bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased prevalence of sublinical brain perfusion abnormalities in patients with autoimmune thyroiditis: evidence of Hashimoto's encephalitis?
Authors: Zettinig Georg , Asenbaum Susanne , Fueger Barbara J. , Hofmann Andrea , Diemling Markus , Mittlboeck Martina , Dudczak Robert 
Published: October 2003

Summaryobjectives  Hashimoto's encephalitis is a term which describes encephalopathy associated with autoimmune thyroiditis, but it is not based on evidence, whether Hashimoto's encephalitis is a distinct clinical entity by itself. In previously reported cases of Hashimoto's encephalitis, abnormal brain perfusion studies have been reported. The aim of this study was to evaluate the prevalence of brain perfusion abnormalities in euthyroid patients with autoimmune thyroiditis.methods  99mTc Ethyl cystein dimer (ECD) single photon emission computed tomography (SPECT) studies were performed in a study group of 41 euthyroid patients with autoimmune thyroiditis and a matched control group of 35 healthy individuals. All study participants had a normal neurological investigation and a detailed neurological history taking. Individuals with known or suspected morphological brain abnormalities were excluded from the study. Zung's Self‐Rating Anxiety Scale (SAS) and Zung's Self‐Rating Depression Scale (SDS) were used to detect depression and mood disorders. Automatic quantification of perfusion was performed with both a voxel‐based analysis as well as a volume‐of‐interest (VOI) based analysis of 46 predefined cortical and subcortical regions. The findings from both groups were compared to a reference template.results  In the voxel‐based analysis, there was a significant difference between patients and controls in the mean volume of perfusion defects deviating 2SD below the normal values (21·8 ml vs. 10·4 ml; P = 0·02). Hyperperfused areas, however, did not differ significantly between study patients and controls. A significant correlation of the perfusion defects with time since diagnosis of autoimmune thyroiditis was seen (r = 0·42). In the VOI‐based analysis, abnormal regions were more frequent in the study group when compared to controls (P < 0·01) However, no topographic pattern was apparent. Regarding neurological findings, no significant difference was found between study patients and controls. However, both the SAS and SDS scores differed significantly between the two groups, but there was neither a correlation between the two scores and perfusion abnormalities nor an association with depression in our study group.conclusions  These findings of impaired brain perfusion in patients with autoimmune thyroiditis further strengthen the hypothesis of a possible cerebral involvement in autoimmune thyroiditis in individual cases. The presence of cerebral hypoperfusion suggests a cerebral vasculitis as the most likely pathogenetic model.
Chromogranin A as serum marker of pituitary adenomas
Authors: Gussi Ilinca‐Lucia , Young Jacques , Baudin Eric , Bidart Jean Michel , Chanson Philippe 
Published: October 2003

Summaryobjective  The diagnostic impact of chromogranin A (CgA) measurement has been studied in various neuroendocrine tumours (NET) such as pheochromocytomas, gastrinomas and neuroblastomas. Clinically nonfunctioning pituitary adenomas (NFPA) are generally diagnosed on tumoural symptoms or hypopituitarism and, except for gonadotrophins and their free subunits which may be increased in the case of gonadotrophinomas, markers of endocrine secretory activity are lacking not only for diagnostic purpose but also in the postoperative follow‐up of these patients. As the presence of CgA has been demonstrated by immunohistochemistry in pituitary adenomas, we performed this study to further assess the sensitivity of CgA measurement in sporadic pituitary adenomas using a new, specific, sandwich immunoassay.subjects  We first completed a basal normative data set obtained using this assay by studying four healthy men (49 ± 13 years old), five healthy premenopausal women (35·8 ± 7·5 years old) and five healthy postmenopausal women (49·1 ± 4·6 years old) basally and after TRH administration. Twenty‐seven patients [12 men (64·2 ± 11·8 years), even premenopausal women (38·4 ± 5·7 years) and eight postmenopausal women (67·7 ± 10·3 years)] with NFPA, 15 acromegalic patients [nine men (45 ± 13·3 years), six women (52 ± 14·9 years)] and 19 patients with a prolactin‐secreting adenoma [four men (41·2 ± 18 years) and 15 women (31·2 ± 7·5 years), with a macroadenoma (n = 11) or a microadenoma (n = 8)] had basal and TRH‐stimulated measurement of CgA. A gonadotrophin‐releasing hormone (GnRH)‐stimulation test was also performed in two, four and four patients, respectively. All patients had sporadic pituitary adenomas.measurements  Serum CgA was measured using a solid‐phase two‐site immunoradiometric assay based on monoclonal antibodies that bind to two distinct contiguous epitopes within the 145–245 region of CgA.results  Mean basal CgA concentration in 14 normal subjects was 80·2 ng/ml (SD: 31·7; range 19–124). A cut‐off value for normal range was thus set at 125 ng/ml. TRH injection did not change significantly the CgA levels, peak values remaining less than 124 ng/ml. Three out of 27 subjects with NFPA (11%) had elevated basal CgA levels (576, 143, 241 ng/ml, respectively). Serum levels of CgA were not influenced by TRH in any of the NFPA subjects (including those three with increased basal levels). One out of 15 acromegalic patients (6·6%) and one out of 19 hyperprolactinemic patients (5·2%) had elevated serum basal CgA which did not significantly increase after TRH administration. In the remaining patients TRH‐tests did not modify CgA levels. GnRH administration did not modify CgA levels.conclusions  CgA serum levels measurement, assessed with a novel assay, does not provide a helpful marker for the clinical management of functioning and NFPA.
Ghrelin concentrations in healthy children and adolescents
Authors: Whatmore A. J. , Hall C. M. , Jones J. , Westwood M. , Clayton P. E. 
Published: October 2003

Summaryobjective  In addition to its regulation by GH releasing hormone (GHRH) and somatostatin, release of GH from the pituitary is modulated by a third factor, ghrelin, which is expressed in high concentration in the stomach and is present in the circulation. Ghrelin has also been shown to cause weight gain by increasing food intake and decreasing fat utilization. Ghrelin is a potential candidate hormone to influence nutrient intake and growth. Its role through normal childhood and adolescence has not been fully defined.design  Cross‐sectional study in 121 healthy children (65 male, 56 female) aged 5–18 years, in whom height, weight, body mass index (BMI), pubertal status and measurements of IGF‐I, IGFBP‐3, IGFBP‐1 and leptin were available.methods  Serum ghrelin concentrations have been measured in radioimmunoassay (RIA; Phoenix, AZ, USA) that detects active and inactive human ghrelin. Relationships between ghrelin and anthropometric data and growth factors were assessed by correlation and regression analyses.results  Ghrelin was detected in all samples, with a median concentration of 162 pg/ml, range 60–493 pg/ml. Prepubertal children had higher ghrelin concentrations than those in puberty [218 pg/ml (n = 42) and 157 pg/ml (n = 79), P < 0·001], with significant negative correlations between ghrelin and age (rs = −0·39, P < 0·001) and pubertal stage (rs = −0·42, P < 0·001). The decrease in ghrelin with advancing pubertal stage/age was more marked in boys than girls. In the whole group, ghrelin was negatively correlated to BMI SD (rs = −0·24, P = 0·006) and to weight SD (rs = −0·24, P = 0·008) but not height sds. Ghrelin was also negatively correlated to IGF‐I (rs = −0·48, P < 0·001), IGFBP‐3 (rs = −0·32, P < 0·001) and leptin (rs = −0·22, P = 0·02) but not IGF‐II. It was positively related to IGFBP‐1 (rs = +0·46, P < 0·001). In stepwise multiple regression, 30% of the variability in ghrelin through childhood could be accounted for by log IGF‐I (24%) and log IGFBP‐1 (6%).conclusions  The fall in ghrelin over childhood and with puberty does not suggest that it is a direct growth‐promoting hormone. However in view of the negative relationship with IGF‐I and the positive relationship with IGFBP‐1, this fall in ghrelin could facilitate growth acceleration over puberty.
Update on genetic and clinical aspects of primary hyperparathyroidism
Authors: Miedlich S. , Krohn K. , Paschke R. 
Published: October 2003

SummaryPrimary hyperparathyroidism (pHPT) is a common endocrine disorder that predominantly affects postmenopausal women. It is mostly caused by solitary tumours within the parathyroid glands. Although the pathophysiology of pHPT is still incompletely understood, recent studies provide new clues on the development and cellular growth of tumours within the parathyroids associated with hypersecretion of parathyroid hormone and hypercalcaemia. The natural course of pHPT is rather benign. Nowadays, it has become an oligo‐ or asymptomatic disease often only detected by routine blood tests. These facts raise the question whether to perform parathyroidectomy on oligo‐ and asymptomatic patients with pHPT or whether it is possible to monitor these patients without surgery. The aim of this article is to review the literature as regards (i) the pathophysiological mechanisms that underlie parathyroid neoplasia and (ii) the defective calcium‐sensing in patients with pHPT (iii) environmental and/or genetic risk factors that predispose to or promote parathyroid neoplasia, as well as (iv) alternative approaches to treat oligo‐ and asymptomatic patients with pHPT medically.
Mechanisms of nitrate tolerance: potential roles of folate
Authors: Bellisarii F. Iachini , Gallina S. , Zimarino M. , De Caterina R. 
Published: October 2003

AbstractMore than 100 years since their introduction in cardiovascular therapy, nitrates continue to be widely used in ischaemic heart disease despite incomplete knowledge of their intimate mechanism of action. Particularly, the development of a progressive attenuation of their efficacy over prolonged use (tolerance) continues to be the subject of current investigation. Newer findings point to the role of increased intracellular oxidative stress as a mechanism for tolerance and to folic acid derivatives as pharmacologic means to attenuate its development. This paper reviews nitrate mechanism of action, the history of nitrate tolerance and newer findings related to the use of folate to prevent this phenomenon.
Increased skeletal muscle expression of PKC‐θ but not PKC‐α mRNA in type 2 diabetes: inverse relationship with in‐vivo insulin sensitivity
Authors: Gray S. , Idris I. , Davis K. R. , Donnelly R. 
Published: October 2003

AbstractBackground  Increases in PKC‐θ (the major isoenzymic form of PKC in skeletal muscle) protein and isozyme activity have been reported in skeletal muscle from patients with type 2 diabetes mellitus (T2DM) and dietary‐induced rodent models of insulin resistance, but the underlying biochemical mechanism is unclear and muscle PKC‐θ mRNA expression has not been previously reported in patients with T2DM or in relation to in‐vivo measurements of insulin sensitivity.Methods  Diet‐only treated patients with T2DM (n = 7) and healthy nondiabetic controls (n = 7) of similar BMI attended the clinical research unit on two occasions, 1 week apart, for a skeletal muscle biopsy 2 h after a 75‐g oral glucose load and measurement of whole‐body insulin sensitivity using the euglycaemic hyperinsulinaemic clamp.Results  Type 2 DM patients were insulin resistant (M‐value 3·0 ± 0·4 vs. 8·6 ± 0·8 mg glucose kg−1 min−1) with fasting hyperinsulinaemia (306 ± 116 vs. 34 ± 9 pmol L−1, P < 0·001) and hypertriglyceridaemia (3·6 ± 0·7 vs. 1·3 ± 0·3 mmol L−1, P < 0·01) relative to controls. Semi‐quantitative RT‐PCR showed that expression of PKC‐θ mRNA (relative to GAPDH mRNA) was 6‐fold higher in T2DM subjects (0·63 + 0·25% vs. 0·09 + 0·07%, P < 0·001), whereas there was no difference in expression of PKC‐α mRNA between the two groups. Expression of PKC‐θ mRNA was inversely correlated with insulin sensitivity (M) and positively correlated with fasting serum insulin concentration (P < 0·02).Conclusions  This is the first clinical study of PKC‐θ mRNA expression in human diabetic skeletal muscle. The results indicate that transcriptional up‐regulation of PKC‐θ may at least partly contribute to the increased muscle PKC‐θ signalling in T2DM, and that PKC‐θ mRNA may be inversely related to in‐vivo insulin sensitivity.
Acute haemodynamic effects of losartan in anaesthetized cirrhotic rats
Authors: Heller J. , Shiozawa T. , Trebicka J. , Hennenberg M. , Schepke M. , Neef M. , Sauerbruch T. 
Published: October 2003

AbstractBackground  Portal hypertension in cirrhosis is the result of increased intrahepatic vascular resistance to portal outflow as well as increased portal tributary blood flow. The angiotensin II type 1 receptor antagonist losartan has been suggested as a portal pressure‐lowering drug in patients with cirrhosis.Aim  To investigate the systemic and splanchnic haemodynamic effects of different doses of losartan.Methods  In 35 anaesthetized rats with secondary biliary cirrhosis, 3, 10 or 30 mg of losartan kg−1 or solvent were administered intravenously. Ten sham‐operated rats served as controls. Mean arterial pressure and portal pressure were measured by catheters in the femoral artery or portal vein. Systemic and splanchnic haemodynamics and mesenterico‐systemic shunt rate were determined by the coloured microsphere method.Results  Losartan reduced portal pressure (sham: 9·1 ± 0·4. cirrhosis: 19·3 ± 1·1, after 3 mg kg−1 of losartan 16·4 ± 0·4, after 10 mg kg−1 of losartan 15·6 ± 0·6, after 30 mg kg−1 of losartan 14·9 ± 0·6 mmHg) without reducing portal sinusoidal resistance. However, in cirrhotic rats it reduced portal tributary blood flow (sham: 4·3 ± 0·6. cirrhosis: 8·6 ± 1·4, after 3 mg kg−1 of losartan 3·8 ± 0·7, after 10 mg kg−1 of losartan 4·7 ± 0·5, after 30 mg kg−1 of losartan 5·9 ± 0·9 mmHg). This was owing either to an increase in splanchnic vascular resistance at the 3 mg kg−1 dose or to a reduction in the splanchnic perfusion‐pressure gradient secondary to a reduction in mean arterial pressure at the 10 and 30 mg kg−1 doses (mean arterial pressure: sham: 109·7 ± 4·8. cirrhosis: 109·4 ± 2·8, after 3 mg kg−1 of losartan 99·7 ± 2·9, after 10 mg kg−1 of losartan 89·9 ± 3·4, after 30 mg kg−1 of losartan 81·0 ± 2·9 mmHg).Conclusions  Low doses of losartan reduce portal hypertension by an increase in splanchnic vascular resistance without hypotensive side‐effects on arterial pressure.
COX‐2 inhibition and prostaglandin receptors in experimental nephritis
Authors: Waldner C. , Heise G. , Schrör K. , Heering P. 
Published: October 2003

AbstractBackground  Renal cyclooxygenases (COX) produce the prostaglandins (PG) E2, I2 and thromboxane (TxA2), which interact with distinct G protein‐coupled receptors. We investigated the expression of the three EP receptors EP2, EP3 and EP4 and the receptors for PGI2 (IP) and TxA2 (TP) in rats with passive Heymann nephritis (PHN). We studied their regulation by COX‐2 inhibition with celecoxib.Materials and methods  Four groups of Wistar rats were studied: healthy rats (group A), healthy rats treated with celecoxib (group B), rats with PHN (group C), and rats with PHN receiving celecoxib (group D). Expression of the mRNA for all receptors in the renal cortex and for the EP3 receptor in cultured mesangial cells (MCs) was determined by semiquantitative reverse transcriptase polymerase chain reaction. Stable prostaglandin metabolites were measured in the urine by radioimmunoassay.Results  Rats with PHN (group C) showed an 1·8‐fold increase of cortical EP3 receptor mRNA expression as compared with controls (group A). In celecoxib‐treated PHN rats (group D) the mRNA expression of the EP3 and EP4 receptors was significantly reduced to 1·0‐fold and 0·7‐fold induction, respectively. Furthermore, the excretion of bicyclo‐prostaglandin E2 (PGE2) was inhibited by celecoxib. No changes were observed in the expression of the other PG‐receptors. In cultured MC, PGE2 enhanced the EP3 mRNA expression.Conclusions  These data suggest a predominant role of the EP3 receptor in the transduction of PGE2‐actions in PHN. It was concluded that COX‐2‐dependent PGE2 is able to potentiate its effects in the kidney by up‐regulating its own receptors.
Low concentrations of intravenous polygelines promote low‐molecular weight proteinuria
Authors: Veldman B. A. J. , Schepkens H. L. E. , Vervoort G. , Klasen I. , Wetzels J. F. M. 
Published: October 2003

AbstractBackground  Previously we observed that atrial natriuretic peptide (ANP)‐induced albuminuria was accompanied by an increase in urinary excretion of the low‐molecular weight protein (LMW protein) β2‐microglobulin (β2‐m), suggesting that the albuminuria may at least partly be the result of blockade of tubular protein reabsorption. However, in our experiments ANP was dissolved in the polygeline Haemaccel® (Hoechst, Behring‐Werke, Marburg Germany) to prevent adhesion of ANP to the infusion system. Anecdotal reports have shown that high dosages of polygelines such as Haemaccel® or Gelofusine® (Braun NPBI Oss, the Netherlands) may influence tubular protein handling. In the present study we have evaluated the effect of a low and high doses of the polygeline Haemaccel® on proteinuria. In addition, we have reassessed the effects of ANP.Materials and methods  We measured urinary β2‐microglobulin (β2‐m) and albumin excretion in healthy volunteers after infusion of a high‐dose pure Haemaccel® (0·04 mL kg−1 min−1 for 60 min), a low‐dose Haemaccel® (0·01 mL kg−1 min−1 for 60 min followed by infusion of 0·02 mL kg−1 min−1 for 60 min) and a low‐dose Gelofusine® (dose comparable to the low‐dose Haemaccel®). In addition we performed similar studies using ANP dissolved in saline and Haemaccel®.Results  Infusion of Haemaccel® caused a dose‐dependent increase in urinary excretion of β2‐m. There were no differences between Haemaccel® and Gelofusine®. After infusion of ANP dissolved in Haemaccel® urinary β2‐m excretion increased from 0·05 ± 0·03 µg min−1 to 27 ± 10 µg min−1 and urinary albumin excretion increased from 4·5 ± 1·1 µg min−1 to 9·7 ± 6·3 µg min−1 (P < 0·05). During ANP + saline infusion, urinary β2‐m excretion did not change, whereas the urinary albumin excretion increased from 5·3 ± 1·5 µg min−1 to 7·9 ± 2·4 µg min−1 (P < 0·05).Conclusions  Our study demonstrates that even low doses of the polygelines Haemaccel® and Gelofusine® profoundly attenuate the tubular reabsorption of the low‐molecular weight protein β2‐m. Atrial natriuretic peptide does not affect tubular protein reabsorption. Therefore, the rise in albuminuria during ANP infusion most likely reflects alterations in glomerular permeability.
New concepts in bilirubin encephalopathy
Authors: Ostrow J. D. , Pascolo L. , Shapiro S. M. , Tiribelli C. 
Published: October 2003

AbstractRevised concepts of bilirubin encephalopathy have been revealed by studies of bilirubin toxicity in cultured CNS cells and in congenitally jaundiced Gunn rats. Bilirubin neurotoxicity is related to the unbound (free) fraction of unconjugated bilirubin (Bf), of which the dominant species at physiological pH is the protonated diacid, which can passively diffuse across cell membranes. As the binding affinity of plasma albumin for bilirubin decreases strikingly as albumin concentration increases, previously reported Bfvalues were underestimated.Newer diagnostic tests can detect reversible neurotoxicity before permanent damage occurs from precipitation of bilirubin (kernicterus). Early toxicity can occur at Bfonly modestly above aqueous saturation and affects astrocytes and neurons, causing mitochondrial damage, resulting in impaired energy metabolism and apoptosis, plus cell‐membrane perturbation, which causes enzyme leakage and hampers transport of neurotransmitters.The concentrations of unbound bilirubin in the cerebro‐spinal fluid and CNS cells are probably limited mainly by active export of bilirubin back into plasma, mediated by ABC transporters present in the brain capillary endothelium and choroid plexus epithelium. Intracellular bilirubin levels may be diminished also by oxidation, conjugation and binding to cytosolic proteins.These new concepts may explain the varied susceptibility of neonates to develop encephalopathy at any given plasma bilirubin level and the selective distribution of CNS lesions in bilirubin encephalopathy. They also can suggest better strategies for predicting, preventing and treating this syndrome.
Four peptides decrease the number of human pancreatic adenocarcinoma cells
Authors: Vesely B. A. , McAfee Q. , Gower W. R. , Vesely D. L. 
Published: October 2003

AbstractBackground  Long‐acting natriuretic peptide, vessel dilator, kaliuretic peptide and atrial natriuretic peptide are four peptide hormones synthesized by the same gene. Their main known biologic properties are sodium and water excretion and blood pressure lowering in both animals and humans.Methods and materials  These four peptide hormones, each at their 1‐µm concentrations, were evaluated for their ability to decrease the number and/or proliferation of human pancreatic adenocarcinoma cells in culture at 24, 48, 72 and 96 h.Results  Vessel dilator, long‐acting natriuretic peptide, kaliuretic peptide and atrial natriuretic peptide decreased the number of human pancreatic adenocarcinoma cells in culture by 65% (P < 0·001), 47% (P < 0·01), 37% (P < 0·05) and 34% (P < 0·05), respectively, within 24 h. This decrease was sustained without any proliferation of the cancer cells occurring in the 3 days following this decrease in number. The mechanism of these peptide hormones’ decrease in cancer cell number and antiproliferative effects was a 83% (P < 0·001) or greater inhibition of DNA synthesis but not owing to enhanced apoptosis, i.e. programmed cell death. The two known mediators of these peptide hormones’ mechanism(s) of action, i.e. cyclic GMP and prostaglandin E2, inhibited DNA synthesis in these adenocarcinoma cells by 51% and 23%, respectively.Conclusions  Four peptide hormones significantly decrease the number of pancreatic adenocarcinoma cells within 24 h and inhibit the proliferation of these cells for at least 96 h. Their mechanism of doing so is via inhibition of DNA synthesis mediated in part by cyclic GMP.
The disturbance of drilling mud on rock formation and a method for error elimination on acoustic log curves
Authors: Wei Changjiang , Li Jianjun , Liu Baohua , Xu Shizhe 
Published: October 2003

ABSTRACTErrors in acoustic logs have a significant influence on the assessment of formations, the description of oil deposits and modelling using synthetic seismograms. The elimination of these errors is a problem that many researchers have been trying to solve for many years. We derive theoretical formulae for calculating the radial depth of investigation of acoustic logging, and analyse the relationship between the error in acoustic interval transit time and the altered zone thickness. We explain in detail how mud affects the acoustic interval transit time. We also describe the variation of altered zone thickness with time and a method for calculating the altered zone thickness. Finally, we present a set of new methods that can be directly applied to correct the disturbing influence on acoustic curves. Our results are obtained based on the fact that acoustic velocities in the altered zone show a small lateral variation. Examples are given of analysing the acoustic log data, which are collected from a BS well at three different times. This paper is significant both for selection of the acoustic logging device with proper transmitter‐to‐receiver distance (spacing) and improvement of the device.