bluuebunny/crossref_metadata_2025 huggingface dataset:
Slow and fast changes in transmural pulmonary artery pressure in obstructive sleep apnoea
Authors: Marrone O , Bonsignore MR , Romano S , Bonsignore G
Published: October 2003

Our purpose was to assess how pulmonary artery pressure changes in relation to hypoxia and oesophageal pressure during obstructive sleep apnoeas. Transmural systolic pulmonary artery pressure (Ppa,STM), oxyhaemoglobin saturation (SaO2) and oesophageal pressure were analysed in two samples of consecutive obstructive apnoeas in each of four patients. In the first samples (samples A; probably recorded during non-rapid eye movement (NREM) sleep), SaO2 swings were small and repetitive. In the second samples (samples B; probably recorded during rapid eye movement (REM) sleep), they were large and more variable. Oesophageal pressure oscillated similarly in the two groups of samples. In all cases, transmural systolic pulmonary artery pressure progressively increased throughout apnoeas, and subsequently decreased in the interapnoeic periods. However, both early and end-apnoeic transmural systolic pulmonary artery pressure, remained stable in samples A; whilst they progressively increased in samples B. Transmural systolic pulmonary artery pressure at the beginning of each apnoea was inversely correlated with SaO2 at the end of the preceding apnoea. These results suggest that transmural systolic pulmonary artery pressure is influenced by SaO2, but does not vary at the same speed as SaO2. In all cases, beat-by-beat analysis showed, as expected, that the lower the oesophageal pressure, the higher the transmural systolic pulmonary artery pressure however, at each oesophageal pressure level, transmural systolic pulmonary artery pressure was more variable and higher, in samples B. In conclusion, transmural systolic pulmonary artery pressure in obstructive apnoeas shows rapid changes, which reflect oesophageal pressure variations, and slower changes, which are likely to be caused by SaO2.
Longitudinal lung function study in heterozygous PiMZ phenotype subjects
Authors: Tarjan E , Magyar P , Vaczi Z , Lantos A , Vaszar L
Published: October 2003

It is a matter of controversy whether subjects who are heterozygous (PiMZ) for alpha 1-antitrypsin deficiency are at risk of developing pulmonary emphysema. To assess the role of MZ phenotype in the development of abnormal lung function the authors performed a 10 year follow-up study of 28 PiMZ subjects, compared to 28 matched-paired normal PiMM subjects. Maximal expiratory flows and mechanical properties of the lungs were studied, in order to determine the changes of the lung function parameters characteristic of pulmonary emphysema. Total lung capacity and residual volume increased, whereas forced expiratory volume in one second, expiratory flows, diffusing capacity of the lungs for carbon monoxide, and static transpulmonary pressures decreased in the PiMZ patients. The majority of the controlled functional parameters were found to deteriorate significantly in PiMZ patients during the 10 year period. Trypsin inhibitory capacity in the PiMZ group (mean +/- SD) was 0.65 +/- 0.17 mg.ml-1 as compared to 1.52 +/- 0.3 mg.ml-1 in the PiMM group. These changes exceeded the values expected as physiological changes due to ageing. The findings in the present longitudinal study--especially the decrease in elasticity, which is the primary pathophysiological damage in alpha 1-antitrypsin deficiency--support the concept that the PiMZ phenotype is a risk factor for the development of pulmonary emphysema at younger age than in those without the deficiency.
Effects of combined inspiratory muscle and cycle ergometer training on exercise performance in patients with COPD
Authors: Wanke T , Formanek D , Lahrmann H , Brath H , Wild M , Wagner C , Zwick H
Published: October 2003

Cycle ergometer training plays an important role in the rehabilitation of patients with chronic obstructive pulmonary disease (COPD), but the usefulness of specific inspiratory muscle training as part of pulmonary rehabilitation remains uncertain. To determine whether inspiratory muscle training could intensify the known beneficial effects of cycle ergometer training on exercise performance in these patients, we compared the effect of an 8 week inspiratory muscle training combined with cycle ergometer training with that of an 8 week cycle ergometer training alone on inspiratory muscle performance and general exercise capacity. Patients were randomly assigned to the two training groups; 21 patients received additional inspiratory muscle training (Group 1) and 21 did not (Group 2). Maximal sniff assessed oesophageal and transdiaphragmatic pressures served as parameters for global inspiratory muscle strength and diaphragmatic strength, respectively. The duration for which the patient could breathe against a constant inspiratory pressure load was used as an index of inspiratory muscle endurance. Exercise capacity was determined by an incremental symptom-limited cycle ergometer test. After the training period, inspiratory muscle performance improved significantly in the patients with inspiratory muscle training, but not in those without. Both training regimens increased maximal power output and oxygen uptake, but this improvement was significantly greater in the patients with inspiratory muscle training than in those without.(ABSTRACT TRUNCATED AT 250 WORDS)
Immune-inflammatory functions of fibroblasts
Authors: Jordana M , Sarnstrand B , Sime PJ , Ramis I
Published: October 2003

Inflammation is a response that has evolved over millions of years to become an extremely complex process. This complexity reflects the host's need to deal effectively with a wide variety of potentially injurious agents, as well as the need to incorporate an adequate set of checks and balances. An inappropriately checked response, which occurs rarely, results in disease, either acute or chronic. However, in most instances, inflammation is a beneficial response, essential for survival. Inflammation comprises an extensive network of cellular interactions implemented by an overwhelming number of molecules. One category of signal includes soluble products, such as neuropeptide, lipid mediators, cytokines and growth factors, most of which can be produced by inflammatory/haemopoietic cells. However, resident structural cells can also produce many of these products and, on this basis only, fibroblasts, epithelial, endothelial and smooth muscle cells should be considered as active contributors to the regulation of the inflammatory response. Extracellular matrix (ECM) proteins comprise another category of signals. Whilst the most recognized activities of these proteins are those concerned with providing structural tissue integrity, it is clear that they also have powerful inductive effects. Indeed, ECM proteins can influence the shape, movement and state of activation of inflammatory cells in the tissue. Recent evidence indicates that these signals may also play substantial roles in homing of inflammatory cells to certain sites and in the handling of a number of cytokines and growth factors. In so far as fibroblasts are the main producers of ECM proteins, these new data establish an indirect but important role for fibroblasts in the regulation of the inflammatory response.
Respiratory muscles during ventilatory support
Authors: Fitting JW
Published: October 2003

Knowledge of the fate and behaviour of the respiratory muscles during ventilatory support is important for the guidance of clinical care. Full support facilitates muscle metabolic repletion, but exposes them to the risk of disuse atrophy. The effect of partial support varies according to the selected mode: assisted mechanical ventilation (AMV) and synchronized intermittent mechanical ventilation (SIMV) result in much less respiratory muscle rest than generally anticipated. On the other hand, inspiratory pressure support (IPS) is able to rest the respiratory muscles and to prevent fatiguing contractions. Opposite interventions have been proposed in case of difficult weaning: either to unload the respiratory muscles by using partial support, or to overload them according to a training programme. The optimal strategy is not known and may combine both approaches.
Proinflammatory potential of the airway epithelium in bronchial asthma
Authors: Raeburn D , Webber SE
Published: October 2003

Histopathological studies of asthmatic airways removed postmortem or by bronchial biopsy show marked inflammatory changes, notably epithelial cell disruption and damage, and the presence of large numbers of eosinophils. The epithelial damage is seen in mild, asymptomatic asthmatics as well as in patients who have died in status asthmaticus. Damage to the epithelium may also correlate with bronchial hyperreactivity. The epithelium has been suggested to be a target for inflammatory cell mediators and cytokines. Recently, the airway epithelium has itself been shown to produce and release several proinflammatory mediators and cytokines, and to express adhesion molecules for inflammatory cells. The epithelium, thus, may actively participate in the inflammatory changes in asthma, where it may be a source as well as a target. Drug therapy aimed at preventing inflammatory changes in the epithelium, such as cytokine and adhesion molecule expression, may be an important step forward in halting disease progression in asthma.
The earliest history of diaphragm physiology
Authors: Derenne JP , Debru A , Grassino AE , Whitelaw WA
Published: October 2003

The diaphragm was recognized as a distinct anatomical structure in the earliest Greek writings. However, the precise description of wounds suffered by warriors during the Trojan war by Homer was not tied to any particular function. The diaphragm was assimilated to the region that harbours thought. The first physiologic explanations of respiration by Empedocles in the 5th century BC and the concepts introduced by Plato and Hippocrates did not include a significant participation of the diaphragm. Aristole was the first to link respiration to a particular organ and a specific movement of the thorax. However, he considered that it was the heart which caused the lungs to expand by heating them, and the lungs in turn forced the thorax to dilate, a concept which was to survive until the 17th century. As in Aristole's theory the diaphragm played no role in respiration and was just a fence separating the thorax from the abdomen. A major break through occurred in Alexandria in the 4th and 3rd century BC: Herophilus was the first to recognize that muscles were the agents of movement and Erasistratus performed animal experiments which showed that the respiratory muscles were the agents of respiratory movements, thus opening the way to the later discoveries of Galen.
Fourier analysis versus multiple linear regression to analyse pressure-flow data during artificial ventilation
Authors: Peslin R , Gallina C , Saunier C , Duvivier C
Published: October 2003

Respiratory resistance (Rrs) and elastance (Ers) are commonly measured in artificially-ventilated patients or animals by multiple linear regression of airway opening pressure (Pao) versus flow (V') and volume (V), according to the first order model: Pao = P0 + Ers.V + Rrs.V', where P0 is the static recoil pressure at end-expiration. An alternative way to obtain Rrs and Ers is to derive them from the Fourier coefficients of Pao and V' at the breathing frequency. A potential advantage of the second approach over the first is that it should be insensitive to a zero offset on V' and to the corresponding volume drift. The two methods were assessed comparatively in six tracheotomized, paralysed and artificially ventilated rabbits with and without adding to V' an offset equal to 5% of the mean unsigned flow. The 5% flow offset did not modify the results of Fourier analysis, but increased Rrs and Ers from linear regression by 15.8 +/- 4.6% and 4.55 +/- 0.64%, respectively. Without additional offset, differences between the two methods averaged 30.2 +/- 14.0% for Rrs and 9.3 +/- 6.2% for Ers. The differences almost completely disappeared (2.47 and 0.61%, respectively) when the flow signal was zero-corrected using the assumption that inspired and expired volumes were the same. After induced bronchoconstriction, however, Ers was still slightly larger by linear regression than by Fourier analysis, which may result from nonlinearities and/or frequency dependence of the parameters. We conclude that the regression method requires zero flow correction and that Fourier analysis is an attractive alternative.
Necrobacillosis (Lemmiere's syndrome): a rare cause of necrotizing pneumonia
Authors: Dykhuizen RS , Olson ES , Clive S , Douglas JG
Published: October 2003

The cases of four young and previously healthy patients with necrobacillosis are reported. All four patients presented with acute pharyngotonsillitis and pulmonary infiltrates due to metastatic abscesses, and had neutrophil leucocytosis and hypoalbuminaemia. Blood cultures grew Fusobacterium necrophorum and each patient responded to metronidazole.
Bronchioloalveolar carcinoma with bronchorrhoea treated with erythromycin
Authors: Suga T , Sugiyama Y , Fujii T , Kitamura S
Published: October 2003

Recent reports have shown that erythromycin inhibits bronchial hypersecretion, and, accordingly, erythromycin was administered to a patient with bronchioloalveolar carcinoma with bronchorrhoea. After administration of erythromycin, marked reduction in the volume of sputum was observed, and the patient's quality of life was improved. It is concluded that erythromycin may reduce hypersecretion in bronchioloalveolar carcinoma.
Unusual manifestations of giant cell arteritis: pulmonary nodules, cough, conjunctivitis and otitis with deafness
Authors: Zenone T , Souquet PJ , Bohas C , Vital Durand D , Bernard JP
Published: October 2003

The major manifestations of giant cell arteritis have been well described. Pulmonary manifestations, however, are rare. We report the case of a 75 year old woman with temporal arteritis, presenting with atypical manifestations, i.e. nodular pulmonary lesions, dry cough, rhinitis, conjunctivitis, and otitis with hearing loss. We conclude that overlapping features of giant cell arteritis and Wegener's granulomatosis occur in some patients.
Effective use of cyclosporin in sarcoidosis: a treatment strategy based on computed tomography scanning
Authors: O'Callaghan CA , Wells AU , Lalvani A , Dhillon PD , Hansell DM , Mitchell DN
Published: October 2003

Cyclosporin was used successfully in a patient with severe pulmonary sarcoidosis, a poor response and unacceptable side-effects from corticosteroid therapy. Computed tomography (CT) scanning initially suggested reversible disease, and subsequently detected improvement earlier than other indices of disease activity. This information was critical in the decision to commence and to continue cyclosporin. The literature on the use of cyclosporin in sarcoidosis is reviewed.
Dyspnoea persisting after surgery for a vascular ring
Authors: Bron AO , Mensen EA , Dijkman JH , Huysmans HA , Aalbers R
Published: October 2003

We present the case of a 25 year old woman who, 3 yrs after resection of a vascular ring, had persisting complaints of episodic dyspnoea. This was caused by compression of the distal trachea and ostium of the right main bronchus by the descending part of the remaining right-sided aorta. Probable mechanisms are discussed.
Clinical Utility of an Immunoradiometric Assay for Parathyroid Hormone (1–84) in Primary Hyperparathyroidism
Authors: Silverberg Shonni J. , Gao Ping , Brown Ijeoma , LoGerfo Paul , Cantor Tom L. , Bilezikian John P.
Published: October 2003

The reliable diagnosis of primary hyperparathyroidism depends on the measurement of PTH. The PTH assays in widespread use measure not only the hormone but also hormone fragments, thus limiting the clinical utility of the assays. A new immunoradiometric assay (IRMA) using an antigenic determinant at the extreme amino-terminal of the PTH molecule detects only full-length PTH (1–84). We compared three PTH assays and determined the presence of PTH (1–84) and PTH fragments in serum and parathyroid adenomas of patients with primary hyperparathyroidism. We studied 56 patients with primary hyperparathyroidism. PTH levels were increased in 63% using the midmolecule RIA; in 73% in the “intact” IRMA; and in 96% in the PTH (1–84)-IRMA. The PTH (1–84)-IRMA correlated with the other assays (midmolecule RIA R = +0.736; P < 0.0001; “intact”-IRMA R = +0.951; P < 0.0001) and indices of disease activity (serum calcium R = +0.511, P < 0.0001; alkaline phosphatase R = +0.489, P = 0.001; and radius bone density R = −0.366, P < 0.01). In 21 consecutive patients undergoing parathyroidectomy, 18 had parathyroid adenomas. Intact PTH was higher than PTH (1–84)-IRMA in both serum and glandular homogenates from these patients. Similar proportions of PTH (1–84) and hormone fragments were found in both adenomas [66 ± 3% of “intact” PTH-reflected PTH (1–84) and sera (73 ± 2% of “intact” PTH reflected PTH (1–84)]. We conclude that the PTH (1–84)-IRMA offers improved diagnostic sensitivity in patients with primary hyperparathyroidism than other currently available assays. This study also provides evidence that both PTH (1–84) and PTH fragments are produced in parathyroid adenomas and that peripheral metabolism of hormone and fragment does not alter the proportion of bioactive hormone.
Octreotide Abolishes the Acute Decrease in Bone Turnover in Response to Oral Glucose
Authors: Clowes Jackie A. , Allen Heather C. , Prentis Donna M. , Eastell Richard , Blumsohn Aubrey
Published: October 2003

Feeding or oral intake of glucose results in an acute suppression of bone turnover. This does not appear to be mediated by insulin. Several gastrointestinal hormones modulate bone turnover in vitro and may mediate this response. We examined whether inhibiting the production of gastrointestinal hormones using octreotide could block glucose-mediated suppression of bone turnover. Fifteen subjects were each studied on four occasions in a randomized, single-blind, crossover study after receiving 1) oral placebo, iv saline; 2) oral glucose, iv saline; 3) oral glucose, iv octreotide; or 4) iv octreotide alone. We measured serum C-terminal telopeptide of type I collagen, urinary N-terminal telopeptide of type I collagen, osteocalcin, procollagen type I N-terminal propeptide, PTH, insulin, ionized calcium, and glucose over 4 h. All bone turnover markers decreased significantly after oral glucose (P < 0.001). At 120 min serum C-terminal telopeptide decreased by 45 ± 2%, urinary N-terminal telopeptide by 31 ± 7%, osteocalcin by 16 ± 1%, and procollagen type I N-terminal propeptide by 8 ± 1%. There was no significant decrease in bone turnover in response to oral glucose during octreotide infusion. Octreotide alone resulted in a significant increase in all bone turnover markers (P < 0.05) and PTH (P < 0.01). We conclude that octreotide completely abolishes the bone turnover response to glucose intake and increases PTH secretion. The apparent bone turnover response to feeding is probably mediated by an octreotide-inhibitable endocrine factor.
Cushing’s Syndrome Due to Medullary Thyroid Carcinoma: Diagnosis by Proopiomelanocortin Messenger Ribonucleic Acid in Situ Hybridization
Authors: Smallridge R. C. , Bourne K. , Pearson B. W. , van Heerden J. A. , Carpenter P. C. , Young W. F.
Published: October 2003

Medullary thyroid carcinoma (MTC) rarely causes ectopic ACTH syndrome. We describe a 38-yr-old man with renal stones who had a 5-cm MTC removed in 1992. He was RET-protooncogene positive (codon 618). Serum calcitonin was 1597 pg/ml postoperatively. In 1996 he had rib fractures, bruising, weakness, and three to four stools per day. Laboratory studies revealed an elevated 24-h urine-free cortisol (780 μg/d), epinephrine (66 μg/d), and calcium (558 mg/d). Baseline serum cortisol was 23.9 μg/dl and decreased to 12.9 and 4.5 μg/dl after 2 mg and 8 mg dexamethasone suppression, respectively. Plasma ACTH was 170 pg/ml and decreased to 75 and 24 pg/ml after dexamethasone. Bone density t-score was −4.3 (trochanter). Computed tomography scans showed multiple cervical nodes and 2-cm right adrenal nodule. Magnetic resonance imaging (MRI) scan showed a prominent, homogeneous pituitary; the adrenal MRI scan was not typical for a pheochromocytoma. Serum CRH was less than 6.6 pg/ml. Bilateral adrenalectomy revealed two adjacent right adrenal pheochromocytomas and corrected the elevated urine cortisol (30 μg/d), epinephrine (0 μg/d), and calcium (281 mg/d) but not plasma ACTH (125 pg/ml). Neck dissection reduced calcitonin by 96% (5300 to 120 pg/ml) and ACTH by 91% (125 to 11 pg/ml). Carcinoembryonic antigen was reduced from 32.0 to 2.3 ng/ml. Immunohistochemical stain was negative for ACTH in the MTC-positive lymph nodes and the pheochromocytoma. Proopiomelanocortin mRNA by in situ hybridization was positive in the MTC but not in the pheochromocytoma. A repeat pituitary MRI scan was normal. The differential diagnosis of ACTH-dependent Cushing’s syndrome in this case included pituitary disease or ectopic ACTH, either from medullary thyroid carcinoma or pheochromocytoma. ACTH stains were unrevealing, but proopiomelanocortin mRNA in situ hybridization in MTC tissue and plasma ACTH response to neck dissection confirmed MTC as the source of ectopic ACTH.
Association of Morphological Characteristics with Precocious Puberty and/or Gelastic Seizures in Hypothalamic Hamartoma
Authors: Jung H. , Probst E. Neumaier , Hauffa B. P. , Partsch C.-J. , Dammann O.
Published: October 2003

The pathogenesis of central precocious puberty (PP) and/or gelastic seizures due to a hypothalamic hamartoma (HH) is still under debate. We evaluated the association of clinical symptoms with morphology and localization of the HH in 34 patients.

The majority (86.4%) of HHs in patients with isolated PP (n = 22; 68.2% females) revealed a parahypothalamic position without affecting the third ventricle (91%). Half of them were pedunculated, and 40.9% showed a diameter less than 10 mm. In contrast, 11 of 12 patients with seizures, eight of whom were male, presented with a sessile intrahypothalamic hamartoma, 10 of which distorted the third ventricle. Logistic regression analysis revealed an increased relative risk (RR) for epilepsy in males (RR, 4.3; 95% confidence interval, 0.96–19). However, combination of the risk factor gender with intrahypothalamic position (RR, 19; 1.3–285) and distortion of the third ventricle (RR, 10; 0.6–164) reduced the risk associated with male gender to 1.1.

The position of a HH and involvement of the third ventricle are likely to be more predictive for clinical characteristics than size and shape. Male gender was associated with an intrahypothalamic HH and epilepsy, suggesting a sexually dimorphic developmental pattern of this heterotopic mass.
Effect of Pamidronate Treatment in Children with Polyostotic Fibrous Dysplasia of Bone
Authors: Plotkin Horacio , Rauch Frank , Zeitlin Leonid , Munns Craig , Travers Rose , Glorieux Francis H.
Published: October 2003

Intravenous infusions with the bisphosphonate compound pamidronate decrease bone pain and reportedly can lead to refilling of dysplastic lesions in adults with fibrous dysplasia (FD) of bone. Here we describe the effects of this treatment approach in 18 children and adolescents (age at start of therapy, 6.2–17.5 yr; eight girls) with polyostotic FD, who received pamidronate for 1.2–9.1 yr (median, 3.8 yr). Treatment cycles with pamidronate (1–1.5 mg/kg·d on 3 consecutive days) were given every 4 months. Levels of serum alkaline phosphatase and urinary collagen type I N-telopeptide were elevated at baseline and decreased continuously during the first 3 yr of therapy. There was no radiographic evidence of filling of lytic lesions or thickening of the bone cortex surrounding the lesions in any patient. Histomorphometric results in dysplastic bone tissue of patients receiving pamidronate (n = 7; time of therapy, 1.4–4.8 yr) were similar to those of patients without medical therapy (n = 9). No serious side effects were noted. In conclusion, pamidronate therapy appears to be safe in children and adolescents with polyostotic FD. However, we found no clear evidence that pamidronate has an effect on dysplastic lesions in such patients.
Reversible Metaphyseal Dysplasia, a Novel Bone Phenotype, in Two Unrelated Children with Autoimmunepolyendocrinopathy-Candidiasis-Ectodermal Dystrophy: Clinical and Molecular Studies
Authors: Harris Mark , Kecha Ouafae , Deal Cheri , Howlett C. Rolfe , Deiss Dorothee , Tobias Vivienne , Simoneau-Roy Judith , Walker Jan
Published: October 2003

We report the association of an undescribed, reversible metaphyseal dysplasia (RMD) with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in two patients, one homozygous and one heterozygous for a 13-bp deletion in exon 8 of the autoimmune regulator (AIRE) gene. One patient also had a novel deletion in exon 6, resulting in a frameshift mutation and introduction of a STOP codon in exon 10. Their APECED phenotypes differed, but both patients developed progressive skeletal deformities and growth failure from early childhood. Radiological examination suggested a generalized abnormality of endochondral ossification, with irregular, flared, radioopaque regions in the metaphyses, subjacent to the growth plates. Histopathology in patient 1 showed islands of calcified cartilage within bone, consistent with impaired coupling of cartilage resorption with vascular invasion and ossification. Despite discordance for puberty, both patients experienced radiological resolution of their bone disease in their mid-teens, with improvement in histopathology in patient 1. RMD may constitute a rare phenotypic variation of APECED, possibly resulting from autoimmunity directed against skeletal proteins. We also demonstrated AIRE expression in chondrocytes derived from human fetal growth plates, primary culture of human chondrocytes, and two chondrosarcoma cell lines, suggesting a potential role for abnormal AIRE expression in the development of RMD.
Auxology Is a Valuable Instrument for the Clinical Diagnosis of SHOX Haploinsufficiency in School-Age Children with Unexplained Short Stature
Authors: Binder Gerhard , Ranke Michael B. , Martin David D.
Published: October 2003

SHOX (short stature homeobox-containing gene) mutations causing haploinsufficiency have been reported in some individuals with idiopathic short stature and in many patients with Leri-Weill-dyschondrosteosis. Around 80% of SHOX mutations are complete gene deletions, whereas diverse point mutations account for the rest. The aim of this study was to estimate the prevalence of SHOX mutations in children with idiopathic short stature and to give an unbiased characterization of the haploinsufficiency phenotype of such children. We recruited 140 children (61 girls), in our clinic, with idiopathic short stature, which was defined by the presence of normal IGF-I and free T4; a normal karyotype in females; the absence of endomysium antibodies, of chronic organic, psychological, or syndromatic disease; and by the lack of clear signs of any osteodysplasia. Height, arm span, and sitting height were recorded, and subischial leg length was calculated. Two highly polymorphic microsatellite markers located around the SHOX coding region (CA-SHOX repeat and DXYS233) were PCR-amplified with fluorescent primers and separated in an automatic sequencing machine. Analysis of parental DNA was performed in the probands who had only one fragment size of each of both markers. SHOX haploinsufficiency caused by a SHOX deletion was confirmed in three probands (2%), all females, who carried a de novo deletion through loss of the paternal allele. Their auxological data revealed a significant shortening of arms and legs in the presence of a low-normal sitting height, when compared with the other 137 children tested. Therefore, the extremities-trunk ratio (sum of leg length and arm span, divided by sitting height) for total height was significantly lower in the three SHOX haploinsufficient probands, in comparison with the whole group. This observation was confirmed with the auxological data of five additional patients (four females) previously diagnosed with SHOX haploinsufficiency; all but the youngest girl had height-adjusted extremities-trunk ratios more than 1 sd below the mean. All children with SHOX haploinsufficiency exhibited at least one characteristic radiological sign of Leri-Weill-dyschondrosteosis in their left-hand radiography, namely triangularization of the distal radial epiphysis, pyramidalization of the distal carpal row, or lucency of the distal ulnar border of the radius. Our observations suggest that it is rational to limit SHOX mutation screening to children with an extremities-trunk ratio less than 1.95 + 1/2 height (m) and to add a critical judgment of the hand radiography.
Oxidative Stress Is Associated with Adiposity and Insulin Resistance in Men
Authors: Urakawa Hideki , Katsuki Akira , Sumida Yasuhiro , Gabazza Esteban C. , Murashima Shuichi , Morioka Kohei , Maruyama Noriko , Kitagawa Nagako , Tanaka Takashi , Hori Yasuko , Nakatani Kaname , Yano Yutaka , Adachi Yukihiko
Published: October 2003

To investigate the direct relationship of oxidative stress with obesity and insulin resistance in men, we measured the plasma levels of 8-epi-prostaglandin F2α (PGF2α) in 14 obese and 17 nonobese men and evaluated their relationship with body mass index; body fat weight; visceral, sc, and total fat areas, measured by computed tomography; and glucose infusion rate during a euglycemic hyperinsulinemic clamp study.

Obese men had significantly higher plasma concentrations of 8-epi-PGF2α than nonobese men (P < 0.05). The plasma levels of 8-epi-PGF2α were significantly correlated with body mass index (r = 0.408; P < 0.05), body fat weight (r = 0.467; P < 0.05), visceral (r = 0.387; P < 0.05) and total fat area (r = 0.359; P < 0.05) in all (obese and nonobese) men. There was also a significant correlation between the plasma levels of 8-epi-PGF2α and glucose infusion rate in obese men (r = −0.552; P < 0.05) and all men (r = −0.668; P < 0.01). In all subjects, the plasma levels of 8-epi-PGF2α were significantly correlated with fasting serum levels of insulin (r = 0.487; P < 0.01).

In brief, these findings showed that the circulating levels of 8-epi-PGF2α are related to adiposity and insulin resistance in men. Although correlation does not prove causation, the results of this study suggest that obesity is an important factor for enhanced oxidative stress and that this oxidative stress triggers the development of insulin resistance in men.
Direct Measurements of the Permeability Surface Area for Insulin and Glucose in Human Skeletal Muscle
Authors: Gudbjörnsdóttir Soffia , Sjöstrand Mikaela , Strindberg Lena , Wahren John , Lönnroth Peter
Published: October 2003

To elucidate mechanisms regulating capillary transport of insulin and glucose, we directly calculated the permeability surface (PS) area product for glucose and insulin in muscle.

Intramuscular microdialysis in combination with the forearm model and blood flow measurements was performed in healthy males, studied during an oral glucose tolerance test or during a one-step or two-step euglycemic hyperinsulinemic clamp.

PS for glucose increased significantly from 0.29 ± 0.1 to 0.64 ± 0.2 ml/min·100 g after oral glucose tolerance test, and glucose uptake increased from 1.2 ± 0.4 to 2.6 ± 0.6 μmol/min·100 g (P < 0.05). During one-step hyperinsulinemic clamp (plasma insulin, 1.962 pmol/liter), PS for glucose increased from 0.2 ± 0.1 to 2.3 ± 0.9 ml/min·100 g (P < 0.05), and glucose uptake increased from 0.6 ± 0.2 to 5.0 ± 1.4 μmol/min·100 g (P < 0.05). During the two-step clamp (plasma insulin, 1380 ± 408 and 3846 ± 348 pmol/liter), the arterial-interstitial difference and PS for insulin were constant. The PS for glucose tended to increase (P = not significant), whereas skeletal muscle blood flow increased from 4.4 ± 0.7 to 6.2 ± 0.8 ml/min·100 ml (P < 0.05).

The present data show that PS for glucose is markedly increased by oral glucose, whereas a further vasodilation exerted by high insulin concentrations may not be physiologically relevant for capillary delivery of either glucose or insulin in resting muscle.
Correlation between the Loss of Thyroglobulin Iodination and the Expression of Thyroid-Specific Proteins Involved in Iodine Metabolism in Thyroid Carcinomas
Authors: Gérard A.-C. , Daumerie C. , Mestdagh C. , Gohy S. , de Burbure C. , Costagliola S. , Miot F. , Nollevaux M.-C. , Denef J.-F. , Rahier J. , Franc B. , De Vijlder J. J. M. , Colin I. M. , Many M.-C.
Published: October 2003

Progress in biotechnology has provided useful tools for tracing proteins involved in thyroid hormone synthesis in vivo. Mono- or polyclonal antibodies are now available to detect on histological sections the Na+/I− symporter (NIS) at the basolateral pole of the cell, the putative iodide channel (pendrin) at the apical plasma membrane, thyroperoxidase (TPO), and members of the NADPH-oxidase family, thyroid oxidase 1 and 2 (ThOXs), part of the H2O2-generating system. The aim of this study was to correlate thyroglobulin (Tg) iodination with the presence of these proteins. Tg, T4-containing Tg, NIS, pendrin, TPO, ThOXs, and TSH receptor (TSHr) were detected by immunohistochemistry on tissue sections of normal thyroids and various benign and malignant thyroid disorders. Tg was present in all cases. T4-containing Tg was found in the adenomas, except in Hurthle cell adenomas. It was never detected in carcinomas. NIS was reduced in all types of carcinomas, whereas it was detected in noncancerous tissues. Pendrin was not expressed in carcinomas, except in follicular carcinomas, where weak staining persisted. TPO expression was present in insular, follicular carcinomas and in follicular variants of papillary carcinomas, but in a reduced percentage of cells. It was below the level of detection in papillary carcinomas. The H2O2-generating system, ThOXs, was found in all carcinomas and was even increased in papillary carcinomas. Its staining was apical in normal thyroids, whereas it was cytoplasmic in carcinomas. The TSHr was expressed in all cases, but the intensity of the staining was decreased in insular carcinomas. In conclusion, our work shows that all types of carcinomas lose the capacity to synthesize T4-rich, iodinated Tg. In follicular carcinomas, this might be due to a defect in iodide transport at the basolateral pole of the cell. In papillary carcinomas, this defect seems to be coupled to an altered apical transport of iodide and probably TPO activity. The TSHr persists in virtually all cases.
Adiposity Contributes to Differences in Left Ventricular Structure and Diastolic Function with Age in Healthy Men
Authors: Gates Phillip E. , Gentile Christopher L. , Seals Douglas R. , Christou Demetra D.
Published: October 2003

We sought to examine the influence of adiposity in age-associated changes in the left ventricle (LV) in a cohort of 113 healthy men, aged 20–79 yr, by measuring LV structure and diastolic function (echocardiography), whole body composition, and regional adiposity (dual energy x-ray absorptiometry). Aging was associated with increased levels of adiposity, greater wall thickness to chamber radius ratio, LV concentric remodeling, and reduced LV diastolic function (all P < 0.05). Bivariate correlation analysis showed that mean LV wall thickness, a concentric LV morphology, and diastolic function were related to adiposity (r = −0.63 to 0.51; all P < 0.05). The relation between age and both mean LV wall thickness and concentric remodeling was reduced after controlling for percentage total body fat (by 38% and 54%, respectively), percentage abdominal fat (by 42% and 62%), and the abdominal/thigh fat ratio (by 35% and 46%). The diastolic function-age relation was reduced after controlling for percentage total body fat (by 35%), percentage abdominal fat (by 39%), and the abdominal/thigh fat ratio (by 29%). There were no apparent differences in the contribution of percentage total body fat, percentage abdominal fat, or abdominal/thigh fat to the association between age and LV structure/diastolic function. We conclude that increasing adiposity contributes to the LV remodeling/reduced diastolic function that occurs with aging in healthy men.
The Hypoparathyroidism of Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Protective Effect of Male Sex
Authors: Gylling Mikhail , Kääriäinen Essi , Väisänen Riitta , Kerosuo Laura , Solin Marja-Liisa , Halme Leena , Saari Seppo , Halonen Maria , Kämpe Olle , Perheentupa Jaakko , Miettinen Aaro
Published: October 2003

In autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, hypoparathyroidism (HP) is the most common endocrine component. It occurs in most (but not all) patients. Determinants of its occurrence are unknown, and there is no proof for its autoimmune nature. Recently, the Ca2+-sensing receptor (CaSR) was reported to be an autoantigen in HP. With our group of 90 patients, we aimed at identifying the determinants and pathomechanism of HP. For the determinants, we evaluated gender and the HLA class II. For the pathomechanism, we searched for parathyroid autoantibodies, including antibodies against CaSR and PTH. Also, we studied whether AIRE is expressed in the human parathyroid, because its absence could be a pathogenetic factor. We found a clear gender linkage with lower and later incidence in males. Of the 14 patients who had escaped HP, 13 were males. This was associated with adrenal failure, which was the first or only endocrinopathy in 47% of males vs. 7% of females. In contrast, we found no linkage to the HLA class II. By immunofluorescence, 19% of the patients had antibodies to parathyroid epithelia. By immunoblotting, these recognized several parathyroid proteins. No antibodies were observed against the CaSR or PTH. By RT-PCR, AIRE mRNA was not found in the parathyroid.
The Pathophysiology of Diabetes Involves a Defective Amplification of the Late-Phase Insulin Response to Glucose by Glucose-Dependent Insulinotropic Polypeptide—Regardless of Etiology and Phenotype
Authors: Vilsbøll T. , Knop F. K. , Krarup T. , Johansen A. , Madsbad S. , Larsen S. , Hansen T. , Pedersen O. , Holst J. J.
Published: October 2003

The effect of the insulinotropic incretin hormone, glucagon-like peptide-1 (GLP-1), is preserved in typical middle-aged, obese, insulin-resistant type 2 diabetic patients, whereas a defective amplification of the so-called late-phase plasma insulin response (20–120 min) to glucose by the other incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), is seen in these patients. The aim of the present investigation was to evaluate plasma insulin and C-peptide responses to GLP-1 and GIP in five groups of diabetic patients with etiology and phenotype distinct from the obese type 2 diabetic patients. We studied (six in each group): 1) patients with diabetes mellitus secondary to chronic pancreatitis; 2) lean type 2 diabetic patients (body mass index < 25 kg/m2); 3) patients with latent autoimmune diabetes in adults; 4) diabetic patients with mutations in the HNF-1α gene [maturity-onset diabetes of the young (MODY)3]; and 5) newly diagnosed type 1 diabetic patients. All participants underwent three hyperglycemic clamps (2 h, 15 mm) with continuous infusion of saline, 1 pmol GLP-1 (7–36)amide/kg body weight·min or 4 pmol GIP pmol/kg body weight·min. The early-phase (0–20 min) plasma insulin response tended to be enhanced by both GIP and GLP-1, compared with glucose alone, in all five groups. In contrast, the late-phase (20–120 min) plasma insulin response to GIP was attenuated, compared with the plasma insulin response to GLP-1, in all five groups. Significantly higher glucose infusion rates were required during the late phase of the GLP-1 stimulation, compared with the GIP stimulation. In conclusion, lack of GIP amplification of the late-phase plasma insulin response to glucose seems to be a consequence of diabetes mellitus, characterizing most, if not all, forms of diabetes.
Final Height and Body Mass Index among Adult Survivors of Childhood Brain Cancer: Childhood Cancer Survivor Study
Authors: Gurney James G. , Ness Kirsten K. , Stovall Marilyn , Wolden Suzanne , Punyko Judy A. , Neglia Joseph P. , Mertens Ann C. , Packer Roger J. , Robison Leslie L. , Sklar Charles A.
Published: October 2003

The objectives of this study were 1) to compare final height and body mass index (BMI) between adult survivors of childhood brain cancer and age- and sex-matched population norms, 2) to quantify the effects of treatment- and cancer-related factors on the risk of final height below the 10th percentile (adult short stature) or having a BMI of 30 kg/m2 or more (obesity). Treatment records were abstracted and surveys completed by 921 adults aged 20–45 yr who were treated for brain cancer as children and were participants in the multicenter Childhood Cancer Survivor Study. Nearly 40% of childhood brain cancer survivors were below the 10th percentile for height. The strongest risk factors for adult short stature were young age at diagnosis and radiation treatment involving the hypothalamic-pituitary axis (HPA). The multivariate odds ratio for adult short stature among those 4 yr of age or younger at diagnosis, relative to ages 10–20 yr, was 5.67 (95% confidence interval, 3.6–8.9). HPA radiation exposure increased the risk of adult short stature in a dose-response fashion (trend test, P < 0.0001). Adjuvant chemotherapy was not an independent risk factor for adult short stature. BMI distribution in survivors did not differ appreciably from that of population norms; however, in females, young age at diagnosis and HPA radiation dose (trend test, P < 0.001) were associated with risk of obesity. Except for patients treated with surgery only, survivors of childhood brain cancer are at very high risk for adult short stature, and this risk increases with radiation dose involving the HPA. We did not find a corresponding elevated risk for obesity.
Phenotypic and Genetic Heterogeneity in Congenital Generalized Lipodystrophy
Authors: Agarwal Anil K. , Simha Vinaya , Oral Elif Arioglu , Moran Stephanie A. , Gorden Phillip , O’Rahilly Stephen , Zaidi Zohra , Gurakan Figen , Arslanian Silva A. , Klar Aharon , Ricker Alyne , White Neil H. , Bindl Lutz , Herbst Karen , Kennel Kurt , Patel Shailesh B. , Al-Gazali Lihadh , Garg Abhimanyu
Published: October 2003

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near complete absence of adipose tissue from birth. Recently, mutations in 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2) and Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) genes were reported in pedigrees linked to chromosomes 9q34 and 11q13, respectively. There are limited data regarding phenotypic differences between the various subtypes of CGL. Furthermore, whether there are additional loci for CGL remains unknown. Therefore, we genotyped 45 pedigrees with CGL for AGPAT2 and BSCL2 loci and compared the phenotypes in the various subtypes. Twenty-six pedigrees harbored mutations, including seven novel variants, in the AGPAT2 gene, and 11 pedigrees harbored mutations in the BSCL2 gene, including five novel variants. Eight pedigrees had no substantial alterations in either gene. Of these, three informative pedigrees showed no linkage to markers spanning the AGPAT2 and BSCL2 loci, and in six of the affected subjects, the transcripts of AGPAT2 and BSCL2 were normal. All subtypes of CGL showed high prevalence of diabetes, hypertriglyceridemia, and acanthosis nigricans. However, patients with BSCL2 mutations had lower serum leptin levels, an earlier onset of diabetes, and higher prevalence of mild mental retardation compared with other subtypes. We conclude that besides AGPAT2 and BSCL2, there may be additional loci for CGL. The genetic heterogeneity in CGL patients is accompanied by phenotypic heterogeneity.
Polyethylene dispersions in bitumen: The effects of the polymer structural parameters
Authors: Yousefi Ali Akbar
Published: October 2003

Polymer‐modified bitumens are very important to the transportation sector. Polyethylene is one of the most used polymers in bitumen modification. The effects of the structural parameters of polyethylene on its dispersion in bitumen and the performance of the resulting polymer‐modified bitumens were studied. With the addition of different polyethylenes to bitumen, the performance of bitumen at high temperatures increased as the polymer melt‐flow index (MFI) decreased. At low temperatures, the performance of bitumen decreased as the polyethylene MFI decreased. Furthermore, a decrease in the polyethylene MFI intensified its dispersion instability. At very low MFIs, the dispersions were unstable, even under the very high shear forces applied by a double mixer. Moreover, changes in the polyethylene MFI did not improve the dispersion stability at an elevated temperature (165°C). © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3183–3190, 2003
Effect of stabilization on creep crack growth in high‐density polyethylene
Authors: Pinter G. , Lang R. W.
Published: October 2003

Polyolefins, particularly polyethylene, are known to fail via crack initiation and crack propagation when exposed to multiaxial long‐term static stresses at elevated temperatures. Using concepts of linear elastic fracture mechanics, this article describes and discusses the effects of stabilization on the kinetics of creep crack growth (CCG) in high‐density polyethylene (PE‐HD) and the failure micromechanisms involved. As for the influence of stabilization, six PE‐HD formulations (two polymer types, each with three stabilizer systems) were investigated. CCG initiation times and CCG rates were determined at 60 and 80°C in distilled water as functions of the crack tip stress field characterized by the stress intensity factor. Although no influence of the stabilizer type was found in either polymer type for CCG initiation times and CCG rates at high crack speeds, significant effects of the added stabilizer type and concentration were detected for low CCG rates. The observed phenomena were explained in terms of local aging processes in the immediate vicinity of the crack tip, which were controlled by the presence and content of various stabilizers. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3191–3207, 2003
Synthesis and characterization of poly(1,3‐thiazol‐2‐yl‐carbomoyl) methyl methacrylate: Its metal complexes and antimicrobial activity studies
Authors: Soykan Cengiz , Erol İbrahim , Kırbağ Sevda
Published: October 2003

Poly(1,3‐thiazol‐2‐yl‐carbomoyl) methyl methacrylate [poly(TCMMA)] is prepared in dimethyl sulfoxide using 2,2′‐azobisisobutyronitrile as an initiator at 60°C. Poly(TCMMA) is characterized by IR and 1H‐NMR spectroscopic techniques. Cadmium(II), copper(II), and nickel(II) chelates of poly(TCMMA) were synthesized. An elemental analysis of the polychelates suggests a metal/ligand ratio of 1:2. The polychelates are further characterized by IR and magnetic susceptibility measurements. The thermal properties of the polymer and metal chelates are also discussed. The molecular weights of the poly(TCMMA) are determined by the gel permeation chromatography technique. The antimicrobial activities of the polymer and metal chelates are tested against Staphylococcus aureus COWAN I (bacteria), Escherichia coli ATCC 25922 (bacteria), Listeria monocytogenes SCOTTA (bacteria), Bacillus subtilis LMG (bacteria), Enterobacter aeroginosa CCM 2531 (bacteria), Klebsiela pneumania FMCS (bacteria), Candida albicans CCM 314 (Mayo yeast), and Saccharamyces cerevisiae UGA 102 (Mayo yeast). © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3244–3251, 2003