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M Helm

Publications and source records attributed to M Helm.

At least 37 records · Page 2Linked to original sources
PubMed1999

Search for differences in post-transcriptional modification patterns of mitochondrial DNA-encoded wild-type and mutant human tRNALys and tRNALeu(UUR).

Post-transcriptional modifications are characteristic features of tRNAs and have been shown in a number of cases to influence both their structural and functional properties, including structure stabilization, amino-acylation and codon recognition. We have developed an approach which allows the investigation of the post-transcriptional modification patterns of human mitochondrial wild-type and mutant tRNAs at both the qualitative and the quantitative levels. Specific tRNA species are long-term labeled in vivo with [32P]orthophosphate, isolated in a highly selective way, enzymatically digested to mononucleotides and then subjected to two-dimensional thin layer chromatographic analysis. The wild-type tRNALysand the corresponding tRNALyscarrying the A8344G mutation associated with the MERRF (Myoclonic Epilepsy with Ragged Red Fibers) syndrome exhibit the same modified nucleotides at the same molar concentrations. By contrast, a quantitatively different modification pattern was observed between the wild-type tRNALeu(UUR)and its counterpart carrying the A3243G mutation associated with the MELAS (Mitochondrial Myopathy, Encephalopathy with Lactic Acidosis and Stroke-like episodes) syndrome, the latter exhibiting a 50% decrease in m2G content. Complementary sequencing of tRNALeu(UUR)has allowed the localization of this modification at position 10 within the D-stem of the tRNA. The decreased level of this modification may have important implications for understanding the molecular mechanism underlying the MELAS-associated mitochondrial dysfunction.

Autoradiography↗
PubMed1999

[Cardiac troponin T as a biochemical marker of myocardial injury early after trauma. Diagnostic value of a qualitative bedside test].

INTRODUCTION: To evaluate within a trauma population the diagnostic value of a qualitative test (TROPT Rapid Assay) for the specific detection of circulating cardiac troponin T (cTnT) in comparison with the traditionally used CK/CK-MB ratio especially in the early in-hospital phase. METHODS: Prospective study in trauma patients over a 12-month period. Multifaceted diagnostic approach to myocardial cell injury based on quantitative as well as qualitative cTnT and CK-MB/CK measurements, electrocardiographic (ECG) and echocardiographic (TTE) findings. SETTING: A regional trauma centre, the Federal Armed Forces Medical Centre Ulm, Germany. SUBJECTS: One hundred and twenty-five patients with major blunt trauma admitted to the Federal Armed Forces Medical Centre Ulm between October 1995 and November 1996. RESULTS: The TROPT Rapid Assay results significantly correlated with the results of the quantitative cTnT determinations (P < 0.001; sensitivity 1.0 and 0. 86/specificity 0.96 and 0.94 upon hospital admission and completion of diagnostic procedures). There was no significant correlation between CK-MB/CK ratio and quantitative cTnT findings. Upon hospital admission all patients whose quantitative cTnT measurement showed a positive test result (>/= 0.2 microg/l) also had a positive TROPT Rapid Assay result (negative prediction value 1.0). There was a significant correlation of TROPT Rapid Assay results and the diagnosis of a concomitant rising "chest trauma" (P < 0.002). While a significant correlation between the TROPT Rapid Assay results and specific ECG changes was observed (P < 0.008), the findings relating to CK-MB/CK ratio did not show any significant relation to specific ECG or specific TTE changes. A significant correlation between TROPT Rapid Assay results and myocardial lesion related specific therapeutic interventions was observed (P < 0.01; specificity 1.0, sensitivity 0.11). CONCLUSIONS: Within a multifaceted diagnostic approach to blunt cardiac trauma, cTnT should replace CK-MB as the biochemical marker of choice. The TROPT Rapid Assay is a test which rapidly and accurately enables the trauma team to differentiate patients with and without myocardial cell injury. It does not efficiently identify trauma patients at risk for the development of cardiac complications.

Adolescent↗
PubMed1999

[Quality of emergency ventilation. A prospective study of trauma patients].

INTRODUCTION: The prehospitaly initiated endotracheal intubation and controlled ventilation, is especially in multi-system-trauma cases, recognized to be the "gold standard". Thus especially in view of the increasing demands being placed upon the quality of prehospital emergency treatment in general, the quality of such prehospital induced ventilation, is becoming of increasing importance. Thereby we must take into consideration the limited possabilities, which are afflicted with a high degree of uncertainess, which we have at our disposal to effectively evaluate the efficiency of emergency ventilation. The purpose of our study within a collective of severely traumatized patients, was to determine the quality of prehospitaly induced ventilation with regards to the adequacy of oxygenation and ventilation and as a result of our findings, to identify areas for procedural optimization. RESULTS: The prospective study over an one year period involved n = 104 trauma cases (male: 79; female: 25/age: 39.8 +/- 20.8 years/ISS: 28.1 +/- 15.3) whose prehospital emergency treatment required and included endotracheal intubation and controlled ventilation. All patients were subject to a prehospital pulse oxymetric monitoring, whereas none were subject to an objectivating apparatus monitoring of ventilation: 94.2% of the patients were upon admission adequately oxygenated (paO2 > 80 mmHg); only one patient was hypoxemic (paO2 < 60 mmHg). 46.2% were adequately ventilated (paCO2: 35-45 mmHg), 43.2% however were hyperventilated (paCO2 < 35 mmHg), and 10.6% hypoventilated (paCO2 > 45 mmHg). A statistical significant relation between hyper-/hypoventilation and the degree of severity of trauma as well as to the individual injury pattern was not evident. However with reference to age: The group of > 60 years of age were significantly more frequently hyperventilated (paCO2 < 30 mmHg: 31.2%; p < 0.05). A noteworthy accumulation of hypoventilation was experienced amongst the group of patients, who during the prehospital treatment phase were hemodynamic instable (shock index > 1). CONCLUSION: In summary it is evident, that as a rule, even very severe traumatized patients can prehospitaly be adequately oxygenated and that such oxygenation can with the assistance of pulse oxymetric monitoring be effectively controlled. Remaining problem is the emergency physicians ability to evaluate and control ventilation. The prehospital determination of minute volume (MV) in accordance with the presently valid recommendation: MV = 100-150 ml/kg body weight, in the majority of trauma cases results in inadequate ventilation. The introduction of an objectifying monitoring method is therefore urgently required.

Adolescent↗
PubMed1998

Characterization and selectivity of catalytic antibodies from human serum with RNase activity.

IgG purified from sera of several patients with systemic lupus erythematosus and hepatitis B are shown to present RNA hydrolyzing activities that are different from the weak RNase A-type activities found in the sera of healthy donors. Further investigation brings evidence for two intrinsic activities, one observed in low salt conditions and another specifically stimulated by Mg2+ions and distinguishable from human sera RNases. Cleavage of RNA substrates by the latter activity is not sequence-specific but sensitive to both subtle conformational and/or drastic folding changes, as evidenced by comparative analysis of couples of structurally well-studied RNA substrates. These include yeast tRNAAsp and its in vitro transcript and human mitochondrial tRNALys-derived in vitro transcripts. The discovery of catalytic antibodies with RNase activities is a first step towards creation of a new generation of tools for the investigation of RNA structure.

Antibodies, Catalytic↗
PubMed1998

Sequences outside recognition sets are not neutral for tRNA aminoacylation. Evidence for nonpermissive combinations of nucleotides in the acceptor stem of yeast tRNAPhe.

Phenylalanine identity of yeast tRNAPhe is governed by five nucleotides including residues A73, G20, and the three anticodon nucleotides (Sampson et al., 1989, Science 243, 1363-1366). Analysis of in vitro transcripts derived from yeast tRNAPhe and Escherichia coli tRNAAla bearing these recognition elements shows that phenylalanyl-tRNA synthetase is sensitive to additional nucleotides within the acceptor stem. Insertion of G2-C71 has dramatic negative effects in both tRNA frameworks. These effects become compensated by a second-site mutation, the insertion of the wobble G3-U70 pair, which by itself has no effect on phenylalanylation. From a mechanistic point of view, the G2-C71/G3-U70 combination is not a "classical" recognition element since its antideterminant effect is compensated for by a second-site mutation. This enlarges our understanding of tRNA identity that appears not only to be the outcome of a combination of positive and negative signals forming the so-called recognition/identity set but that is also based on the presence of nonrandom combinations of sequences elsewhere in tRNA. These sequences, we name "permissive elements," are retained by evolution so that they do not hinder aminoacylation. Likely, no nucleotide within a tRNA is of random nature but has been selected so that a tRNA can fulfill all its functions efficiently.

Base Sequence↗
PubMed1998

The presence of modified nucleotides is required for cloverleaf folding of a human mitochondrial tRNA.

Direct sequencing of human mitochondrial tRNALysshows the absence of editing and the occurrence of six modified nucleotides (m1A9, m2G10, Psi27, Psi28 and hypermodified nucleotides at positions U34 and A37). This tRNA folds into the expected cloverleaf, as confirmed by structural probing with nucleases. The solution structure of the corresponding in vitro transcript unexpectedly does not fold into a cloverleaf but into an extended bulged hairpin. This non-canonical fold, established according to the reactivity to a large set of chemical and enzymatic probes, includes a 10 bp aminoacyl acceptor stem (the canonical 7 bp and 3 new pairs between residues 8-10 and 65-63), a 13 nt large loop and an anticodon-like domain. It is concluded that modified nucleotides have a predominant role in canonical folding of human mitochondrial tRNALys. Phylogenetic comparisons as well as structural probing of selected in vitro transcribed variants argue in favor of a major contribution of m1A9 in this process.

Cloning, Organism↗
PubMed1998

[Reduced muscular oxygen tension and nerve impulse transmission from antishock hose. Reduction of oxygen tension in the tibial muscle and impulse transmission in the peroneal nerve from pneumatic -1 pressure from antishock hose].

OBJECT OF THE STUDY: The aim of the study was to assess, whether the pneumatic pressure of an antishock-trouser (AST) of 20-40 mm Hg induces a decreased oxygenation of the anterior tibial muscle and attenuates muscular response potential (MRP) of n. peronaeus profundus? METHODS: Among 22 normotensive, healthy volunteers the AST were tested by applying pressure values between 0 and 100 mm Hg and measuring the intracompartmental pressure, the muscular oxygen pressure as well as the MRP by electroneurographic means within a period of 6 hours. RESULTS: The median initial intracompartmental pressure value of the m. tibialis anterior was 12.0 mm Hg (Q25%/Q75%: 8.9/17.3), the muscular oxygen pressure 14.8 mm Hg (Q25%/Q75%: 11.5/22.0). Transmission of the pneumatic AST-leg segment pressure to the muscle: 97.7% (Q25%/Q75%: 89.2/99.8). Already in the low AST pressure field (20-40 mm Hg) a severe hypoxia occurred in one case. A reduction of MRP was noticed at an AST pressure rate of 10 mm Hg. In 5 of 6 cases AST pressure values of 60 mm Hg led to pathological pO2-values within 5-20 minutes. Almost without exception AST-pressure rates < 60 mm Hg resulted in an anoxia of the muscle and loss of the MRP. CONCLUSIONS: We should demand that the AST are only applied with models where the pressure generated within the single segments can be controlled by pressure gauge. The application of the AST seems to be justified for polytraumatised in severe haemorrhagic shock where the risk of a local tissue ischemia with systemical consequences must deliberately be accepted.

Adult↗
PubMed1998

Isoleucylation properties of native human mitochondrial tRNAIle and tRNAIle transcripts. Implications for cardiomyopathy-related point mutations (4269, 4317) in the tRNAIle gene.

A growing number of mutated mitochondrial tRNA genes have been found associated with severe human diseases. To investigate the potential interference of such mutations with the primordial function of tRNAs, i.e. their aminoacylation by cognate aminoacyl-tRNA synthetases, a human mitochondrial in vitro aminoacylation system specific for isoleucine has been established. Both native tRNAIleand isoleucyl-tRNA synthetase activity have been recovered from human placental mitochondria and the kinetic parameters of tRNA aminoacylation determined. The effect of pathological point mutations present in the mitochondrial gene encoding tRNAIlehas been tackled by investigating the isoleucylation properties of wild-type and mutated in vitro transcripts. Data show that: (i) modified nucleotides contribute to efficient isoleucylation; (ii) point mutation A4269G in the gene (A-->G at nt 7 in the tRNA), associated with a cardiomyopathy, does not affect aminoacylation significantly; (iii) point mutation A4317G (A-->G at nt 59 in the tRNA), reported in a case of fatal infantile cardiomyopathy, induces a small but significant decrease in isoleucylation. The potential implications of these findings on the understanding of the molecular mechanisms involved in the expression of pathology are discussed.

Adenine↗
PubMed1997

Is the activity of soluble CD14 enhanced following major trauma?

BACKGROUND: The molecule CD14 acts as a receptor for the protein-bound endotoxin (lipopolysaccharide [LPS]) complex and mediates the cellular effects of LPS. The soluble formation, sCD14, is supposed to neutralize circulating LPS (i.e., LPS antagonist) or transfer LPS effects to endothelial cells (i.e., LPS agonist). OBJECTIVE: To elucidate the release of sCD14 per se in patients with major trauma in the early posttrauma period. Our a priori hypothesis was that sCD14 release depends on the plasma LPS concentration simultaneously measured. PATIENTS: In a prospective study, 65 patients with multiple injuries (Injury Severity Score, 9-75) were enrolled. The patients were rescued by the medical helicopter service and directly admitted to our clinics. The plasma concentrations of sCD14 (enzyme immunoassay) and LPS (chromogenic limulus amebocyte lysate test) were analyzed. The first blood sample was collected immediately at the accident site. The following samples were drawn at intervals from 2 hours to daily for 2 weeks. RESULTS: Sixty-one patients survived the observation time. Immediately after trauma, their mean sCD14 level was not different from that of healthy individuals. Two hours later, a pronounced increase of sCD14 was observed and sustained throughout the observation period. Even nonsurvivors showed an increased sCD14 release, but less pronounced. In all patients, plasma LPS levels were elevated during the first 12 hours. CONCLUSIONS: Major trauma caused an increased release of sCD14. This elevation, however, was not correlated to LPS levels or to the severity of trauma (estimated by trauma scores). We found no evidence that sCD14 levels are of prognostic value regarding survival. Furthermore, the release of sCD14 did not occur in an LPS-neutralizing manner, but rendered possible an LPS-independent mechanism.

Adolescent↗
PubMed1997

[Diagnosis of blunt thoracic trauma in emergency care. Use of continuous pulse oximetry monitoring].

Chest trauma cases benefit to a great degree from adequate, timely initiated and consistent prehospital treatment. However, prehospital determination and evaluation of blunt chest trauma is associated with a high degree of uncertainty. The purpose of our study was to examine and determine, in a collective of 255 trauma patients, the value of additional prehospital pulse oximetric monitoring regarding the optimization of the emergency physician's diagnosis and treatment of blunt chest trauma. We conclude from our findings that, in addition to the physical examination, with the application of pulse oximetry the prehospital diagnosis of lung contusion as well as the early detection of tension pneumothorax are more accurate. Therefore, the combination of physical examination and pulse oximetric monitoring is a requirement for the optimization of prehospital diagnosis and therapy in blunt chest trauma.

Adolescent↗
PubMed1997

[Liberation of soluble CD14 (sCD 14) in plasma of trauma patients].

Membrane-fixed CD14 acts as a receptor for the protein-bound endotoxin (LPS) complex and mediates the cellular effects of endotoxin. Soluble CD14 (sCD14) is suggested to neutralize circulating LPS, i.e., acting as an endotoxin antagonist. The aim of this study was to elucidate the release of both sCD14 and endotoxin in traumatized patients, starting from the earliest phase after trauma. A total of 15 patients (O ISS = 19, 9-75) suffering major trauma were enrolled in this prospective study. Blood samples were collected as early as immediately at the site of accident, on hospital admission, and thereafter hourly, then daily. For patients (O ISS = 47) died within 24 h because of their severe injuries. Immediately after the accident as well as during the first 2 h after hospital admission, the mean sCD14 levels of surviving patients did not differ from those of healthy volunteers (n = 53). Thereafter, however, sCD14 increased continuously in the trauma group. The concentrations remained elevated throughout the entire observation period. There was, however, no relation between the sCD14 release and the pattern or the severity of injury. In contrast, endotoxin levels revealed a pattern-specific release. The highest plasma concentrations of LPS were observed in patients suffering from (additional) thoracic injury. On the basis of these results we conclude that the release of sCD14 after trauma does not reflect a strict principle such as action/reaction caused by the appearance of endotoxin immediately after the injury. Soluble CD14 is more likely release by an endotoxin-independent mechanism.

Adolescent↗
PubMed1996

[Intraosseous puncture in preclincal emergency medicine. Experiences of an air rescue service].

UNLABELLED: In prehospital emergency treatment, the timely establishment of a secure vascular access, especially in infants and small children, can be difficult or even impossible. An alternative to the puncture of peripheral or central veins is intraosseous (IO) puncture However, experience with this method in prehospital emergency medicine within the Federal Republic of Germany is extremely limited at present. After intensive theoretical and practical training of our trauma anaesthesiologists, IO puncture was introduced in our rescue helicopter program "Christoph 22" as an alternative to peripheral or central venous puncture in the prehospital treatment of patients up to 6 years of age. IO puncture is indicated after a maximum of three failed peripheral venous puncture attempts. The purpose of this study was to collect data and summarise first-hand experience on the prehospital use of the IO method as well as the practicability of our prescribed IO puncture algorithm in order to subject them to critical review and evaluation. MATERIALS AND METHODS: A restrospective study by the rescue helicopter service "Christoph 22" was carried out for the period 1 June 1993-31 August 1995. RESULTS: In a total of 1,455 primary rescue missions flown, the proportion of patients < and = 6 years of age, was 6.2% (n = 90). Ten patients in this partial collective (11.1%) were subjected to IO puncture (Fig. 3). In all of these cases (10/10), the first IO puncture attempt was successful. A standardized puncture technique was performed using the proximal tibia. The time required to successful placement of the IO infusion line was < and = 60 s in all cases. Complications, especially incorrect needle position, did not occur during the study period. Materials infused by IO infusion before hospitalisation included crystalloids (Lactated Ringer's, Päd OP) as well as colloids (hydroxyethylstarch, human albumin), adrenaline, atropine, ketamine, thiopentone, diazepam, fentanyl, succinylcholine, and vecuronium (Table 3). Prehospital induction of general anaesthesia using the IO infusion line was required by 2/10 children; dosage and onset of administered drugs was described by the trauma anaesthesiologists as being similar to that using an i.v. infusion line. Seven of the patients had been treated prior to the arrival of the rescue helicopter team by other emergency medical personnel; in all of these cases multiple peripheral and in 3 additional central venous puncture attempts had failed (duration of attempts: 10-50 min). Upon arrival of the rescue helicopter, 5 of these patients had been pulseless and non-breathing (Table 2). CONCLUSION: The IO infusion technique has proven to be a simple, fast, and safe alternative method of emergent access to the vascular system.

Aircraft↗
PubMed1996

[Semiquantitative capnometry--helpful in verification of tube position in trauma patients?].

Severely injured patients, in particular, benefit from initiation of endotracheal intubation and controlled ventilation before hospital admission. The most frequent and most serious mishap of this emergency procedure is inadvertent esophageal tube placement. A reliable and simple determination of proper tube placement involves capnometry, the measurement of carbon dioxide concentration during the respiratory cycle. The purpose of this study was to evaluate the dependability of semi-quantitative capnometry in verifying proper tube placement in the prehospital treatment of trauma patients. First, we determined and tested the suitability of the equipment used in this study (STAT CAP) in 40 patients under controlled hospital conditions; subsequently, we tested it under prehospital conditions on 40 trauma patients. Within the two study groups, the STAT CAP proved to be of high sensitivity (1.0) and specificity (1.0) in identifying tracheal tube position immediately after intubation manoeuvre, even in patients with a shock index > 1 (n = 14) and patients with cardiac arrest (n = 3). In cases of tracheal tube position, a CO2 signal was noted after two ventilations, on average, in both study groups. The average initial CO2 value recorded amongst the hospital study group was 30-50 mmHg, against 20-30 mmHg in the prehospital trauma group. The traditional signs used to verify endotracheal tube placement (direct visualization of the vocal cords and auscultation of breath sounds upon the chest) failed in three cases amongst the prehospital trauma group; in all of these cases the STAT CAP detected the (tracheal) tube placement correctly. We conclude that the STAT CAP reliably detects tracheal placement of endotracheal tube in non-arrested patients. In the arrested patient, interpretation of CO2 nonappearance requires caution. In addition to the traditional clinical signs, semi-quantitative capnometry is a meaningful supplement to verify tracheal tube placement in the prehospital management of trauma patients.

Adolescent↗
PubMed1995

Data processing in prehospital emergency medicine.

Information about the use of data processing systems in prehospital emergency medicine were collected, using a questionnaire sent to all German rescue helicopter bases. Twenty-seven of the 42 German rescue helicopter bases returned the questionnaire. At present, only 15 of them take advantage of electronic data processing. All of them enter their data manually by keyboard, automatic data transfer by means of a bar code reader is available at one base only. The stored data are used for statistical analysis (n = 15), quality assessment (n = 10), administration (n = 10), research (n = 9) and education (n = 7). Based on the data of this survey, one fifth of those who replied use their computer only for administrative purposes, the other also manage patient and mission data with their computer systems. Today, documentation of a rescue mission consists of patient data, vital data, mission data and information about the procedures carried out. The use of a computer system, however, requires more time and work than a handwritten record, when most of the data have to be entered manually using a keyboard. Future developments may include automated data transfer and digitization of handwritten documents to decrease the workload of the staff. For the automation of data transfer, configuration and synchronisation a standardized interface in all medical devices is required. There is a clear need for the use of data processing systems in emergency medicine.

Aircraft↗
PubMed1995

[Accidental hypothermia in trauma patients. Is it relevant to preclinical emergency treatment?].

Trauma patients are at great risk of accidental hypothermia (body temperature [BT] < 36 degrees C). Hypothermia influences the functioning of all organ systems and can lead to pathological changes, which in turn additionally complicate the trauma. Furthermore, hypothermia can, e.g., by influencing blood coagulation (reduction of thrombocyte aggregation, increased fibrinolysis) have a markedly unfavourable impact upon the in-hospital surgical treatment of the trauma patient. In a prospective study involving 302 trauma patients treated during primary helicopter rescue missions over a 1-year period, we studied the following factors: (1) incidence and degree of severity of hypothermia; (2) seasonal influence; (3) possibility of individual risk groups within the study group; (4) changes in BT during the prehospital treatment phase; and (5) their consequences for emergency treatment. METHOD. BT was taken upon commencement of emergency treatment and upon release of the patient to the receiving hospital. To avoid possible damage to the patient's tympanic membrane by the thermometer probe, we excluded all patients under 16 years of age and those with an indication of an ear or temporal-bone injury. In all cases standardized patient positioning was applied. The statistical evaluation was performed utilizing descriptive presentations and the Mann-Whitney U test and chi-square test. RESULTS. During study period, a total of 302 trauma patients were treated. On 228 of these, prehospital temperature monitoring was performed (151 males and 77 females, average age 41.8 years). Because of the established criteria for exceptions and equipment malfunction, no monitoring was performed on 74 patients. Traffic accidents (69%) were the major cause of injury (Table 2), predominantly the group with NACA III (32%), followed by NACA IV (22%) and NACA V (18%) (Table 3); 27% had multi-system trauma. BT monitoring disclosed that 49.6% or almost every second trauma patient, had hypothermia. The proportion of hypothermia II degrees (BT 34 degrees-30 degrees C) versus hypothermia III degrees (BT < 30 degrees C) was 6.6% to 0.5%. Our statistical evaluation did not disclose any significant connection between season of the year and frequency of accidental hypothermia. Special risk factors in regard to frequency and degree of severity turned out to be "entrapment" (98.1% of patients with an entrapment trauma [ET] versus 34.5% without such; P < 0.001) and age (56.8% of patients > 65 years of age without ET and 100% with ET; P < 0.001) (Figs. 2, 3). No significant changes in BT were noted during the prehospital treatment phase. Clinical symptoms pointing to hypothermia or other indicators, i.e., shivering, were only noted in 4.4% of the cases where the patients BT was below normal. CONCLUSION. Based upon our findings, accidental hypothermia poses a relevant problem in the prehospital treatment of trauma patients. It is not limited to a special season of the year. The variability or total absence of definite diagnostic symptoms underlines the necessity for prehospital BT monitoring, whereby tympanic-membrane thermometry has proven to be a worthwhile method.

Adolescent↗