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Biomedical subjects

M Horn

Publications and source records attributed to M Horn.

At least 91 records · Page 5Linked to original sources
PubMed1996

Effect of organic nitrates on ex vivo platelet aggregation and fibrinolysis in man.

Previous in vitro studies have suggested that nitric oxide-releasing agents can increase the fibrinolytic capacity while platelet aggregability is decreased. We have therefore directly compared the influence of organic nitrates on ex vivo platelet aggregation and the fibrinolytic system in 16 healthy volunteers. Each subject received glyceryl trinitrate (GTN, 2 x 32 mg patches), isosorbide-dinitrate (ISDN, 120 mg p.o.), isosorbide-5-mononitrate (ISMN, 50 mg p.o.), and placebo in a randomized double-blind manner. Ex vivo platelet aggregation, activities and concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) were measured before, 90 and 150 minutes after drug intake. GTN, ISDN, and ISMN were equipotent in respect to their hemodynamic responses. Platelet aggregation induced with a low (1 microM) but not with a high (4 microM) agonist concentration (adenosine diphosphate, ADP) was reduced after GTN and ISDN. ISMN had no influence on aggregation. An increase of t-PA activity was significantly reduced after GTN and ISDN (p<0.05), whereas t-PA concentrations were not affected by the nitrates. A decrease of PAI-1 activity after ISMN and placebo was not apparent after GTN and ISDN. In the case of GTN, the decrease of PAI-1 concentration was delayed. In conclusion, GTN and ISDN did not increase the fibrinolytic capacity but decreased the reversible phase of ADP-induced platelet aggregation, while ISMN had neither an effect on the fibrinolytic system nor on platelet aggregation.

Adenosine Diphosphate↗
PubMed1996

'Malignant' middle cerebral artery territory infarction: clinical course and prognostic signs.

BACKGROUND: Although the clinical features of space-occupying ischemic stroke are well known, there are limited prospective data on the clinical course of complete middle cerebral artery territory infarction and on the predisposing factors leading to subsequent herniation and brain death. METHODS: The clinical course of patients with complete middle cerebral artery territory infarction, defined by computed tomography and vascular imaging, was evaluated. Initial clinical presentation was assessed by the Scandinavian Stroke Scale and the Glasgow Coma Scale. Serial computed tomography with measurement of midline and septum pellucidum shift and data on the presence and location of vascular occlusion by angiography or Doppler ultrasound were obtained directly after admission. Time course and outcome were analyzed with regard to the clinical findings on admission and at follow-up. The functional status of surviving patients was assessed using the Barthel Index. RESULTS: Fifty-five patients with complete middle cerebral artery territory infarction caused by occlusion of either the distal intracranial carotid artery or the proximal middle cerebral artery trunk were studied. In all patients, embolic infarction was presumed. The mean Scandinavian Stroke Scale score on admission was 20, and the time course of deterioration varied between 2 and 5 days. Forty-nine patients required ventilator assistance during the acute stage of disease. Only 12 patients (22%) survived the infarct. The cause of death was transtentorial herniation with subsequent brain death in 43 patients. Survivors had a mean Barthel Index score of 60 (range, 45 to 70). CONCLUSIONS: The prognosis of complete middle cerebral artery territory stroke is very poor and can be estimated by early clinical and neuroradiological data within the first few hours after the onset of symptoms. A space-occupying mass effect develops rapidly and predictably over the initial 5 days after presentation. Herniation occurred as an end point in 43 (78%) of these patients.

Adult↗
PubMed1996

Prevention of indwelling central venous catheter sepsis.

In an attempt to decrease the incidence of central venous catheter sepsis in children with cancer, we conducted a study to evaluate the benefit of adding broad-spectrum antibiotics to the catheter "flush solution." In a prospective, placebo-controlled, double-blinded, randomized trial, 69 children with different types of malignancies were studied. The central venous catheters in these children were flushed with either the standard solution (normal saline + 100 U/ml of heparin) or the study solution (25 microgram/ml of both amikacin and vancomycin added to the standard solution). At the conclusion of the study, 64 children with a total of 67 indwelling central venous lines were assessable. The total catheter days on study were 20,700 days, with a median of 323 catheter days per patient. We documented 10 events of catheter-related infections (0.49 events/1,000 catheter days at risk). Five of these events were catheter-related sepsis (0.24 sepses/1,000 catheter days): two were fungal and three were bacterial. Due to the low incidence of catheter-related sepsis in this study, no statement regarding the prophylactic use of antibiotics could be made. The extremely low rate of catheter-related sepsis reported herein may be retrospectively attributed to continuous staff education regarding aseptic techniques in handling these catheters. Staff education is essential, and probably the most effective factor in preventing catheter-related sepsis.

Adolescent↗
PubMed1996

A novel two-nucleotide deletion in the ornithine transcarbamylase gene causing fatal hyperammonia in early pregnancy.

Ornithine transcarbamylase (OTC) deficiency shows X-linked inheritance. Typically, symptomatic females (who constitute 15%-20% of all carriers) have markedly reduced enzyme activity and show first symptoms in late infancy or early childhood. Here we present the case of a previously asymptomatic 24-year-old woman who died of severe hyperammonemia associated with orotic aciduria but normal OTC activity in the fourth month of pregnancy. DNA analysis revealed a novel mutation in form of the deletion of two nucleotides (T892, G893) in exon 9 of the OTC gene, leading to a frame shift and an aberrant gene product. We suggest that OTC deficiency should be suspected in any patient who presents with hyperammonia in the presence of otherwise normal liver function.

Adult↗
PubMed1996

Preservation of left ventricular mechanical function and energy metabolism in rats after myocardial infarction by the angiotensin-converting enzyme inhibitor quinapril.

We tested whether angiotensin-converting enzyme (ACE) inhibitor therapy with quinapril prevents the deterioration of mechanical function and high-energy phosphate metabolism that occurs in chronically infarcted heart. Rats were subjected to ligation of the left anterior descending coronary artery (LAD) or sham operation. Four groups were studied: sham-operated rats (n = 10), rats with myocardial infarction (MI, n = 9), sham-operated quinapril-treated rats (n = 8), and infarcted quinapril-treated (n = 13) rats. Treated rats received 6 mg/kg/day of the ACE inhibitor quinapril orally, initiated 1 h after MI or sham operation. Eight weeks after LAD ligation or sham operation, hearts were isolated and buffer-perfused isovolumically. High-energy phosphate metabolism and intracellular pH were continuously recorded with 31P-nuclear magnetic resonance (NMR) spectroscopy. Hearts were subjected to 15-min control, 30-min hypoxia (95% N2/5% CO2, and 30-min reoxygenation. Left ventricular developed pressure (LVDP) was reduced in infarcted hearts (58 +/- 10 vs. 98 +/- 9 mm Hg in sham, p < 0.05), and this reduction was partially prevented by quinapril (78 +/- 8 mm Hg). ATP content of residual intact myocardium after sham operation or MI was unchanged. Creatine phosphate was reduced in infarcted hearts (107 +/- 10 vs. 138 +/- 5% of control ATP, p < 0.05), and quinapril prevented this decrease (131 +/- 8%). Therefore, quinapril preserved both function and high-energy phosphate metabolism in the chronically infarcted heart. However, when hearts were subjected to acute hypoxia, susceptibility to acute metabolic stress was substantially increased in both quinapril-treated groups: ATP content at end-hypoxia was reduced to 31 +/- 7 and 37 +/- 6% in sham and infarcted quinapril-treated groups, whereas ATP in untreated sham and infarcted hearts was 66 +/- 6 and 66 +/- 3% of baseline values (p < 0.05 untreated vs. quinapril treated). Likewise, recovery of LVDP during reoxygenation was impaired by quinapril treatment (15 +/- 7 and 15 +/- 4 mm Hg in quinapril-treated sham and MI vs. 73 +/- 9 and 46 +/- 9 mm Hg in untreated sham and MI groups, p < 0.05 untreated vs. quinapril treated). The most likely explanation for the unexpected finding of increased susceptibility to acute metabolic stress in the quinapril-treated groups is reduced wall thickness leading to increased wall stress. The preservation of high-energy phosphate content in residual intact hearts after MI may contribute to the beneficial effects of ACE inhibitors after MI.

Adenosine Triphosphate↗
PubMed1996

Protective effect of the specific endothelin-1 antagonist BQ610 on mechanical function and energy metabolism during ischemia/reperfusion injury in isolated perfused rat hearts.

Endothelin-1 (ET-1) has been suggested to be involved in the pathophysiology of ischemia/reperfusion injury, but direct proof for this is still sparse. We tested whether protection of high-energy phosphate metabolism contributes to the beneficial effects of ETA receptor antagonists during ischemia/reperfusion. In isolated, buffer-perfused rat hearts, isovolumic function was measured by a left ventricular (LV) balloon, and 31P nuclear magnetic resonance spectra were continuously recorded. Two protocols were performed: (a) 15-min control, 30-min total, global ischemia, and 15-min reperfusion; and (b) 15-min control, 15-min total, global ischemia, and 30-min reperfusion. Treatment with BQ610 (1.75 micrograms/min) or saline was started during control and continued throughout the protocol. BQ610 did not affect function or energy metabolism under control conditions. In BQ610-treated hearts subjected to 30-min ischemia, time to ischemic contracture was significantly delayed (treated 10.6 +/- 0.4 min; untreated 8.1 +/- 0.7 min), and end-diastolic pressure (EDP) remained lower (after 30-min ischemia 26 +/- 2 vs. 35 +/- 2 mm Hg). In addition, recovery of mechanical function in BQ610-treated hearts was accelerated during reperfusion. BQ610 did not affect ATP but significantly accelerated and increased creatine phosphate (51 +/- 7 vs. 37 +/- 3%) recovery on reperfusion after 30-min ischemia. BQ610-treated hearts subjected to 15-min ischemia also showed lower EDP during ischemia and accelerated recovery of mechanical function during reperfusion. However, in this case, there were no differences in high-energy phosphate concentrations between treated and untreated hearts. We conclude that the protective action of BQ610 on mechanical function during ischemia/reperfusion injury can be but is not consistently associated with beneficial effects on cardiac high-energy phosphate metabolism.

Adenosine Triphosphate↗
PubMed1996

Neuropeptides accentuate interleukin-4 induced human immunoglobuline E synthesis in vitro.

Corticotropin releasing factor, adrenocorticotropic hormone (ACTH) and alpha-melanocyte stimulating hormone either inhibit or enhance in a dose-dependent fashion an interleukin-4 (IL-4) driven human IgE synthesis in vitro. Here, we show that culture conditions strongly influence the earlier observed dose- and donor-dependent effects of adrenocorticotropic hormone. The effect of ACTH on IgE synthesis became only apparent late during culture periods, suggesting an indirect effect via the cellular microenvironment rather than by acting directly at the level of B-cell isotype switching. Thus, we studied other proopiomelanocortin (POMC) derived peptides and neuropeptides known to influence the cellular microenvironment. Indeed, similar modulatory effects on IgE synthesis were also observed by the addition of other proopiomelanocortin-derived peptides such as alpha-, beta-, and gamma-endorphins as well as by the opioid binding pentapeptide Leu-enkephalin. Furthermore the neuropeptide substance P accentuated an IL-4 or an IL-4 and anti-CD40 antibody driven class switch to IgE. In contrast to ACTH, substance P interfered not only with IgE synthesis but also with the synthesis of the other immunoglobulin isotypes. Thus, systemically acting neuroendocrine peptides such as ACTH and locally acting neuropeptides such as the enkephalins and substance P can modulate the magnitude of an IL-4 induced IgE response.

Adrenocorticotropic Hormone↗
PubMed1996

[Reversible cerebral MRI findings in acute microangiopathic hemolytic anemia].

A case of acute microangiopathic hemolytic anemia in a 29-year-old primiparous patient is presented. Following an unsuspicuous pregnancy and uncomplicated delivery, the patient developed upper abdominal symptoms and transient psychopathologic abnormalities 2 days after delivery. Because of a series of generalized tonic-clonic seizures and respiratory distress she was admitted to the Neuro ICU. Focal neurological symptoms were absent, and CSF analysis was normal. Laboratory findings indicated hemolytic anemia with fragmented erythrocytes in smear specimens, thrombocytopenia, reticulocytosis, marked elevation of liver and pancreatic enzymes, and microhematuria. T2-weighted MR scans of the brain discluded multiple ischemic lesions of the cerebral white and gray matter, caudate nucleus and pons, displaying a hemodynamic pattern. Specific treatment included administration of corticosteroids, repeated plasmapheresis with substitution by fresh frozen plasma and antithrombin III. A control MR performed on the 3rd day of treatment demonstrated the absence of nearly all abnormal findings previously obtained. During a 3-week clinical course the patient showed full recovery, including normalization of hematologic and neuroradiologic findings. This case demonstrates ischemic cerebral lesions in acute microangiopathic hemolytic anemia to be potentially reversible if specific treatment is provided.

Adult↗
PubMed1996

[Minimally invasive myocardial revascularization. Initial experience with myocardial revascularization without extracorporeal circulation].

The authors present an account on the first phase of application of minimally invasive techniques of revascularization of the heart into clinical practice at their department. Since December 1994 to the end of January 1995 in selected 15 patients from a total of 240 patients with IHD 16 arterial and 8 venous grafts were sutured on the beating heart from median sternotomy. None of the patients died and none need reoperation. All patients are free from anginous complaints after operation and their clinical condition is satisfactory. Revascularization of the heart by means of arterial and venous grafts on the beating heart from median sternotomy is a technically reproducible method which enables us to elaborate further minimally invasive procedures for the treatment of IHD. The presented paper is a preliminary communication without claims of statistical validity of the achieved results.

Aged↗
PubMed1996

[Minithoracotomy in cardiac surgery. Initial experience with closure of an atrial septal defect with a minithoracotomy].

The authors describe their own modification of closure of an atrial septal defect (ASD) from right anterolateral minothoracotomy. This minimally invasive approach was selected in girls and women. Right anterolateral thoracotomy was used in 1987 to 1994 in twelve female patients. With regard to the general trend towards aesthetic surgery the authors use at present minimal anterolateral right-sided thoracotomy which with regard to its close relationship with the right atrium makes a safe surgical access to the atrial septum possible. Extracorporeal circulation is implemented by cannulation of the iliac artery in the groin, venous return is ensured by cannulas inserted into the venae cavae in the surgical field (by the auricle of the right atrium into the vena cava superior and the right atrial wall into the vena cava inferior). The operation itself is performed with electric fibrillation of the heart and tightening of the venous tourniquets. Between January 1995 till March 1996 the authors made by the thus modified approach a closure of the ASD type secundum in four female patients age 17, 29, 35 and 40 years. ASD was located always in the fossa ovalis and was repaired by direct suture. The duration of the extracorporeal circulation was on average 30 minutes. The length of the skin incision was 8-10 cm. The operation was free from complications. The cosmetic result is excellent and is consistent with principles of aesthetic surgery. If an arterial cannula is inserted into the groin minithoracotomy can be recommended for closure of ASD with extracorporeal circulation as a safe method.

Adolescent↗
PubMed1995

Selective quantitative analysis of the intensity of immunohistochemical reactions.

The present study reports a new method for the densitometric measurement of the intensity of immunohistochemical reactions. This method is based on a programm for the Kontron VIDAS image analysis system and has been designed for the measurement of small differences in the relative intensity of immunohistochemical reactions. Immunohistochemistry was performed with the avidin-biotin-peroxidase complex and diaminobenzidine-HCl and H2O2 for enzyme visualization. Several methods for shade correction and image processing were elaborated. The study was carried out on gerbil Purkinje cells using monoclonal antibodies raised against calbindin D28k. Prerequesites of correct measurement were standardized preparation, i.e., identical thickness of the paraffin sections, identical performance of immunohistochemistry, and avoidance of any counterstaining. The evaluation of small intensity differences of immunohistochemical reactions was found to be feasible either by substractive shade correction and standardized normalization or by shade correction by division by a reference image and standardized thresholding. Small differences in antigen concentration were not detectable without additional image processing.

Animals↗
PubMed1995

Contributions of 31P-magnetic resonance spectroscopy to the understanding of dilated heart muscle disease.

In the present work, we studied clinical and haemodynamic correlates of impaired cardiac high-energy phosphate metabolism in patients with heart failure due to dilated cardiomyopathy (DCM). Myocardial 31P-magnetic resonance (MR) spectra were obtained at 1.5 T in 14 volunteers and 23 patients with DCM (mean ejection fraction 34%) in order to quantify the creatine phosphate (CP)/ATP ratio. In addition, patients underwent cardiac catheterization and echocardiography. Compared to volunteers (2.02 +/- 0.11), CP/ATP ratios were significantly reduced in DCM patients (1.54 +/- 0.10; P < 0.05), indicating impaired high-energy phosphate metabolism. CP/ATP ratios correlated with the clinical severity of heart failure estimated from the NYHA class (r = 0.47, P < 0.01); also, CP/ATP correlated with left ventricular ejection fraction (r = 0.54, P < 0.01) and left ventricular end-diastolic wall thickness (r = 0.51, P < 0.01). Thus, 31P-MR spectroscopy can detect abnormal cardiac high-energy phosphate metabolism in patients with heart failure due to DCM. These abnormalities correlate with clinical and haemodynamic parameters. Future studies will have to determine whether 31P-MR spectroscopy can contribute to the routine clinical evaluation of patients with heart failure.

Adenosine Triphosphate↗
PubMed1995

Neuron-specific enolase in gerbil brain and serum after transient cerebral ischemia.

BACKGROUND AND PURPOSE: The sensitivity and validity of serum neuron-specific enolase as a marker of brain injury were tested after global cerebral ischemia. METHODS: Sixty-nine Mongolian gerbils were perfusion fixed after variable reperfusion after 5-minute (group 1) or 15-minute (group 2) bilateral carotid occlusion. Neuron-specific enolase was analyzed by an enzyme immunoassay in serum of control, sham-operated, and ischemic animals before euthanasia and in nonischemic gerbil brains. Brains were processed for histology, immunohistochemistry, and morphometric evaluation of ischemic neuronal damage. RESULTS: After cerebral ischemia, loss of neuronal immunoreactivity was closely associated with increased neuron-specific enolase serum levels, which were significantly elevated by 24 hours (group 1) or by 4 hours (group 2) of reperfusion (P < .001). Response of serum levels depended on the duration of preceding ischemia, and maximum concentrations were approximately 3-fold (group 1) or 20-fold (group 2) those of nonischemic control. Morphological damage became apparent 48 hours (group 1) or 12 hours (group 2) after ischemia, as indicated by histological and morphometric data. CONCLUSIONS: Significantly elevated neuron-specific enolase serum levels could be demonstrated as a consequence of ischemia-induced cytoplasmic loss of neuron-specific enolase in central nervous system neurons, corresponded quantitatively to the severity of cerebral ischemia, and were detectable before irreversible neuronal injury. Therefore, analysis of serum neuron-specific enolase is suggested to be both a valuable diagnostic tool in clinical management of the initial stages of global cerebral ischemia and a prognostic parameter during the postischemic course.

Animals↗
PubMed1995

Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction.

The purpose of this study was to test the hypothesis that energy metabolism is impaired in residual intact myocardium of chronically infarcted rat heart, contributing to contractile dysfunction. Myocardial infarction (MI) was induced in rats by coronary artery ligation. Hearts were isolated 8 wk later and buffer-perfused isovolumically. MI hearts showed reduced left ventricular developed pressure, but oxygen consumption was unchanged. High-energy phosphate contents were measured chemically and by 31P-NMR spectroscopy. In residual intact left ventricular tissue, ATP was unchanged after MI, while creatine phosphate was reduced by 31%. Total creatine kinase (CK) activity was reduced by 17%, the fetal CK isoenzymes BB and MB increased, while the "adult" mitochondrial CK isoenzyme activity decreased by 44%. Total creatine content decreased by 35%. Phosphoryl exchange between ATP and creatine phosphate, measured by 31P-NMR magnetization transfer, fell by 50% in MI hearts. Thus, energy reserve is substantially impaired in residual intact myocardium of chronically infarcted rats. Because phosphoryl exchange was still five times higher than ATP synthesis rates calculated from oxygen consumption, phosphoryl transfer via CK may not limit baseline contractile performance 2 mo after MI. In contrast, when MI hearts were subjected to acute stress (hypoxia), mechanical recovery during reoxygenation was impaired, suggesting that reduced energy reserve contributes to increased susceptibility of MI hearts to acute metabolic stress.

Adenosine Diphosphate↗
PubMed1994

Okadaic acid treatment leads to a fragmentation of the trans-Golgi network and an increase in expression of TGN38 at the cell surface.

Okadaic acid (OA) is a protein phosphatase inhibitor which has, among other properties, previously been shown to induce a fragmentation of the cisternae of the Golgi stack [for review, see Lucocq (1992) J. Cell Sci. 103, 875-880]. The effects of OA an reversible and mimic intracellular events which occur during mitosis. To date, due to a lack of endogenous marker proteins, the effects of OA on the trans-Golgi network (TGN) has not been studied. Certain drugs, e.g. Brefeldin A (BFA), have different effects on the morphology of the Golgi stack and the TGN; it is therefore relevant to ask what effect(s) OA has on the TGN. We now present data from a study in which we have used antibodies to TGN38, an integral membrane protein predominantly localized to the TGN of rat NRK cells [Luzio, Brake, Banting, Howell, Braghetta and Stanley (1990) Biochem. J. 270, 97-102], to investigate the effects of OA on this organelle. OA induces a reversible fragmentation of the TGN. This fragmentation occurs with similar kinetics to that observed within the Golgi stack, and is independent of protein synthesis. The sensitivity of the TGN to OA is similar to that of the Golgi stack. The fragmentation of the TGN induced by OA also leads to a 10-fold increase in the level of TGN38 expressed at the plasma membrane.

Amino Acid Sequence↗
PubMed1994

Carotid endarterectomy without arteriography: the preeminent role of the vascular laboratory.

The classic workup of patients considered for carotid endarterectomy (CE) has included contrast arteriography to delineate the nature and extent of the arterial pathology. Noninvasive testing (NIT) consisting of duplex scanning plus sound spectrum analysis is an alternative method for accurately evaluating the carotid bifurcation. The accuracy of our laboratory in comparing NIT to contrast arteriography has been established by use of the guidelines suggested by the Intersocietal Commission for the Accreditation of Vascular Laboratories. Forty-two patients underwent CE based on NIT alone. Seventeen had hemispheric transient ischemic attacks or minor strokes, six had amaurosis fugax, three had nonspecific symptoms, and 16 were asymptomatic. NIT identified a severe stenosis that was limited to the carotid bifurcation; the internal carotid artery distal to the bulb was normal. The predicted stenotic atherosclerotic lesion was confirmed at operation in all patients. One patient had a high bifurcation that required an extension of the original incision. Of three undiagnosed kinked distal internal carotid arteries found at operation, only one required surgical correction. No transient ischemic attacks, strokes, or deaths occurred postoperatively. CE can be performed in selected patients based on NIT alone, obviating the mortality, morbidity, and cost of arteriography. This algorithm demands that the NIT is unequivocal and the accuracy of the testing laboratory is established and maintained according to published standards.

Arteriosclerosis↗