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Biomedical subjects

C Krüger

Publications and source records attributed to C Krüger.

At least 37 records · Page 2Linked to original sources
PubMed1999

Pharmacokinetic and clinical evaluation of serious infections in premature and newborn infants under therapy with imipenem/cilastatin.

Efficacy and pharmacokinetic parameters of imipenem/cilastatin (I/C) were investigated in a retrospective evaluation in 104 premature and newborn infants. Patients enrolled in this investigation constituted a particularly high risk group with extreme prematurity, perinatal asphyxia and amnion infection as well as various malformations. In 15 of the 104 infants serum concentrations were measured for drug monitoring and determination of optimal total daily dosage. A total daily dose of 50 mg/kg birth weight for premature and newborn infants divided into two doses led to imipenem peak concentrations of 17.7 mg/l +/- 9.2 mg/l (range: 1.95-38.05) and trough levels were 2.35 mg/l +/-1.02 (range 2.34-10.88) in premature infants. Imipenem peak concentrations of 20.6 +/- 10.8 (range 3.94-32.3) and trough levels of 0.43 +/- 0.17 (range 0.16-0.94) were measured in newborns. The half-life of elimination was 3.3 h and 1.86 h, respectively. Six of the 104 treated patients died, five of them of causes unrelated to infection. Seizures occurred in 8.9% of patients during therapy with I/C compared with 5.8% of a large survey of premature and newborn infants in our intensive care unit (ICU). However, the severity of illness of these two groups cannot be compared. I/C can be expected to constitute effective therapy in premature and newborn infants with serious nosocomial infections even after failure of other broad spectrum antibiotics.

Bacteremia↗
PubMed1998

Immunoreactive renin concentrations in healthy children from birth to adolescence.

We establish normative data for immunoreactive renin concentration in serum of healthy children. In a retrospective study, surplus sera of 281 healthy children, aged 0-18 years, were collected from the laboratory. The determinations were performed with a commercially available two-site immunoradiometric assay. Functional sensitivity was 4.0 mU/l, inter-assay and intra-assay variance were 7.0-18.3% and 3.8-7.5%, respectively. In umbilical cord and during the first 4 days of life, renin concentrations (geometric mean) were significantly higher (P < 0.05) than in older infants and children [umbilical cord: 155.2 mU/l; newborn infants (2-4 days of life): 90.9; newborn infants (5-7 days of life): 32.5; 2 weeks-3 months: 40.8; 4 months-1 year: 54.5; 1-3 years: 46.3; 3-5 years: 48.5; 5-7 years: 51.6; 7-11 years: 38.5; 11-15 years: 37.7; 15-18 years: 31.9]. Newborn infants delivered by Caesarian section had significantly lower renin concentrations in umbilical cord than those delivered vaginally (P < 0.02). Considering the methodological advantages and disadvantages of plasma renin activity and renin concentration assays, renin measurement was at least as valuable and accurate as plasma renin activity determination.

Adolescent↗
PubMed1998

[Reconstruction of the frontobasal skull after tumor operations and trauma. Transplant selection and functional outcome].

Defects of the frontoorbital complex subsequent to extensive tumor surgery or severe trauma often result in aesthetic and functional disharmonies. The long-term results of rehabilitation related to different materials and techniques are the subject of this study. From 1974 to 1996 altogether 127 patients with bony defects of the orbit and/or the skull base underwent surgery. All patients' data were documented prospectively from 1984 onwards. The results following reconstruction with autologous calvarian transplants in 52 patients were compared to those of a control group which received iliac bone or PMMA implants. Eighty-one bony defects (64%) resulted from tumor resection; 37 patients (29%) suffered from the effects of trauma. In 67 cases (53%) reconstruction was performed primarily, in 51 cases (40%) secondarily. Free or pedicled soft-tissue transplants were necessary in order to separate the orbit and the neurocranium in 26% of the defects. On the other hand, small, isolated defects of the orbital roof (7%) were left without any reconstructive procedure. Contrary to the iliac bone grafts, the calvarian transplants resisted secondary resorption. Postoperative infections appeared in two cases; loss of transplants was avoided entirely in the group of calvarian reconstructions in contrast to the alloplasts. The selection of a suitable donor site area and rigid fixation with microplates led to excellent esthetic results even in cases with large defects.

Adolescent↗
PubMed1998

Severe pulmonary hypertension in a neonate caused by premature closure of the ductus arteriosus following maternal treatment with diclofenac: a case report.

The administration of non-steroidal antiinflammatory drugs (NSAID) has occasionally been related to fetal and neonatal cardiopulmonary, gastrointestinal, cerebral and renal complications. This report describes a term newborn with severe persistent pulmonary hypertension due to premature closure of the ductus arteriosus following a 5 day maternal treatment with diclofenac two weeks before delivery. Pulmonary hypertension only responded to unusually high doses of inhaled NO. The treatment was necessary for 22 days suggesting structural alteration of pulmonary vasculature. The child recovered, but tricuspid regurgitation persisted, presumably because of irreversible ischemic damage of one papillary muscle. This is the first reported case of persistent pulmonary hypertension of the newborn (PPHN) in association with maternal diclofenac treatment and represents a most severe form of PPHN induced by NSAID.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Dual effect of digitalis glycosides on norepinephrine release from human atrial tissue and bovine adrenal chromaffin cells: differential dependence on [Na+]i and [Ca2+]i.

It was the aim of the present study (1) to characterize the influence of Na+/K(+)-ATPase inhibition by the digitalis glycoside ouabain on both spontaneous and nicotine-evoked norepinephrine release from the human heart; and (2) to further investigate the role of glycoside-induced changes in [Na+]i and [Ca2+]i (determined by microfluorimetry) for catecholamine release. The latter experiments were performed in bovine adrenal medullary chromaffin cells (BCC), an established cell culture model for sympathetic nerves. Ouabain (1-1000 mumol/l) exerted a dual effect on norepinephrine release (determined by HPLC) from incubated human atrial tissue: (I) Ouabain induced a concentration-dependent increase in norepinephrine release, that was calcium-independent and almost completely prevented by blockade of the uptake1-carrier by desipramine (1 mumol/l). The characteristics of this release process are consistent with a non-exocytotic mechanism. (II) In addition, ouabain augmented the nicotine-evoked (1-100 mumol/l) calcium-dependent norepinephrine release, which can be considered to be exocytotic. Na+/K(+)-ATPase inhibition also reduced the threshold concentration of nicotine from 10 to 1 mumol/l and it delayed the rapid tachyphylaxis of its norepinephrine releasing effect in human atrial tissue. In BCC, ouabain increased [Na+]i, [Ca2+]i and [3H]-norepinephrine release in parallel. Under calcium-free conditions, not only the ouabain-induced increase in [Na+]i, but also [3H]-norepinephrine release were enhanced. The ouabain-induced [3H]-norepinephrine release was always closely related to changes in [Na+]i, indicating a key role of [Na+]i for this calcium-independent non-exocytotic norepinephrine release. In addition, pretreatment with ouabain (1 mmol/l) augmented the nicotine-evoked (0.1-10 mumol/l) increments in [Na+]i, [Ca2+]i and [3H]-norepinephrine release. As nicotine-induced norepinephrine release depends on an increase in both [Na+]i and [Ca2+]i, these findings are indicative of an ouabain-mediated facilitation of exocytosis. In conclusion, increasing [Na+]i and [Ca2+]i inhibition of Na+/K(+)-ATPase by ouabain triggers non-exocytotic norepinephrine release, and facilitates nicotine-evoked exocytotic norepinephrine release.

Adrenal Medulla↗
PubMed1997

Baroreflex sensitivity and heart rate variability in conscious rats with myocardial infarction.

The baroreflex sensitivity (BRS) and the heart rate variability (HRV) were studied in conscious rats after myocardial infarction (MI; induced by coronary artery ligation) and after sham operation (SH). BRS was determined by linear regression of R-R interval vs. arterial pressure changes induced by nitroprusside or methoxamine (intravenous bolus). HRV was calculated from 3-min electrocardiogram recordings. Left ventricular end-diastolic pressure and plasma atrial natriuretic peptide were increased after MI; plasma norepinephrine and basal heart rate (HR) remained unchanged. At 3 and 28 days after MI, BRS was reduced as indicated by decreased reflex bradycardia (RB) (MI, 0.66 +/- 0.13 and 0.78 +/- 0.07 ms/mmHg; SH, 1.27 +/- 0.16 and 1.48 +/- 0.14 ms/mmHg, respectively; P < 0.05 MI vs. SH). At 56 days after MI, BRS was normalized. RB was unaffected by atropine 3 and 28 days after MI but reduced in all other groups. The increase of basal HR by atropine 3 and 28 days after MI was less than in all other groups. HRV (SD of mean N-N interval, coefficient of variance, low- and high-frequency power; studied at 28 and 56 days) was similar in all groups. It is concluded that BRS is transiently depressed in rats with left ventricular dysfunction after MI probably due to a reduced reflex vagal activity. Even though basal HR and HRV are unchanged after MI, a temporary attenuation of tonic vagal activity is unmasked after autonomic blockade.

Analysis of Variance↗
PubMed1996

Value of direct measurement of active renin concentrations in congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

UNLABELLED: In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, measurement of plasma renin activity (PRA) has been the method of choice in diagnosing salt loss and in monitoring adequacy of mineralocorticoid replacement therapy. Due to methodological problems in PRA determinations, direct immunoradiometric assays for the measurement of active renin concentration have been developed. We measured PRA and active renin concentrations simultaneously in 39 patients with CAH (30 salt-wasting, 9 simple virilizing) to evaluate the potential role of this new method in the management of this disease. PRA was determined with an enzymatic assay (sample volume: 2 x 1000 microliters plasma), active renin concentration with a direct immunoradiometric assay (sample volume: 2 x 200 microliters plasma or serum). We found a highly significant correlation between active renin and PRA in our patients (P < 0.001), as previously shown in healthy subjects. Active renin was as reliable as PRA to assess the quality of mineralocorticoid replacement. CONCLUSION: In children, active renin determination is preferable to PRA determination because of methodological advantages and a smaller sample volume. It correlates well with PRA and determines the activation of the renin-angiotensin system as precisely as PRA. Active renin determination is useful in the surveillance of mineralocorticoid replacement therapy in CAH.

Adolescent↗
PubMed1996

De novo direct duplication 3 (p25-->pter): a previously undescribed chromosomal aberration.

We report on a case of de novo direct duplication for the distal part of chromosome 3p: 46,XY,dir dup (3) (p25-->pter). At the age of 4 years and 7 months, the boy presented with moderate growth and mental retardation, muscular hypotonia, hypoplasia of the left kidney, a short neck, and a square-shaped face characterized by a broad and flat nasal bridge, slight epicanthus, and full cheeks. So far, only a few cases with such a small distal 3p duplication have been described, and none of them has a de novo direct duplication for this region. In our patient, dysmorphic signs are less impressive, and developmental delay is relatively moderate.

Abnormalities, Multiple↗
PubMed1996

Problems with salivary 17-hydroxyprogesterone determinations using the Salivette device.

After introduction of the Salivette device for saliva sampling, an increase of approximately 50 ng/l was noted normal values of salivary 17-hydroxyprogesterone in our laboratory compared with previous results obtained by collection of saliva by direct spitting. To further investigate this observation systematically, 17-hydroxyprogesterone was measured in saliva of 22 healthy adults after sampling without and with the Salivette and in 15 samples of distilled water rinsed over the cotton wool swab of the Salivette. The measurements were performed with a commercially available [125I]17-hydroxyprogesterone radioimmunoassay. All steps in assay performance were exactly the same. In both series, salivary 17-hydroxyprogesterone concentrations significantly increased by 40 ng/l (p < 0.05) with use of the Salivette. The variance of the differences covered a wide range. Our results confirmed that the use of the Salivette increased salivary 17-hydroxyprogesterone values by approximately 40 ng/l. This bias is unacceptable for the establishment of reference values, as these are in the range of 20-70 ng/l in the morning. Thus, at least with our assay, the use of the Salivette is discouraged. We speculate that the cotton wool swabs contain a material. possibly derived from the biological source of the cotton wool, which cross-reacts with the antibody in the assay or affects binding affinity.

17-alpha-Hydroxyprogesterone↗
PubMed1995

Soluble lipopolysaccharide receptor (CD14) is released via two different mechanisms from human monocytes and CD14 transfectants.

The receptor for lipopolysaccharide LPS (CD14) exists in a membrane-associated (mCD14) and a soluble form (sCD14). Previous studies indicate that monocytes produce sCD14 by limited proteolysis of the membrane-bound receptor. In this study we demonstrate that human monocytes also produce sCD14 by a protease-independent mechanism. To investigate the molecular nature of this second pathway we studied sCD14 formation in the monocytic cell line Mono Mac 6 (MM6) and in CD14 transfectants. Both MM6 and the CD14 transfectants constitutively produce sCD14 by a protease-independent mechanism. Structural analysis of sCD14 produced by the CD14 transfectants reconfirmed the presence of the COOH terminus predicted from the cDNA. Since glycosylphosphatidylinositol anchor attachment is associated with the removal of a hydrophobic C-terminal signal peptide, our finding demonstrates that the transfectants secrete sCD14 which escaped this posttranslational modification. Identical results obtained for sCD14 derived from peritoneal dialysis fluid of a patient with kidney dysfunction show the in vivo relevance of this pathway for sCD14 production.

Amino Acid Sequence↗
PubMed1995

Altered diastolic [Ca2+]i handling in human ventricular myocytes from patients with terminal heart failure.

To investigate whether the slow diastolic decay of [Ca2+]i in myocardium of patients with heart failure is a result of alterations of the Ca2+ adenosine triphosphatase of the sarcoplasmic reticulum of the sarcolemma, [Ca2+]i transients were recorded in voltage-clamped ventricular cells isolated from hearts of patients with terminal heart failure or from undiseased donor hearts. To isolate the [Ca2+]i-reuptake function of the sarcoplasmic reticulum, myocytes were dialyzed via the patch pipette with Na(+)-free solution and incubated in Ca(2+)-free and Na(+)-free solution to inhibit Na+/Ca2+ exchange. After superfusion with Ca(2+)-containing, Na(+)-free medium, the sarcoplasmic reticulum was loaded with Ca2+ through repetitive voltage-clamp pulses to +10 mV. Under these conditions, [Ca2+]i decay was significantly slower in myocytes from patients with heart failure (538 +/- 66 msec) than in controls (305 +/- 16 msec; p < 0.05). After the addition of 10 mmol/L of caffeine, [Ca2+]i levels did not show appreciable decay between two voltage-clamp pulses in diseased and undiseased myocytes. We conclude that diastolic decay of [Ca2+]i in ventricular myocytes from patients with terminal heart failure is partially the result of a decreased rate of Ca2+ reuptake by the sarcoplasmic reticulum. Sarcolemmal Ca2+ adenosine triphosphatase does not contribute significantly to cytoplasmic [Ca2+]i removal during an individual heartbeat.

Calcium↗
PubMed1995

Nicotine-induced exocytotic norepinephrine release in guinea-pig heart, human atrium and bovine adrenal chromaffin cells: modulation by single components of ischaemia.

The influence of single components of myocardial ischaemia, such as anoxia, substrate withdrawal, hyperkalemia and extracellular acidosis, on nicotine-induced norepinephrine (NE) release was investigated in the isolated perfused guinea-pig heart, in incubated human atrial tissue and in cultured bovine adrenal chromaffin cells (BCC). In normoxia, nicotine (1-1000 mumol/l) evoked a concentration-dependent release of NE (determined by high pressure liquid chromatography and electrochemical detection) from guinea-pig heart and human atrium. In contrast to selective anoxia (Po2 < 5 mmHg) or glucose withdrawal, respectively, anoxia in combination with glucose withdrawal (5-40 min) markedly potentiated nicotine-induced NE release both in guinea-pig heart and human atrium. The sensitization of cardiac sympathetic nerve endings to nicotine was characterized by a lower threshold concentration and an approximate two-fold increase of maximum NE release, peaking after 10 min of anoxia and glucose withdrawal. Cyanide intoxication (1 mmol/l) combined with glucose withdrawal resulted in a similar increase of nicotine-induced sympathetic transmitter release both in guinea-pig heart and human atrium. In contrast, the nicotine-induced (10 mumol/l) NE overflow was only slightly potentiated by 10 min of global ischaemia in guinea-pig heart. Both hyperkalemia ([K+] 16 mmol/l) and acidosis (pH 6.8-6.0) distinctly attenuated the stimulatory effect of nicotine in guinea-pig heart and human atrium under normoxic conditions. Consistent with an exocytotic release mechanism, NE release was dependent on the presence of extracellular calcium under all conditions tested. Furthermore, NE overflow from guinea-pig heart was accompanied by a release of the exocytosis marker neuropeptide Y (NPY; determined by radioimmunoassay). In BCC, nicotine (1-10 mumol/l) evoked a release of NE and NPY and a transient rise of [Ca2+]i (determined with fura-2) during normoxia which were both dependent on the presence of extracellular calcium. Both hyperkalemia and acidosis markedly reduced the exocytotic release of sympathetic transmitters and the corresponding [Ca2+]i-transients. These data demonstrate that nicotine-induced cardiac exocytotic NE release is markedly potentiated during short-term anoxia in combination with glucose withdrawal. In contrast, a brief period of ischaemia causes only a slight sensitization of cardiac sympathetic nerve endings to nicotine. This discrepancy may be due to an attentuation of nicotine-evoked NE release by hyperkalemia and by acidosis. The protective effect of these factors against anoxia-induced sensitization to nicotine appears to be related to the inhibition of nicotine-evoked [Ca2+]i-transients.

Adrenal Medulla↗
PubMed1995

PDGF and TGF-beta contribute to the natural course of human IgA glomerulonephritis.

PDGF and TGF-beta are known mediators of mesangial cell proliferation and matrix expansion. The presence of these regulatory factors was examined in 30 renal biopsies from patients with IgA glomerulonephritis (IgA-GN) at the mRNA and protein level. Normal renal tissue served as control. The mRNA expression of PDGF A/B chains, PDGF-beta R and TGF-beta 1 was evaluated by means of RT/PCR with subsequent Southern blot hybridization and/or non-radioactive in situ hybridization. In addition, PDGF-AB/BB, PDGF-beta R, TGF-beta isoforms (beta 1, beta 1 + 2, beta 2 + 3), the small TGF-beta 1 latency associated peptide (TGF-beta 1 LAP) and the extracellular matrix proteins tenascin and decorin were analyzed by immunocytochemistry. The expression of growth factors was correlated with light microscopic and clinical features. Compared to normal control kidneys, an increased expression of PDGF-BB/PDGF-beta R mRNAs and the corresponding proteins was observed in all biopsies with IgA-GN. Up-regulation was related to the degree of glomerular proliferation and the extent of fibrosing interstitial lesions. In contrast, there was a discordance between TGF-beta 1 mRNA and protein expression (evaluated by immunocytochemistry). In all biopsies, irrespective of the stage of the disease, abundant TGF-beta 1 transcripts were detected, whereas TGF-beta 1 immunoreactivity was expressed to a lesser degree and disclosed a more variable staining pattern. In patients with significant proliferative glomerular lesions and minor tubulointerstitial alterations, TGF-beta 1 positivity was confined to areas of glomerular proliferation, whereas in cases with more severe histology including sclerosing lesions TGF-beta 1 immunoreactivity was less prominent. The distribution and the intensity of TGF-beta 1 LAP staining commonly exceeded the positivity noted for TGF-beta 1, indicating only limited TGF-beta 1 activation. A decreased reactivity for tenascin accompanied the morphological features of glomerular sclerosis. The staining patterns and the fact that only very few inflammatory cells, particularly CD68 positive monocytes/macrophages, were detected in glomeruli confirm that predominantly resident glomerular cells (mesangial and endothelial cells) are the major source of up-regulated growth factor production in IgA-GN. Since the expression of PDGF-AB/BB paralleled the severity of proliferative glomerular changes, PDGF seems to represent a potential indicator of activity in this condition. It is suggested that an imbalance between PDGF and TGF-beta (by restricted translation and/or activation) production contribute to the progressive nature of IgA-GN.

Adult↗
PubMed1995

Binding of lipopolysaccharide (LPS) to an 80-kilodalton membrane protein of human cells is mediated by soluble CD14 and LPS-binding protein.

Activation of cells by bacterial lipopolysaccharide (LPS) plays a key role in the pathogenesis of gram-negative septic shock. The 55-kDa glycoprotein CD14 is known to bind LPS and initiate cell activation. However, there must be additional LPS receptors because CD14 is linked by a glycosylphosphatidyl inositol anchor to the cell membrane and therefore unable to perform transmembrane signalling. Searching for potential LPS receptors, we investigated the binding of LPS to membrane proteins of the human monocytic cell line Mono-Mac-6. Membrane proteins were electrophoretically separated under reducing conditions, transferred to nitrocellulose, and exposed to LPS, which was visualized with anti-LPS antibody. Smooth- and rough-type LPS, as well as free lipid A, bound to a variety of proteins in the absence of serum. However, in the presence of serum, additional or preferential binding to a protein of approximately 80-kDa was observed. Experiments with differently acylated lipid A structures showed that the synthetic tetraacyl compound 406 was still able to bind, whereas no binding was detected with the bisacyl compound 606. The 80-kDa membrane protein was also detected on human peripheral blood monocytes and endothelial cells. The serum factors mediating the binding of lipid A to the 80-kDa membrane protein were identified as soluble CD14 and LPS-binding protein. From these results, we conclude that this 80-kDa protein is a candidate for the hypothetical molecule for LPS and/or LPS-CD14 recognition and signal transduction.

Acute-Phase Proteins↗
PubMed1995

Role of [Na+]i and [Ca2+]i in nicotine-induced norepinephrine release from bovine adrenal chromaffin cells.

Intracellular free sodium ([Na+]i) and calcium ([Ca2+]i) concentrations were determined by sodium-binding benzofuran isophthalate (SBFI) and fura 2 microfluorimetry, respectively, in bovine adrenal chromaffin cells (BCC). Validation of SBFI microfluorimetry by in vitro and in vivo calibration revealed a reliable assessment of [Na+]i within a range of 1-30 mM in single BCC. Nicotine (0.1-10 microM) induced concentration-dependent increases of both [Na+]i (from 3.3 +/- 0.1 to 25.6 +/- 0.4 mM, n = 76, P < 0.001) and [Ca2+]i (from 64 +/- 1 to 467 +/- 16 nM, n = 87, P < 0.001), which were accompanied by an increase in [3H]norepinephrine (NE) release. Consistent with an exocytotic release mechanism, nicotine-induced increments of [Ca2+]i and [3H]NE release were reduced under calcium-free conditions and by gadolinium chloride (40 microM), whereas [Na+]i was not affected. In contrast, a parallel attenuation of nicotine-evoked changes in [Na+]i, [Ca2+]i, and [3H]NE release was observed during reduction of the extracellular sodium concentration. The nicotine-evoked responses were neutralized by the nicotinic receptor antagonist hexamethonium (100 microM) but not by blockade of voltage-dependent sodium channels (1 microM tetrodotoxin). In conclusion, the nicotine-induced exocytotic release of [3H]NE is triggered by an increase in [Ca2+]i, which is facilitated by sodium influx through the nicotinic receptor ionophore.

Adrenal Glands↗