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Biomedical subjects

F K Tegtmeyer

Publications and source records attributed to F K Tegtmeyer.

At least 19 recordsLinked to original sources

Inhibition of granulocyte activation by surfactant in a 2-yr-old female with meningococcus-induced ARDS.

Activated polymorphonuclear neutrophils (PMNs) play a crucial role in acute respiratory distress syndrome (ARDS) via extracellular release of reactive cell products such as elastase. Surfactant has proved valuable in restoring lung function in ARDS. The significance of its immunomodulatory properties with respect to this effect has not yet been clarified. The aim of the present study was to determine the anti-inflammatory effects of surfactant administration in an infant with ARDS. During the acute phase of ARDS in a 2-yr-old female, levels of PMN-derived elastase complexed with alpha1-protease inhibitor (E-alpha1PI) were measured in both arterial and central venous blood samples obtained simultaneously. The results were correlated with oxygen demand and plasma concentrations of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) after endotracheal administration of surfactant (Alveofact 60 mg x kg x body weight(-1)). In the present case, for the first time, a higher E-alpha1PI concentration was detected in arterial blood (4.51 mg x L(-1)) than in central venous blood (2.28 mg x L(-1)). After administration of surfactant, these concentrations and the arteriovenous difference decreased, indicating that during ARDS, most PMN degranulation takes place in the pulmonary vascular bed and is inhibited by surfactant administration. Simultaneously, TNF-alpha and IL-6 plasma concentrations decreased within hours and lung function was restored. This local inhibition of polymorphonuclear neutrophil activation by exogenous surfactant may play a key role in the early improvement in lung function after surfactant administration.

Child, Preschool↗

Do cardiac output and serum lactate levels indicate blood transfusion requirements in anemia of prematurity?

BACKGROUND: Whether and when to transfuse in anemia of prematurity is highly controversial. Some authors suggest transfusions simply if the hemoglobin (Hb) level is below a defined normal range. Others propose the use of clinical or laboratory parameters in anemic patients to decide whether to transfuse or not. HYPOTHESIS: A decreasing amount of circulating Hb should cause a compensatory increase in cardiac output (CO) and an increase in arterial serum lactate. MATERIALS AND METHODS: In 56 anemic preterm infants (not in respiratory or hemodynamic failure) we analyzed CO after the first week of life using a Doppler sonographic method. At the same time serum lactate levels, Hb levels and oxygen saturation were registered. Nineteen of these patients were given transfusion when they demonstrated clinical signs of anemia by tachycardia > 180/min, tachypnea, retractions, apneas and centralization (group 2). The remaining 37 patients were not transfused (group 1). Serum lactate, CO, heart rate (HR), oxygen delivery, respiratory rate, capillary refill and Hb were analyzed in both groups and in group 2 before and 12-24 h after transfusion. Data between groups 1 and 2 and in group 2 before and after transfusion were compared. RESULTS: In the 56 patients studied no linear correlation between Hb and CO or between Hb and serum lactate was found. Nor could any correlation be demonstrated between the other variables studied. Examining the subgroups separately, a negative linear correlation was demonstrated between serum lactate and oxygen delivery in group 2. No other significant correlations were detected. However, when the pre- and post-transfusion data were compared in group 2 (increase of Hb from 9.45 (SD 3.44) to 12.5 (SD 3.8) g/100 ml), the CO decreased from 281.3 (SD 162.6) to 224 (SD 95.7) ml/kg per min (p < 0.01) and serum lactate decreased significantly from 3.23 mmol/l (SD 2.07) before to 1.71 (SD 0.83) after transfusion. Oxygen delivery was 35.8 (+/- 0.19) ml/kg per min group 1, 27.8 (+/- 0.05) pre- and 43.4 (+/- 0.07) post-transfusion in group 2 (p < 0.01). CONCLUSIONS: CO measurements and serum lactate levels add little information to the decision-making process for blood transfusions, as neither CO nor serum lactate levels correlate with HB levels in an otherwise asymptomatic population of preterm infants. In infants where the indication for blood transfusion is made based on traditionally accepted clinical criteria, serum lactate is an additional laboratory indicator of impaired oxygenation, as it correlates significantly with oxygen delivery. A significant lower oxygen delivery in patients in whom blood transfusion is indicated and an increase in oxygen induced by transfusion demonstrate the value of these criteria in identifying preterm infants who benefit from transfusion.

Anemia, Neonatal↗

In vitro modulation of induced neutrophil activation by different surfactant preparations.

Endotracheal surfactant administration has gained an important role in the treatment of respiratory failure. Polymorphonuclear neutrophil granulocyte (PMN) activation mediated by chemoattractants, such as interleukin-8 (IL-8), neutrophil-activating peptide-2 (NAP-2) and formylated bacterial oligopeptides, has been found to be involved in the pathophysiology of acute respiratory failure. We investigated potential modulating effects of commercial surfactant preparations (Exosurf, Alveofact, Curosurf and Survanta) on spontaneous and chemoattractant-induced PMN function. Isolated cytochalasin B (CytB)-treated PMNs from healthy adults were incubated with increasing concentrations of surfactant. The response of the cells was measured in terms of elastase release from the lysosomes within 30 min. The PMNs showed no direct activation by any of the surfactants tested. However, when cells were stimulated with suboptimal dosages of chemokines, such as IL-8 (2 nM) or NAP-2 (100 nM), or formyl-methionyl-leucyl-phenylalanine (fMLP) (50 nM), and co-incubated with increasing concentrations of surfactant (0.05-8 mg.mL-1) the release of elastase was markedly modulated depending on the surfactant preparation used. Whilst Exosurf and Alveofact showed only modest effects on the elastase release induced by all three mediators, Curosurf and Survanta markedly inhibited the cellular response in a dose-dependent manner. At concentrations above 1 mg.mL-1, Curosurf and Survanta decreased the IL-8-, NAP-2- and fMLP-induced elastase release by 83, 67 and 90%, and by 82, 75 and 80%, respectively. In conclusion, exogenous surfactant may modulate the inflammatory response of the airways by affecting the chemoattractant-induced polymorphonuclear neutrophil activation. Surfactant preparations with inhibiting properties on neutrophil activation may participate in the prevention of neutrophil-induced lung damage.

Adult↗

[Intraosseous puncture as vascular access in pediatric emergency and intensive care medicine].

In paediatric resuscitation scenarios, emergency physicians have sufficient skills in endotracheal intubation. They are successful in about 80% of the cases as US studies indicate. However, vascular access is much more of a critical problem and emergency physicians succeed in only 50%. Therefore, intraosseous access has become an internationally widely used and accepted method for venous access. In Germany, however, only case reports concerning this technique have been published. Based on the authors' experience shared with Sussmane and Raszynski in the US, we used the technique of intraosseous access in 18 paediatric resuscitative situations. Eleven patients survived who would not have done so without quick intravenous access. As complications we recorded a minor fracture, one compartment syndrome, which did not require surgical intervention, and a postmortally discovered minor fat embolism, which was of no clinical significance. Courses teaching this method should be offered in Germany to spread knowledge of this life-saving technique.

Catheters, Indwelling↗

Plasma concentration of elastase-alpha 1-proteinase inhibitor complex in surfactant-treated preterm neonates with respiratory distress syndrome.

Although exogenous surfactant replacement improves respiratory distress syndrome (RDS) of immature neonates, it may not prevent subsequent lung damage and development of bronchopulmonary dysplasia associated with polymorphonuclear neutrophil (PMN)-activation. We therefore wanted to assess whether surfactant administration would be associated with activation of circulating PMNs. Since elastase-alpha 1-proteinase inhibitor (E-alpha 1-PI) has proved to be a sensitive indicator of intravascular PMN activation, we studied E-alpha 1-PI plasma concentration in preterm neonates during the treatment of RDS with a bovine surfactant preparation (group I: n = 23). Results were compared with those from a retrospective control group treated by ventilation alone (group II: n = 13), and with a reference group of 92 newborns (group III). Following surfactant administration, median E-alpha 1-PI concentration increased significantly (day 1 80.5 vs Day 2,234 micrograms.l-1), and exceeded the upper limit of the reference range of 274 micrograms.l-1 in seven patients, with a maximal value of 1,881 micrograms.l-1 after multiple surfactant administrations. In contrast, 12 infants from Group II showed no increase in median E-alpha 1-PI levels (Day 1,107 vs Day 2,107 micrograms.l-1), and remained within the reference range (Day 1,125 micrograms.l-1; Day 2,107 micrograms.l-1) of the 92 newborns without respiratory impairment, infection, birth-trauma or asphyxia. From these results, it is concluded that surfactant may trigger a transient, mainly local, inflammatory response, reflected by increased levels of E-alpha 1-PI, and may exert a dose-related pathogenic influence on the course and prognosis of RDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchopulmonary Dysplasia↗

Elastase alpha 1-proteinase inhibitor and lactoferrin concentrations in endotracheal aspirates of ventilated newborns.

Bacterial colonization of the tracheo-bronchial tree is common and an established risk factor for infection in ventilated newborns. Elastase, a highly active proteinase, and lactoferrin, an iron-binding protein and potential modulator of the inflammatory process, are both major constituents of either azurophilic or primary granules of neutrophilic granulocytes, released by activation of these cells during the inflammatory response. Since both elastase, complexed with its major inhibitor alpha 1-proteinase inhibitor (E alpha 1-Pl), and lactoferrin (Lf) are indicators of granulocyte activation during bacterial infection, they may indicate infectious inflammation at the tracheobronchial site. To study whether these substances in a single suction probe may serve this purpose, we obtained 82 tracheo-bronchial aspirates routinely from 16 ventilated newborns with a median gestational age of 31.5 (range, 25-39) weeks for laboratory analysis and bacterial cultures. Systemic inflammatory response by differential white blood cell count and C-reactive protein (CRP) was monitored simultaneously. The median E alpha 1-Pl level was significantly elevated in culture-positive aspirates (1,005 micrograms/L; range, less than 30-29,240 micrograms/L) in contrast to culture-negative samples (158 micrograms/L; range, less than 30-1,408 micrograms/L). In addition to a diagnostic sensitivity of 77%, E alpha 1-Pl offered a high specificity of 88%, a positive predictive value of 97%, and a negative predictive value of 73%. In contrast, median Lf concentration (10.6; range, 0.3-58.3 mg/L vs. 11.7; range, 1.6-158 mg/L) showed no correlation with culture results. Of the culture-positive aspirates 36% corresponded with systemic signs of an acute inflammatory response, such as elevated I/T-ratio and CRP.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗

Elastase alpha 1 proteinase inhibitor complex, granulocyte count, ratio of immature to total granulocyte count, and C-reactive protein in neonatal septicaemia.

In a prospective study elastase alpha 1-proteinase inhibitor (E alpha 1PI), polymorphonuclear (PMN) count, the immature to total neutrophil count ratio (I/T ratio), and C-reactive protein (CRP) were analysed in 74 patients (76 cases) with neonatal septicaemia at the time of initial clinical symptoms. At that early stage of the disease, 94% of the patients had abnormal values for E alpha 1PI, 71% for I/T ratio, 61% for PMN count, and only 54% for CRP. PMN count was a poor indicator of septicaemia. Neutropenia, present in 26% of all patients, was related to normal E alpha 1PI in only 4 patients. The combined use of E alpha 1 and I/T ratio was the most sensitive indicator. In all patients irrespective of causative bacteria or disease onset at least one of these parameters was elevated. In early-onset septicaemia (n = 31), normal CRP values occurred significantly more often (63%) than in late-onset sepsis (33%). Even in five of the seven fatal cases, initial CRP measurements were normal. The sensitivity of PMN count and I/T ratio did not differ significantly between early- and late-onset septicaemia. Laboratory changes observed in 18 newborns during the first 3 days of the septic episode show that the rate of pathological values for E alpha 1PI and I/T ratio was highest at the time of initial clinical symptoms and decreased on days 2 and 3. In contrast, CRP reached maximal values as late as day 2 (88% abnormal values), followed by a decrease on day 3. We conclude that the use of E alpha 1PI may improve the laboratory detection of neonatal septicaemia especially if used in combination with I/T ratio.

Bacteremia↗

Prophylactic low-dose vancomycin treatment in very-low-birth-weight infants.

For the prophylaxis of septicemia with coagulase-negative staphylococci in a high-risk very-low-birth-weight population, we administered 5 mg/kg of vancomycin every 12 h. Distribution volume and half-life of vancomycin were determined. Serum peak and trough levels were obtained on day 3 of treatment. With this low-dose regimen, serum concentrations in the therapeutic range were achieved in 35 of the 45 patients. Distribution volume and half-life were 0.692 liters/kg and 7.4 h, respectively. The distribution volume was not related to the gestational age; the half-life in the group of patients with a gestational age < 30 weeks was considerably higher. The 10 small-for-gestational-age children had a significantly smaller distribution volume. The vancomycin trough levels correlated with the serum creatinine concentrations and, therefore, with the gestational age. Our study indicates that this low vancomycin dose is sufficient in very-low-birth-weight infants to achieve therapeutic serum levels, being suitable for both prophylaxis and sepsis therapy.

Creatinine↗

[The significance of the initial respiratory parameters in assessing the severity of ARDS in children].

In adults, the course and outcome of the acquired respiratory distress syndrome (ARDS) are closely related to the initial respiratory situation. Respiratory indices are frequently used for prognostic purposes and hence for the institution of new techniques such as extracorporeal lung support. The validity of these indices to predict the outcome in pediatric ARDS patients has not been examined as yet. We studied respiratory indices in 69 pediatric ARDS patients. METHODS. Out of 69 pediatric ARDS patients with various underlying diseases (Table 1), we chose 21 with a paO2/FiO2 ratio less than 150 mm Hg at some point to test the prognostic significance of a respiratory severity index (RSI), i.e., mean airway pressure x alveolar-arterial pO2 difference (A-aDo2)/paO2, a respiratory index (RI), i.e., A-aDO2-paO2/paO2, and other respiratory parameters (Table 2). Postsurgical patients, patients with incurable diseases, clearly non-respiratory deaths, and those treated with extracorporeal membrane oxygenation were excluded. We looked for statistical differences between survivors and nonsurvivors and correlations between ventilator days, intensive care unit (ICU) days, and hospital days and these indices. RESULTS. We did not find a significant difference between all respiratory indices tested at admission to the ICU and 24 h later between survivors and nonsurvivors (Table 3). Nonsurvivors initially had significantly higher blood pressures and lower heart rates. Both RSI and RI were significantly correlated to days on the ventilator, days in the ICU, and days in the hospital (Table 4). Initial multiorgan failure was significantly more common in nonsurvivors. CONCLUSIONS. Initial lung dysfunction as indicated by respiratory indices does not predict the outcome in pediatric ARDS. The underlying disease, hemodynamic situation, and age have to be considered in relation to the degree of lung dysfunction to determine new therapeutic strategies such as extracorporeal support.

Child↗

[Poisoning with volatile hydrocarbons. 3 cases and a review].

BACKGROUND: Volatile crude oil derivates (hydrocarbons) are becoming more and more widely used in homes and during leisure activities. This leads to a high rate of intoxications with these products in children (5% of all pediatric intoxications, 25% of all lethal intoxications). Clinical courses, pathophysiology, and therapy of these intoxications are referred and studied. METHODS: Based on a literature review and 3 cases reports with different clinical courses, intoxications with volatile hydrocarbons are analyzed. RESULTS: The inhalation of volatile hydrocarbons causes an ARDS. This explains the high mortality. Early oxygen-treatment with PEEP-ventilation, however, facilitates a favourable outcome without residual defects as we demonstrate in one case. Another patient needs prolonged ventilatory support after a delayed start of therapy. A third patient cannot be saved even with ECMO. CONCLUSIONS: Initial pulmonary symptoms after hydrocarbon intoxication, such as coughing and cyanosis, are signs for a severe course. Immediate hospitalization with repetitive chest x-rays and adequate instant therapy are the only option to reduce the high mortality of this intoxication.

Child↗

Air embolism and pulmonary interstitial emphysema in a preterm infant with hyaline membrane disease.

A preterm infant with severe hyaline membrane disease requiring extreme mechanical ventilation developed pulmonary air leaks with consecutive shock. The chest roentgenogram showed bilateral pulmonary interstitial emphysema and gas within the heart silhouette as well as in the hepatic veins, inferior v. cava, portal vein, and many abdominal vessels. The respiratory and circulatory failure by massive systemic gas embolism resulted in death.

Embolism, Air↗

[Trauma caused by shaking the infant--a special form of child abuse].

The shaking of infants is an often underestimated cause of head-injuries in children. Without any external signs the diagnosis can be missed. The combination of subdural hematoma of typically interhemispheric site and retinal bleeding is pathognomonic of the shaked-baby syndrome. It is caused by acceleration-deceleration movements of the head. We present three patients with whiplash-shaken-injuries who were admitted to our hospital with impaired consciousness or in coma. With little external signs of injury more detailed investigations revealed other, older injuries suggesting previous abuse. The outcome was not favourable. Two of the children were discharged with minor or mild psychomotor retardation and one child was severely handicapped. As in the battered-child-syndrome a good history, assessing child specific and familial risk-factors and the socioeconomic background are most important to confirm a diagnosis. This type of injury is usually part of the spectrum of child abuse.

Brain Damage, Chronic↗

[The treatment of severe pulmonary hypertension in newborn infants using extracorporeal membrane oxygenation or conventional measures. An interinstitutional comparison].

In a two years retrospective study we analyzed neonates from a US and a German neonatal center with pulmonary hypertension (persistent fetal circulation--PFC). The US patients were treated with Extracorporeal Membrane Oxygenation (ECMO) the german patients with conventional methods as hyperventilation, catecholamines, and vasodilators. Both groups fulfilled the classical ECMO entrance criteria: an alveolar-arterial oxygen difference greater than 610 mmHg and an oxygenation index (i.e. mean airway pressure x FiO2 x 100/paO2 of greater than 40 mmHg. We compared anamnestic and respiratory parameters with the t-test for independent groups or the chi-square test accordingly. With one patient in each group the mortality was not significantly different and the rate of meconium aspirations was the same. The APGAR score at 5 min was significantly lower in the US group, prenatal care was undertaken in significantly less US than german patients. Time intervals between delivery and important therapeutic interventions as intubation, hyperventilation, first catecholamines were not significantly different between both groups. Also worst paO2, pH, and paCO2 were not significantly different. Mechanical ventilation was more aggressive in the US group, i.e. higher intermittent-mandatory-ventilation-rate and peak inspiratory pressure. On the one hand our studies demonstrate that even patients fulfilling ECMO criteria still have a good chance with conventional treatment. On the other hand differences in APGAR scores and prenatal care might indicate that hypoxic-ischemic influences alter the US-group morbidity.

Apgar Score↗

[Elastase-alpha 1-proteinase inhibitor complex (E alpha 1 PI) and lactoferrin plasma concentrations in viral and bacterial infections].

Typical alterations of the white blood cell count are often missed during the acute course of infectious diseases. Activiation and degranulation of granulocytes are followed by elevation of E alpha 1 PI and lactoferrin plasma concentrations under these conditions. The aim of our study was the evaluation of the diagnostic significance of these granulocyte parameters in relation with the absolute granulocyte count in infected pediatric patients. A total number of 106 patients at the age of 1 day to 16 years were studied. 25 children suffered from viral, 26 from localized and 23 from systemic bacterial infections, 32 children exhibiting no signs of infection served as controls. Results of the study are given as medians and ranges. Total granulocyte count was elevated above controls (4.8; 2.2-12.7/nl) only in patients with localized bacterial infections (13.3; 5.5-36.5/nl). E alpha 1 PI and lactoferrin plasma concentrations correlated well (r = 0.72) and were found to be significantly elevated in patients with localized bacterial infections (856; 363-4820 micrograms/l and 748; 206-2078 micrograms/l) and septicemia respectively (661; 256-2078 micrograms/l and 871; 160-9550 micrograms/l). A clearcut differentiation of septic and locally infected patients was given by the ratio of E alpha 1 PI and total granulocyte counts. Significantly elevated E alpha 1 PI concentrations of patients exhibiting viral infections (295; 86-690 micrograms/l) may suggest effective granulocyte activation under this condition. Finally we conclude that E alpha 1 PI and lactoferin plasma concentration related to total granulocyte counts in infected patients may serve as a helpful indicator of granulocyte activation during the acute course of the disease.

Adolescent↗

Proteinase-antiproteinase imbalance in meningitis: determination of alpha 1 proteinase inhibitor (alpha 1PI), elastase-alpha 1PI complex, and elastase inhibition capacity in cerebrospinal fluid.

Mortality and long-term neurologic sequelae are still frequent complications of meningitis despite effective antibiotic treatment. This suggests that pathogen-independent inflammatory mechanisms may play an important role in the course of this illness. Neutrophil granulocytes form the primary immune defense in meningitis. Once activated, these cells release elastase into the cerebrospinal fluid (CSF). Elastase may induce tissue damage if local antiproteinase capacity is low as under normal conditions. To define the relevance of this mechanism we studied 22 patients with meningitis. Concentrations of elastase in complex with the main antiproteinase alpha 1-proteinase inhibitor (elastase-alpha 1 PI), alpha 1-proteinase inhibitor (alpha 1PI), and elastase inhibition capacity (EIC) were measured in CSF of 9 patients with bacterial meningitis (BM), aged 1 month-14 years; 13 patients with non-bacterial meningitis (NBM), aged 1 month-15 years; and 20 patients in whom meningitis was excluded after spinal tap (control group), aged 6 months-15 years. The concentration of elastase-alpha 1PI in the BM group (median 552 micrograms/l) was significantly higher than in either the NBM group (median 30 micrograms/l, p less than 0.01) or the control group (median 30 micrograms/l, p less than 0.01). Similarly, the alpha 1PI-concentration in the BM group was significantly higher (median 113 mg/l) than either the NBM group (median 13.7 mg/l, p less than 0.025) or the control group (median 6.3 mg/l, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Variation of alpha 1-antitrypsin glycoprotein microheterogeneity in hepatic postresuscitation disease.

Microheterogeneity of the glycoprotein alpha 1-antitrypsin has been investigated sequentially by high resolution isoelectric focusing in a child with the proteinase inhibitor MS phenotype after near-drowning. A band-splitting with additional cathodal fractions exhibited migration from the most cathodic to the anodic positions of the glycoprotein isoforms in the course of post-resuscitation disease. The pattern may reflect the time- and stage-dependent hypoxic and post-hypoxic effects on hepatocellular metabolic zonation.

Humans↗