A compact device for the deterministic generation of medium-sized bubbles.

The subject of the actual work is an experimental apparatus for the temporal reproducible production of gas bubbles within a condensed phase. The bubbles are produced by using a piston-cylinder system by means of gas displacement. The excitation of the piston is realized by an electromagnetic coil, which is operated by microprocessor controlled output stages. The existing modules are capable of producing variable-sized bubbles of 2 mm < d eq < 4 mm with frequencies of up to 70 Hz.

Early conception factor lateral flow assays for pregnancy in the mare.

The ECF lateral flow assay test is marketed to detect non-pregnancy in mares. The objectives of the present study were to determine the accuracy of the ECF test, the accuracy of the electronic reader accompanying the ECF test, and agreement between two human readers and the electronic reader. Serum samples were collected from anestrus, cycling but not inseminated, and inseminated mares, and were evaluated with the ECF test (EDP Biotech Company, Knoxville, TN, USA) at The Ohio State University and at the EDP Biotech Laboratory. Specificity ranged from 0.07 to 0.16, the negative predictive value ranged from 0.15 to 0.33, and accuracy ranged from 0.43 to 0.52. The electronic reader did not add improve the accuracy or predictive values of the test. Based on the electronic reader, 80.0% of the serum samples collected from the anestrus mares were false positives; Readers 1 and 2 had 60.0 and 33.3% false positives, respectively. For samples collected during the estrous cycle, 83.9% were false positives by the electronic reader, whereas Readers 1 and 2 had 43.7 and 26.4% false positives. We concluded that, regardless of whether the test strips were evaluated by a human or electronic reader, this assay was not accurate for determination of the non-pregnant mare.

Short-term outcome in infants with a birthweight less than 501 grams.

AIM: To report survival and morbidity until discharge in preterm infants <501 g with life support started immediately after birth. METHODS/STUDY DESIGN: Cohort study of all preterm infants with birthweights < 501 g born in three tertiary perinatal centres between 1 January 1998 and 31 December 2001 (gestational age (GA) 25.2 [21.0-30.7] wk; birthweight 435 [290-500] g; median [range]). RESULTS: A total of 107 infants with birthweights <501 g were born. Twenty-nine were stillborn. A prenatal decision to initiate life support immediately after birth was reached in 9/37 (24%) infants <24.0 wk GA and in 39/42 (93%) infants > or =24.0 wk GA. Survival was 3/37 (8%) and 26/41 (63%) in infants <24 wk GA and > or =24.0 wk GA, respectively. Twenty-nine of the 48 infants with immediate life support (60%) survived (95% CI: 46-75%). Forty-two of these 48 (88%) infants were small for gestational age. No infant without immediate life support survived (0/30). Twenty-three (79%) survivors developed chronic lung disease (CLD) and eight (28%) received photocoagulation for retinopathy of prematurity (ROP). CONCLUSION: In this population of extremely low birthweight infants, survival was higher than in previous studies when life support was provided immediately after birth. Short-term morbidity was similar to other studies. The presented data on survival support our concept to offer immediate life support after birth in preterm infants with birthweights <501 g. The long-term outcome of these infants needs to be assessed urgently.

Treatment of severe Candida infections in high-risk patients in Germany: consensus formed by a panel of interdisciplinary investigators.

Now that modern medicine can provide increasing chances of cure to patients with formerly incurable disorders, therapy-related complications play the key role in outcome. Thus, among opportunistic infections, severe candidiasis remains a challenge. A multidisciplinary panel of 20 investigators was formed to find a consensus on antifungal strategies for various underlying conditions in neutropenic and non-neutropenic patients. To record their preferences, the investigators used an anonymous voting system. Among antifungal agents, fluconazole emerged as the major alternative to the classic amphotericin B, being therapeutically at least equivalent but clearly less toxic. Factors that restrict the use of fluconazole include pretreatment with azoles, involvement of resistant species like Candida krusei, and an inability to exclude aspergillosis. Flucytosine can be reasonably combined with both amphotericin B and fluconazole. Within the limited antifungal armamentarium, amphotericin B lipid formulations and itraconazole also appear useful and require further investigation. The general consensus of the group is that antifungal agents should be administered at sufficient dosages, rather early, and often empirically.

Effect of positive end expiratory pressure on functional residual capacity and compliance in surfactant-treated preterm infants.

UNLABELLED: Positive end expiratory pressure is routinely used when ventilating preterm infants. Elevation of PEEP increases lung volume, as does surfactant treatment. The purpose of this study was to investigate the effect of various levels of PEEP within the range of 0.2 to 0.4 kPa on lung volume, compliance and gas exchange. We measured functional residual capacity, compliance of the respiratory system and arterial blood gases in 20 infants (median birth weight 1240 g, range 660-1690 g; median gestational age 28 weeks, range 24-32 weeks; postnatal age 3-4 days). The infants were studied at 72 hours after their last dose of natural surfactant. At this time the patients were routinely nursed at 0.3 kPa of PEEP, the PEEP level was lowered to 0.2 kPa or raised to 0.4 kPa in random order. The PEEP level was then changed to the third level 0.4 kPa or 0.2 kPa. Each new setting was maintained for 20 min before FRC, compliance and blood gases were measured. FRC was assessed using SF6 washout technique. Increasing PEEP from 0.2 to 0.3 to 0.4 kPa resulted in increases in FRC (p < 0.01) and oxygenation (ns) in all infants. In 16 infants compliance decreased and paCO2 increased with elevation of PEEP. Only in 4 infants compliance increased and CO2 fell. CONCLUSION: In the majority of our infants reduction of PEEP from 0.4 to 0.2 kPa resulted in increases in compliance and CO2 reduction. Our results might suggest that relatively low levels of PEEP < 0.3 kPa may be appropriate at 72 hours after surfactant replacement. Furthermore, these results underline the importance of PEEP test in clinical practice.

Effect of PEEP and suction via chest drain on functional residual capacity and lung compliance after surgical repair of congenital diaphragmatic hernia: preliminary observations in 5 patients.

BACKGROUND/PURPOSE: Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypoplasia that limits survival. The authors' knowledge on lung mechanics and lung volumes in these patients with hypoplastic lungs is still limited. Therefore, the authors performed measurements of functional residual capacity (FRC), compliance of the respiratory system (CRS), and tidal volume in 5 full-term infants (gestational age, 38 to 40 weeks; birth weight, 2,800 to 3,530 g) before and after surgical repair of neonatal CDH. METHODS: The authors studied the influence of different levels of positive end-expiratory pressure (PEEP) and suction via inserted ipsilateral chest tube connected to a water seal on lung volume and lung mechanics. A computerized tracer gas (SF6) washout method was used for serial measurements of FRC. Compliance of the respiratory system was determined according to insufflatory method. RESULTS: The authors found a preoperative compliance between 1.5 and 3.9 mL/kPa/kg and a preoperative FRC between 9.1 and 12.9 mL/kg indicating severe hypoplasia of the lungs in all patients. Immediately after surgical repair of CDH, compliance decreased to 85% (78% to 91%) of preoperative value, and FRC increased to 132% (110% to 150%) of preoperative value under mechanical ventilation while at 4 cm of water of PEEP and at -10 cm of water of suction via chest drain with the need of high fraction of inspired oxygen. After reduction of PEEP from 4 to 2 or 1 cm of water and lowering suction from -10 cm of water to -2 or 0 cm of water FRC decreased to 103% (80% to 122%) of preoperative value and compliance, and tidal volume improved to 135% (110% to 147%) of preoperative value resulting in increased alveolar ventilation, correction of acidosis and improvement in oxygenation. During the first days after surgery inadequate high PEEP or strong suction via chest tube drainage resulted in increase in FRC paralleled by decrease in compliance indicating overdistension of these hypoplastic lungs. CONCLUSIONS: The data show that overdistension of hypoplastic lungs in infants with CDH can be detected and excluded by repeated measurements of FRC and compliance in these critical ill infants. These data might help setting appropriate ventilator parameters, adequate suction via chest drain, and thereby improve gas exchange and outcome.

Treatment of candidal infections with fluconazole in neonates and infants.

UNLABELLED: To study the therapy, efficacy and safety of fluconazole in candidal mycoses during neonatal phase and infancy a case review in 53 newborns and infants was performed. The majority of these patients were premature with a median birth weight of 1120 g and born within gestational week 23-38. The median age at the onset of fluconazole treatment was 5 weeks. All patients had underlying diseases and several risk factors, which favored the occurence of a systemic candidal mycosis. Systemic candidiasis was the most frequent diagnosis (75.5%). Fluconazole was administered at a daily dosage of 5-6 mg/kg for a median duration of 21 days. The hepatic, renal and hematologic functions were assessed before, one, two, and three weeks after start of treatment. Yeasts were identified in 37 patients. The most common fungus isolated at baseline was Candida albicans (68%). Clinical cure or improvement was reported in 31 out of 38 patients (81.6%). Mycological cure was achieved in 25 out of 32 newborns and infants. Despite the limited number of patients with outcome data, these preliminary results of a small cohort clearly indicate the effective antifungal therapy with fluconazole in neonates and infants. No serious side effects were observed in fluconazole-treated patients. Two patients with megaureter-megacystis-hydronephrosis syndrome and severe meningoencephalitis showed a mild increase in liver enzymes. - CONCLUSION: Fluconazole seems to be an effective therapy for systemic and other forms of candidiasis in infants including very low birth weight infants (VLBWI; <1500 g). These favorable safety and efficacy data are similar to results obtained with fluconazole in older children and adults. These findings, however, must be supported by larger trials. The recommended daily dose is 5 mg/kg body weight. Only in VLBWI the dosage interval within the first two weeks of life should be prolonged up to 3 days and fluconazole serum levels should be monitored.

Administration of fluconazole in children below 1 year of age.

For this review, 78 studies regarding the use of fluconazole in a total of 726 children below 1 year of age were evaluated. The range of fluconazole dosage was 2-50 mg kg-1 day-1, with 162 days being the maximum duration of treatment. According to current experience, fluconazole seems to be well tolerated and efficacious against systemic candidosis and candidaemia in children below 1 year of age, including neonates and very low-birthweight infants (VLBWIs). The recommended daily dosage is 6 mg kg-1. (In Germany, fluconazole is approved for children between 1 and 16 years in cases in which there is no therapeutic alternative for treatment of systemic infections caused by Candida spp. and Cryptococcus neoformans in a dosage of 3-6 mg kg-1 day-1 and for superficial Candida infections in a dosage of 1-2 mg kg-1 day-1.) In patients with impaired renal function, the daily dose should be reduced in accordance with the guidelines given for adults. In neonates during the first 2 weeks of life, this dosage should be administered only every 72 h. In weeks 2-4 of life, the same dose should be given every 48 h, following which daily dosing is appropriate. This posology is derived from the age-related pharmacokinetics of fluconazole, with a higher volume of distribution and a prolonged plasma elimination half-life, especially during the first month of life. Drug monitoring during treatment should be performed to ensure therapeutic plasma concentrations of fluconazole within a range between 4 and 20 micrograms ml-1. The benefit of fluconazole should be investigated in prospective studies for treatment of systemic candidosis with administration of higher dosages as well as for early empiric therapy in VLBWIs.

[Use of fluconazole in children less than 1 year old: review]. / Anwendung von Fluconazol bei Kindern < 1 Jahr: Ubersicht.

For this review, 78 publications for use of fluconazole in children below 1 year of age were evaluated with a total of 726 patients. The range of fluconazole dosage was 2-50 mg/kg/day with 162 days as maximum duration of treatment. According to the present experience, fluconazole seems to be an efficacious and well tolerated therapy against systemic candidosis and candidemia in children below 1 year of age, including neonates and very low birth-weight infants (VLBWI). The recommended daily dosage is 6 mg/kg. In patients with impaired renal function, the daily dose should be reduced in accordance with the guidelines given for adults. In neonates during the first two weeks of life, this dosage should be administered only every 72 hours. In weeks two to four of life, the same dose should be given every 48 hours. After that daily dosing is appropriate. This posology is derived from the age-related pharmacokinetics of fluconazole with a higher volume of distribution and a prolonged plasma elimination half life especially during the first month of life. Drug monitoring during treatment should be performed to ensure therapeutic plasma concentrations of fluconazole within a range between 4 and 20 micrograms/ml. The benefit of fluconazole should be investigated in prospective studies for treatment of systemic candidosis with administration of higher dosages as well as for early empiric therapy in VLBWI.

[Candida infections in infancy and early childhood]. / Candida-Infektionen im Säuglings- und Kleinkindesalter.

Candida infections in infancy can manifest themselves as skin, mucosal or systemic candidiasis. Eighty to nintey percent of all candida infections in this age group are caused by Candida albicans. Whereas in neonates, infections mostly occur sub partu, in older children predisposing underlying diseases get an increasing etiological importance. The diagnosis is based on microscopic and cultural detection of yeast as well as on the course of the titers of Candida antigen and antibodies. For topical antifungal treatment of skin and mucosa infections, different preparations of the polyenes nystatin and amphotericin B have been proven to be most effective. In systemic candidiasis the combination of amphotericin B and 5-flucytosin is the treatment of choice. In view of the potential severe side effects of this combination therapy, fluconazol as a sole treatment represents an effective alternative. Prophylaxis against Candida infections comprises sticking to hygienic regimes, mycological surveillance of risk groups and oral application of antimycotics.

Characteristics and DNA-sequence of a cryptic haloalkanoic acid dehalogenase from Agrobacterium tumefaciens RS5.

Agrobacterium tumefaciens RS5 harbors two different hydrolytic haloalkanoic acid dehalogenase genes, one coding for a nonstereospecific enzyme (DhlS5II) and a second for a cryptic L-isomer-specific dehalogenase (DhlS5I). The latter gene was cloned and expressed in Escherichia coli. Biochemical characterization and sequence analysis of dhlS5I shows its membership to the class of the L-isomer-specific hydrolytic dehalogenases. Highest homology of 72% was found to the dehalogenase LdexYL from Pseudomonas sp. YL. Both enzymes share an unusual high temperature optimum of 65 degrees C. Controlled by a vector promoter, high specific dehalogenase activities up to 32 U mg-1 protein were obtained in E. coli, and putatively, owing to its own sigma70-dependent promoter, a constitutive low-level expression of dhlS5I of 0.4 U mg-1 protein was measured.

[Noninvasive ventilation of a 4-year-old boy with severe central late onset hypoventilation syndrome]. / Nichtinvasive Beatmung bei einem vierjährigen Jungen mit schwerem zentralen "late onset"-Hypoventilationssyndrom.

BACKGROUND: In the literature we found only five reports about noninvasive ventilation in cases with central hypoventilation syndrome. PATIENT AND METHOD: We report about a 4-year-old boy with severe late onset hypoventilation syndrome. During an interval of 3 months with nasal mask ventilation during sleep he showed an excellent cognitive and statomotoric development. After this time, he needed a noninvasive ventilation with a negative pressure system. RESULTS AND DISCUSSION: In our opinion, noninvasive nasal mask ventilation is a modern method in the treatment of patients with central hypoventilation syndrome. Tracheotomy is only necessary during the first year of life.

Homologous Plasmids from Soil Bacteria Encoding D,L-Halidohydrolases

We isolated and characterized D,L-halidohydrolases fromfive different soil bacteria. Three of these bacterial strains bear plasmidswith sizes of approximately 60 kb. Curing and mating experiments indicatedthat these three plasmids pFL160, pFL170, and pFL190 encoded a dehalogenase.Owing to their biochemical characterization, these halidohydrolases wereclosely related among each other and to the DhlIV halidohydrolase, encoded byplasmid pFL40 from Alcaligenes xylosoxidans ssp.denitrificans ABIV. Restriction enzyme patterns as well asDNA-hybridization experiments with an internal fragment of dhlIVrevealed a high degree of homology among each of these four plasmids andtheir dehalogenase genes.

Isolation and Characterization of Dehalogenases from2,2-Dichloropropionate-Degrading Soil Bacteria

Five bacterial strains were isolated from polluted soilscapable of degrading 2,2-dichloropropionate. In crude extracts, dehalogenaseactivity against haloacetates and longer-chained 2-haloalkanoic acids couldbe detected. Results from activity staining indicated that all bacterialstrains expressed a single dehalogenase. In further biochemicalcharacterization, two types of D,L-specific 2-haloalkanoic acid dehalogenaseswere described, which are different from each other not only in molecularweight and electrophoretic mobility, but also in sensitivity towards thiolreagents. Dehalogenases of these strains have been shown to be inducible andare catalyzing halide hydrolysis with inversion of product configuration.

Radiological changes after therapeutic use of surfactant in infants with respiratory distress syndrome.

The aims of this study were to determine the incidence of typical chest radiography findings - (1) uniform improvement, (2) asymmetrical improvement, (3) no improvement or (4) interstitial emphysema - after therapeutic use of surfactant and to analyse clinical course and outcome. Chest radiographs of 138 infants of very low birth weight treated with surfactant were analysed. Twenty-eight infants with a diagnosis other than typical respiratory distress syndrome (RDS), i. e., sepsis, congenital pneumonia and congenital malformation, were excluded. In 110 patients with clinical and radiological evidence of typical RDS (median gestational age 28 weeks, median birth weight 1070 g) adequate chest radiographs from before and within 72 h after surfactant treatment were available. The time of surfactant application ranged between 1 and 12 h after birth. The most common finding after surfactant treatment was uniform or asymmetrical improvement of pulmonary aeration (80 of 110 patients). Patients with uniform clearing had the best long-term outcome. Asymmetrical clearance was often localised on the right side or in central regions of the lung, and usually disappeared after retreatment with surfactant without clinical significance. In 11 patients no change in aeration was found and retreatment was absolutely ineffective. Development of pulmonary inter- stitial emphysema after surfactant treatment was a grave prognostic sign: 73 % of these infants died within the first 2 weeks of life compared with 10 % of those with uniform or asymmetrical improvement of ventilation.

[Noninvasive nocturnal nasal mask ventilation (NIPPV) in childhood and adolescence. Dresden experiences with 11 patients]. / Nichtinvasive nächtliche nasale Maskenbeatmung (NIPPV) im Kindes- und Jugendalter. Dresdener Erfahrungen mit elf Patienten.

BACKGROUND: There are only small experiences with mechanical ventilation via nasal mask in childhood. PATIENTS AND METHODS: Eleven patients using NIPPV (9 patients aged 4 to 18 years and 2 patients with cystic fibrosis aged 20 and 25 years). RESULTS: NIPPV was effective in all 11 patients. Seven patients needed supplemental oxygen. Theophyllin, Almitrin and Salbutamol could support the nasal ventilation in special conditions. CONCLUSION: Intermittent ventilation via nasal mask is a noninvasive and effective treatment of chronic respiratory failure in childhood. Monitoring with continuous pulse-oximetry is necessary.

[Effect of orally administered polyene antimycotics on the intestinal colonization with yeasts: possibilities and limitations]. / Einfluss oral verabreichter Polyenantimykotika auf die Hefepilzbesiedlung des Darmtraktes: Möglichkeiten und Grenzen.

On the basis of intestinal yeast colonization different consequences for therapeutic and prophylactic administration of polyene antimycotics have to be drawn. Immunocompromised neutropenic patients should orally receive polyene antifungal drugs (nystatin or amphotericin B) for a long time during the period of increased risk for systemic candidosis. The level of daily dosing is dependent on age, physiological status of the gastrointestinal tract, and underlying disease of the patient. In immunocompetent persons the normal commensal yeast flora should not be suppressed by antifungal chemoprophylaxis if no clinical indications are present, because permanent eradication of yeast in the intestinal tract ist not attainable. About 5 to 15 days after finishing the administration of polyene antimycotics the fungi are detectable again in the faeces in low quantities. The influence of orally administered polyene drugs in the intestinal tract may be detected shortly after starting the application. Thus efficient concentrations of nystatin and amphotericin B are continuously present in the faeces 24 to 48 hours after beginning until 2 to 10 days after finishing the administration. During this time the quantity of yeast in the faeces is evidently reduced or not longer detectable by fungal culture. The oral administration of polyene antimycotics for a long time in persons without immunodepression and without heavy intestinal yeast colonization is not justified.

[Lethal meningeal encephalitis from Cryptococcus neoformans var. neoformans in a girl without serious immunodeficiency]. / Tödliche Meningoenzephalitis durch Cryptococcus neoformans var. neoformans bei einem Mädchen ohne schwerwiegende Immundefekte.

Case report on a lethal meningo-encephalitis due to Cryptococcus neoformans in a 14-year-old girl without serious immunodeficiency inclusive HIV-infection. The detection of high quantities of cells of Cryptococcus neoformans (about 10,000/ml) and high levels of Cryptococcus antigen (up to 1:2048) in the cerebrospinal fluid are remarkable. The patient was treated with a triple combination of amphotericin B, flucytosine and fluconazole. After 18 days the cerebrospinal fluid was sterile. Nevertheless considerable lesions of the brain arised. The patient died from the Cryptococcus infection on day 74 of the antimycotic therapy. Cryptococcosis should be included into the differential diagnosis of the chronic lymphocytic pleocytosis of the cerebrospinal fluid connected with symptoms of intracranial pressure and ocular symptoms.

[Amphotericin B level in feces and serum during oral administration in newborns at risk]. / Amphotericin B-Spiegel in Faeces und Serum während oraler Verabreichung bei Risikoneugeborenen.

The aim of this study was to determine the efficacy of orally administered amphotericin B (Ampho B) on the elimination and suppression of yeasts in the orointestinal tract and on the clinical success regarding the Ampho B concentrations in faeces and serum. A total of 23 newborns at risk suffering from oral and/or cutaneous candidosis and massive colonization of yeasts in the orointestinal tract received Ampho-Moronal suspension (Squibb-Heyden, München) for 10 days: newborns < 1500 g 4 x 20 mg Ampho B/d and newborns > 1500 g 4 x 40 mg/d. Ampho B was detected in concentrations between 0.6 and 20 micrograms/g in the faeces of all patients 24 hours after beginning and 2-6 days after the end of the application. During this time Ampho B concentrations between 0.06 and 0.58 microgram/ml were also detected in the serum of the newborns. During the administration of Ampho-Moronal suspension for 10 days the initial available yeasts were eliminated in 18 patients (78%) out of the faeces. In 7 out of 17 patients (41%) the oral and cutaneous candidosis was cured. After finishing the administration of Ampho-Moronal Candida albicans was isolated again from the faeces during the following 5 days in half of the newborns who had reached negative mycological findings during the prophylaxis. For that reason Ampho-Moronal should be prophylactically administered for a longer time during the period of increased risk for systemic mycosis.

[Intestinal excretion of nystatin during and after oral administration to newborn infants at risk]. / Zur intestinalen Ausscheidung von Nystatin während und nach oraler Applikation bei Risikoneugeborenen.

The concentrations of nystatin excreted with faeces during and after oral application of 3 x 150,000 IU/d, either continuously for 14-21 days or every second day were determined in 42 newborns at risk by means of a bioassay (agar diffusion test). Results indicate that nystatin is distributed heterogeneously in the gastrointestinal tract. The excretion occurs discontinuously. 24 to 48 h after beginning of therapy there were effective concentrations of nystatin in the faeces. The daily application of 3 x 150,000 IU nystatin is recommended.