Search PubMed⌕ Search

Biomedical subjects

O Linderkamp

Publications and source records attributed to O Linderkamp.

At least 73 records · Page 4Linked to original sources

Effects of red cell transfusion on pulmonary blood flow and right ventricular systolic time intervals in neonates.

UNLABELLED: Blood transfusion increases blood volume and blood viscosity of the neonate. Since both volume expansion and increase in blood viscosity may be associated with increased pulmonary artery pressure, we studied effects of transfusion (10 ml of red blood cells per kilogramme of body weight) on right ventricular output and right systolic time intervals by means of pulsed-Doppler echocardiography in 38 preterm infants with a mean (SD) gestational age of 28 (5) weeks (range 25-34), birth weight 1060 (395) g (range 480-1910), actual body weight 1875 (450) g (range 820-2790) and postnatal age of 44 (23) days (range 17-105). After transfusion, packed cell volume and haemoglobin increased significantly from 0.26 (0.044) to 0.38 (0.046), and from 8.2 (1.6) g/l to 12.8 (1.9), respectively. Blood viscosity increased from 1.78 (0.3) mPa to 2.68 (0.4) by 33%. Right ventricular output decreased significantly from 320 (57) ml/kg/min to 290 (70) due to decrease in heart rate by 7%. Blood pressure and right ventricular stroke volume did not change. There was a significant increase in pulmonary red cell transport (right ventricular output times packed cell volume) of 21%. Right ventricular pre-ejection period (RPEP), right time peak velocity (RTPV), right ventricular ejection time (RVET), and ratios of RTPV/RVET(c). RPEP:RVET did not change after transfusion. CONCLUSIONS: These results suggest that neither pulmonary artery pressure nor right ventricular function changed as a result of transfusion in spite of rising blood volume and blood viscosity.

Anemia, Neonatal↗

L-selectin activates JNK via src-like tyrosine kinases and the small G-protein Rac.

Selectin and alpha 4 beta 7-integrins have been shown to mediate transient leucocyte interactions with endothelial cells which is a crucial step in the initial immune response to pathogens. We have previously shown that stimulation of T lymphocytes via L-selectin results in activation of a signalling cascade from the L-selectin molecule via the tyrosine kinase p56lck and tyrosine phosphorylation of L-selectin to the stimulation of p21Ras and Rac proteins. In the present study we demonstrate that stimulation of Jurkat T lymphocytes via L-selectin results in an activation of Jun N-terminal kinase (JNK) but not of p38-K. L-selectin-initiated activation of JNK is mediated by src-like tyrosine kinases and the small G-protein Rac 1/2, since genetic or pharmacological inhibition of p56lck or Rac proteins prevent the stimulation of JNK by L-selectin. Thus, the data point to a novel signalling cascade from L-selectin via src-like tyrosine kinases and Rac proteins to JNK.

Blotting, Western↗

Effects of bolus tube feeding on cerebral blood flow velocity in neonates.

AIM: To study continuously cerebral blood flow velocity in the middle cerebral artery before, during, and after tube feeding in neonates. METHOD: Cerebral blood flow velocity was measured in 14 neonates using a Doppler ultrasound device. Blood pressure, respiration, and oxygen saturation were monitored. RESULTS: Mean blood flow velocity decreased from 37 cm/s before feeding to 33 cm/s (P < 0.001) 5 to 11 minutes after feeding. Prefeeding values were reached after 17 minutes. Arterial blood pressure, respiration patterns, and oxygen saturation did not change significantly during the study period. CONCLUSION: Tube feeding in preterm infants may decrease cerebral perfusion, despite unchanged blood pressure and unchanged oxygen saturation.

Blood Flow Velocity↗

Alternative pathway activation of the complement system in preterm infants with early onset infection.

The increased incidence of infection in preterm neonates has been related in part to their relative deficiency of most complement components, because complement is known to participate in the defense against bacterial and viral infections. In a prospective study, complement activation products were determined in 52 preterm infants. Twenty preterm infants suffered from proven early onset infection, 11 infants were presumed to suffer from infection, which could not be confirmed. Twenty-one preterm infants without infection or perinatal asphyxia formed the control group. EDTA plasma was obtained within the first 6 h after birth, and follow-up examinations were done in 15 patients with proven infection during the next 24 h. The complement activation products C3a-desArg, C3bBbP, and sC5b-9 were measured with enzyme immunoassay systems. In preterm neonates with early onset infection, a significant elevation of C3a-desArg was found in the very early course of the disease. C3a-desArg generation resulted from alternative pathway activation as shown by a concurrent increase of C3bBbP concentration. In addition, significantly higher concentrations of sC5b-9 predicted infection in the first few hours after birth. Thus, despite very low levels of native complement proteins, preterm babies are able to generate remarkable amounts of activation products of the complement cascade. The elevation of these activation products preceded by hours significant changes of routine laboratory markers of infection, such as leukocyte count, differential blood count, and C-reactive protein. Thus they might help to identify preterm neonates with severe systemic infection earlier than other laboratory parameters.

Age of Onset↗

L-selectin activates the Ras pathway via the tyrosine kinase p56lck.

Selectins mediate rolling, the initial step of leukocyte adhesion to endothelial cells [Springer, T. A. (1995) Annu. Rev. Physiol. 57, 827-872 and Butcher, E. C. (1991) Cell 67, 1033-1036]. In this study we show that L-selectin triggering of Jurkat cells using different antibodies or glycomimetics resulted in activation of the src-tyrosine kinase p56lck; tyrosine phosphorylation of intracellular proteins, in particular mitogen-activating protein kinase and L-selectin; and association of Grb2/Sos with L-selectin. This association correlated with an activation of p21Ras, mitogen-activating protein kinase, Rac2, and a transient increase of 2-O synthesis. Stimulation of the Ras pathway by L-selectin requires functional p56lck, since p56lck-deficient Jurkat cells (JCaM1.6) do not show tyrosine phosphorylation, association of L-selectin with Grb2/Sos, and activation of Ras upon L-selectin triggering. Transfection of JCaM1.6 cells with p56lck reconstitutes the observed signaling events. Genetic inhibition of Ras or Rac2 prevented Rac2 stimulation and 2-O synthesis, respectively. The specificity and the physiological significance of the observed signaling cascade is indicated by stimulation of L-selectin-transfected P815, L-selectin-positive CEM or peripheral blood lymphocytes resulting in the same activation events as in Jurkat cells. Our results point to a signaling cascade from L-selectin via p56lck, Grb2/Sos, Ras, and Rac2 to 2-O.

Animals↗

Fas-induced apoptosis is mediated by activation of a Ras and Rac protein-regulated signaling pathway.

Fas induces apoptosis in lymphocytes via a poorly defined intracellular signaling mechanism. We and others have previously demonstrated the involvement and significance of a signaling cascade from the Fas receptor via sphingomyelinases and ceramide to Ras in apoptosis (Gulbins, E., Bissonette, R., Mahboubi, A., Nishioka, W., Brunner, T., Baier G., Baier-Bitterlich, G., Byrd, C., Lang, F., Kolesnick, R., Altman, A., and Green, D. (1995) Immunity 2, 341; Cifone, M. G., DeMaria, R., Roncali, P., Rippo, M. R., Azuma, M., Lanier, L. L., Santoni, A., and Testi, R. (1994) J. Exp. Med. 180, 1547-1552; Gill, B. M., Nishikata, H., Chan, G., Delovitch, T. L., and Ochi, A. (1994) Immunol. Rev. 142, 113-126). Here, we demonstrate an activation of the small G-proteins Rac 1 and Rac 2 after Fas receptor triggering. Expression of a transdominant inhibitory Ras mutant (N17Ras) prevents Rac 1 and Rac 2 stimulation, suggesting a signaling cascade from the Fas receptor via Ras to Rac 1 and Rac 2. Genetic and pharmacological inhibition of Ras or Rac 1 and Rac 2 stimulation blocks Fas-induced apoptosis, pointing to an important function of a Ras and Rac protein-regulated signaling pathway in Fas-mediated programmed cell death.

Adaptor Proteins, Signal Transducing↗

Activation of the Ras signaling pathway by the CD40 receptor.

The CD40 receptor is an important molecule regulating B lymphocyte proliferation, maturation, Ab class switching, and cell survival. In the present study, we identified signal transduction events triggered by cross-linking the CD40 receptor. Stimulation of Daudi B cells with anti-CD40 resulted in activation of p21ras, an important switch point in the regulation of cell growth and differentiation. Ras activation correlated with a stimulation of Rac1 and MEK-1 as well as tyrosine phosphorylation of phosphatidylinositol 3-kinase. Inhibition of endogenous Ras by transfection of transdominant inhibitory Ras prevented tyrosine phosphorylation or stimulation of phosphatidylinositol 3-kinase, Rac1, or MEK-1 upon CD40 receptor triggering, proving an activation of the Ras pathway by CD40. Ras activation was partially inhibited by either herbimycin A or calphostin pretreatment and completely inhibited by preincubation with a combination of both inhibitors, indicating a synergistic role for protein tyrosine kinases and diglycerides in Ras activation after CD40 stimulation. In support of a role for diglycerides, we detected a 30 +/- 5% decrease of cellular phosphatidylcholine content, correlating with a threefold increase of diacylglycerol synthesis induced by CD40. Supporting a role for protein tyrosine kinase, we measured a five- to eightfold stimulation of p56lyn and p58blk kinase activity. These results suggest the activation of the Ras pathway via an additive function of src kinases and phospholipases that may be important in the mediation of biologic effects after CD40 receptor engagement.

Antibodies, Monoclonal↗

Metabolic rate and energy balance in very low birth weight infants during kangaroo holding by their mothers and fathers.

The aim of the study was to compare effects of maternal and paternal kangaroo care on oxygen consumption, carbon dioxide production, energy expenditure, skin and rectal temperatures, heart and respiratory rates, arterial saturation, and behavioral states. Eleven preterm infants with gestational age of 28 to 31 weeks, birth weight of 560 to 1390 gm, and postnatal age of 8 to 48 days were studied before, during, and after maternal and paternal kangaroo care. Skin temperature (lower leg) increased significantly during both maternal (36.2 +/- 0.9 degrees vs 36.9 +/- 1.2 degrees C) and paternal (36.3 +/- 0.9 degrees vs 36.8 +/- 0.9 degrees C) kangaroo care. The other parameter changed neither during maternal nor during paternal kangaroo care. We conclude that both maternal and paternal kangaroo care have no adverse effects on energy expenditure.

Body Temperature↗

Severe hyperchloriduria-hyperkaliuria: a new congenital renal tubular abnormality?

A female infant, aged 5 weeks, had metabolic alkalosis associated with severe electrolyte disturbances. In addition to findings typically seen in patients with Bartter syndrome or hyperprostaglandin E syndrome, she had massive urinary excretion of prostaglandins E2 and E-M, normal calcium metabolism, hyperphosphaturia, and severe hyperchloriduria and hyperkaliuria with limited response to indomethacin. These findings may represent a new congenital renal tubular abnormality.

Bartter Syndrome↗

Effects of group-A streptolysin O on neonatal and adult red blood cell deformability and haemolysis.

Neonates are more susceptible than adults to many Gram-positive and Gram-negative bacterial infections. Whereas group B streptococcus causes life-threatening infections in neonates, group A beta-haemolytic streptococcus infections rarely occur in neonates. To test the hypothesis that group A streptococcus may have different effects on neonatal and adult red blood cells (RBCs), haemolysis and deformability (rheoscope) of RBCs from adults, full-term and pre-term neonates were studied during 60 min incubation with 1 haemolytic unit (HU) mL-1 group A streptolysin O (SLO). SLO incubation of adult RBCs resulted in almost linearly increasing time-dependent haemolysis reaching 82%, whereas haemolysis of neonatal RBCs was below 60% after 1 h. After 60 min SLO incubation, RBC deformation was significantly (P < 0.05) more reduced in adults than in full-term and preterm neonates. An inverse overall relationship (r = 0.68) between SLO-induced haemolysis and RBC deformation was found after 60 min of SLO incubation. We conclude that SLO causes less haemolysis and less impairment of RBC deformation in neonates than in adults. The decreased RBC deformation of unhaemolysed RBC indicates that, before lysis, mechanical RBC membrane properties are altered by SLO.

Adult↗

Fas-induced programmed cell death is mediated by a Ras-regulated O2- synthesis.

Fas induces apoptosis in lymphocytes via a poorly defined intracellular signalling cascade. Previously, we have demonstrated the involvement and significance of a signalling cascade from the Fas receptor via sphingomyelinases and ceramide to Ras in Fas-induced apoptosis. Here we demonstrate rapid and transient synthesis of reactive oxygen intermediates (ROI) via activation of Ras after Fas. Genetic inhibition of Ras by transfection of transdominant inhibitory N17Ras blocked Fas-mediated ROI synthesis and programmed cell death. Likewise, the antioxidants N-acetyl-cysteine and N-t-butyl-phenylnitrone abolished Fas-induced cell death, pointing to an important role for Ras-triggered ROI synthesis in Fas-mediated programmed cell death.

Acetylcysteine↗

Group B Streptococcus impairs erythrocyte deformability in neonates more than in adults.

Group B beta-haemolytic Streptococcus (GBS) may cause severe septic shock and death in neonates, whereas this is rarely the case in adults. As impaired red blood cell (RBC) deformability might disturb microcirculation in septic shock, the in vitro effects of GBS (1.7 x 10(8) cfu/ml) on RBC deformation (rheoscope) and haemolysis were studied in blood from preterm infants, term neonates, and adults. Furthermore, RBC deformation was studied in term neonates with GBS sepsis. RBC deformation at a shear stress of 4 Pa decreased significantly within 5 minutes of GBS incubation in preterm infants (-13%) and term neonates (-9%). In adults RBC deformation did not change during the first 15 minutes, but decreased significantly after 30 (-10%) and 60 minutes (-13%). In the term infants there was little further decrease in RBC deformation between 5 and 60 minutes of GBS incubation; RBC deformation in preterm infants decreased by 19% after 60 minutes compared with the preincubation values. RBC deformation in septic neonates was significantly decreased at shear stresses of 1, 2, and 3 Pa (-19%, -18%, and -9%). Sixty minutes of incubation of RBC from adults and neonates with GBS and without GBS resulted in haemolysis below 4%. It is concluded that neither neonatal nor adult RBC are haemolysed by GBS. In vitro, neonatal RBC deformability is more impaired than that in adults. This may contribute to the high risk of neonates for compromised microcirculation and circulatory shock as a result of GBS sepsis.

Adult↗

Effects of Leboyer childbirth on left- and right systolic time intervals in healthy term neonates.

The Leboyer birth method requires that the newborn infant is placed on the mothers abdomen and the cord is clamped when it stops pulsating. Since late cord-clamping may result in marked hypervolemia and polycythemia of the neonate, we studied right and left ventricular systolic time intervals by means of pulsed-Doppler echocardiography. Left and right ventricular preejection periods (LPEP, RPEP), right time peak velocity (RTPV), left and right ventricular ejection times (LVET, RVET), and ratio of RTPV/RVET(c) corrected for heart rate were studied in 15 fullterm neonates with early (< 10s) cord clamping and in 15 fullterm neonates delivered according to Leboyer (cord clamping after 3 min) on day 1 (2-4 h after birth) and day 5. After Leboyer birth hematocrit was significantly increased on day 1 (0.61 +/- 0.06 vs. 0.53 +/- 0.07) and on day 5 (0.57 +/- 0.02 vs. 0.50 +/- 0.07). Blood pressure was similar in both groups and increased by about 10% from day 1 to day 5. LVET and RVET were not affected by the mode of placental transfusion, thereby suggesting normal left and right ventricular function after Leboyer birth. The LPEP/LVET (0.36 +/- 0.09 vs. 0.30 +/- 0.08) and RPEP/RVET ratio (0.41 +/- 0.11 vs. 0.33 +/- 0.08) were significantly higher in the Leboyer group (p < 0.05) compared to the early cord clamped group suggesting higher systemic and pulmonary resistance. RPEP decreased significantly by 17% in the control group from day 1 to day 5 (p < 0.05), but did not change in the Leboyer group. In the Leboyer group RPEP/RVET ratio decreased significantly from day 1 to day 5, whereas the control values did not change during the first five days. RTPV:RVET(c) is inversely related to pulmonary artery pressure. A normal ratio is > 0.35, or greater. Mean ratio of RTPV : RVET(c) was significantly lower in the Leboyer group (0.31 +/- 0.08) on day 1 compared to the control group (0.41 +/- 0.09; p < 0.05), but did not differ on day 5. The results suggest that Leboyer delivery was associated with transiently increased pulmonary and systemic resistance, whereas right and left ventricular functions were not affected. This may be explained by increased blood viscosity due to increased hematocrit.

Constriction↗

[Diode laser coagulation of stage 3+ retinopathy of prematurity].

BACKGROUND: Laser photocoagulation in retinopathy of prematurity (ROP) appears to have fewer adverse effects and to be at least as effective as cryotherapy. METHODS: To evaluate the efficacy and safety of diode laser photocoagulation we examined 50 eyes affected by stage 3+ ROP in 30 very low birth weight infants (gestational age 24-29 weeks, mean +/- SD 26.5 +/- 1.4 weeks; birth weight 480-1400 g, 898 +/- 208 g) in a prospective (uncontrolled) clinical study. Photocoagulation treatment was performed using a diode laser (810 nm) with a laser indirect ophthalmoscope delivery system. Follow-up ranged from 3 to 23 months (10.5 +/- 6.4 months). RESULTS: In 46 (92%) of the 50 eyes ROP regressed after a single laser treatment and the outcome was a flat, attached retina. Two eyes (4%) had a second laser session and one other eye (2%) had additional retinal detachment surgery, resulting in the regression of ROP and a flat, attached retina. Thus, the success rate was 98% (49 out of 50 eyes). In 1 (2%) of the 50 eyes treatment failed and ROP progressed to stage 5, although additional retinal detachment surgery was performed. No adverse side effects of diode laser treatment were noted, except for a small amount of retinal/preretinal bleeding in the ridge in 8 eyes (16%) and slight postoperative anterior chamber bleeding in 1 eye (2%) with dense tunica vasculosa lentis. There were neither lenticular opacities nor cataract formation. CONCLUSION: Diode laser photo coagulation using the laser indirect ophthalmoscope for stage 3+ ROP was easy to administer. Laser treatment had only minor side effects and was at least as effective as cryotherapy.

Female↗

[Rheologic changes in stored erythrocyte concentrates].

We studied the effect of two different preservation solutions on mean corpuscular volume (MCV), red cell deformability and flow in narrow tubes in red blood cell concentrates. Blood from 10 healthy blood donors was processed in parallel in SAG-M (S-RBC) as well as in PAGGS-M (P-RBC) in identical aliquots. Samples were studied at days 0, 7, 14, 28 and 42 of storage. MCV was determined using a Du Pont cell counter. Whole cell deformability was determined in a Myrenne Rheodyn. Viscosity reduction in narrow tubes was determined by means of capillary viscosimetry. P-RBC showed a constant MCV over the entire storage period. In contrast, MCV of S-RBC increased and MCHC decreased during storage. P-RBC showed similar deformability and viscosity reduction during storage, whereas deformability decreased and viscosity reduction became less pronounced for S-RBC. Our study shows superior rheological properties of P-RBC. Thus, PAGGS-M may provide better hemoglobin flux and oxygen transport to tissues than SAG-M.

Blood Preservation↗

Diode laser photocoagulation for stage 3+ retinopathy of prematurity.

BACKGROUND: Laser photocoagulation in retinopathy of prematurity (ROP) appears to have fewer adverse effects than cryotherapy and seems to be at least as effective. METHODS: To evaluate the efficacy and safety of diode laser photocoagulation, we included 42 eyes with stage 3+ ROP of 24 preterm infants (gestational age 24-29 weeks, mean +/- SD 26.6 +/- 1.3 weeks; birth weight 480-1400 g, 896 +/- 196 g) in a prospective clinical study. Photocoagulation treatment was performed using a diode laser (810 nm) with a laser indirect ophthalmoscope delivery system. Follow-up ranged from 3 to 16 months (8.8 +/- 4.0 months). RESULTS: In 39 (93%) of 42 eyes ROP regressed after a single laser treatment and the outcome was a flat, attached retina. One eye (2%) had a second laser session and another eye (2%) had additional retinal detachment surgery, resulting in the regression of ROP and a flat, attached retina. Thus, the success rate was 41 (98%) out of 42 eyes. In one (2%) of the 42 eyes treatment failed and ROP progressed to stage 5, although additional retinal detachment surgery was performed. No adverse side effects of diode laser treatment were noticed except for a small amount of retinal/preretinal bleeding in the ridge in five eyes (12%) and a small postoperative anterior chamber hemorrhage in one eye (2%) with dense tunica vasculosa lentis. Neither lenticular opacities nor cataract formation were encountered. CONCLUSION: Diode laser photocoagulation for stage 3+ ROP showed only minor side effects and was at least as effective as cryotherapy treatment.

Female↗

Diode laser photocoagulation for threshold retinopathy of prematurity in eyes with tunica vasculosa lentis.

PURPOSE: To determine possible side effects of diode laser photocoagulation for threshold retinopathy of prematurity in eyes with tunica vasculosa lentis. METHODS: In a prospective clinical study, threshold retinopathy of prematurity was treated in 14 eyes of seven consecutive preterm infants with tunica vasculosa lentis (birth weight, 480 to 980 g; mean +/- S.D., 777 +/- 175 g; gestational age, 24 to 27 weeks; mean +/- S.D., 25.7 +/- 0.9 weeks) by using the diode laser indirect ophthalmoscope. Main outcome measure was the incidence of adverse treatment effects. Follow-up included anterior segment examination with a hand-held slit lamp and ranged from seven to 17 months (12.6 +/- 3.5 months). RESULTS: The tunica vasculosa lentis did not interfere with photocoagulation in any of the 14 eyes. Laser power ranged from 200 to 400 mW (260 +/- 52 mW). Duration of a single spot was 200 msec. Number of burns ranged from 1,060 to 2,132 (1,556 +/- 315). Retinopathy of prematurity regressed in all eyes, and the outcome was a flat, attached retina. A small amount of postoperative anterior chamber bleeding was noticed in one eye (7% of the eyes, 14% of the patients). There were neither lenticular opacities nor cataract formation. CONCLUSION: Diode laser photocoagulation with the laser indirect ophthalmoscope can be used safely in eyes with tunica vasculosa lentis. At the laser energy levels used in our study, no transient lens opacities or cataract formation occurred. However, the results of this study are limited by a relatively small number of patients and a relatively short follow-up.

Capillaries↗