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Biomedical subjects

D Petersen

Publications and source records attributed to D Petersen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Primary central nervous system lymphoma: from clinical presentation to diagnosis.

Immunocompetent patients with primary central nervous system lymphoma (PCNSL) present with a median age of 55 years, immunosuppressed patients with a median age of 40 years. They show a broad range of signs and symptoms. Symptoms of increased intracranial pressure and personality change are most frequent, followed in frequency by ataxia and hemiparesis. The median time from onset of symptoms to diagnosis is 3-5 months in immunocompetent patients and 2 months in immunodeficient patients. The time to diagnosis can be considerably longer in patients with slowly developing personality change or fluctuating symptoms due to spontaneous or steroid-induced remission of so-called sentinel lesions. Native CT scans show iso- or hyperdense lesions with homogenous contrast enhancement. T1-weighted MRI scans show hypointense and T2-weighted scans hyperintense lesions. The definitive diagnosis of PCNSL requires biopsy. In some cases, however, the definitive diagnosis may exclusively be made by the demonstration of malignant B-lymphocytes in the cerebrospinal fluid.

Adult↗
PubMed1999

Endogenous serum levels of thrombopoietic cytokines in healthy whole-blood and platelet donors: implications for plateletpheresis.

Serum concentrations of the thrombopoiesis-enhancing cytokines thrombopoietin (TPO), erythropoietin (EPO), interleukin (IL)-6 and IL-11 were determined in 119 healthy whole-blood (WBD) and 101 platelet donors (PD) prior to donation. The 90% TPO reference interval in WBD of 64-867 pg/ml (median 163, 100% range 45-7572) was significantly higher than in PD of 56-524 (median 122, range 44-801, P = 0.004), whereas their platelet counts were lower (P < 0.001). EPO levels were not different (WBD 7.7 +/- 3.8, PD 8.0 +/- 4.9 IU/l), IL-6 and IL-11 were below the detection limit in >/=90% of cases (IL-6 < 3.2 pg/ml, IL-11 < 31.2 pg/ml). None of the cytokines correlated with platelet counts, other blood parameters, or in the PD group with the frequency of platelet donations within the last 6 months. We conclude that plateletpheresis does not lead to a lasting increase of thrombopoietic cytokines and provide reference data for potential platelet mobilization strategies with recombinant growth factors.

Adult↗
PubMed1998

Safety and toxicity of amphotericin B in glucose 5% or intralipid 20% in neutropenic patients with pneumonia or fever of unknown origin: randomised study.

OBJECTIVE: To compare the feasibility of treatment, safety, and toxicity of intravenous amphotericin B deoxycholate prepared in either glucose or intralipid for empirical antimycotic treatment of neutropenic cancer patients. DESIGN: Single centre stratified, randomised non-blinded phase II study. SETTING: University hospital providing tertiary clinical care. SUBJECTS: 51 neutropenic patients (leukaemia (35), lymphoma (11), solid tumours (5)) with refractory fever of unknown origin (24) or pneumonia (27). INTERVENTIONS: Amphotericin B 0.75 mg/kg/day in 250 ml glucose 5% solution or mixed with 250 ml intralipid 20%, given on eight consecutive days then alternate days, as a 1-4 hour infusion. MAIN OUTCOME MEASURES: Feasibility of treatment, subjective tolerance (questionnaire), and objective toxicity (common toxicity criteria of the National Cancer Institute). RESULTS: Study arms were balanced for age, sex, underlying malignancy, renal and liver function, and pre- and concomitant treatment with antibiotics and nephrotoxic agents. No statistically significant or clinically relevant differences were found between the treatment groups for: daily or cumulative dose and duration of treatment with amphotericin B; incidence and time of dose modifications or infusion duration changes related to toxicity; dose or duration of symptomatic support with opiates, antipyretics, or antihistamines; renal function; subjective tolerance; most common toxicity scores; course of infection; and incidence of treatment failures. Patients treated with amphotericin B in intralipid were given fewer diuretics (P<0.05) and therefore had more peripheral oedema (P<0.01) and needed less potassium supplementation (P<0.05) than patients given amphotericin in glucose. Acute respiratory events were more common in the intralipid arm (P<0.05). CONCLUSIONS: Amphotericin B 0.75 mg/kg/day in intralipid given on eight consecutive days then alternate days provides no benefit and is associated with potential pulmonary side effects possibly because of fat overload or an incompatibility of the two drugs.

Adolescent↗
PubMed1998

Lesion location influences perception of homonymous scotomata during flickering random dot pattern stimulation.

An attempt was made to clarify whether the site of postchiasmal lesions affects subjective perception of homonymous visual field defects during stimulation with flickering random dot patterns (white noise-field). Out of 56 patients with homonymous hemianopia, 38 (68%) perceived scotomata in this situation, but 18 (32%) discerned none at all. Neuroradiologic superposition of cerebral lesions detected by computed tomography (CT) or magnetic resonance imaging (MRI) showed that nearly all patients who perceived their scotomata had lesions involving the primary visual cortex or the perigeniculate region, whereas those who received no scotoma had lesions centered within the optic radiation. Functional MRI of six normal subjects during stimulation with flickering random dot patterns indicated predominant activation of the primary visual cortex. Since noise-field defects were most frequently perceived by patients whose lesion involved the primary visual cortex, it appears that the sensitivity of noise-field campimetry depends on the site of damage in the visual pathway. The explanation for this may be that damage to long-range horizontal connections impairs filling-in processes.

Adolescent↗
PubMed1998

Sustained decrease of peripheral lymphocytes after allogeneic blood stem cell aphereses.

48 healthy donors underwent peripheral blood stem cell (PBSC) apheresis for allogeneic transplantation beginning on day 4 of G-CSF (2 x 5 microg/kg) mobilization. In one to four (median two) large-volume mononuclear cell aphereses, a median of 55.9 x 10(9) of lymphocytes (range 21.0-109.2 x 10[9]) were collected, an amount comparable to lymphocyte numbers removed by therapeutic lymphaphereses in autoimmune diseases. Mean peripheral lymphocyte counts decreased from premobilization values of 2.31 x 10(9)/l to 1.31 x 10(9)/l at a median of 34 d (1 month) and 1.53 x 10(9)/l at a median of 327 d (11 months). The decrease in peripheral lymphocyte counts was significantly correlated with the number of lymphocytes removed and the number of aphereses. Neutrophil and platelet counts returned to normal values after 1 month whereas monocyte counts and haemoglobin concentrations were significantly decreased at 1 month but not at 11 months.

Female↗
PubMed1998

Deficits and recovery of first- and second-order motion perception in patients with unilateral cortical lesions.

Unilateral lesions in the posterior parietal cortex can degrade motion perception in the contralesional visual hemifield. Our aim was to investigate whether deficits caused by cortical lesions may be different for first- and second-order motion perception, and to study the time scale of any potential recovery. In nine patients with circumscribed lesions mainly in the parietal and fronto-parietal cortex, thresholds for direction discrimination were measured for stimuli presented peripherally in their ipsi- and contralesional hemifield. Subjects had to identify the direction of a vertically moving object embedded in a background of dynamic random dot noise. The object consisted of various proportions of signal and noise dots. Signal dots were either (a) coherently moving in the same direction as the object (first-order), (b) stationary (second-order: drift-balanced), or (c) coherently moving in the opposite direction (second-order: theta). Noise dots were flickering. Two patients showed significant threshold elevations for all three types of motion stimuli presented in their contralesional hemifield, while thresholds for ipsilesional targets were unaffected. Neither showed any selective deficit of first- versus second-order motion perception, but second-order motion was more impaired. Their lesions probably included the motion area V5-MT, which was spared in the other seven patients. One of the patients, who was retested several times during a 27-month postlesional period, showed complete recovery for first- and second-order motion direction discrimination, as well as for the detection of speed differences.

Adult↗
PubMed1998

Clinical presentation and therapeutic outcome in 26 patients with primary CNS lymphoma.

This retrospective study analyzes clinical features and therapeutic outcome in 26 immunocompetent patients with primary central nervous system lymphoma (PCNSL). Most patients presented with personality changes. PCNSL lesions were mainly iso- or hyperdense, enhancing lesions on CT scan, hypointensive on T1-, and hyperintensive on T2-weighted MRI. Multiple lesions were found in about 60% of patients. Nine of 11 patients receiving radiotherapy alone showed complete remission (CR). Median survival time after diagnosis (MST) was 13 months. Seven patients received intravenous and intrathecal methotrexate, radiotherapy, and postirradiation intravenous cytarabine. Six of these patients had CR and 5 patients are alive in CR after a median follow-up of 12 months. Five patients received various other radiochemotherapy regimens (MST 6 months), and 3 patients died before receiving any radio- or chemotherapy. Our preliminary treatment results show a tendency to improved survival with radiochemotherapy. This is consistent with pertinent data from the literature which favors radiochemotherapy for patients with PCNSL.

Adrenal Cortex Hormones↗
PubMed1998

Acute disseminated encephalomyelitis following Pontiac fever.

We report the case of a 35-year-old woman who developed headache and psychosis and gradually became comatose within 3 weeks after a flu-like infection. MRI revealed bifrontal demyelination consistent with acute disseminating encephalomyelitis (ADEM). Two different cerebrospinal fluid samples were positively tested for Legionella cincinnatiensis by direct sequencing of a PCR-amplified Legionella-specific fragment. This result made it possible to interpret the initial symptoms as Pontiac fever. We think it most likely that this is a case of ADEM following the very rare situation of a systemic infection with L. cincinnatiensis. A review of the literature on Legionella-associated encephalopathy suggests that some of these cases may also have had ADEM.

Adult↗
PubMed1997

False perception of motion in a patient who cannot compensate for eye movements.

We are usually unaware of the motion of an image across our retina that results from our own movement. For instance, during slow-tracking eye movements we do not mistake the shift of the image projected onto the retina for motion of the world around us, but instead perceive a stable world. Following early suggestions by von Helmholtz, it is commonly believed that this spatial stability is achieved by subtracting the retinal motion signal from an internal reference signal, such as a copy of the movement command (efference copy). Object motion is perceived only if the two differ. Although this concept is widely accepted, its anatomical underpinning remains unknown. Here we describe the case of a patient with bilateral extrastriate cortex lesions, suffering from false perception of motion due to an inability to take eye movements into account when faced with self-induced retinal image slip. This is indicated by the fact that during smooth-pursuit eye movements, he perceives motion of the stationary world at a velocity that corresponds to the velocity of his eye movement; that is, he perceives the raw retinal image slip uncorrected for his own eye movements. We suspect that this deficiency reflects damage of a distinct parieto-occipital region that disentangles self-induced and externally induced visual motion by comparing retinal signals with a reference signal encoding eye movements and possibly ego-motion in general.

Adult↗
PubMed1997

Deletion within the D17S34 locus in a primitive neuroectodermal tumor.

Loss of heterozygosity on chromosome 17p13.3 is frequently observed in solid tumors, and the presence of a tumor suppressor gene has been predicted in this region of chromosome 17. We have analyzed a primitive neuroectodermal tumor sample exhibiting loss of heterozygosity at the D17S34 locus, a commonly used telomeric marker on the short arm of chromosome 17. The remaining allele showed a rearrangement. Cosmids spanning the D17S34 locus and probes from that region were used to demonstrate a 9-kb deletion within the D17S34 locus and were found to contain evolutionary, conserved sequences. Genetic alterations in this region may also affect expression of immediately adjacent genes, such as ABR, and could be a common mechanism in the causation of primitive neuroectodermal tumors.

Chromosomes, Human, Pair 17↗
PubMed1997

[Indications for contrast medium administration in MR-angiography of cerebral blood vessels].

Time-of-flight MR-angiography of large volumes is limited by the occurrence of saturation effects, which lead to low signal in both veins and arteries. Alternatively to a number of other MRA-techniques, intravenous application of paramagnetic contrast media in combination with 3D-pulse sequences with or without flow refocussing allows the depiction of slow vessels in large volumes without technical extra expenses. The main intracranial indication is anatomical 3D-imaging of normal and dysplastic cerebral veins with high spatial resolution, and the additional depiction of the venous drainage in AVMs, when unenhanced MRA shows only the arteriel supply and the nidus. In large cerebral aneurysms, bridging veins and venous sinuses, partial thromboses can easily be differentiated from slow flow. Contrast-enhancing tumors can be depicted together with normal or displaced vessels. Improvements of arterial signal due to contrast media with currently used routine MRA techniques are clinically not significant. Signal loss due to spin dephasing in vessels with complex flow is not influences by contrast media. Results of contrast-enhanced MRA are determined by the timing of injection. Since arteries and veins are both imaged with high signal intensity, improvements of postprocessing procedures for secondary vessel segmentation are necessary.

Blood Flow Velocity↗
PubMed1997

Magnetic resonance images of 91 children with different causes of short stature: pituitary size reflects growth hormone secretion.

UNLABELLED: In order to validate an association between pituitary size and severity of growth hormone deficiency (GHD) we evaluated the magnetic resonance images (MRI) of 107 children with different causes of short stature. Ninety-one MRIs were evaluable (64 male, 27 female; age: 9.1 +/- 3.9 years). The levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3), and tests of GH stimulation and spontaneous secretion, led to the following subgroups: severe isolated GHD (SIGHD) (GH < 7 ng/ml) (n = 21); partial, isolated GHD (GH 7-10 ng/ml) (n = 22); multiple pituitary hormone deficiency (MPHD) (n = 13); neurosecretory dysfunction (n = 10); non-classifiable diagnosis (NC) (n = 13); idiopathic short stature (n = 9); and intra-uterine growth retardation (n = 3). Pituitary height (PHT) was measured and hypoplasia was assumed when PHT was < -2 SDS. An ectopic posterior pituitary with missing stalk and a hypoplastic anterior pituitary was present in 12 (57%) SIGHD cases, 12 (92%) MPHD cases and 1 patient from the NC group. An isolated hypoplastic anterior pituitary was observed in 15%-33% of the other groups. PHT (mm; mean, SD) in MPHD (1.7 +/- 0.5) was lower than in SIGHD (2.7 +/- 1.0, P < 0.05), with PHT of both groups being lower than in all the other groups (3.8 +/- 0.9, P < 0.0001). PHT SDS correlates with IGF-I SDS (r = 0.48, P < 0.0001), IGFBP-3 SDS (r = 0.46, P < 0.0001) and the highest peaks in tests of GH stimulation and GH spontaneous secretion (r = 0.36, P < 0.0001). In contrast to all the other groups, no correlation with age was observed in MPHD and SIGHD. Breech delivery was recorded in up to 26% of patients in all seven groups. Surprisingly, only 1 out of 23 patients with an ectopic posterior pituitary was born by breech delivery, suggesting that ectopia of the posterior lobe is not necessarily related to breech delivery. CONCLUSION: PHT is significantly correlated with GH secretion in several types of short stature. Patients with ectopic posterior pituitary, missing stalk and hypoplastic anterior pituitary either suffer from SIGHD or MPHD, and this anatomical defect is not necessarily related to breech delivery.

Adolescent↗
PubMed1997

The importance of pial blood supply to the development of peritumoral brain edema in meningiomas.

In a retrospective analysis, the authors studied the pial and dural blood supplies in 74 intracranial meningiomas and quantified their associated peritumoral brain edema (PTBE). The extent and localization of pial blush in relation to the total tumor volume were determined angiographically. The amount of edema and tumor size were calculated using computerized tomography. The edema-tumor volume ratio was defined as Edema Index (EI). There were 49 meningiomas with PTBE; of those tumors, 46 were supplied by pial vessels, and three were supplied exclusively by dural vessels. Tumors without PTBE showed no pial blush. The mean EI in meningiomas with pial blush was significantly larger (EI = 3) than in meningiomas without pial supply (EI = 1.1; p < 0.0001). Meningiomas with a smaller pial supply than dural supply had a significantly smaller mean EI than tumors with a pial supply equal to or greater than the dural supply (EI = 2.9 vs. EI = 3.7; p < 0.015). In 69.9% of cases with pial blood supply, major portions of the edema were located adjacent to the tumor region supplied by pial vessels. Edema index differences among tumors of different subgroups, as defined by size or histology, were significantly related to the pial supply in each subset. Thus, pial blood supply may be associated with the development of PTBE in meningiomas.

Adult↗
PubMed1996

Extended long-term culture reveals a highly quiescent and primitive human hematopoietic progenitor population.

Long-term culture-initiating cells (LTC-IC) are hematopoietic progenitors able to generate colony-forming unit-cells (CFU) after 5 to 8 weeks (35 to 60 days) of culture on bone marrow (BM) stroma and represent the most primitive progenitors currently detectable in vitro. We have recently reported that long-term cultures initiated with CD34+CD38- cells from BM or cord blood are able to continue generating CFU for at least 100 days, ie, beyond the standard LTC-IC period. In this report, single-cell cultures from cord blood and retroviral marking of cord blood and BM were used to study whether the subpopulation of CD34+CD38- cells able to generate CFU beyond 60 days ("extended long-term culture-initiating cells" or ELTC-IC) are functionally distinct from LTC-IC in terms of timing of initial clonal proliferation and generative capacity. All cord blood LTC-IC formed clones of greater than 50 cells by day 30. In contrast, cord blood ELTC-IC proliferated later in culture, 50% forming clones after day 30. Although efficient retroviral marking of LTC-IC was seen (25% to 45%), marking of ELTC-IC was inefficient (< 1%), consistent with a more quiescent progenitor population. There was a positive correlation between time of clonal proliferation and generative capacity. ELTC-IC generated threefold to fourfold more progeny than did LTC-IC (P < .002). These studies show that there is a functional hierarchy of progenitors in long-term culture which correlates with their level of quiescence. By extending the LTC-IC assay, a more primitive progenitor may be studied that may be functionally closer to the human long-term repopulation stem cell in vivo.

ADP-ribosyl Cyclase↗
PubMed1996

Mouse T cell membrane proteins Rt6-1 and Rt6-2 are arginine/protein mono(ADPribosyl)transferases and share secondary structure motifs with ADP-ribosylating bacterial toxins.

Mono ADP-ribosylation is a posttranslational protein modification that has been implicated in the regulation of key biological functions in bacteria as well as in animals. Recently, the first cDNAs for eucaryotic mono(ADPribosyl)transferases were cloned and found to exhibit significant sequence similarity only to one other known protein, the T cell differentiation antigen Rt6. In this paper we describe secondary structure analyses of Rt6 and related proteins and show conserved structure motifs and amino acid residues consistent with a common ancestry of these eucaryotic proteins and bacterial ADP-ribosyltransferases. Moreover, we have expressed soluble mouse Rt6-1 and Rt6-2 gene products in which C-terminal tags (FLAG-His6) replace the native glycosylphosphatidylinositol anchor signal sequences. Purified recombinant Rt6-2, but not Rt6-1, shows NAD+ glycohydrolase activity, which is inhibited by the arginine analogue agmatine. Immunoprecipitation of recombinant Rt6-1 and Rt6-2 with anti-FLAG M2 antibody followed by incubation with [32P]NAD+ leads to rapid and covalent incorporation of radioactivity into the light chain of the M2 antibody. The bound label is resistant to treatment with HgCl2 but sensitive to NH2OH, characteristic of arginine-linked ADP-ribosylation. These results demonstrate that Rt6-1 and RT6-2 possess the enzymatic activities typical for NAD+-dependent arginine/protein mono(ADPribosyl)transferases (EC 2.4.2.31). They are the first such enzymes to be molecularly characterized in the immune system.

ADP Ribose Transferases↗