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Biomedical subjects

K Becker

Publications and source records attributed to K Becker.

At least 235 records · Page 13Linked to original sources

Design and validation of an intelligent patient monitoring and alarm system based on a fuzzy logic process model.

The process of patient care performed by an anaesthesiologist during high invasive surgery requires fundamental knowledge of the physiologic processes and a long standing experience in patient management to cope with the inter-individual variability of the patients. Biomedical engineering research improves the patient monitoring task by providing technical devices to measure a large number of a patient's vital parameters. These measurements improve the safety of the patient during the surgical procedure, because pathological states can be recognised earlier, but may also lead to an increased cognitive load of the physician. In order to reduce cognitive strain and to support intra-operative monitoring for the anaesthesiologist an intelligent patient monitoring and alarm system has been proposed and implemented which evaluates a patient's haemodynamic state on the basis of a current vital parameter constellation with a knowledge-based approach. In this paper general design aspects and evaluation of the intelligent patient monitoring and alarm system in the operating theatre are described. The validation of the inference engine of the intelligent patient monitoring and alarm system was performed in two steps. Firstly, the knowledge base was validated with real patient data which was acquired online in the operating theatre. Secondly, a research prototype of the whole system was implemented in the operating theatre. In the first step, the anaesthetists were asked to enter a state variable evaluation before a drug application or any other intervention on the patient into a recording system. These state variable evaluations were compared to those generated by the intelligent alarm system on the same vital parameter constellations. Altogether 641 state variable evaluations were entered by six different physicians. In total, the sensitivity of alarm recognition is 99.3%, the specificity is 66% and the predictability is 45%. The second step was performed using a research prototype of the system in anaesthesiological routine. The evaluation of 684 events yielded a sensitivity, specificity and predictability of the alarm recognition of more than 99%.

Anesthesiology↗

TRAMP, a novel apoptosis-mediating receptor with sequence homology to tumor necrosis factor receptor 1 and Fas(Apo-1/CD95).

A novel member of the tumor necrosis factor (TNF) receptor family, designated TRAMP, has been identified. The structural organization of the 393 amino acid long human TRAMP is most homologous to TNF receptor 1. TRAMP is abundantly expressed on thymocytes and lymphocytes. Its extracellular domain is composed of four cysteine-rich domains, and the cytoplasmic region contains a death domain known to signal apoptosis. Overexpression of TRAMP leads to two major responses, NF-kappaB activation and apoptosis. TRAMP-induced cell death is inhibited by an inhibitor of ICE-like proteases, but not by Bcl-2. In addition, TRAMP does not appear to interact with any of the known apoptosis-inducing ligands of the TNF family.

Adaptor Proteins, Signal Transducing↗

Trophic effect of angiotensin II in neonatal rat cardiomyocytes: role of endothelin-1 and non-myocyte cells.

1. Angiotensin II (AII) and the endothelins (ET) are known to be potent trophic stimuli in various cells including cardiomyocytes. In order to characterize further these effects we studied, in neonatal rat ventricular cardiomyocytes, the effects of several endothelin-receptor antagonists and the AT1-receptor antagonist losartan on AII- and endothelin-induced inositol phosphate (IP)-formation (assessed as accumulation of total [3H]-IPs in myo-[3H]-inositol prelabelled cells) and increase in rate of protein synthesis (assessed as [3H]-phenylalanine incorporation). 2. Endothelin (10 pM-1 microM) concentration-dependently increased IP-formation (max. increase at 100 nM ET-1: 130 +/- 14% above basal, n = 25) and [3H]-phenylalanine incorporation (max. increase at 1 microM: 52 +/- 4% above basal, n = 16) with an order of potency: ET-1 > > ET-3. Both effects were antagonized by the ETA/ETB-receptor antagonist bosentan and the ETA-receptor antagonist BQ-123, but not affected by the ETB-receptor antagonist IRL 1038 and the AT1-receptor antagonist losartan. 3. Pretreatment of the cells with 500 ng ml-1 pertussis toxin (PTX) overnight that completely inactivated PTX-sensitive G-proteins did not attenuate but rather enhance ET-1-induced IP-formation. On the other hand, in PTX-pretreated cardiomyocytes ET-1-induced [3H]-phenylalanine incorporation was decreased by 39 +/- 5% (n = 5). 4. All (1 nM-1 microM) concentration-dependently increased IP-formation (max. increase at 1 microM: 42 +/- 7% above basal, n = 16) and [3H]-phenylalanine incorporation (max. increase at 1 microM: 29 +/- 2%, n = 9). These effects were antagonized by losartan, but they were also antagonized by bosentan and BQ-123. 5. In well-defined cultures of cardiomyocytes (not contaminated with non-myocyte cells) All failed to increase [3H]-phenylalanine incorporation: addition of non-myocyte cells to the cardiomyocytes restored All-induced increase in [3H]-phenylalanine incorporation. 6. We conclude that, in rat neonatal ventricular cardiomyocytes, (a) the ET-1-induced increase in rate of protein synthesis (through ETA-receptor stimulation) involves at least two signalling pathways: one via a PTX-insensitive G-protein coupled to IP-formation, and the other one via a PTX-sensitive G-protein, and (b) the trophic effects of All are brought about via local ET-1 secretion upon AT1-receptor stimulation in neonatal rat ventricular non-myocyte cells.

Angiotensin II↗

Topical benzocaine anaesthesia lacks analgesic effects in painful non-acid oesophagitis.

BACKGROUND: No established treatment exists for pain relief in symptomatic non-acid oesophagitis. One of the most common topical anaesthetics is benzocaine which has been demonstrated to produce excellent analgesia on oral mucous membranes. METHODS: In a prospective, placebo-controlled, balanced, single-blinded study, 26 patients with retrosternal discomfort or odynophagia due to painful non-acid oesophagitis were treated either with oral benzocaine 0.75% solution (n = 14) or with benzocaine-free solvent (placebo, n = 12) at a daily dose of 20-40 mL, for up to 6 consecutive days (median 5.5 days). During the study period patients recorded subjective pain scores for both complaints on visual analogue scales. RESULTS: Benzocaine did not affect pain scores for any of the two symptoms, nor did it alter global subjective or objective assessment of therapy outcome in treated compared to untreated subjects (P > 0.05). There was a non-significant tendency for placebo patients to stop prematurely their study medication more often, because of lack of analgesic efficacy (P = 0.098). CONCLUSIONS: Topical benzocaine cannot be recommended for routine symptomatic pain relief in non-acid oesophagitis. By indirect evidence, it is assumed that pain perception of non-acid oesophagitis is not preferentially mediated by superficially located mucosal nociceptors.

Administration, Topical↗

Degradation of quillaja saponins by mixed culture of rumen microbes.

Quillaja saponin (QS) was incubated at 39 degrees C in an in vitro medium containing rumen liquor from a cow fed a roughage diet. No degradation of QS was observed up to 6 h of fermentation. Incubation for 9, 12 and 24 h decreased the content of QS by 16%, 45% and 100%. The content of QS did not decrease when incubated for 24 h in the medium containing autoclaved rumen liquor, suggesting that rumen microbes have enzyme(s) capable fo degrading QS. The fate of QS will help gain a better understanding of mechanisms of action of QS on rumen fermentation, and its beneficial effects mediated by binding to ammonia.

Animals↗

The degradability characteristics of fifty-four roughages and roughage neutral-detergent fibres as described by in vitro gas production and their relationship to voluntary feed intake.

Fifty-four roughages of known voluntary dry-matter intakes (DMI; range 7.8-35.2 g/kg live weight per d) were examined in vitro in a gas production test. Samples (200 mg) of roughage and roughage neutral-detergent fibre (NDF) respectively were incubated in a mixed suspension of rumen contents for 96 h and the gas volumes recorded after 4, 6, 8, 12, 24, 30, 36, 48, 54, 60 and 96 h. The kinetics of gas production were derived from the volume recordings described by the exponential equation Y = A + B(l-e-ct) where A is the intercept and ideally reflects the fermentation of the soluble and readily available fraction of the feed, B describes the fermentation of the insoluble (but with time fermentable) fraction and c the fractional rate at which B is fermented per h; A + B describes total fermentation. In vitro true dry matter (TD) and NDF degradabilities (NDF-D) after 24 h incubation were also determined. Of the variation in DMI, 75% was accounted for by the in vitro gas production parameters A, B and c in stepwise multiple regressions; 82% of the variation in DMI was explained by the parameters (ANDF + BNDF) and cNDF as obtained from the incubation of roughage NDF. The rate constants (c) were less important than parameters related to the extent of gas production, accounting for only 6.5 (whole roughage) and 4.1% (NDF) of the variation in DMI. There was no statistical advantage in the use of the exponential model describing extent and rate of fermentation over some of the simple gas volume measurements: 75% of the variation in DMI was accounted for by in vitro gas production of whole roughage after 8 h of incubation. On average gas production from NDF measured from 24-96 h accounted for 81% of the variation in DMI. A combination of gas volume measurements after a short period of incubation (4-8 h) with a concomitant determination of NDF-D after many hours (> or = 24 h) can render NDF preparations and long incubation times redundant. A method is suggested to obtain two results for DMI prediction in one single incubation. Of the variation in DMI 80% was accounted for by the incubation of 500 mg whole roughage when incubation was terminated after 24 h and the residual undegraded substrate quantified.

Animal Feed↗

The relationship between in vitro gas production, in vitro microbial biomass yield and 15N incorporation and its implications for the prediction of voluntary feed intake of roughages.

The relationship between in vitro gas production, concomitant in vitro apparent and true DM degradability has been examined in forty-two roughages. The partitioning of truly-degraded substrate between gas volume and microbial biomass yield and 15N incorporation into cells was also investigated. The relevance of this partitioning for the regulation of DM intake (DMI) was examined for fifty-four roughages. The results can be summarized as follows. In vitro gas production and in vitro apparent and true degradability are highly correlated (P < 0.0001), r being 0.96 and 0.95 respectively. There is an inverse relationship between in vitro gas production and microbial biomass yield (r--0.67, (P < 0.0001) and also 15N enrichment (P < 0.001) when the variables were related to a given unit of substrate truly degraded. Selecting roughages by in vitro gas production may well be a selection against maximum microbial yield and a combination of in vitro gas volume measurements with a complementary determination of the substrate truly degraded is proposed, to calculate a partitioning factor (PF) reflecting the variation of short-chain fatty acid production per unit substrate degraded. PF is calculated as the ratio, substrate truly degraded: gas produced by it. PF was highly significant (P < 0.0001) in DMI prediction when included in stepwise multiple correlations together with in vitro gas volume variables reflecting the extent and rate of gas production; 11% of the variation in DMI was accounted for by the PF. The total model, including extent and rate of gas production and the PF, accounted for 84% of the variation in DMI. Roughages producing proportionally less gas per unit substrate truly degraded had higher feed intakes.

Animal Feed↗

Granulated polyamide as external marker to estimate total faecal excretion of grazing cattle in extensive management systems.

Granulated polyamide (PA) was tested for use as an external marker to estimate faecal DM (FDM) excretion of Zebu cattle (Bos indicus). The study was conducted in Mali, using seven and eighteen animals respectively in four field trials and six indoor experiments. Cattle ate fresh or dry pasture vegetation and half the animals were additionally supplemented with crop byproducts. Gelatine capsules containing 35, 40 or 45 g PA were administered orally at 12 h intervals. Estimates of FDM were based on the average marker concentration in faeces and were correlated with the actual excretion measured by total faecal collection. The pre-measurement period required to establish equilibrium for regular marker dosing was determined at 4 d. Except for diets with a N content of less than 9.26 g/kg organic matter, marker recovery averaged 98.1 (SE 0.93)% (n 62), and was not influenced by diet composition and the quantity of feed ingested (P > 0.05). Estimates of FDM based on average PA concentrations in faecal samples were correlated to the actual excretion with r 0.98 (n 62; P < or = 0.001). Since the PA concentration in individual faecal grab-samples is not correlated with either sample mass or sampling time, accurate estimates of FDM require a grab-sampling schedule that covers the 24 h day. However, estimates of FDM were found to be acceptable if calculations are based on the average PA concentration in the sub-total of samples collected during the day or during night respectively (r 0.95, n 29; P < or = 0.001 in both cases). It is concluded that the use of PA marker is a simple and inexpensive method resulting in reliable estimates of FDM. Since sophisticated analytical procedures are not required to recover PA in faecal samples, the marker is particularly suitable for application in extensive grazing systems and in studies conducted in less-developed countries.

Analysis of Variance↗

Characterization and natural course of cardiac autonomic nervous dysfunction in HIV-infected patients.

OBJECTIVE: To examine the degree, pattern, and natural history of cardiac autonomic nervous dysfunction in patients infected with HIV. DESIGN: Cross-sectional and prospective longitudinal cohort study. SETTING: Primary care and tertiary referral university centre. PARTICIPANTS: Thirty-five consecutive HIV-infected patients who had either not yet developed AIDS (15 pre-AIDS patients) or who were at the Centers for Disease Control and Prevention (CDC) AIDS stage (n = 20), and 29 healthy age- and sex-matched HIV-negative controls. METHODS: Computer-aided power spectral analysis of 15 standardized parameters of heart-rate variability (HRV). RESULTS: Pre-AIDS patients as a group did not exhibit any HRV parameters to be significantly different from healthy controls (P > 0.017), whereas AIDS patients demonstrated reduced HRV in 14 parameters (93.3%) compared with healthy subjects (p > 0.017). Median proportion of abnormal HRV parameters (< 10th percentile of controls) per individual was 9.1% in pre-AIDS patients and 61.3% in AIDS patients (P = 0.0347). Progressive CDC stages inversely correlated to 10 HRV parameters (66.7%; -0.50 < or = r < or = -0.36; P < 0.05). Follow-up testing in 10 pre-AIDS and six AIDS patients after 6-16 months (median, 12.5 months) did not reveal deterioration of HRV (P < 0.05). A dysautonomia symptom score correlated to 10 HRV parameters (66.7%; -0.14 < r < -0.55; P < 0.05). CONCLUSIONS: Cardiac autonomic nervous dysfunction is severe in AIDS patients, although not significant in pre-AIDS patients. Cardiac autonomic nervous dysfunction proceeds with HIV disease progression, although its individual course is slow.

Adolescent↗

Intestinal protein leakage in the acquired immunodeficiency syndrome.

Body wasting, protein catabolism, and hypoalbuminemia are complicating features of the acquired immunodeficiency syndrome (AIDS). Given their multifactorial causes, the contributing role of intestinal protein loss has not yet been fully elucidated. To quantify enteric protein leakage, determination of fecal alpha 1-antitrypsin (AAT) excretion has been established as an accurate and reliable endogenous marker. We estimated AAT concentration by standard immune nephelometry in duplicate random stool samples of 49 patients with AIDS, and we compared it to that of 43 patients with chronic inflammatory bowel disease and to 34 healthy controls. When compared with healthy persons, patients with AIDS had increased fecal AAT excretion regardless of current opportunistic intestinal infections and fecal AAT excretion similar to that of patients with quiescent chronic inflammatory bowel disease. The ratio of fecal and serum AAT concentration was not different between AIDS patients and healthy controls, although it was consistently increased in those with chronic inflammatory bowel disease. Significant intestinal protein leakage occurs in patients with AIDS, probably due to primary impairment of gut permeability. Enteric protein loss may be an important feature of human immunodeficiency virus-associated enteropathy with altered mucosal barrier function.

AIDS-Related Opportunistic Infections↗

Specific pattern of circulating endothelial adhesion molecules in HIV-associated Kaposi's sarcoma.

BACKGROUND: Circulating endothelial adhesion molecules have been found to be increased in states of immune activation, but little is known about their significance in the assessment of endothelial neoplasms. One of the most common tumors supposed to be derived from endothelial origin is HIV-associated Kaposi's sarcoma (KS). METHODS: Plasma concentrations of sCD54 (= intercellular adhesion molecule-1), sCD106 (= vascular cell adhesion molecule-1), and sCD62E (= E-selectin) were quantified by sandwich ELISA in 54 AIDS patients who were either free of active opportunistic disorders (n = 15, AIDS controls), or suffering from acute infections (n = 16), or exhibiting KS (n = 23), and in 18 age- and sex-matched healthy HIV-negative controls. RESULTS: Both sCD54 and sCD106 plasma levels were consistently increased in all AIDS patients irrespective of concurrent opportunistic disorders (p < 0.005), while sCD62E levels were not altered in AIDS patients without KS (p > 0.05). In KS patients, sCD62E concentrations were decreased both compared to healthy (p = 0.0007) and to AIDS controls (p = 0.04), and stimulated sCD54 levels were less elevated than those of AIDS controls (p = 0.02). Plasma concentrations of all three adhesion molecules did not correlate to KS tumor stage. CONCLUSION: There appears to be a specific pattern of circulating endothelial adhesion molecules in AIDS patients with associated KS. Although the present findings do not support a role for their determination as tumor markers, they might be involved in KS tumor pathogenesis.

AIDS-Related Opportunistic Infections↗

Occult eutopic Cushing's syndrome--failure of simultaneous bilateral petrosal sinus sampling to diagnose pituitary-dependent Cushing's syndrome.

Simultaneous bilateral inferior petrosal sinus (IPS) sampling has been repeatedly proposed to be a highly specific approach for the diagnosis of Cushing's disease and 100% sensitivity in detecting autonomous pituitary ACTH secretion by an adenoma has been reported in a large series. We now report on a patient suffering from ACTH-dependent Cushing's syndrome in whom repeated bilateral IPS sampling failed to detect a central/peripheral gradient diagnostic for autonomous pituitary ACTH secretion during initial evaluation. Applying lysine vasopressin as the corticotroph secretatogue, the maximum central/peripheral gradient was 1.0 before and 1.1 following stimulation. Moreover, results of high dose dexamethasone and corticotrophin releasing hormone administration suggested ectopic ACTH secretion. Since thorough diagnostic procedures failed to localise a suspected carcinoid tumour, occult ectopic Cushing's syndrome was diagnosed. Eight years later, a pituitary macroadenoma was detected by magnetic resonance imaging (MRI), IPS catheterisation then revealed a maximal central/ peripheral gradient of 9.3 before and 20.4 after the intravenous administration of lysine vasopressin. Resected tumour tissue was classified as a typical densely granulated ACTH cell adenoma. We conclude that repeated MRI scans should be included in the follow-up of patients with a diagnosis of occult ectopic Cushing's syndrome to avoid the risk of overlooking 'occult eutopic Cushing's syndrome'.

Adenoma↗

Near-infrared spectroscopy and spectral mapping of Jupiter and the Galilean satellites: results from Galileo's initial orbit.

The Near Infrared Mapping Spectrometer performed spectral studies of Jupiter and the Galilean satellites during the June 1996 perijove pass of the Galileo spacecraft. Spectra for a 5-micrometer hot spot on Jupiter are consistent with the absence of a significant water cloud above 8 bars and with a depletion of water compared to that predicted for solar composition, corroborating results from the Galileo probe. Great Red Spot (GRS) spectral images show that parts of this feature extend upward to 240 millibars, although considerable altitude-dependent structure is found within it. A ring of dense clouds surrounds the GRS and is lower than it by 3 to 7 kilometers. Spectra of Callisto and Ganymede reveal a feature at 4. 25 micrometers, attributed to the presence of hydrated minerals or possibly carbon dioxide on their surfaces. Spectra of Europa's high latitudes imply that fine-grained water frost overlies larger grains. Several active volcanic regions were found on Io, with temperatures of 420 to 620 kelvin and projected areas of 5 to 70 square kilometers.

Ammonia↗

Randomized trial with early-stage Hodgkin's disease testing 30 Gy vs. 40 Gy extended field radiotherapy alone.

PURPOSE: To evaluate whether or not a total dose (TD) of 30 Gy is sufficient for treatment of assumed subclinical Hodgkin's Disease compared to 40 Gy TD with early stage Hodgkin's Disease (ESHD). METHODS AND MATERIALS: In a prospective multicenter trial, 376 patients with laparotomy-proven ESHD stages PS IA to PS IIB without risk factors such as large mediastinum, massive splenic involvement, extranodal disease, elevated erythrocyte sedimentation rate (ESR), and/or three or more involved lymph node areas were randomly allocated either to receive (ARM A) 40 Gy TD extended field-radiotherapy (EF-RT) or (ARM B) 30 Gy TD EF-RT plus 10 Gy TD involved field-radiotherapy (IF-RT), both arms without any chemotherapy. Three hundred sixty-six of these patients were evaluable for early and long-term response, such as remission status, freedom from treatment failure (FFTF), and overall survival (OAS). For quality control, all planning and verification films as well as dose charts were prospectively reviewed by a panel of four experts, all heads of a radiotherapy department, where protocol violations (PV) were seen either with regard to errors in treatment technique, treatment volume, in TD and/or in dose/time-relationship. RESULTS: Treatment resulted in a complete remission (CR) of 98%; in a 5-year FFTF of 76%, and a 5-year OAS of 97%. There was no difference between the two arms in favor of 40 Gy EF compared to 30 Gy EF regarding FFTF and OAS, without any in field relapse throughout the EF volumes. Expectedly, 5-years FFTF was significantly influenced by the quality of radiotherapeutical procedures: 70% with protocol violations (PV) vs. 82% without PV. CONCLUSION: Subclinical involvement in ESHD without risk factors is sufficiently treated by a TD of 30 Gy without chemotherapy, leading to a 5-years FFTF of 82% and a 5-year OAS of 97% in a multicenter treatment setting, where quality assurance is mandatory.

Adolescent↗

Molecular cloning and characterization of a putative glutathione reductase gene, the PfGR2 gene, from Plasmodium falciparum.

Recently, glutathione reductase (GR) has emerged as a promising target for antiparasitic drugs. The central role of GR in cellular antioxidant defence, the particular susceptibility of intracellular parasites like Plasmodium falciparum to oxidative stress, and successful inhibitor studies substantiate this approach. However, more information is required on the structural and functional characteristics of GR from malarial parasites and differences from the enzyme of host erythrocytes. We have identified a putative P. falciparum GR gene coding for a polypeptide (PfGR2) of 500 amino acids that exhibits 40-45% sequence identity with GR enzymes from other species. 18 out of 19 residues contributing to glutathione binding are identical in the putative PfGR2 and human GR. According to Southern blot analysis, the PfGR2 gene is present as a single-copy gene. It is expressed during the intraerythrocytic life cycle. Stage-specific Northern blot analysis demonstrates that the PfGR2 gene is only weakly transcribed in ring, early trophozoite, and segmenter stages; major transcription occurs in the late trophozoite/early schizont stage. This is consistent with the high glutathione reductase activity found in early schizonts. Other data also suggest that PfGR2 corresponds to the enzyme isolated from parasitized erythrocytes. These criteria include the subunit molecular mass (56.2 kDa), the N-terminal sequence (VYDLIVIGGGSGGMA), the presence of specific sequence motifs at ligand-binding sites, and, as demonstrated by Western blotting, the occurrence of a unique chain segment in the core of the central domain. In view of these data, the function(s) of PfGR2 as well as PfGR1, the product of another GR-like gene of P. falciparum (Müller et al., 1995) should be carefully assessed.

Amino Acid Sequence↗