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Biomedical subjects

H Schroeder

Publications and source records attributed to H Schroeder.

At least 55 records · Page 3Linked to original sources
PubMed1997

The role of striatal glutamatergic system in haloperidol-induced dopamine receptor supersensitivity and effects of monosialoganglioside GM1.

The mechanism underlying the action of ganglioside GM1 on the increase of haloperidol-induced dopamine receptor supersensitivity was studied using the method of chemically stimulated (3H)-D-aspartate release in rat striatal slices. After a 3-week chronic haloperidol treatment the transmitter release was reduced by about 30%, with a further reduction to 40% when GM1 was applied chronically as well. This suggests that the downregulation of the glutamatergic system by chronic haloperidol treatment is potentiated by gangliosides. The acute effect of gangliosides on the stimulated (3H)-D-aspartate release from striatal slices was tested by adding GM1 to the superfusion medium. When given at a concentration of 10(-4) M, GM1 did not alter the amino acid release itself. GM1 did, however, reduce the haloperidol-enhanced (3H)-D-aspartate release to control levels and elevated the glutamate-stimulated (3H)-D-aspartate release. Binding experiments indicate that gangliosides do not directly interact with glutamate or dopamine receptors. The data are discussed in view of earlier findings that GM1 potentiates the behavioral supersensitivity following chronic haloperidol treatment without directly altering dopamine receptor supersensitivity.

Animals↗
PubMed1997

Monitoring of methotrexate and 7-hydroxymethotrexate in saliva from children with acute lymphoblastic leukemia receiving high-dose consolidation treatment: relation to oral mucositis.

The purpose of the study was to find out if saliva concentrations of methotrexate (MTX) and its main metabolite, 7-hydroxymethotrexate (7-OHMTX), can predict oral mucositis in children with acute lymphoblastic leukemia (ALL) after treatment with high-dose consolidation therapy. We have also studied the relationship between the concentrations of MTX and 7-OHMTX in saliva and the unbound concentrations in plasma. Twelve patients (36 infusions) were studied during treatment with high-dose MTX as remission consolidation therapy (5-8 g/m2 by 24 h i.v. infusion followed by leucovorin rescue). Plasma and saliva concentrations of MTX and 7-OHMTX were determined concomitantly by HPLC at 20 h and at various times following infusion. Unbound plasma concentrations of MTX and 7-OHMTX were determined after ultrafiltration. Oral toxicity was graded according to the WHO criteria (grade 0-4). The concentrations of MTX and 7-OHMTX in saliva were not directly related to the development of mucositis. In patients with oral mucositis (WHO grade 1 or greater), the ratio to 7-OHMTX and MTX in saliva at 20 h was significantly lower than in patients without symptoms (p = 0.014, Mann Whitney rank sum test), but not at 42 and 66 h after starting the infusion. The salivary concentration of 7-OHMTX at 20 h ranged from undetectable (less than 1 nmol/l) to 1.6 micromol/l. No significant correlation was found between the unbound and total plasma concentrations of MTX and 7-OHMTX and the drug concentrations in saliva at different points in time. The concentrations of 7-OHMTX in saliva were 11, 23 and 13% of the unbound plasma concentrations at 20, 42 and 66 h, respectively, after starting the infusion. The respective median corresponding values for MTX were 1.6, 16.1 and 61.6%. The results suggest that determinations of saliva concentrations of MTX and 7-OHMTX may predict oral mucositis. This opens up the possibility of early identification of patients at high risk of developing oral mucositis in order to intensify topical or systemic treatment of these patients.

Child↗
PubMed1997

Suspected primary immunodeficiency syndrome in three related Irish wolfhounds.

Three related Irish wolfhound dogs less than one year old presented with a history of chronic nasal discharge and signs of lower respiratory tract disease. These responded well to treatment initially but were chronically recurring. Cursory evaluation of the immune system (full blood counts, globulin determination and fractionation, electrophoresis and lymphocyte blastogenesis) seemed to indicate a cell-mediated immunodeficiency which, because of the age of the patients, is strongly suspected to be primary.

Animals↗
PubMed1996

Methotrexate plasma pharmacokinetics: importance of assay method.

Intravenous methotrexate (MTX) therapy is widely used for treatment of various neoplastic diseases in children. The optimization of the MTX dose and/or the subsequent leucovorin rescue is based on pharmacokinetic data calculated from plasma concentrations collected after cessation of the MTX administration. The influence of the MTX assay method on the subsequent pharmacokinetic evaluation was studied in 13 children with acute lymphoblastic leukemia. Plasma samples were collected after administration of MTX (5-8 g/m2) as 24 h infusions. All samples were analyzed by five different analytical procedures, viz. liquid chromatography (LC), enzyme inhibition assay (EIA), two fluorescence polarization immunoassays (FPIA1 and FPIA2) and enzyme multiplied immunoassay (EMIT). Using measurements from the four non-chromatographic procedures, only about 50% of determined pharmacokinetic parameters (area under the plasma concentration time curve, calculated by the trapezoidal rule and from pharmacokinetic modelling, and the terminal half life time) were within the range 75-125% of the values obtained from LC data. We conclude that the clinical outcome of MTX therapy using estimated MTX pharmacokinetics as guidelines for proper dosing of MTX and/or leucovorin rescue might be affected by the lack of accuracy of non-chromatographic procedures for MTX analysis. There is still a need for improving the accuracy of the procedures aimed at therapeutic drug monitoring of MTX.

Adolescent↗
PubMed1996

Lipid-modified, cysteinyl-containing peptides of diverse structures are efficiently S-acylated at the plasma membrane of mammalian cells.

A variety of cysteine-containing, lipid-modified peptides are found to be S-acylated by cultured mammalian cells. The acylation reaction is highly specific for cysteinyl over serinyl residues and for lipid-modified peptides over hydrophilic peptides. The S-acylation process appears by various criteria to be enzymatic and resembles the S-acylation of plasma membrane-associated proteins in various characteristics, including inhibition by tunicamycin. The substrate range of the S-acylation reaction encompasses, but is not limited to, lipopeptides incorporating the motifs myristoylGC- and -CXC(farnesyl)-OCH3, which are reversibly S-acylated in various intracellular proteins. Mass-spectrometric analysis indicates that palmitoyl residues constitute the predominant but not the only type of S-acyl group coupled to a lipopeptide carrying the myristoylGC- motif, with smaller amounts of S-stearoyl and S-oleoyl substituents also detectable. Fluorescence microscopy using NBD-labeled cysteinyl lipopeptides reveals that the products of lipopeptide S-acylation, which cannot diffuse between membranes, are in almost all cases localized preferentially to the plasma membrane. This preferential localization is found even at reduced temperatures where vesicular transport from the Golgi complex to the plasma membrane is suppressed, strongly suggesting that the plasma membrane itself is the preferred site of S-acylation of these species. Uniquely among the lipopeptides studied, species incorporating an unphysiological N-myristoylcysteinyl- motif also show substantial formation of S-acylated products in a second, intracellular compartment identified as the Golgi complex by its labeling with a fluorescent ceramide. Our results suggest that distinct S-acyltransferases exist in the Golgi complex and plasma membrane compartments and that S-acylation of motifs such as myristoylGC- occurs specifically at the plasma membrane, affording efficient targeting of cellular proteins bearing such motifs to this membrane compartment.

Acylation↗
PubMed1996

Evaluation of clinical assays for measuring high-dose methotrexate in plasma.

Four routine assays commonly used for monitoring plasma methotrexate (MTX) during high-dose therapy were validated by HPLC as the comparison method. MTX and its main metabolite, 7-hydroxymethotrexate (7-OHMTX), were analyzed by HPLC with postcolumn derivatization and fluorometric detection. About 200 clinical plasma samples from 13 children with acute lymphoblastic leukemia who received 5-8 g/m2 MTX as 24-h infusions were analyzed. The fraction of measured concentrations of MTX that were within 75-125% of the values obtained by HPLC were 64.5% for enzyme inhibition assay, 56.4% for fluorescence polarization immunoassay with polyclonal antibodies (FPIA1; Abbott), 58.9% for FPIA2 (with monoclonal antibodies; Abbott), and 46.4% for enzyme-multiplied immunoassay (Emit; Syva). All nonchromatographic procedures were subject to interferences from MTX plasma metabolites or endogenous substances. The interference from 7-OHMTX was, however, somewhat less pronounced for FPIA2 (monoclonal) than for FPIA1 (polyclonal).

Child↗
PubMed1996

Allogeneic bone marrow transplantation in first remission for children with very high-risk acute lymphoblastic leukemia: a retrospective case-control study in the Nordic countries. Nordic Society for Pediatric Hematology and Oncology (NOPHO).

Among children with high-risk (HR) ALL there are subgroups with very-high-risk (VHR) features and poor prognosis despite developments in conventional chemotherapy for childhood ALL. We evaluated the outcome of VHR-ALL in children receiving allogeneic BMT (allo-BMT) in first remission (1CR) in a retrospective case-control study. In the population-based ALL material of the five Nordic countries, 22 children with VHR-ALL have undergone allo-BMT in 1CR between 1981-1991. We compared the outcome in these 22 children with 44 closely matched control patients who received conventional chemotherapy on HR-ALL protocols, as well as with a group of 405 children representing the remaining HR-ALL patients in the Nordic ALL database. The disease-free survival at 10 years was 73% in children receiving allo-BMT in 1CR, 50% in the matched controls (P = 0.02), and 59% in the remaining HR-ALL patients. The good prognosis of the allo-BMT group was due to a low relapse rate of 9%, as opposed to 41% in the group of matched controls. The superiority of allo-BMT as therapy in 1CR was mainly apparent in those with a very high WBC of > or = 100 x 10(9)/I at diagnosis; in the allo-BMT group 9/10 survived, as opposed to 8/20 of the matched controls (P = 0.03). We conclude that allo-BMT in 1CR should be seriously considered for children with a matched sibling donor and a VHR-ALL with WBC of > or = 100 and other established VHR criteria.

Adolescent↗
PubMed1996

Rapid determination of fecal fat by Fourier transform infrared analysis (FTIR) with partial least-squares regression and an attenuated total reflectance accessory.

Fecal lipid content is usually determined by titrimetric or gravimetric methods, but these methods are time consuming and involve dangerous solvents. We have developed a new method of measuring fecal lipids by Fourier transform infrared spectrometry (FTIR) with an attenuated total reflectance accessory that is fast and requires no solvents. The spectra of stools from 4000 to 750 cm-1 were analyzed, and the lipid concentrations were measured by using a calibration curve prepared by partial least-squares analysis of data from 34 stools. The linearity of the method was tested by mixing low-lipid stools with lipid-overloaded stools to give a range of 0.5-15% lipid. The prediction residual values were -0.49-0.78% for calibrators, and -2.55-2.34% for unknown samples. There was good agreement between the fecal lipids measured by gravimetric (x) and FTIR(y) methods: y = 0.87x + 5.5. The standard error of prediction was 1.07%.

Calibration↗
PubMed1995

Outcome after first relapse in children with acute lymphoblastic leukemia: a population-based study of 315 patients from the Nordic Society of Pediatric Hematology and Oncology (NOPHO).

UNLABELLED: This study reports the outcome after relapse of acute lymphoblastic leukemia (ALL) in a population-based study of 809 children over 1 year of age diagnosed July 1981 through June 1986 and with non-B acute lymphoblastic leukemia in the five Nordic countries. By January 1994, 315 children had suffered at least one relapse. The bone marrow was involved in 216 cases. There were 69 isolated CNS relapses, 25 isolated testicular recurrences and five relapses in other extramedullary sites. Of the 315 children with relapse, 94 are still in a second complete remission 12-138 (median: 78) months after relapse. The overall probability of a second event free survival (P-2.EFS) and survival after relapse was 0.28 and 0.33 respectively. The probability of remaining in second remission at 11 years was significantly correlated to the duration of first remission (P < 0.001), the site of relapse (P < 0.001) and gender (P = 0.004). The P-2.EFS for early, intermediate, and late bone marrow involved relapses were 0.08, 0.19, and 0.50 respectively. For early, intermediate and late isolated CNS relapses the P-2.EFS were 0.21, 0.38 and 0.61, respectively. The P-2.EFS for boys with isolated testicular relapses was 0.69. Girls with isolated CNS relapse (P < 0.001) and with bone marrow involved relapse (P = 0.04) had a significantly better prognosis than boys. Children with initial high risk criteria, especially T-ALL and mediastinal mass who relapsed, had a very poor prognosis. CONCLUSION: In this population-based study, about 30% of children with ALL obtained a long second remission and possible cure.

Adolescent↗
PubMed1995

Behavioral and metabolic consequences of neonatal exposure to diazepam in rat pups.

The short-term consequences of a neonatal exposure to diazepam (DZP) on neurobehavioral development and postnatal changes in local cerebral metabolic rates for glucose (LCMRglcs) in selected regions were studied in rats. Rat pups received a daily subcutaneous injection of 10 mg/kg DZP or of the dissolution vehicle from Postnatal Day 2 (P2) to 21 (P21). DZP did not affect the static righting reflex tested at P4 but increased suspension time at P10 and time to complete a 180 degrees pivoting on an inclined plane at P9. In a locomotor coordination test performed at P20, swimming or climbing on a vertical pole was not affected by DZP while the drug impaired the ability of the rat to place its hind-paws on the horizontal platform after climbing. Likewise, DZP induced marked decreases (19-45%) in LCMRglcs in most structures studied at P10, P14, and P21. The results of the present study show that neonatal DZP treatment induces motor deficits that appear to be quite subtle, to concern mainly posture and body balance. They are not apparent in tasks such as swimming or climbing but become obvious in more difficult tasks such as achieving a horizontal quadruped position on a platform after a climbing phase. Decreases in cerebral energy metabolism appear to be mainly located in areas controlling posture and body balance and are partly correlated with the locomotor impairments recorded in the present study.

Animals↗
PubMed1995

Transient pancytopenia preceding acute lymphoblastic leukemia (pre-ALL).

Pancytopenia followed by a period of spontaneous recovery may precede the diagnosis of acute lymphoblastic leukemia (pre-ALL). Although both pre-ALL and myelodysplastic syndromes are preleukemic in a strictly temporal sense, there are several marked differences between the two conditions. We present eight children with pre-ALL who represented 2% of all cases of childhood ALL. The bone marrow was normo- or hypocellular with increased reticulin fibrosis during the pre-ALL phase. No cytogenetic abnormalities were found at the pre-ALL phase, but had developed at the time of overt leukemia in four of the six children examined. Based on the findings in our patients and on cases reported in the literature, we argue that pre-ALL is likely to represent a paraneoplastic syndrome early in the leukemic development that might be mediated via inhibitory properties related to clonally expanding but still cytogenetically normal cells. The findings may indicate a multistep pathogenesis of ALL.

Adolescent↗
PubMed1994

Short- and long-term effects of neonatal diazepam exposure on local cerebral glucose utilization in the rat.

The short- and long-term consequences of a neonatal exposure to diazepam (DZP) on the postnatal changes in local cerebral metabolic rates for glucose (LCMRglcs) were studied by the quantitative autoradiographic [14C]2-deoxyglucose method in a total number of 66 brain structures of freely moving rats. Rat pups received a daily subcutaneous injection of 10 mg/kg DZP, of the dissolution vehicle or of saline from postnatal day 2 (P2) to 21 (P21). The animals were studied at 4 ages, P10, P14, P21 and P60. DZP induced a decrease in LCMRglcs which was restricted to 13 areas at P10, mainly sensory and limbic regions. At P14, the treatment had significant metabolic effects on 48 structures belonging to all functional systems. By P21, 23 brain areas were still affected by the treatment, mainly sensory, limbic and motor areas. At P60, i.e. at about 40 days after the end of drug exposure, LCMRglcs still decreased in 14 brain regions which were mainly sensory and limbic structures. The structures most sensitive to both short- and long-term consequences of the anticonvulsant treatment are mammillary body, limbic cortices and sensory regions. The dissolution vehicle increased LCMRglcs in a few brain regions at P14 and P60, whereas it decreased metabolic levels in 5 brain regions at P21. The results of the present study show that the brain appears to be particularly vulnerable to the treatment at P14, period of active brain growth, whereas by P21, the drug is actively metabolized and a tolerance to the treatment may occur. The long-term effects of the treatment are in good accordance with the well-known effects of DZP on anxiety, sedation and memory. The structures most sensitive to early neonatal DZP exposure are the mammillary body, limbic cortices and sensory regions that all contain a high density of benzodiazepine binding sites.

Aging↗
PubMed1994

Effects of early chronic diazepam treatment on incorporation of glucose and beta-hydroxybutyrate into cerebral amino acids: relation to undernutrition.

The effects of early chronic diazepam (DZP) exposure on blood glucose and ketone body concentration and glucose and beta-hydroxybutyrate (beta HB) utilization for regional cerebral amino acid biosynthesis were studied in suckling rats. The animals were treated from postnatal day 2 (P2) to 21 (P21) by a daily subcutaneous injection of 10 mg/kg DZP or of the dissolution vehicle and studied at P5, P10, P14 and P21, together with an additional group of food-restricted rats obtained by an increase in litter size. DZP treatment induced a 9-26% decrease in body and brain weight. Undernutrition decreased body weight by 20-24% at all ages whereas brain weight was relatively spared. DZP and N-desmethyldiazepam concentrations decreased with age and were cleared from brain and plasma by 6-8 hrs after the injection. DZP decreased plasma glucose concentrations by 6-12% at P5, P14 and P21, whereas undernutrition did not change plasma glucose concentrations, except for a 7% decrease at P14. DZP treatment had no consequences on circulating concentrations of both ketone bodies while undernutrition increased their concentration by 45-362% at all ages. The conversion of [14C]glucose into cerebral amino acids was reduced by DZP at P5 and P10. The cerebral concentration of neurotransmitter amino acids was not affected by DZP treatment which only increased the amount of neutral amino acids mainly in the cerebellum at P5 and P10. After [U-14C]glucose injection, specific radioactivities of cerebral amino acids were mostly decreased by DZP from P5 to P14 and significantly increased at P21. With [3-14C] beta HB as a precursor, specific radioactivities of neurotransmitter amino acids were increased by DZP. In conclusion, P5 and P10 rats appear to be most sensitive to DZP effects whereas some tolerance to the drug seems to develop by P21. The lack of effects of DZP on blood ketone body concentrations compared to food restriction as well as the relative sparing of brain weight in undernourished rats confirms that the cerebral metabolic consequences of early DZP exposure on brain energy metabolism are mostly direct effects not mediated by sedation-induced undernutrition.

3-Hydroxybutyric Acid↗
PubMed1994

Systemic phaeohyphomycosis caused by Xylohypha bantiana in a dog.

An 8-year-old, Maltese-cross bitch presented with chronic neck and back pain and an acute onset of circling, hyperaesthesia and constant crying. Clinical examination revealed temporal muscle atrophy, an abnormal hanging reflex, cervical rigidity and severe hepatomegaly. Ultrasonography of the liver showed several disseminated, poorly demarcated, hypoechoic areas which on fine needle aspirates, contained large numbers of pigmented fungal hyphae. Cerebrospinal fluid examination revealed fungal hyphae and numerous Ehrlichia canis morulae. A diagnosis of systemic phaeohyphomycosis secondary to ehrlichiosis was proposed. Treatment was unsuccessful and the dog was euthanased. At necropsy, multiple yellowish-green to black, necro-granulomatous foci were found throughout the liver parenchyma and similar foci were present in the spleen, renal cortices and adrenal glands. Irregular, multifocal, grey to black foci of malacia were present in both the grey and the white matter of the brain. On histopathological examination pigmented fungal hyphae were demonstrated in the liver, spleen, kidneys, portal lymph node and adrenals, as well as in the brain. Cultures of various organs yielded a fungal organism identified as Xylohypha bantiana.

Animals↗
PubMed1993

Generalised Listeria monocytogenes infection in a dog.

A 6-year-old Doberman bitch was presented for an acute onset of circling, hemiparesis and depression. Clinical examination revealed conjunctivitis, abdominal pain, anaemia, decreased facial sensation, decreased jaw, tongue and pharyngeal tone, decreased conscious proprioception, decreased flexor withdrawal reflexes, and abnormal hemiwalking and hemistanding. Pancytopaenia was evident on haematological evaluation. Bone marrow cytology revealed a bacterial infection. Cerebrospinal fluid analysis was normal. Despite antibiotic treatment, the dog died. On autopsy, widespread multifocal inflammatory lesions were found to be present in the lungs, liver, spleen, meninges, lymph nodes, adrenal glands and kidneys. Listeria monocytogenes was isolated in pure culture from these organs and tissues. Histopathological examination showed numerous gram-positive intracellular rod-shaped bacteria seen in all the above-mentioned organs.

Animals↗
PubMed1992

Effects of the acute administration of a new trimethylxanthine derivative, S 9977-2, on local cerebral blood flow and glucose utilization in the rat.

S 9977-2 is a new trimethylxanthine derivative with promnesic properties. Its effects on cerebral glucose utilization and blood flow were studied by means of quantitative autoradiography. S 9977-2 was injected intravenously into adult rats at doses of 0.1, 1.0 and 10 mg/kg. At 0.1 mg/kg, S 9977-2 induced a significant increase in cerebral glucose utilization over control values in two white matter areas and in the vestibular nucleus. At 1.0 mg/kg, glucose utilization was affected in 14 areas out of the 63 studied, mainly limbic regions such as the hippocampus, raphe nuclei and locus coeruleus, as well as some posterior areas. Conversely, after the injection of 10 mg/kg S 9977-2, cerebral glucose utilization was similar to that of control rats. At the three doses tested, S9977-2 did not induce any significant variation in local rates of cerebral blood flow compared to those of controls. Likewise, S 9977-2 did not change the level of coupling between cerebral blood flow and metabolism, except at 10 mg/kg, where a relative hypoperfusion at a constant metabolic level was recorded. These data show that, at 1.0 mg/kg, S 9977-2 increased glucose utilization in hippocampal areas, an effect which may be related to the promnesic properties of this compound at the same dose. Moreover, at low doses, the lack of change in the level of coupling between cerebral blood flow and metabolism is indicative of the rather selective action of this compound, compared to that of caffeine. Thus S9977-2 should have therapeutic effects, mainly via its promnesic properties, without having many side effects.

Animals↗