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Biomedical subjects

P Bergmann

Publications and source records attributed to P Bergmann.

At least 19 recordsLinked to original sources

Anemia in children with cancer is associated with decreased erythropoietic activity and not with inadequate erythropoietin production.

A defect in erythropoietin (EPO) production has been advocated as being the main cause of anemia presented at time of diagnosis or during treatment by adults with solid tumors. On the basis of this defect, anemic cancer patients, both adults and children, have been treated with recombinant human EPO (rHuEPO). To further elucidate the pathophysiology of anemia in children with cancer, we measured serum soluble transferrin receptor (sTfR), a quantitative marker of erythropoiesis, and serum EPO at time of diagnosis and during chemotherapy in children suffering from solid tumor or leukemia. We determined serum EPO in 111 children (55 leukemia, 56 solid tumors) at time of diagnosis. In the last 44 patients (23 leukemia and 21 solid tumors), sTfR levels were also measured. Serum EPO together with sTfR levels were also determined in 60 children receiving chemotherapy (29 leukemia, 31 solid tumors). These results were compared with those obtained from appropriate control groups. In all patients, we found a highly significant correlation between the logarithm of EPO (log[EPO]) and the hemoglobin (Hb) level. In all subsets of patients, sTfR levels were inappropriately low for the degree of anemia. Neither leukemic nor solid tumor groups showed a significant inverse relationship between log(sTfR) and the Hb level as would be expected in anemic patients with appropriate marrow response. Thus, in children with cancer, anemia is associated with a decreased total bone marrow erythropoietic activity which, in contrast to what has been reported in anemic cancer adults, is not related to defective EPO production.

Adolescent

Increased osteoclast-like cells formation in long-term bone marrow cultures from patients with a spinal cord injury.

Patients with a spinal cord section loose a significant amount of bone. After paraplegia, bone loss occurs below the lesional level and is the more dramatic in iliac bones and in the metaphyseal area of long bones. A peak of urinary calcium and hydroxyprolinuria is observed approximately 6 weeks after their lesion. To further understand the mechanisms underlying the bone damage, we used long-term bone marrow cultures to compare osteoclast-like (OCL-like) cell formation above and below the lesional level. Seven paraplegic, one quadriparetic, one quadriplegic patients and five normal subjects were investigated. Six weeks after their spinal cord section, the number of OCL-like cells formed in iliac bone marrow cultures was significantly greater than those formed in sternal bone marrow cultures for all paraplegic patients tested. No significant differences were seen between iliac and sternal bone marrow cultures for the quadriparetic, the quadriplegic patient, or for the five normal subjects. Conditioned media (CM) from iliac marrow of paraplegic patients increased OCL-like cell formation in normal bone marrow cultures. IL-1, TNF-alpha, IL-6, and PGE2 were measured in the CM after 3 weeks of culture. IL-6 was found to be significantly higher in iliac CM compared with sternal CM in six out of seven paraplegic patients. In two patients, addition of an anti-IL-6 monoclonal antibody to the marrow cultures significantly decreased the number of OCL-like cells formed at 3 weeks. We conclude that paraplegia caused by a cord section locally induces an increase in the capacity of progenitors to form OCL-like cells in long-term bone marrow cultures. A locally increased IL-6 production in the marrow below the lesional level could be partly responsible for this observation.

Bone Marrow Cells

Sotalol associated torsades de pointes tachycardia in a 15-month-old child: successful therapy with magnesium aspartate.

Torsades de points (Tdp) is a form of ventricular tachycardia, and its occurrence in childhood is very rare. In adult patients treated with sotalol, Tdp has been reported to the occur with an incidence of 2%-4%. In children who are treated with sotalol, occurrence of Tdp has been reported in only a single case. A 15-month-old girl with Wolff-Parkinson-White syndrome developed recurrent syncopal attacks. She had been treated with sotalol 1.5 mg/kg daily since shortly after birth because of recurrent episodes of paroxysmal supraventricular tachycardia. ECG monitoring exhibited frequent Tdp tachycardia. Serum electrolyte levels were normal. Echocardiographic analysis excluded a structural heart defect and did not show any signs of myocardial infection. Sotalol treatment was stopped and an infusion with lidocaine was started. Despite this therapy the Tdp continued. Magnesium aspartate was then administered, which immediately stopped the Tdp. As no other reason was evident, Tdp in this child has to be judged as a proarrhythmia related to sotalol therapy.

Anti-Arrhythmia Agents

A high-resolution esophageal electrocardiogram for monitoring atrial activity in the hypothermic potassium-arrested heart.

Atrial electrical activities during hypothermic, K(+)-induced cardioplegic arrest correlate with an increased incidence of postoperative supraventricular dysrhythmias in coronary artery bypass graft patients. Surface electrocardiogram (ECG) (S-ECG) may be insufficiently sensitive to detect such activity intraoperatively, and invasive methods are impractical and traumatic. From induction of anesthesia until the end of surgery, esophageal ECG signals were detected with a new bipolar esophageal probe and a new high-resolution preamplifier (frequency range 0.01-2000 Hz). The S-ECG and the esophageal ECG (E-ECG) were evaluated independently in 18 patients. Eight of 18 patients presented during cardioplegic arrest a mean of 483 +/- 119 high-amplitude, biphasic P components (mean amplitude 0.7 +/- 0.1 mV, range 0.35-1.15 mV) per patient (mean 36 +/- 6 [5-59] potentials/min) similar to those coinciding with the surface ECG P-waves during sinus rhythm. Six of these eight patients presented a mean of 29 +/- 11 low atrial activities (mean amplitude 0.14 +/- 0.023 mV; range 0.1-0.25 mV) per patient (mean 8.4 +/- 5.6 [2.3-48] potentials/min) in the E-ECG. In the S-ECG, one patient of these eight presented 26 P waves during cardioplegic arrest simultaneously with activities in the E-ECG. During the first 5 days, seven of eight (88%) patients with atrial activities in the E-ECG versus 3 of 10 (30%) patients without atrial activities developed supraventricular tachyarrhythmias postoperatively (P < 0.05). This new high-resolution E-ECG device detected in a beat-to-beat technique more atrial activity during cardioplegic arrest than a S-ECG and offered the advantages of artifact exclusion and better prediction of postoperative supraventricular dysrhythmias.

Aged

Cyclical pamidronate infusions in postmenopausal osteoporosis.

OBJECTIVES: Until recently, two bisphosphonates, pamidronate (APD) and etidronate were available for clinical purposes. Contrary to etidronate, pamidronate was not extensively studied in osteoporosis. Therefore, we investigated the effect of cyclic intravenous APD treatment in postmenopausal osteoporosis. METHODS: Parameters of bone remodelling and lumbar spine bone mineral density (BMDL) were assessed in 36 postmenopausal women with osteoporosis (BMDL t-score < -2.5). They received five courses of APD. Intervals between courses were defined according to the fasting urinary calcium excretion (UCa/Cr, mg/mg creatinine) which was measured before each APD course and every 2 weeks after the first treatment. The patients were retreated when UCa/Cr had reached baseline levels. Serum biochemical parameters and urinary hydroxyproline (UOHPro/Cr, mg/mg) were measured before each APD. RESULTS: UCa/Cr decreased during 21-28 days after each course but UCa/Cr measured before APD infusion remained unchanged. UOHPro/Cr significantly fell after the third APD (P = 0.02). Serum calcium was however not modified. Parameters of bone remodelling decreased with time: bone-GLA protein (BGP) started to fall after the first APD (P = 0.0001) and continued to decrease until the fourth APD course, alkaline phosphatase (ALP) significantly decreased after the first APD (P = 0.005); intact PTH significantly increased at the fifth APD (P = 0.02). BMDL significantly increased after 1 year treatment: +2.9% of baseline value. CONCLUSIONS: Cyclical pamidronate treatment of postmenopausal osteoprosis appeared to be effective in reducing bone turnover assessed by BGP, ALP and OHPro/Cr. This effect is followed by an increase in vertebral BMD.

Adult

Quantitative ultrasound bone measurements: normal values and comparison with bone mineral density by dual X-ray absorptiometry.

Normative data for qualitative ultrasound (QUS) measurements: speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness were established in 118 healthy women aged 20-86 years and in 42 healthy men aged 22-76 years. The relations between age, weight, height, and QUS were studied. QUS measurements were negatively correlated with age in both sexes. In women, age was accepted as first factor (R2 = 0.39 for SOS, 0.35 for BUA, and 0.45 for stiffness, P < 0.001); weight was accepted as second factor for BUA (R2 = 0.44, P < 0.001). In men, age was the only significant parameter (R2 = 0.41 for SOS, 0.39 for BUA, 0.43 for stiffness, P < 0.001). QUS measurements of the right and left feet were highly correlated unless unilateral foot pathology such as algodystrophy was present. Significant correlations were found between QUS of the calcaneus and dual X-ray absorptiometry (DXA) of the lumbar spine (R = 0.67, P < 0.01 for SOS; R = 0.57, P < 0.02 for BUA; R = 0.65, P < 0.01 for stiffness).

Absorptiometry, Photon

Longitudinal study of the bone mineral content and of soft tissue composition after spinal cord section.

We present the results of a 1 year longitudinal study of bone mineral measurements and soft tissue composition in supra- and infra-lesional areas of 31 patients with a spinal cord injury (level D2-L3). Like others, we observed a rapid decrease of BMC in the paralysed areas, of approximately 4%/month during the first year in areas rich in trabecular bone and of approximately 2%/month in areas containing mainly compact bone. Lean soft tissue mass (muscle mass) decreases dramatically during the first months post injury in the legs, while fat content tends to increase. Though lean mass is better maintained in patients who develop spasticity, the evolution of BMC does not differ significantly between the groups of flaccid and spastic patients. In patients with partial or complete neurological recovery, a deficit in BMC of approximately 10% with regards to the initial value is still observed at 1 year in the lower limbs. The lean mass of the upper limbs increases early after the cord injury, because of intensive rehabilitation. No significant change in BMC was observed in the supra-lesional areas. These data confirm the rapid loss of bone in the paralysed areas of paraplegic patients, which occurs independently of the presence of spontaneous muscle activity or of passive verticalisation. In patients with recovery, BMC does not return to pre-injury values within 1 year. Thus, there would be an interest in preventing bone loss early in the course of the disease.

Absorptiometry, Photon

Glucose, growth hormone, cortisol, and insulin responses to glucagon injection in normal infants, aged 0.5-12 months.

We performed glucagon stimulation tests in 59 normally growing siblings of children who died from sudden infant death syndrome. These investigations were performed to exclude a possible metabolic disorder (found in 4 siblings) as an underlying cause of sudden infant death syndrome. The remaining 55 siblings (32 boys and 23 girls) provide control data for this age range. Testing was performed at 0800 h after a 15-h fast. The median age was 98 days (range, 13-349 days). Plasma glucose and serum cortisol, insulin, and GH were determined before and 30, 60, 90, 120, 150, and 180 min after im injection of 0.1 mg/kg glucagon. No side-effects were observed during the procedure. Asymptomatic hypoglycemia was noted in 11% of the infants at least once between 120-180 min. Basal and peak GH concentrations were greater than 10 micrograms/L in 31% and 80% of the infants, respectively. There was a significant negative correlation between age and basal GH concentration [Spearman's rank correlation coefficient (rs) = -0.37; P < 0.01]. There was a significant correlation between age and glucagon-stimulated cortisol at 120, 150, and 180 min (rs) = 0.41; P < 0.005), but not between age and changes in glucose levels. There was no significant correlation between age and basal cortisol or peak GH concentrations and no difference between boys and girls for any of the variables studied. In conclusion, the glucagon stimulation test is well tolerated in very young subjects. The peak GH response to glucagon injection is independent of age between 0.5-12 months. The age-related increase in the glucagon-stimulated cortisol response despite a similar decrease in glucose suggests the existence of a postnatal maturation in the response of the pituitary-adrenal axis to stress.

Aging

Sex differences in age development of a mouse inbred strain: body composition, adipocyte size and organ weights of liver, heart and muscles.

The mouse inbred strain HLG has only recently been submitted for international registration. It has been widely used in radiological studies. Since these mice tend to become obese, they may be of interest for studies concerning fat metabolism. Therefore, the present ageing study examines the sex-specific development of body weight, body composition, adipocyte size as well as the organ weight of liver, heart and thigh muscles of the inbred strain HLG (54 males/53 virgin females) between day 40 and 360 of life. The body weight development showed a distinct sexual dimorphism, quickly increasing in the case of males but comparatively protracted in females until maturity. Significantly higher values for body and fat-free dry weight as well as body water were found in males of all ages. Body fat and adipocyte diameter were only higher in the 80 and 120 day-old males. Thus, the increase in female body weight resulted largely through a rise in body fat as additionally evidenced by the sex-specific correlation of characteristics. A 2-fold analysis of variance showed sex differences in the relative weights of liver and muscle, but not of the heart. A sex-specific close correlation was observed between body and liver weights in males until day 180. Correlations between body fat and other characteristics were only rarely found. Differences in coefficients of variation largely depended on the characteristics. A higher variability was also found for some characteristics in the youngest groups (40 days). A sex-specific difference was only seen in the case of body fat content for 60 day-old mice (female > male).

Adipocytes

[Sotalol-induced torsade de pointes tachycardia in a 15-month-old infant].

Torsade de pointes (tdp) is a form of ventricular tachycardia whose occurrence in childhood is very rare. In adults treated with sotalol (Sotalex), tdp has been reported to have an incidence of 2-4%. There have been no reports of its occurrence in children treated with sotalol. We report about a 15-month-old girl with Wolff-Parkinson-White syndrome who developed recurrent syncopal attacks. She had been treated with sotalol at 1.5 mg/kg daily since being a newborn because of recurrent episodes of paroxysmal supraventricular tachycardia. Electrocardiogram exhibited frequent tdp tachycardia. Serum electrolyte levels were normal. Echocardiography excluded a structural heart defect and showed no signs of myocardial infection. After sotalol was ceased, infusion with lidocain was started. Despite this therapy the tdp continued. Magnesium aspartate (Magnesiocard) was then administered, and this finally stopped the tdp. As no other cause was evident, tdp in this child must be judged as a proarrhythmia related to sotalol therapy.

Anti-Arrhythmia Agents

Lithium inhibits calcitriol-stimulated formation of multinucleated cells in human long-term marrow cultures.

We observed that lithium (3 mM) blocked the 1,25-dihydroxyvitamin D [1,25-(OH)2D3]-stimulated bone resorption in fetal rat long bones in culture. Because this inhibitory effect was not seen when bone resorption was stimulated by parathyroid hormone or interleukin-1, we reasoned that Li specifically inhibited events involved in the 1,25-(OH)D3-stimulated bone resorption. The increased bone resorption induced by vitamin D in culture is associated with differentiation and/or fusion of osteoclast progenitors. In the present work, we studied the effect of Li on the basal and 1,25-(OH)2D3-stimulated generation of multinucleated osteoclast-like cells (MNC) and MNC containing tartrate-resistant acid phosphatase (TRAP+) in long-term human bone marrow cultures. Total MNC and TRAP+ cells were counted after 3 weeks of culture. In the absence of both lithium and 1,25-(OH)2D3, total MNC and TRAP+ cell numbers were 146 +/- 22 and 110 +/- 18 per well, respectively (mean +/- SEM); in the presence of Li, corresponding figures were 79 +/- 17 and 59 +/- 14. When the generation of MNC and TRAP+ cells was stimulated with 1,25-(OH)2D3, (10(-8) M), total MNC and TRAP+ cells were 521 +/- 66 and 473 +/- 63, respectively, in the absence of Li and 251 +/- 44 and 155 +/- 27 in the presence of Li (p < 0.05). The inhibitory effect of Li was dose dependent and was not observed when the cultures were exposed to parathyroid hormone instead of 1,25-(OH)2D3.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow

Effects of lithium on bone resorption in cultured foetal rat long-bones.

Increased serum calcium has been observed in manic depressive patients treated with lithium (Li), and one of the mechanisms increasing serum calcium could be a sensitizing effect of Li on bone resorption. In a previous study, however, Li has been found slightly to inhibit PTH-stimulated resorption in cultured foetal rat long-bones. In this work, we extended the study of the effects of Li on bone resorption in culture when resorption of foetal rat long-bones was stimulated by factors other than PTH. Li 3 mM had no effect on basal resorption, a slight and inconsistent inhibitory effect on PTH stimulated bone resorption, a moderate and inconstant inhibitory effect on prostaglandin E2 (PGE2) stimulated resorption, and did not significantly affect the enhancement of resorption by interleukin 1 (IL1). The more constant effect of Li was a nearly complete inhibition of the resorption response to 1,25-dihydroxycholecalciferol (1,25(OH)2D3). This study confirms that Li has no stimulatory effect on bone resorption by itself, nor a sensitizing action on the stimulation of resorption by several activators. Conversely, Li has a striking inhibitory effect on bone resorption stimulated by 1,25(OH)2D3.

Animals

Influence of patient's weight on dual-photon absorptiometry and dual-energy X-ray absorptiometry measurements of bone mineral density.

Lumbar spine bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) (Hologic QDR 1000) and by 153Gd dual-photon absorptiometry (DPA) (Novo Lab 22a) in 120 postmenopausal women. Though a high correlation existed between the two techniques, the ratio between DXA and DPA values was not constant. Using DXA we observed a higher dependence of BMD on weight than in the DPA measurements. To investigate the different behaviour of DXA and DPA machines with weight, we analysed the effects of increasing thickness of soft tissue equivalents on the BMD of the Hologic spine phantom and on the BMD equivalent of an aluminium standard tube. Increasing tissue-equivalent thickness caused the phantom BMD measured by DPA to decrease significantly but had not effect on the DXA measurements. The different behaviour of DPA and DXA equipment with regard to the phantoms could account for the differences observed in the relations between BMD and weight in the patients. Using multiple regression we studied the influence of weight and body mass index on the relation between BMD measured by the two techniques. The introduction of either of these variables into the regression resulted in an improvement of the prediction of the DXA values from the DPA values. However, the residual standard error of the estimate was still higher than the combined precision errors of the two methods, so that no simple relation allows a conversion of BMDDPA into BMDDXA. Our results confirm that BMD is positively correlated with weight in postmenopausal women; the influence of weight on BMD is blunted when the Novo Lab 22a DPA machine is used for measuring bone mineral.

Absorptiometry, Photon

Effects of 17 months treatment using recombinant insulin-like growth factor-I in two children with growth hormone insensitivity (Laron) syndrome.

OBJECTIVE: With the availability of recombinant insulin-like growth factor-I (recIGF-I), it was possible to study whether this peptide could promote growth without noticeable side-effects in patients with growth hormone insensitivity syndrome (Laron syndrome). We report data obtained before and during 17 months treatment using recIGF-I, 40 micrograms/kg s.c. twice a day, in two Lebanese siblings. PATIENTS: The boy and the girl showed very short stature (-6.8 and -6.1 SDS), high GH (79 and 147 IU/I), low plasma IGF-I (0.12 and 0.18 U/ml) and undetectable GH-binding protein. Height velocities were 4.3 and 3.8 cm/year before treatment which started at 8.4 and 6.8 years of age, respectively. RESULTS: After 1-8 weeks of therapy, biological evidence of IGF-I effect was obtained from reduction in serum GH and increase in procollagen-I. During the first 6 months of treatment, height velocity increased to 7.8 and 8.4 cm/year without any clinical evidence of side-effects. Between 6 and 12 months, growth response decreased to 6.6 and 6.3 cm/year. Between 12 and 17 months, growth rate returned to pretreatment values. Changes in bone mineral density paralleled growth response and bone maturation increased by 1.5 and 2.0 years during the first 12 months of treatment. Daily assessment of blood sugar showed asymptomatic low values (< 2.8 mM/I) in 11/730 and 22/730 measurements in the boy and the girl, respectively. CONCLUSIONS: Treatment of two patients with growth hormone insensitivity syndrome using 40 micrograms/kg of IGF-I twice a day resulted in increased linear bone growth and bone mineralization as well as increased bone maturation without remarkable adverse events. After 1 year of therapy, growth response could no longer be observed in these two patients.

Bone Density