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Biomedical subjects

J Kreuder

Publications and source records attributed to J Kreuder.

30 records · Page 2Linked to original sources

Clinical and immunological aspects of hepatitis B virus infection in children receiving multidrug cancer chemotherapy.

For two reasons hepatitis B virus infection is an important problem in patients with cancer. First, multidrug cancer chemotherapy may reactivate or worsen a previously benign chronic HBV infection. Second, patients undergoing cancer chemotherapy are at an increased risk of acquiring and spreading HBV which may result in an endemic infection. HBV reactivation may precipitate into a severe acute disease including fulminant hepatitis. In contrast, the acquisition of HBV during cancer chemotherapy commonly takes a mild clinical course but frequently leads to persistently high viremia. This state of immunotolerance to viral antigens allows viral replication without any sign of liver cell destruction. Withdrawal of chemotherapy does not cause significant changes if infection occurred during cytotoxic chemotherapy. Infection with HBV during cancer chemotherapy, therefore, may be considered as a model of an induced antigen-specific immunotolerance. In agreement with this hypothesis, vaccination against HBV during cancer chemotherapy does not prevent spread of HBV in oncology wards as it does not produce significant anti-HBs titers. Furthermore, vaccination even suppresses the immune response to later booster doses after chemotherapy has been withdrawn.

Antineoplastic Agents↗

Clinical and biochemical consequences of copper-histidine therapy in Menkes disease.

Menkes disease (MD) is an X-linked recessively inherited neurodegenerative disorder of copper (Cu) metabolism leading to death in early childhood. Symptoms are attributed to deficient activity of Cu-dependent enzymes. Limited experience has been reported concerning clinical and biochemical consequences of parenteral treatment with copper-(histidine)2-complex (Cu-His) in MD. Cu-His was administered in a 13-week-old boy with MD by daily intramuscular injections. After 6 weeks of therapy, Cu and caeruloplasmin in serum and Cu in CSF were normalized. The excessive dopamine level in CSF was corrected after 3 months of treatment. After 6 weeks of Cu supplementation, complete reduction of epileptic discharges, improved muscular tone and increased motor activities were observed. Developmental regression stopped and was replaced by a slight progression. Death at the age of 19 months was caused by septicaemia due to a fulminant urinary tract infection; there was no evidence of chronic Cu toxicity. These findings suggest that Cu-His supplementation may be a promising palliative treatment in MD.

Bone and Bones↗

Quantification of leukaemic cells based on heteroduplex formation of tal-1 gene sequences after PCR coamplification.

Based on the high sensitivity of the polymerase chain reaction (PCR) several assays have already been described which can be applied to monitor minimal residual disease in patients with leukaemia. However, most of these approaches are only qualitative or semiquantitative at best. Moreover, the semiquantitative assays require rather large-scale procedures such as oligonucleotide hybridization or sampling of aliquots during the exponential phase of PCR amplification, which is time consuming and may be error prone. Using the deletion in the tal-1 gene as a clonal marker of malignant cells, which can be found in about 10-25% of T-cell acute lymphoblastic leukaemia, we have developed a rapid and simple PCR assay for the quantification of residual leukaemic cells. The assay is based on heteroduplex formation between standard and template DNA sequences after coamplification of both DNA sequences in the same PCR reaction. The sensitivity of this PCR approach allows the detection of neoplastic cells at frequency of at least 10(-4). Application of such an assay needs not to be restricted to patients harbouring a tal-1 gene deletion. It may easily be adapted to other clonal DNA markers of blast cells and therefore facilitate monitoring of minimal residual disease in many different kinds of leukaemia.

Base Sequence↗

Mapping of the Menkes locus to Xq13.3 distal to the X-inactivation center by an intrachromosomal insertion of the segment Xq13.3-q21.2.

During a systematic chromosomal survey of 167 unrelated boys with the X-linked recessive Menkes disease (MIM 309400), a unique rearrangement of the X chromosome was detected, involving an insertion of the long arm segment Xq13.3-q21.2 into the short arm at band Xp11.4, giving the karyotype 46,XY,ins(X) (p11.4q13.3q21.2). The same rearranged X chromosome was present de novo in the subject's phenotypically normal mother, where it was preferentially inactivated. The restriction fragment length polymorphism and methylation patterns at DXS255 indicated that the rearrangement originated from the maternal grandfather. Together with a previously described X;autosomal translocation in a female Menkes patient, the present finding supports the localization of the Menkes locus (MNK) to Xq13, with a suggested fine mapping to sub-band Xq13.3. This localization is compatible with linkage data in both man and mouse. The chromosomal bend associated with the X-inactivation center (XIC) was present on the proximal long arm of the rearranged X chromosome, in line with a location of XIC proximal to MNK. Combined data suggest the following order: Xcen-XIST(XIC), DXS128-DXS171, DXS56-MNK-PGK1-Xqter.

Adult↗

[Efficacy and side effects of differential calcium and phosphate administration in prevention of osteopenia in premature infants].

The prevention of osteopenia and frequency of renal and intestinal side effects of mineral supplementation was studied in 24 preterm infants with birth weight under 1,500 g, prospectively (gestational age 26-34 weeks). Calcium intake varied from 2.5 vs. 3.75 vs. 5 mmol/kg/day, phosphate was offered in dose of 2.5 mmol/kg/day. At the expected birth date 40% of infants with low calcium dose showed an activity of serum alkaline phosphatase greater than five times the maximum adult normal value which is defined as a reliable marker; for osteopenia no infant with medium or high calcium intake reached this critical value (p = 0.03). Medium and high calcium doses resulted in an increased risk for hypercalcuria (25 vs. 50%) (p = 0.03). Half of these infants developed typical signs of nephrocalcinosis on ultrasound examination. No significant difference of fecal fat content was observed with increased calcium intake; but more episodes of abdominal distension occurred during the first days of high calcium supplementation (p = 0.03). We conclude, that a calcium intake of 3.75 mmol/kg/day in combination with phosphate 2.5 mmol/kg/day is sufficient for adequate bone mineralization on a low level of side effects. Calcium excretion in urine has to be observed for early diagnosis of nephrocalcinosis.

Alkaline Phosphatase↗

Di-(2-ethylhexyl)-phthalate as plasticizer in PVC respiratory tubing systems: indications of hazardous effects on pulmonary function in mechanically ventilated, preterm infants.

Several PVC medical devices contain the plasticizer Di-(2-ethylhexyl)-phthalate (DEHP) in high concentration. Taken systematically DEHP only has minor toxic effects in the human organism. In three preterm infants artificially ventilated with PVC respiratory tubes unusual lung disorders resembling those observed in hyaline membrane disease, verified both clinically and radiologically, were observed during the fourth week of life. It was assumed that these lung disorders were causally related to the exposure to high doses of DEHP, which was released from the walls of the respiratory tubes. DEHP was found in the lung tissue of one patient who died of pneumothorax soon after birth after being artificially ventilated. It is strongly recommended that for disposable PVC respiratory devices the plasticizer DEHP should be used with more restrictions.

Diethylhexyl Phthalate↗

[The effect of oxedrine on the left ventricle and peripheral vascular resistance].

The sympathomimetic substance oxedrine (Sympatol) influences, by means of its affinity to alpha- and beta-receptors, cardiac performance and peripheral vascular tone. We studied in 12 healthy male volunteers the influence of intravenous oxedrine on left ventricular contractility parameters as estimated by TM-echocardiography, on cardiac index as well as on arterial blood pressure and peripheral vascular resistance. Under continuous intravenous infusion of 4 mg/min oxedrine the systolic and mean arterial blood pressure increased significantly (p less than 0.005) while the diastolic pressure and heart rate remained unchanged. The cardiac index increased (p less than 0.001) and the peripheral vascular resistance decreased significantly (p less than 0.01). The echocardiographically determined left ventricular contractility parameters, i.e. systolic shortening fraction (SF) as well as maximal velocity of shortening of the left ventricular diameter (VCFmin) also increased significantly (p less than 0.001 and 0.005, resp.). An increase in left ventricular contractility and cardiac index with concomitant decrease of peripheral vascular resistance and without increase in heart rate implies an economical increase in cardiac performance under intravenous infusion of oxedrine.

Adult↗

[Cutaneous lesions and blood count changes in a 9-month old girl with glutaric aciduria type I].

Non-specific cutaneous lesions are common in patients suffering from acute myeloid leukemia (AML). Leukemic skin infiltrates are present in about 30% of cases of monoblastic or myelomonocytic leukemia. The appearance of specific skin lesions can precede bone marrow involvement. We report the case of a 9-month-old girl with acute myelogenous leukemia (FAB M5) and glutaric aciduria type I which initially presented with cutaneous lesions, anemia and leukopenia.

Amino Acid Metabolism, Inborn Errors↗

Influence of gestational age and intrauterine growth on leptin concentrations in venous cord blood of human newborns.

BACKGROUND: The ob gene product leptin is involved in the regulation of body weight and energy expenditure, suggesting a potential role of leptin in embryonal and fetal development and progression of pregnancy. In term infants, leptin concentrations showed a positive correlation with birth weight. We aimed at comparing leptin cord blood levels in AGA (appropriate for gestational age) to SGA (small for gestational age) preterm and term newborns. PATIENTS AND METHODS: Ninety-seven human newborns, 47 females and 50 males, 33 born at term and 64 born before 36 weeks of gestation, were studied prospectively. Leptin concentrations in venous cord blood were determined using a specific RIA (radioimmunoassay). RESULTS: In term newborns, mean gestational age (GA) was 39 weeks (wk) (+/- 0.7 wk) and mean birth weight (BW) was 3316 g (+/- 473 g); in preterm newborns (n = 64), mean GA was 30 wk (+/- 5.0 wk) and mean BW was 1398 g (+/- 505 g). Mean standard deviation score of birth weight (BW SDS) was calculated as - 0.47. Mean leptin concentrations in term newborns differed significantly from those in preterm newborns (9.21 +/- 2.63 ng/ml vs. 1.58 +/- 0.88 ng/ml; p < 0.0001). In preterm and term infants, leptin concentrations showed a linear correlation with BW (r = 0.46; p < 0.0001) and GA (r = 0.48; p < 0.0001), respectively. Leptin levels were best predicted by an exponential regression model with GA (Leptin = exp(- 4.41 + 0.14 x GA); r = 0.61; p < 0.0001). Using multivariate regression analysis (r = 0.57; p < 0.0001), we found significant influences of GA (p < 0.00001) and BW SDS (p < 0.05) on leptin levels. No difference was observed between leptin values in AGA versus SGA preterm infants. CONCLUSION: These data suggest fetal leptin levels to be primarily determined by GA and additionally modulated by growth restriction in term newborns. We found a dramatic increase at weeks 33 to 35 of gestation and no modulation by BW SDS in very preterm infants.

Birth Weight↗

[Heart transplantation in infants--a new option].

Nowadays orthotopic heart transplantation is world wide accepted as a therapeutic concept in endstage congestive heart failure. Concerning infants, there are still major objections against this kind of therapy and especially in our country exists only very limited experience. Since march 1988 we have performed an orthotopic heart transplantation in 10 pediatric patients: 5 infants (2-16 years of age) with congestive cardiomyopathy, 1 newborn with endocardial fibroelastosis, 3 newborns with hypoplastic left heart syndrome, and finally 1 infant at the age of 2 years with AV-canal and hypoplastic left ventricle. Until now 6 infants survived and are all at home and in good clinical condition. There have been no signs for chronic rejection or graft atherosclerosis up till now. As demonstrated in the example of the newborn, in whom we performed the first successfully orthotopic heart transplantation in Germany, the clinical course and quality of life are superior to those after other palliative procedures in complex cardiac malformations.

Adolescent↗

Short stature and low IGF-1 and IGFBP-3 despite normal growth hormone secretion in a 4 year-old girl with primary empty sella syndrome.

A 4.1 year-old girl presented with short stature, cleft lip and additional upper incisor. Magnetic resonance imaging showed an empty sella due to a hypoplastic anterior pituitary. IGF-I and IGFBP-3 were at and below the 1st percentile, respectively. In contrast, normal spontaneous growth hormone (GH) secretion (5.5-h nocturnal sampling) was observed and pharmacological provocation raised (GH to levels between 15.4 and 53 micrograms/l. GH-binding protein levels were normal (210 pM). GH therapy led to an increase of growth velocity from 4.5 to 10.8 cm/year and a normalization of IGF-I and IGFBP-3 levels. The findings may imply an abnormal GH secretion pattern or a bioinactive GH in our patient. The data indicate that measurements of IGF-1 and IGFBP-3 may be a more sensitive test for integrative GH activity than GH testing itself.

Body Height↗