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Biomedical subjects

A Horn

Publications and source records attributed to A Horn.

At least 19 recordsLinked to original sources
PubMed2001

Effects of prolonged increased intra-abdominal pressure on gastrointestinal blood flow in pigs.

BACKGROUND: The aim of the study was to investigate the effects of prolonged intra-abdominal pressure on systemic hemodynamics and gastrointestinal blood circulation. METHODS: The intra-abdominal pressure in anesthetized pigs was elevated to 20 mmHg (7 animals), 30 mmHg (7 animals), and 40 mmHg (4 animals), respectively. These pressures were maintained for 3 h by intra-abdominal infusion of Ringer's solution. A control group of seven animals had normal intra-abdominal pressure (IAP). Transit time flowmetry and colored microspheres were used to measure blood flow. RESULTS: An IAP of 20 mmHg did not cause significant changes in systemic hemodynamics or tissue blood flow. An IAP of 30 mmHg caused reduced blood flow in the portal vein, gastric mucosa, small bowel mucosa, pancreas, spleen, and liver. Serum lactate increased in animals with an IAP of 30 mmHg, but microscopy did not disclose mucosal damage in the stomach or small bowel. An IAP of 40 mmHg was followed by severe circulatory changes. CONCLUSIONS: Prolonged IAP at 20 mmHg did not cause changes in general hemodynamics or gastrointestinal blood flow. Prolonged IAP at 30 mmHg caused reduced portal venous blood flow and reduced tissue flow in various abdominal organs, but no mucosal injury. A prolonged IAP of 40 mmHg represented a dangerous trauma to the animals.

Animals↗
PubMed2001

Structural study on the carbohydrate moiety of calf intestinal alkaline phosphatase.

Surprisingly alkaline phosphatase (AP) (EC 3.1.3.1) of calf intestine is found in large amounts, e.g. 80%, within chyme. Most of the enzyme is present as a mixture of four differently hydrophobic anchor-bearing forms and only the minor part is present as an anchorless enzyme. To investigate whether changes in the N-glycosylation pattern are signals responsible for large-scale liberation from mucosa into chyme, the glycans of the two potential glycosylation sites predicted from cDNA were investigated by matrix-assisted laser desorption/ionization and electrospray ionization mass spectrometry in combination with exoglycosidase treatment after tryptic digestion and reversed-phase chromatography. The glycans linked to Asn249 are at least eight different, mainly non-fucosylated, biantennary or triantennary structures with a bisecting N-acetylglucosamine. For the most abundant glycopeptide (40%) the following glycan structure is proposed: [carbostructure: see text]. The glycans linked to Asn410 are a mixture of at least nine, mainly tetraantennary, fucosylated structures with a bisecting N-acetylglucosamine. For the most abundant glycopeptide (35%) the following glycan structure is proposed: [carbostructure: see text]. For the structures the linkage data were deduced from the reported specificities of the exoglycosidases used and the specificities of the transglycosidases active in biosynthesis. The majority of glycans are capped by alpha-galactose residues at their non-reducing termini. In contrast to the glycans linked to other AP isoenzymes, no sialylation was observed. Glycopeptide 'mass fingerprints' of both glycosylation sites and glycan contents do not differ between AP from mucosa and chyme. These results suggest that the observed large-scale liberation of vesicle-bound glycosylphosphatidylinositol (GPI)-anchored AP from mucosa into chyme is unlikely to be mediated by alteration of glycan structures of the AP investigated. Rather, the exocytotic vesicle formation seems to be mediated by the controlled organization of the raft structures embedding GPI-AP. (c) 2001 John Wiley & Sons, Ltd.

Alkaline Phosphatase↗
PubMed2001

Biotinidase determination in serum and dried blood spots--high sensitivity fluorimetric ultramicro-assay.

A miniaturized quantitative biotinidase assay has been developed using biotin 6-amidoquinoline as substrate and the 100-fold enhanced fluorescence of 6-amidoquinoline measured using apolar solvents. Amidoquinoline is measured after deproteinization by ethanol/acetone using individual standardisation and solvent resistant microtiter plates. The assay was optimized for end point determinations of biotinidase activities in serum and for newborn screening using dried blood spots. Serum activities obtained are closely correlated with values obtained using a quantitative validation method (r=0.96). Analytical sensitivity is around 2% of the mean activity (7.01+/-1.92 nmol/min/ml, mean+/-SD) of a healthy control population. With dried blood spots, a close correlation with values obtained using the Wallac-test kit (r=0.92) was found. Biotinidase activities of a healthy population of 651 newborns amount to 0.2429+/-0.07 nmol/min/ml blood. The analytical sensitivity is close to 1% of the mean activity.

Adolescent↗
PubMed2001

Pharmacokinetics of native Escherichia coli asparaginase (Asparaginase medac) and hypersensitivity reactions in ALL-BFM 95 reinduction treatment.

Repeated asparaginase treatment has been associated with hypersensitivity reactions against the bacterial macromolecule in a considerable number of patients. Immunological reactions may range from anaphylaxis without impairment of serum asparaginase activity to a very fast decline in enzyme activity without any clinical symptoms. Previous investigations on a limited number of patients have shown high interindividual variability of asparaginase activity time courses and hypersensitivity reactions in about 30% of patients during reinduction treatment. Therefore, monitoring of reinduction treatment was performed prospectively in 76 children with newly diagnosed acute lymphoblastic leukaemia (ALL). According to the ALL-Berlin-Frankfurt-Münster (BFM) 95 protocol, 10 000 U/m2 body surface area of native Escherichia coli asparaginase (Asparaginase medac) was given on d 8, 11, 15 and 18. In 45/76 children, trough and peak activities were determined with every dose, and also on d 4 and d 11 after the last administration. Data on asparaginase activity were not available from the remaining 31 patients, but information with regard to hypersensitivity reactions only was given. Eighteen out of 76 patients (24%) suffered a clinical hypersensitivity reaction; however, no silent inactivation was observed. Activity in the therapeutic range of greater than 100 U/l for at least 14 d was determined in 43 of the 45 patients who were analysed for enzyme activity.

Adolescent↗
PubMed2001

Endoscopic sphincterotomy in acute gallstone pancreatitis: a prospective study of the late outcome.

OBJECTIVE: To describe the outcome after acute biliary pancreatitis in patients treated during the acute attack by endoscopic sphincterotomy without cholecystectomy. DESIGN: Prospective observational study. SETTING: University hospital, Norway. SUBJECTS: 130 patients with gallstones and acute pancreatitis. In 62 patients with common bile duct stones the bile duct was cleared by sphincterotomy and stone extraction. The remaining 68 patients had prophylactic sphincterotomy. Cholecystectomy was not planned later. MAIN OUTCOME MEASURES: Incidence of recurrent acute pancreatitis and need for cholecystectomy. RESULTS: 21 patients were dead or not available for the follow-up. Consequently 109 patients were followed-up for a median of 39 months (range 23-62). One patient had recurrent pancreatitis. 20 patients had a cholecystectomy later for symptoms related to gallstone disease. Of the rest, 25 patients had moderate or mild gallstone-related symptoms. There was no difference in gallstone-related symptoms between those who had had stones in the bile duct and those who had not. 63 patients had no symptoms related to gallstones. CONCLUSION: Endoscopic sphincterotomy during or immediately after acute gallstone pancreatitis resulted in half the patients being free of symptoms during the next three years.

Acute Disease↗
PubMed2000

Lactate, glucose and O2 uptake in human brain during recovery from maximal exercise.

The metabolic activity of the brain has not been evaluated during physical exercise. In six volunteers substrate uptake by the brain was determined during graded exercise and recovery from maximal exercise by measuring the arterial-internal jugular venous concentration differences(a-v differences). The a-v difference for lactate increased from 0.02 +/- 0.08 mmol l-1 at rest to 0.39 +/- 0. 13 mmol l-1 during exercise and remained positive during 30 min of recovery (P < 0.05). The a-v difference for glucose (0.55 +/- 0.06 mmol l-1 at rest) did not change significantly during exercise, but during the initial 5 min of recovery it increased to 0.83 +/- 0.10 mmol l-1 (P < 0.05). The O2 a-v difference at rest of 3.11 +/- 0.30 mmol l-1 remained stable during exercise, then increased during the initial 5 min of recovery (3.77 +/- 0.52 mmol l-1) and remained high during the subsequent 30 min recovery period (3.62 +/- 0.64 mmol l-1; P < 0.05). Thus the O2/glucose uptake ratio did not change during exercise (pre-exercise 5.95 +/- 0.68; post-exercise 6.02 +/- 1.39) but decreased to 4.93 +/- 0.99 during the initial 5 min of recovery (P < 0.05). When lactate uptake was included, the resting O2/carbohydrate uptake ratio of 5.84 +/- 0.73 was reduced to 4.42 +/- 0.25 during exercise and decreased further during the recovery phase (to 3.79 +/- 0.30; P < 0.05). In contrast, in the resting and immobilised rat, lactate infusion to a level similar to that obtained during maximal exercise in humans did not affect the a-v difference for lactate. The large carbohydrate uptake by the brain during recovery from maximal exercise suggests that brain glycogen metabolism is important in the transition from rest to exercise, since this would explain the significant post-exercise decrease in the O2/carbohydrate uptake ratio.

Adult↗
PubMed2000

Amyloidogenicity of recombinant human pro-islet amyloid polypeptide (ProIAPP).

BACKGROUND: Pancreatic amyloid has been associated with type II diabetes. The major constituent of pancreatic amyloid is the 37-residue peptide islet amyloid polypeptide (IAPP). IAPP is expressed as a 67-residue pro-peptide called ProIAPP which is processed to IAPP following stimulation. While the molecular events underlying IAPP amyloid formation in vitro have been studied, little is known about the role of ProIAPP in the formation of pancreatic amyloid. This has been due in part to the limited availability of purified ProIAPP for conformational and biochemical studies. RESULTS: We present a method for efficient recombinant expression and purification of ProIAPP and a processing site mutant, mutProIAPP, as thioredoxin (Trx) fusion proteins. Conformation and amyloidogenicity of cleaved ProIAPP and mutProIAPP and the fusion proteins were assessed by circular dichroism, electron microscopy and Congo red staining. We find that ProIAPP and mutProIAPP exhibit strong self-association potentials and are capable of forming amyloid. However, the conformational transitions of ProIAPP and mutProIAPP during aging and amyloidogenesis are distinct from the random coil-to-beta-sheet transition of IAPP. Both proteins are found to be less amyloidogenic than IAPP and besides fibrils a number of non-fibrillar but ordered aggregates form during aging of ProIAPP. ProIAPP aggregates are cytotoxic on pancreatic cells but less cytotoxic than IAPP while mutProIAPP aggregates essentially lack cytotoxicity. The Trx fusion proteins are neither amyloidogenic nor cytotoxic. CONCLUSIONS: Our studies suggest that ProIAPP has typical properties of an amyloidogenic polypeptide but also indicate that the pro-region suppresses the amyloidogenic and cytotoxic potentials of IAPP.

Amino Acid Sequence↗
PubMed2000

Pegylated asparaginase (Oncaspar) in children with ALL: drug monitoring in reinduction according to the ALL/NHL-BFM 95 protocols.

Hypersensitivity reactions are relevant adverse effects of asparaginase therapy. Therefore, children treated with native Escherichia coli asparaginase in induction therapy of acute lymphoblastic leukaemia (ALL) or non-Hodgkin's lymphoma (NHL) were switched to the pegylated enzyme for reinduction under drug monitoring. Seventy children, including four patients with allergic reactions during induction, were given one dose of Oncaspar 1,000 U/m2 intravenously. Activity was determined every third or fourth day until it dropped below the limit of quantification. In current reinduction protocols [ALL/NHL-Berlin-Frankfurt-Münster (BFM) 95 trials], four doses of 10,000 U/m2 E. coli asparaginase deplete asparagine for about 2-3 weeks, therefore activities of >/= 100 U/l up to day 14 and >/= 50 U/l up to day 21 were targeted. In 66 patients without an allergic reaction during induction, the mean activity was 606 +/- 313 U/l, 232 +/- 211 U/l and 44 +/- 50 U/l after 1, 2 and 3 weeks respectively. In 44/66 patients, activity was >/= 100 U/l after 14 d. A rapid decline in activity was seen in the remaining 22 patients, including 8/22 patients who showed no activity after 1 week. Toxicity was low and comparable to the native enzymes but, in contrast to about 30% of hypersensitivity reactions with conventional reinduction therapy, no allergic reaction was seen. Substituting 4 x 10,000 U/m2 asparaginase medac for one dose of 1,000 U/m2 Oncaspar was safe and well tolerated. Comparable pharmacokinetic treatment intensity was achieved in about two-thirds of patients.

Adolescent↗
PubMed2000

Gel chromatographic characterization of the hydrophobic interaction of glycosylphosphatidylinositol-alkaline phosphatase with detergents.

The interaction of a glycosylphosphatidylinositol (GPI) protein with different detergents was studied for the first time with a purified protein. Four differently hydrophobic fractions of GPI-alkaline phosphatase (GPI-AP) from calf intestine were used as model proteins. The mode of interaction was determined by investigating (i) the self-aggregation behaviour of the GPI-AP fractions, (ii) the interference of detergents with GPI-AP binding to octyl-Sepharose, and (iii) the elution of GPI-AP bound to octyl-Sepharose. It was shown that polyoxyethylene-type detergents surprisingly interact much stronger than n-octylglucoside with GPI-AP, which is in contrast to the known behaviour of GPI-proteins in natural membranes. Gel filtration chromatography of Triton X-100 at concentrations above the critical micellar concentration yields three different micelle species with apparent molecular weights of about 166, 54, and 16 kDa. GPI-AP fraction II, which is shown to bear only one anchor per dimer, does not bind to any of these micelles. We demonstrate that a complex is formed containing about 150 Triton X-100 molecules and about 4700 molecules of water per molecule of GPI-AP dimer. The experimental findings are in accordance with a simple geometrical model based on the physical data of fatty acids and the arrangement, mean size, and shape of Triton X-100 molecules.

1-Propanol↗
PubMed1999

[Disabilities and handicaps due to hip fractures in the elderly].

OBJECTIVE: to examine mortality, mobility, pain, institutionalization rates six month after hip fractures. DESIGN: observational study, non-selected consecutive patients, time-set protocol. SETTING: urban area (population n = 116,5000), five hospitals. PARTICIPANTS: hip fracture patients (n = 214), age 65 + years (mean 82.4 years). MEASUREMENTS: age, gender, prefracture status, operative procedures, complications, comorbidity, cognition (MMSE), depression (GDS), fear of falling, ADL (Barthel) and mobility and pain status (SAHFE protocol). RESULTS: the incidence for this age group was 636.9/100,000, 31.8% were institutionalized elderly. 84% of the patients were female. Pre-existing comorbidity showed a high prevalence of neurodegenerative (cognitive deficits 53. 6%, Parkinson's disease/syndrome 11.2%) and cerebrovascular diseases (16.8%). Six month postfracture, the mortality was 17.6%. From those surviving 76.2% did walk indoors, 58.5% did also walk outdoors. Independent to dress were 54.6%. Severe pain was reported by 10.2%, whereas 36.9% described no pain. The institutionalization rate at six month was 19.0%. CONCLUSIONS: the study showed considerable mortality, a significant loss in function and social disintegration. Considerable differences were observed for subgroups of patients. Future treatment should focus on risk stratification and include postdischarge training programs. Moreover, preventive strategies should be implemented for high risk groups, such as ambulating patients with a history of stroke. Parkinson's disease and syndrome, dementia and nursing home residents.

Activities of Daily Living↗
PubMed1999

Glycosylphosphatidylinositol-specific phospholipase D in blood serum: is the liver the only source of the enzyme?

In cases of systemic inflammatory response syndrome, sepsis, and septic shock, the activity of glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) in serum amounts to 20 to 25% of the activity found in a healthy control group. The activity of serum GPI-PLD is positively correlated with inflammatory markers and counts of monocytes and stab cells (bands) and negatively correlated with polymorphonuclear neutrophils and lymphocytes in severe diseases. This indicates a yet unknown involvement of the inflammatory system in GPI-PLD liberation and suggests that the liver is not the only source of the plasma enzyme. Plasma was shown to contain an effective inhibitor of GPI-PLD which is soluble in organic solvents. Its concentration in capillary plasma is 20-fold higher than in venous plasma. To find possible other sources of plasma GPI-PLD besides the liver, the GPI-degrading activity was measured in different organs of the rat. Product formation was analysed using [125I]TID-labeled GPI-AP.

Alkaline Phosphatase↗
PubMed1999

Cocaine-induced mood disorder: prevalence rates and psychiatric symptoms in an outpatient cocaine-dependent sample.

This paper attempts to examine and compare prevalence rates and symptom patterns of DSM substance-induced and other mood disorders. 243 cocaine-dependent outpatients with cocaine-induced mood disorder (CIMD), other mood disorders, or no mood disorder were compared on measures of psychiatric symptoms. The prevalence rate for CIMD was 12% at baseline. Introduction of the DSM-IV diagnosis of CIMD did not substantially affect rates of the other depressive disorders. Patients with CIMD had symptom severity levels between those of patients with and without a mood disorder. These findings suggest some validity for the new DSM-IV diagnosis of CIMD, but also suggest that it requires further specification and replication.

Adult↗
PubMed1999

The safety and effectiveness of remifentanil as an adjunct sedative for regional anesthesia.

UNLABELLED: We assessed the sedative potential of continuous infusions of remifentanil with a validated composite alertness scale in 160 patients (ASA physical status I or II) undergoing hip replacement surgery with spinal block (n = 61) or hand surgery using brachial plexus block (n = 93). They were randomized to receive one of the following initial dose regimens in double-blinded fashion: placebo or 0.04, 0.07, or 0.1 microg x kg(-1) x min(-1) remifentanil subsequently titrated to effect. Additional midazolam IV was allowed for adequate sedation as required. The combined analysis of both surgery groups revealed a dose-related increase in achievement of sedation level > or =2 within 15 min of the start of the study drug infusion; all remifentanil dose comparisons with placebo reached significance (P < 0.001). The remifentanil 50% effective dose for a composite sedation level > or =2 within 15 min of the start of drug infusion was estimated as 0.043 microg x kg(-1) x min(-1) (95% confidence interval 0.01, 0.059). The requirement for midazolam decreased with increasing remifentanil dose compared with placebo (P < 0.001). The median time to return to alertness after the end of infusion was 10-12 min in the remifentanil groups and 5 min in the placebo group. Significant incidences of nausea, pruritus, sweating, and respiratory depression were reported during remifentanil infusions compared with placebo. The data suggest that remifentanil may be useful for supplementation of regional anesthesia, provided that ventilation is carefully monitored. IMPLICATIONS: In this dose-finding, placebo-controlled study, remifentanil infusions were used to provide sedation during spinal and brachial plexus regional anesthesia. The 50% effective dose for achievement of sedation was 0.043 microg x kg(-1) x min(-1). Return to alertness occurred after 10-12 min (median time). Remifentanil infusions can be used to supplement regional anesthesia, but this requires careful monitoring of ventilation.

Adjuvants, Anesthesia↗
PubMed1999

Cerebral metabolic response to submaximal exercise.

We studied cerebral oxygenation and metabolism during submaximal cycling in 12 subjects. At two work rates, middle cerebral artery blood velocity increased from 62 +/- 3 to 63 +/- 3 and 70 +/- 5 cm/s as did cerebral oxygenation determined by near-infrared spectroscopy. Oxyhemoglobin increased by 10 +/- 3 and 25 +/- 3 micromol/l (P < 0. 01), and there was no significant change in brain norepinephrine spillover. The arterial-to-internal-jugular-venous (a-v) difference for O(2) decreased at low-intensity exercise (from 3.1 +/- 0.1 to 2. 9 +/- 0.1 mmol/l; P < 0.05) and recovered at moderate exercise (to 3. 3 +/- 0.1 mmol/l). The profile for glucose was similar: its a-v difference tended to decrease at low-intensity exercise (from 0.55 +/- 0.05 to 0.50 +/- 0.02 mmol/l) and increased during moderate exercise (to 0.64 +/- 0.04 mmol/l; P < 0.05). Thus the molar ratio (a-v difference, O(2) to glucose) did not change significantly. However, when the a-v difference for lactate (0.02 +/- 0.03 to 0.18 +/- 0.04 mmol/l) was taken into account, the O(2)-to-carbohydrate ratio decreased (from 6.1 +/- 0.4 to 4.7 +/- 0.3; P < 0.05). The enhanced cerebral oxygenation suggests that, during exercise, cerebral blood flow increases in excess of the O(2) demand. Yet it seems that during exercise not all carbohydrate taken up by the brain is oxidized, as brain lactate metabolism appears to lower the balance of O(2)-to-carbohydrate uptake.

Adult↗