Dynamic protein methylation in chromatin biology.

Post-translational modification of chromatin is emerging as an increasingly important regulator of chromosomal processes. In particular, histone lysine and arginine methylation play important roles in regulating transcription, maintaining genomic integrity, and contributing to epigenetic memory. Recently, the use of new approaches to analyse histone methylation, the generation of genetic model systems, and the ability to interrogate genome wide histone modification profiles has aided in defining how histone methylation contributes to these processes. Here we focus on the recent advances in our understanding of the histone methylation system and examine how dynamic histone methylation contributes to normal cellular function in mammals.

Molecular cloning, expression analysis and assignment of the porcine tumor necrosis factor superfamily member 10 gene (TNFSF10) to SSC13q34-->q36 by fluorescence in situ hybridization and radiation hybrid mapping.

We have cloned the complete coding region of the porcine TNFSF10 gene. The porcine TNFSF10 cDNA has an ORF of 870 nucleotides and shares 85% identity with human TNFSF10, and 75% and 72% identity with rat and mouse Tnfsf10 coding sequences, respectively. The deduced porcine TNFSF10 protein consists of 289 amino acids with the calculated molecular mass of 33.5 kDa and a predicted pI of 8.15. The amino acid sequence similarities correspond to 86, 72 and 70% when compared with human, rat and mouse sequences, respectively. Northern blot analysis detected TNFSF10-specific transcripts (approximately 1.7 kb) in various organs of a 10-week-old pig, suggesting ubiquitous expression. Real-time RT-PCR studies of various organs from fetal (days 73 and 98) and postnatal stages (two weeks, eight months) demonstrated developmental and tissue-specific regulation of TNFSF10 mRNA abundance. The chromosomal location of the porcine TNFSF10 gene was determined by FISH of a specific BAC clone to metaphase chromosomes. This TNFSF10 BAC clone has been assigned to SSC13q34-->q36. Additionally, the localization of the TNFSF10 gene was verified by RH mapping on the porcine IMpRH panel.

Molecular characterisation of congenital glaucoma in a consanguineous Canadian community: a step towards preventing glaucoma related blindness.

Glaucoma is a leading cause of irreversible blindness in Canada. Congenital glaucoma usually manifests during the first years of life and is characterised by severe visual loss and autosomal recessive inheritance. Two disease loci, on chromosomes 1p36 and 2p21, have been associated with various forms of congenital glaucoma. A branch of a large six generation family from a consanguineous Amish community in south western Ontario was affected with congenital glaucoma and was studied by linkage and mutational analysis to identify the glaucoma related genetic defects. Linkage analysis using the MLINK component of the LINKAGE package (v 5.1) showed evidence of linkage to the 2p21 region (Zmax=3.34, theta=0, D2S1348 and D2S1346). Mutational analysis of the primary candidate gene, CYP1B1, was done by direct cycle sequencing, dideoxy fingerprinting analysis, and fragment analysis. Two different disease causing mutations in exon 3, 1410del13 and 1505G-->A, both segregated with the disease phenotype. The two different combinations of these alleles appeared to result in a variable expressivity of the phenotype. The compound heterozygote appeared to have a milder phenotype when compared to the homozygotes for the 13 bp deletion. The congenital glaucoma phenotype for this large inbred Amish family is the result of mutations in CYP1B1 (2p21). The molecular information derived from this study will be used to help identify carriers of the CYP1B1 mutation in this community and optimise the management of those at risk of developing glaucoma.

Genetic heterogeneity of the Coppock-like cataract: a mutation in CRYBB2 on chromosome 22q11.2.

PURPOSE: To identify the genetic defect for the Coppock-like cataract (CCL) affecting a Swiss family, which defect was unlinked to the chromosome 2q33-35 CCL locus. METHODS: A large family was characterized for linkage analysis by slit lamp examination or by the review of drawings made before cataract extraction. The affection status was attributed before genotyping, and the genotyping was masked to the affection status. Two-point and multipoint linkage analyses were performed using the MLINK and the LINKMAP components of the LINKAGE program package (ver. 5.1), respectively. Mutational analysis of candidate genes was performed by a combination of direct cycle sequencing and an amplification refractory mutation system assay. RESULTS: Ten individuals were affected with the CCL phenotype. The disease was autosomal dominant and appeared to be fully penetrant. A new CCL locus was identified on chromosome 22q11.2 within a 11.67-cM interval (maximum lod score [Zmax] = 4.14; theta = 0). Mutational analysis of the CRYBB2 candidate gene identified a disease-causing mutation in exon 6. This sequence change was identical with that previously described to be associated with the cerulean cataract, a clinically distinct entity. CONCLUSIONS: The CCL phenotype is genetically heterogeneous with a second gene on chromosome 22q11.2, CRYBB2. The CCL and the cerulean cataract are two distinct clinical entities associated with the same genetic defect. This work provides evidence for a modifier factor that influences cataract formation and that remains to be identified.

Effects of PEEP on pulmonary mechanics and oxygen transport in the late stages of acute pulmonary failure.

In 23 patients with advanced stages of acute respiratory failure, the value of various parameters for estimating the efficiency of ventilation with PEEP were analysed. PEEP increments of 1 cm of water corresponded to an increase of PaO2 of 2 mmHg. The cardiac output decreased from 8.3 +/- 0.3 l/min mean value at ZEEP to 7.3 +/- 0.3 L/min at a PEEP of +15 cm H2O. Corresponding to this, the oxygen transport showed a decrease from 1042 +/- 62 ml/min to 894 +/- 115 ml/min. The total compliance of 34 ml/cm H2O at ZEEP is already significantly reduced (a sign of the severe respiratory failure) and falls still further at a PEEP of 15 cm H2O to 22 ml/cm H2O. No notable recruitment of non ventilated alveolar spaces can be expected, in spite of the slight increase in the arterial oxygen tension. Taking the "best PEEP" (PEEP with maximum oxygen transport) as a reference point, arterial and mixed venous oxygen tension increase, the cardiac output decreases above this point and the total respiratory compliance shows no obvious changes. In the advanced stage of severe respiratory failure one cannot use the mixed venous oxygen tension or the compliance to find the best PEEP. The danger of barotrauma by PEEP ventilation in cases of significantly reduced compliance has to be considered in the choice of the ventilation pattern. The arterial oxygen tension may lead to a wrong estimation of the total efficiency of PEEP.

[Continuous axillary catheter plexus anesthesia--a method of postoperative analgesia and sympathetic nerve block following hand surgery]. / Die kontinuierliche axilläre Katheter-Plexusanästhesie--eine Methode zur postoperativen Analgesie und Sympathikolyse nach handchirurgischen Eingriffen.

During a period of one year (March 1985 to March 1986) 52 axillary brachial plexus catheters were left in place for two to twelve days. The main indications were postoperative analgesia and sympatholysis after microvascular surgery of the hand. With the continuous infusion of 0.25% or 0.375% bupivacaine, 6-8 ml/h a sufficient effect was seen. There was no evidence of accumulation of the administered drug after a prolonged period of infusion. A steady state of serum levels built up in the range between 0.5 to 1.5 micrograms/ml. There were no toxic side effects by the local anaesthetic agent. In one case an infection of the axillary region developed, which disappeared after removal of the catheter without any consequences. In summary the continuous axillary brachial plexus block is an acceptable method for intra and postoperative analgesia and sympatholysis in microvascular surgery of the hand.

European field tests with HISTKOM telepathology equipment.

HISTKOM telemicroscopy equipment for telepathology is designed for the most challenging application in telepathology: intraoperational frozen section diagnosis. Adapted to this application, it is also excellently suited for all other telepathology modes requesting less sophisticated equipment. The technical concept and user interface are oriented to routine daily pathology. HISTKOM underwent heavy field-tests at several locations. The field-tests designs and the results of five of these are reported in this paper. Telepathology will exploit its advantages in networks hosting participants requesting and offering services. The solution of the interoperability problem caused by different equipment from different suppliers within such a network will be a major task, the solution for which is in progress. The new generation of HISTKOM equipment and software is designed in a modularized concept, allowing the integration of various hardware components from different manufacturers; thus special configurations can be realized easily. HISTKOM is offered as complete turnkey system, but can also be installed in yet existing configurations of the customer if they meet specifications.

[Contusion of the heart]. / Die Contusio cordis.

Whereas heart contusion can be identified by autopsy as a traumatic damage to the heart, clinical diagnosis during life is mostly made by exclusion only and subsequently, the more so since there is no absolutely reliable parameter that permits diagnosis ad hoc. Complications often develop only hours or days after the accident. Heart contusion can be masked by haemorrhagic-traumatic shock and accompanying injuries and delay its diagnosis. Traumatic damage to the myocardium can equal a myocardial infarction. Hence, it is imperative that persons injured in an accident who are suspected of having suffered a contusion of the heart, are placed in an intensive-care ward to recognise complications well in time and to institute therapeutic measures without delay. As is the case with acute myocardial infarction, anaesthesia and surgery can be performed only in case of a vital indication.

[Catheterization of the central veins in the adult (author's transl)]. / Punktion zentraler Venen beim Erwachsenen.

Although the successful treatment of critically ill patients often depends on access to the large veins close to the heart, the indications for this procedure should be strictly limited on account of the attendant risks and potential complications. From the large variety of cannulas, catheters and techniques available for this purpose those systems should be chosen that are simple and safe to use. Seldinger's technique is the method of choice for elective puncture under optimum conditions. If the time factor is important, closed complete systems should be employed. Aseptic puncture and nursing technique is essential to prevent the most common late complication-septicaemia. Radiological verification of the siting of the catheter is important. The various access routes to the central veins carry differing success rate and they also vary in respect of the incidence of complications. This should be borne in mind when deciding on a particular technique. On the other hand, the choice also depends on such factors as technical skill of the physician, the quality of nursing and the expected duration of hospital stay. The peripheral veins of the arm are the safest access for the less experienced physician and for short-lasting catheterization; otherwise the internal jugular vein is the preferred site followed by the subclavian vein. Even if the physician prefers a particular access route he should be familiar with all types of technique since critically ill patients are liable to require changes of the catheter. There is no single technique that will cover all contingencies.

[Problems of intubation using the flexible LF-1 fiberoptic bronchoscope. Development of an intubation aid]. / Probleme bei der Intubation mit dem flexiblen Fiberbronchoskop LF 1. Entwicklung einer Intubationshilfe.

Fiberoptic endotracheal intubation with an endoscope (external diameter 4 mm) especially designed for anesthesiologists proved to be safe providing small-diameter tubes were used. The use of large-diameter tubes (I.D. 7.5-8.5 (mm)) involves a risk of the tip of the tube clinging to the arytenoid cartilages preventing any further advancement. To avoid this complication another special tube has been constructed, which fills the space between the endotracheal tube and the bronchoscope and centers the bronchoscope within the endotracheal tube. When this new tube was used there were no problems either in passing the bronchoscope through this "inner" tube or in withdrawing the inner tube after successful intubation. With the new device it was even possible to pass tubes with wider lumen into the trachea over the fiberscope with minimal difficulty and trauma.

[Mepivacaine in brachial plexus anesthesia in surgical interventions of long duration]. / Mepivacain zur Plexus brachialis-Anaesthesie bei langdauernden operativen Eingriffen.

To evaluate the use of mepivacaine-HCl for continuous axillary brachial plexus block for surgery lasting several hours a prospective study was performed. Mepivacaine-HCl 400 mg was injected every two hours. Over a period of eight to twenty hours there was in all cases adequate analgesia and muscle relaxation for microsurgical repair of limbs. Mean serum levels of mepivacaine-HCl did not exceed the concentration of 5-6 micrograms/ml. There were no side effects caused by the local anaesthetic agent.

[Invasive techniques in emergency medicine. II. Preclinical thorax drainage--indications and technique]. / Invasive Techniken in der Notfallmedizin. II. Präklinische Thoraxdrainage--Indikationen und Technik.

The preclinical tension pneumothorax which even without technical support is easily recognizable, requires immediate decompression. However, there are a number of patients with thoracic injuries such as serial rib fractures or palpable skin emphysema which--in combination with a ventilator--may necessitate the insertion of a thoracic tube. In the preclinical setting this procedure usually only takes place in the ventilated patient. With patients who are respiratorily compensated and are breathing spontaneously, careful control and a conservative approach is advised even if pneumothorax is suspected.

[Alkalinization of mepivacaine for axillary plexus anesthesia using a catheter]. / Alkalisierung von Mepivacain zur axillären Katheterplexusanaesthesie.

One disadvantage of perivascular axillary block using a catheter technique is delayed temporal development of the blockade. Some clinical studies have concluded that pH-adjusted solutions of local anesthetics produce a more rapid onset of blockade. Alkalinization of mepivacaine for brachial block produced conflicting results. In the present study, we attempted to define the effect of alkalinization of mepivacaine 1% on clinical efficacy, onset, and regression in patients undergoing upper extremity surgery with axillary block using the catheter technique. METHODS. Sixty consecutive adult patients (ASA I-II) scheduled for upper extremity surgery under axillary block, were randomly assigned to one of two groups. In a double-blind fashion, 30 patients received 40 ml 1% mepivacaine, the pH of which had been raised to 7.25 by adding 4 ml 8.4% NaHCO3, and 30 received 40 ml commercially prepared 1% mepivacaine hydrochloride solution containing 4 ml 0.9% NaCl (pH 6.0). All patients received axillary block using the catheter technique. After placement of the block, a blinded observer tested sensory and motor blockade after 2 min, 5 min and then every 5 min for 30 min in each of the terminal nerves of the brachial plexus. Sensory blockade was determined by pinprick and graded in accordance with the scale proposed by Hollmèn: 0: Normal sensation of pinprick. 1: pinprick felt as sharp-pointed but weaker compared with the same area in the other upper extremity. 2: Pinprick recognized as touch with a blunt object. 3: No perception of touch. The gradation of motor blockade was 0: normal muscular function; 1: slight depression in muscular function compared with preanesthetic strength; 2: very weak action persisting in muscles; and 3: complete block. The results for each group were compared at every time interval. Duration of blockade was compared by evaluating the rate of regression within the first 2 h after placement of the block in each group. Mepivacaine plasma levels were measured by HPLC in 10 patients of each group prior to injection and 5, 10, 15, 20, 30, 60, and 120 min thereafter. Statistical comparison was made using the chi 2 and t tests. Differences were considered statistically significant when P-values were less than 0.05. RESULTS. The bicarbonate and saline groups were similar with respect to age, height, weight, and sex distribution. Significantly more patients in the bicarbonate group showed onset of motor blockade (grade 1) after 2 min with respect in the axillary, musculocutaneous, radial, and median nerves as well as onset of sensory blockade in the same nerves with a significant difference in blockade of the radial nerve. (ABSTRACT TRUNCATED AT 400 WORDS)

[Treatment of alkyl phosphate poisoning with purified serum cholinesterase (author's transl)]. / Behandlung einer Alkylphosphatintoxikation mit gereinigter Serumcholinesterase

A 26-years-old man injected himself intramuscularly with 3.75 gram of demeton methyl in an attempt to commit suicide. After 36 hours severe symptoms of poisoning developed with loss of consciousness and respiratory arrest. As symptomatic treatment failed to improve his condition has given injections of purified serum cholinesterase. This was followed by a rise in the cholin esterase levels and the increased activity was accompanied by a rapid and definite improvement in the clinical findings. The results clearly indicate the usefulness of this method of treatment. Transfusions of fresh blood to counteract the cholin esterase deficiency are inadvisable because of the risks of complications. Substitution therapy with serum cholinesterase must be accompanied by administration of large doses of atropine.

[Electroencephalographic changes during ethrane anaesthesia in children (author's transl)]. / EEG-Veränderungen bei Kindern während Enflurane-Anästhesie

Continuous electroencephalographic recordings were taken in 25 children who had ethrane-nitrous oxide anaesthesia without a basal anaesthetic. The recordings confirmed the repeatedly reported occurrence of certain abnormal wave patterns distinctive of seizures during ethrane anaesthesia. Although these dysrhythmias were more frequent and more pronounced at higher ethrane concentrations and during hyperventilation, sharp spikes began to appear already at concentrations of 1.0/p.c. without hyperventilation and at moderate depths of anaesthesia. In no case did the usual criteria for assessing depth of anaesthesia provide an indication of over-dosage. Although in the individual case there was a close relationship between the concentration of ethrane in the inhaled mixture and the electroencephalographic changes, the differences between the cases were too great to allow any prediction as to the concentration of ethrane that would bring on the dysrhythmia. Considering that increased cerebral oxygen consumption has been observed to accompany the abnormal wave patterns ethrane is not recommended for use in epileptic children or those with a familial history of epilepsy.

[Flow measurement in blood filters]. / Durchflussmessungen bei Blutfiltern.

Flow rates of compatible mixed packed red cells passing through a 170 micrometers standard blood filter or one of three microfilters with different pore sizes were measured. In spite of the largest pore size of 170 micrometers, the standardfilter shows the slowest flow. The cascade filter "MF 10" with sieves of 200, 50, 20, ad 10 micrometers pore sizes has excellent flow rates due to its large surface area. The "microtrans" with cascades of 150, 50, 10 micrometers pore sizes, good filter properties, low filling volume, and reasonable flow rates seems to be an acceptable microfilter for routine clinical use. If the tube of the infusion system is cut off, then the blood flow increases its speed by about fivefold in spite of different filters.

[Training on nursing personnel for work in recovery and intensive care units (author's transl)]. / Weiterbildung zur Fachschwester/Fachpfleger für Anästhesie und Intensivmedizin.

After prolonged deliberations guide lines have now been agreed upon regarding the training and examination of nursing personnel for work in recovery and intensive care units. The recommendations, as adopted by the German Hospital Association 16th November 1976, cannot be accepted unreservedly. One of the main objections is that the proposed course of training would lead to excessive specialization at too early a stage. The aim should be to provide training of an interdisciplinary character, including anaesthesia.