Hereditary haemochromatosis mutations (HFE) in patients with Type II diabetes mellitus.
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Diabetes Mellitus, Type 2↗
Biomedical subjects
K H Usadel
Publications and source records attributed to K H Usadel.
Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours.
Scintigraphy using [111In-DTPA-d-Phe1]-pentetreotide or pentavalent technetium-99m-dimercaptosuccinic acid [99mTc(V)-DMSA] has been shown to localize well-differentiated and slowly growing neuroendocrine tumours, whereas increased fluorodeoxyglucose (FDG) uptake is associated with malignancy. The aim of this study was to compare the value of fluorine-18 FDG positron emission tomography (PET) with that of somatostatin receptor scintigraphy (SS-R) and dual-radionuclide scintigraphy [SS-R and 99mTc(V)-DMSA = DNS] in detecting malignant neuroendocrine tumours. Fifteen patients with metastasizing gastroenteropancreatic tumours (GEP tumours; n = 7), medullary thyroid carcinomas (MTCs; n = 8) and elevated tumour markers [GEP tumours: 5-hydroxyindoleacetic acid, insulin; MTCs: calcitonin, carcinoembryonic antigen (CEA)] were studied. Prior to PET, all patients with GEP tumours underwent SS-R. DNS was performed in all patients with MTC. Patients had been fasting for at least 12 h and normal glucose plasma levels were confirmed. Sixty minutes after intravenous administration of 18F-FDG (mean: 374 MBq) whole-body PET and regional scans were performed. In addition, the resected tissues were prepared for immunocytochemistry examination (cell cycle-associated Ki-67 antigen). In two patients with less-differentiated GEP tumours associated with high proliferative activity and increased FDG uptake, SS-R failed to detect any lesion. In comparison, in four patients with well-differentiated GEP tumours showing low proliferative activity, SS-R localized four primary tumours, 22 lymph node metastases and 18 malignant liver lesions, whereas 18F-FDG PET demonstrated normal distribution. In one patient with a metastasizing carcinoid (medium proliferative activity) SS-R localized multiple metastases, whereas PET demonstrated low FDG uptake in all known metastases. In patients with recurrent MTC and rapidly increasing CEA levels DNS detected only three lesions in two patients, whereas PET demonstrated one pulmonary, three osseous, 20 mediastinal, ten locoregional, and four liver metastases in seven patients. Twenty-nine malignant lesions were confirmed by follow-up and nine lymph node metastases could be surgically removed. In conclusion, PET imaging of gastroenteropancreatic tumours revealed increased glucose metabolism only in less-differentiated GEP tumours with high proliferative activity and metastasizing MTC associated with rapidly increasing CEA levels. Therefore, additional 18F-FDG PET should be performed only if SS-R or DNS is negative.
Adult↗
Comparison of metabolic and receptor imaging in recurrent medullary thyroid carcinoma with histopathological findings.
Early diagnosis of metastases of medullary thyroid carcinoma (MTC) provides the optimal condition for curative outcome. The aim of this study was to appraise the detection of metastases in patients with recurrent MTC using [111In-DTPA-d-Phe1]-pentetreotide and pentavalent technetium-99m dimercaptosuccinic acid [99mTc(V)-DMSA] in comparison with histopathological findings. Eighteen MTC patients with persistently elevated tumour marker (calcitonin, carcinoembryonic antigen) levels underwent somatostatin receptor scintigraphy using [111In-DTPA-d-Phe1]-pentetreotide (222 MBq) with early (4 h after injection) and delayed (24 h) whole-body scans and single-photon emission tomography (SPET) imaging. Metabolic whole-body and SPET imaging using 500 MBq 99mTc(V)-DMSA was performed 4 h after injection. Metabolic and receptor imaging revealed 51 sites of focal accumulation in the 18 patients investigated. Comparison with histological findings revealed that metabolic and receptor imaging had a sensitivity of 84% for the diagnosis of MTC. Using [111In-DTPA-d-Phe1]-pentetreotide, SPET discovered four lymph node metastases in two patients in whom planar views had previously identified only one lymph node metastasis, and provided no new information in the other 16 patients. In comparison, SPET studies [using 99mTc(V)-DMSA] additionally localized eight lymph node metastases in four patients and confirmed the diagnosis of hepatic metastases (n=5) in another patient in whom conventional imaging modalities and planar views had previously detected only three liver metastases. Overall, lesion detection sensitivities for 99mTc(V)-DMSA and [111In-DTPA-D-Phe1]-pentetreotide were 69% and 29%, respectively. Five surgically removed foci were adjudged false-positive with respect to MTC metastases. False-positve results were caused by lymphadenitis, an enchondroma and a pheochromocytoma (histologically proven). The smallest lesion identified by metabolic imaging was a 6 mm in diameter lymph node metastasis located in the upper mediastinum. Somatostatin receptor scintigraphy only demonstrated tumour sizes more than 1 cm in diameter. These preliminary results suggest that the combination of metabolic [99mTc(V)-DMSA] and receptor ([111In-DTPA-D-Phe1]-pentetreotide) imaging is more sensitive for tumour localization in patients with recurrent MTC than the use of only one radiopharmaceutical. However, neither 99mTc(V)-DMSA nor [111In-DTPA-D-Phe1]-pentetreotide is specific for MTC and false-positive scintigraphic findings have to be considered. Furthermore, somatostatin receptor scintigraphy cannot visualize small tumour sites (<1 cm). Further studies are needed to evaluate the role of combined metabolic and receptor imaging in the management of patients with recurrent MTC.
Carcinoma, Medullary↗
Effect of CsA versus FK 506 on insulin sensitivity and insulin response using a modeling technique.
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Blood Glucose↗
1st meeting of the German Interest Group for Geronto-Endocrinology.
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Endocrinology↗
Microcirculation in hyperglycemic patients with IDDM without diabetic complications--effect of low-dose angiotensin-converting enzyme inhibition.
In patients with insulin-dependent diabetes mellitus (IDDM) angiotensin-converting enzyme inhibitors (ACEI) have been demonstrated to have beneficial effects in the secondary prevention of microvascular complications. There are only few data available regarding the effect of ACEI on microcirculation in patients with IDDM without any microvascular complications. In addition, there is little knowledge about ACEI action during acute hyperglycemia. In a pilot study nine patients with IDDM without any clinical signs of diabetic complications (5 females, 4 males, aged 33.3 +/- 1.0 years, duration of diabetes 11.4 +/- 3.0 years, HbA1 7.2 +/- 0.2% [normal range 4.8-7.4%], BMI 21.4 +/- 0.5 [kg/m2]) received 1.25 mg of the ACEI ramipril (Delix, Hoechst Marion Roussel, Frankfurt) over 4 weeks. Nine healthy volunteers (4 females, 5 males, age 27.4 +/- 1.1 years, HbA1 5.9 +/- 0.2% (p < 0.01 vs patients), BMI 22.2 +/- 0.9 [kg/m2]) served as controls. Using nailfold capillaroscopy we determined capillary blood cell velocity (CapiFlow, Lawrenz Electronics, Sulzbach, Germany) before and during post-occlusive hyperemia (200 mmHg for 3 minutes) as a provocative test. Before and after treatment patients were studied during hyperglycemia (blood glucose 250-350 mg/dl). Treatment with low-dose ramipril resulted in a significant decrease in the time to peak capillary blood cell velocity during post-occlusive hyperemia (17.8 +/- 7.7 vs 57.4 +/- 12.8 s, p < 0.01) in hyperglycemic patients. This effect was absent in healthy volunteers. Hemodynamic and metabolic parameters remained unchanged throughout the study in both groups. These data demonstrate that low-dose therapy with the ACEI ramipril is able to improve microcirculation in hyperglycemic patients with type 1 diabetes mellitus also before microvascular complications are evident. Prospective studies are necessary to evaluate whether this effect might be clinically relevant in the primary prevention of diabetic microangiopathy.
Adult↗
Interferon-gamma gene microsatellite polymorphisms in patients with Graves' disease.
Although some of the susceptibility to Graves' disease is conferred by genes in the human leucocyte antigen (HLA) region on the short arm of chromosome 6, other genetic factors must also predispose. Among the cytokines involved in thyroid autoimmunity interferon-gamma (IFN-gamma) plays a key role in the pathogenesis of Graves' disease. We therefore analyzed the first intron of the IFN-gamma gene for a dinucleotide (CA) repeat polymorphism on chromosome 12q. Two hundred two Caucasian patients with Graves' disease and 214 Caucasian controls were analyzed by polymerase chain reaction (PCR) and subsequent polyacrylamide gel electrophoresis technique: eight different alleles designated as IFN-gamma*1 to IFN-gamma*8 could be differentiated. Among Graves' disease patients IFN-gamma*5 (12.9% vs. 6.8%, p < 0.04) was significantly more frequent whereas IFN-gamma*2 (2.5% vs. 9.8%, p < 0.002) was significantly less frequent. Patients positive for the genetic susceptibility marker HLA DQA1*0501 had significantly more IFN-gamma*3 alleles (13.6% vs. 2.6%, p < 0.009) and IFN-gamma*5 alleles (22.1% vs. 7.6%, p < 0.03) compared with DQA1*0501 positive controls. Also, among patients with endocrine ophthalmopathy IFN-gamma*3 (17.9% vs. 4.2%, p < 8 x 10(-6)) and IFN-gamma*5 (18.9% vs. 7.0%, p < 0.003) were significantly more frequent compared with controls. Although a significant association of IFN-gamma microsatellite polymorphism was observed, only a small proportion of Graves' disease patients have these markers. Thus, it is likely that the detected microsatellite polymorphisms play only a minor role in the susceptibility to Graves' disease.
Alleles↗
Metabolic (PET) and receptor (SPET) imaging of well- and less well-differentiated tumours: comparison with the expression of the Ki-67 antigen.
[111In-DTPA-D-Phe1]-pentetreotide has been shown to localize well-differentiated and slowly growing neuroendocrine tumours, whereas increased FDG uptake is associated with malignancy. This prospective study explores the role of metabolic (PET) and receptor (SPET) imaging in well- and less well-differentiated tumours--gastroenteropancreatic (GEP) tumours, medullary thyroid carcinomas (MTC) and thymic carcinomas--in comparison with the expression of the Ki-67 antigen. Ten patients with GEP tumours, five with MTC and five with thymic carcinomas were studied. Prior to PET, somatostatin receptor scintigraphy (SRS) was performed in all patients. Sixty minutes after the intravenous administration of 18F-FDG (370 MBq), whole-body PET was performed. In addition, the resected tissues were prepared for immunocytochemistry examination (cell cycle-associated Ki-67 antigen). Preoperative SRS detected multiple primary tumours and metastatic lesions in four patients with well-differentiated carcinoids (low Ki-67 expression). Whole-body PET demonstrated normal distribution of FDG in all of these patients. In patients with recurrent MTC and rapidly increasing CEA levels, SRS showed no in vivo somatostatin receptor expression, whereas whole-body PET localized 24 locoregional lymph node metastases with increased FDG uptake. Immunocytochemistry of the resected lymph nodes demonstrated high Ki-67 expression associated with a high proliferative activity. Similar results in receptor scintigraphic and metabolic behaviour were obtained from patients with metastasizing thymic carcinomas (high Ki-67 expression). In conclusion, SRS has been shown to localize well-differentiated GEP tumours. In contrast, FDG PET is only valuable for predicting malignancy in less well-differentiated GEP tumours and malignant MTC associated with rapidly increasing CEA levels. Therefore, an additional 18F-FDG PET procedure should only be performed if SRS is negative. Furthermore, our preliminary results suggest that increased FDG metabolism reflects the invasiveness of thymic carcinomas.
Adult↗
CTLA4 codon 17 dimorphism in patients with rheumatoid arthritis.
The genetic susceptibility to rheumatoid arthritis is conferred by genes in the human leukocyte antigen (HLA) region on chromosome 6, but additional genes may be involved to determine disease susceptibility. We have studied the distribution of the CTLA4 exon 1 polymorphism (49 A/G) in rheumatoid arthritis. This dimorphism at codon 17 results in an amino acid exchange (Thr/Ala) in the leader peptide of the expressed protein and was analyzed by PCR, SSCP and RFLP in 258 Caucasian rheumatoid arthritis patients and 456 controls. Rheumatoid arthritis patients were characterized by a decreased frequency of homozygotes for the Thr-17 substitution (32% versus 39%) and an overrepresentation of patients heterozygous for the Thr/Ala substitution (54% versus 46%). Gene frequencies for the Ala/Thr substitution differed only marginally from controls. In contrast, analyses of the CTLA4 exon 1 polymorphism with respect to HLA-DRB1*04 revealed significantly more patients with Ala in the homozygous (19% versus 15% controls) or heterozygous state (54% versus 39% controls) and less homozygous for Thr (27% versus 46% controls), with a particular increase of Ala/Ala genotypes among rheumatoid arthritis patients carrying the HLA-DRB1*0401 subtype. Among HLA-DRB1*04 negative rheumatoid arthritis patients, we observed no difference between the allele frequencies of the Ala-17 or Thr-17 substitution.
Abatacept↗
CTLA-4 promoter variants in patients with Graves' disease and Hashimoto's thyroiditis.
Graves' disease (GD) and Hashimoto's thyroiditis (HT) are T-cell mediated organ-specific autoimmune disorders with a genetic predisposition. The cytotoxic T-lymphocyte antigen 4 (CTLA-4) molecule is the predominant receptor for B7 on activated T cells and represents a negative regulator for T-cell function. Since the CTLA-4-guanine at position 49 of exon 1 is associated with susceptibility to GD as well as to HT and IDDM, we investigated a recently detected cytosine/thymine substitution at position -318 within the CTLA-4 promoter region in patients with GD and HT. 125 patients with GD were significantly more often homozygous for cytosine (86% vs. 73% in controls, P=0.006) and less frequently heterozygous for cytosine and thymine (14% vs. 27%, P=0.008). In 64 patients with HT, the distribution was similar but not significant (81% homozygous for cytosine and 16% heterozygous). When correlating the promoter and the exon 1 polymorphism we found the strongest linkage between thymine (promoter) and adenine (exon 1). In conclusion, a promoter variant of the CTLA-4 gene represents an additional risk marker for GD and HT, but their predisposition is linked to the exon 1 alleles.
Abatacept↗
Lymphocyte transfer in streptozotocin-induced diabetes: adhesion of donor cells to islet endothelium.
The interaction between intravenously transferred lymphocytes derived from spleens of multiple low-dose streptozotocin-diabetic mice with islet, exocrine pancreatic, and gastric mucosal endothelium of nondiabetic recipient mice was investigated by in vivo microscopy. Donor lymphocytes were stained with acridine red in vitro. The adoptive transfer of these cells from diabetic donor animals resulted in significantly increased lymphocyte rolling (4.46 +/- 1.32%, P < 0.05) and adhesion (3.86 +/- 1.04%, P < 0.05) in islets of nondiabetic recipients that had been pretreated with a single subdiabetogenic dose of streptozotocin. No increased endothelial interaction was noted in nonpretreated recipients or in experiments with nondiabetic donors. Rolling (1.19 +/- 0.61 to 2.71 +/- 0.62%) and adhesion (0.61 +/- 0.33 to 2.80 +/- 0.97%) of donor lymphocytes were low in exocrine pancreatic and gastric mucosal control tissue. It is concluded that, in this animal model, lymphocytes from diabetic donors interact preferentially with recipient islet endothelium. However, additional stimulation of recipient islet endothelium by exogenous factors is necessary to enable transferred cells to adhere to pancreatic islets.
Animals↗
Soluble ICAM-1 reduces leukocyte adhesion to vascular endothelium in ischemia-reperfusion injury in mice.
Ischemia-reperfusion injury is a pathogenic factor in the course of many clinical disorders, such as myocardial infarction, stroke, organ transplantation, burns, and circulatory shock. The extent of ischemia-reperfusion injury is dependent on the number of infiltrating leukocytes. With in vivo microscopy, we evaluated the effect of the recombinant form of soluble murine intercellular adhesion molecule-1 (ICAM-1) on ischemia-reperfusion injury in an animal model. A mesenteric vein was occluded with a clamp for 45 min. During a reperfusion period of 30 min, the number of leukocytes rolling along the endothelium and the number of adherent leukocytes were measured with and without pretreatment with recombinant ICAM-1. The number of leukocytes rolling along the endothelial surface increased more than twofold during postischemic perfusion (P < 0.05). Recombinant ICAM-1 had no effect on leukocyte rolling. In the control group, firm adherence of leukocytes was increased 10-fold. Recombinant ICAM-1 dose dependently reduced firm adhesion to the endothelium in response to prior ischemia. After 30 min, reperfusion pretreatment with recombinant ICAM-1 inhibited leukocyte adherence from 512 +/- 123 to 166 +/- 34 leukocytes/mm2 (P < 0.01). We demonstrate here for the first time that soluble recombinant ICAM-1 is able to reduce leukocyte adherence to mesenteric venules in postischemic reperfusion injury dose dependently. Because soluble ICAM-1 is naturally circulating in human serum, the therapeutic use of soluble recombinant forms of ICAM-1 may represent a physiological way to protect against ischemiareperfusion injury.
Analysis of Variance↗
Modulation of human thyrotropin oligosaccharide structures--enhanced proportion of sialylated and terminally galactosylated serum thyrotropin isoforms in subclinical and overt primary hypothyroidism.
Enhanced sialylation of thyrotropin (TSH) prolongs its metabolic clearance rate and thus increases the hormone's in vivo bioactivity. This has been shown for hypothyroid rats and for recombinant human TSH, but there are few data on the sialylation of human serum TSH. The aim of this work was to further study sialylated human serum TSH, its precursors bearing terminal galactose residues, and the role of pharmacological doses of thyrotropin-releasing hormone (TRH) on their secretion under different degrees of primary hypothyroidism. We analyzed serum TSH in patients with subclinical (n = 9) and overt primary hypothyroidism (n = 13) compared with euthyroid individuals (n = 12) and human standard pituitary TSH (IRP 80/558). Blood was drawn before and 30 min after intravenous administration of 200 micrograms TRH, and TSH was purified by immunoaffinity concentration. The content of sialylated (sialo-) TSH and isoforms bearing terminal galactose (Gal-TSH, asialo-Gal-TSH) was measured by Ricinus communis (RCA 120) affinity chromatography in combination with enzymatic cleavage of sialic acid residues. TSH immunoreactivity was measured by an automated second generation TSH immunoassay. Pituitary TSH contained 16.5 +/- 0.8% Gal-TSH. In euthyroid individuals the proportion of Gal-TSH was 14.6 +/- 1.9%, whereas TSH in patients with subclinical and overt primary hypothyroidism contained 23.9 +/- 3.5% (P < 0.05 vs euthyroid individuals) and 21.1 +/- 1.7% Gal-TSH respectively. The mean ratio of asialo-Gal TSH was 23.8 +/- 0.6% for pituitary TSH, 35.7 +/- 4.2% in euthyroid individuals, 48.0 +/- 3.3% in patients with subclinical, and 61.5 +/- 3.8% (P < 0.001 vs euthyroid individuals) in patients with overt primary hypothyroidism. For pituitary TSH the calculated proportion of sialo-TSH was 6.5 +/- 0.2%, for euthyroid individuals 20.3 +/- 2.8%, for patients with subclinical hypothyroidism 24.1 +/- 3.0%, and for patients with overt primary hypothyroidism 40.7 +/- 3.0% (P < 0.001 vs euthyroid individuals). The proportions of Gal-TSH, asialo-Gal-TSH, and sialo-TSH did not differ significantly before and after TRH administration in the individuals studied. Our data show that patients with subclinical and overt primary hypothyroidism have a markedly increased proportion of serum TSH isoforms bearing terminal galactose and sialic acid residues, which may represent a mechanism for the further stimulation of thyroid function. Pharmacological doses of TRH cause an increased quantity of TSH to be released, but do not significantly alter the proportion of sialylated or terminally galactosylated TSH isoforms.
Adult↗
CTLA4 gene haplotypes cannot protect from IDDM in the presence of high-risk HLA DQ8 or DQ2 alleles in German families.
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Abatacept↗
[Therapy of diabetic nephropathy. Effects of ACE inhibition on microcirculation].
The development of diabetic microangiopathies is of decisive importance for the long-term prognosis of diabetes mellitus. For example, diabetic nephropathy is one of the the most common causes of terminal kidney failure. Primary prevention of diabetic nephropathy is best achieved by establishing good metabolic control. To ensure early pharmacological intervention of incipient diabetic nephropathy, screening for microalbuminuria is recommended at least once a year. A major element in the pathogenesis of diabetic nephropathy is a disordered microcirculation characterized by abnormal hemodynamics with elevated capillary pressure and microvascular resistance. Angiotensin converting enzyme inhibitors (ACE inhibitors) effectively act on these pathophysiological events by dilation of the vasa efferentia of the glomeruli. By means of videocapillaroscopy and laser doppler imaging also distinct changes in microcirculation can be detected. Investigations with these methods provided evidence that ACE inhibitors might also be useful in the primary prevention of diabetic nephropathy. Therefore, ACE inhibitors are useful pharmaceutical agents in the treatment of diabetic nephropathy.
Angiotensin-Converting Enzyme Inhibitors↗
Glycosylation variants of human TSH selectively activate signal transduction pathways.
The oligosaccharide chains of pituitary glycoprotein hormones such as human thyroid-stimulating hormone (hTSH) have been shown to be important in biosynthesis, subunit association, secretion and bioactivity. However, the exact biological significance of these glycosylation variants (isoforms) remains controversial. The aim of this paper is to investigate the role of hTSH glycosylation variants in signal transduction. Human pituitary standard TSH (2nd International Reference Preparation 80/558; IRP-hTSH) was treated with neuraminidase, fractionated by isoelectric focusing (IEF) and affinity chromatography using the lectins concanavalin A (Con A) and lentil. To determine the in vitro bioactivity of these hTSH isoforms, simultaneous measurement of cAMP formation and inositol phosphates release was applied in two different cell systems (CHO cells stably and Cos-7 cells transiently transfected with hTSHR cDNA). Desialylated TSH variants showed a significantly increased ratio of bioactivity to immunoreactivity for cAMP production in CHO-R cells (B/I ratio desialylated variants: 3.54 +/- 0.005; B/I ratio sialylated variants: 2.84 +/- 0.01 P < 0.05). Testing the bioactivity of hTSH glycosylation variants isolated by IEF, we found basic variants to be significantly more active than acidic ones in stimulating the cAMP formation in CHO-R cells (B/I ratio basic variants: 9.92 +/- 0.64; neutral variants: 5.98 +/- 0.07; acidic variants: 2.80 +/- 0.12; P < 0.01). There were no differences in stimulation of IP-release. High-mannose TSH variants (firmly bound to Con A) showed greater potency to stimulate cAMP formation and IP-release in both CHO-R and Cos-7 cells than biantennary TSH variants (weakly bound to Con A). Both core-fucosylated (lentil-bound) and core-unfucosylated (lentil-unbound) TSH variants proved to be strong stimulators of cAMP release in CHO and Cos-7 cells. In CHO-R (Cos-7) cells, 400 microU/ml core-fucosylated TSH stimulated cAMP formation 14(2.6)-fold, core-unfucosylated TSH 7.3(2.3)-fold over control values. In contrast to our findings of cAMP activation by both core-fucosylated and core-unfucosylated TSH variants, release of IPs was stimulated only by, core-fucosylated (lentil-bound) TSH variants and not by TSH variants lacking core-fucose residues (lentil-unbound TSH). This was true for both CHO-R and Cos-7 cells. The lentil-unbound TSH therefore showed an identical differential activation of signal transduction pathways in two different cell systems: strong stimulation of the cAMP-cascade without activation of IPs release (P < 0.05). In conclusion, we showed for the first time for TSH that the two dominant intracellular signal transduction systems (cAMP formation and IPs release) are activated to different degrees by hTSH glycosylation variants.
Animals↗
[Clinical value of somatostatin receptor scintigraphy. Studies of pre- and intraoperative localization of gastrointestinal and pancreatic tumors].
BACKGROUND: [111In-DTPA-D-Phe1]-pentetreotide scintigraphy is able to detect neuroendocrine tumors not shown by radiological methods. PATIENTS AND METHODS: In 270 patients with neuroendocrine gastroenteropancreatic tumors (GEP tumors) 400 somatostatin receptor scintigraphies were performed. 70 patients (38 female, 32 male, aged 28 to 74 [56 +/- 12.6] years) underwent surgery and follow-up over 2 years. The aim of the present study was the comparison of preoperative somatostatin receptor scintigraphy with radiological methods (sonography, CT) and intraoperative localization of GEP tumors with a hand-held gamma-probe. RESULTS: Somatostatin receptor scintigraphy was successful in localizing primary tumors in all patients. Liver- and lymph node metastases could be visualized with a sensitivity of 94 and 95 percent. In 7 patients 35 lesions could be identified by intraoperative tumor localization using a hand held gamma probe. Radiological methods identified only 11, surgical palpation 15 and preoperative somatostatin receptor scintigraphy 27 lesions. CONCLUSION: Somatostatin receptor scintigraphy improves detection of small and occult GEP tumors. Intraoperative probe counting with a hand-held gamma probe can identify tumors even when they are small and impalpable, but receptor positive.
Adult↗
The effect of verapamil on mitochondrial calcium content in normoxic, hypoxic and reoxygenated rat liver.
Calcium channel blockers protect cells against ischaemia-reperfusion injury. In the present study, the effect of verapamil on mitochondrial calcium content was investigated in situ in normoxic, hypoxic and reoxygenated rat liver. Subcellular distribution of exchangeable calcium ions, which form an electron-dense precipitate with antimonate, was demonstrated with the glutaraldehyde-osmium antimonate technique. Calcium precipitates were quantified morphometrically using automatic image analysis. In normoxic liver, the mitochondrial calcium content formed a gradient decreasing from the periportal to perivenous regions. The low mitochondrial calcium content in perivenous regions remained unaffected in all experimental conditions. In hypoxic and reoxygenated liver, the calcium content in mitochondria of the periportal areas was significantly reduced. Verapamil pretreatment levelled the calcium gradient in normoxic liver by reducing the periportal calcium content. Verapamil had no effect on the mitochondrial calcium content in hypoxic liver. In contrast, in verapamil-pretreated reoxygenated liver, the mitochondrial calcium content in periportal mitochondria increased significantly, thus restoring the zonal calcium gradient. In conclusion, these data suggest that modulations of mitochondrial calcium content in the periportal region of the liver lobule may play an important role in the protective effects of verapamil against ischaemia-reperfusion injury.
Animals↗