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Biomedical subjects

M Weninger

Publications and source records attributed to M Weninger.

At least 19 recordsLinked to original sources

L-arginine reduces glomerular basement membrane collagen N epsilon-carboxymethyllysine in the diabetic db/db mouse.

The present study was carried out to examine the effect of L-arginine on advanced stage nonenzymatic glycosylation end products in glomerular basement membrane (GBM) as represented by carboxymethyllysine (CML). Twelve db/db mice were given a solution containing a daily dosage of L-arginine of 50 mg/kg body weight orally. Twelve db/db mice served as controls. At the end of the 4-months study period treated animals had significantly lower concentrations of CML (0.084 +/- 0.008, 0.071-0.098 nmol/mumol OH-proline; mean +/- SD, range, p less than 0.01) compared to untreated controls (0.11 +/- 0.018, 0.095-0.152 nmol/mumol OH-proline). In addition, there was a significant positive correlation between GBM thickness and concentrations of CML (r = 0.86, p less than 0.001). We conclude that reduction of CML concentrations in treated db/db mice possibly reflects a beneficial effect of L-arginine on advanced stage nonenzymatic glycosylation end-products in GBM. In addition, measuring CML concentrations might have future clinical implications as a noninvasive parameter for basement membrane thickening.

Administration, Oral

External ventricular drainage for treatment of rapidly progressive posthemorrhagic hydrocephalus.

Twenty-seven newborn infants (birth weight, 1503 +/- 776 g; gestational age, 31 +/- 3 wk) (mean +/- standard deviation) with rapidly progressive posthemorrhagic hydrocephalus and increased intracranial pressure were treated by external ventricular drainage. The progression of hydrocephalus was arrested during the drainage period in each patient. The drainage was kept in place for 23 +/- 9 days, the longest drainage period being 48 days. In 16 of 23 surviving patients, progressive ventricular dilation recurred after removal of the drainage, requiring a definitive shunt implantation (nine ventriculoatrial, seven ventriculoperitoneal). For the remaining seven infants, no further therapy was necessary. Implantation of the permanent shunt was done days 28 to 88 (body weight, 2400 +/- 950 g). Bacterial cultures from cerebrospinal fluid and/or the tip of the ventriculostomy catheter were negative in 175 instances and positive in 11 instances (7 patients). No clinical or biochemical evidence of ventriculitis was noted. Four of the 27 patients died of causes unrelated to external ventricular drainage. Twenty-three infants survived. Seventeen of 23 survivors suffered from intraventricular hemorrhage Grade 3; in 7, neurological and developmental outcomes were classified as normal; 9 patients experienced mild to moderate paresis and/or mild to moderate developmental delay; and only 1 patient was severely retarded. Six patients with parenchymal lesions had severe motor and/or developmental handicaps. We consider external ventricular drainage an effective and safe therapy in newborn infants with rapidly progressive posthemorrhagic hydrocephalus and increased intracranial pressure. The ultimate outcome, however, depends mainly on the mode and the extent of the primary brain lesion.

Brain Damage, Chronic

[Collodion baby with transition to mild lamellar ichthyosis.Clinical course, histopathology and ultrastructural findings].

The case of a collodion baby in whom the condition evolved into a mild form of lamellar ichthyosis is presented. The clinical course was impressive: the hard, collodion-like horny membrane started to crack soon after the birth and had detached completely at the 9th day of life; after a few more days, almost complete clearing of the skin had occurred. At the age of 10 months, the child had only a very mild lamellar ichthyosis. Whereas light microscopy revealed only compact hyperkeratosis on the 1st day of life, electron microscopy suggested a favourable prognosis even at this early stage, which has been corroborated by the ensuing clinical course.

Dermatologic Agents

Heat flux from the head surface in healthy newborns and in newborns with cerebral pathology.

Scalp heat flux of fetuses during labor was shown to be related to metabolic and circulatory factors. We therefore investigated whether heat flux from the head of newborns was also related to cerebral pathology. Heat flux from the head was measured in three groups: Group A consisted of 7 newborn infants with micro- and/or hydrocephalus and with cerebral asphyxia, who were considered to have decreased heat flux from the head due to decreased heat production. Group B consisted of 3 newborn infants with hypoplastic left heart syndrome, who were considered to have increased heat flux from the head due to low cerebral blood flow and, thus, decreased heat convection from the brain. Group C consisted of 17 randomly selected healthy neonates, who served as controls. Heat flux from the head was measured by heat flux transducers attached to the skin of the forehead. The effective operative temperature in the incubator was measured with thermistors. The heat flux from the head of neonates with micro-and/or hydrocephalus and of neonates with cerebral asphyxia was distinctly below, the heat flux from the head of the neonates with hypoplastic left heart syndrome were above two standard deviations of the mean of the heat flux of healthy neonates. The results suggest that heat flux from the head is related to the metabolic or circulatory condition of the underlying brain.

Asphyxia Neonatorum

Pharmacokinetics of intra-arterial indomethacin treatment for patent ductus arteriosus.

We present pharmacokinetic data of prolonged, intra-arterial indomethacin treatment (i.e. induction plus maintenance dose) for symptomatic patent ductus arteriosus (sPDA) in 26 ventilated premature infants. sPDA was assessed by two-dimensional and pulsed Doppler echocardiography. Permanent ductal closure occurred in 20 (76%) infants. Plasma levels of indomethacin were 1.18 +/- 0.74; 1.8 +/- 1.0; 1.51 +/- 0.93 and 1.25 +/- 0.98 micrograms/ml (mean +/- SD) at 12, 24, 48 and 72 h after initial dose administration. All except one patient who responded with ductal closure, showed plasma levels above 0.25 microgram/ml throughout the 3 day treatment period and no case of sPDA reopening was noted. Although target concentrations over time were not defined, the data indicate that the maintenance levels measured were within the therapeutic range. A negative correlation was found for plasma drug levels and postnatal age (r = 0.52; P less than 0.01). Volume of drug distribution was 0.23 +/- 0.18 l/kg, total clearance 0.1 +/- 0.11 ml/min and elimination constant 0.06 +/- 0.05 h-1 (mean +/- SD). The great variation in pharmacokinetic data reflects the heterogeneity of the population studied with respect to extracellular fluid space, cardiovascular status, serum protein and other parameters.

Ductus Arteriosus, Patent

Cerebral blood flow in newborn infants with and without mechanical ventilation.

The influence of mechanical ventilation with low mean airway pressure (MAP) on cerebral blood flow (CBF) veolocity in newborn infants was assessed in fifteen ventilated infants by Duplex Doppler Sonography (Duplex DS). As a control, CBF velocities were examined in 15 age and weight matched non-ventilated infants. For quantitation, maximal systolic velocity, enddiastolic velocity and the semiquantitative Pourcelot index were determined as representative flow variables. There was no significant difference of these flow variables between ventilated and non-ventilated infants. The pH, pO2 and pCO2 did not differ significantly between the two groups and there was no correlation between the flow variables, pH, pO2, pCO2 or MAP. Mechanical ventilation with low MAP is not associated with adverse effects on cerebral hemodynamics in newborn infants when significant alterations of the blood gases are avoided.

Cerebral Arteries

Biochemical and morphological effects of human hepatic alkaline phosphatase in a neonate with hypophosphatasia.

Enzyme replacement-therapy for a severely affected premature boy (birthweight: 2,380 g, GA: 36 weeks) with hypophosphatasia was attempted by infusions of purified human hepatic alkaline phosphatase. Treatment (1.2 IU/kg/min) started at age three weeks and was repeated in weekly intervals until age 10 weeks, when the child died. Samples of alkaline phosphatase were diluted with 10 ml of physiological saline and infused over 30 min via an umbilical arterial catheter. No toxic or allergic side effects were observed. Serum alkaline phosphatase activity increased from 3 IU/L before treatment to a maximum level of 195 IU/L with a half-life time between 37 and 62 hours. Urinary excretion of phosphoethanolamine decreased during therapy from a maximal level of 9.5 to 5.5 mumol/mg creatinine (normal: less than 0.4 mumol/mg creatinine). Calcium, phosphorus, parathormone and 1,25-diOH vitamin D levels were within normal range. Sequential radiographic studies showed no improvement of bone mineralization. Bone morphology was studied by light and electron microscopy before treatment and post mortem. The borderline between mineralized and unmineralized matrix was more distinct after treatment and on the electron microscopical level initial spots of mineralization were more frequent between the collagen fibrils compared to the biopsy specimen before treatment. In contrast to previous studies however, only woven and bundle bone structures were studied from the tibial crest, where the lack of osteoblast-like cells upon the newly formed osteoid matrix was prominent.

Alkaline Phosphatase

[Discrimination between epileptic and non-epileptic seizures using defined prolactin studies].

Prolactin blood levels (HPRL) increase within 20 minutes postictally after generalized epileptic, especially generalized tonic-clonic seizures and return to normal values within one hour. Elevated HPRL levels were also observed after complex partial seizures, but usually in less extent, exceeding normal ranges only slightly. Therefore baselin HPRL measurements are necessary for estimation of spontaneous fluctuations in comparison to changes after seizures. Unchanged PRL levels after attacks do not support their epileptic origin. Rage attacke showed no clear pattern of PRL changes.

Adolescent

[External ventricle drainage in newborn infants with rapidly growing posthemorrhagic hydrocephalus].

14 newborn infants (birth weight: 1830 +/- 930 gms, gestational age 33 +/- 4 wks) (mean +/- SD) with rapidly progressive posthaemorrhagic hydrocephalus and increased intracranial pressure were treated by means of external ventricular drainage. Progression of hydrocephalus was arrested during the drainage period in each patient. The drainage was kept in place for 20 +/- 12 days, the longest drainage period being 48 days. 8 of 10 surviving patients showed recurrence of progressive ventricular dilatation, 5 required a ventriculoatrial and 3 a ventriculoperitoneal shunt. The other 2 infants required no further therapy. Implantation of a permanent shunt was performed at day 28 to 88 after delivery, at the time of implantation the weight of the infants was 2400 +/- 950 gms (lowest weight 1650 gms). Bacterial cultures of ventricular liquor were negative in 66 and positive in 7 instances. Clinical and biochemical evidence of ventriculitis was absent in all patients. 4 of the 14 patients died of causes unrelated to external ventricular drainage. 10 infants survived. 7 out of 10 survivors suffered from IVH 3; 6 subsequently showed normal neurological development and one was retarded. 3 patients with parenchymal lesions (2 patients: IVH 4, 1 patient: primarily intraparenchymal haemorrhage) had neurological handicaps. We consider external ventricular drainage to be an effective form of therapy in newborn infants with rapidly progressive posthaemorrhagic hydrocephalus and increased intracranial pressure because this treatment achieves prompt and sustained decrease in intraventricular pressure without complications.

Cerebral Hemorrhage

[Prognostic significance of the onset of infection in newborn infants].

Between September 86 and May 87 we reviewed the case histories of 25 newborns (gestational age: 33-41 weeks, birth weight: 1280-3600 g) with septicaemia proved by positive blood cultures. Two groups are formed: Group A: onset of sepsis within the first 48 hours of life (10 newborns), group B: onset of sepsis after 48 hours of life (15 newborns). No differences in gestational age and birth weight were found between the groups. Amnionitis was found in 8 mothers (80%) of group A, however, we found only 2 (13%) mothers with amnionitis in group B. All patients in group A had signs of the respiratory distress syndrome and their clinical condition was poor. Only the CRP was helpful in the laboratory diagnosis of septicaemia. In group B sepsis was diagnosed in 11 (73%) patients by means of a raised CRP and an increased immature neutrophil count. Only 4 patients of this group showed clinical deterioration. The following bacteria were cultured: Group A: E. coli 4, b-streptococci 3, Klebsiella 3. Group B: Staph, aureus 8, Strept. faecalis 5, Pseudomonas 2. In group A 3 patients died and 3 patients developed meningitis with neurological sequelae. In group B non of the patients died, but 2 patients developed osteomyelitis.

Bacteria

The determination of urinary 3-trans-hydroxyproline (3 OHP). II. Normal values in neonates, infants and preschool children.

3-trans-hydroxyproline is a hydroxyproline isomer present in collagens. It is more abundant in basement membrane collagen (collagen type IV) where it can be found in a relation of 12 per 1000 amino acid residues. This implicates its probable use as a marker substance for collagen type IV metabolism. Up to now only hydrolyzed urine samples were examined for the presence of this amino acid, thus indicating total urinary excretion. We are reporting the free urinary 3 OHP content of neonates, infants and preschool children. Neonates (n = 23) showed mean excretion of 0.363 micrograms/mg creatinine (SD +/- 0.127), SEM 0.026, min. 0.197, max. 0.598. Infants (n = 11) showed mean excretion of 1.501 micrograms/mg creatinine (SD +/- 0.468), SEM 0.141, min. 0.908, max. 2.553. Preschool children (n = 16) had a mean excretion of 1.442 micrograms/mg creatinine (SD +/- 0.637), SEM 0.159, min. 0.318, max. 2.342. As determined by statistical calculations, neonates differed from infants and preschool children significantly (p less than 0.0005). Infants did not differ from preschool children, however (p less than 0.4). The reason for the low urinary excretion of 3 OHP in the neonatal period could be explained by the low enzyme activities which are physiologically observed in this developmental period in general and in the special case of a presumably low activity of the 3-prolyl-hydroxylase. Infants and preschool children presented levels 5 times higher than their neonatal mates, probably reflecting the increased 3-prolyl-hydroxylase activity which in turn is a marker of collagen synthesis.

Child Development