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Biomedical subjects

R M Wagner

Publications and source records attributed to R M Wagner.

At least 19 recordsLinked to original sources

Characterization of digestive proteolytic activity in Lygus hesperus Knight (Hemiptera: Miridae).

The tarnished plant bug, Lygus hesperus Knight, is a pest that causes considerable economic losses to vegetables, cotton, canola, and alfalfa. Detailed knowledge of its digestive physiology will provide new opportunities for a sustainable pest management approach to control this insect. Little is known about the different protease class contributions to the overall digestion of a specific protein. To this end, the proteolytic activities in female adult L. hesperus salivary gland and midgut homogenates were quantified over a range of pH's and time points, and the contribution of different classes of proteases to the degradation of FITC-casein was determined. In the salivary gland, serine proteases were the predominant class responsible for caseinolytic activity, with the rate of activity increasing with increasing pH. In contrast, both aspartic and serine proteases contributed to caseinolytic activity in the midgut. Aspartic protease activity predominated at pH 5.0 and occurred immediately after incubation, whereas serine protease activity predominated at pH 7.5 after a 9h delay and was resistant to aprotinin. The salivary serine proteases were distinctly different from midgut serine proteases, based on the tissue-specific differential susceptibility to aprotinin and differing pH optima. Collectively, the caseinolytic activities complement one another, expanding the location and pH range over which digestion can occur.

Animals↗

Potential benefits of Anaesthesia Information Management Systems for multicentre data evaluation: risk calculation of inotropic support in patients undergoing cardiac surgery.

OBJECTIVE: The aim of this study was to test the hypothesis whether it is easily possible to transfer and apply the methods of data extraction and analysis of a performed study to a data pool of a different medical centre using the same type of Anaesthesia Information Management System (AIMS). For this purpose the objective of a study in cardiac anaesthesia, investigated at the University Hospital Giessen, was applied to the data pool of the Heart Centre Siegburg. RESEARCH DESIGN AND METHODS: The Giessen study evaluated factors related to the use of positive inotropic drugs (PIDs) in adults undergoing elective cardiac surgery with cardiopulmonary bypass (CPB). The same objective and methods were applied to data of 1672 patients of the Heart Centre Siegburg. In both centres anaesthetic procedures were recorded with the AIMS NarkoData. Existing database queries were adapted according to the Siegburg database configuration for detection of patients having received PIDs during or after weaning from CPB. RESULTS: It was revealed that data from the Siegburg database using the same data model and configuration, were identical to the Giessen database except for a few items only. Thus database queries of the Giessen study could be applied to the new data pool requiring no considerable additional input. CONCLUSIONS: We could demonstrate that multicentre data analysis in anaesthesia using AIM systems can be carried out successfully. Once the methods of data extraction and analysis are established they can be transferred to data pools of different centres without requiring additional time, personnel and material resources.

Aged↗

Uptake, flow, and digestion of casein and green fluorescent protein in the digestive system of Lygus hesperus Knight.

Selected compounds were used to study physiological processes associated with digestion in the western tarnished plant bug, Lygus hesperus Knight. Durations of passage and rates of absorption, digestion, and excretion were determined for a digestible protein (casein), a non-digestible protein (green fluorescent protein, GFP), and a non-digestible carbohydrate (dextran). Dextran was used as a control to monitor the non-absorptive flow rate of ingesta through the digestive system. Fluorescent tracking of FITC-conjugates of casein and dextran, as well as immunoblotting and immunofluorescent staining of casein and GFP, were used to monitor the degradation (in vitro) and ingestion, digestion, and distribution (in vivo) of the respective compounds. Under our experimental conditions, L. hesperus took discrete meals, feeding and excreting at 2-3 h intervals. Rate of food passage was variable. FITC-dextran was found in the fecal material of most insects by 6-8 h after treatment initiation; by 12 h, 95% of ingested FITC-dextran was recovered from all insects. FITC-casein was digested extensively in in vitro homogenates of gut, hemolymph, and salivary gland. In vivo, FITC-casein was ingested and partially absorbed as a holoprotein into the hemolymph. Ingested FITC-casein was partially degraded in the gut and hemolymph within 2 h of ingestion, and no holoprotein was found after 12 h. In contrast, there was no detectable degradation of GFP in hemolymph, gut, and salivary gland homogenates after 24 h of incubation. Ingested GFP was not degraded in gut or hemolymph up to 8 h after treatment initiation, but did transfer to the hemolymph as a holoprotein. Analysis of immunohistological images confirmed that GFP bound to gut epithelial cell brush-border membranes. However, the mechanism by which GFP and casein pass as holoproteins into the hemolymph remains unknown.

Animals↗

Testis ecdysiotropin, an insect gonadotropin that induces synthesis of ecdysteroid.

Testes of lepidoptera synthesized ecdysteroid in a somewhat different temporal pattern than the prothoracic glands that release ecdysteroid to the hemolymph. Brain extracts from Heliothis virescens and Lymantria dispar induced testes to synthesize ecdysteroid, but did not affect prothoracic glands. The testis ecdysiotropin (LTE) was isolated from L. dispar pupal brains by a series of high-pressure chromatography steps. Its sequence was Ile-Ser-Asp-Phe-Asp-Glu-Tyr-Glu-Pro-Leu-Asn-Asp-Ala-Asp-Asn-Asn-Glu-Val-Leu-Asp-Phe-OH, of molecular mass 2,473 Daltons. The predominant signaling pathway for LTE was via G(i) protein, IP3, diacylglycerol and PKC; a modulating pathway, apparently mediated by an angiotensin II-like peptide, was controlled via G(s) protein, cAMP, and PKA. Testis ecdysteroid caused isolated testis sheaths to also synthesize a growth factor that induced development of the male genital tract. The growth factor appeared to be a glycoprotein similar to vertebrate alpha-1-glycoprotein. A polyclonal antibody to LTE indicated LTE-like peptide in L. dispar brain medial neurosecretory cells, the suboesophageal, and other ganglia, and also in its target organ, the testis sheath. LTE immunoreactivity was also seen in testis sheaths of Rhodnius prolixus. LTE-like immunoactivity was also detected in developing optic lobes, antennae, frontal ganglia, and elongating spermatids of developing L. dispar pupae. This may indicate that LTE has a role in development as well as stimulation of testis ecdysteroid synthesis. Published 2001 Wiley-Liss, Inc.

Amino Acid Sequence↗

Regulation of corpora allata in females of Pyrrhocoris apterus (Heteroptera) (a mini-review).

Mechanisms for the transduction of photoperiodic and food signals to the corpus allatum (CA) are described. The focus of this paper is on the control of the CA by the brain in adult females of the firebug, Pyrrhocoris apterus. By using surgical interventions to the neuroendocrine complex of brain-subesophageal ganglion-corpora cardiaca-CA (BR-SG-CC-CA) in vivo and in vitro we were able to identify two regulatory pathways. (1) Slow regulation of the CA activity (stimulation or inhibition) needs a relatively long period of time to be accomplished (several d) in vivo and is associated with changes of the gland cell volume and ultrastructure. The stimulated or inhibited activity of the CA is maintained during short-term incubation of the isolated CA in vitro. (2) Fast inhibition of the CA activity is reversible during short-term incubation in vitro; the CA can be switched from lower to higher activity and vice versa, depending on the presence or absence of the BR-SG in the medium. Both slow and fast regulatory factors originate in the pars intercerebralis of the brain and in intact neuroendocrine complex they reach the CA via nerves. A slow inhibitor, induced by short d, causes reproductive diapause. A fast inhibitor prevents ovarian maturation in starved nondiapausing females. A slow stimulator, induced by feeding under long d, overcomes the fast inhibition of the CA, thereby stimulating vitellogenesis. Food signals are transmitted to the brain via humoral pathways.

Animals↗

Changes in blood lymphocyte populations after multiple trauma: association with posttraumatic complications.

OBJECTIVE: To study the frequency of several lymphocyte subsets, circulating cytokines, and prostaglandin plasma values at their time course over a period of 14 days in severely injured trauma patients in relation to the development of sepsis and multiple organ failure (MOF). DESIGN: Prospective study. SETTING: An operative intensive care unit (ICU) of a university hospital. PATIENTS: Sixty-eight consecutive severely injured trauma patients. INTERVENTIONS: Patients were separated into patients without sepsis and MOF (group 1, n = 51), and patients who developed sepsis and MOF (group 2, n = 17) during their stay in the ICU. Therapy was adjusted to the standards of modern intensive care management by physicians who were not involved in the study. MEASUREMENTS AND MAIN RESULTS: In arterial blood samples, the profile of lymphocyte subset frequencies was performed by flow cytometry and, together with interleukin (IL)-1, IL-10, tumor necrosis factor (TNF)-alpha soluble TNF-alpha receptor 1 (sTNF-alpha r1 [p55]), and prostaglandin E2 (PGE2alpha)-alpha, serially measured after arrival in the ICU (baseline value) and during the next 14 days. Mean plasma IL-1 (29.3 +/- 5.8 [SD] pg/mL), TNF-alpha (138.5 +/- 22.4 pg/mL), and soluble TNF-alpha r1 (6.1 +/- 0.3 ng/mL) values were significantly higher in group 2 patients before clinical evidence of sepsis and MOF. With the onset of severe infections in group 2 patients, IL-1, TNF-alpha, and sTNF-alpha r1 values decreased, while immunosuppressive IL-10 (191.7 +/- 29.1 pg/mL) and PGE2alpha (87.7 +/- 20.4 pg/mL) values further increased and remained elevated during the time course. Analysis of lymphocyte subsets revealed a fall in total lymphocyte levels, in CD4+ T lymphocytes, and natural killer (NK) cells, but no change in CD8+ T lymphocyte subset. Despite a marked change in the T helper (CD4+) to T suppressor (CD8+) ratio (from 1:1.72 to 1:1.10), patients without MOF (group 1) had no significant difference in any of the markers tested compared with baseline values. In addition to the inverse CD4+/CD8+ T cell ratio (from 1:1.75 to 1:0.91) and increased activated T cells, each of these markers was significantly elevated and peaked before the onset of MOF in group 2 patients. CONCLUSIONS: A severely depressed cellular immune response associated with increased suppressive mediators might be closely related to the development of severe sepsis and MOF in trauma patients. Therefore, an in-depth understanding of the deficits in host defense following multiple trauma will provide the basis for therapeutic interventions.

Adult↗

Analysis of the desmoplakin gene reveals striking conservation with other members of the plakin family of cytolinkers.

Members of the plakin family of cytolinker proteins integrate filaments into cellular networks and anchor these networks to the plasma membrane. Their importance is supported by the existence of cell and tissue fragility disorders caused by mutations in certain family members. In this study, the human gene encoding desmoplakin (DSP) was characterized and its structure compared with the related family members: plectin, bullous pemphigoid antigen 1 (BPAG1), envoplakin (EVPL) and periplakin (PPL). Sequence analysis of genomic clones was carried out in combination with a PCR-based strategy to define intron-exon borders. DSP was mapped using the GB4 radiation hybrid mapping panel to the interval between markers D6S296 and AFM043 x f2, corresponding to cytogenetic band 6p24. In addition, the murine gene (Dsp) was mapped to mouse chromosome 13 by interspecific backcross mapping. DSP encompasses approximately 45 kb organized into 24 exons and 23 introns, and the pattern of intron-exon borders bears a striking resemblance to other members of the plakin family. Notable features include the fact that a single large exon encodes the entire C-terminus of each gene. In contrast, the N-termini comprise numerous smaller exons with conservation of many intron-exon borders. Detailed characterization and mapping of these genes will facilitate their further evaluation as targets of genetic disorders and provide insights into the evolutionary relationships among molecules in this emerging gene family.

Amino Acid Sequence↗

Structure-function analysis of Lymantria testis ecdysiotropin: a search for the active core.

A structure-function study was performed on the synthetic 21 residue neuropeptide, Lymantria testis ecdysiotropin (LTE), originally isolated from brains of Lymantria dispar pupae. The peptide induces ecdysteroid synthesis by testis sheaths of various lepidopteran species. LTE, as well as synthetic LTE 1-11, 11-21, and 11-15, stimulated synthesis in larval and pupal testes of Lymantria dispar at concentrations of 10(-9) to 10(-15) M; LTE 16-21 was weakly active, and an elongated LEU-LTE was inhibitory to synthesis at all but extremely low concentrations (10(-15) M). Since the sequence and polarity of residues in LTE 1-11, 11-15, and 11-21 are quite different, several parts of the molecule must activate receptors which initiate the cascade, resulting in ecdysiogenesis in Lepidopteran testes.

Amino Acid Sequence↗

The spectrum and spatial distribution of cyanogen in comet Hale-Bopp (C/1995 O1) at large heliocentric distance.

Optical spectra of comet Hale-Bopp (C/1995 O1) at a heliocentric distance of 6.45 astronomical units showed emission from cyanogen gas. The spatial distribution of cyanogen was considerably more diffuse and extended compared to the spatial profile of the dust or grains which were sharply peaked near the center. This behavior is consistent with comets at smaller heliocentric distances suggesting the same or a similar formation mechanism. A cyanogen gas production rate of (1.2 +/- 0.3) x10(26) molecules per second was derived. A model band profile derived from fluorescence equilibrium calculations for the comet's heliocentric velocity and distance agrees with the observed band profile.

Cosmic Dust↗

Naturally occurring analogs of Lymantria testis ecdysiotropin, a gonadotropin isolated from brains of Lymantria dispar pupae.

Lymantria testis ecdysiotropin (LTE) was isolated from the most prominent peptide peak corresponding to an active fraction obtained by high pressure liquid chromatographic (HPLC) separation of a homogenate of 13,000 Lymantria dispar pupal brains. In this work we examined the other active fractions from this separation as well as a second HPLC separation of an additional 2,300 pupal brains. Bioassay of the ecdysteroidogenic effects of each peak on L. dispar testes allowed detection of 20 peptide peaks with testis ecdysiotropic activity in addition to LTE. Of these, ten peptides were purified and sequenced. All of them were comparable to LTE in molecular weight. The amino acid sequences of five of the peptides were similar enough to LTE to be considered to be members of an LTE family. However, the other five peptides had no significant homology with LTE or with each other. A BLAST database search indicated LTE family homology with portions of inhibitory peptides such as those inhibiting cytolysis. In contrast, non-LTE ecdysiotropic peptides, in which undetermined residues designated X were assumed to be cysteine, were strikingly homologous to portions of vertebrate and invertebrate zinc finger peptides and to vertebrate and invertebrate virus proteins.

Amino Acid Sequence↗

The influence of acute preoperative plasmapheresis on coagulation tests, fibrinolysis, blood loss and transfusion requirements in cardiac surgery.

OBJECTIVE: Withdrawal of autologous plasma and reinfusion after cardiopulmonary bypass (CPB) offers the opportunity of improving patients' haemostasis and reducing homologous blood consumption in cardiac surgery. The influence of acute, preoperative plasmapheresis (APP) on coagulation tests, fibrinolysis, blood loss and transfusion requirements was investigated in elective aortocoronary bypass patients. METHODS: Forty patients were randomized to a control or pheresis group. The pheresis group had platelet-rich plasmapheresis (PRP-group, n = 20) performed before incision and the platelet-rich plasma (PRP) was returned after CPB. The control group (n = 20) was managed without pheresis. All patients had serial coagulation studies, including prothrombin split products (F1/F2), fibrinopeptide A (FPA), protein C (PC), thrombomodulin (TM), tissue-plasminogen-activator (t-PA), plasminogen-activator-inhibitor (PAI 1), fibrinopeptide B beta 15-42 (FPB beta 15-42), haemoglobin and platelet counts determined intra- and postoperatively. Chest tube drainage and transfusion requirements were recorded. RESULTS: APP had no negative effects on the quality of PRP. The platelet count of the withdrawn autologous plasma was 239 +/- 33 x 10(9)/l. From the end of the operation (after retransfusion of autologous plasma) until the first postoperative day platelet counts were significant higher in the PRP-group (P > 0.05). Plasma concentrations of modified antithrombin III (ATM), F1/F2 and FPA increased (166-290% from baseline) and PC- and TM-antigen decreased (11-49% from baseline) to a different extent for both groups throughout CPB. t-PA-activity increased intraoperatively peaking at the end of CPB (PRP-group: 4.8 +/- 0.8 IU/ml, control-group: 8.1 +/- 2.3 IU/ml)(P > 0.05). With onset of CPB PAI-1 levels decreased and were further reduced after CPB in control patients in comparison to PRP-patients (P < 0.05). FPB beta 15-42 occurred in peak concentrations after neutralisation of heparin by protamine. Only PRP-patients showed baseline values of coagulation and fibrinolytic parameters on the next morning (P < 0.05). Total postoperative blood loss during the first 24 h was 503 +/- 251 ml (PRP-group) and 937 +/- 349 ml in the control-group (P < 0.05). None of the PRP-patients received allogeneic blood, whereas five control-patients received 11 units of packed red cells (P < 0.05). CONCLUSIONS: The findings suggest that in elective cardiac surgery heparin cannot prevent generation of both thrombin and fibrin, born throughout CPB and postoperatively. The use of PRP withdrawn immediately preoperatively is an attractive technique to reduce allogeneic blood usage and preoperative blood loss, especially in patients in whom withdrawal of autologous whole blood cannot be performed.

Aged↗

Concentration of cefamandole in plasma and tissues of patients undergoing cardiac surgery: the influence of different cefamandole dosage.

OBJECTIVE: To develop an improved regimen of antibiotic prophylaxis in cardiac surgery, three antibiotic prophylactic regimens for patients scheduled to have elective cardiothoracic surgery involving a median sternotomy were evaluated. DESIGN: A prospective, randomized, unblinded study. SETTING: A university teaching hospital. PARTICIPANTS: Sixty-nine men scheduled for elective coronary artery bypass grafting (CABG) with extracorporeal circulation (ECC) were included in the study. INTERVENTIONS: The patients were selected at random to receive 2 g of cefamandole (CM) at induction of anesthesia (group 1, n = 24), or 2 g of CM at the beginning of anesthesia followed by an additional dose (2 g) immediately after onset of cardiopulmonary bypass (CPB) (group 2, n = 22), or 4 g of CM just at the initiation of anesthesia (group 3, n = 23). Samples from the mammary artery, sternum, and plasma were obtained at various intervals after injection of the antibiotic (10 minutes intravenously) to compare antibiotic levels, assayed for CM concentrations, with high-pressure liquid chromatography (HPLC) and plasma bactericidal activity as well as infectious complications in these sites as a function of time for the three groups. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in biometric data, duration of hospitalization, or management of cardiopulmonary bypass, including urinary tract drainage and infusion volume. The mean plasma t1/2 (distributive or alpha-phase) before bypass was 51.7 +/- 16.7 minutes for group 1 and 2 patients and 54.9 +/- 15.9 minutes for group 3 patients. CM plasma values were significantly higher in group 2 (170.3 +/- 105.8 micrograms/mL) than in groups 1 and 3 (111.8 +/- 42.2 micrograms/mL, 101.2 +/- 57.2 micrograms/mL) at the end of bypass periods (p < 0.05). The antibiotic contents of mammary artery and sternum samples of group 2 (15.6 +/- 4.7 micrograms/mL, 9.5 +/- 4.7 micrograms/mL) were significantly higher after completion of CPB compared with group 1 (5.7 +/- 1.9 micrograms/mL, 3.8 +/- 2.9 micrograms/mL) and group 3 (6.3 +/- 3.5 micrograms/mL, 3.6 +/- 1.8 micrograms/mL) (p < 0.05). There were no significant differences in distribution of micro-organisms among the three groups, but two patients of groups 1 and 3 with plasma and tissue CM levels below minimal inhibitor concentration (MIC90) for Hemophilus influencea, E coli, Proteus ssp and Klebsiella ssp after completion of CPB, respectively, developed a pneumonia postoperatively caused by Hemophilus influencea (1), E coli (1) and Klebsiella ssp (2) (p < 0.05). CONCLUSIONS: It would be preferable to infuse the antibiotic shortly before the operative procedure. However, to keep tissue and plasma CM values more than MIC90 for common pathogens during the time period studied, a second infusion of 2 g of CM administered after onset of CPB suggests better protection against the risk of microbial infections. Therefore, the findings might be important for the choice of antibiotic prophylaxis, particularly for high-risk patients.

Adult↗

In vitro metabolism of an insect neuropeptide by neural membrane preparations from Lymantria dispar.

Neural membrane fractions, prepared from brain-subesophageal ganglion complexes of the adult lepidopteran Lymantria dispar, contain at least two peptidases capable of metabolizing locust adipokinetic hormone-I in vitro. The initial fragments, pGlu1-Leu2-Asn3 and Phe4-Thr5-Pro6-Asn7-Trp8-Gly9-Thr10, result from the action of an endopeptidase with properties similar to those reported for neutral metalloendopeptidase in Schistocerca gregaria and mammalian endopeptidase 24.11. The heptapeptide is further degraded by an aminopeptidase that exhibits kinetic properties similar to those described for aminopeptidase 3.4.11.2. These enzymes appear to be responsible for the first two steps in AKH catabolism in L. dispar.

Amino Acid Sequence↗

Effects of pipecuronium and pancuronium on cerebrospinal fluid pressure in neurosurgical patients.

Arterial hypertension and/or tachycardia may alter intracranial pressure in neurosurgical patients. We compared the effects of pancuronium 0.1 mg/kg and pipecuronium 0.1 mg/kg given as i.v. bolus on cerebrospinal fluid (CSF) pressure in 2 groups of 10 patients each scheduled for intracranial surgery in the supine position. Before surgery, no patient presented clinical symptoms of elevated intracranial pressure (ICP). Anesthesia was induced and maintained with fentanyl and midazolam. Ventilation with 50% nitrous oxide in oxygen was adjusted to maintain arterial pCO2 at 30-35 mmHg. After induction of anesthesia, CSF pressure was registered via a lumbar subarachnoid catheter before and 3, 5, 10, and 30 min after pipecuronium or pancuronium administration. Hemodynamics were monitored using radial and pulmonary artery catheters. All variables underwent analyses of variance for repeated measures with p < 0.05 considered significant. Mean CSF pressure decreased insignificantly from 15 +/- 5 mmHg (before injection) to 14 +/- 4 mmHg in patients given pipecuronium and from 13 +/- 4 mmHg to 10 +/- 3 mmHg in the pancuronium group without significant differences between the study groups. Heart rate and arterial pressure increased significantly (p < 0.001) in patients given pancuronium but remained stable after pipecuronium. Onset and duration of neuromuscular blockade were comparable between groups. Based on our results, pipecuronium is a safe alternative to pancuronium during neurosurgical procedures in patients without abnormally high intracranial pressure.

Adult↗

The identification of two myoinhibitory peptides, with sequence similarities to the galanins, isolated from the ventral nerve cord of Manduca sexta.

Two new myoinhibitory peptides, Mas-MIP I and Mas-MIP II, were identified from the ventral nerve cord of the adult tobacco hornworm, Manduca sexta. Sequences obtained by a combination of automated Edman degradation and electrospray mass spectrometry were, respectively, AWQDLNSAW and GWQDLNSAW. The native peptides were found to co-elute with synthetic C-terminal amides on a reverse phase HPLC system. When applied to isolated ilea (anterior hindgut) of adult M. sexta, both peptides were found to significantly reduce the rate of peristalsis, or abolish peristalsis entirely, at concentrations of 1 x 10(-9) M. Both peptides share sequence similarities with Lom-MIP, a previously identified myoinhibitory peptide from Locusta migratoria, and with the N-terminal portion of vertebrate peptides in the galanin family.

Abdomen↗

Isolation and identification of a pheromonotropic neuropeptide from the brain-suboesophageal ganglion complex of Lymantria dispar: a new member of the PBAN family.

A pheromonotropic peptide was isolated from brain-suboesophageal ganglion complexes of the adult female gypsy moth, Lymantria dispar, using a 5-step HPLC purification protocol and an in vivo bioassay in Helicoverpa zea. The intact peptide was sequenced by automated Edman degradation. The L. dispar pheromone biosynthesis activating neuropeptide (Lyd-PBAN) is a C-terminally amidated 33-amino acid peptide with a molecular weight of 3881. The peptide was synthesized using Fmoc procedures. Lyd-PBAN has sequence homology with Hez-PBAN (81.8%) and Bom-PBAN-I (66.7%). All three PBANs share the C-terminal hexapeptide sequence, Tyr-Phe-Ser-Pro-Arg-Leu-NH2. In addition, the C-terminal pentapeptide sequences of Pseudaletia pheromonotropin (Pss-PT), Bombyx diapause hormone (Bom-DH), the locustamyotropins (Lom-MT) and leucopyrokinin (Lem-PK) are identical or have a high degree of homology to the C-terminus of PBANs.

Amino Acid Sequence↗

[Intracranial hemorrhage and hemostasis. Monitoring patients after intracranial hemorrhage by determination and follow-up of activation products of blood coagulation].

OBJECTIVE: The aim of the study was to improve the detection of small hemorrhages with minimal symptoms and of unruptured aneurysms after a subdural and subarachnoid bleeding by the control of the intravascular hemostatic system. DESIGN: Prospective, open study. SETTING: Neurosurgical intensive care unit of a university hospital. PATIENTS: 44 patients undergoing a cranial trepanation. Patients of group 1 (control n = 11) had an intrasellar hypophysoma, patients of group 2 (n = 12) a chronic subdural hematoma without a previous traumatic incident and patients of group 3 (n = 15) a subarachnoid hemorrhage caused by an intracranial aneurysm. INTERVENTIONS: After cranial trepanation changes of plasmatic hemostasis have been assessed by means of immunologically determined parameters of coagulation. The investigation included blood parameters (hemoglobin, hematocrit, thrombocytes), clotting status (prothrombin time, partial thromboplastin time, thrombin time, fibrinogen, plasminogen, antithrombin III [AT III] activity and proteinase inhibitors), as well as immunological methods such as fibrinopeptide A (FPA), thrombin-antithrombin III (TAT), protein C and factor XIII activity (F XIII activity). RESULTS: In comparison to group 1 (control) a significant difference (p < 0.001) was seen in groups 2 and 3 for thrombin-antithrombin III (TAT), fibrinopeptide A (FPA), protein C, and the antithrombin III activity. Intra- and postoperatively increased TAT levels in groups 2 (16.9 ng/ml) and 3 (21.1 ng/ml) and decreased protein C levels (group 2: 61% and group 3: 58%) demonstrated an intravascular thrombin generation. On account of the elevated FPA levels in groups 2 (6.5 ng/ml) and 3 (5.7 ng/ml) and decreased AT III activity in groups 2 (58%) and 3 (62%), this thrombin generation was only incompletely compensated. Caused by proteolytic thrombin effects, another sign for a thrombin-induced turnover of clotting factors is the significant reduction (p < 0.001) of F XIII activity in groups 2 (40%) and 3 (44%). In comparison to group 1 this significantly reduced F XIII activity in groups 2 and 3 was correlated (r = 0.99) to changes in FPA and TAT plasma levels, an indication of latent chronic clotting activity. No significant difference was found concerning total amount of infusion, intra- and postoperative blood loss and blood parameters. Eight patients (group 2: 5 patients, group 3: 3 patients) showed a rebleeding episode without operative interventions. In these patients increased clotting activity (TAT, FPA, protein C) caused by proteolytic thrombin effects was combined with a factor XIII activity smaller than 40%. CONCLUSION: The results of the recent study indicated that immunologically determined TAT, FPA, protein C, factor XIII and AT III activities might serve to improve management in patients with intracranial bleeding events. In view of these parameters the evaluation of risks for a rebleeding is improved. A decrease of the plasma factor XIII activity under 40% associated with a latent clotting activity induced by a thrombin generation caused a higher risk of rebleeding after an initial intracranial bleeding event. The necessity of substituting factor XIII in such cases should be elucidated to minimize risks of rebleeding.

Aneurysm, Ruptured↗