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Biomedical subjects

M Ries

Publications and source records attributed to M Ries.

At least 55 records · Page 3Linked to original sources

Dose-dependent protective effect of BPC 157 on capsaicin-induced rhinitis in rats.

Protection of BPC 157 on capsaicin-induced rhinitis was studied in Wistar rats for its effect on mastocyte infiltration, degranulation and inflammatory cell infiltration. Animals were pretreated with 10 microg/kg, 10 ng/kg or 2 ml saline i.p. and capsaicin (0.05 ml/nostril of 1750 nmol/l sol.) was applied intranasally. They were then euthanized at 1, 3 and 12 h after capsaicin provocation. Nasal mucosa was analyzed and scored for mastocyte infiltration, degranulation and inflammatory cell infiltration. BPC 157 pretreatment significantly prevented mastocyte infiltration at 1 h. Polymorphonuclear leukocyte infiltration was significantly reduced in rats pretreated with 10 microg/kg BPC 157. A dose-dependent effect of BPC 157 pretreatment was demonstrated only for polymorphonuclear leukocyte infiltration at 12 h.

Administration, Intranasal↗

Congenital intracerebral teratoma: a rare differential diagnosis in newborn hydrocephalus.

Congenital hydrocephalus is caused by a broad spectrum of underlying disorders. In the majority of cases it is due to aqueductal stenosis and other distinct congenital anomalies, like Arnold-Chiari malformation. Nevertheless, in the differential diagnosis rare conditions such as cerebral malignancies must also be considered. We present two cases of congenital intracerebral teratoma as a differential diagnosis in congenital obstructive hydrocephalus. A teratoma is suggested when a rapidly growing hydrocephalus with a central calcified and vascularized mass is found sonographically. Regular cerebral structures usually cannot be detected. Early diagnosis in such cases is of clinical importance as the prognosis of congenital intracerebral teratoma is generally very poor.

Brain Neoplasms↗

Molecular and functional properties of fetal plasminogen and its possible influence on clot lysis in the neonatal period.

The blood fibrinolytic system essentially consists of proteolytic enzyme activation processes leading to the formation of the fibrin-degrading enzyme plasmin. It is thus the counterpart of the blood coagulation system. It differs physiologically in newborns compared with adults. In newborns, the plasma levels of plasminogen, the inactive plasmin precursor, are relatively low, and a correlation between maturity and plasminogen levels is observed. Newborn plasminogen has been purified, characterized, and compared with adult plasminogen and does exist in a fetal form with an increased concentration of sialic acid, similar to fetal fibrinogen. We review the molecular and functional properties of fetal plasminogen and its possible influence on clot lysis and thrombolytic therapy in the neonatal period.

Blood Coagulation↗

In vitro fibrinolysis after adding low doses of plasminogen activators and plasmin generation with and without oxidative inactivation of plasmin inhibitors in newborns and adults.

PURPOSE: The aim of this study was to investigate in vitro fibrinolysis after adding low doses of plasminogen activators and to determine the functional role of plasmin inhibitors in newborns and adults. PATIENTS AND METHODS: We have studied the kinetics of in vitro fibrinolysis after adding low doses of urokinase (UK) and recombinant tissue plasminogen activator (rt-PA) by use of a microtiter clot lysis assay. Additionally, we have determined plasmin generation with and without oxidative inactivation of plasmin inhibitors in newborns and adults. RESULTS: The 50% lysis time in the clot lysis assay correlated with the activator dose and was significantly shorter in newborns at rt-PA concentrations of < 0.21 microgram/ml. When UK was used as an activator, the 50% lysis time was slightly but significantly prolonged in newborns at concentrations of 140-200 IU/ml, whereas we could find lower values (non-significant) at 110 and 80 IU/ml. Plasmin generation after oxidative inactivation of plasmin inhibitors was significantly lower in newborns, even when compared with adult plasma, which was diluted 50%. However, in a physiological plasma milieu (containing natural inhibitors), there were no differences in plasmin generation when streptokinase (SK) was used as an activator and only minor differences when UK was used. CONCLUSIONS: Our data indicate a more rapid clot lysis at low UK and rt-PA concentrations in newborns despite significantly reduced plasminogen levels. The results of the plasmin generation experiments suggest a diminished effect of plasmin inhibitors towards fetal plasmin, which raises an explanation for the concentration-related differences in the clot lysis assay. The experience with thrombolytic agents in newborns is limited. Most dosage regimens for thrombolytic therapy in children or adults consist of an initial bolus infusion, followed by low-dose continuous treatment. Based on the results of our clot lysis experiments, we think that especially the continuous infusion of plasminogen activators after bolus administration should not be enhanced in newborns compared to older children or adults.

Adult↗

The role of alpha 2-antiplasmin in the inhibition of clot lysis in newborns and adults.

The fibrinolytic system is involved in a wide variety of biological phenomena and differs physiologically in newborns compared to older children or adults. Newborn's plasminogen differs from adult plasminogen in carbohydrate composition, cell binding and activation kinetics. The fetal plasminogen has an increased concentration of sialic acid similar to fetal fibrinogen. In a previously reported study on plasminogen activation kinetics, we demonstrated differences in the reaction kinetics between fetal plasmin and plasmin inhibitors as compared to the reaction between adult plasmin and inhibitors. Hitherto, there are no investigations on the role of alpha 2-antiplasmin in the inhibition of clot lysis in newborns. We studied the contributions of purified alpha 2-antiplasmin to the regulation of fibrin clot lysis by use of a microtiter clot lysis assay. The lysis time of clots without adding purified alpha 2-antiplasmin correlated to the activator dose. When purified alpha 2-antiplasmin was incorporated at final concentrations ranging from 10 to 40 micrograms/ml, strong dose-dependent inhibition resulting in a prolongation of 50% lysis time was observed. The inhibition in newborns at all alpha 2-antiplasmin concentrations was less pronounced than that of the adults if 50% lysis time was < 55 min. If 50% lysis time was > 55 min. the prolongation of 50% lysis time was more pronounced in newborn than in adult plasma. The fact that we have less effects of alpha 2-antiplasmin in newborn infants at short reaction times despite the lower plasminogen levels, is consistent with slower reaction kinetics between plasmin and alpha 2-antiplasmin in newborns. These differences raise an explanation for the findings of Idell et al. [Am J Respir Crit Care Med 1994; 149:767-775] in premature baboons with neonatal respiratory distress syndrome (RDS). The knowledge of different reaction kinetics between plasmin and alpha 2-antiplasmin and the role of alpha 2-antiplasmin in the inhibition of clot lysis in newborns can be helpful to elucidate the significance of the fetal fibrinolytic system in neonatal RDS and to establish treatment strategies for fibrinolytic therapy of progressive RDS.

Adult↗

[Magnetic resonance imaging in the diagnosis of doubtful cases of small melanoma of the choroid].

The main complementary procedures used to diagnose a choroidal melanoma are A- and B-mode ultrasonography, fluorescein angiography and magnetic resonance imaging (MRI). With MRI the malignant tumour has unique MRI signature owing to the paramagnetic properties of melanin. MRI can thus help in making the differential diagnosis and in estimating tumour extension. The advantage of MRI is that it provides complementary information that, when added to the results of the other investigative techniques, results in a quasi certain diagnosis. Three clinical cases are discribed.

Adenocarcinoma↗

Severe intracranial hemorrhage in a newborn infant with transplacental transfer of an acquired factor VII:C inhibitor.

We describe a woman in whom inhibitors to factor VIII:C developed in her first pregnancy. The neonate had a factor VIII:C level of 1% and an inhibitor titer of 5.2 Bethesda units. After an uneventful vaginal delivery, the boy had an intracranial hemorrhage at 5 days of age. To our knowledge, this is the first report of a bleeding complication in a newborn infant with transplacental transfer of an acquired factor VIII:C inhibitor.

Cerebral Hemorrhage↗

Age-related differences in a clot lysis assay after adding different plasminogen activators in a plasma milieu in vitro.

PURPOSE: The fibrinolytic system is involved in a wide variety of biological phenomena and differs physiologically in newborns compared to older children or adults. Because the newborn has hypoplasminogenemia and a possible existence of a dysfunctional plasminogen with normal adult levels of plasminogen activator inhibitor type 1 and alpha 2-antiplasmin and elevated levels of plasminogen activator inhibitor type 2, it could be expected that the response to standard concentrations and doses of plasminogen activators would be reduced. PATIENTS AND METHODS: We have studied the kinetics of in vitro fibrinolysis after adding different concentrations of streptokinase(SK), urokinase(UK), and recombinant tissue plasminogen activator(rt-PA) by use of a microtiter clot lysis assay. RESULTS: Geometrical dilution rows showed characteristic dose response curves. After clot formation a rapid lysis was seen with all plasminogen activators. The 50% lysis time correlated to the plasminogen activator dose and showed no differences among normal adults, children aged 1-6 years, and children age 7-14 years. Newborns demonstrated a significantly prolonged 50% lysis time with all urokinase concentrations. The 50% lysis time with recombinant tissue plasminogen activator and streptokinase was significantly prolonged only at high concentrations, whereas we could not see any differences at lower concentrations. CONCLUSION: The experience with thrombolytic agents in newborns is limited, and no controlled investigations have been reported. Our results of the fibrinolytic potential in a plasma milieu in vitro after adding different plasminogen activators can be helpful to establish dosage guidelines for thrombolytic therapy in newborns and older children.

Adolescent↗

[Thrombolysis of modified Blalock-Taussig shunts in childhood with recombinant tissue-type plasminogen activator].

Since 1983, when c-DNA was isolated, recombinant tissue plasminogen activator (rtPA), an endothelial-cell-produced activator of fibrinolysis is used, more increasingly often in therapy of thrombosis. Whereas some studies have been published regarding efficacy and safety rtPA in different thrombotic states of adults, only case reports exist in children. Doses vary widely (0.8-6 mg/kg/d), bleeding complications are reported in up to 50%. We report on four infants with complex cyanotic congenital heart disease who developed an early post-operative thrombosis of a modified Blalock-Taussig shunt. By local low dosage application of rtPA we could achieve a complete lysis of the thrombus in three of our four patients. In one patient we were unsuccessful due to a distal stenosis of the shunt. This infant required repeat surgery with creation of a central aortopulmonary shunt. We saw severe bleeding in one, requiring transfusion of packed cells, and formation of a perigraft reaction in another patient. In our experience local application of rtPA in low doses is a good therapeutical option in patients with thrombosis of aorto-pulmonary shunts, especially in the first postoperative days.

Dose-Response Relationship, Drug↗

Sonographic demonstration of multiple intrahepatic meconium masses in a newborn with meconium peritonitis.

We report on a patient with atresia of the colon transversum and a large meconium pseudocyst adherent to the liver. Sonography additionally revealed multiple cystic structures due to intrahepatic meconium masses. Surgical evacuation of the meconium pseudocyst resulted in massive diffuse hemorrhage from the liver which could not be stopped. The child died intraoperatively due to hemorrhagic shock. Histologically the intrahepatic meconium masses were surrounded by various degrees of necrosis and hemorrhage without a well-defined capsule of fibrous granulation tissue.

Colonic Diseases↗

Thrombolysis of a modified Blalock-Taussig shunt with recombinant tissue plasminogen activator in a newborn infant with pulmonary atresia and ventricular septal defect.

A 10 day old infant with pulmonary atresia, ventricular septal defect, and collateral pulmonary blood supply through a left sided ductus arteriosus developed complete shunt thrombosis four days after the creation of a modified Blalock-Taussig shunt. Recombinant tissue plasminogen activator was given locally into the proximal end of the shunt as two bolus injections of 0.1 mg/kg and two bolus injections of 0.2 mg/kg over 10 minutes, followed by a continuous infusion of 1.4 mg/kg/day for 16 hours and 0.7 mg/kg/day for 18 hours with systemic low dose heparin 5 IU/kg/h. This resulted in complete clot dissolution and reperfusion without haemorrhagic complications and without laboratory signs of systemic fibrinolytic activation.

Abnormalities, Multiple↗

[Total cavopulmonary anastomosis: risk factors and results in patients under 4 years of age].

In recent years, an increasing number of modified Fontan-operations has been performed in children younger than 4 years of age. The purpose of this study was to identify preoperative risk factors in this age group. From February 1990 until February 1993, we performed in our center a modified Fontan-operation using the technique of total cavopulmonary anastomosis (TCPA) in 37 consecutive patients (17 pts. < 4 years = group I, 20 pts. > 4 years = group II). Early postoperative mortality occurred in patients of group I only (n = 3 pts.). All of these patients had additional preoperative risk factors. Pulmonary vascular resistance (PVRI) > 2 U x m2 was a significant risk factor for the younger patients while pulmonary artery size alone (expressed as the McGoon-ratio or Nakata-index) could not be identified as a separate risk factor. Using two additional indices (McGoon-ratio/PVRI and Nakata-index/PVRI), we were able to identify patients with unfavorable postoperative hemodynamics as high-risk patients. In our experience, TCPA can be performed in patients younger than 4 years of age with a low mortality, if there are no additional preoperative risk factors. For high-risk patients we recommend either a bidirectional Glenn-anastomosis as a first step procedure or a TCPA with fenestration of the intraatrial tunnel-patch.

Adolescent↗

[Aorto-left ventricular tunnel with origin in the left sinus of Valsalva: a rare cause of congenital aortic insufficiency].

Aortico-left-ventricular tunnel is a rare congenital cardiac lesion that often results in severe aortic insufficiency in infancy. Normally, the defect appears immediately above the right coronary sinus of Valsalva and consists of a tunnel-like connection between the aortic root and the left ventricle. The differential diagnosis to coronary artery fistulae and ruptured aneurysms of the sinus of Valsalva is often difficult. We describe a patient with an aortico-left-ventricular tunnel originating from the left aortic sinus. Similar findings have been described in only three case reports. Additionally, in our case there was a stenosis in the midportion of the tunnel which was connected to an intraseptal aneurysm communicating with the left ventricular chamber via a "septal" defect. The infant underwent successful surgical correction of this malformation at 1 year and 5 months of age.

Angiocardiography↗

Transport of cefadroxil in rat kidney brush-border membranes is mediated by two electrogenic H+-coupled systems.

The transport characteristics of the aminocephalosporin [3H]cefadroxil have been studied in brush-border membrane vesicles (BBMV) of rat kidney cortex by a rapid filtration technique and by use of a potential sensitive fluorescent dye. Influx of [3H]cefadroxil (0.25 microM) into BBMV as a function of time displayed a pronounced overshoot phenomenon in the presence of a transmembrane pH gradient (pHin > pHout). Evidence for an electrogenic cefadroxil/H+-symport in the presence of an inwardly directed proton gradient is provided by the demonstration of: 1) reduced uptake in the presence of a protonophore; 2) reduced uptake under voltage clamp conditions; and 3) increased uptake in the presence of a valinomycin-induced inside negative K+-diffusion potential. pH-gradient dependent uptake of [3H]cefadroxil as a function of substrate concentration revealed the presence of multiple carrier systems. By kinetic analysis, a high-affinity carrier system (Km, 8.8 +/- 1.3 microM) and a low-affinity system (Km, 2.62 +/- 0.80 mM) could be resolved. The high-affinity transport system was found to be very specific for substrates (cephalosporins and di- and tripeptides) carrying an alpha-amino group. By use of a potential sensitive fluorescent dye 3,3'-dipropylthiadicarbocyanine iodide, the low-affinity transport system was characterized with respect to its driving force and its kinetic features. This transporter was found also to be electrogenic in nature, representing a second cefadroxil/H+-symport system. In summary, our studies demonstrate for the first time uphill transport of cefadroxil in kidney BBMV mediated by multiple carrier systems. Transport is rheogenic, energized by the proton motive force and shared by other aminocephalosporins as well as di- and tripeptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Brain abscesses in neonates--report of three cases.

We report three newborns with brain abscesses. Two infants suffered from Serratia marcescens meningitis and one infant had enterococcal sepsis and meningitis. Brain abscesses were detected by cerebral sonography. Outcome in one infant with S. marcescens infection was poor. This patient developed multicystic encephalo-malacia and severe developmental retardation. In the other patient with S. marcescens infection surgical drainage of the abscess was performed. The outcome was good both in this infant and in the patient with enterococcal brain abscess.

Brain Abscess↗

Polyposis of the gallbladder associated with metachromatic leukodystrophy.

We report on two children with metachromatic leukodystrophy and polyposis of the gallbladder. In both patients ultrasound examination revealed a small gallbladder with a thickened echogenic wall and multiple polypoid masses. In one patient diagnosis of gallbladder polyposis was made 6 months before the first neurological symptoms occurred. As gallbladder polyposis is a rare phenomenon in childhood, metachromatic leukodystrophy should be excluded.

Child, Preschool↗