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Biomedical subjects

B Nielsen

Publications and source records attributed to B Nielsen.

At least 19 recordsLinked to original sources
PubMed1992

[Granulocyte-macrophage colony-stimulating factor. Treatment of patients with highly malignant lymphomas and acute lymphoblastic leukemias after autologous bone marrow transplantation].

We have evaluated the effect of intravenous infusions of granulocyte-macrophage colony-stimulating factor (GM-CSF) in ten patients undergoing autologous bone marrow transplantation after total body irradiation (11 Gy) and cyclophosphamide (120 mg/kg) conditioning for malignant lymphomas or acute lymphoblastic leukaemias. Mild side effects related to GM-CSF were seen in six patients, of whom one chose to discontinue treatment. Compared to a historic control group consisting of six patients treated with an identical conditioning regimen, a tendency was seen towards a more rapid neutrophil regeneration and a decreased need for erythrocyte transfusions. Moreover, a statistically significant improvement in thrombocyte related parameters was demonstrated. In contrast, there were no significant differences in severe toxicity, days on i.v. antibiotics, septic episodes or duration of hospitalization. In conclusion, it seems that GM-CSF treatment is of value in patients undergoing AKMT.

Adolescent↗
PubMed1992

Evidence for an association between hairy cell leukemia and renal cell and colorectal carcinoma.

BACKGROUND: Hairy cell leukemia (HCL) has been associated with several disease states. In this study, a possible association is reported between HCL and renal cell carcinoma (RCC) and colorectal carcinoma (CRC). METHODS: A retrospective study of the case records of 50 patients with HCL in a study of alpha-interferon (alpha-IFN) treatment of HCL. RESULTS: Three of 50 patients with HCL studied had RCC, and 2 of these also had CRC. In addition, two other patients had CRC. The other malignant lesions developed either before or after the diagnosis of HCL. In all patients, the HCL responded to alpha-interferon (alpha-IFN), but in four patients, the second lesion was diagnosed during IFN treatment. CONCLUSIONS: These findings could indicate that IFN does not correct a possible common basic etiologic defect and shows that even early CRC and RCC do not respond to the IFN doses administered. These findings should be considered in future trials of IFN treatment of these diseases. The authors also recommend a reevaluation of the frequency of second malignant lesions in HCL; this may be important particularly with the increased survival in patients with HCL who receive alpha-IFN treatment.

Adult↗
PubMed1992

Excitatory amino acid receptor ligands. Synthesis and biological activity of 3-isoxazolol amino acids structurally related to homoibotenic acid.

The 3-isoxazolol amino acid (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA, 2) and the isomeric compound (RS)-2-amino-3-(3-hydroxy-4-methylisoxazol-5-yl)propionic acid (4-methylhomoibotenic acid, 4a) are potent agonists at the AMPA subtype of central excitatory amino acid receptors. Using 4a as a lead structure, the amino acids 4c-e, in which the 4-methyl group of 4a is replaced by substituents of different size and polarity, were synthesized. Attempts to synthesize 4-(bromomethyl)homoibotenic acid (4f), a potential receptor alkylating agent, were unsuccessful. 4-Butylhomoibotenic acid (4c) and 4-(2-hydroxyethyl)homoibotenic acid (4e) were equipotent as inhibitors of [3H]AMPA binding (IC50 = 2 microM) and showed similar excitatory activity in the rat cortical slice preparation. 4d did not show significant affinity for AMPA receptor sites, but turned out to be a weak N-methyl-D-aspartic acid (NMDA) receptor antagonist. However, like 4c,e, 4d did not significantly affect the binding of the competitive NMDA antagonist, [3H]CPP, or the noncompetitive NMDA antagonist, [3H]MK-801. None of the amino acids 4c-e showed detectable affinity for [3H]kainic acid binding sites. Like the parent compound 4a (IC50 = 0.18 microM), 4c (IC50 = 0.18 microM), 4e (IC50 = 0.14 microM), and in particular 4d (IC50 = 0.02 microM) were effective inhibitors of calcium chloride-dependent [3H]glutamic acid binding, whereas AMPA is inactive (IC50 greater than 100 microM) in this binding assay. Thus, 4d is an effective and highly selective inhibitor of calcium chloride-dependent [3H]glutamic acid binding and may be a useful tool for studies of the physiological relevance and pharmacological importance of this binding affinity.

Animals↗
PubMed1992

[Pattern of choice in preparation of attempted suicide by poisoning--with particular reference to changes in the pattern of prescriptions].

This investigation was initiated in 1990 to investigate the choice of preparation in cases of attempted suicide treated in the Emergency Unit in Odense University Hospital during the past decade. The results show that 1) an increase has occurred particularly among young women in the use of analgesics obtainable without prescription (e.g. 13% of young women employed paracetamol as the toxic agent), 2) the number of persons employed dextropropoxyphene did not decrease and 3) a great increase was observed in the number of cases of poisoning with ketobemodoni chloridum. In 1985, several barbiturates were withdrawn from the Danish Medical Codex and this was followed by a decrease in the number of cases of poisoning among women but not among men. At present, approximately 10% of men who poison themselves still employ barbiturates. The number of cases of poisoning with barbiturates in men is thus not reduced but phenobarbital is the preparation of choice. The authors conclude that more attention and care should be paid when prescribing dextropropoxyphene, ketobemodoni chloridum and phenobarbital and the availability of paracetamol without prescription must be debated critically.

Adult↗
PubMed1992

[Psychiatric diseases among the homeless in Funen County].

The purpose of the study was to investigate whether deinstitutionalization of psychiatric patients had produced a clientele of homeless mentally ill people which is not treated. During week 47, 1990, 94 of the 129 residents 73%) in the institutions for homeless people in the County of Funen (population 459,000) were examined for mental illness by a psychiatrist. Diagnoses were made using the ICD-8 classification. Social data were recorded. Eighty-nine per cent were men, 59% were aged 30-49 years, 93% were single, and source of incomes for 80% were public assistance or disability pensions. More than half had been sentenced for crime at least once. The majority suffered from severe psychosocial strain. In 91% a psychiatric diagnosis was established, the most frequent being alcoholism (73%) and personality or character disorder (70%). Psychoses were found in 10 cases or 11%. About 29% required psychiatric treatment. The conclusion was that deinstitutionalization in the County of Funen had not resulted in influx of psychotic persons to institutions for the homeless people.

Adult↗
PubMed1992

Stereoselective effects of AMOA on non-NMDA receptors expressed in Xenopus oocytes.

Pharmacological characterization of the action of the novel non-N-methyl-D-aspartate (non-NMDA) antagonist AMOA (2-amino-3-[3-(carboxymethoxy)-5-methylisoxazol-4-yl]propionate) on glutamate receptors was investigated in Xenopus oocytes injected with mouse brain mRNA. AMOA (150 microM) produced a nearly parallel shift to the right of the dose-response curve for kainate-induced currents. AMOA was found to have two different effects on AMPA receptors: 1) currents elicited by low concentrations of AMPA (6 microM) were inhibited by AMOA with an IC50 value of 160 +/- 19 microM and 2) currents elicited by high concentrations of AMPA (100 microM) were potentiated with an IC50 value of 88 +/- 22 microM. The maximal potentiating effect of AMOA on AMPA currents was around 170%. Furthermore, the two opposing effects of AMOA on AMPA responses are specific for the L-configuration of AMOA. This unusual antagonistic/agonistic property of AMOA may explain its unusual properties with regard to antagonism of non-NMDA receptor-mediated events previously described.

Animals↗
PubMed1992

Sequential, morphological, and antidonor antibody analysis in a hamster-to-rat heart transplantation model.

The pathogenesis and the mechanism of accelerated graft rejection in concordant xenotransplantation are unclear. The histopathological features and kinetics neither fulfill the criteria of classic hyperacute rejection nor resemble an accelerated type of first-set allograft reaction. The aim of this study was to investigate the mechanism of concordant xenograft rejection in relation to the early morphological changes in hamster hearts transplanted to unmodified rat recipients by sequential, immunohistological analysis of grafts, regional lymph nodes, and spleens and to correlate these results to the production of antidonor antibodies, as determined by a flow cytometric assay. Histopathological features were characterized by a gradually increasing myocytolysis with fragmentation and loss of myofilaments. The first slight signs were observed a few hours after transplantation. Later, vascular changes developed, evolving into a leukocytoclastic type of vasculitis, eventually with thrombosis. No significant interstitial lymphocyte infiltration was present, but neutrophilic granulocytes and macrophages appeared. In addition, a distinct increase in B cells in spleens and lymph nodes was noted. Low levels of preformed antidonor antibodies did not increase during the first 48 h; however, significant amounts of species-, but not donor-, specific antibodies were demonstrated at the time of rejection. These data, together with the morphological observations, indicate a primarily humoral xenograft rejection in this model. Minor damage to graft myocytes a few hours after transplantation, progressing to vascular changes within 24-48 h, further suggests that preformed antidonor antibodies directed against endothelial or myocyte determinants may play an initiating role in the pathogenesis of unmodified, concordant xenograft rejection.

Animals↗
PubMed1992

Evidence against brain stem cooling by face fanning in severely hyperthermic humans.

To achieve a hyperthermic state 11 subjects exercised at 35 degrees C air temperature in a water-impermeable outfit, until their oesophageal temperature (Tes) exceeded 39 degrees C. Changes of brain stem temperature were assessed by the interspike intervals of auditory evoked potentials, which depend on brain stem temperature. These were recorded at rest before exercise (condition A), after exercise during a period when heat loss from the face was prevented by covering the head with a plastic hood (condition B), and again during face fanning (condition C). An increase in Tes from 37.14 +/- 0.25 degrees C to 39.05 +/- 0.15 degrees C (A to B) produced a significant reduction in interspike intervals, indicating an increase in brain stem temperature. Changing from conditions B to C, Tes and interspike intervals remained constant, indicating no change of brain stem temperature in spite of face fanning. Thus, even in severely heat stressed humans face fanning is not able to lower brain stem temperature significantly below that of the rest of the body core.

Adult↗
PubMed1992

Prevalence and causes of albuminuria in non-insulin-dependent diabetic patients.

A prospective study of the prevalence and causes of persistent albuminuria (greater than 300 mg/24 hr) was conducted in non-insulin-dependent diabetic (NIDDM) patients, age less than 66 years, attending a diabetic clinic during 1987. All eligible patients (N = 370) were asked to collect at least one 24-hour urine sample for albumin analysis. Urine collection was obtained in 224 males and 139 females (98%). Fifty patients (7 women) suffered from persistent albuminuria (13.8%). The prevalence of albuminuria was significantly higher in males (19%) than in females (5%). A kidney biopsy was performed in 35 patients (70%). The kidney biopsies revealed diffuse and/or nodular diabetic glomerulosclerosis in 27 patients (77%), while the remaining eight patients (23%) had a variety of non-diabetic glomerulopathies, such as minimal lesion and mesangioproliferative glomerulonephritis. Diabetic retinopathy was present in 15 of 27 patients (56%) with diabetic glomerulosclerosis, while none of the eight patients with a non-diabetic glomerulopathy had retinopathy. Our cross sectional study has revealed a high prevalence of albuminuria and of non-diabetic glomerulopathy as a cause of this complication in NIDDM patients. Presence of diabetic retinopathy strongly suggests that a diabetic glomerulopathy is the cause of albuminuria. Albuminuric non-insulin-dependent diabetic patients without retinopathy require further evaluation, that is, kidney biopsy.

Aged↗
PubMed1992

Simultaneous determination of chromium(III) and chromium(VI) in aqueous solutions by ion chromatography and chemiluminescence detection.

A method for the simultaneous determination of chromium(iii) and chromium(vi) in a flow system based on chemiluminescence was developed. A Dionex cation-exchange guard column was used to separate chromium(iii) from chromium(vi), and chromium(vi) was reduced by potassium sulfite, whereupon both species were detected by use of the luminol-hydrogen peroxide chemiluminescence system. Linear calibration for both species was established over the concentration range 1-1000 micrograms l-1. The precision at the 20 micrograms l-1 level was 3.5% for chromium(iii) and 3.3% for chromium(vi), respectively. The detection limit was 0.5 micrograms l-1 for both species. Data were in agreement with Zeeman-effect background corrected atomic absorption spectrometry measurements.

Chromatography, High Pressure Liquid↗
PubMed1992

Induced and down-regulated proteins in the human cultured hairy cell leukemia line JOK-1 and the Burkitt's lymphoma cell line Daudi during incubation with interferon-alpha: a kinetic study.

To elucidate the mechanism of action of interferon-alpha (IFN-alpha), the effect on cell proliferation and protein synthesis in the human hairy cell leukemia line JOK-1 and the Burkitt's lymphoma cell line Daudi were investigated. While Daudi cells were inhibited in proliferation and in total protein synthesis, no effect was seen on JOK-1 cells. However, high-resolution two-dimensional gel electrophoresis showed that four polypeptides were induced in JOK-1 cells after IFN-alpha incubation, while an additional 11 were induced and two down-regulated in Daudi cells. Kinetic studies revealed that the changes in JOK-1 cells were only temporary (within 8-16 h) and small to moderate in magnitude (less than four-fold). In Daudi cells, the changes for two of these polypeptides were early (within 2 h), for most of them prolonged (at least 24 h), and for three of them of great magnitude (between 6- and 30-fold). Quantitative analytical assessments indicated that four IFN-alpha-inducible polypeptides, present in low amounts of untreated cells, were highly expressed only in sensitive Daudi cells upon IFN-alpha treatment. This observation might indicate a role for these polypeptides in the inhibition of cell proliferation in Daudi cells. Furthermore, six of the other IFN-alpha-modulated polypeptides were synthesized constitutively in JOK-1 cells at levels comparable to those achieved in IFN-alpha-treated Daudi cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Burkitt Lymphoma↗
PubMed1992

Bacterial meningitis in elderly patients: clinical picture and course.

We reviewed the case records of 48 patients aged 60 years and older with a diagnosis of acute bacterial meningitis made during the period 1976-88. Predisposing conditions were present in 26 patients (54%) and concurrent infections in 24 patients (50%). Streptococcus pneumoniae accounted for 41% of all isolates and 56% were Gram-positive organisms. The most common symptoms were fever (79%), meningism (54%) and change in mental status (69%). Sixty-three per cent of the patients survived. Increased fatality was associated with absence of typical symptoms and signs and was presumably due to a delay in diagnosis. Other clinical and biochemical variables and antimicrobial therapy before admission to hospital and the presence of underlying disease were not associated with outcome.

Acute Disease↗
PubMed1992

Hydroxylated analogues of 5-aminovaleric acid as 4-aminobutyric acidB receptor antagonists: stereostructure-activity relationships.

The (R) and (S) forms of 5-amino-2-hydroxyvaleric acid (2-OH-DAVA) and 5-amino-4-hydroxyvaleric acid (4-OH-DAVA) were designed as structural hybrids of the 4-aminobutyric acidB (GABAB) agonist (R)-(-)-4-amino-3-hydroxybutyric acid [(R)-(-)-3-OH-GABA] and the GABAB antagonist 5-aminovaleric acid (DAVA). (S)-(-)-2-OH-DAVA and (R)-(-)-4-OH-DAVA showed a moderately potent affinity for GABAB receptor sites in rat brain and showed GABAB antagonist effects in a guinea pig ileum preparation. The respective enantiomers, (R)-(+)-2-OH-DAVA and (S)-(+)-4-OH-DAVA, were markedly weaker in both test systems. All four compounds were weak inhibitors of GABAA receptor binding in rat brain, and none of them significantly affected synaptosomal GABA uptake. Based on molecular modeling studies it has been demonstrated that low-energy conformations of (R)-(-)-3-OH-GABA, (S)-(-)-2-OH-DAVA, and (R)-(-)-4-OH-DAVA can be superimposed. These conformations may reflect the shapes adopted by these conformationally flexible compounds during their interaction with GABAB receptors. The present studies emphasize the similar, but distinct, constraints imposed on agonists and antagonists for GABAB receptors.

Amino Acids↗
PubMed1992

Three years' continuous low-dose interferon-alpha treatment of hairy-cell leukaemia: evaluation of response and maintenance dose.

Thirty-six HCL patients were treated with 2 x 10(6) U/m2 IFN-alpha-2b three times weekly for 24 months, followed by 12 months of treatment with one of three doses ranging from 0.5 x 10(6) U to 2 x 10(6) U/m2. For most patients the response continued to improve during the whole treatment period, and there were no cases of disease progression during treatment. Patients with disease of short duration before IFN treatment and/or non-splenectomized patients seemed to respond more slowly than others, but there were no differences between patients treated with the different IFN doses. Toxicity was usually WHO grade 1 or 2. The continued improvement in a large number of patients even with very small IFN doses might indicate that only a small number of true complete responses are reached after 24 months of treatment, thus explaining the reported high relapse rate after early discontinuation of treatment. It therefore seems worthwhile--also from a cost/benefit point of view--to test long-term or continuous IFN-alpha treatment at other centres.

Follow-Up Studies↗
PubMed1992

Interferon-alpha-induced changes in surface antigens in a hairy-cell leukemia (JOK-1), and a Burkitt's lymphoma cell line (Daudi) during in vitro culture.

In further studying the mechanism of action of IFN-alpha in HCL, we cultured the HCL cell line JOK-1 and the IFN-sensitive Burkitt cell line Daudi with and without IFN-alpha and investigated the changes in density of a number of surface antigens by use of mAb and flow cytometry analyses. During culture with IFN-alpha, reproducible changes were induced in both cell lines, which were qualitatively similar but differed quantitatively with small and transient changes in JOK-1. Significant decreases in surface antigen expression were observed for CD 19, 23, 37, and for IgM on both cell lines. Moreover, decreases were seen for CD 10, 22, 45, and MHC class II on Daudi, and for CD 20, 21, 27, and 40 on JOK-1. By contrast, only a few antigens increased in density, including CD 39, A96/G8 and SC9, on both cell lines, CD 22 on JOK-1, and CD 21 on Daudi. The increase in CD 39, A96/G8 and SC9 was probably directly related to the mechanism of action of IFN-alpha, whereas the other changes were most consistent with an unspecific inhibition of protein synthesis, possibly due to an accumulation of cells in G0, even though a differentiating effect cannot be ruled out. Thus, the unique in vivo effect of IFN-alpha in HCL was not paralleled by a specific direct effect on JOK-1 in vitro. Our findings therefore do not support the theory that IFN's mechanism of action in vivo is a direct effect on HC, but suggest that indirect effects are involved.

Antigens, CD↗
PubMed1992

The histology at various stages of acute rejection in concordant xenogeneic heart transplantation. A sequential study in rodents.

In an attempt to describe early morphologic changes in heterotopic xenogeneic heart transplantation a sequential study was performed in a hamster-to-rat model. Mild morphologic changes observed after four to six h were characterized by slight interstitial edema and focal myocyte damage with fragmentation and loss of myofibrillar elements. No lymphocytic infiltration appeared. Moderate morphologic changes observed after 12-24 h were characterized by moderate interstitial edema, and the appearance of mild hemorrhage and scattered extravasated neutrophilic granulocytes. The myocardium had more widespread areas with myocyte damage, sometimes with small foci of necrotic cells and adjacent neutrophilic granulocytes and macrophages. Vascular changes with perivascular edema and swelling of the endothelium were seen and a few neutrophilic granulocytes could be found in the vessel walls. No lymphocytic infiltration appeared. Severe morphologic changes observed after 44-48 h or at the time of complete rejection were characterized by severe interstitial hemorrhage, appearance of widespread necrosis and marked vascular changes with development of leukocytoclastic-like vasculitis, possibly with thrombosis. Only a few lymphocytes appeared. The findings were essentially different from those observed in allogeneic heart transplantations, where classical first-set allograft rejection was seen. In normal donor hearts and syngeneic transplanted hearts used as controls, no significant morphologic changes were demonstrated. On the basis of this study we consider xenogeneic acute rejection to be primarily of the humoral type.

Animals↗