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Biomedical subjects

J Simák

Publications and source records attributed to J Simák.

At least 19 recordsLinked to original sources

[New Apgar score? A multi-centre study dealing with the evaluation of the neonate NEOMOD scoring system for the first day of life].

OBJECTIVE: To compare the predictive accuracy of the NEOMOD score and the Apgar score as concerns prediction of mortality and affection of the central nervous system (CNS) in neonates. DESIGN: Prospective multi-centre clinical study. SETTING: Mother and Child Care Institute, Prague; Thomayer's Faculty Hospital with a Policlinic, Prague. METHODS: All neonates with a gestation age > or =35 weeks of pregnancy, hospitalised in the intensive care units of the cooperating hospitals in the period 1998-2002, were included in the study. For all the neonates, the NEOMOD score was established in the first 24 hours and the Apgar score was established in the 1st, 5th and 10th minutes of their lives. The aim was to establish the predictive accuracy of the scoring systems for mortality and affection of CNS in the first 28 days of life. RESULTS: 620 patients participated in the study; 16 patients (1.90%) died by the 28h day. The predictive accuracy for mortality expressed as AUS - the area under receiver operating characteristic (ROC) curve reached the highest level for NEOMOD AUC = 0.96. AUC for the Apgar score was 0.84 in the 1st minute; it was 0.84 in the 5th minute and it was 0.88 in the 10th minute. The predictive accuracy for affection of CNS was AUC = 0.76 in the case of NEOMOD; in the case of Apgar, AUC was 0.71, 0.74 and 0.77 in the 1st, 5th and 10th minute, respectively. CONCLUSION: The NEOMOD system proved a high accuracy in the prediction of neonatal mortality in a group of patients with a gestation age > or =35 weeks of pregnancy. The predictive accuracy of NEOMOD was higher than that of the Apgar score. The predictive accuracy of both the NEOMOD and Apgar scores for affection of CNS in the neonatal period was low.

Apgar Score↗

Postnatal increase of procalcitonin in premature newborns is enhanced by chorioamnionitis and neonatal sepsis.

BACKGROUND: To determine the influence of chorioamnionitis and neonatal sepsis on procalcitonin (PCT) levels in very-low-birth-weight (VLBW) infants within the first week of life. DESIGN: PCT serum levels were measured in cord blood 1 h after delivery and on day 3 and day 7 of life. Chorioamnionitis and neonatal sepsis within the first week were monitored. RESULTS: Chorioamnionitis was present in eight of 37 patients (21.6%). PCT on day 3 was increased in both the "No chorioamnionitis" (2.54 ng mL(-1), SEM 0.51) and "Chorioamnionitis" (6.96 ng mL(-1), SEM 2.93) groups of VLBW infants compared with the 1st hour values (0.45 and 0.58 ng mL(-1) SEM 0.07 and 0.11, respectively, P < 0.001) of the same patients. The postnatal gain was higher in the "Chorioamnionitis" group (P < 0.01). Neonatal sepsis was diagnosed (after exclusion) in 12 of 32 patients (37.5%). Mean values of maximum PCT in patients with and without sepsis were 8.41 ng mL(-1) (SEM 1.87) and 3.02 ng mL(-1) (SEM 1.38), respectively (P < 0.05). Sensitivity to sepsis of PCT, ratio of immature to total neutrophils (I : T), and C-reactive protein (CRP) were 75%, 50% and 25%, respectively. CONCLUSIONS: In the group of VLBW infants the PCT level within 72 h of delivery was markedly increased in patients with chorioamnionitis. Compared with I : T and CRP, PCT appears to be a more sensitive marker of neonatal sepsis.

C-Reactive Protein↗

Angiopoietin-1, angiopoietin-2 and Tie-2 in tumour and non-tumour tissues during growth of experimental melanoma.

Tumour progression is dependent on the formation of new vessels in tumour tissue. Tumour cells produce a variety of factors that influence vessel growth and maintenance both in tumour and tumour-adjacent tissues. Angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2) and their tyrosine kinase receptor Tie-2 have been shown to play an important role in the processes of growth and remodelling of normal as well as tumour vessels. We studied gene expression of the angiogenic factors Ang-1 and Ang-2 and of their tyrosine kinase receptor Tie-2 in the tumour and non-tumour tissues of mice bearing the experimental melanoma B16. Using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR we measured Ang-1, Ang-2 and Tie-2 mRNA levels in the tumour, bone marrow, liver and spleen. Melanoma tissue overexpressed Ang-2 mRNA compared with spleen, liver and bone marrow of normal mice, suggesting its role during melanoma progression. On the other hand, there was a significant decrease in Ang-2 mRNA level in bone marrow cells collected on days 5 and 10 of tumour growth compared with the expression of Ang-2 mRNA in the bone marrow of normal mice and those collected on days 15 and 20 of tumour growth. These data demonstrate, for the first time, an ectopic effect of the tumour on the gene coding for an angiogenic factor, and also suggest that tumour growth may influence angiogenesis and/or vasculogenesis in distant organs.

Angiopoietin-1↗

Characterization of multiple organ dysfunction syndrome in very low birthweight infants: a new sequential scoring system.

To define multiple organ dysfunction in newborns, we established a sequential scoring system NEOMOD (Neonatal Multiple Organ Dysfunction Score). It was developed to describe the process of increasing physiologic derangement in critically ill newborns. It provides, during the first 28 days of life, information concerning function of organ systems having a primary influence on mortality in very low birth weight (VLBW) infants. Our scoring system has been used in 142 VLBW infants. It evaluates moderate (1 point) or severe dysfunction (2 points) in 7 organ systems (central nervous system, cardiovascular, renal, respiratory, and gastrointestinal systems, and hemocoagulation and acid-base balance) in 24-h intervals from day 1 to 28 of life. Maximum possible value of NEOMOD was 14 points. Receiver operating characteristic curve was used for assessing predictive accuracy of maximum NEOMOD score obtained by daily scoring for mortality rate. AUC (area under curve) attained by NEOMOD was 0.95 for mortality within the first 28 days and 0.91 for hospital mortality, respectively. In the study group, NEOMOD score of > or = 9 was associated with 100% mortality. An analysis of specific organ dysfunctions in the non-survivors group (n = 16) disclosed, in all patients, dysfunction of more than two organ systems 24 h before death. Similar to critically ill adults, secondary multiple organ dysfunction can be described also in a majority of critically ill VLBW infants. NEOMOD scores may help to evaluate daily the severity of the syndrome and risk of death.

Female↗

Fenfluramine-induced pulmonary vasoconstriction: role of serotonin receptors and potassium channels.

The anorexic agent fenfluramine considerably increases the risk of primary pulmonary hypertension. The mechanism of this effect is unknown. The appetite-reducing action of fenfluramine is mediated by its interaction with the metabolism of serotonin [5-hydroxytryptamine (5-HT)] in the brain. We tested the hypothesis that the pulmonary vasoconstrictive action of fenfluramine is at least in part mediated by 5-HT receptor activation. In addition, we sought to determine whether pharmacological reduction of voltage-gated potassium (K(V)) channel activity would potentiate the pulmonary vascular reactivity to fenfluramine. Using isolated rat lungs perfused with Krebs-albumin solution, we compared the inhibitory effect of ritanserin, an antagonist of 5-HT(2) receptors, on fenfluramine- and 5-HT-induced vasoconstriction. Both 5-HT (10(-5) mol/l) and fenfluramine (5 x 10(-4) mol/l) caused significant increases in perfusion pressure. Ritanserin at a dose (10(-7) mol/l) sufficient to inhibit >80% of the response to 5-HT reduced the response to fenfluramine by approximately 50%. A higher ritanserin dose (10(-5) mol/l) completely abolished the responses to 5-HT but had no more inhibitory effect on the responses to fenfluramine. A pharmacological blockade of K(V) channels by 4-aminopyridine (3 x 10(-3) mol/l) markedly potentiated the pulmonary vasoconstrictor response to fenfluramine but was without effect on the reactivity to 5-HT. These data indicate that the pulmonary vasoconstrictor response to fenfluramine is partly mediated by 5-HT receptors. Furthermore, the pulmonary vasoconstrictor potency of fenfluramine is elevated when the K(V)-channel activity is low. This finding suggests that preexisting K(V)-channel insufficiency may predispose some patients to the development of pulmonary hypertension during fenfluramine treatment.

4-Aminopyridine↗

[Procalcitonin--a marker of systemic infection and multiorgan dysfunction: characteristics of the gene and protein].

Procalcitonin (PCT) is a protein consisting of 116 aminoacids with molecular weight 13 kDa. It is encoded by CALC-1 gene. According to the basic and clinical research results PCT appears to be a highly sensitive and specific marker reflecting severity of the systemic inflammatory response to infectious stimuli. Despite the investigation focused on CALC-1 gene, little is known about the biology of PCT and cellular sources of PCT during inflammation. One of the possible sources may be human peripheral blood mononuclear cells. PCT is an indicator of bacterial infections minimally stimulated by viral infections, autoimmune diseases and tumors.

Biomarkers↗

[Prevention of venous thromboembolism].

Deep venous thrombosis and pulmonary embolism, the epidemiologically most important forms of thromboembolic disease still remain one of the most serious problems in medicine. The authors summarize some epidemiological data, the incidence and risk of the disease with regard to the patients condition and the type of insult. The authors mention possible methods of non-specific prevention, types and effectiveness of specific primary and secondary pharmacoprophylaxis and describe physical prophylactic methods. The review offers recommendations for prevention with regard to the assessed risk of the patient and type of insult with special attention to the use of nadroparine.

Anticoagulants↗

Development of multiple organ failure in critically ill newborns under AT III substitution.

Criteria for the AT III substitution were fulfilled by 33 infants. Mean birth weight was 1321 g (480 g up to 2860 g), and mean gestational age was 29 weeks (23-39 weeks). AT III substitution in dosing of 5 u/kg/hr was administered to all patients as well as standard heparin 10 u/kg/hr. Initial plasma level of AT III in the study group prior to start of the substitution was 45 +/- 17% activity of normal plasma of adult donor. The value increased up to 90 +/- 32% after 24 hours and up to 113 +/- 38% at the end of the therapy. Eight patients died (24%). Considerable decrease of the Neonatal Therapeutic Intervention Scoring System (NTISS), indicating a level of multiple organ dysfunction, was observed as early as after the first 48 hours of AT III therapy in the entire group (p < 0.01). Extensive increase of platelet count (p < 0.05) occurred after 48 hours of AT III therapy in survivors. Except for a severe sepsis in one case, no clinical signs of increased bleeding occurred during the AT III therapy, and the clinical signs of pre-existing bleeding even disappeared in 5 cases. Analysis of the group of 8 deceased patients revealed irreversible organ dysfunction in 7 cases present prior to the start of AT III substitution. In conclusion, during the AT III substitution, no bleeding, no clinical side effects but improvement in multiple organ dysfunction including increase in platelet count was recorded.

Anticoagulants↗

[Extracorporeal membrane oxygenation in the treatment of severe pulmonary hypertension in a neonate after surgery for laparoschisis].

The authors describe the case of newborn with laparoschisis in whom severe idiopathic pulmonary hypertension during postoperative period developed and initiation of extracorporeal membrane oxygenation (ECMO) to maintain circulatory stability and adequate oxygenation was necessary. ECMO was performed for 75 hours with maximum extracorporeal support up to 50% of cardiac output (Biomedicus pump BP 50, Jostra oxygenator M8). Patient was successfully weaned and switched to conventional ventilation and nitric oxide inhalation with consequent extubation. No bleeding complications were observed during ECMO in connection with surgical repair of laparoschisis.

Extracorporeal Membrane Oxygenation↗

[Effect of natural surfactant on mortality and morbidity in neonates with a birth weight below 1500 grams].

OBJECTIVE OF STUDY: Evaluation of the natural surfactant in treatment of the respiratory distress syndrome (RDS) on the mortality and morbidity of neonates with a birth weight lower than 1500 g. TYPE OF STUDY: Retrospective analysis of data. SETTING: Department:perinatological centre, Institute for Mother and Child, Prague. METHOD: A total of 442 neonates with birth weights under 1500 g were evaluated. During period I/1994-XII/1998 271 neonates were analyzed (Group A). The results of the total neonatal mortality and morbidity were compared with results of care provided to 171 patients during I/1989-XII/1993 before introduction of the surfactant. Surfactant therapy was used in 134 patients of group A (9%) with RDS who met the standard indication criteria. The initial surfactant dose (Alveofact R Boehringer Ingelheim, GFR) depended on the ventilation parameters and was 50 mg/kg and in severe forms of RDS 100 mg/kg. The total cumulative dose did not exceed 200 mg/kg. The data were assembled in a database used in the Institute for the Care of Mother and Child and evaluated using the statistical programme EpiInfo (CDC, USA). RESULTS: In the group of neonates with a birth weight lower than 1000 g 110 neonates in group A were evaluated and 61 in group B. Surfactant was administered to 77 infants of the treated group (70%). Statistically significant differences were recorded: in the total mortality (A: 29 vs. B: 79%, p < 0.0001, the number of neonates who died during UPV (A: 32% vs. B: 80%, p < 0.0001), incidence of PVH-IVH grade I-IV (A: 29% vs. B: 67%, p < 0.0001). In the group of neonates with a birth weight of 1000 to 1499 g 161 children were evaluated in group A and 110 in group B. Alveofact was administered to 57 neonates of the treated group (35%). Statistically significant differences were recorded: in the total mortality (A: 4%, vs. B: 31%, p < 0.0001), the number of neonates who died during UBPV (A: 7% vs. B: 45%, p < 0.0001), incidence of perintraventricular grade I-IV (A: 11% vs. B: 35%, p < 0.0001), incidence of patent ductus arteriosus (A: 6% vs. B: 15%, p < 0.02), incidence of pneumothorax (A: 7% vs. B: 18%, p < 0.01) and in the incidence of posthaemorrhagic hydrocephalus (A: 2% vs. B: 11%, p < 0.01). There was a statistically significant difference in the incidence of BPD to the disadvantage of group A (A: 16% vs. B: 8%, p < 0.01). CONCLUSION: The study confirmed the favourable effect of the introduction of surfactant in the treatment of RDS and on the general mortality and morbidity of neonates with a birth weight below 1500 g.

Czech Republic↗

[Extracorporeal membrane oxygenation in the treatment of acute respiratory failure in full-term neonates].

OBJECTIVE OF STUDY: Evaluation of success of extracorporeal membrane oxygenation, EMCO) in the treatment of acute respiratory failure in mature neonates. TYPE OF STUDY: Clinical pilot study of the EMCO centre. SETTING: Institute for the Care of Mother and Child, Prague. MATERIAL AND METHOD: In 12 consecutive patients with severe acute respiratory distress syndrome and/or circulatory failure of different etiology who met the indication criteria the method of venoarterial EMCO was used. RESULTS: Venoarterial extracorporeal membrane oxygenation was successful in 75% patients who survived. Four patients died (1x syndrome of cerebral death associated with severe hypoxic-ischaemic encephalopathy, 2x severe irreversible haemorrhage, into the abdominal and thoracic cavity, 1x periventricular intraventricular haemorrhage grade III.). The mean period of EMCO was 71.4 +/- 31.7 hours (range 25-130 hours). On comparison of the surviving group (S) and the non-surviving group (NS) there was a significant difference in the necessity of continuous inotropic adrenaline support during EMCO. In patients who died necropsy confirmed irreversible multiorgan failure. CONCLUSION: In indicated cases extracorporeal membrane oxygenation remains the method of choice in critically ill mature neonates. A prognostically adverse factor is the necessity of inotropic support and haemodialysis during EMCO.

Acute Disease↗

Surface expression of major membrane glycoproteins on resting and TRAP-activated neonatal platelets.

Platelets of full-term newborns and those of healthy adult donors were compared for constitutive expression of surface glycoproteins (GP) Ia-IIa, GP Ib, GP IIb-IIIa, and GP IV and for their activation responses to an agonist by detection of surface expression of activation markers P-selectin and CD63. Resting neonatal platelets showed significantly lower expression of GP Ia-IIa, GP Ib, and GP IIb-IIIa. In contrast, the expression of GP IV was significantly higher compared with platelets of adults. The expression of activation markers P-selectin and CD63 was assessed after in vitro activating of platelets with 0-15 microM human thrombin receptor-activating peptide. At low concentrations of thrombin receptor-activating peptide, the extent of surface expression of activation markers did not differ significantly between adult and neonatal platelets. However, after activation with 15 microM thrombin receptor-activating peptide, the extent of surface expression of P-selectin and CD63 was significantly lower in neonatal platelets. Because of ethical reasons, our study was conducted on neonates with a moderate neonatal hyperbilirubinemia. The remote possibility that hyperbilirubinemia could influence the expression of platelet surface receptors and the reactivity of neonatal platelet cannot be excluded. The role of higher expression of GP IV on neonatal platelets, also seen in certain hematologic malignancies in adults, remains to be elucidated. The lower expression of platelet adhesive receptors and the limited ability to up-regulate granular glycoproteins may play a role in the impairment of function of neonatal platelets.

Adult↗

[Adhesion receptors of the vascular endothelium and their role in acute inflammation].

Vascular endothelium plays a key role in regulation of the inflammatory response. Adhesion molecules (selectins, immunoglobuline receptors, integrins, cadherins and connexins) expressed on the endothelial cells surface, take part in several interactions. In normal circumstances, they mediate endothelial cell-matrix interactions and regulate vascular permeability. During the process of inflammation the surface expression of adhesion molecules changes. Those receptors then participate in the interactions between leukocytes and activated endothelium surface, in the process of leukocyte activation and in their extravasation. Soluble forms of several adhesion molecules are released into the circulating blood. Plasma levels of soluble adhesion molecules may be a diagnostic marker of the systemic endothelial injury.

Acute Disease↗

[Delayed surgery in congenital diaphragmatic hernia without drainage of the ipsilateral hemithorax].

The objective of the investigation was to evaluate the success of a new therapeutic protocol in patients with congenital diaphragmatic hernia (CDH). During the period from 1/1994 till 12/1998 41 patients with CDH were admitted. In 36 patients (88%) left-sided CDH was diagnosed, in 4 patients (10%) right-sided CDH and one neonate (2%) bilateral CDH. Fifteen cases (37%) of CDH were assessed prenatally. Twenty-two children (54%) were treated by inhalation of nitric oxide (INO) and 4 patients (10%) by extracorporeal membrane oxygenation. The total incidence of associated developmental defects was 20% and the total mortality 34%. On comparison of the surviving (group S, n = 27) and the non-surviving NS, n = 14) patients statistically significant differences were found in the Apgar score during the first minute (S: 5.9 +/- 0.5 vs. NS: 3.4 +/- 0.7, p < 0.008), in the oxygenation index (OI) two hours after admission (S: 11.9 +/- 2.9 vs. NS: 27.7 +/- 8.3, p < 0.03), in the alveolo-arterial oxygen difference (AaDO2) 2 hours and 12 hours after admission (S: 369 +/- 47 torr and 237 +/- 47 torr resp. vs. NS: 552 +/- 29 torr and 557 +/- 26 torr resp., p < 0.02) and in the need to start extracorporeal membrane oxygenation (S: 3.7% vs. NS: 21.4%, p < 0.009). The investigation confirmed a reduced mortality of neonates with CDH by introducing new therapeutic methods. Risk factors are early prenatal diagnosis, the presence of associated developmental defects, high values of oxygenation and ventilation with the necessity to start nitric oxide inhalation.

Administration, Inhalation↗

Severe coagulopathy after a bite of a green bush viper (Atheris squamiger): case report and biochemical analysis of the venom.

A 34 year old male bitten by an adult Atheris squamiger snake developed symptoms of nausea, vomiting, diarrhea which were followed by drowsiness and impaired breathing. Local hemorrhage, edema and pain at the bite-site occurred, but no systemic bleeding or hemorrhagic diathesis developed. All clinical and laboratory parameters were in the normal range except for afibrinogenemia, thrombocytopenia and slight proteinuria. Replacement therapy (fibrinogen and platelet concentrates) and treatment of shock stabilized the patient within 2d and coagulation returned to normal. Atheris squamiger venom was subjected to biochemical and biological analysis. The LD50 of the venom was 5 mg/kg (mice, s.c.). It produced local hemorrhage corresponding to about 25% of the activity of puff adder venom (Bitis arietans). In vitro the venom had a fibrinogen-converting activity, it did not activate purified prothrombin but very likely contained a F V and Ca2+-dependent prothrombin activator. The venom exhibited strong platelet-aggregating activity, which was not inhibited by protease inhibitors and by EDTA or EGTA. The venom also aggregated acetylsalicylic acid treated platelets indicating, that the arachidonic acid pathway was not essential for activation. Rat serum rapidly inhibited the platelet-aggregating activity of the venom; human serum, however, had only a partial inhibitory effect. Preliminary experiments showed that platelet-aggregating activity may be separated from fibrinogen-converting activity by anion-exchange chromatography.

Adult↗

Changes in alveolar-arterial oxygen difference and oxygenation index during low-dose nitric oxide inhalation in 15 newborns with severe respiratory insufficiency.

UNLABELLED: We evaluated changes in alveolar-arterial oxygen differences (AaDO2) and oxygenation index (OI) during inhalation of low-dose nitric oxide (INO) in 15 newborns with severe respiratory insufficiency: congenital diaphragmatic hernia (CDH) -6, asphyxial lung disease -4, meconium aspiration syndrome (MAS) -2, respiratory distress syndrome -2, persistent pulmonary hypertension of newborn -1. Their mean birth weight was 2522 g (1030-3200 g, SD +/- 575), mean gestational age 36 weeks (29-39 weeks, SD +/- 3.2), mean initial AaDO2 = 607 mm Hg (574-628 mm Hg, SD +/- 14) and mean initial OI = 32 (6-57, SD +/- 12). INO was performed using the Pulmonox system (Messer Griesheim, Austria) at conventional regimens of mechanical ventilation. The initial value of 20 ppm nitric oxide (NO) was decreased 6 h later, first to 15 ppm and then, as quickly as possible, to 3 ppm. The mean inhalation period was 51 h (6-131 h, SD +/- 42). The initial value of AaDO2 and OI decreased significantly within the first 6 h of INO (P < 0.001). After the first 6 h, 4 patients died: 1 with MAS of an extrapulmonary cause and 3 CDH patients because of pulmonary hypoplasia. In the remaining 11 patients the decrease in AaDO2 and OI during the first 24 h of INO was highly significant (P < 0.0001). CONCLUSION: In a heterogeneous group of 15 newborns with severe respiratory insufficiency, the initial AaDO2 and OI decreased significantly within the first 6 h of INO.

Birth Weight↗

Platelet membrane receptors during short cardiopulmonary bypass--a flow cytometric study.

To elucidate a mechanism of platelet dysfunction during extracorporeal circulation, we performed a study on the surface expression of platelet adhesive receptors (GPIb, GPIIb-IIIa) and activation markers (GMP140, GP53) during short cardiopulmonary bypass (CPB). Ten paediatric patients, age 6-13 years, with atrial or atrioventricular septal defects were studied. The mean CPB time was 52 min (21-110 min). During CPB, a significant drop in platelet count was observed, but not below 130 x 10(3)/microliter. The expression of platelet GPIb decreased slightly during CPB and the decrease was not significant. The decrease of GPIIb-IIIa was significant, but only in samples collected either at the end of CPB (89 +/- 13%, p < 0.05) or before leaving the operating room (74 +/- 14%, p < 0.05). The value of surface expression of platelet activation markers (GMP140, GP53) during CPB was in the range of values for resting platelets. Our results suggest that generalized CPB-induced defects of primary haemostasis are not directly connected to circulation of activated degranulated platelets or to loss of platelet adhesive receptors GPIb-IX and GPIIb-IIIa.

Adolescent↗