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S Wagner

Publications and source records attributed to S Wagner.

At least 109 records · Page 6Linked to original sources

[Surgical treatment of injuries of the thoracolumbar transition. 2: Operation and roentgenologic findings].

The authors report on a prospective multicenter study with regard to the operative treatment of acute fractures and dislocations of the thoracolumbar spine (T10-L2). The study should analyze the operative methods currently used and determine the results in a large representative collective. This investigation was realized by the working group "spine" of the German Trauma Society. Between September 1994 and December 1996, 682 patients treated in 18 different traumatology centers in Germany and Austria were included. Part 2 describes the details of the operative methods and measured data in standard radiographs and CT scans of the spine. Of the patients, 448 (65.7%) were treated with posterior, 197 (28.9%) with combined posterior-anterior, and 37 (5.4%) with anterior surgery alone. In 72% of the posterior operations, the instrumentation was combined with transpedicular bone grafting. The combined procedures were performed as one-stage operations in 38.1%. A significantly longer average operative time (4:14 h) was noted in combined cases compared to the posterior (P < 0.001) or anterior (P < 0.05) procedures. The average blood loss was comparable in both posterior and anterior groups. During combined surgery the blood loss was significantly higher (P < 0.001; P < 0.05). The longest intraoperative fluoroscopy time (average 4:08 min) was noticed in posterior surgery with a significant difference compared to the anterior group. In almost every case a "Fixateur interne" (eight different types of internal fixators) was used for posterior stabilization. For anterior instrumentation, fixed angle implants (plate or rod systems) were mainly preferred (n = 22) compared to non-fixed angle plate systems (n = 12). A decompression of the spinal canal (indirect by reduction or direct by surgical means) was performed in 70.8% of the neurologically intact patients (Frankel/ASIA E) and in 82.6% of those with neurologic deficit (Frankel/ASIA grade A-D). An intraoperative myelography was added in 22% of all patients. The authors found a significant correlation between the amount of canal compromise in preoperative CT scans and the neurologic deficit in Frankel/ASIA grades. The wedge angle and sagittal index measured on lateral radiographs improved from -17.0 degrees and 0.63 (preoperative) to -6.3 degrees and 0.86 (postoperative). A significantly (P < 0.01) stronger deformity was noted preoperatively in the combined group compared to the posterior one. The segmental kyphosis angle improved by 11.3 degrees (8.8 degrees with inclusion of the two adjacent intervertebral disc spaces). A significantly better operative correction of the kyphotic deformity was found in the combined group. In 101 (14.8%) patients, intra- or postoperative complications were noticed, 41 (6.0%) required reoperation. There was no significant difference between the three treatment groups. Of the 2264 pedicle screws, 139 (6.1%) were found to be misplaced. This number included all screws, which were judged to be not placed in an optimal direction or location. In seven (1.0%) patients the false placement of screws was judged as a complication, four (0.6%) of them required revision. The multicenter study determines the actual incidence of thoracolumbar fractures and dislocations with associated injuries and describes the current standard of operative treatment. The efforts and prospects of different surgical methods could be demonstrated considering certain related risks. The follow-up of the population is still in progress and the late results remain for future publication.

Adolescent↗

Competition between n-alkane-assimilating yeasts and bacteria during colonization of sandy soil microcosms.

An n-alkane-assimilating strain of Candida tropicalis was selected in sandy soil inoculated with microorganisms from contaminated sites. Competition experiments with n-alkane utilizers from different strain collections confirmed that yeasts overgrow bacteria in sandy soil. Acidification of the soil is one of the colonization factors useful for the yeasts. It can be counteracted by addition of bentonite, a clay mineral with high ion exchange capacity, but not, however, by kaolin. Strains of different yeast species showed different levels of competitiveness. Strains of Arxula adeninivorans, Candida maltosa, and Yarrowia lipolytica overgrew strains of C. tropicalis, C. shehatae or Pichia stipitis. Two strains of C. maltosa and Y. lipolytica coexisted during several serial transfers under microcosm conditions.

Alkanes↗

Role of the intra-arterial calcium stimulation test in the preoperative localization of insulinomas.

The aim of this study was determination of the significance of the arterial stimulation test with venous sampling (ASVS) in the preoperative localization of insulinoma. Eleven patients with endogenous hyperinsulinism underwent preoperative transabdominal US, spiral computer tomography (spiral CT), MRI, endoscopic ultrasound (EUS) as well as angiography (DSA) combined with ASVS. The results were compared with intraoperative findings, intraoperative ultrasound (IOUS) and histopathology. There were no complications related to the ASVS test. In 11 patients the tumor could be localized with the various modalities as follows: US 1 of 11 (9%), MRI 3 of 10 (30%), spiral CT 4 of 11 (36%), EUS 5 of 10 (50%), DSA 8 of 11 (73%), and ASVS 10 of 11 (91%). In 2 patients the tumors were intraoperatively neither palpable nor detectable by IOUS, and consequently the intraoperative management was governed by information provided by DSA combined with the ASVS test. Ten patients had solitary benign insulinomas and 1 patient with multiple endocrine neoplasia I had two tumors adjacent to each other in the pancreatic tail. Arterial stimulation test with venous sampling was the most sensitive preoperative test for regionalizing the insulinoma in our set of patients. It can be performed safely in the course of a regular DSA examination and may affect intra-operative management in patients in whom the tumors are not detectable by palpation or IOUS.

Adolescent↗

Alteration of c-mpl-mediated signal transduction in CD34(+) cells from patients with myelodysplastic syndromes.

OBJECTIVE: Megakaryocytic differentiation is frequently defective in patients with myelodysplastic syndromes (MDS). As underlying mechanisms, deregulated thrombopoietin receptor (c-mpl)-mediated signaling pathways have been suggested. This study therefore examined whether the impaired signaling in MDS and AML cells includes alterations of c-mpl itself or postsignaling events. METHODS: Bone marrow-derived CD34(+) cells from healthy donors, patients with MDS (RA, RAEB-T), and patients with AML after MDS were isolated by MACS. Expression of c-mpl cDNA was studied by RT-PCR. Thrombopoietin dependent activation of STAT proteins and MAP Kinase p42(erk-2)/44(erk-1) was analyzed by Western blot. RESULTS: Both splicing isoforms of c-mpl (c-mpl-p and c-mpl-k) were expressed in all of the CD34(+) cells examined. Analysis of the c-mpl cDNA revealed no sequence abnormality. We show c-mpl dependent activation of the transcription factors STAT3 and STAT5 as well as MAP Kinase p42(erk-2)/44(erk-1) in CD34(+) cells from healthy individuals. Cells derived from RA patients revealed low basal levels of phosphorylated STAT3 and STAT5 molecules. This phosphorylation was enhanced by stimulation with recombinant thrombopoietin (PEG-rHuMGDF). STAT1 failed to be activated by PEG-rHuMGDF in CD34(+) cells from healthy donors as well as from patients with MDS. In RAEB-T and AML M7 the constitutive expression levels of STAT1, 3, 5, and MAPK were markedly upregulated, resulting in a strong activation of STAT3 and 5 by PEG-rHuMGDF. Despite its high expression, the level of MAPK phosphorylation was not increased in RA or RAEB-T compared to the normal control, and was completely undetectable in AML M7. CONCLUSION: These results suggest that the defective megakaryopoiesis in MDS is not caused by a lack of c-mpl and that STAT3 and STAT5 may contribute to the malignant phenotype of the leukemic cells.

Anemia, Refractory↗

Helicobacter pylori reduces intracellular glutathione in gastric epithelial cells.

Helicobacter pylori infection has been associated with stimulation of gastric mucosal reactive oxygen species (ROS) production, and it was postulated that ROS production is due to neutrophil infiltration and activation. The aim of this study was to investigate the direct effect of H. pylori on ROS formation in gastric epithelial cells in vitro. The human gastric cancer cell line HM02 was incubated with H. pylori for 24 hr, and the effects on cell number and the intracellular radical scavenger reduced glutathione (GSH) were assessed. H. pylori caused a concentration-dependent reduction of cellular GSH concentrations over a broad bacteria-to-cell ratio (1.4-42) in the absence of cell necrosis. The radical scavengers MnTBAP (a cell permeable superoxide dismutase) and ebselen provided protection against H. pylori-induced decrease in cellular GSH concentrations. We conclude that H. pylori directly decreases cellular GSH concentrations in gastric epithelial cells. We suggest that this effect is caused by the release of ROS by H. pylori.

Azoles↗

Pharmacokinetics of SDZ RAD and cyclosporin including their metabolites in seven kidney graft patients after the first dose of SDZ RAD.

AIMS: The aim of the study was to investigate the pharmacokinetics and metabolism of the new immunosuppressant SDZ RAD during concomitant therapy with cyclosporin in stable renal transplant patients. Furthermore, we studied the influence of SDZ RAD on the pharmacokinetics of cyclosporin at steady state levels. METHODS: SDZ RAD was administered orally in different doses (0.25-15 mg day-1) to seven patients, who were on standard cyclosporin-based immunosuppression. The blood concentrations of both drugs including their main groups of metabolites were measured simultaneously by LC/electrospray-mass spectrometry. RESULTS: The mean area under the blood concentration-time curve to 12 h (AUC(0,12 h)) was 4244 +/- 1311 microg l-1 h for cyclosporin before SDZ RAD treatment and 4683 +/- 1174 microg l-1 h (P = 0.106) on the day of SDZ RAD treatment (95% CI for difference -126, 1003). On both study days Cmax, and tmax of cyclosporin were not significantly different. The metabolite pattern of cyclosporin did not change. The pharmacokinetic data of SDZ RAD dose-normalized to 1 mg SDZ RAD were as follows: AUC(0,24 h): 35.4 +/- 13.1 microg l-1 h, Cmax: 7.9 +/- 2.7 microg l-1 and tmax: 1.5 +/- 0.9 h. The metabolites of SDZ RAD found in blood were hydroxy-SDZ RAD, dihydroxy-SDZ RAD, demethyl-SDZ RAD, and a ring-opened form of SDZ RAD. CONCLUSIONS: A single dose of SDZ RAD did not influence significantly the pharmacokinetics of cyclosporin. The most important metabolite of SDZ RAD was the hydroxy-SDZ RAD, its AUC(0,24 h) being nearly half that of the parent compound SDZ RAD.

Administration, Oral↗

Hev b 9, an enolase and a new cross-reactive allergen from hevea latex and molds. Purification, characterization, cloning and expression.

Natural rubber latex allergy is an IgE-mediated disease that is caused by proteins that elute from commercial latex products. A complementary DNA (cDNA) coding for Hev b 9, an enolase (2-phospho-D-glycerate hydrolyase) and allergen from latex of the rubber tree Hevea brasiliensis, was amplified by PCR. The PCR primers were designed according to conserved regions of enolases from plants. The obtained cDNA amplification product consisted of 1651 bp and encoded a protein of 445 amino-acid residues with a calculated molecular mass of 47.6 kDa. Sequence comparisons revealed high similarities of the Hevea latex enolase to mold enolases that have been identified as important allergens. In addition, the crucial amino-acid residues that participate in the formation of the catalytic site and the Mg2+ binding site of enolases were also conserved. Hevea latex enolase was produced as a recombinant protein in Escherichia coli with an N-terminal hexahistidyl tag, and purified by affinity chromatography. The yield amounted to 110 mg of purified Hev b 9 per litre of bacterial culture. The recombinant allergen bound IgE from latex, as well as mold-allergic patients, in immunoblot and ELISA experiments. The natural enolase was isolated from Hevea latex by (NH4)2SO4 precipitation and ion exchange chromatography. The natural and the recombinant (r)Hev b 9 showed equivalent enzymatic activity. Patients' IgE-antibodies preincubated with rHev b 9 lost their ability to bind to natural (n) Hev b 9, indicating the identity of the B-cell epitopes on both molecules. Cross-reactivity with two enolases from Cladosporium herbarum and Alternaria alternata was determined by inhibition of IgE-binding to these enolases by rHev b 9. Therefore, enolases may represent another class of highly conserved enzymes with allergenic potentials.

Adult↗

Malignant peritoneal mesothelioma with mimicry of pseudomyxoma peritonei in a patient with a history of perforated sigmadiverticulitis.

We describe a 57-year-old man who presented with diffuse abdominal pain, abdominal enlargement, vomitus, dyspnea and a weight loss of 30 kg within 6 months. These acute symptoms were preceded by an episode of ascites and an acute sigmadiverticulitis 7 months ago. Ultrasonography and computed tomography were suggestive of pseudomyxoma peritonei. However, malignant mesothelioma peritonei was diagnosed by open surgery with biopsy for histological examination. Despite R-2-resection of the tumor and following open hyperthermic intraperitoneal chemotherapy with initial remarkable recovery the patient died 5 months after therapeutical intervention. Malignant peritoneal mesothelioma is an extremely rare tumor with great diagnostic and therapeutic difficulties. We report a case including diagnostical work up and the medical surgical therapy of this disease.

Biopsy↗

Protein kinase calpha targeting is regulated by temporal and spatial changes in intracellular free calcium concentration [Ca(2+)](i).

Protein kinase C (PKC) isoforms exert specific intracellular functions, but the different isoforms display little substrate specificity in vitro. Selective PKC isoform targeting may be a mechanism to achieve specificity. We used a green fluorescent fusion protein (GFP) to test the hypothesis that local changes in [Ca(2+)](i) regulate translocation of PKCalpha and that different modes of Ca(2+) and Ca(2+) release play a role in PKCalpha targeting. We constructed deletion mutants of PKCalpha to analyze the Ca(2+)-sensitive domains and their role in targeting. Confocal microscopy was used and [Ca(2+)](i) was measured by fluo-3. The fusion protein PKCalpha-GFP was expressed in vascular smooth muscle cells and showed a cytosolic distribution similar to the wild-type PKCalpha protein. The Ca(2+) ionophore ionomycin induced a speckled cytosolic PKCalpha-GFP distribution, followed by membrane translocation, while depolarization by KCl induced primarily membrane translocation. Selective voltage-operated Ca(2+) channel opening led to a localized accumulation of PKCalpha-GFP near the plasma membrane. Opening Ca(2+) stores with InsP(3), thapsigargin, or ryanodine induced a specific PKCalpha-GFP targeting to distinct intracellular areas. The G-protein-coupled receptor agonist thrombin induced a rapid translocation of the fusion protein to focal domains. The tyrosine kinase receptor agonist PDGF induced Ca(2+) influx and led to a linear PKCalpha-GFP membrane association. PKCalpha-GFP deletion mutants demonstrated that the C2 domain, but not the catalytic subunit, is necessary for Ca(2+)-induced PKCalpha targeting. Targeting was also abolished when the ATP binding site was deleted. We conclude that PKCalpha can rapidly be translocated to distinct intracellular or membrane domains by local increases in [Ca(2+)](i). The targeting mechanism is dependent on the C2 and ATP binding site of the enzyme. Localized [Ca(2+)](i) changes determine the spatial and temporal targeting of PKCalpha.

Adenosine Triphosphate↗

Superparamagnetic iron oxide-enhanced MRI of atherosclerotic plaques in Watanabe hereditable hyperlipidemic rabbits.

RATIONALE AND OBJECTIVES: Inflammatory atherosclerotic plaques are characterized by increased endothelial permeability and multiple macrophages. Blood-pool MRI contrast agents like superparamagnetic iron oxide (SPIO) have an affinity for the monocyte-macrophage system and thus, may label inflammatory plaques. The objective was to demonstrate SPIO uptake in plaques of atherosclerotic rabbits by MRI and histology. METHODS: Aortas of anesthetized Watanabe hereditable hyperlipidemic rabbits were studied with a moderately T2*-weighted gradient-echo sequence at 1.5 T. Four groups of five animals each were studied: (1) without ultrasmall SPIO (carboxydextran coating; particle size, 25 nm; estimated plasma half-life, 6 hours) or with imaging after intravenous injection of SPIO at a dose (micromol Fe/kg) and postcontrast time delay (hours) of 50/8 (2), 50/24 (3), or 200/48 (4). In vivo MRI was compared with corresponding ex vivo histological iron stains. RESULTS: Animals receiving 200 micromol Fe/kg demonstrated areas of focal signal loss clearly confined to the aortic wall on a mean of 24 +/- 9 (31% +/- 11%) of 76 +/- 5 images compared with 0 +/- 0 of 76 +/- 5 images in controls (P = 0.009). The number of images with this finding in groups 2 and 3 was not significantly different compared with controls. By microscopy, SPIO-iron was seen in the endothelial cells and subendothelial intimal macrophages of atherosclerosis-prone aortic wall segments. Atherosclerotic lesions demonstrating iron uptake also showed a high macrophage content. CONCLUSIONS: SPIO accumulates in aortic plaques of atherosclerotic rabbits, producing a characteristic MRI finding. As SPIO accumulates in plaques with increased endothelial permeability and a high macrophage content, two established features of plaque inflammation, it may have a potential for noninvasive assessment of inflammatory atherosclerotic plaques.

Animals↗

Apoptosis and intestinal barrier function.

The signal transduction pathways of the induction of apoptosis in the gastrointestinal tract have in part been discovered. However, almost nothing is known about the functional influence of apoptotic signals on intestinal barrier function. In this study the effect of camptothecin-induced apoptosis in HT-29/B6 monolayers and the influence of apoptosis on epithelial barrier function were characterized. We demonstrated that camptothecin causes a decrease of transepithelial resistance and an increase in fluxes of the paracellular marker [3H]mannitol. Camptothecin increased the apoptotic rate and the conductance of single-cell apoptosis as measured by the conductance scanning technique. We conclude that in our model of HT-29/B6 cells camptothecin is a potent inductor of apoptosis that causes significant barrier defects measured by the Ussing chamber technique and the conductance scanning technique. Based on these results we are able to investigate the effect of other cytokines--TGF-beta, for instance, and its role in apoptotic conditions.

Apoptosis↗

Levofloxacin pharmacokinetics and serum bactericidal activities against five enterobacterial species.

After oral administration of 500 mg of levofloxacin to 12 volunteers, we investigated the pharmacokinetics and serum bactericidal activities (SBAs) against five strains of members of the family Enterobacteriaceae. Pharmacokinetic data were as follows: maximum concentration in serum, 6.36 +/- 0.57 mg/liter; area under the concentration-time curve, 43.6 +/- 6.23 mg. h/liter; elimination half-life 4.23 +/- 0.87 h. SBAs were present for 24 h against Escherichia coli and Citrobacter freundii. The SBAs at 1, 12, and 24 h after administration against E. coli were 1:108, 1:29, and 1:7, respectively, and those against Citrobacter freundii were 1:74, 1:25, and 1:7, respectively. The SBAs were present for 12 h against the other three organisms tested. The SBAs against Serratia marcescens were 1:28 and 1:9 at 1 and 12 h, respectively; the SBAs against Klebsiella pneumoniae were 1:25 and 1:7 at 1 and 12 h, respectively; and the SBAs against Enterobacter cloacae were 1:24 and 1:10 at 1 and 12 h, respectively.

Adult↗

Role of vacA and cagA in Helicobacter pylori inhibition of mucin synthesis in gastric mucous cells.

The aim of this study was to investigate the effect of Helicobacter pylori on the function of gastric mucous cells. H. pylori (10(4) to 10(7) CFU/well) was incubated with the mucin-producing gastric cell line HM02 for 12 and 24 h. Mucin synthesis and secretion were determined by the incorporation of D-N-[acetyl-(14)C]glucosamine into intracellular and released high-molecular-weight glycoproteins. cagA-positive, cytotoxin-producing and non-cytotoxin-producing H. pylori strains impaired the incorporation of D-N-[acetyl-(14)C]glucosamine into intracellular glycoproteins. Significant inhibition of mucin synthesis was noted after 12 and 24 h of cocultivation with a bacterial load of >/=10(5) bacteria (bacterium/cell ratio = 0.25). The cagA-positive, cytotoxin-producing strains (HP64, HP57, and HP87) caused significantly stronger inhibition of intracellular mucin synthesis than the cagA-positive, non-cytotoxin-producing strains (HP05, HP83, and HP84). The cagA-negative, non-cytotoxin-producing strains (HP01, HP04, and HP85) did not affect intracellular mucin synthesis. The results indicate that H. pylori directly impairs mucin synthesis in gastric mucous cells and that cytotoxic cagA-positive strains cause more profound inhibition of mucin synthesis. We suggest that the increased inhibitory effect of cagA-positive, cytotoxin-producing strains on mucin synthesis can be considered one possible factor responsible for the increased risk of developing peptic ulceration with these H. pylori strains.

Acetylglucosamine↗

Expression of leptin and leptin receptor isoforms in the human stomach.

BACKGROUND: Leptin is an important regulator of food intake and energy expenditure. Initially it was thought to be expressed exclusively in and secreted by adipocytes. Recently, leptin expression was also noted in other tissues, including rat gastric mucosa. Information on leptin and leptin receptor expression in the human stomach is lacking. AIM: To investigate expression of leptin and its corresponding receptors in human gastric epithelial cells. METHODS: Fundic and antral gastric mucosal biopsies, primary cultures of human gastric epithelial cells, and the human gastric cancer cell line AGS were screened for expression of leptin and different leptin receptor isoform mRNA by reverse transcriptase-polymerase chain reaction. Immunohistochemistry was performed for localisation of leptin and leptin receptor proteins in gastric mucosa. RESULTS: mRNA of leptin and its four receptor isoforms (huOB-R, long receptor isoform; huB219.1-3, short receptor isoforms) was detected in gastric mucosal biopsies, cultured human gastric epithelial cells, and gastric cancer cells. Immunohistochemistry demonstrated that chief as well as parietal cells were reactive to leptin and leptin receptors. CONCLUSIONS: Leptin and leptin receptors are expressed in human gastric mucosa. These findings suggest a paracrine and/or autocrine effect of leptin on gastric epithelial cell function.

Biopsy↗

Uncommon metastasis of a glioblastoma multiforme in liver and spleen.

A case of a glioblastoma multiforme is presented. Craniotomy was performed with total resection of the right temporal tumor. Postoperatively, the patient received adjuvant radiotherapy, but 6 months after therapy he developed severe nausea and weight loss. Recurrence of an intracranial tumor in the right temporal region with nodules in the liver and spleen were detected by CT scan. Fine-needle biopsies of the liver confirmed the diagnosis of a glioblastoma metastasis with characteristic immunohistochemical staining for glial fibrillary acidic protein. This rare case of an intracerebral glioblastoma metastasizing to liver and spleen was managed by systemic chemotherapy.

Brain Neoplasms↗

New hypointense lesions on MRI in relapsing-remitting multiple sclerosis patients.

BACKGROUND: Preliminary observational studies with multiple sclerosis (MS) patients have reported strong correlations between an increase in hypointense lesion load (black holes) on T1-weighted spin echo images, and an increase in disability. OBJECTIVE: We assessed the relationship of hypointense lesions to the clinical course of disease among 50 relapsing-remitting MS patients in the controlled setting of a randomized clinical trial. METHODS: Fifty patients with relapsing-remitting disease were enrolled in a randomized double-blind two-arm (cladribine vs. placebo) clinical trial of 1-year duration. All patients had monthly clinical evaluations and MRIs over the course of the trial. Multivariate techniques were used to identify predictors of clinical severity from information on exacerbations, MRIs, baseline clinical parameters, and demographics. RESULTS: At baseline, clinical severity is weakly related to counts of black holes, with rank correlations between counts and clinical scores (EDSS and SNRS) of absolute magnitude 0.3. Rates of appearance of new black holes over the course of the trial are higher for patients with more severe disease at baseline (EDSS > or = 4) than for the less severe patients. Changes in clinical severity over the course of the trial are best predicted by baseline neurologic scores and numbers of exacerbations, with black holes adding no further improvement in prediction. CONCLUSIONS: Numbers of exacerbations seem more critical to short-term clinical outcomes in relapsing-remitting MS, as reflected by patients' clinical scores, rather than black holes. Various imaging methods and MRI indices capture complementary information relating to MS disease processes. The determination of which processes are affected by different drugs should lead to more effective treatment of MS patients.

Cladribine↗

Low frequency of autoantibodies to the human Na(+)/I(-) symporter in patients with autoimmune thyroid disease.

Several studies suggest that the sodium-iodide symporter (NIS) may represent a major autoantigen in autoimmune diseases of the thyroid. The aim of the present paper was to investigate the importance of autoantibodies to human NIS (hNIS-Ab) in patients suffering from Hashimoto's thyroiditis (HT) and Graves' disease (GD). Full-length human NIS (hNIS) was cloned from thyroid tissue, expressed by in vitro transcription and translation in the presence of [(35)S]methionine, and used to analyze autoantibodies in a direct binding assay. The structurally similar glucose transporter, GLUT-2, was produced in the same system as control protein. Autoradiography revealed that full-length hNIS was expressed, recognized by a NIS monoclonal antibody, and strongly bound by some sera from patients with autoimmune thyroid disease, which did not react with the GLUT-2 control protein. Using the 95.2th percentile of healthy controls as threshold for positivity, 19 of 177 (10.7%) patients with GD and 15 of 72 (20.8%) patients with HT had hNIS-Ab, respectively. Applying more stringent cut-off criteria (99.4th percentile of normal controls), hNIS-Ab were found in only 5.6% of patients with GD and 6. 9% of patients with HT. In HT significantly higher hNIS-Ab levels were observed compared with GD and normal controls (P: < 0.001). There was no correlation between hNIS-Ab and TSH receptor antibodies and only a weak correlation to thyroid peroxidase antibodies (P: < 0. 05). Comparison of hNIS-Ab, thyroid peroxidase, and TSH receptor antibodies in individual sera revealed that the additional detection of hNIS-Ab did not increase the diagnostic power for GD or HT. Our data indicate that hNIS is not a major antigen in autoimmune thyroid disease, as it is the target of humoral autoimmunity in only a few patients with GD and HT. The frequency of hNIS-Ab may be lower than that reported in previous studies.

Adolescent↗

Pathophysiology of impaired right and left ventricular function in chronic embolic pulmonary hypertension: changes after pulmonary thromboendarterectomy.

STUDY OBJECTIVES: This study sought to evaluate the pathophysiology of left and right heart failure in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who were hospitalized to undergo pulmonary thromboendarterectomy (PTE). DESIGN: Thirty-nine patients (16 women and 23 men; mean +/- SD age, 55+/-12 years) with severe CTEPH were examined before and 13+/-8 days after PTE by way of transthoracic echocardiography and right heart catheterization. MEASUREMENTS AND RESULTS: Examination results confirmed in all cases that before surgery the right ventricles were enlarged and systolic function was impaired. Moderate to severe tricuspid valve regurgitation was observed. Left ventricular eccentricity indexes reflected a leftward displacement of the interventricular septum. End-diastolic left ventricular size and systolic function had decreased, and the left ventricular filling pattern showed impaired diastolic function. After surgery, mean pulmonary artery pressure was significantly lower (48+/- 10 mm Hg vs. 25+/-7 mm Hg; p<0.05). The calculated end-diastolic and end-systolic right ventricular areas had decreased: 30+/-7 cm(2) vs 21 +/-5 cm(2) (p<0.05) and 24+/-6 cm(2) vs. 14+/-4 cm(2) (p<0.05), respectively. Right ventricular fractional area change had increased (20+/-7% vs. 33+/-8%; p<0.05). Most of the patients exhibited a marked decrease in the severity of tricuspid regurgitation. Septal motion, left ventricular systolic function, and diastolic filling pattern returned to normal values (early to late diastolic left ventricular inflow ratio, 0.70+/-0.33 vs. 1.35+/-0.51; p<0.05). The mean cardiac index also improved (2.7+/-0.6 L/min/m(2) vs. 3.7+/-0.8 L/min/m(2)). CONCLUSIONS: In CTEPH, functions are impaired in the right as well as the left ventricles of the heart. Improved lung perfusion and the reduction of right ventricular pressure overload are direct results of PTE, which in turn bring a profound reduction of right ventricular size and a recovery of systolic function. Normalization of interventricular septal motion as well as improved venous return to the left atrium lead to a normalization of left ventricular diastolic and systolic function, and the cardiac index improves.

Adult↗