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Biomedical subjects

S Jakob

Publications and source records attributed to S Jakob.

At least 19 recordsLinked to original sources

Stimulation induced variability of pulse plethysmography does not discriminate responsiveness to intubation.

BACKGROUND: Hypnotic depth but not haemodynamic response to painful stimulation can be measured with various EEG-based anaesthesia monitors. We evaluated the variation of pulse plethysmography amplitude induced by an electrical tetanic stimulus (PPG variation) as a potential measure for analgesia and predictor of haemodynamic responsiveness during general anaesthesia. METHODS: Ninety-five patients, ASA I or II, were randomly assigned to five groups [Group 1: bispectral index (BIS) (range) 40-50, effect site remifentanil concentration 1 ng ml(-1);Group 2: BIS 40-50, remifentanil 2 ng ml(-1); Group 3: BIS 40-50, remifentanil 4 ng ml(-1); Group 4: BIS 25-35, remifentanil 2 ng ml(-1); Group 5: BIS 55-65, remifentanil 2 ng ml(-1)]. A 60 mA tetanic stimulus was applied for 5 s on the ulnar nerve. From the digitized pulse oximeter wave recorded on a laptop computer, linear and non-linear parameters of PPG variation during the 60 s period after stimulation were computed. The haemodynamic response to subsequent orotracheal intubation was recorded. The PPG variation was compared between groups and between responders and non-responders to intubation (anova). Variables independently predicting the response were determined by logistic regression. RESULTS: The probability of a response to tracheal intubation was 0.77, 0.47, 0.05, 0.18 and 0.52 in Groups 1-5, respectively (P<0.03). The PPG variability was significantly higher in responders than in non-responders but it did not improve the prediction of the response to tracheal intubation based on BIS level and effect site remifentanil concentration. CONCLUSION: Tetanic stimulation induced PPG variation does not reflect the analgesic state in a wide clinical range of surgical anaesthesia.

Adult↗

The MLL recombinome of acute leukemias.

Chromosomal rearrangements of the human MLL gene are a hallmark for aggressive (high-risk) pediatric, adult and therapy-associated acute leukemias. These patients need to be identified in order to subject these patients to appropriate therapy regimen. A recently developed long-distance inverse PCR method was applied to genomic DNA isolated from individual acute leukemia patients in order to identify chromosomal rearrangements of the human MLL gene. We present data of the molecular characterization of 414 samples obtained from 272 pediatric and 142 adult leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) was determined and several new TPGs were identified. The combined data of our study and published data revealed a total of 87 different MLL rearrangements of which 51 TPGs are now characterized at the molecular level. Interestingly, the four most frequently found TPGs (AF4, AF9, ENL and AF10) encode nuclear proteins that are part of a protein network involved in histone H3K79 methylation. Thus, translocations of the MLL gene, by itself coding for a histone H3K4 methyltransferase, are presumably not randomly chosen, rather functionally selected.

Acute Disease↗

[Water jet dissection in fatty tissue].

BACKGROUND: The first report about the use of water-jet dissection in surgery dates 1982. The advantage compared to conventional cutting is the preservation of vessels and nerves, thus facilitating the precise coagulation thereafter. Devices of the new generation with coherent jet are used in liver surgery in order to reduce blood loss. The use of water-jet dissectors in other fields of surgery is currently under investigation. The preparation of vessels in fatty tissue is of special interest for plastic surgeons. The technical parameters of the hydro- or water-jet device have to be optimised. METHOD: Abdominal fat tissue of fresh cadavers was cut under standardised conditions with different parameters of the dissector. The depth of the cuts and the morphology of the blood vessels were analysed. RESULTS: Between 20 and 60 Bar cutting pressure of the water-jet and one single pass the cuts are 8 mm deep. Deeper cuts can be achieved by repeated application on the same cut. When using 40 Bar and 5 passes the cutting depth is 1.7 cm. Higher pressure as 50 or 60 Bar do not lead to deeper cuts. The water-jet dissection leads to a water uptake of the cut tissue. Morphologically all the vessels, lying in the cut are undamaged if the pressure doesn't exceed 40 Bar pressure range. CONCLUSION: The optimal pressure for water-jet dissection of fatty tissue lies between 30 and 40 Bar. Higher pressure does not lead to deeper cuts, but increases the risk of vessel damage. The vessels in the remain morphologically intact if he cutting pressure lies below 50 Bar. The effect of the mechanical irritation of the vessels has to be investigated in vivo, before using the water-jet dissector for preparation of blood vessels in humans e.g. for flap dissection.

Adipose Tissue↗

Metabolic effects of vasoactive agents.

After adequate volume resuscitation, the mainstay of therapy in critically ill patients with shock is treatment with vasoactive substances to restore haemodynamics or to improve regional perfusion. These agents include adrenoceptor agonists with inotropic combined with either vasoconstricting or vasodilating effects, and predominantly vasodilating drugs such as prostacyclin and related compounds. However, vasoactive agents not only affect the cardiovascular system, but also have profound metabolic effects. The interdependence of vasoactive drugs with metabolism may be relevant regarding adequate oxygen and substrate delivery to cover actual organ needs. Therefore, the profiles of these metabolic effects have to be considered during their therapeutic administration.

Journal Article↗

Influence of intraduodenally infused olive and coconut oil on postprandial exocrine pancreatic secretions of growing pigs.

The effect of dietary vegetable oils differing in fatty acid composition that were infused directly into the duodenum on exocrine pancreatic secretions in pigs has not previously been studied. The objective of the present study was to determine the acute response of the exocrine pancreas to vegetable oils with various fatty acid profiles under prandial conditions. Six growing pigs (BW 13.2 kg) were surgically prepared with pancreatic duct catheters and duodenal reentrant T-cannulas. The animals were fed twice a day (1000 and 1600) a commercial weaner diet at a rate of 2% of BW. Beginning with the morning feeding, olive oil, coconut oil, or saline as a control were infused in boluses every 5 min in total 0.1% of BW over a period of 1 h directly into the duodenum according to a 3 x 3 Latin square design. Pancreatic juice was collected over a period of 4 h, beginning 1 h preprandially (0900) until 3 h postprandially (1300). A time effect was observed after the infusion of olive oil on the volume of secretion, on protein contents and outputs, as well as on lipase contents and outputs and on colipase contents. The infusion of saline and coconut oil changed the runs of the curves for lipase and colipase outputs. No time x treatment interactions were observed regarding volume of secretion, protein contents and outputs, trypsin contents and outputs, and lipase outputs. The runs of the curves for lipase contents were different between the olive oil and saline treatment and between the olive oil and coconut oil treatment. The runs of the curves for the olive oil and saline treatment differed from each other regarding colipase contents. Pooled values of colipase outputs were elevated after coconut oil treatment, and a positive correlation between trypsin and colipase contents was found. Under prandial conditions, the exocrine pancreas responds differently in its acute secretion to different vegetable oils due to the differences in the fatty acid profiles.

Animals↗

Detection of artifacts in monitored trends in intensive care.

In intensive care, decision-making is often based on trend analysis of physiological parameters. Artifact detection is a pre-requisite for interpretation of trends both for clinical and research purposes. In this study, we developed and tested three methods of artifact detection in physiological data (systolic, mean and diastolic artery and pulmonary artery pressures, central venous pressure, and peripheral temperature) using pre-filtered physiological signals (2-min median filtering) from 41 patients after cardiac surgery. These methods were: (1) the Rosner statistic; (2) slope detection with rules; and (3) comparison with a running median (median detection). After tuning the methods using data from 20 randomly chosen patients, the methods were tested using the data from the remaining patients. The results were compared with those obtained by manual identification of artifacts by three senior intensive care unit physicians. Out of an average of 22,480 data points for each variable, the three observers labelled 0.98% (220 data points) as artifacts. The inter-observer agreement was good. The average (range) sensitivity for artifact detection in all variables in the test database was 66% (33-92%) for the Rosner statistic, 64% (24-98%) for slope detection and 72% (41-98%) for median detection. All methods had a high specificity (> or = 94%). Slope detection had the highest mean positive prediction rate (53%; 21-85%). When the performance was measured by the cost function, slope detection and running median performed equally well and were superior to Rosner statistics for systemic arterial and central venous pressure and peripheral temperature. None of the methods produced acceptable results for pulmonary artery pressures. We conclude that median filtering of physiological variables is effective in removing artifacts. In post-operative cardiac surgery patients, the remaining artifacts are difficult to detect among physiological and pathophysiological changes. This makes large databases for tuning artifact algorithms mandatory. Despite these limitations, the performance of running median and slope detection were good in selected physiological variables.

Algorithms↗

[Endoscopic use of the water jet dissector in the cerebral ventricle system--an experimental study].

Endoscopic surgery in the cerebral ventricle is limited by the small number of suitable instruments and bleedings obscuring the visibility. The water jet cutter allows the dissection of tissue, generally leaving vessels intact. Therefore it could be an additional instrument for neuroendoscopic purposes. In this preclinical study the employment of the water jet dissector under endoscopic conditions was evaluated. Incision-experiments (n = 80) on the ventricular system of fresh porcine brain were carried out under endoscopic view. To achieve similarity to the ventricular system, specimens were dissected in liquid medium (Ringer's-lactate, 37 degrees C). The depths of incision were measured digitally and histological examination of the tissue was performed. Depending on the applied pressure, distance from cutting nozzle to tissue and cutting velocity, the depths of incision ranged from 0.12 mm up to 2.4 mm. The water jet dissector is good to handle under endoscopic conditions and vessels are preserved. Based on these factors, this instrument is predestinated for further neuroendoscopic application. Prior to clinical application our results will have to be tested on living, perfused cerebral tissue.

Animals↗

The influence of potato fibre on exocrine pancreatic secretions and on plasma levels of insulin, secretin and cholecystokinin in growing pigs.

The effect of a potato fibre preparation on exocrine pancreatic secretions and on gastrointestinal hormone levels in plasma was studied in three 8 weeks old piglets that were surgically fitted with a jugular vein catheter for blood sampling, a pancreatic duct catheter and a T-shaped duodenal cannula for collection of pancreatic juice. The animals were fed for 2 weeks a control diet (experimental period 1), thereafter for 2 weeks the control diet supplemented with 2% potato fibre (experimental period 2) and for another 2 weeks the control diet again (experimental period 3). Additionally, intraduodenal (i.d.) infusions of the experimental diet, the control diet and potato fibre as well as i.v. infusions of a solution containing cholecystokinin (CCK) and secretin were administered. Potato fibre in the diet evoked in tendency an increase in the volume of secretion of pancreatic juice and a significant increase both in the mean values of the total protein content and total activities of lipase, trypsin and alpha-amylase when compared to the control diet. The i.d. infusion of the control diet, experimental diet and fibre infusate as well as the i.v. administration of the hormone infusate led to a spontaneous secretory response of the exocrine pancreas. Besides gastrointestinal hormones, such as CCK, other factors such as short chain fatty acids may be involved in the regulation of the exocrine pancreas.

Animals↗

Fats infused intraduodenally affect the postprandial secretion of the exocrine pancreas and the plasma concentration of cholecystokinin but not of peptide YY in growing pigs.

In pigs, the spontaneous secretion of the exocrine pancreas and the release of cholecystokinin (CCK) and peptide YY (PYY) after intraduodenal infusion of fully saturated synthetic fats differing in chain length was studied. Growing pigs (n = 6) were prepared with pancreatic duct catheters, duodenal T-cannulas and catheters placed in the jugular vein. The pigs were fed 2 g/100 g body twice daily. Beginning with the morning feeding, a medium-chain triglyceride (MCT: glycerol tricaprylate), a long-chain triglyceride (LCT: glycerol tristearate) or saline was infused at a rate of 0.1 g/100 g body. Pancreatic juice was collected, beginning 1 h preprandially until 3 h postprandially. Blood samples were obtained 15 min preprandially and 15, 45, 90 and 150 min postprandially. The infusion of MCT evoked a change in the trend of the curve for the volume of secretion of pancreatic juice, lipase and colipase concentrations and outputs. The trend of the curve did not change over time for CCK and PYY. Differences between the trends of the curves for the saline and MCT treatment were observed for volume of secretion, protein output, lipase content and output, trypsin and colipase output. Differences in the trends of the curves between MCT and LCT were obtained for the outputs of protein, lipase and colipase. Plasma CCK levels were lower as a result of the MCT treatment compared with the saline and LCT treatments. The results suggest an immediate, distinguished response of the porcine exocrine pancreas to fats differing in chain length.

Animals↗

Judgment analysis in clinical nephrology.

To ameliorate the clinical performance of nephrologists, improving their clinical judgment is crucial. No methodology for judgment analysis in nephrology is currently available. Therefore, we designed a trial to assess the intraphysician consistency of the judgment of typical non-end-stage renal disease (ESRD) patients by 24 board-certified nephrologists. The participants were asked to analyze cases to determine the interobserver variability with respect to diagnosis, therapy, prognosis, and strategy of follow-up. They were unaware that every patient was presented on 2 occasions separated by a period of 6 months. Of the 1,288 questionnaires that were completed, 28 cases belonged to 1 of the following 3 groups: (A) patients once with, once without renal histology, (B) patients twice without histology, and (C) patients twice with histology. Only cases of group (A) differed at the 2 occasions of assessment with respect to knowledge of histology. The results from the first and second assessment were compared and analyzed. The median (95% confidence interval) percentages of changed diagnoses were 64% (59% to 68%), 50% (44% to 62%), and 33% (26% to 47%) in groups A, B, and C, respectively, indicating large intraobserver variability. The frequency of changes in diagnoses declined with the degree of confidence in the first diagnosis in all 3 groups. The subjective desire to know the histology was without impact on the frequency of changes in diagnoses. However, a knowledge of the histology enhanced the degree of confidence in the diagnoses. Interestingly, the enormous variability in changing diagnoses from one analysis to the other was not reflected by corresponding changes in the judgment of prognosis, therapy to be prescribed, or strategy of follow-up. The individual judgment with respect to diagnosis of clinical cases is inconsistent and highly dependent on the subjective degree of confidence in the diagnosis. The practical relevant consequences traditionally derived from a diagnosis (therapy, prognosis, and strategy of follow-up) are only marginally, if at all, affected by changing the diagnosis. Thus, the utility of "diagnosis" for judgment analysis in clinical nephrology should be reconsidered.

Adult↗

Diurnal pattern of choline concentrations in serum of pigs as influenced by dietary choline or lecithin intake.

Athletes especially experience a significant decrease in plasma choline concentrations during exercise which can be compensated in part by consumption of lecithin, a natural source of choline. In addition, the effect of lecithin on plasma choline concentrations in humans is obviously considerably greater and more prolonged than that of an equivalent amount of choline salts. Serum choline acts as a precursor for the synthesis of acetylcholine, which, in turn, acts as a neurotransmitter. The effect of dietary choline derived from either choline chloride or lecithin on the diurnal pattern of free choline concentrations in serum was studied using the pig as a potential model for humans. Six barrows, average initial body weight 120 kg, were fitted with permanent catheters in the jugular vein to determine the diurnal pattern of serum choline concentrations as affected by dietary choline or lecithin intake. The pigs were fed two semi-purified diets twice daily (1,500 g each meal) that contained corn, casein and a mineral-vitamin premix supplemented with equal amounts of choline (480 mg/kg) from either choline chloride or lecithin (BIOFOSFATIN). The diets supplemented with choline were fed at 08.00 h in the morning and the experiment was carried out according to a 3 x 2 cross-over design. All pigs received the basal diet that contained 450 mg/kg choline at the evening feeding (20.00 h). Following an adaptation period of 6 d, blood was collected on d 7; 0.5 h before the morning feeding and 1, 2, 4, 6, 8, 10 and 12 h postprandially. The determination of serum choline concentrations was carried out by tandem-mass spectroscopy. There were no differences (p > 0.05) between the two diurnal patterns of the serum choline concentrations. Both diurnal patterns showed a postprandial peak at 0.5 h (2.71 mg/l for choline chloride and 2.35 mg/l for lecithin supplementation) and decreased after 2 h postprandially to the preprandial concentrations. In conclusion, there were no differences (p > 0.05) in the diurnal patterns of serum choline concentrations in pigs after consumption of dietary choline chloride or lecithin, which is in contrast to corresponding studies in humans.

Animal Feed↗

Thymic selection of CD8+ single positive cells with a class II major histocompatibility complex-restricted receptor.

We describe mice that express a transgenic T cell receptor alpha/beta (TCR-alpha/beta) specific for peptide 111-119 from influenza hemagglutinin presented by I-Ed class II major histocompatibility complex (MHC) molecules. The transgenic TCR is expressed on CD4+8- as well as CD4-8+ mature T cells even in mice that are deficient in rearrangement or do not express endogenous TCR-alpha genes. The CD4-8+ T cells require I-Ed class II MHC molecules for positive selection and can be activated to proliferate and to kill by I-Ed molecules presenting the relevant peptide. Full maturation of these cells, however, also requires the presence of class I MHC molecules. The results are compatible with the notion that T cell maturation requires multiple receptor-ligand interactions and establish an exception to the rule that class II-restricted TCRs are exclusively expressed by mature CD4+8- cells.

Animals↗

The influence of hydrochlorothiazide on the pharmacokinetics of enalapril in elderly patients.

In a randomized, cross-over, single-dose study of 19 elderly hypertensive patients (aged 62-84 y, SBP greater than 160 mmHg, DBP greater than 100 mmHg, creatinine clearance 11-93 ml.min-1) we have studied the pharmacokinetics of the angiotensin converting enzyme (ACE) inhibitor enalapril after a single oral dose of either 10 mg enalapril or 10 mg enalapril + 25 mg hydrochlorothiazide. The pharmacokinetics of enalapril were unaffected by hydrochlorothiazide, but there was a significant reduction in renal clearance and a significant increase in AUC(0-24 h) of enalaprilat after hydrochlorothiazide, resulting in higher serum concentrations of the active drug. This was independent of the individual degree of renal impairment and might be due either to an initial reduction of GFR by hydrochlorothiazide or to interference with the tubular secretion of enalaprilat. The relationships between serum enalaprilat and serum ACE activity were similar after both treatments, both consistent with a value for Ki of enalaprilat of about 0.1 nmol.l-1. Thus, serum ACE activity was not affected by hydrochlorothiazide but completely reflected the pharmacokinetics of enalaprilat in both treatments.

Administration, Oral↗

Major and minor birth malformations and antiepileptic drugs.

In a study of infants of parents with epilepsy, malformations were twice as prevalent in these children as in controls. Children of mothers with epilepsy had more minor anomalies than those of fathers with epilepsy or controls. At 1 year of age, a greater number of minor anomalies was seen in children of mothers with epilepsy who had received treatment with antiepileptic drugs (AEDs) during pregnancy, whereas at 4 years, no difference was observed. Type of epilepsy, seizures during pregnancy, plasma levels of phenytoin or phenobarbital in the medium range, and fetal intrauterine growth did not correlate with the number of minor anomalies. We suggest that the special genetic background that predisposes to epilepsy also renders the fetus more vulnerable to major and minor anomalies. Although linkage between epilepsy and malformation is stronger than between AEDs and malformations, valproate, phenytoin, and phenobarbital show specific teratogenic effects. In addition, all AEDs unspecifically increase the number of minor anomalies. Under therapeutic conditions, valproate may be regarded as considerably teratogenic and all other observed AEDs as weakly teratogenic.

Abnormalities, Drug-Induced↗

The relationship between long latency responses and height.

Long latency responses to electrical stimulation of nerve trunks in upper and lower extremities were studied in 83 healthy subjects. The latency differences between the late responses, M2, and the segmental reflexes, M1, on the hand correlated with the height, confirming a transcortical reflex loop. Corresponding to the possible polysynaptic spinal origin of the late reflex response on the lower leg, there was no correlation with height. Therefore, it is not possible to calculate the intraspinal conduction time from long latency reflex examinations.

Adult↗

Fetal growth, major malformations, and minor anomalies in infants born to women receiving valproic acid.

The association of fetal and neonatal distress, birth measurements, major malformations, and minor anomalies was studied prospectively in 14 infants of women with epilepsy who were receiving valproic acid (VPA) monotherapy and in 12 infants of women with epilepsy who were receiving VPA in combination with other anticonvulsant drugs. Comparison was made with 26 matched-pair controls and 116 controls from a larger study of antiepileptic drugs. During the first trimester, total VPA serum concentrations were well above therapeutic levels (100 to 184 micrograms/ml) in two women receiving high VPA doses (2000 and 1500 mg daily). Although dosage remained the same, serum concentrations decreased during pregnancy to therapeutic levels (33.9 to 57.0 micrograms/ml). The VPA percent free fraction increased in the third trimester and was threefold higher at birth. Almost half of the infants exposed to VPA monotherapy were distressed during labor, and 28% had low Apgar scores. Fetal and neonatal distress may be caused by the high VPA percent free fraction during labor and at birth. Mean body measurements at birth after VPA monotherapy were comparable to those in the matched control group, but were reduced in the group of infants receiving VPA combination therapy. Four infants exposed to VPA monotherapy were born with major malformations. The median number of minor anomalies was four times higher in infants whose mothers received VPA alone or VPA combination therapy than in controls. Seven infants had a pattern of craniofacial and digital anomalies that was distinctly different from that observed after in utero exposure to other anticonvulsant medications. The occurrence of major malformations and the number of minor anomalies may be dose related.

Abnormalities, Drug-Induced↗