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Biomedical subjects

H Geiger

Publications and source records attributed to H Geiger.

At least 19 recordsLinked to original sources
PubMed2006

Epstein-barr virus-associated posttransplant lymphoproliferative disorder of donor origin after simultaneous pancreas-kidney transplantation limited to pancreas allograft: A case report.

A 45-year-old man was admitted with fever and elevated pancreas enzymes 6 months after simultaneous pancreas-kidney transplantation (SPKT). Function of the allografts was normal. Bacterial and fungal infections were excluded, while Epstein-Barr virus (EBV)-polymerase chain reaction (PCR) was positive. However, screening for EBV-associated lymphoma was negative. EBV infection did not respond to antiviral therapy. After an 18F-Fluorodeoxyglucose positron emission tomography positive signal and an abnormal computed tomography scan of the pancreas transplant, a biopsy revealed a diffuse large monomorphic B-cell lymphoma, which was confined to the grafted organ. Its origin was assigned to the donor by microsatellite analysis. Reduction of immunosuppression and immunotherapy with rituximab was unsuccessful. After 10 weeks, the patient developed an acute hemolytic uremic syndrome which required explantation of the allografts. Subsequent to the intervention, fever disappeared, EBV DNA became undetectable and lymphoma screening remained negative. In posttransplant lymphoproliferative disorder of donor origin after SPKT, transplantectomy may be a curative therapy.

Adult↗
PubMed2006

Evaluation of type 1 diabetics for simultaneous pancreas-kidney transplantation with regard to cardiovascular risk.

The main cause of death for diabetic patients and patients on dialysis is coronary artery disease (CAD). The most common cause of graft loss following simultaneous pancreas and kidney transplantation (SPK) is death with a functioning graft due to CAD. Therefore, careful pretransplantation evaluation of CAD is mandatory. In our series, every patient undergoes a noninvasive cardiac function test like dobutamine stress echocardiography (DSE) or myocardial thallium scintigraphy using adenosine to induce medical stress. Thirty patients were evaluated for SPK: 15 patients with myocardial scintigraphy and 8 with DSE. Seven investigations showed pathological findings and we performed coronary angiograms, none of which showed coronary artery stenosis. Seven primary coronary angiograms were performed: four due to a history of CAD and three as a primary diagnostic. Following SPK one patient died at 21 days after transplantation due to myocardial infarction. He had a history of CAD with angioplasty and stent implantation. Noninvasive cardiac function tests like DSE or myocardial scintigraphy are reliable methods to evaluate CAD in patients with diabetic nephropathy awaiting SPK. In case of a suspicious finding or a history of CAD, a coronary angiogram should be performed to assess the need for revascularization. Following this algorithm we may further reduce the mortality of SPK.

Adult↗
PubMed2006

C-reactive protein induced activation of MAP-K and RANTES in human renal distal tubular epithelial cells in vitro.

AIMS: C-reactive protein (CRP) is a component of the acute-phase reaction to inflammation, severe tissue injury, and infection. Investigations have shown that CRP concentration is highly increased in the urine during acute renal graft dysfunction and, therefore, may affect tubular cell metabolism. Nevertheless, no data about the effects of CRP on human renal tubular epithelial cells are available. METHODS: Human renal distal tubular cells (DTC) were isolated immunomagnetically and cultured. Cells were stimulated with affinity chromatography pure native CRP from human ascites (10 - 0.001 microg/ml). Phosphorylation of MAP-K was assessed by Westernblot analysis. Release of RANTES and interleukin-6 was evaluated with an enzyme immunoassay. Cytotoxic effects of CRP were determined by a commercially available Live/Dead assay and MTT assay. Effects on cell proliferation were analyzed by a fluorimetric assay. RESULTS: Westernblot analysis clearly showed that CRP activates the MAP-K pathway of DTC. CRP upregulated RANTES expression of DTC in a significant and dose-dependent manner. CRP (10 microg/ml) induced a 12.3-fold upregulation, CRP 1 or 0.1 microg/ml induced a 6.3-/2.8-fold RANTES upregulation, respectively. Interleukin-6 synthesis was not influenced. Cytotoxic, proliferative or apoptotic effects were not observed at the concentrations used. CONCLUSIONS: We demonstrated an activating effect of CRP on DTC in vitro. In vivo, this effect of CRP might be part of the immune activation cascade during episodes of renal graft rejection or bacterial infections.

C-Reactive Protein↗
PubMed2005

Coeliac disease in children with Type 1 diabetes mellitus: the effect of the gluten-free diet.

PATIENTS AND METHODS: We assessed the frequency of coeliac disease in 281 children with Type 1 diabetes and the effect of gluten-free diet (GFD) in newly diagnosed cases. Serological screening was performed using anti-gliadin and anti-endomysium antibodies. Data were obtained about clinical symptoms, height and weight-for-height. RESULTS: A small intestinal biopsy was recommended to 18 patients (6.4%) with positive serological results and 12 children agreed. Nine of them had coeliac disease. Three out of nine coeliac children complained about gastrointestinal symptoms. On a GFD, the symptoms disappeared in two patients. Iron-deficiency anaemia was present in four subjects and disappeared in the three patients who accepted the GFD. In three patients (33%), coeliac disease was asymptomatic. Height and weight-for-height were in the normal range for all patients. For well-complying patients, there was a significant increase in height standard deviation at diagnosis and on follow-up (-0.28 vs. +0.35) (P = 0.03). Changes in weight-for-height were not significant (-4.0% vs. +1.4%) (P = 0.28). There was a trend to an improvement in HbA(1c) (8.0 vs. 7.3%) (P = 0.05). CONCLUSIONS: Serological screening is effective. There is a therapeutic benefit for some screening-detected patients, but confirmatory studies are needed.

Adolescent↗
PubMed2005

Enhanced expression of group IIA secreted phospholipase A2 by elevated glucose levels in cytokine-stimulated rat mesangial cells and in kidneys of diabetic rats.

BACKGROUND: Group IIA secreted phospholipase A2 (sPLA2-IIA) has been implicated in various inflammatory processes including the kidney. Previously it has been shown that potent proinflammatory cytokines such as interleukin 1beta (IL-1beta) increase sPLA2-IIA expression and secretion in rat mesangial cells. AIM: The present study examines the effects of glucose on sPLA2-IIA regulation in interleukin-1beta (IL-1beta) treated mesangial cell cultures and in diabetic kidneys of Sprague-Dawley rats. MATERIALS AND METHODS: Rat mesangial cells were grown either in low glucose (5.55 mM D-Glucose) or high glucose (25 mM) conditions followed by assessment of sPLA2-IIA transcription, expression and secretion after 24 h. The model of streptozotocin induced diabetes mellitus in Sprague-Dawley rats was used for the in vivo experiments. Diabetic kidneys where examined for sPLA2-IIA-mRNA and -protein expression as well as IL-1beta-levels at 2, 4 and 6 weeks after induction of diabetes mellitus. RESULTS: Increased concentration of glucose had a weak, but significant stimulatory effect on sPLA2-IIA expression, which was markedly up-regulated (2-3-fold) in IL-1beta treated mesangial cells compared to the levels obtained in low glucose medium. Concerning the underlying mechanism, we found that high concentration of glucose increased the activity of the rat sPLA2-IIA-promoter, whereas mRNA stability was not affected. Furthermore, the in vivo experiments revealed a marked up-regulation of sPLA2-IIA mRNA and protein in the diabetic rat kidneys 2 - 4 weeks after induction. Since the strong up-regulation of sPLA2-IIA in vitro under high glucose conditions occurred mainly in presence of cytokine, we measured the levels of IL-1beta in diabetic kidneys by ELISA. We detected rat IL-1beta only in diabetic, but not in control rat kidneys. CONCLUSIONS: The changes of sPLA2-IIA expression under increased glucose concentrations as well as in diabetic rat kidneys suggest a function of this enzyme as an acute phase protein providing lipid autacoids that may contribute to early changes in the course of diabetic nephropathy.

Analysis of Variance↗
PubMed2004

gp91phox-containing NADPH oxidase mediates endothelial dysfunction in renovascular hypertension.

BACKGROUND: Isoforms of the NADPH oxidase contribute to vascular superoxide anion (*O2-) formation and limit NO bioavailability. We hypothesized that the endothelial gp91phox-containing NADPH oxidase is predominant in generating the O2- to scavenge endothelial NO and thus is responsible for the development of endothelial dysfunction. METHODS AND RESULTS: Endothelial dysfunction was studied in aortic rings from wild-type (WT) and gp91phox-knockout (gp91phox-/-) mice with and without renovascular hypertension induced by renal artery clipping (2K1C). Hypertension induced by 2K1C was more severe in WT than in gp91phox-/- mice (158+/-2 versus 149+/-2 mm Hg; P<0.05). Endothelium-dependent relaxation to acetylcholine (ACh) was attenuated in rings from clipped WT but not from clipped gp91phox-/- mice. The reactive oxygen species (ROS) scavenger Tiron, PEG-superoxide dismutase, and the NADPH oxidase inhibitory peptide gp91ds-tat enhanced ACh-induced relaxation in aortae of clipped WT mice. Inhibition of protein kinase C, Rac, and the epidermal growth factor receptor kinase, elements involved in the activation of the NADPH oxidase, restored normal endothelium-dependent relaxation in vessels from clipped WT mice but had no effect on relaxations in those from gp91phox-/- mice. Relaxations to exogenous NO were attenuated in vessels from clipped WT but not clipped gp91phox-/- mice. After removal of the endothelium or treatment with PEG-superoxide dismutase, NO-induced relaxations were identical in vessels from clipped and sham-operated WT and gp91phox mice. CONCLUSIONS: These data indicate that the formation of O2- by the endothelial gp91phox-containing NADPH oxidase accounts for the reduced NO bioavailability in the 2K1C model and contributes to the development of renovascular hypertension and endothelial dysfunction.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed2002

Expression of osteopontin (Eta-1) in Crohn disease of the terminal ileum.

BACKGROUND: The causes of Crohn disease (CD) are still regarded as unknown, but impaired mucosal immunoregulation with activation of T-helper-1 (Th-1) cytokine responses is probably involved and may contribute to the morphological changes. We investigated a possible role of osteopontin (Opn) in the pathogenesis of CD. This glycoprotein has been suggested to be involved in the generation of Th-1-type immune responses; moreover, it carries anti-inflammatory activities. METHODS: Ileal samples from CD patients--both actively inflamed and inactive areas as well as unaffected intestinal specimens from controls (normal ileum)--were investigated by Western blot analysis, immunohistochemistry and in situ hybridization. RESULTS: In normal gut, Opn was found to be regularly expressed by plasma cells (CD 38) and a subset of lamina propria mononuclear cells (MNC) as well as by intestinal epithelial cells (IEC). In active CD, immunohistochemistry and in situ hybridization analysis revealed a loss of Opn expression by IEC adjacent to ulcerative lesions, whereas especially plasma cells (CD 38) in the vicinity of such lesions were found to express the molecule. In addition, a slight overexpression of Opn protein was found in metaplastic crypts. However, quantitative analysis of total Opn protein in the ileal mucosa of CD patients did not reveal any difference vis-à-vis control tissues. CONCLUSIONS: The constitutive expression of Opn in normal gut indicates that it is involved in intestinal immune homeostasis. Downregulation of Opn expression in IEC might favour the disintegration of the epithelial barrier. The expression of Opn in lamina propria plasma cells could contribute to disease chronification, probably by affecting cell survival.

Adult↗
PubMed2001

Direct measurement of OH radicals from ozonolysis of selected alkenes: a EUPHORE simulation chamber study.

Reactions of ozone with alkenes can be a significant source of hydroxyl radicals in the atmosphere. In the present paper, the formation of OH radicals in the ozonolysis of selected alkenes under atmospheric conditions was directly observed. The experiments were carried out in the European photoreactor EUPHORE (Valencia, Spain). OH radicals were quantitatively detected by means of laser-induced fluorescence (LIF) using a new analytical instrument, which has been constructed on the basis of an existing setup already established in field studies. The OH radicals observed resulted directly from the reaction of ozone with the corresponding alkene. There was no indication that OH radicals were produced in the system by secondary processes. The experimentally observed concentration-time profiles of OH and ozone were excellently described by chemical modeling using explicit reaction mechanisms. The following OH yields were derived: 2,3-dimethyl-2-butene: (1.00 +/- 0.25); 2-methyl-2-butene: (0.89 +/- 0.22); trans-2-butene: (0.75 +/- 0.19); alpha-pinene: (0.91 +/- 0.23). In addition, the experiments carried out were modeled using the Regional Atmospheric Chemistry Mechanism (RACM), an established condensed chemical model applied in tropospheric chemistry. For 2,3-dimethyl-2-butene, 2-methyl-2-butene, and trans-2-butene the calculated concentration-time profiles of OH and ozone are in quite good agreement with the experimental data. However, in the case of alpha-pinene, the model fails for the simulation of OH due to the high grade of mechanism condensation, which results in a poor characterization of the primary reaction products.

Air Pollutants↗
PubMed2001

Long-term results after microvascular decompression in essential hypertension.

BACKGROUND AND PURPOSE: In 1998, 8 patients with severe, intractable arterial hypertension and MR tomography-demonstrated neurovascular contact of a looping artery at the root entry zone of cranial nerves IX and X, causing neurovascular compression, underwent neurosurgical decompression. The short-term results showed a normalization of blood pressure with a markedly reduced antihypertensive drug regimen in 7 patients. To determine the longer-term outcome concerning blood pressure and secondary organ damage after neurovascular decompression, we studied these 8 operated patients prospectively for a mean follow-up of 3.5 years after surgical intervention. METHODS: Eight hypertensive patients who had undergone microsurgical decompression were monitored every 6 months after surgery to assess blood pressure (by 24-hour ambulatory pressure readings) and the need for antihypertensive medication. To evaluate secondary organ damage, echocardiographic assessment of left ventricular hypertrophy, fundoscopic assessment of hypertensive lesions, and analysis of renal function and proteinuria were done. RESULTS: Three of the 8 operated patients remained normotensive in the long-term period with decreased antihypertensive medication. Two patients required gradual increases of antihypertensive medication after the first postoperative year, after which arterial blood pressure levels were 10% to 15% lower than preoperative levels. Three patients suffered serious cardiovascular and renal complications, with the incidence of lethal intracerebral hemorrhage in 1 patient and end-stage renal disease in 2 patients, of whom 1 experienced sudden cardiac death. CONCLUSIONS: The long-term results verify that microsurgical decompression is a successful alternative therapy in a certain subgroup of patients with arterial hypertension due to neurovascular compression. However, the relevance of the looping artery in the other cases, who did not improve, is not clear. Prospective studies to elucidate the pathophysiological role of neurovascular abnormalities and arterial hypertension are needed.

Adult↗
PubMed2001

Age- and stage-specific regulation patterns in the hematopoietic stem cell hierarchy.

The molecular mechanisms that regulate self-renewal and differentiation of very primitive hematopoietic stem and progenitor cells in vivo are still poorly understood. Despite the clinical relevance, even less is known about the mechanisms that regulate these cells in old animals. In a forward genetic approach, using quantitative trait linkage analysis in the mouse BXD recombinant inbred set, this study identified loci that regulate the genetic variation in the size of primitive hematopoietic cell compartments of young and old C57BL6 and DBA/2 animals. Linked loci were confirmed through the generation and analysis of congenic animals. In addition, a comparative linkage analysis revealed that the number of primitive hematopoietic cells and hematopoietic stem cells are regulated in a stage-specific and an age-specific manner.

Aging↗
PubMed2001

Multiple adenomas and hepatocellular carcinoma in a renal transplant patient with glycogen storage disease type 1a (von Gierke disease).

We report on a 42-year-old female patient with glycogen storage disease type 1a (von Gierke disease, GSD 1a) who developed hepatic adenomas and finally a hepatocellular carcinoma 10 years after renal transplantation. The tumor was resected; however, the patient died 6 months later as a result of fulminant carcinoma recurrence. In patients who have GSD 1a with terminal renal failure, combined liver and kidney transplantation may be considered at an early stage of the disease.

Adenoma↗
PubMed2001

Angiotensin II infusion increases plasma erythropoietin levels via an angiotensin II type 1 receptor-dependent pathway.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) have been shown to lower hematocrit and erythropoietin (EPO), but a direct link between angiotensin II (Ang II) and EPO in humans has not been shown. METHODS: Placebo or Ang II was infused for six hours in nine healthy male volunteers with and without blockade of the Ang II subtype 1 receptor (AT1R). EPO concentrations were measured 3, 6, 12, and 24 hours after the start of the infusion. RESULTS: Ang II raised the mean arterial pressure by about 20 mm Hg. Consistent with the known diurnal variation, EPO levels rose significantly (P < or = 0.02) during the day in all groups. During Ang II infusion, EPO levels rose to significantly higher levels after 6 and 12 hours compared with placebo [9.9 +/- 3.5 vs. 7.2 +/- 3.1 mU/mL (3 h, P = NS); 16.9 +/- 4.5 vs. 8.8 +/- 3.7 mU/mL (6 h, P = 0.01); 17.0 +/- 8.6 vs. 11.1 +/- 4.7 mU/mL (12 h, P = 0.01)] and returned to baseline after 24 hours (7.9 +/- 3.8 vs. 10.6 +/- 8.6 mU/mL, P = NS). With AT1R blockade, blood pressure remained normal during Ang II infusion, and EPO levels were never significantly different from placebo [6.8 +/- 4.8, 10.5 +/- 5.6, 13.1 +/- 9.0, and 12.4 +/- 10.1 mU/mL at 3, 6, 12, and 24 h after infusion, respectively, P = NS]. CONCLUSIONS: Ang II increases EPO levels in humans. This increase requires the participation of AT1R.

Adult↗
PubMed2001

Expression of multidrug resistance P-glycoprotein in kidney allografts from cyclosporine A-treated patients.

BACKGROUND: The multidrug resistance (MDR) gene product P-glycoprotein (P-gp) is a transmembrane efflux pump for hydrophobic, potentially toxic compounds, including the immunosuppressant cyclosporine A (CsA). We have previously shown that CsA increases P-gp expression in proximal tubule and endothelial cells in vitro. The aim of the present study was to investigate the in vivo relevance of these observations in renal allograft biopsies from CsA-treated patients. METHODS: P-gp expression was determined by immunohistochemistry of paraffin sections using two different monoclonal antibodies (UIC2 and MRK16). Biopsies were taken from CsA-treated renal transplant patients with different histopathological diagnoses (N = 79) and were compared with biopsies from normal human kidneys (N = 13) or with allograft biopsies from patients under a CsA-free immunosuppression (N = 15). Moreover, biopsies from 10 donor kidneys before implantation and during rejection episodes ("zero biopsies") were investigated. RESULTS: P-gp expression in biopsies with acute tubular necrosis (ATN; N = 10) after CsA treatment was significantly higher in arterial endothelia, proximal tubules, and epithelial cells of Bowman's capsule (BC), whereas P-gp was sparsely induced in CsA nephrotoxicity (N = 19) compared with controls. Acute cellular (N = 30) and vascular rejection (N = 10) or chronic allograft nephropathy (N = 10) after CsA was associated with strong P-gp expression in infiltrating leukocytes and increased P-gp expression in arterial endothelia, proximal tubules, and BC. In contrast, biopsies of patients treated with a CsA-free immunosuppression regimen did not show increases in P-gp expression compared with controls. Zero biopsies showed a weak, homogeneous, nonpolarized expression of P-gp in tubules and an increased expression of P-gp after CsA therapy in the brush border, arterial endothelia, and BC. CONCLUSIONS: CsA treatment was associated with increased P-gp expression in parenchymal cells of kidney transplants with ATN, acute or chronic transplant rejection, but P-gp was not increased in patients with CsA nephrotoxicity. This indicates that CsA induces its own detoxification by P-gp and that inadequate up-regulation of P-gp in renal parenchymal cells contributes to CsA nephrotoxicity. Increased expression of P-gp in infiltrating leukocytes correlated with the severity of allograft rejection, suggesting that P-gp may decrease the immunosuppressive efficacy of CsA. Thus, individual differences in the P-gp induction response of CsA-exposed renal parenchymal cells and/or infiltrating leukocytes may predispose to either CsA nephrotoxicity or rejection, respectively.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Effects of continuous haemofiltration vs intermittent haemodialysis on systemic haemodynamics and splanchnic regional perfusion in septic shock patients: a prospective, randomized clinical trial.

BACKGROUND: Parameters of splanchnic regional perfusion, like intramucosal pH (pHi) and pCO(2) (pCO(2)i), may predict outcome in septic shock patients. Continuous venovenous haemofiltration (CVVH) has been considered beneficial in haemodynamically unstable septic shock patients. In a prospective, randomized, clinical study, we investigated whether CVVH, in comparison to intermittent haemodialysis (IHD), is able to improve splanchnic regional perfusion in critically ill patients. METHODS: Thirty septic shock patients with acute renal failure were randomized to either CVVH (n=20) or IHD (n=10) groups for renal replacement therapy. Patient characteristics at baseline were not different in terms of severity of illness (APACHE II scores), haemodynamics, and pHi/pCO(2)i values. Systemic haemodynamics, oxygen transport variables, and splanchnic regional perfusion parameters were measured at 0.5, 2, 4 and 24 h after initiation of renal replacement therapy. There were no major changes in vasopressor support throughout the 24-h study period. RESULTS: In contrast to IHD, CVVH caused a decrease in heart rate (-3+/-11 vs +9+/-8/min, P<0.01) and an increase in systolic blood pressure (+12+/-1 vs -5+/-17 mmHg, P<0.05) after 2 h. After 24 h, increased systemic vascular resistance was found in the CVVH group in comparison with the IHD group (+312+/-755 vs -29+/-89 dyne/cm(5), P<0.05) and was accompanied by a decrease in cardiac output (-1.54+/-1.4 vs -0.25+/-0.9 l/min, P<0.01). However pHi values remained constant throughout the 24-h study period in both groups and were not different between the groups (CVVH 7.19+/-0.1 vs IHD 7.19+/-0.1, n.s.) as did the pCO(2)i values (CVVH +7+/-17 vs IHD 0+/-15 mmHg, n.s.) and pCO(2) gap values (CVVH +6+/-15 vs IHD +5+/-12 mmHg, n.s.). CONCLUSIONS: Despite different changes of systemic haemodynamics between CVVH and IHD, CVVH did not improve parameters of splanchnic regional perfusion like pHi, pCO(2)i or pCO(2) gap in septic shock patients.

Acid-Base Equilibrium↗
PubMed2000

Induction of RANTES, HLA-DR, and intercellular adhesion molecule-1 on highly purified distal tubular cells from human kidney.

BACKGROUND: Expression of proinflammatory molecules by tubular epithelial cells plays an important role in renal allograft rejection and inflammatory kidney diseases. Different studies from patients with acute rejection point to the involvement of distal tubular segments. At present no in vitro system for the human distal tubule is established. METHODS: Human distal tubular cells were isolated immunomagnetically. Cultured cells were stimulated with cytokines (interferon-gamma, tumor necrosis factor-alpha, interleukin-1beta, or a cytokine mix). Secretion of RANTES (regulated upon activation, normal T-cell expressed and secreted) was evaluated with an enzyme-linked immunoassay. Expression of HLA-DR and intercellular adhesion molecule (ICAM)-1 was assessed by flow cytometric analysis and immunofluorescence studies. RESULTS: Our data clearly indicate that distal tubular cells express RANTES, HLA-DR, and ICAM-1 in response to a mixture of specific cytokines. Dexamethasone inhibited the induced expression of RANTES and HLA-DR significantly, but not that of ICAM-1. CONCLUSIONS: We demonstrate an appropriate in vitro system for the human distal tubule. The present study proves the involvement of the distal tubular segment during inflammatory kidney diseases.

Cells, Cultured↗