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Biomedical subjects

T Peters

Publications and source records attributed to T Peters.

At least 37 records · Page 2Linked to original sources

[A comparison of the Proseal laryngeal mask to the standard laryngeal mask on anesthesized, non-relaxed patients].

It was our goal to compare the Proseal-laryngeal mask airway (PLMA) with the classical laryngeal mask airway (LMA) in a german multicenter trial. Handling of the instruments and application criteria were to be tested. 7 anaesthesia departments were able to take part in this study. 280 patients could be investigated after approval of the ethics committee of the medical faculty of the university of Goettingen. 145 patients received the PLMA and 135 the LMA. The surgical interventions were small to moderate procedures with a duration of at least 20 minutes in the sections general surgery, trauma/orthopedic surgery, urology, vascular surgery, gynecology, ENT-surgery and ophthalmology. There was equivalence of the two instruments PLMA and LMA concerning duration and ease of insertion, endoscopic position check, observations on emergence, potential for injury and some postoperative complaints. This equivalence could be confirmed statistically. Laryngospasm was observed in three, Bronchospasm in two patients with the PLMA, in no one with the LMA. In one case of laryngospasm and another of bronchospasm a mechanism of supraglottic laryngeal stenosis has been involved which may occur in rare instances with the PLMA. This mechanism is due to the double cuff of the PLMA with the instruments proximity to the laryngeal inlet. The seal pressure in both groups differs significantly (p = 0.001). The mean value for the seal pressure was 29,3 +/- 0,21 mbar for the PLMA and 20,9 +/- 0,21 mbar for the LMA. In the PLMA the gastric tube could be positioned with the first attempt in 118 patients, with the second attempt in 17 cases. In 10 patients the gastric tube could not be placed. Contrary to the LMA the tip of the PLMA cuff may be bent in some cases with loss of airway safety and positioning of the gastric tube. The symptoms sore throat and painful swallowing on the first postoperative day were more frequent with LMA application. These differences could be confirmed statistically (sore throat p = 0.01, painful swallowing p = 0.04). They may be explained by the more rigid LMA compared to the PLMA and by the fact that the LMA in this study was older than the PLMA, loosing plasticizer. The drainage tube within the PLMA offers safety from aspiration in patients with no primary aspiration risk, additional reassurance for a correct position and a better stability of the airway. Our data may support a wider indication range for the PLMA compared with the LMA. The PLMA may be applied in laparoscopies and lower abdominal surgical interventions. Careful clinical observation will show, if the minimal invasiveness of the PLMA offers an advantage for these patients. The PLMA should not be applied in patients with increased aspiration risk.

Adolescent↗

Kinetics of hepatitis C (HCV) viraemia and quasispecies during treatment of HCV associated cryoglobulinaemia with pulse cyclophosphamide.

OBJECTIVE: To investigate the effect of pulse cyclophosphamide treatment on hepatitis C virus (HCV) kinetics and quasispecies in interferon alpha (IFNalpha) resistant HCV related cryoglobulinaemic vasculitis. METHODS: Reports on two patients with severe manifestations of HCV related cryoglobulinaemia who failed to respond to interferon alpha are given. Both patients were treated with pulse cyclophosphamide (750-1000 mg/month for six and 11 months, respectively). HCV RNA was quantified and HCV quasispecies determined in cryoprecipitates and supernatants before and during treatment. RESULTS: Cryocrit and complement activation decreased in both patients with rebound of cryocrit in one case during continuing pulse cyclophosphamide treatment. Vasculitic symptoms improved. Alanine aminotransferase (ALT) levels and HCV viral load (0.2-0.4 log) increased slightly and reached pretreatment levels after cyclophosphamide was stopped. A highly heterogeneous quasispecies was found in the cryoprecipitate and supernatant of one patient, whereas the viral population was homogeneous in the other patient. After six cycles of cyclophosphamide, viral distances decreased non-significantly. However, phylogenetic analysis showed the evolution of distinct viral strains in one patient and replacement of the main viral population by another population in the second patient. CONCLUSIONS: Immunosuppressive treatment with pulse cyclophosphamide has a temporary limited effect on HCV associated cryoglobulinaemia and leads to a reversible increase of ALT levels and HCV viral load. Short term immunosuppression does not affect the viral heterogeneity as measured by amino acid and nucleotide distances in the hypervariable region 1 of HCV. A change of quasispecies was observed, but further studies are needed to evaluate if this does affect the outcome of IFNalpha treatment in such patients.

Aged↗

Molecular recognition of sialyl Lewis(x) and related saccharides by two lectins.

The interaction of sialyl Lewis(x), Lewis(x), and alpha-L-Fuc-(1-->3)-beta-D-GlcNAc with isolectin A from Lotus tetragonolobus (LTL-A), and with Aleuria aurantia agglutinin (AAA) was studied using NMR experiments and surface plasmon resonance. Both lectins are specific for fucose residues. From NMR experiments it was concluded that alpha-L-Fuc-(1-->3)-beta-D-GlcNAc and Lewis(x) bound to both lectins, whereas sialyl Lewis(x) only bound to AAA. Increased line broadening of 1H NMR signals of the carbohydrate ligands upon binding to AAA and LTL-A suggested that AAA bound to the ligands more tightly. Further comparison of line widths showed that for both lectins binding strengths decreased from alpha-L-Fuc-(1-->3)-beta-D-GlcNAc to Lewis(x) and were lowest for sialyl Lewis(x). Surface plasmon resonance measurements were then employed to yield accurate dissociation constants. TrNOESY, QUIET-trNOESY, and trROESY experiments delivered bioactive conformations of the carbohydrate ligands, and STD NMR experiments allowed a precise epitope mapping of the carbohydrates bound to the lectins. The bioactive conformation of Lewis(x) bound to LTL-A, or AAA revealed an unusual orientation of the fucose residue, with negative values for both dihedral angles, phi and psi, at the alpha(1-->3)-glycosidic linkage. A similar distortion of the fucose orientation was also observed for sialyl Lewis(x) bound to AAA. From STD NMR experiments it followed that only the L-fucose residues are in intimate contact with the protein. Presumably steric interactions are responsible for locking the sialic acid residue of sialyl Lewis(x) in one out of many orientations that are present in aqueous solution. The sialic acid residue of sialyl Lewis(x) bound to AAA adopts an orientation similar to that in the corresponding sialyl Lewis(x)/E-selectin complex.

Carbohydrate Conformation↗

[Occupational lead poisoning due to deficient protective measures at the work place].

UNLABELLED: Occupational lead poisoning due to deficient protective measures at the work place. HISTORY AND ADMISSION FINDINGS: A 27-year-old man who was working in the mixing plant of a company manufacturing synthetic materials, was admitted with colicky upper abdominal pain, loss of appetite and postprandial nausea for 3 weeks. On examination he had pain without guarding over the abdomen. INVESTIGATIONS: He had a normochronic anaemia (haemoglobin 12.5. g/dl). Ultrasound of the abdomen revealed splenomegaly. Gastroscopy excluded an ulcer. Deep duodenal biopsy showed Giardia intestinalis histologically. DIAGNOSIS, TREATMENT AND COURSE: As part of the differential diagnosis of abdominal colic and anaemia, lead poisoning was found, with the lead level markedly elevated to 1776 microgram/l. Penicillamine treatment rapidly reduced the blood lead level, but it had not yet become normal after 4 months. Exposure to lead at his work place was discovered. Subsequent tests there by the federal agency for occupational protection revealed massive deficiencies in protective measures. CONCLUSION: In present conditions abdominal colic must be viewed as a cardinal symptom of lead poisoning. Blood levels must be obtained as part of the differential diagnosis of abdominal pain of uncertain aetiology. If the diagnosis has been established and an occupational risk is possible, the appropriate occupational organizations and, if necessary, federal agency must be informed in order to exclude occupational exposure to lead. In Germany there still exist marked deficiencies in the protection of workers occupationally exposed to lead. Notification is essential to protect others similarly at risk.

Adult↗

[A new combined surgical interventional method for univentricular palliation of congenital heart defects].

UNLABELLED: Total cavo-pulmonary anastomosis is frequently performed to palliate patients with a broad variety of congenital heart defects with functionally univentricular hearts precluding biventricular circulation. In patients with risk factors for primary repair a stepwise approach is frequently chosen with initial creation of an aorto-pulmonary shunt followed by a Glenn anastomosis or hemifontan procedure. Finally a total cavo-pulmonary connection is completed surgically. The aim of this feasibility study was to develop a combined surgical-interventional approach for creation of a total cavo-pulmonary anastomosis which reduces the number of surgical interventions, precludes extracorporeal circulation and intracardiac sutures, putting the patients at risk for subsequent rhythm disturbances. METHODS: A Glenn anastomosis was created in 10 sheep without cardio-pulmonary bypass. The superior vena cava was banded superior to the cavo-atrial junction leaving a minimal lumen for subsequent interventional balloon dilatation and implantation of a stent graft. A 15 mm Gore-Tex tube was sutured around the inferior vena cava intrapericardially to provide resistance for subsequent interventional stent implantation. Total cavo-pulmonary anastomosis was completed interventionally by dilating the banded vena cava superior and connection of the inferior vena cava to the superior vena cava by implanting an Aneurx covered stent graft. RESULTS: All animals survived the combined surgical-interventional procedure. Stent deployment was possible without causing obstruction to the hepatic veins. Neither stent dislocation nor rhythm disturbances were encountered. CONCLUSIONS: Total cavo-pulmonary anastomosis can be achieved without intracardiac sutures and cardio-pulmonary bypass by use of a combined surgical-interventional approach using the Aneurx covered stent graft.

Animals↗

Lateral epicondylitis.

Satisfactory treatment of lateral epicondylitis results from correct diagnosis followed by a well-controlled operative or nonoperative treatment program. Many options for nonoperative and operative treatment exist for lateral epicondylitis. More study is needed on outcomes of both nonoperative treatment and operative treatment so that each patient can attain maximal improvement. Balanced assessments of specific patient populations, along with definitions of the optimal treatment for each group, are required. This will allow physicians to integrate the available information and improve patient care.

Adrenal Cortex Hormones↗

Bambi is coexpressed with Bmp-4 during mouse embryogenesis.

Signaling of TGF-beta superfamily members is tightly controlled by an elaborate network of regulators (for recent review see Trends Genet. 15 (1999) 3; Genes Dev. 14 (2000) 627). Recently, the transmembrane protein BAMBI (BMP and activin membrane-bound inhibitor) has been shown to interfere with Bmp and activin-like signaling by inhibiting Tgf-beta type I receptor activation (Nature 401 (1999) 480). In striking contrast to other Bmp antagonists like noggin (Cell 86 (1996) 599) or chordin (Cell 86 (1996) 589), BAMBI is strictly coexpressed with Bmp-4 during early Xenopus embryogenesis. The grouping of genes according to their shared complex spatial expression pattern and their involvement in the same biological signaling pathway has been referred to as synexpression group. This concept facilitates prognoses about the roles of a group member with unknown function. Apparently, only a minority of genes is organized in synexpression groups and up to now they have mainly been described in yeast and Xenopus (for review see Nature 402 (1999) 483). In the frog, BAMBI is a member of the Bmp-4 synexpression group (Nature 401 (1999) 480). We identified two murine homologues of BAMBI one of which, named Bambi-psi, is a pseudogene. We show that the spatiotemporal expression pattern of Bambi closely matches that of Bmp-4 during mouse embryonic development. Moreover, we show that Bambi expression is induced in mouse embryonic fibroblasts by Bmp-4. Hence, we provide first evidence for the existence of an evolutionarily conserved Bmp-4 synexpression group in mammals.

Amino Acid Sequence↗

Expression of Irx6 during mouse morphogenesis.

Iroquois (Irx) proteins comprise a family of homeodomain-containing transcription factors involved in patterning and regionalization of embryonic tissues in both vertebrates and invertebrates. The six murine Irx genes are organized in two clusters, each consisting of three genes. Irx1, Irx2 and Irx4 belong to the IrxA cluster on chromosome 13, whereas Irx3, Irx5 and Irx6, comprising the IrxB cluster, are located on chromosome 8 (Peters et al., Genome Res. 10 (2000) 1453). Developmental expression patterns have so far only been reported for five Irx genes. Here, we investigated the expression pattern of Irx6 during mouse morphogenesis and early organogenesis. The pattern was found to be much more restricted compared to the other five Irx genes, and its level of expression was much lower.

Animals↗

Gene and cluster-specific expression of the Iroquois family members during mouse development.

Mammalian homologues of the Drosophila Iroquois homeobox gene complex, involved in patterning and regionalization of differentiation, have recently been identified (Mech. Dev., 69 (1997) 169; Dev. Biol., 217 (2000) 266; Dev. Dyn., 218 (2000) 160; Mech. Dev., 91 (2000) 317; Dev. Biol., 224 (2000) 263; Genome Res., 10 (2000) 1453; Mech. Dev., 103 (2001) 193). The six members of the murine family were found to be organized in two cognate clusters of three genes each, Irx1, -2, -4 and Irx3, -5, -6, respectively (Peters et al., 2000). As a basis for further study of their regulation and function we performed a comparative analysis of the genomic organization and of the expression patterns of all six Irx genes. The genes are expressed in highly specific and regionalized patterns of ectoderm, mesoderm and endoderm derived tissues. In most tissues the pattern of expression of the clustered genes, especially of Irx1 and -2 and of Irx3 and -5, respectively, closely resembled each other while those of Irx4 and -6 were very divergent. Interestingly, the expression of cognate genes was found to be mutually exclusive in adjacent and interacting tissues of limb, heart and the laryncho-pharyncheal region. The results indicate that the Irx genes are coordinately regulated at the level of the cluster.

Animals↗

[Automated swinging flashlight test in patients with optic nerve diseases].

AIM OF THE STUDY: The swinging flashlight test is an objective method to diagnose a lesion of the anterior visual pathways. However, errors and faults may easily alter the test's results. Hence, the value of the swinging flashlight test depends highly on the examiner's skills. Therefore an automated and objective procedure was developed which is independent from the examiner. METHODS: A binocularly measuring instrument adapted for video pupillography was supplied with two arrays of light emitting diodes in front of each eye of the subject. By means of this illumination, pupillary light reflexes are elicited alternately. Pupil size is registered continuously, and after artifact elimination, the response amplitudes of the pupils are determined as a mean of right and left pupil. Responses elicited via right and left eye are compared. By varying the stimulus intensity it is possible to measure the amount of the relative afferent pupillary defect. The procedure was tested in 31 patients with optic nerve disorders. RESULTS: The measurements were easily feasible, stable and reliable. Correlation between the relative afferent pupillary defect detected manually by grey filter compensating and with the automated procedure proved to be high. Both variables correlated highly significant with a Spearman rank coefficient of 0.65. If the clinical test is regarded as the golden standard, the automated swinging flashlight test is able to detect 85% of the relative afferent pupillary defects > or = 0.3 logE and 94% of the defects > or = 0.6 logE. CONCLUSION: The automated swinging flashlight test can be recommended to exclude influences by the examiner or if the exact amount of the relative afferent pupillary defect is desired, e.g. when monitoring therapeutic effects in optic nerve diseases. Furthermore, an automated swinging flashlight test could serve as a screening test.

Adult↗

Pharmacokinetic/pharmacodynamic evaluation of the NHE inhibitor eniporide.

The aim of this study was to investigate the pharmacokinetics and pharmacodynamics of the new cardioprotective sodium/proton exchange (NHE-1) inhibitor eniporide in humans. Eniporide was administered intravenously to healthy volunteers in doses between 2.5 and 100 mg. Concentrations of parent drug and its metabolite were measured by HPLC, and the data were analyzed by noncompartmental and compartmental pharmacokinetic methods. Platelet-swelling time was determined in each subject as a biomarker to assess pharmacodynamic activity. Eniporide showed linear pharmacokinetics with an average half-life of approximately 2 hours. The mean total body clearance was 34.4 L/h. The mean volume of distribution (Vdss) was 77.5 L, and the mean residence time was 2.3 hours. An average of 43% of the dose was recovered unchanged from urine. A pharmacokinetic two-compartment model was found suitable to provide excellent curve fits of the measured plasma concentration profiles. Plasma concentrations of the major metabolite were lower than that of the parent drug. An average of 27% of the dose was found in urine as that metabolite. The effect on platelet swelling could be well characterized by a direct Emax model. The average concentration for half-maximum effect (IC50) was 12 ng/mL. Eniporide was found to have predictable linear pharmacokinetics in the investigated dose range. Platelet-swelling time was shown to be a reproducible individual biomarker for pharmacodynamic activity, with great potential for a surrogate that predicts clinical outcome, since this effect is mediated through the same mechanism of action (NHE-1 inhibition) as the desired cardioprotective activity. Pharmacokinetic/pharmacodynamic modeling allowed a first estimate of the degree of NHE inhibition in the investigated dose range.

Adolescent↗

Guidelines and educational outreach visits from community pharmacists to improve prescribing in general practice: a randomised controlled trial.

OBJECTIVES: To evaluate the effectiveness of guidelines with or without one-to-one educational outreach visits by community pharmacists in improving general practice prescribing for non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: Cluster randomised trial of 20 general practices within Avon, England. Practices were randomised to three groups: control; mailed guidelines; mailed guidelines plus educational outreach visits. General practitioners (GPs) in the latter group received two one-to-one outreach visits from community pharmacists. Changes in prescribing were measured using outcomes derived from prescribing analysis and cost (PACT) data. The primary outcome measure was change in the volume of prescribing for ibuprofen, diclofenac and naproxen as a percentage of total NSAID prescribing. Six secondary outcomes included other measures of prescribing quality and volume. A cost-benefit analysis was performed. RESULTS: No significant differences were observed for the primary outcome measure: practices receiving outreach visits prescribed only 2.1% [95% confidence interval (CI): -0.8 to 5.0] more of the three recommended NSAIDs than the control practices did and 1.6% (95% CI: -1.4 to 4.7) more than practices that received guidelines only. Following adjustment for multiple comparisons, only one secondary outcome showed a statistically significant difference between the groups: the proportion of prescribing of the five most frequently used drugs was 2.2% (95% CI: 0.9 to 3.6) higher in the educational outreach group compared with the control group. A net increase in costs was shown with both interventions. CONCLUSIONS: Although good prescribing at baseline in the participating practices limited the capacity for improvement, this trial provides no evidence that guidelines with or without educational outreach visits from community pharmacists lead to substantial improvements in prescribing behaviour.

Anti-Inflammatory Agents, Non-Steroidal↗

Day in, day out: the everyday therapy of community clinics.

This paper describes the timing and nature of therapy provided within a recent randomised controlled trial (RCT) of preschool speech and language therapy services. There is literature that describes and evaluates speech and language therapy but there is little indication of how this is translated into everyday practice. The study collected data from 21 speech and language therapists (SLTs) in 16 community clinics. The areas targeted, goals, approaches used, the frequency and timing of contact for the 68 children who received treatment were documented. The data show that several aspects of therapy were frequently targeted simultaneously, that approaches were combined and that the frequency of therapy did not vary with severity. The discussion will consider the gap between published programmes and everyday practice and the implications for effectiveness.

Child, Preschool↗

Who's afraid of the randomised controlled trial? Parents' views of an SLT research study.

Evidence-based health care is now a reality within the national health service (NHS) and the randomised controlled trial (RCT) is the linchpin of this movement. In modern health care, there has also been a shift towards understanding client perspectives. With regard to clients' participation in research, much consideration has been given to ethical issues and barriers to participation. However, less attention has been paid to the participants' views of clinical trials and understanding how they construe the research. This paper reports a study of the attitudes of parents whose children took part in an RCT. Data were collected from the parents of 20 children, using qualitative in-depth interviews. Parents talked about the meaning of their participation, their motivation for taking part and their understanding of the nature of the trial. The implications of the findings for future research will be considered.

Attitude↗

Mapping the binding of synthetic disaccharides representing epitopes of chlamydial lipopolysaccharide to antibodies with NMR.

A NMR study of the binding of the synthetic disaccharides alpha-Kdo-(2-->4)-alpha-Kdo-(2-->O)-allyl 1 (Kdo, 3-deoxy-D-manno-oct-2-ulopyranosonic acid) and alpha-Kdo-(2-->8)-alpha-Kdo-(2-->O)-allyl 2, representing partial structures of the lipopolysaccharide epitope of the intracellular bacteria Chlamydia, to corresponding monoclonal antibodies (mAbs) S23-24, S25-39, and S25-2 is presented. The conformations of 1 bound to mAbs S25-39 and of 2 bound to mAbs S23-24 and S25-39 were analyzed by employing transfer-NOESY (trNOESY) and QUIET-trNOESY experiments. A quantitative analysis of QUIET-trNOESY buildup curves clearly showed that S25-39 recognized a conformation of 1 that was similar to the global energy minimum of 1, and significantly deviated from the conformation of 1 bound to mAb S25-2. For disaccharide 2, only a qualitative analysis was possible because of severe spectral overlap. Nevertheless, the analysis showed that all mAbs most likely bound to only one conformational family of 2. Saturation transfer difference (STD) NMR experiments were then employed to analyze the binding epitopes of the disaccharide ligands 1 and 2 when binding to mAbs S23-24, S25-39, and S25-2. It was found that the nonreducing pyranose unit was the major binding epitope, irrespective of the mAb and the disaccharide that were employed. Individual differences were related to the engagement of other portions of the disaccharide ligands.

Animals↗