bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiinflammatory Effects of Angiotensin II Subtype 1 Receptor Blockade in Hypertensive Patients With Microinflammation
Authors: Fliser Danilo , Buchholz Konrad , Haller Hermann
Published: August 2004

Background—

Experimental studies revealed proinflammatory properties of angiotensin II. We evaluated antiinflammatory effects of the angiotensin II subtype 1 receptor antagonist olmesartan medoxomil alone and in cotherapy with the HMG-CoA reductase inhibitor pravastatin in patients with essential hypertension and microinflammation.

Methods and Results—

We measured a panel of vascular inflammation markers, including high-sensitivity C-reactive protein, and lipid levels during 12 weeks of therapy with olmesartan (n=100) or placebo (n=99) in a prospective double-blind multicenter study. Pravastatin was added to the double-blind therapy at week 6 in both treatment arms. Blood pressure control was achieved with addition of hydrochlorothiazide. Olmesartan treatment had already significantly reduced serum levels of high-sensitivity C-reactive protein (−15.1%;
P
<0.05), high-sensitivity tumor necrosis factor-α (−8.9%;
P
<0.02), interleukin-6 (−14.0%;
P
<0.05), and monocyte chemotactic protein-1 (−6.5%;
P
<0.01) after 6 weeks of therapy, whereas placebo treatment (ie, blood pressure reduction) had no major effect on inflammation markers. After 12 weeks of therapy, high-sensitivity C-reactive protein (−21.1%;
P
<0.02), high-sensitivity tumor necrosis factor-α (−13.6%;
P
<0.01), and interleukin-6 (−18.0%;
P
<0.01) decreased further with olmesartan and pravastatin cotherapy, but treatment with pravastatin alone (ie, cotherapy with placebo) did not significantly alter inflammation markers. In contrast, addition of pravastatin led to a significant (
P
<0.001) reduction in LDL cholesterol serum concentrations in the olmesartan and placebo treatment groups (−15.1% and −12.1%, respectively).

Conclusions—

Angiotensin II receptor blockade significantly reduces vascular microinflammation in patients with essential hypertension by as early as week 6 of therapy. This antiinflammatory action of angiotensin II receptor antagonists may contribute to their beneficial cardiovascular effects.
Increased Collagen Type I Synthesis in Patients With Heart Failure of Hypertensive Origin
Authors: Querejeta Ramón , López Begoña , González Arantxa , Sánchez Eloy , Larman Mariano , Martínez Ubago José L. , Díez Javier
Published: August 2004

Background—

We investigated whether increased collagen type I synthesis and deposition contribute to enhancement of myocardial fibrosis and deterioration of cardiac function in patients with hypertensive heart disease (HHD).

Methods and Results—

We studied 65 hypertensives with left ventricular hypertrophy subdivided into 2 groups: 34 patients without heart failure (HF) and 31 patients with HF. Transvenous endomyocardial biopsies of the interventricular septum were performed to quantify the amount of fibrotic tissue and the extent of collagen type I deposition. The carboxy-terminal propeptide of procollagen type I (PIP), an index of collagen type I synthesis, was measured by radioimmunoassay in serum samples from the coronary sinus and the antecubital vein. Compared with normotensives, the amount of collagen tissue, the extent of collagen type I deposition, and coronary and peripheral PIP were increased (
P
<0.01) in the 2 groups of hypertensives. These parameters were also increased (
P
<0.01) in HF hypertensives compared with non-HF hypertensives. Coronary PIP was higher (
P
<0.01) than peripheral PIP in hypertensives but not in normotensives. The amount of collagen tissue was inversely correlated with the ejection fraction and directly correlated with both coronary and peripheral PIP in all hypertensives.

Conclusions—

These findings suggest that an excess of cardiac collagen type I synthesis and deposition may be involved in the enhancement of myocardial fibrosis that accompanies the development of HF in HHD. In addition, our data show that the heart secretes PIP via the coronary sinus into the peripheral circulation in patients with HHD. Thus, PIP determined in peripheral blood can be a useful marker of myocardial fibrosis in these patients.
Inhibition of Cyclooxygenase-2 in the Rat Renal Medulla Leads to Sodium-Sensitive Hypertension
Authors: Zewde Tewabech , Mattson David L.
Published: August 2004

Cyclooxygenase-2 expression in the renal medulla is regulated by dietary salt intake. The present study was performed to determine the influence of chronic inhibition of medullary cyclooxygenase-2 on arterial blood pressure in conscious Sprague-Dawley rats maintained on a high-salt (4% NaCl) or a low-salt (0.4% NaCl) diet. Rats were uninephrectomized and instrumented with femoral arterial and femoral vein or renal medullary interstitial catheters. Each rat received a continuous medullary or intravenous infusion of saline (0.5 mL per hour) for 3 control days, followed by infusion of the cyclooxygenase-2 inhibitor NS-398 (10 mg/kg per day) for 5 days. Medullary interstitial infusion of NS-398 significantly increased mean arterial pressure in the 4% NaCl group from 126±2 to 146±2 mm Hg (n=6) but did not alter blood pressure in the 0.4% NaCl group (n=6). Intravenous infusion of NS-398 to rats on the 4.0% NaCl diet also failed to alter mean arterial pressure (n=5). To test the blood pressure effect of a mechanistically different inhibitor of cyclooxygenase-2, an antisense oligonucleotide against cyclooxygenase-2 (18-mer; 8 nmol per hour) was infused into the renal medulla of rats maintained on a high-salt diet. Administration of the antisense oligonucleotide reduced cyclooxygenase-2 immunoreactive protein by 36% and significantly increased mean arterial pressure from 127±2 to 147±2 mm Hg (n=6). Renal medullary interstitial infusion of a scrambled oligonucleotide did not alter arterial pressure (n=5). These results demonstrate the importance of cyclooxygenase-2 in the renal medulla in maintaining blood pressure during high-salt intake.
Whose Swadeshi? Contending Nationalisms among Indian Christians
Authors: Tharamangalam Joseph
Published: August 2004

The current resurgence of Hindu fundamentalism in India is broadly situated in the search for a pan-Indian Hindu identity, and in the assertion of a pan-Indian "Hindutva" (Hindu-ness) that is claimed to be the true heritage of Indians. This discourse inevitably involves the demarcation of the "Hindu" from the "other" — minorities defined as less Indian, if not foreign. Historical grievances are constructed against them and used to justify attacks on them. These "others", however, have their own discourses, their own constructions of identities, and their own articulations of historical grievances; and these are not necessarily defensive, or reactions to the Hindu fundamentalist discourse. This paper discusses the nationalist discourse of Indian Christians during the anti-colonial struggles and in the post-colonial era; an era that contained not only a rejection of Western colonial domination, but also a critique of Western hegemony over Christianity itself. Included in this discourse are the celebration of indigenous Christian traditions on the one hand, and the "Inculturation" (or simply, Indianization) of Christianity in such areas as the liturgy and even theology. Ironically, however, this process, spearheaded by the "upper caste" Christian elite, led to an oppositional discourse of the subaltern "lower caste" Christians, who resent what they see as "Sanskritization" or even "Brahminization". They have attempted to formulate their own forms of inculturation, including a sophisticated Dalit Theology. This paper examines the dialectic of these discourses, situating these in their specific historical, local-global contexts.
Religion across Borders: Transnational Religious Ties
Authors: Ebaugh Helen Rose
Published: August 2004

The fact that recent immigrants to the United States continue to participate in the daily life of the society from which they emigrate is true for religious identities and behaviours as well as in political, economic and family life. This paper describes transnational religious ties between immigrants in six American religious congregations; and family, friends and co-religionists in the home country. In addition to monetary exchanges that benefit religious purposes, there are also exchanges of norms, practices, and social capital. The varied pathways whereby remittances are exchanged are also described. The religious exchanges between home and host countries impact global religious systems.
Subaltern Studies 1 and Collective Memories in Piana degli Albanesi: Methodological Reflections on a Historiographical Encounter
Authors: Fracchia Joseph
Published: August 2004

The following essay is a set of reflections prompted by my encounter with the writings of several Subaltern Studies authors during the period in which I was working on collective memories in the Siculo-Albanian village, Piana degli Albanesi. My encounter with Subaltern Studies, though limited, has been richly suggestive in providing new ways of thinking about collective memories, and perhaps also in rethinking a major point of theoretical contention within Subaltern Studies itself. This essay will address both of these issues. It is organized around two problem complexes emerging from the historiographical affinities between Subaltern Studies and Pianese peasants, both immediately pertinent to the study of collective memory: the delineation of collectives and the class framework of experience; and (subaltern) bodies as sites of memory. Encounters, however, are seldom one-way streets. Woven into my analysis of collectives and their memories is a comment on, possibly a contribution to, the theoretical debate that resulted in an abrupt shift in the intellectual history of Subaltern Studies from its initial focus on reconstructing forms of peasant consciousness to its later concern with deconstructing discourses.
POSIDONIAN THOUGHTS—ANCIENT AND MODERN
Authors: Bloch René
Published: August 2004

Strabo's history of Judaism (Geography 16.2.35ff.), which is most probably copied from Posidonius, focuses less on the past which is idealized than on the present which is criticized—as is common in descriptions of a "golden age" which later deteriorates. The Posidonian thought that the Jewish religion declined made its way into Tacitus' mostly hostile ethnography of Judaism. Modern scholars, especially in the 19th century, when commenting on Posidonius and Tacitus sympathized from a quite different perspective with that very idea of a Jewish decline.
Gravity Reduces the Tibia When Using a Tibial Guide that Targets the Intercondylar Roof
Authors: Howell Stephen M. , Lawhorn Keith W.
Published: August 2004

Background

Reduction of the tibia relative to the femur with the knee in maximum extension is required to correctly position the tibial tunnel in the sagittal plane when using a guide that targets the intercondylar roof. The authors found no studies that determined (1) whether gravity reduces the tibia and (2) whether roof impingement is prevented without a roofplasty and without positioning the tibial tunnel too posteriorly.

Methods

The position of the tibia relative to the femur was measured from a lateral radiograph of the treated knee in maximum extension with and without the tibial guide and of the contralateral normal knee in extension in single-leg stance (control).

Results

The position of the tibia with and without the tibial guide was not different (P = .33, not significant) and was only 0.7 mm more posterior than the control knee (P = .0075). A roofplasty was not required, and the clearance was 2 mm or less.

Conclusion

Gravity reduces the tibia on the femur when using a guide that targets the intercondylar roof. The use of a tibial guide that targets the intercondylar roof prevents roof impingement without a roofplasty and without positioning the tibial tunnel too posteriorly.
Evaluation of Hamstring Strength and Tendon Regrowth after Harvesting for Anterior Cruciate Ligament Reconstruction
Authors: Tadokoro Kou , Matsui Nobuzo , Yagi Masayoshi , Kuroda Ryosuke , Kurosaka Masahiro , Yoshiya Shinichi
Published: August 2004

Background

It is generally thought that tissue regeneration and good functional recovery can be expected after anterior cruciate ligament reconstruction using the hamstring tendons. However, persistent strength deficit in deep knee flexion has also been reported.

Hypothesis

Morphologic regeneration of the harvested hamstring tendon is not necessarily associated with its functional recovery.

Study Design

Retrospective follow-up study.

Method

Twenty-eight patients who underwent anterior cruciate ligament reconstruction with hamstring graft were evaluated after a minimum period of 2 years. Status of tendon regrowth was assessed by magnetic resonance imaging. To specifically analyze the functional deficit after graft harvest, the isometric hamstring strength was examined in a sitting position at 90° of flexion and a prone position at 90° and 110° of flexion. Then, the strength data were correlated with the extent of tendon regeneration.

Results

In 22 of the 28 patients, a regrowth of the semitendinosus tendon was found, whereas regeneration of the gracilis tendon was observed in 13 patients. In the evaluation of hamstring strength, the isometric peak torque was reduced to 86.2%, 54.6%, and 49.1%, respectively, in the aforementioned 3 postures as compared with the contralateral side.

Conclusions

Significant functional deficit of hamstring strength remains regardless of morphologic regeneration.
Isokinetic Evaluation of Internal/External Tibial Rotation Strength after the Use of Hamstring Tendons for Anterior Cruciate Ligament Reconstruction
Authors: Armour Tanya , Forwell Lorie , Litchfield Robert , Kirkley Alexandra , Amendola Ned , Fowler Peter J.
Published: August 2004

Background

Evaluation of the knee after an anterior cruciate ligament reconstruction with the use of the semitendinosus and gracilis (hamstring) autografts has primarily focused on flexion and extension strength. The semitendinosus and gracilis muscles contribute to internal tibial rotation, and it has been suggested that harvest of these tendons for the purpose of an anterior cruciate ligament reconstruction contributes to internal tibial rotation weakness.

Hypothesis

Internal tibial rotation strength may be affected by the semitendinosus and gracilis harvest after anterior cruciate ligament reconstruction.

Study Design

Prospective evaluation of internal and external tibial rotation strength.

Methods

Inclusion criteria for subjects (N = 30): unilateral anterior cruciate ligament reconstruction at least 2 years previously, a stable anterior cruciate ligament (<5-mm side-to-side difference) at time of testing confirmed by surgeon and KT-1000 arthrometer, no history of knee problems after initial knee reconstruction, a normal contralateral knee, and the ability to comply with the testing protocol. In an attempt to minimize unwanted subtalar joint motion, subjects were immobilized using an ankle brace and tested at angular velocities of 60°/s, 120°/s, and 180°/s at a knee flexion angle of 90°.

Results

The mean peak torque measurements for internal rotation strength of the operative limb (60°/s, 17.4 ± 4.5 ft-lb; 120°/s, 13.9 ± 3.3 ft-lb; 180°/s, 11.6 ± 3.0 ft-lb) were statistically different compared to the nonoperated limb (60°/s, 20.5 ± 4.7 ft-lb; 120°/s, 15.9 ± 3.8 ft-lb; 180°/s, 13.4 ± 3.8 ft-lb) at 60°/s (P = .012), 120°/s (P = .036), and 180°/s (P = .045). The nonoperative limb demonstrated greater strength at all speeds. The mean torque measurements for external rotation were statistically similar when compared to the nonoperated limb at all angular velocities.

Conclusions

We have shown through our study that patients who undergo surgical intervention to repair a torn anterior cruciate ligament with the use of autogenous hamstring tendons demonstrate with weaker internal tibial rotation postoperatively at 2 years when compared to the contralateral limb.
Quantitative Assessment of Glenohumeral Translation in Baseball Players
Authors: Sethi Paul Michael , Tibone James E. , Lee Thay Q.
Published: August 2004

Background

Objective data quantifying differences in glenohumeral range of motion in baseball pitchers versus position players are established. There is limited information objectively comparing glenohumeral laxity in this same population.

Hypothesis

Baseball pitchers have greater difference in side-to-side anteroposterior translation of their throwing shoulders compared with position players.

Study Design

Prospective cross-sectional study.

Methods

Cutaneous electromagnetic sensors quantified anteroposterior shoulder translation of college and professional baseball players. Range of motion was measured.

Results

Nineteen position players and 37 pitchers were studied. Pitchers had a significant increase in external rotation of the dominant arm as compared with the nondominant arm (P = .02); the difference was not significant in position players (P = .34). The mean range of motion for pitchers’ dominant arm was 110° external rotation to 68° internal rotation, and it was 100° external rotation to 85° internal rotation for position players (P = .278). The mean anteroposterior translation in pitchers’ dominant arm was 33.30 mm and 29.84 mm in the nondominant side (P = .0001). This difference was not present in position players (P = .88). One of 19 position players had a side-to-side shoulder translation difference greater than 3 mm, compared with 22 of 37 pitchers (P = .0001).

Conclusions

Pitchers have a greater amount of glenohumeral translation in the dominant arm. This difference is not seen in position players. These differences make the side-to-side comparison less useful in pitchers and should be considered when making therapeutic decisions.
Bone Morphogenetic Protein–7 (Osteogenic Protein–1) Promotes Tendon Graft Integration in Anterior Cruciate Ligament Reconstruction in Sheep
Authors: Mihelic Radovan , Pecina Marko , Jelic Mislav , Zoricic Sanja , Kusec Vesna , Simic Petra , Bobinac Dragica , Lah Boris , Legovic Dalen , Vukicevic Slobodan
Published: August 2004

Background

Bone morphogenetic proteins induce new bone both in patients with bone defects and at extraskeletal sites in animals. After anterior cruciate ligament rupture, tendon graft fixation into a bone tunnel is a widely used method for anterior cruciate ligament reconstruction.

Hypothesis

Bone morphogenetic protein–7 applied to the bone-tendon interface enables better integration of a free tendon graft into the surrounding bone.

Study Design

Controlled laboratory study.

Methods

The anterior cruciate ligament was reconstructed using a free tendon graft in the right rear knees of 30 one-year-old male sheep. Recombinant human bone morphogenetic protein–7 (25 μg) was applied randomly to the bone-tendon interface in 15 animals, and a vehicle was applied in 15 control animals. At 3 weeks, 10 animals from each group were sacrificed, and the remaining sheep were sacrificed at 6 weeks after surgery. Subsequently, histologic analysis and mechanical testing were performed. In another group of 20 sheep, the same procedure was used and mechanical testing was performed after 3 weeks.

Results

More new bone was formed at the bone-tendon interface in the knees treated with bone morphogenetic protein–7 as compared histologically with similar areas in control animals, creating areas of dense trabecular network with significantly greater invasion of the tendon fibrous tissue into the bone marrow space. Mechanical testing showed greater strain resistance to force (368 N) in the knees treated with bone morphogenetic protein–7 than in control specimens (214 N). There was no difference between mechanical testing of samples from 3 and 6 weeks after surgery.

Conclusion

Bone morphogenetic protein–7 promotes complete tendon graft integration into the newly formed surrounding trabecular bone in the reconstruction of the anterior cruciate ligament.

Clinical Relevance

Bone morphogenetic protein–7 in tendon graft integration might be successfully used in reconstructive surgery of ligaments.
Diagnostic Accuracy of Clinical Assessment, Magnetic Resonance Imaging, Magnetic Resonance Arthrography, and Intra-Articular Injection in Hip Arthroscopy Patients
Authors: Byrd J. W. Thomas , Jones Kay S.
Published: August 2004

Background

Hip arthroscopy has defined elusive causes of hip pain.

Hypothesis/Purpose

It is postulated that the reliability of various investigative methods is inconsistent. The purpose of this study is to evaluate the diagnostic accuracy of these methods.

Study Design

Retrospective review of prospectively collected data.

Methods

Five parameters were assessed in 40 patients: clinical assessment, high-resolution magnetic resonance imaging, magnetic resonance imaging with gadolinium arthrography, intra-articular bupivacaine injection, and arthroscopy. Using arthroscopy as the definitive diagnosis, the other parameters were evaluated for reliability.

Results

Hip abnormality was clinically suspected in all cases with 98% accuracy (1 false positive). However, the nature of the abnormality was identified in only 13 cases with 92% accuracy. Magnetic resonance imaging variously demonstrated direct or indirect evidence of abnormality but overall demonstrated a 42% false-negative and a 10% false-positive interpretation. Magnetic resonance arthrography demonstrated an 8% false-negative and 20% false-positive interpretation. Response to the intra-articular injection of anesthetic was 90% accurate (3 false-negative and 1 false-positive responses) for detecting the presence of intra-articular abnormality.

Conclusions

In this series, clinical assessment accurately determined the existence of intra-articular abnormality but was poor at defining its nature. Magnetic resonance arthrography was much more sensitive than magnetic resonance imaging at detecting various lesions but had twice as many false-positive interpretations. Response to an intra-articular injection of anesthetic was a 90% reliable indicator of intra-articular abnormality.
Incidence and Location of bone Bruises after Acute Posterior Cruciate Ligament Injury
Authors: Mair Scott D. , Schlegel Theodore F. , Gill Thomas J. , Hawkins Richard J. , Steadman J. Richard
Published: August 2004

Background

In patients suffering from an anterior cruciate ligament injury, the incidence and location of bone bruises are well documented. This study reports data regarding bone bruises after acute posterior cruciate ligament injury.

Hypothesis

Bone bruises associated with posterior cruciate ligament injury are common, and their location differs from those seen with anterior cruciate ligament injury.

Study Design

Retrospective cohort study.

Methods

Thirty-five consecutive patients were identified as having a grade II or III posterior cruciate ligament tear, with an intact anterior cruciate ligament, in which a magnetic resonance imaging scan had been obtained within 20 days of injury. Magnetic resonance imaging scans were reviewed to document bone bruises, associated medial or lateral ligamentous injury, and meniscal and chondral abnormalities.

Results

Of the 35 patients, 29 (83%) had a bone bruise in at least one location. Bone bruises were found throughout the joint, more widely dispersed than is commonly seen with anterior cruciate ligament injury. Also, 29 patients had magnetic resonance imaging findings of associated ligamentous injury. Lateral bone bruises were associated with medial collateral ligament injury, whereas medial bone bruises correlated with posterolateral injury.

Conclusions

The incidence of bone bruises associated with posterior cruciate ligament injury is similar to that seen with anterior cruciate ligament injury. Their location is more widely dispersed. The location of a bone bruise should lead to careful magnetic resonance imaging inspection and physical examination for ligamentous injury to the opposite side of the joint. Truly isolated posterior cruciate ligament injuries are rare, as most occur with osseous and some degree of associated ligamentous injury.
Distinctive gene expression profiles of CD34 cells from patients with myelodysplastic syndrome characterized by specific chromosomal abnormalities
Authors: Chen Guibin , Zeng Weihua , Miyazato Akira , Billings Eric , Maciejewski Jaroslaw P. , Kajigaya Sachiko , Sloand Elaine M. , Young Neal S.
Published: August 2004

Aneuploidy, especially monosomy 7 and trisomy 8, is a frequent cytogenetic abnormality in the myelodysplastic syndromes (MDSs). Patients with monosomy 7 and trisomy 8 have distinctly different clinical courses, responses to therapy, and survival probabilities. To determine disease-specific molecular characteristics, we analyzed the gene expression pattern in purified CD34 hematopoietic progenitor cells obtained from MDS patients with monosomy 7 and trisomy 8 using Affymetrix GeneChips. Two methods were employed: standard hybridization and a small-sample RNA amplification protocol for the limited amounts of RNA available from individual cases; results were comparable between these 2 techniques. Microarray data were confirmed by gene amplification and flow cytometry using individual patient samples. Genes related to hematopoietic progenitor cell proliferation and blood cell function were dysregulated in CD34 cells of both monosomy 7 and trisomy 8 MDS. In trisomy 8, up-regulated genes were primarily involved in immune and inflammatory responses, and down-regulated genes have been implicated in apoptosis inhibition. CD34 cells in monosomy 7 showed up-regulation of genes inducing leukemia transformation and tumorigenesis and apoptosis and down-regulation of genes controlling cell growth and differentiation. These results imply distinct molecular mechanisms for monosomy 7 and trisomy 8 MDS and implicate specific pathogenic pathways.
Tests for finding complex patterns of differential expression in cancers: towards individualized medicine
Authors: Lyons-Weiler James , Patel Satish , Becich Michael J , Godfrey Tony E
Published: August 2004

Background

Microarray studies in cancer compare expression levels between two or more sample groups on thousands of genes. Data analysis follows a population-level approach (e.g., comparison of sample means) to identify differentially expressed genes. This leads to the discovery of 'population-level' markers, i.e., genes with the expression patterns A > B and B > A. We introduce the PPST test that identifies genes where a significantly large subset of cases exhibit expression values beyond upper and lower thresholds observed in the control samples.

Results

Interestingly, the test identifies A > B and B < A pattern genes that are missed by population-level approaches, such as the t-test, and many genes that exhibit both significant overexpression and significant underexpression in statistically significantly large subsets of cancer patients (ABA pattern genes). These patterns tend to show distributions that are unique to individual genes, and are aptly visualized in a 'gene expression pattern grid'. The low degree of among-gene correlations in these genes suggests unique underlying genomic pathologies and high degree of unique tumor-specific differential expression. We compare the PPST and the ABA test to the parametric and non-parametric t-test by analyzing two independently published data sets from studies of progression in astrocytoma.

Conclusions

The PPST test resulted findings similar to the nonparametric t-test with higher self-consistency. These tests and the gene expression pattern grid may be useful for the identification of therapeutic targets and diagnostic or prognostic markers that are present only in subsets of cancer patients, and provide a more complete portrait of differential expression in cancer.
Scavenger properties of cultivated pig liver endothelial cells
Authors: Elvevold Kjetil H , Nedredal Geir I , Revhaug Arthur , Smedsrød Bård
Published: August 2004

Background

The liver sinusoidal endothelial cells (LSEC) and Kupffer cells constitute the most powerful scavenger system in the body. Various waste macromolecules, continuously released from tissues in large quantities as a consequence of normal catabolic processes are cleared by the LSEC. In spite of the fact that pig livers are used in a wide range of experimental settings, the scavenger properties of pig LSEC has not been investigated until now. Therefore, we studied the endocytosis and intracellular transport of ligands for the five categories of endocytic receptors in LSEC.

Results

Endocytosis of five 125I-labelled molecules: collagen α-chains, FITC-biotin-hyaluronan, mannan, formaldehyde-treated serum albumin (FSA), and aggregated gamma globulin (AGG) was substantial in cultured LSEC. The endocytosis was mediated via the collagen-, hyaluronan-, mannose-, scavenger-, or IgG Fc-receptors, respectively, as judged by the ability of unlabelled ligands to compete with labelled ligands for uptake. Intracellular transport was studied employing a morphological pulse-chase technique. Ninety minutes following administration of red TRITC-FSA via the jugular vein of pigs to tag LSEC lysosomes, cultures of the cells were established, and pulsed with green FITC-labelled collagen, -mannan, and -FSA. By 10 min, the FITC-ligands was located in small vesicles scattered throughout the cytoplasm, with no co-localization with the red lysosomes. By 2 h, the FITC-ligands co-localized with red lysosomes. When LSEC were pulsed with FITC-AGG and TRITC-FSA together, co-localization of the two ligands was observed following a 10 min chase. By 2 h, only partial co-localization was observed; TRITC-FSA was transported to lysosomes, whereas FITC-AGG only slowly left the endosomes. Enzyme assays showed that LSEC and Kupffer cells contained equal specific activities of hexosaminidase, aryl sulphates, acid phosphatase and acid lipase, whereas the specific activities of α-mannosidase, and glucuronidase were higher in LSEC. All enzymes measured showed considerably higher specific activities in LSEC compared to parenchymal cells.

Conclusion

Pig LSEC express the five following categories of high capacity endocytic receptors: scavenger-, mannose-, hyaluronan-, collagen-, and IgG Fc-receptors. In the liver, soluble ligands for these five receptors are endocytosed exclusively by LSEC. Furthermore, LSEC contains high specific activity of lysosomal enzymes needed for degradation of endocytosed material. Our observations suggest that pig LSEC have the same clearance activity as earlier described in rat LSEC.
Tissue Doppler echocardiography – A case of right tool, wrong use
Authors: Thomas George
Published: August 2004

Background

The developments in echocardiography or ultrasound cardiography (UCG) have improved our clinical capabilities. However, advanced hardware and software capabilities have resulted in UCG facilities of dubious clinical benefits. Is tissue Doppler echocardiography (TDE) is one such example?

Presentation of the hypothesis

TDE has been touted as advancement in the field of echocardiography. The striking play of colors, impressive waveforms and the seemingly accurate velocity values could be deceptive. TDE is a clear case of inappropriate use of technology.

Testing the hypothesis

To understand this, a comparison between flow Doppler and tissue Doppler is made. To make clinically meaningful velocity measurements with Doppler, we need prior knowledge of the line of motion. This is possible in blood flow but impossible in the complex myocardial motion. The qualitative comparison makes it evident that Doppler is best suited for flow studies.

Implications of the hypothesis

As of now TDE is going backwards using an indirect method when direct methods are better. The work on TDE at present is only debatable 'research and publication' material and do not translate into tangible clinical benefits. There are several advances like curved M-mode, strain rate imaging and tissue tracking in TDE. However these have been disappointing. This is due to the basic flaw in the application of the principles of Doppler. Doppler is best suited for flow studies and applying it to tissue motion is illogical. All data obtained by TDE is scientifically incorrect. This makes all the published papers on the subject flawed. Making diagnostic decisions based on this faulty application of technology would be unacceptable to the scientific cardiologist.
Mitochondrial haplogroups in Basque multiple sclerosis patients
Authors: Otaegui D , Sáenz A , Martínez-Zabaleta M , Villoslada P , Fernández-Manchola I , de Arcaya A álvarez , Emparanza J I , de Munain A López
Published: August 2004

Previous studies have suggested that mitochondrial metabolism and/or mitochondrial DNA (mtDNA) could be, in conjunction with other genetic or environmental factors, a risk factor for the development of multiple sclerosis (MS). One of these studies establishes that mitochondrial haplogroup JT is a risk factor for developing the disease, in particular the visual manifestations [optic neuritis (ON)]. Nevertheless, as distribution of these haplogroups varies between populations, the observed association may be due to a slanted sample with no physiopathological value. This hypothesis was checked with MS patients, originals from Basque country (this population has peculiar genetic characteristics) and from other Spanish regions. We concluded that such an association does not exist. By contrast, a decrease could be seen in the frequency of the JT haplogroup in the ON group and in the MS-Basque group. That trend could be a protective effect, which needs to be verified in further investigations.
T1 relaxation maps allow differentiation between pathologic tissue subsets in relapsing-remitting and secondary progressive multiple sclerosis
Authors: Castriota-Scanderbeg A , Fasano F , Filippi M , Caltagirone C
Published: August 2004

In an attempt to clarify whether T1 relaxation time mapping may assist in characterizing the pathological brain tissue substrate of multiple sclerosis (MS), we compared the T1 relaxation times of lesions, areas of normal-appearing white matter (NAWM) located proximal to lesions, and areas of NAWM located distant from lesions in 12 patients with the relapsing-remitting and 12 with the secondary progressive (SP) subtype of disease. Nine healthy volunteers served as controls. Calculated mean T1 values were averaged across all patients within each clinical group, and comparisons were made by means of the Mann-Whitney U-test. Significant differences were found between all investigated brain regions within each clinical subgroup. Significant differences were also detected for each investigated brain region among clinical subgroups. While T1 values of NAWM were significantly higher in patients with SP disease than in normal white matter (NWM) of controls, no differences were detected when corresponding brain areas of patients with RR MS were compared with NWM of controls. T1 maps identify areas of the brain that are damaged to a different extent in patients with MS, and may be of help in monitoring disease progression.
Bone strength in multiple sclerosis: cortical midtibial speed-of-sound assessment
Authors: Achiron Anat , Edelstein Shmuel , Ziev-Ner Y , Givon Uri , Rotstein Zeev , Barak Yoram
Published: August 2004

It has been previously suggested that multiple sclerosis (MS) patients are at increased risk for osteoporosis due to reduced mobility, decreased exposure to sunlight and recurrent steroid treatment. In order to systematically evaluate bone strength we assessed 256 MS patients (171 females, 75 males) through quantitative ultrasound measurement of cortical bone. Tibial speed of sound (SOS, m/sec) was measured at midpoint of the tibial shaft using a Soundscan 2000 (Myriad Ultrasound Systems, Rehovot, Israel) and results were compared to age- and gender-matched population norms. T-score distribution in male MS patients was similar to normal population. In contrast, for female MS patients T-score distribution was significantly different from population norms, reflected by increased SOS in 30.4% (T-score intervals 1- and-2 above normal values;P/0.001), compared with 7.4% in controls. These findings held true for both female patients younger and older than 45 years of age. Increased neurological disability and specifically motor involvement were more frequent in female patients with increased SOS (PB/0.05). Bone strength was preserved in MS patients. In a subgroup of female patients increased SOS was conceivably related to spasticity.
An open-label safety and drug interaction study of natalizumab (Antegren™) in combination with interferon-beta (Avonex®) in patients with multiple sclerosis
Authors: Vollmer T L , Phillips J T , Goodman A D , Agius M A , Libonati M A , Giacchino J L , Grundy J S
Published: August 2004

In this open-label drug-interaction trial, we studied 38 patients with relapsing-remitting multiple sclerosis (MS) who received 3.0 or 6.0 mg/kg of natalizumab as a single intravenous (IV) infusion during stable treatment with intramuscular (IM) interferon beta-1a 30 mg (IFNβ-1a; Avonex®). To assess the pharmacokinetic (PK) interaction of natalizumab and IFNβ-1a, serum concentration-time data for both agents were collected and analysed. Biologic response markers of IFNβ-1a activity, b2-microglobulin and neopterin, were also assessed to determine effects of natalizumab on IFNβ-1a pharmacodynamics (PD). Further, safety and immunogenicity were evaluated.

The combination of drug therapies was well tolerated. Although natalizumab serum concentrations (and corresponding PK exposure measures) appeared to be somewhat elevated in the presence of IFNβ-1a, when compared to the same dose (6.0 mg/kg) administered alone in a concurrent comparator study, the differences were generally small and unlikely to be clinically relevant. In general, natalizumab had no apparent clinically relevant effects on the PK or PD properties of IFNβ-1a. The presence of antibodies to IFNβ-1a and natalizumab was relatively low. Overall, the study provided safety, immunogenicity, PK and PD data to support a combination strategy for the use of natalizumab and IFNβ-1a in the treatment of patients with relapsing-remitting MS. A large clinical study is currently in progress to evaluate the efficacy and long-term safety of this combination drug therapy.
Guided intrathecal baclofen administration by using soleus stretch reflex in moderate-severe spastic multiple sclerosis patients with implanted pump
Authors: Nielsen J F , Sinkjær T
Published: August 2004

We tested the hypothesis that changes in soleus stretch reflex was correlated to changes in intrathecal baclofen dose in 12 multiple sclerosis patients with moderate-severe spasticity treated with intrathecal baclofen pump. Twice patients were evaluated clinically and biomechanically. The short-latency soleus stretch reflex was elicited by rotating the ankle joint 48 with a velocity from 3.1 to 1808/s. There was a strong correlation between changes in intrathecal baclofen dose and amplitude of the short-latency stretch reflex (r=- 0.88, PB < 0.001), which means that with an increase in baclofen dose there is a decrease in the amplitude. In contrast, no correlation exists between changes in intrathecal baclofen dose and clinical assessment of spasticity by using the Ashworth scale. The amplitude of the stretch reflex was very small (5 mV) compared with previous findings (> 50 μV), which indicates an effective antispastic effect of intrathecal baclofen. We suggest that clinical evaluation of spasticity using Ashworth scale is insensitive to detect minor changes in moderate-severe spasticity and consequently might not be very useful in evaluating spasticity in relation to ambulatory filling of baclofen pumps. The soleus stretch reflex might be useful in situations when there is doubt about the effect of intrathecally administered baclofen.
Frontal parenchymal atrophy measures in multiple sclerosis
Authors: Locatelli Laura , Zivadinov Robert , Grop Attilio , Zorzon Marino
Published: August 2004

The aim of this study was to establish whether, in a cross-sectional study, the normalized measures of whole and regional brain atrophy correlate better with tests assessing the cognitive function than the absolute brain atrophy measures. The neuropsychological performances and disability have been assessed in 39 patients with relapsing-remitting multiple sclerosis (MS). T1- and T2-lesion load (LL) of total brain and frontal lobes (FLs) were measured using a reproducible semiautomated technique. The whole brain volume and the regional brain parenchymal volume (RBPV) of FLs were obtained using a computerized interactive program, which incorporates semiautomated and automated segmentation processes. Normalized measures of brain atrophy, i.e., brain parenchymal fraction (BPF) and regional brain parenchymal fraction (RBPF) of FLs, were calculated. The scan-rescan, inter- and intrarater coefficient of variation (COV) and intraclass correlation coefficient (ICC) have been estimated. The RBPF of FLs showed an acceptable level of reproducibility which ranged from 1.7% for intrarater variability to 3.2% for scan-rescan variability. The mean ICC was 0.88 (CI 0.82-0.93). The RBPF of FLs demonstrated stronger magnitudes of correlation with neuropsychological functioning, disability and quantitative MRI lesion measures than RBPV. These differences were statistically significant: P=0.001 for Stroop Color Word Interference test, P=0.001 for Paced Auditory Serial Addition Test, P=0.04 for Standard Raven Progressive Matrices, P=0.049 for Expanded Disability Status Scale, P=0.01 for T2-LL of FLs and P< 0.001 for T1-LL of FLs. BPF demonstrated significant correlations with tests assessing cognitive functions, whereas BPAV did not. The correlation analysis results were supported by the results of multiple regression analysis which showed that only the normalized brain atrophy measures were associated with tests exploring the cognitive functions. These data suggest that RBPF is a reproducible and sensitive method for measuring frontal parenchymal atrophy. The normalized measures of whole and regional brain parenchymal atrophy should be preferred to absolute measures in future studies that correlate neuropsychological performances and brain atrophy measures in patients with MS.
Neural Systems for Individual Song Recognition in Adult Birds
Authors: GENTNER T Q
Published: August 2004

Abstract: The songbird auditory system is an excellent model for neuroethological studies of the mechanisms that govern the perception and cognition of natural stimuli (i.e., song), and the translation of corresponding representations into natural behaviors. One common songbird behavior is the learned recognition of individual conspecific songs. This chapter summarizes the research effort to identify the brain regions and mechanisms mediating individual song recognition in European starlings, a species of songbird. The results of laboratory behavioral studies are reviewed, which show that when adult starlings learn to recognize other individual's songs, they do so by memorizing large sets of song elements, called motifs. Recent data from single neurons in the caudal medial portion of the mesopallium are then reviewed, showing that song recognition learning leads to explicit representation of acoustic features that correspond closely to specific motifs, but only to motifs in the songs that birds have learned to recognize. This suggests that the strength and tuning of high‐level auditory object representations, of the sort that presumably underlie many forms of vocal communication, are shaped by each animal's unique experience.
Songbirds and the Revised Avian Brain Nomenclature
Authors: REINER ANTON , PERKEL DAVID J. , MELLO CLAUDIO V. , JARVIS ERICH D.
Published: August 2004

Abstract: It has become increasingly clear that the standard nomenclature for many telencephalic and related brainstem structures of the avian brain is based on flawed once‐held assumptions of homology to mammalian brain structures, greatly hindering functional comparisons between avian and mammalian brains. This has become especially problematic for those researchers studying the neurobiology of birdsong, the largest single group within the avian neuroscience community. To deal with the many communication problems this has caused among researchers specializing in different vertebrate classes, the Avian Brain Nomenclature Forum, held at Duke University from July 18‐20, 2002, set out to develop a new terminology for the avian telencephalon and some allied brainstem cell groups. In one major step, the erroneous conception that the avian telencephalon consists mainly of a hypertrophied basal ganglia has been purged from the telencephalic terminology, and the actual parts of the basal ganglia and its brainstem afferent cell groups have been given new names to reflect their now‐evident homologies. The telencephalic regions that were incorrectly named to reflect presumed homology to mammalian basal ganglia have been renamed as parts of the pallium. The prefixes used for the new names for the pallial subdivisions have retained most established abbreviations, in an effort to maintain continuity with the pre‐existing nomenclature. Here we present a brief synopsis of the inaccuracies in the old nomenclature, a summary of the nomenclature changes, and details of changes for specific songbird vocal and auditory nuclei. We believe this new terminology will promote more accurate understanding of the broader neurobiological implications of song control mechanisms and facilitate the productive exchange of information between researchers studying avian and mammalian systems.
Bilateral Control and Interhemispheric Coordination in the Avian Song Motor System
Authors: SCHMIDT MARC F. , ASHMORE ROBIN C. , VU ERIC T.
Published: August 2004

Abstract: Birdsong is a complex learned motor behavior controlled by an interconnected network of vocal control nuclei that are present in both cerebral hemispheres. Unilateral lesions of song nuclei in the left or the right hemisphere result in different effects on song structure, suggesting that normal song output results from the activation of two parallel but functionally different motor pathways. Because each syringeal half is innervated primarily by ipsilateral motor structures and activity in both halves is tightly coordinated during singing, motor commands originating from both hemispheres must be tightly coordinated to produce the appropriate vocal output. This coordination occurs despite the absence of direct interhemispheric connections between song control nuclei. In this article, we discuss how motor commands in nucleus HVC, a key forebrain song control region, are coordinated by precisely timed inputs that act to synchronize premotor activity in both hemispheres. Synchronizing inputs are tightly linked to syllable and note onset, which suggests that bilaterally organized circuits in the midbrain or brainstem act in specifying higher‐order song features, such as duration, order, and possibly even structure of individual song syllables. The challenge ahead lies in identifying the networks that generate the synchronizing timing inputs and to determine how these inputs specify the motor commands in HVC. Resolving these issues will help us gain a better understanding of how pattern‐generating networks in the midbrain/brainstem interface with forebrain circuits to produce complex learned behaviors.