +/- 310 nerve cells/mm3 for the medial part, this difference of 48 +/- 4% being highly significant. On the other hand, no difference between sexes could be shown. 7. The mean of the absolute number of nerve cells was 306000 for male and 286000 for females, the difference of 7% not being significant. 8. The volumetric nerve cell densities were found to be 1.58 +/- 0.15 vol% lateral and 1.99 +/- 0.16 vol% medial, the difference of 27% being significant. No differences between sexes were found. 9. The linear dimensions of the nerve cells of the medial part were about 10% smaller than those of the nerve cells of the lateral part. The mean fresh volume of a nerve cell was 8070 mum3 in the lateral portion and 6960 mum3 in the medial portion, the nerve cells of pars lateralis being just as large as the nerve cells of the lateral segment of the pallidum (8100 mum3). 10. The parameters determined showed good correlations with corresponding data of the pallidum. The fresh volume and the absolute numbers of nerve cells of the nucleus subthalamicus were better correlated with the pallidum laterale than with the pallidum mediale.

[Morphometrical-statistical structure analysis of human striatum, pallidum and subthalamic nucleus]. / Morphometrisch-statistische Strukturanalysen des Striatum, Pallidum und Nucleus subthalamicus beim Menschen

1. A morphometric-statistical analysis was carried out of fifteen hemispheres of thirteen normal brains of human adults. 2. A comparison of the volumes and the cell densities studied in serial sections is only meaningful if the results are corrected for shrinkage, which varies interindividually to a great extent. 3. The mean of the fresh volume of the striatum of the male subjects (10.2 cm3) was 12% higher than that of the female subjects (9.0 cm3), the difference not being significant. The putamen was 13% bigger on the average than the caudate nucleus. The size of the two nuclei was strictly correlated (r = 0.81). 4. The relative volume of the striatum in percent of the hemisphere volume amounted to 1.87% in males and 1.97% in females, of the putamen 0.99% (male) and 1.05% (female), of the caudate nucleus 0.88% and 0.92%, respectively. 5. The mean of the numerical density of small striatal nerve cells (kl. Nz) -- corrected for shrinkage -- came to 1100 kl. Nz/mm3, without evidence of being dependent of sex or age. 6. The corrected numerical density of the large striatal nerve cells (gr. Nz) had a mean of 65 gr. Nz/mm3 with a wide range of 49 to 78 gr. Nz/mm3, without a significant influence of sex or age. 7. The relation of kl. Nz/gr. Nz was on an average of 171:1 with a range of 130:1 to 258:1. 8. The mean of the corrected numerical density of glial cells (Gz) was found to be 41000 Gz/mm3 with a range of 34500 to 49200. Neither a difference between sexes nor a dependency of age was found. 9. The glia index (Gz/Nz) showed a mean of 37:1 with a range of 3.2:1 to 4.7:1. 10. The total number of small striatal cells averaged 100 million for males and 105 Million for females; for the large striatal cells the means were 670 thousand (male) and 570 thousand (female). Differences due to sex failed to be significant. 11. The total number of glial cells decreases with age. The mean of 408 million for males exceeded the mean of 380 million for females by 7% but without significance. 12. The volumetric density of nerve cells of males (4.03 Vol.-%) and females (4.14 Vol.-%) differed very little. 13. The mean fresh volume of a single small nerve cell in the striatum was calculated to be about 3600 mum3, ranging from 2600 to 4600 mum3. 14. The striatal nerve cells reached a total volume of 423 mm3 in males and 374 mm3 in females. 15. The mean of the diameter of the nucleus of the small nerve cells was calculated to be 8.64 mum in males and 8.70 mum in females.

Cystic fibrosis transmembrane conductance regulator inhibits epithelial Na+ channels carrying Liddle's syndrome mutations.

Epithelial Na+ channels (ENaC) are inhibited by the cystic fibrosis transmembrane conductance regulator (CFTR) upon activation by protein kinase A. It is, however, still unclear how CFTR regulates the activity of ENaC. In the present study we examined whether CFTR interacts with ENaC by interfering with the Nedd4- and ubiquitin-mediated endocytosis of ENaC. Various C-terminal mutations were introduced into the three alpha-, beta-, and gamma-subunits of the rat epithelial Na+ channel, thereby eliminating PY motifs, which are important binding domains for the ubiquitin ligase Nedd4. When expressed in Xenopus oocytes, most of the ENaC stop (alpha-H647X, beta-P565X, gamma-S608X) or point (alpha-P671A, beta-Y618A, gamma-P(624-626)A) mutations induced enhanced Na+ currents when compared with wild type alpha,beta,gamma-rENaC. However, ENaC currents formed by either of the mutant alpha-, beta-, or gamma-subunits were inhibited during activation of CFTR by forskolin (10 micromol/l) and 3-isobutyl-1-methylxanthine (1 mmol/l). Antibodies to dynamin or ubiquitin enhanced alpha,beta,gamma-rENaC whole cell Na+ conductance but did not interfere with inhibition of ENaC by CFTR. Another mutant, beta-T592M,T593A-ENaC, also showed enhanced Na+ currents, which were down-regulated by CFTR. Moreover, activation of ENaC by extracellular proteases and xCAP1 does not disturb CFTR-dependent inhibition of ENaC. We conclude that regulation of ENaC by CFTR is distal to other regulatory limbs and does not involve Nedd4-dependent ubiquitination.

The first-nucleotide binding domain of the cystic-fibrosis transmembrane conductance regulator is important for inhibition of the epithelial Na+ channel.

The cystic-fibrosis transmembrane conductance regulator (CFTR) functions as a cAMP-regulated Cl- channel and as a regulator of other membrane conductances. cAMP-dependent activation of CFTR inhibits epithelial Na+ channels (ENaC). The specificity of interaction between CFTR and ENaC was examined by coexpression of ENaC and ATP-binding cassette (ABC) proteins other than CFTR. In addition, we identified domains within CFTR that are of particular importance for the inhibition of ENaC. To that end, two-electrode voltage-clamp experiments were performed on Xenopus oocytes coexpressing ENaC together with CFTR, the multidrug resistance protein MDR1, the sulfonyl urea receptor SUR1, or the cadmium permease YCF1. Except for CFTR, none of the other ABC proteins were able to inhibit ENaC. Several truncated versions of CFTR were examined for their inhibitory effects on ENaC. In fact, it is shown that C-terminal truncated CFTR is able to inhibit ENaC on activation by intracellular cAMP. Moreover, the data also show that an intact first-nucleotide binding domain (NBF-1) is important for inhibition of ENaC. We conclude that NBF-1 of CFTR contains a CFTR-specific regulatory site that down-regulates ENaC. It is speculated that this regulatory site also is needed for CFTR-mediated interactions with other membrane proteins and that it is not present in NBF-1 of other ABC proteins.

Cystic fibrosis and CFTR.

Cystic fibrosis (CF) is a complex disease affecting epithelial ion transport. There are not many diseases like CF that have triggered such intense research activities. The complexity of the disease is due to mutations in the CFTR protein, now known to be a Cl(-) channel and a regulator of other transport proteins. The various interactions and the large number of disease-causing CFTR mutations is the reason for a variable genotype-phenotype correlation and sometimes unpredictable clinical manifestation. Nevertheless, the research of the past 10 years has resulted in a tremendous increase in knowledge, not only in regard to CFTR but also in regard to molecular interactions and completely new means of ion channel and gene therapy.

Molecular and functional characterization of s-KCNQ1 potassium channel from rectal gland of Squalus acanthias.

Functional and pharmacological data point to the involvement of KCNQ1/IsK potassium channels in the basolateral potassium conductance of secretory epithelia. In this study, we report the cloning and electrophysiological characterization of the KCNQ1 protein from the salt secretory rectal gland of the spiny dogfish (Squalus acanthias). The S. acanthias KCNQ1 (s-KCNQ1) cDNA was cloned by polymerase chain reaction (PCR) intensive techniques and showed overall sequence similarities with the KCNQ1 potassium channel subunits of Man, mouse and Xenopus laevis of 64, 70 and 77%, respectively, at the translated amino acid level. Analysis of s-KCNQ1 expression on a Northern blot containing RNA from heart, rectal gland, kidney, brain, intestine, testis, liver and gills revealed distinct expression of 7.4-kb s-KCNQ1 transcripts only in rectal gland and heart. Voltage-clamp analysis of s-KCNQ1 expressed in Xenopus oocytes showed pronounced electrophysiological similarities to human and murine KCNQ1 isoforms, with a comparable sensitivity to inhibition by the chromanol 293B. Coexpression of s-KCNQ1 with human-IsK (h-IsK) induced currents with faster activation kinetics and stronger rectification than observed after coexpression of human KCNQ1 with h-IsK, with the voltage threshold of activation shifted to more negative potentials. The low activation threshold at approximately -60 mV in combination with the high expression in rectal gland cells make s-KCNQ1 a potential candidate responsible for the basolateral potassium conductance.