bluuebunny/crossref_metadata_2025 huggingface dataset:
Thickened Pituitary Stalk on Magnetic Resonance Imaging in Children with Central Diabetes insipidus
Authors: Czernichow Paul , Garel Catherine , Léger Juliane
Published: April 2003

Magnetic resonance imaging (MRI) has revealed isolated pituitary stalk thickening (PST) in certain cases of idiopathic or secondary central diabetes insipidus (DI) due to infiltrative processes. Twenty-six children with DI and PST underwent cerebral MRI at the age of 8 ± 4 years and were followed (n = 25) by clinical and MRI evaluation for 5.5 ± 3.6 and 3.0 ± 2 years, respectively, but given no treatment other than hormonal substitutive therapy. Patients were subdivided into groups according to the etiology of the DI: germinoma (n = 4), Langerhans’ histiocytosis (n = 5) or ‘idiopathic’ DI with PST (n = 17). Complete anterior pituitary evaluation in 24 of the 26 patients revealed that 14 children were suffering from associated growth hormone deficiency and 7 had multiple hormone deficiencies. At the first MRI evaluation, pituitary stalk enlargement varied from 2.2 to 9.0 mm. The anterior pituitary gland was found to be normal (n = 12), small (n = 8) or enlarged (n = 6). At the final evaluation, a change in MRI features had occurred in 16 patients: morphological and/or signal changes in the PST (n = 16; 6 of whom showed an increase in PST) and changes in anterior pituitary gland size (n = 8; 3 of whom had increased and 5 had decreased). The presence of a growing suprasellar mass with a progressively enlarging pituitary stalk was demonstrated in the 6 patients who had shown increased pituitary stalk enlargement 1.8 ± 1.6 years after the first MRI. In 4 of these patients, a diagnosis of germinoma was made 1.3 ± 0.6 years after PST identification by MRI at the onset of DI, but the other 2 patients showing a suprasellar mass were still categorized as ‘idiopathic’ at the final clinical evaluation performed 7.8 and 12.3 years after DI onset. In 10 patients (all but 1 with Langerhans’ histiocytosis, showing ‘idiopathic’ DI) the pituitary stalk enlargement was diminished after 2.0 ± 1.9 years of MRI follow-up, and there was a complete reversal of pituitary stalk enlargement in 5 patients. We conclude that the natural history of ‘idiopathic’ isolated central DI with PST is unpredictable. Although germinoma should always be considered during the first 3 years of follow-up in patients presenting isolated DI with PST by repeated investigations every 3–6 months, it remains an infrequent etiology, affecting only 15% of cases in our study.
Catch-Up Growth in Short-at-Birth NICU Graduates
Authors: Seminara Salvatore , Rapisardi Gherardo , La Cauza Francesca , Mattei Patrizia , Donzelli Gianpaolo
Published: April 2003

The statural catch-up growth, defined as reaching at least tenth length/height percentile (P10) for normal population standards (–1.28 SD score, SDS), was studied in 73 infants short at birth (length < P10 for gestational age) admitted to NICU. Mean gestational age at birth was 35.2 weeks (range 29–41) and mean birth length standard deviation score –2.31 (–4.52/–1.46). Infants were measured at birth, at 3, 6, 12, 18, and 24 months corrected age and then once a year until 6 years chronological age. Statural catch-up growth was studied, with reference both to normal population standards and to individual genetic target. With reference to normal population standards, 44% of infants had caught-up at 3 months of age, 51% at 3 years, 66% at 4 years and 73% at 6 years. In the case of individual genetic targets, a similar trend was present, but the absolute values were slightly higher from 4 to 6 years (73 vs. 66% and 78 vs. 73%, respectively). Statistically significant changes in mean standard deviations score for chronological age were present from birth to 3 months, 3 to 12 months, 3 to 4 years and 5 to 6 years (p < 0.05). No differences were found in this trend of recovery when considering ponderal index (PI) at birth (symmetrical vs. asymmetrical), sex (male vs. female) or gestational age (p > 0.05). In the majority of cases infants with short stature at birth admitted to a NICU had a statural catch-up growth within the first years of life. This is more evident when considered in relation to individual genetic target rather than to normal population standards.
Antenatal and Early Postnatal Dexamethasone Treatment Decreases Cortisol Secretion in Preterm Infants
Authors: Karlsson Riikka , Kallio Jaana , Toppari Jorma , Scheinin Mika , Kero Pentti
Published: April 2003

Glucocorticoids are used antenatally to accelerate the maturation of fetal respiratory and cardiovascular systems when a threat of preterm delivery exists. Postnatally, they are used to prevent and treat respiratory distress syndrome. This study investigates the effects of antenatal (ACT) and early postnatal corticosteroid treatment (PCT) on serum cortisol and plasma catecholamine and adenosine 3′,5′-cyclic monophosphate (cAMP) concentrations in preterm neonates. The infants in the ACT group had a significantly lower cortisol concentration than the infants in the non-ACT group on the first day of life. After birth, the infants were further divided into non-PCT and PCT groups. PCT suppressed cortisol levels significantly after 2 days, and the cortisol levels were still lower 2 days after discontinuation of PCT. No effect of PCT on plasma cAMP or catecholamine concentrations was observed. The results indicate that both ACT and a short PCT can significantly suppress basal cortisol levels in preterm infants.
A Novel Nonsense Mutation of the KAL Gene in Two Brothers withKallmann Syndrome
Authors: Jansen C. , Hendriks-Stegeman B.I. , Jansen M.
Published: April 2003

Kallmann syndrome (KS), defined by the association of hypogonadotropic hypogonadism and anosmia or hyposmia, can be caused by mutations in the KAL gene on Xp 22.3. This gene encodes an extracellular matrix glycoprotein called anosmin-1, which belongs to the class of cell adhesion molecules. In the absence of a functional KAL protein, migration of both olfactory and gonadotropin-releasing hormone neurons is arrested. A defective anosmin-1 molecule may also play a role in the development of synkinesia and renal agenesis, which are exclusively seen in the X-linked form of KS. We describe the clinical presentation and molecular diagnosis of the defect in two brothers with KS. An X-linked mode of transmission was assumed on the basis of synkinesia and the presence of oligomenorrhoea in the mother. A novel nonsense mutation was found in exon 13 of the KAL gene, encoding the region of the fourth fibronectin type III repeat of anosmin-1, which results in an apparently nonfunctional truncated protein.
McCune-Albright Syndrome Associated with Non-Autoimmune Type of Hyperthyroidism with Development of Thyrotoxic Crisis
Authors: Isotani Haruhiko , Sanda Koji , Kameoka Keiichi , Takamatsu Junta
Published: April 2003

We report on a patient having McCune-Albright syndrome (MAS) associated with non-autoimmune hyperthyroidism associated with thyrotoxic crisis. Polyostotic fibrous dysplasia developed at age 8, and café-au-lait pigmentation was noted on the skin. At age 18, he developed hyperthyroidism with multiple adenomatous changes. The hyperthyroidism had been controlled with an antithyroid drug, but the antithyroid medication was discontinued by the patient at age 23. One year later, thyrotoxic crisis developed with fever, convulsions and loss of consciousness. Thyroid function tests showed serum concentrations of free T4 of 5.1 ng/dl, and serum TSH of <0.1 μU/ml. Serum thyroglobulin concentrations were markedly increased (1,280 ng/ml). Three major thyroid-related autoantibodies (TSH receptor antibody, antithyroglobulin, and antimicrosomal antibodies) were not detected in serum. Serum GH concentrations were increased, and not suppressed by the glucose tolerance test, but increased paradoxically by TRH. The thyrotoxic crisis was ameliorated by treatment with a β-adrenergic receptor-blocking agent, glucocoroticoid, iodine, antithyroid drug, and antibiotics. The cause of thyroidal defect in our patient is not considered to be autoimmune hyperthyroidism, but hyperthyroidism due to constitutive activation of Gsα by inhibition of its GTPase. This paper describes, as far as we know, the first case of MAS associated with thyrotoxic crisis. Because hyperthyroidism in this patient recurred quickly after discontinuation of the antithyroid drug, the mode of treatment for MAS-associated hyperthyroidism appears to be total surgical ablation or repetitive radioiodine therapy.
Human Immunodeficiency Virus Type 2 Infection in Spain
Authors: Machuca Ana , Soriano Vincent , Gutiérrez Mayte , Holguín Africa , Aguilera Antonio , Caballero Estrella , Cilla Gustavo
Published: April 2003

The first cases of human immunodeficiency virus type 2 (HIV-2) infection in Spain were identified in 1988, in 3 African immigrants living in Barcelona. Since then, up to December 1998, 92 individuals with HIV-2 infection have been reported in Spain. Most are adult men, infected through heterosexual contacts, originating from West African countries, and currently living in the largest urban Spanish cities. Fifteen individuals have developed AIDS, meanwhile the rest remain asymptomatic. For 22 subjects, HIV-2 subtyping was performed on proviral DNA, 16 being infected with subtype A (8 Spanish born and 8 African immigrants) and the remaining with subtype B (two Spanish born and 4 originating from Equatorial Guinea). Coinfection with HIV-1 was demonstrated in 9 individuals. In conclusion, HIV-2 is currently circulating in Spain with a low prevalence and without evidence for increase over time.
TTV Positivity and Transfusion History in Non-B, Non-C Hepatocellular Carcinoma Compared with HBV- and HCV-Positive Cases
Authors: Kim Soo Ryang , Hayashi Yoshitake , Kudo Masatoshi , Imoto Susumu , Song Kyung Boo , Ando Kenji , Shintani Shigeyuki , Koterazawa Toshihiro , Kim Ke Ih , Taniguchi Miyuki
Published: April 2003

The prevalence of TT virus (TTV) and its rate of transmission through transfusion were investigated to determine its possible hepatocarcinogenic role in non-B, non-C hepatocellular carcinoma (HCC) as compared with that in hepatitis B virus (HBV)- and hepatitis C virus (HCV)-positive HCC. Its transfection route in TTV-positive cases was also studied. Serum was positive for TTV in 77.8% (7/9) of HBV-positive, 36.4% (12/33) of HCV-positive, and 63.6% (7/11) of non-B, non-C cases of HCC. The rate of transmission through transfusion was 52.4% (11/21) in HBV-positive, 40.1% (61/152) in HCV-positive, 33.3% (2/6) in HBV+HCV-positive, and 40% (8/20) in non-B, non-C HCCs, while it was 48.3% (14/29) in TTV-positive and 39.3% (11/28) in TTV-negative cases. The association between TTV and HCC was limited, and the main route of infection of TTV was not through transfusion.
Persistent TT Virus Infection Does Not Contribute to the Development of Non-A to -G Hepatocellular Carcinoma
Authors: Shimizu Toshihiro , Moriyama Mitsuhiko , Tanaka Naohide , Arakawa Yasuyuki
Published: April 2003

We tested the sera of patients with non-A, non-B, non-C, non-G (non-A to -G) hepatocellular carcinoma (HCC) for the presence of TT virus (TTV) DNA and clinicopathologically elucidated the relationship between TTV infection and hepatocarcinogenesis. The study cohort consisted of 19 patients with non-A to -G HCC. Detection of TTV DNA was performed by the nested polymerase chain reaction according to a previously published method. TTV DNA was detected in the sera of 9 (47.4%) of the 19 patients with non-A to -G HCC. The clinical background factors and blood biochemical parameters of the TTV-DNA-positive and -negative HCC patients did not significantly differ. Three TTV-DNA-positive and 2 TTV-DNA-negative patients underwent surgical resection of the HCC. The histological findings in the non-cancerous liver tissue of the TTV-DNA-positive and -negative patients did not significantly differ. In conclusion, TTV infection does not affect the features of non-A to -G HCC.
A Vestigial X Open Reading Frame in Duck Hepatitis B Virus
Authors: Lin Bo , Anderson David A.
Published: April 2003

Duck hepatitis B virus (DHBV) appears to lack a homologue of the X protein found in mammalian hepadnaviruses. By replacing stop codons in the corresponding region of the DHBV genome, a hypothetical protein which closely matches the hydrophilicity profile of X proteins can be predicted, despite limited sequence homology. We conclude that a full-length X protein was once a common feature of the hepadnaviruses, conserved in structure but not sequence.
Multiple Conformational Epitopes Are Recognized by Natural and Induced Immunity to the E7 Protein of Human Papilloma Virus Type 16 in Man
Authors: Malcolm Karen , Meschede Wolfgang , Pawlita Michael , Koutsky Laura A. , Frazer Ian H.
Published: April 2003

The reactivity of sera from patients with cervical cancer with the E7 protein of human papilloma virus type 16 (HPV16) was estimated using a novel non-radioactive immunoprecipitation assay and four established protein- and peptide-based immunoassays. Six of 14 sera from patients with cervical cancer and 1 of 10 sera from healthy laboratory staff showed repeated reactivity with E7 in at least one assay. Four of the 7 reactive sera were consistently reactive in more than one assay, but only one was reactive in all four assays. Following immunization with E7, 2 of 5 patients with cervical cancer had increased E7-specific reactivity, measurable in one or more assays. No single assay was particularly sensitive for E7 reactivity, or predictive of cervical cancer. Mapping of E7 reactivity to specific E7 peptides was unsuccessful, suggesting that natural or induced E7 reactivity in human serum is commonly directed to conformational epitopes of E7. These results suggest that each assay employed in this study measures a different aspect of E7 reactivity, and that various reactivities to E7 may manifest following HPV infection or immunization. This finding is of significance for monitoring of E7 immunotherapy and for serological screening for cervical cancer.
Remodelling and Enhanced Myogenic Tone in Cerebral Resistance Arteries Isolated from Genetically Hypertensive Brattleboro Rats
Authors: Dunn William R. , Wallis Sarah J. , Gardiner Sheila M.
Published: April 2003

In this study, we examined the structural and functional properties of cerebral resistance arteries isolated from normotensive (Di/N), and hypertensive (Di/H), vasopressin-deficient rats. Di/H rats had a significantly higher mean arterial blood pressure (MAP, 159 ± 3 mm Hg) than Di/N rats (125 ± 2 mm Hg). Vessels were set up in a pressure myograph, and the internal diameter and wall thickness were determined at increasing intraluminal pressures under passive (calcium-free) conditions. Arteries were then pressurized to the MAP of the animal, from which they were isolated and fixed with glutaraldehyde, embedded in araldite, sectioned and examined histologically. Under passive conditions, the middle cerebral artery (MCA) from Di/H rats had a smaller internal diameter than the MCA isolated from Di/N rats at all distending pressures. This smaller internal diameter of vessels from hypertensive rats is characteristic of eutrophic inward remodelling, whereby a similar amount of wall material is organized around a smaller lumen, without vascular growth or an alteration in artery distensibility. We have previously shown that similar structural alterations occur in mesenteric resistance arteries isolated from Di/H rats. In the presence of extracellular calcium (1.6 mmol/l), the MCA isolated from Di/H rats had significantly more intrinsic tone than the MCA isolated from Di/N rats in the pressure range of 10–110 mm Hg, although arteries from both strains had a similar myogenic index. The increased intrinsic constriction was a specific enhancement of pressure-induced tone, since responses to the thromboxane mimetic, U46619, were decreased, rather than increased, in the MCA isolated from Di/H rats. Furthermore, it is unlikely that the increased intrinsic tone in arteries isolated from Di/H rats was due to an impaired endothelial function since responses to the endothelium-dependent vasodilator, bradykinin, were enhanced in these vessels compared to arteries isolated from Di/N rats.
Antihypertensive Effect of All-cis-5,8,11,14,17-Icosapentaenoate of Aged Rats Is Associated with an Increase in the Release of ATP from the Caudal Artery
Authors: Hashimoto Michio , Shinozuka Kazumasa , Shahdat Hossain M. , Kwon Young Mi , Tanabe Yoko , Kunitomo Masaru , Masumura Sumio
Published: April 2003

Fish oils have been shown to lower blood pressure in hypertensive subjects. All-cis-5,8,11,14,17-icosapentaenoate (EPA), one of the ω–3 polyunsaturated fatty acids, is known to be one of the major active components in fish oil that has beneficial effects on the cardiovascular system. However, little is known about the antihypertensive effect of EPA alone on blood pressure. In the present study, we have determined the spontaneous and noradrenaline-evoked release of ATP, ADP, AMP, and adenosine from caudal arteries of aged (100 weeks old) Wistar rats which were fed a standard diet or a high cholesterol diet, treated with EPA. Dietary EPA administration increased plasma and caudal arterial EPA concentrations and repressed increases in blood pressure with advancing age in both aged rats with and without hypercholesterolemia. In addition, noradrenaline (1 µmol/l) evoked a significantly greater release of purines from the caudal arteries of EPA-administered aged rats compared to both sets of control rats. Regression analysis revealed a significant relationship between the total amount of purines released from the artery and blood pressure. These results suggest that administration of EPA to aged rats increases the release of ATP from the vascular endothelial cells, leading to repression of the blood pressure rise seen with advancing age.
Pulsatile Stretch and Shear Stress: Physical Stimuli Determining the Production of Endothelium-Derived Relaxing Factors
Authors: Busse Rudi , Fleming Ingrid
Published: April 2003

Mechanical forces generated at the endothelium by fluid shear stress and pulsatile stretch are important in ensuring the continuous release of vasoactive endothelial autacoids. Although the mechanism by which endothelial cells are able to detect and convert these physical stimuli into chemical signals is unclear, this process involves the activation of integrins, G proteins and cascades of protein kinases. The constitutive endothelial nitric oxide synthase (NOS III), classified as a Ca2+/calmodulin-dependent isoform, can be activated by shear stress and isometric contraction in the absence of a maintained increase in [Ca2+]i via a mechanism involving its redistribution within the cytoskeleton/caveolae and the activation of one or more regulatory NOS-associated proteins. Thus it would appear that the intracellular cascades activated by Ca2+-elevating receptor-dependent agonists, such as bradykinin, and hemodynamic stimuli are distinct. Rhythmic vessel distension is also able to elicit the synthesis of superoxide anions and the endothelium-derived hyperpolarizing factor which play a role in modulating arterial compliance in certain vascular beds.
Reactivity of Small Intramyocardial Arteries from Atherosclerotic and Non-Atherosclerotic Human Hearts
Authors: Chester Adrian H. , Borland Julie A.A. , Morrison Karen J.M. , Amrani Mohamed , McG. Thom Simon , Yacoub Magdi H.
Published: April 2003

Little is known about how the vascular reactivity of the coronary microcirculation is affected by upstream atherosclerotic disease. We have examined, with a wire myograph, the responses of intramyocardial arteries from hearts in which the epicardial vessels were either free of atherosclerotic lesions (non-diseased group) or were affected by atherosclerosis (diseased group). Vasodilator responses of preconstricted vessels to substance P (84.1 ± 12.6 compared to 42.0 ± 19.7%) were less in vessels from the diseased group (p < 0.05). In contrast, the relaxation to bradykinin (70.2 ± 21.2 compared to 100.6 ± 7.9%) was increased in vessels from the diseased group (p < 0.05). The dilator responses to acetylcholine, adenosine diphosphate, histamine and sodium nitroprusside showed no significant differences between arteries from each group. 5-Hydroxytryptamine was without any significant vasodilator effect in arteries from either group. Assessment of contractile function revealed that the responses to 5-hydroxytryptamine, acetylcholine, U46619, endothelin-1 and L-NG-monomethylarginine in each group were not significantly different. Histamine, noradrenaline and dopamine were without any significant contractile response. These results demonstrate that upstream atherosclerosis does not confer any global impairment of endothelium-dependent vasorelaxant responses or smooth muscle hyperreactivity to vasoconstrictors in the arteries that penetrate the myocardium.
Arteriolar Remodeling in Skeletal Muscle of Rats Exposed to Chronic Hypoxia
Authors: Price Richard J. , Skalak Thomas C.
Published: April 2003

The topological structure of the arteriolar network is an important determinant of microvascular resistance. In several normal and pathological conditions, this network topology is remodeled such that adequate tissue perfusion and oxygenation are maintained. The objective of this study was to quantify the extent of arteriolar remodeling in skeletal muscle of rats chronically exposed to 10% oxygen for 18 ± 3.6 days. Arcade arteriolar (AA) and transverse arteriolar networks that had been immunofluorescently labeled for smooth muscle α-actin and smooth muscle myosin heavy chain were observed in whole-mount gracilis muscles from hypoxic and weight-matched control rats. Eight muscles from 4 animals were used for analysis in each group. The percentage (± SD) of terminal arteriolar endings that were positive for smooth muscle α-actin, but negative for smooth muscle myosin heavy chain increased significantly (p < 0.05) from 29.2 ± 8.0 in controls to 70.7 ± 9.0 in hypoxia, indicating that the rate of terminal arteriolar development was elevated in the hypoxic animals. The number of AA loops/muscle (± SD) increased significantly from 9.6 ± 2.3 in controls to 14.4 ± 4.6 in hypoxia. This increase in AA loops/muscle was due primarily to a large increase in the number of small-diameter (<15 µm) AA segments/muscle, suggesting that new AA loops were formed via the recent anastomosing of developing small-diameter terminal arterioles. The results demonstrate that exposure to chronic hypoxia stimulates significant remodeling of both the arcade and transverse arteriolar networks in skeletal muscle.
Blockade of Ca2+-Activated K+ Channels Inhibits Proliferation of Human Endothelial Cells Induced by Basic Fibroblast Growth Factor
Authors: Wiecha Johannes , Münz Benedikt , Wu Yongjian , Noll Thomas , Tillmanns Harald , Waldecker Bernd
Published: April 2003

Basic fibroblast growth factor (bFGF) exerts angiogenic and mitogenic properties in human tissue. Since changes in ion currents modulate essential Ca2+-dependent intracellular pathways in endothelial cells, we have investigated a possible contribution of Ca2+-activated K+ channels (BKCa) on bFGF-induced endothelial cell proliferation. The patch-clamp technique was used to identify BKCa and to study their modulation by bFGF in cultured endothelial cells of human umbilical cord veins (HUVEC). Cell counts of HUVEC were carried out on different days to analyze bFGF-induced cell proliferation and its influence by the specific BKCa blocker iberiotoxin (IBX). Using single-channel recordings, we found characteristic BKCa with a single-channel slope conductance of 170.3 ± 2.1 pS (n = 7), half-maximal activation at internal pCa = 5.7 (n = 5; test potential: 80 mV), and dose-dependent block by IBX (25–100 nmol/l). In cell-attached patches bFGF (50 ng/ml) caused a significant increase in the open-state probability (NPo) after 6 min at test potentials of 80 and 100 mV (n = 28; p < 0.001), respectively, which lasted up to 30 min. After preincubation with pertussis toxin (100 ng/ml; 4 h) bFGF superfusion did not cause a significant increase in BKCa activity until 25 min had passed (n = 20; p < 0.01). Addition of 100 nmol/l IBX to the pipette solution caused a total block of BKCa within 2 min in cell-attached patches, whereas bFGF (50 ng/ml) was not able to activate BKCa. When incubated with IBX (25–100 nmol/l) every 2 days, bFGF-induced proliferation of HUVEC was significantly decreased by 50 (–41%) and 100 nmol/l (–50%) IBX (n = 5; p < 0.001) after 7 days. We conclude that activation of BKCa by bFGF may play an important role in bFGF-induced proliferation of human endothelial cells and thus might be important in the process of angiogenesis and vascular remodelling.
A New Computerized Biomechanical Perfusion Model for ex vivo Study of Fluid Mechanical Forces in Intact Conduit Vessels
Authors: Gan Li-ming , Sjögren Lena Selin , Doroudi Roya , Jern Sverker
Published: April 2003

We have developed a new computerized biomechanical ex vivo perfusion system for intact conduit vessels in which a wide range of combinations of intraluminal pressure, fluid flow and shear stress could be set and maintained at target levels in mammalian conduit vessels under controlled metabolic conditions. Mean wall shear stress is calculated using the formula:τ = 1/2 * (ΔP/L)3/4 * (8ηQ/Π)1/4.Accuracy of the wall shear stress calculation was validated by ultrasonographic imaging of the vessel radius. In a series of simulation experiments, the hemodynamic homeostasis functions of the system were challenged by generating a wide range of vascular resistance in artificial vessels and by pharmacologically induced changes in vascular tone in intact human vessels. Despite rapid changes in vessel resistance, shear stress and pressure, or flow and pressure were maintained well at target levels. Shear- and pressure-stimulated production of the vasodilator prostaglandin E2 (PGE2) was used to validate the biological relevance of the model. PGE2 release was significantly more stimulated by high (25 dyn/cm2) compared to low (<4 dyn/cm2) shear (ANOVA, p = 0.012). High compared to low intraluminal pressure depressed the production of PGE2 (ANOVA, p = 0.019). In summary, the computerized perfusion model appears to offer new possibilities of investigating the complex interplay between fluid mechanics and the vascular wall.
Evaluation of Absolute Cerebral Blood Flow by Laser-Doppler Scanning – Comparison with Hydrogen Clearance
Authors: Uranishi Ryunosuke , Nakase Hiroyuki , Sakaki Toshisuke , Kempski Oliver S.
Published: April 2003

A major limitation of laser-Doppler (LD) flowmetry, which enables noninvasive and continuous recording of tissue perfusion, is its inability to evaluate the absolute cerebral blood flow (CBF). Using a computer-controlled micromanipulator, the LD scanning technique provides information on the brain microcirculation in many different locations, information which is not available from a single stationary probe. The purpose of the current study was to examine whether LD scanning estimates can be calibrated for the absolute CBF by comparing LD scanning with the hydrogen clearance (HC) method. In Wistar rats (n = 31) including old rats (122–123 weeks old, n = 8), the CBF was altered using the global ischemia model by bilateral carotid artery occlusion coupled with hypobaric hypotension. The CBF was determined simultaneously by the LD scanning technique and HC at each mean arterial blood pressure step, and the correlation of CBF between the two techniques was analyzed. CBF measured by LD scanning was expressed as LD units. Absolute CBF values obtained by methods were correlated (r = 0.87), and the formula to calibrate absolute CBF values from LD units was y = 1.8x – 0.6. On the other hand, in old rats the formula to calibrate the absolute values was different (y = 1.3x + 8.3, r = 0.85). The results suggest that CBF data obtained by LD scanning could be calibrated into absolute blood flow values in particular circumstances, and that LD scanning could compensate in part for the weakness of LD flowmetry.
Effects of Diabetes and Insulin Treatment of Diabetic Rats on Hyaluronan and Hyaluronectin Production in Injured Aorta
Authors: Chajara Abdesslam , Raoudi Maha , Delpech Bertrand , Courel Marie-Noëlle , Leroy Marcelle , Basuyau Jean Pierre , Levesque Hervé
Published: April 2003

The present study was conducted to determine the effect of diabetes with and without insulin treatment on the production of hyaluronen (HA) and distribution of hyaluronectin (HN) in the rat aorta 14 days after injury with a catheter balloon. Injury increased intima-media wet weight (+11%) and DNA content (+37.5%). This increase was slightly enhanced in untreated diabetic rats (+14.7% for wet weight and +48.9% for DNA content) and was significantly greater in diabetic rats treated with insulin (+28.9% for wet weight and +54% for DNA content). HA content increase in the injured aorta of nondiabetic rats (+43.6%) was similar in untreated diabetic (+44.7%) and more pronounced in diabetic rats treated with insulin (+91.3%). HA was markedly expressed in the neointima of nondiabetic rats, particularly near the lumen of the aorta. In untreated diabetic rats, HA was present throughout the neointima and not mainly close to the lumen. HA staining in the neointima of diabetic rats treated with insulin was similar to that in nondiabetic rats. HN was strongly expressed throughout the neointima of all groups. Injury enhanced the production of a high molecular mass HN (>400 kDa); this was not observed either in untreated or in insulin-treated diabetic rats. In conclusion, insulin treatment promoted the proliferative response of aorta to injury and this was associated mainly with increased HA production. This finding suggests that HA, which has been shown to play a crucial role in smooth muscle cell proliferation and migration, may be involved in the promoting effect of insulin treatment on arterial wall reaction to injury.
Evidence for Structural Alterations in Resistance Arteries of Patients with Severe Congestive Heart Failure
Authors: Mengden T. , Douven C. , Vetter H. , Düsing R.
Published: April 2003

Congestive heart failure (CHF) is characterized by an increase in total peripheral resistance. It was the specific aim of this study to investigate whether structural factors participate in the increased peripheral resistance that can be observed in severe heart failure. We determined forearm vascular resistance (FVR) at rest and after 10 min ischemia (Rmin; mm Hg/ml/min/100 ml) using venous occlusion plethysmography. Rmin was studied since it is largely dependent on the structural characteristics of resistance arteries. 24 patients with CHF [71.5 ± 2.3 years; New York Heart Association (NYHA) functional class I–IV] with no history of arterial hypertension and casual arterial blood pressure < 140/90 mm Hg and 24 normotensive healthy control subjects (52.5 ± 4.1 years) were included in our study. The patients were subdivided into those with ‘mild’ (NYHA class I and II; n = 10) and ‘severe’ (NYHA class III and IV; n = 14) heart failure. There were no significant differences between the two groups for echocardiographically determined ejection fraction and mean arterial blood pressure. Resting FVR averaged 40.5 ± 4.4 mm Hg/ml/min/100 ml in control subjects and was 43.6 ± 7.9 (nonsignificant vs. control) and 51.0 ± 5 mm Hg/ml/min/100 ml (p < 0.05 vs. control) in patients with mild and severe CHF, respectively. No significant correlation between age and Rmin could be demonstrated in either the patient or the control group. Furthermore, Rmin did not differ between patients with mild CHF and control subjects. However, Rmin was significantly elevated in patients with severe CHF (5.7 ± 0.39 mm Hg/ml/min/100 ml) as compared to patients with mild CHF (4.0 ± 0.39 mm Hg/ml/min/100 ml; p < 0.05) and controls (4.5 ± 0.26 mm Hg/ml/min/100 ml; p < 0.05). In conclusion, our study supports the concept that structural alterations contribute to the increased peripheral resistance in patients with heart failure. These changes are correlated with the severity of clinical symptoms.
Relationships between Endothelium-Dependent Vasodilation, Serum Vitamin E and Plasma Isoprostane 8-Iso-PGF2α Levels in Healthy Subjects
Authors: Sarabi Mahziar , Vessby Bengt , Basu Samar , Millgård Jonas , Lind Lars
Published: April 2003

Due to the reported associations between a low intake of vitamin E and atherosclerosis on one hand, and between endothelial dysfunction and atherosclerosis on the other hand, we investigated the relationship between endothelium-dependent vasodilation and serum levels of vitamin E (α- and γ-tocopherol) as well as the lipid peroxidation markers malondialdehyde and 8-iso-PGF2α in a healthy population. Healthy subjects (31 men and 25 women), aged between 20 and 69 years, underwent measurements of forearm blood flow (FBF) at rest and during local infusion of 2 and 4 μg/min of methacholine (Mch, to evaluate endothelium-dependent vasodilation) and 5 and 10 μg/min of sodium nitroprusside (SNP, to evaluate endothelium-independent vasodilation, and during reactive hyperemia using venous occlusion plethysmography. Serum α-tocopherol concentration was significantly related to the index of endothelial function (r = 0.46, p < 0.01), defined as the ratio between the maximal dilatations during Mch and SNP infusions. Serum γ-tocopherol levels were positively related to the maximal FBF during reactive hyperemia (r = 0.54, p < 0.01) in women only. Furthermore, in women only, plasma 8-iso-PGF2α levels were inversely related to the relative increases in FBF during both Mch and SNP infusions (r = –0.58 and r = –0.59, p < 0.01 for both). The results show a relationship between the levels of α-tocopherol and endothelial vasodilatory function, suggesting a beneficial role for this potent lipid-soluble antioxidant also in a population sample of apparently healthy subjects. Furthermore, in women, the accumulation of lipid peroxidation products such as 8-iso-PGF2α seems to be associated with an impaired vasodilation in general.
Blockade of Angiotensin II Type 1 Receptors: Effect on Carotid and Radial Artery Structure and Function in Hypertensive Humans
Authors: Benetos A. , Gautier S. , Laflèche A. , Topouchian J. , Frangin G. , Girerd X. , Sissmann J. , Safar M.E.
Published: April 2003

Converting-enzyme inhibition reduces cardiovascular hypertrophy in hypertensive subjects. Whether the blockade of angiotensin II type 1 (AT1) receptors reduces arterial hypertrophy has never been investigated. In a double-blind study versus placebo in subjects with essential hypertension, the effect of the AT1 blocker irbesartan (150 mg/day for 8 weeks) on blood pressure, wall thickness, diameter and stiffness of the common carotid and radial arteries was studied, using echotracking techniques of high resolution. With irbesartan, mean blood pressure decreased significantly and proportionally to the baseline levels of active renin, and angiotensin I and II. There was a significant decrease in radial artery wall thickness. The percent change from baseline (± SEM) was –10.51 ± 3.42 versus 6.18 ± 4.77. There was no significant change in diameter or distensibility. This effect was correlated neither to blood pressure changes nor to hormonal baseline levels of the renin-angiotensin system. Carotid wall thickness and diameter were unchanged. Thus a 2-month treatment with an AT1 antagonist significantly reduced radial but not carotid artery wall thickness. Blood pressure reduction could be explained on the basis of circulating renin-angiotensin activity. On the contrary, radial artery wall thickness reduction was independent of the baseline circulating renin-angiotensin activity and was not correlated with the effects of AT1 blockade on blood pressure, thus implying the involvement of local hemodynamic and/or cellular mechanisms.
Neural Endothelin in Hypertension: Increased Expression in Ganglia and Nerves to Cerebral Arteries of the Spontaneously Hypertensive Rat
Authors: Milner Pamela , Loesch Andrzej , Burnstock Geoffrey
Published: April 2003

Endothelin has previously been localised in perivascular nerves of the rat basilar artery. Considering its potent vasoconstrictor and mitogenic properties on vascular smooth muscle, the potential role of a neural source of this peptide in hypertension has been investigated. The trigeminal, superior cervical and sphenopalatine ganglia of Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) at 16 weeks of age have been examined for immunolocalisation of endothelin at the light and electron microscope level. At the light microscope level, neurones immunopositive for endothelin were detected in these ganglia of the SHR but were not seen in ganglia from WKY rats. This difference was particularly marked in the trigeminal ganglia where endothelin-positive neurones colocalised with substance P immunoreactivity. Using in situ hybridisation techniques, endothelin-1 mRNA was localised to the cytoplasm of neurones in the ganglia and was more prominent in the SHR. At the electron microscope level, endothelin-immunoreactivity was localised at the peripheral perikarya of some neuronal cell bodies of the trigeminal, superior cervical and sphenopalatine ganglia of WKY rats but was more prominent with heavy labelling throughout the cytoplasm of neurones in the SHR. Notably, in the trigeminal ganglia of the SHR only, some endothelin-immunopositive nerve fibres appeared to be damaged and contained vacuoles with granular material. Ultrastructural examination of the basilar artery revealed an increased number of endothelin-positive axons in the SHR, but these axons usually showed selective damage. In summary, in the SHR, there was a marked increase in endothelin particularly in sensory neurones projecting to the basilar artery which also appear to be undergoing degenerative changes. An increased neural source of endothelin in the SHR may contribute to the development of hypertension or may be a consequence of selective degenerative change.
Static versus Dynamic Distensibility of the Carotid Artery in Humans
Authors: Lénárd Zsuzsanna , Fülöp Daniel , Visontai Zsuzsanna , Jokkel Gábor , Reneman Robert , Kollai Mark
Published: April 2003

In clinical studies, the elastic behavior of central arteries is usually assessed by measuring dynamic distensibility. In this study, we aimed to investigate how dynamic and static distensibility of the common carotid artery (Ddyn and Dstat, respectively) are related in 28 healthy volunteers of 20–71 years. The carotid diameter and its change with the pressure pulse were measured using an ultrasound echo-tracking device. Arterial blood pressure was measured by Finapres and carotid pressure was determined by applanation tonometry. Ddyn was determined at rest using the pressure pulse, while Dstat was determined during pressor responses induced by handgrip or cold pressor test. Data are given as mean ± 1 SD. In younger subjects (<35 years), Dstat did not differ from Ddyn (7.0 ± 3.4 vs. 6.5 ± 2.1·10–3·mm Hg–1, respectively), whereas in older subjects (>35 years), Dstat was significantly higher than Ddyn (3.8 ± 1.4 vs. 2.1 ± 0.9· 10–3·mm Hg–1, p < 0.001). For all subjects, Dstat and Ddyn decreased with increasing age and mean arterial pressure (MAP). Using stepwise multiple regression analysis, the strongest predictor of Dstat proved to be MAP, while that of Ddyn was age. Dstat was found to be linearly related to the hysteresis loop area of the pressure-diameter relation (r = 0.94), i.e. to vessel wall viscosity. It is concluded that, with increasing age, static distensibility overestimates the distension capacity of large arteries.
Cerebral Hemodynamic Response to CO2 Tests in Patients with Internal Carotid Artery Occlusion: Modeling Study and in vivo Validation
Authors: Ursino Mauro , Lodi Carlo Alberto , Russo Giuseppe
Published: April 2003

The aim of this work was to analyze the cerebral hemodynamics in patients with internal carotid artery (ICA) occlusion during CO2 dynamical tests. The study was performed using an original mathematical model of cerebral hemodynamics. The model includes the circle of Willis, the microvascular circulation in the territories of each cerebral artery, cortical anastomoses, intracranial pressure, the cerebrospinal fluid circulation, the brain venous circulation and two regulation mechanisms: autoregulation and CO2 reactivity. Model predictions are compared with real data obtained on 20 healthy subjects (group A) and 14 patients with unilateral ICA stenosis (group B) during CO2 tests. The percent changes in Doppler middle cerebral artery velocity per mm Hg of CO2 pressure variations (reactivity index, RI) were separately computed during hypocapnia and hypercapnia. In group A, the reactivity index was practically the same in both sides. Patients in group B had a significantly lower CO2 reactivity in the side ipsilateral to the occlusion (hypocapnia RI: 1.06 ± 1.6 vs. 2.3 ± 0.8%/mm Hg; hypercapnia: 0.9 ± 0.8 vs. 2.4 ± 1.0%/mm Hg). Our model can explain these results very well, assuming values for the diameter of the communicating arteries in the range reported in the clinical literature. Moreover, computer simulations suggest that patients with a small diameter of both communicating arteries (as low as 0.4–0.5 mm) exhibit a dramatic fall in CO2 reactivity in the ipsilateral side compared with the contralateral one, with the appearance of paradoxical responses. A decrease in ipsilateral RI reactivity, however, may also depend on the presence of a significant stenosis of the contralateral ICA.
Thrombospondin-1 Induces Endothelial Cell Apoptosis and Inhibits Angiogenesis by Activating the Caspase Death Pathway
Authors: Nör Jacques E. , Mitra Raj S. , Sutorik Michelle M. , Mooney David J. , Castle Valerie P. , Polverini Peter J.
Published: April 2003

Thrombospondin-1 (TSP1) is a potent natural inhibitor of angiogenesis. Although TSP1 has been reported to induce endothelial cell apoptosis in vitro and to downregulate neovascularization in vivo, the molecular mechanisms that link these two processes have yet to be established. Here we report that TSP1 mediates endothelial cell apoptosis and inhibits angiogenesis in association with increased expression of Bax, decreased expression of Bcl-2, and processing of caspase-3 into smaller proapoptotic forms. The ability of TSP1 to induce both endothelial cell apoptosis in vitro and to suppress angiogenesis in vivo was blocked by the caspase-3 inhibitor z-DEVD-FMK. TSP1 also attenuated VEGF-mediated Bcl-2 expression in endothelial cells in vitro and angiogenesis in vivo. Furthermore, TSP1 induced endothelial cell apoptosis and inhibited neovascularization in sponge implants in SCID mice. We conclude that TSP1 induces endothelial cell apoptosis and inhibits neovascularization by altering the profile of survival gene expression and activating caspase-3.
Ascorbate Transport in Pig Coronary Artery Smooth Muscle: Na+ Removal and Oxidative Stress Increase Loss of Accumulated Cellular Ascorbate
Authors: Holmes Melanie E. , Samson Sue E. , Wilson John X. , Dixon S. Jeffrey , Grover Ashok K.
Published: April 2003

Pig deendothelialized coronary artery rings and smooth muscle cells cultured from them accumulated ascorbate from medium containing Na+. The accumulated material was determined to be ascorbate using high-performance liquid chromatography. We further characterized ascorbate uptake in the cultured cells. The data fitted best with a Hill coefficient of 1 for ascorbate (Kasc = 22 ± 2 μM) and 2 for Na+ (KNa = 84 ± 10 mM). The anion transport inhibitors sulfinpyrazone and 4,4′-diisothiocyanatostilbene-2,2′-disulfonate (DIDS) inhibited the uptake. Transferring cultured cells loaded with 14C-ascorbate into an ascorbate-free solution resulted in a biphasic loss of radioactivity – an initial sulfinpyrazone-insensitive faster phase and a late sulfinpyrazone-sensitive slower phase. Transferring loaded cells into a Na+-free medium increased the loss in the initial phase in a sulfinpyrazone-sensitive manner, suggesting that the ascorbate transporter is bidirectional. Including peroxide or superoxide in the solution increased the loss of radioactivity. Thus, ascorbate accumulated in coronary artery smooth muscle cells by a Na+-dependent transporter was lost in an ascorbate-free solution, and the loss was increased by removing Na+ from the medium or by oxidative stress.
Mortality in Kuwait: Pattern and Seasonality
Authors: Moussa Mohamed A.A. , El Sayed Ali M.
Published: April 2003

This paper examines total and cause-specific mortality of the Kuwaiti population through a variety of life table models. Seasonality of diseases underlying mortality was also measured using the Fourier (cosinor) analysis. Results showed significant decline in total and infant mortality. Life table analysis showed that cardiovascular disease, accidental injury and malignant disease were the main causes of death in Kuwait and that ischemic heart disease was the major component of cardiovascular disease. The Fourier analysis showed a winter peak seasonality in January for total mortality, cardiovascular and respiratory diseases, and no seasonality for malignant disease, congenital anomalies or perinatal disease. Overall, Kuwait has the seasonal timing of developed countries for total mortality, cardiovascular and respiratory diseases due to the rapid changes in the life-style of people towards westernization. In conclusion, the study demonstrated the usefulness of national mortality statistics in measuring the force of mortality, and the ability of life table methods to assess the various roles that diseases may exhibit in the death process.
Computed Tomography for Evaluation of Adrenal Dysfunction: A 10-Year Follow-Up
Authors: Gupta Renu , Ammini A.C. , Berry M.
Published: April 2003

Objective: To evaluate the computed tomography (CT) morphology of the adrenal glands of patients with adrenal dysfunction. Methods: CT examination of adrenal glands was performed in 331 consecutive patients with symptoms suggestive of adrenal dysfunction. CT was performed using 4-mm contiguous sections for the adrenal area. Intravenous contrast was injected in 78 cases of the adrenal mass lesions. Results: We analyzed 331 consecutive CT scans performed over a 10-year period. One hundred and twenty-seven patients had hypercortisolism, 23 had unilateral adrenal tumor, 18 had bilateral adrenal hyperplasia and 86 had normal adrenals. The CT diagnosis was confirmed at surgery in all 23 unilateral adrenal tumors except in 1 case (tuberculosis in a hyperplastic adrenal gland). Among the 91 cases of hypertension, 86 were being evaluated for pheochromocytoma and 5 for Conn’s syndrome. Forty-three had adrenal pheochromocytoma (1 bilateral) and 10 had extra-adrenal pheochromocytoma detectable on CT. Two of the 5 cases of hyperaldosteronism (Conn’s syndrome) had adrenal tumor. Adrenal enlargement was observed in 17 of the 33 cases of Addison’s disease. Four of them were cases of histoplasmosis. Conclusion: CT scanning is a sensitive tool for the imaging of adrenal glands. Both neoplastic and inflammatory lesions can alter adrenal gland morphology. Our results highlight the importance of studying adrenal morphology. CT morphology is helpful to decide the modality of treatment.
Social and Moral Implications Arising from Genetic Screening and Genetic Engineering
Authors: Goldspink Geoffrey , MacDermot Kay D. , Novo Francisco J.
Published: April 2003

The development of techniques for altering the genetic make-up of humans as well as animals has proceeded at a much faster pace than the discussion of the moral and social implications. The human genome project aims at sequencing all the genes that are required to form a human being. The use of genetic profiles that appear to deviate from the ideal for assessing individuals for jobs or insurance cover is an aspect of this new science that will probably continue to present ethical problems. There are unquestionable benefits from treating hitherto incurable diseases using gene therapy and also from being able to produce pharmacologically active proteins in bacteria. Examples are given of how these are open to abuse. The development of techniques for cloning mammals including man also provides a moral dilemma as to where to draw the line between cloning human cells to reconstruct diseased organs and cloning a whole person. Therefore a total ban world-wide on cloning human tissue is perhaps impracticable and undesirable.