bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Renal Failure with Severe Loin Pain and Patchy Renal Ischemia after Anaerobic Exercise in Patients with or without Renal Hypouricemia
Authors: Ishikawa Isao
Published: April 2003

Acute renal failure induced by rhabdomyolysis after strenuous exercise is well known. We describe here a new type of acute renal failure with severe loin pain which develops after anaerobic exercise (ALPE), for example, 200-meter track racing. The patients complained of severe loin pain several hours after exercise and presented at the emergency room. Since our first description 118 cases have been reported. The serum creatinine concentration was 4.7 ± 2.9 mg/dl (mean ± SD) at the initial examination and 6.0 ± 3.0 mg/dl at maximum. Forty-nine of 96 cases whose serum uric acid levels were described revealed renal hypouricemia (51.0%). A specific risk factor is suggested by the fact that acute renal failure recurred after exercise in 20 of 118 cases. The creatine phosphokinase and serum myoglobin concentrations were normal or only slightly elevated, suggesting damaged type 2 muscle fibers. Renal computed tomography scans, performed several hours to 1–2 days after contrast medium administration, revealed multiple wedge-shaped areas of contrast enhancement. Forty-six of 50 cases examined by delayed computed tomography scan revealed bilateral wedge-shaped contrast enhancement. Although less efficient, radioisotopic scans, such as a methylene diphosphonate bone scan, have also been employed to detect patchy accumulation of isotopes in the kidneys (12 of 19 cases). The pathogenesis of ALPE may be patchy vasoconstriction of the renal vessels, because of its wedge-shaped distribution and its reversibility. Such vascular spasm would account for the renal pain. The prognosis was good, although 20 of 109 cases required dialysis treatment. In conclusion, there are two types of exercise-induced acute renal failure: one is the well-known myoglobin-induced acute renal failure, and the other is ALPE that may be nonmyoglobin induced or induced by myolysis of type 2 muscle fibers due to anaerobic exercise. One hundred and eighteen cases of ALPE were collected from the literature, and half of the cases were found to display renal hypouricemia.
Mechanisms of Cisplatin Resistance in Clear Cell Carcinoma of the Ovary
Authors: Itamochi Hiroaki , Kigawa Junzo , Akeshima Ryoji , Sato Shinya , Kamazawa Shunji , Takahashi Masakuni , Kanamori Yasunobu , Suzuki Mitsuaki , Ohwada Michitaka , Terakawa Naoki
Published: April 2003

Resistance of clear cell carcinoma (CCC) of the ovary to platinum-based chemotherapy is associated with a poor prognosis. However, the mechanism underlying the resistance of CCC to platinum has not yet been understood. We conducted the present study to clarify the mechanism of cisplatin (CDDP) resistance in CCC cells. Eleven CCC and 5 serous adenocarcinoma (SAC) cell lines were used in this study. The IC50 to CDDP ranged from 1.3 to 18.0 µM for CCC cells and from 2.2 to 13.0 µM for SAC cells. There was no correlation between multidrug resistance-associated protein expression and the sensitivity to CDDP in CCC cells. In contrast, the doubling time for CCC cells was significantly longer than that for SAC cells (61.4 vs. 29.8 h). A significant reverse correlation between the S-phase fraction and the response to CDDP was observed (r = 0.647, p < 0.05). The present study suggests that the resistance of CCC to CDDP may be caused by low cell proliferation.
Acquired Resistance of Pancreatic Cancer Cells towards 5-Fluorouracil and Gemcitabine Is Associated with Altered Expression of Apoptosis-Regulating Genes
Authors: Shi Xin , Liu Shengli , Kleeff Jörg , Friess Helmut , Büchler Markus W.
Published: April 2003

Objectives: Resistance to chemotherapy is a major cause of treatment failure and poor prognosis in pancreatic cancer. Inasmuch as most effects of chemotherapeutic agents are mediated via the activation of apoptosis, the cytotoxic effects of gemcitabine and 5-fluorouracil (FU) in correlation with apoptosis-regulating genes in pancreatic cancer cell lines were analyzed. Methods: The cytotoxic effects of 5-FU and gemcitabine in AsPC-1, Capan-1, Mia-PaCa-2 and T3M4 pancreatic cancer cell lines were assessed by growth assays, and mRNA expression levels of pro-apoptotic and anti-apoptotic genes of the Bcl-2 family were analyzed by RNAse protection assays. Results: Pancreatic cancer cells displayed a wide range of responses towards 5-FU (IC50 0.22–4.63 µM) and gemcitabine (11.51–42.2 nM). After repeated treatment with 5-FU, the IC50 values in Capan-1 and T3M4 cells increased 2.1- and 1.8-fold, respectively, compared to their parental cells. Following recurrent treatment with gemcitabine, the IC50 values in Capan-1 cells increased significantly (1.5-fold, p < 0.01). RNase protection assay showed a negative correlation between bcl-xL and mcl-1 mRNA expression levels and the sensitivity to 5-FU and gemcitabine after 5-FU and gemcitabine treatment. The bax/bcl-2 ratio maintained relatively stable following 5-FU/gemcitabine treatment and reflected the chemotherapeutic sensitivity of these cell lines. Conclusions: These findings reveal that pancreatic cancer cell lines are generally resistant to 5-FU and are more sensitive towards gemcitabine. The bax/bcl-2 ratio is predictive of chemotherapy sensitivity, whereas bcl-xL and mcl-1 mRNA levels following repeated exposure to 5-FU or gemcitabine are associated with resistance to these drugs. These findings suggest that the activation of anti-apoptotic genes after repeated drug exposure contributes to chemoresistance of pancreatic cancer cells and that blockage of anti-apoptotic genes might enhance chemosensitivity in pancreatic cancer.
High-Dose 5-Fluorouracil with Uridine-Diphosphoglucose Rescue Increases Thymidylate Synthase Inhibition but Not 5-Fluorouracil Incorporation into RNA in Murine Tumors
Authors: Codacci-Pisanelli Giovanni , van der Wilt Clasina L. , Smid Kees , Noordhuis Paul , Voorn Daphne , Pinedo Herbert M. , Peters Godefridus J.
Published: April 2003

5-Fluorouracil (5FU) shows a steep dose response curve in several experimental systems, but the clinical use of high doses is hampered by the toxic side effects of this drug. Uridine diphosphoglucose (UDPG) rescue allows an increase in the maximum tolerated dose of 5FU in mice from 100 (FU100) to 150 mg/kg (5FU150+UDPG) and the higher dose is more effective than the standard treatment against several tumors. In the present paper we report on the effect of high-dose 5FU on thymidylate synthase (TS) levels and on 5FU incorporation into RNA. In the resistant murine tumor (Colon 26A) high-dose 5FU inhibited TS catalytic activity 8 h after treatment (4-fold; p = 0.00041) and the inhibition persisted until day 3 (p < 10–4). Standard-dose 5FU did not significantly inhibit TS activity. In a relatively sensitive tumor (Colon 26-10), there was no difference in the initial extent of TS inhibition by the two 5FU doses, but TS was still inhibited (2-fold) on day 3 after (5FU150+UDPG) while it was within the normal range after 5FU100. In both tumor types TS activity showed an impressive rebound (3-fold) on days 3–7, and this occurred after both 5FU doses. In Colon 26A, however, a new 5FU injection on day 7 was still able to inhibit TS but not as effectively as the first dose. 5FU incorporation into RNA reached similar peak values (8 pmol/µg RNA) after the two 5FU doses, but the clearance was faster in mice receiving UDPG rescue. We conclude that UDPG does not interfere with the extent of TS inhibition by 5FU, but UDPG allows the use of a higher dose of 5FU resulting in enhanced TS inhibition. UDPG, however, increases 5FU clearance from RNA. In this experimental system the inhibition of TS seems essential in order to obtain a good antitumor activity, while 5FU incorporation into RNA does not seem to play a role in the antitumor activity of 5FU. Since preliminary results indicate that UDPG is well tolerated by patients, the use of higher 5FU doses may improve the response rate of human tumors.
Interaction of Fibronectin with Human Colon Adenocarcinoma Cells: Effect on the in vivo Tumorigenic Capacity
Authors: López-Conejo M. Teresa , Olmo Nieves , Turnay Javier , López de Silanes Isabel , Lizarbe M. Antonia
Published: April 2003

Fibronectin (FN) modulates the behavior of the poorly differentiated, human colon adenocarcinoma-derived BCS-TC2 cells by promoting adhesion through the α5β1-integrin, as this effect is blocked by anti-α5 and β1 chain antibodies. BCS-TC2 cells are not tumorigenic in vivo, but are able to form tumors when coinjected with FN in nude mice. From these tumors, a tumorigenic cell subline (BCS-TC2.FN) was established. In vivo passaging of BCS-TC2.FN cells in the absence of FN allowed the selection of another tumorigenic subline (BCS-TC2.FN2). The new sublines are characterized by: (1) increased differentiation, (2) slightly higher adhesion to FN, and (3) a higher uptake of [3H]thymidine, less dependent on the presence of serum or FN. No significant modifications in α5-chain surface levels were observed in the tumor-derived sublines, suggesting that the amount of α5β1-integrin is not related to tumorigenicity. Within the heterogeneous parental cells, FN seems to favor the selection of a cell subpopulation that presents phenotypic and genotypic alterations that are stably maintained throughout in vitro culture and in vivo passaging. These cell lines constitute a model system that may help to extend our knowledge on the events underlying tumor progression and malignancy of colorectal cancer, and the influence of extracellular matrix components and their receptors in these processes.
Common C677T Polymorphism of the Methylenetetrahydrofolate Reductase Gene and the Risk of Venous Thromboembolism: Meta-Analysis of 31 Studies
Authors: Ray J.G. , Shmorgun D. , Chan W.S.
Published: April 2003

Background: Although the common 677 C → T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene is implicated in the development of hyperhomocysteinemia, its correlation with venous thromboembolism (VTE) remains controversial. We conducted a meta-analysis of previously published studies to clarify the role of the MTHFR 677 TT homozygous genotype in association with VTE. Methods and Results: Relevant articles were retrieved from a systematic search of Medline and Embase from 1990 to September 2001. Two independent reviewers abstracted data on the characteristics of the cases with VTE and controls without VTE. We pooled the rates of the MTHFR 677 TT genotype in both groups, as well as the odds ratio (OR) of VTE in the presence of the TT versus CC or CT genotypes. In 31 published studies, comprising 4,901 cases and 7,886 controls, the pooled prevalence of the MTHFR 677 TT genotype was slightly higher among cases (14.3%) than controls (11.7%), conferring a borderline degree of heightened risk [pooled OR (ORp) 1.2, 95% confidence interval (CI) 1.1–1.4]. After excluding cases with a classic thrombophilia factor, the pooled prevalence rates of the MTHFR 677 TT genotype among 11 studies were 17.7 and 12.3%, respectively (ORp 1.5, 95% CI 1.2–1.9). Conclusions: The classic MTHFR C677T gene polymorphism is weakly associated with an increased risk of VTE. It is unlikely that the purported relationship between hyperhomocysteinemia and VTE is mediated by this gene defect to a substantial degree, although other undiscovered gene polymorphisms may explain this association. Until more compelling data are made available, we do not recommend that testing for the MTHFR C677T polymorphism be routinely included as part of any clinical thrombophilia assessment.
Plasma Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 Levels in Acute Myocardial Infarction
Authors: Ganti Apar Kishor , Potti Anil , Yegnanarayan Radha
Published: April 2003

The cause of the circadian variation in the incidence of acute myocardial infarction (AMI) has not been identified. Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) have opposing effects on thrombi. Hence, the extent of the clot, the size of the infarct and outcome of patients could depend on t-PA and PAI-1 levels. In an effort to elucidate the pathophysiologic basis of circadian variation of AMI, we investigated the presence of a possible corresponding circadian variation in the levels of endogenous t-PA and PAI-1 in patients diagnosed to have AMI and the effects of hypertension, diabetes and site of the infarct on these levels. We estimated the levels of t-PA and PAI-1 in platelet-poor plasma of 42 patients with AMI on admission, using the enzyme-linked immunosorbant assay. Although not statistically significant, patients having an AMI in the morning hours had the highest t-PA:PAI-1 ratio. The normal circadian variation in PAI-1 levels was lost in patients with AMI, probably due to the disease process. Also, the t-PA levels in hypertensive patients were significantly lower than in nonhypertensives. PAI-1 levels were also significantly lower in patients with anteroseptal than in inferior and anterolateral AMI. This relationship between the fibrinolytic potential and the site of infarction needs further study. Furthermore, t-PA levels on admission were significantly lower in survivors and may have a predictive value in determining the outcome.
Modulation of Bcl-2 Family Proteins in Primary Endothelial Cells during Apoptosis
Authors: Molostvov G. , Morris A. , Rose P. , Basu S.
Published: April 2003

We studied the expression of Bcl-2 family proteins during cytokine- and verotoxin (VT)-induced apoptosis in primary human umbilical vein endothelial cells (HUVECs). Our experiments demonstrated that high initial expression of Bcl-2 protein was significantly downregulated in HUVECs treated with IFN-γ whereas TNF-α gave a less pronounced decrease in Bcl-2 level. Treatment with the combination of cytokines was more efficient in downregulating Bcl-2 protein. HUVECs pretreated with cytokines and incubated with VT gave a further significant decrease in Bcl-2 level. Simultaneous measurement of Bcl-xl level did not reveal any significant changes. Bax protein was upregulated in HUVECs stimulated with TNF-α alone or in combination with IFN-γ. However, addition of VT did not give any further increase in Bax level suggesting that Bax upregulation is more important for cytokine- rather than VT-mediated apoptosis. Total endothelial cell growth factor deprivation gave a significant increase in apoptosis accompanied by a decrease of Bcl-2 in apoptotic cells while Bcl-xl and Bax levels were unaffected. Our data indicate that anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax are reciprocally regulated during apoptosis, whilst Bcl-xl is essentially unaffected. This implies that Bcl-2/Bax ratio rather than Bcl-xl controls apoptosis in primary endothelial cells.
Platelets and Anticoagulant Capacity in Patients with Inflammatory Bowel Disease
Authors: Larsen Torben Bjerregaard , Nielsen Jens Nederby , Fredholm Lisbeth , Lund Erik D. , Brandslund Ivan , Munkholm Pia , Hey Henrik
Published: April 2003

Patients with inflammatory bowel disease (IBD) are susceptible to thromboembolic complications. Several mechanisms can be responsible, including abnormal regulation of coagulation activity, disturbances of fibrinolysis, inflammatory reactions and thrombocytosis. The aim of this study was to assess hemostatic alterations in these parameters during exacerbation of disease. We studied disease activity in 99 IBD patients receiving anti-inflammatory therapy, in relation to: procoagulant markers, i.e. prothrombin fragment F1 + 2 (F1 + 2), D-dimer and platelet count, anticoagulant markers, i.e. protein C, protein S and antithrombin, and a mediator of inflammation (IL-6). Coagulation activity and platelet count were increased during active disease in IBD patients compared with those in a state of remission. The IL-6 concentrations were positively correlated with disease activity and thrombocytosis in patients with ulcerative colitis, but no association with the anticoagulant capacity could be demonstrated except for a decrease in protein C during high disease activity.
A Case of Beare-Stevenson Cutis gyrata Syndrome Confirmed by Mutation Analysis of the Fibroblast Growth Factor Receptor 2 Gene
Authors: Akai Takuya , Iizuka Hideaki , Kishibe Miyuki , Kawakami Shigehiko , Kobayashi Azusa , Ozawa Tetsuo
Published: April 2003

This paper reports a case of Beare-Stevenson cutis gyrata syndrome confirmed by DNA analysis of the patient’s fibroblast growth factor receptor (FGFR) genes. At birth, the patient had ocular proptosis, a red nevus with skin tags on her forehead and an umbilical stump. She developed craniosynostosis, craniofacial dysmorphism and hydrocephalus. Her treatment included forehead and facial advancement and a ventriculoperitoneal shunt. Analysis of the FGFR genes revealed that she was heterozygous for a missense mutation in exon 10 for the FGFR2 protein, resulting in an amino acid substitution of cysteine for tyrosine at residue 375 (Tyr375Cys). This is the fourth case of Beare-Stevenson cutis gyrata syndrome confirmed by mutation analysis of the FGFR genes.
Schizophrenia and Related Disorders: Experience with Current Diagnostic Systems
Authors: Bertelsen Aksel
Published: April 2003

Schizophrenia and related disorders include a variety of psychotic disorders in the major classification systems, ICD-10 and DSM-IV, with only partial concordance between the two systems. They both rely on demonstrated reliability, but which disorders are the most valid still has to be determined. Particularly for the ICD-10 disorders, only few studies examining external validity have appeared. Disorders of uncertain validity include ‘schizo-affective disorders’ which in ICD-10 contain the DSM-IV psychotic mood disorders with first-rank symptoms or bizarre delusions; ICD-10 ‘schizotypal disorder’ which in DSM-IV is a personality disorder; the ICD-10 ‘acute and transient psychotic disorders’ and the DSM-IV ‘brief psychotic disorder’. Concerning diagnostic criteria, the reliability and validity of Schneiderian first-rank symptoms, ‘bizarre’ delusions and the Bleulerian ‘negative’ symptoms have been questioned. Validity studies in these areas are needed before it will be possible to provide major reconstructions for future diagnostic systems. One may hope that, eventually, one common worldwide psychiatric classification will be available.
Mood Disorders: Review of Current Diagnostic Systems
Authors: Paykel Eugene S.
Published: April 2003

In their sections on mood disorders, both ICD-10 and DSM-IV represent considerable advances on ICD-9 in drawing affective disorders together in one section, distinguishing bipolar disorder from unipolar, including dysthymia and using clear definitions. Problems with ICD-10 include complexity, use of different clinical and research definitions, emphasis on single versus recurrent episodes and the lack of some clinically useful subtypes. DSM-IV is less complex but assigns separate unjustified categories of medical and substance-induced mood disorders, and fails to code its useful qualifiers. Both classifications preserve categories for psychotic depression and melancholia/somatic syndrome, which are better coded in ICD-10. The severity distinctions could usefully be extended to a milder category of minor depression. It is also recommended that the two classifications be brought together, with small differences in definitions ironed out and a single set used both clinically and for research, the simpler DSM-IV organisation, the omission of the categorisations of single versus recurrent and mood disorder due to general medical or substance abuse disorders, and the inclusion of coding for some subtypes such as seasonal and postpartum.
Values in Psychiatric Diagnosis: Executive Summary of a Report to the Chair of the ICD-12/DSM-VI Coordination Task Force (Dateline 2010)
Authors: Fulford K.W.M.
Published: April 2003

This paper reproduces the executive summary of a report on values in psychiatric diagnosis commissioned by the chair of the ICD-12/DSM-VI Co-ordination Task Force, newly established in 2010 following the publication of ICD-11 and DSM-V. The report describes a programme of research on values in psychiatric diagnosis carried out in the first decade of the twenty-first century. This programme paralleled the twentieth-century programme of research on the descriptive (or factual) elements in diagnosis. The report includes concrete proposals for re-drafting key sections of DSM and corresponding sections of ICD. These proposals add values to, rather than subtracting science from, psychiatric classification. This is shown to have put psychiatry at the leading edge of twenty-first century medical science by 2010.
Socio-Cultural and Global Health Perspectives for the Development of Future Psychiatric Diagnostic Systems
Authors: Lee Sing
Published: April 2003

Psychiatric diagnosis and classification reflect the social and political context of an era and are embedded in it. In the last few decades, culture-bound syndromes reported in non-Western societies constituted the major focus of contention over the validity and universality of psychiatric diagnosis. In contemporary times, social, economic, and political factors, such as the hegemony of the DSM discourse, the managed care culture, pharmaceutical forces, and the global burden of disease study, have virtually made culture-bound syndromes ‘disappear’. Once widely believed to be rare outside of the developed West, depression has rapidly become the master narrative of mental health worldwide. In the context of global mental health, the field of psychiatric classification must go beyond routine debates over categories. In order to address the growing discrepancy between needs and services, international cultural psychiatry must engage key social forces, such as psychiatric epidemiology, primary care psychiatry, integration of diagnostic systems, stigma, and advocacy.
Comprehensive Diagnosis: A Conceptual Basis for Future Diagnostic Systems
Authors: Mezzich Juan E.
Published: April 2003

A discussion of the objectives of diagnosis, participants and architecture leads to the consideration of diagnostic schemas of increasing complexity. Examined first is the conventional case of single-label diagnosis. The case of multiple illness formulation is considered concerning the plurality of mental disorders as well as of general medical disorders. The formulation of a whole clinical condition where contextualized pathology and problems are described is then followed by the consideration of positive aspects of health as well as quality of life. Finally, a comprehensive diagnostic model is reviewed. It integrates a standardized multiaxial formulation (illness, disabilities, contextual factors and quality of life) and an idiographic personalized formulation (culturally informed and contextualized clinical problems, patient’s assets pertinent to care, and expectations of health restoration and promotion as jointly understood by clinician, patient and family). Such integrative diagnostic schemas may offer a richer informational basis for clinical description and care as well as a more effective focus for the surveillance of population health.
Third Cuban Glossary of Psychiatry (GC-3): Key Features and Contributions
Authors: Otero-Ojeda Angel A.
Published: April 2003

The GC-3 is the third edition of a long-standing and serial effort to annotate and adapt the mental disorders component of the International Classification of Diseases (ICD) to Cuban realities and needs. The Cuban Glossary since its first edition in 1975 distinctively utilizes a bottom-up and multidisciplinary developmental approach. The GC-3 as an adaptation of ICD-10 has rescued and refined the concept of neurosis and facilitated its placement throughout pertinent sections of the international classification. It has also facilitated the identification of prodromic phases of various recurrent disorders. The GC-3 endorses the view that a diagnosis should deal with several important clinical aspects in addition to illness senso stricto and that it should have a prominent therapeutic orientation. In line with this, a multiaxial schema has been included in GC-3, adding three axes to the triaxial ICD-10 adult psychiatry schema. Empirical studies are being carried out to appraise the clinical use and usefulness of the GC-3 hexaxial schema.
Latin American Guide for Psychiatric Diagnosis (GLDP)
Authors: Berganza Carlos E. , Mezzich Juan E. , Jorge Miguel Roberto
Published: April 2003

Culturally competent diagnostic systems are necessary for an effective and ethical clinical practice, as cultural diversity of patients increase around the world. Latin American psychiatrists hold a long-standing commitment to this enterprise. Recently, two main Latin American adaptations to the international psychiatric classification have emerged: the Cuban Glossary of Psychiatry, and the project of the Latin American Guide for Psychiatric Diagnosis (GLADP). Keeping ICD-10 as the basis for nosological organization, GLADP is being developed with contributions by mental health professionals from Latin American countries. GLADP comprises 4 parts: (1) historical and cultural framework, (2) comprehensive diagnosis and formulation, (3) psychiatric nosology and (4) appendixes.
Mast Cell-Derived VEGF Enhances the Passage of IgE FE-3 through the Rat Aortic Endothelial Cell Monolayer
Authors: Nakasone Toshiyuki , Hanashiro Kazuhiko , Nakamura Mariko , Sunakawa Hajime , Kosugi Tadayoshi
Published: April 2003

Background: It is well known that the IgE-mediated allergic reaction in various extravascular tissues is induced by the mutual interaction of IgE, target cells (mast cells, MCs) and allergens. However, so far little has been known about the detailed mechanism whereby IgE in the circulating blood is transferred to the extravascular tissue. To examine whether or not MCs are involved in the permeability of IgE across rat aortic endothelial cells (RAECs) in vitro, we determined the permeability constant (PC) of dinitrophenyl-specific rat IgE (IgE FE-3) using a dual chamber system. Methods: Isolated RAECs obtained by a primary explant technique were seeded on a collagen-coated membrane in the upper chamber. MCs were collected from the peritoneal cavity of Wistar rats and suspended in the lower chamber. The time-dependent changes in concentration of IgE FE-3 (IgE) in the upper and lower chambers were measured by IgE capture ELISA after addition of IgE (10 µg/ml) to the upper chamber. Results: The cultured medium of IgE-stimulated MCs significantly increased the PC of IgE (9.86 ± 0.46 × 10–6 cm/s), as compared to the value to which calcium ionophore A 23187-stimulated MCs increased the PC of IgE (7.97 ± 0.21 × 10–6 cm/s). The increase of PC by IgE-stimulated MCs was most strongly inhibited by suramin (92.3% ± 1.89), and was weakly inhibited by tranexamic acid, cimetidine and diphenhydramine. In addition, the PC of IgE was increased with the increase in the MC-derived vascular endothelial growth factor/permeability factor (VEGF). Conclusions: After IgE is transferred from the circulating blood to the extravascular tissue, it may bind to FcΕRI of the MC and the other FcΕRI-bearing cells. The MC is then activated through the interaction of IgE and FcΕRI. Release of VEGF from the activated MC increases, and the VEGF enhances the permeability of IgE.
Effect of Intranasal Administration of CV-11974, a Type 1 Angiotensin II Receptor Antagonist, on Airway Hyperresponsiveness and Airway Inflammation Induced by Antigen Inhalation in Guinea Pigs
Authors: Myou Shigeharu , Fujimura Masaki , Kita Toshiyuki , Watanabe Kazuyoshi , Hirose Tatsuki , Tachibana Hideki , Ishiura Yoshihisa , Nakao Shinji
Published: April 2003

Background: Angiotensin II is a putative mediator in asthma, but the effect of topical administration of type 1 angiotensin II (AT1) receptor antagonists on allergic airway reactions is not known. Objective: To investigate the effect of intranasal administration of CV-11974, an AT1 receptor antagonist, and of PD123319, a type 2 angiotensin II (AT2) receptor antagonist, on antigen-induced airway reactions in guinea pigs. Methods: Thirty minutes after intranasal topical administration of CV-11974 (0.1 or 1.0 mg/ml) or PD123319 (10 mg/ml) into the airways, the animals were given an antigen challenge. Airway hyperresponsiveness and bronchoalveolar lavage fluid were analyzed 24 h after the antigen challenge. Results: Although these compounds did not inhibit antigen-induced early-phase bronchoconstriction or late-phase airway eosinophilia, intranasal administration of CV-11974 (but not PD123319) inhibited antigen-induced airway hyperresponsiveness in a dose-dependent manner 24 h after the antigen challenge. Conclusion: Intranasal administration of an AT1 receptor antagonist reduces antigen-induced airway hyperresponsiveness.
Significance of Carbohydrate Epitopes in a Latex Allergen with β-1,3-Glucanase Activity
Authors: Yagami Takeshi , Osuna Hiroyuki , Kouno Masumi , Haishima Yuji , Nakamura Akitada , Ikezawa Zenro
Published: April 2003

Background: One of the latex allergens, Hev b 2, has β-1,3-glucanase activity. The entire sequence of this allergen is already known. There is one potential N-glycosylation site in this molecule (27Asn). Heterogeneous glycosylation of this Asn residue could be a source of the multiplicity of natural Hev b 2. Possible participation of the carbohydrate epitopes of latex β-1,3-glucanase isoenzymes in their IgE-binding capacity and cross-reactivity was investigated in this study. Methods: β-1,3-Glucanase isoenzymes were separated based on their affinities for concanavalin A. IgE-binding capacity and cross-reactivity were examined by immunoblotting and enzyme-linked immunosorbent assay (ELISA). Sequence heterogeneity among the isoenzymes was probed by peptide mass mapping after lysyl endopeptidase digestion. To clarify the relation to Hev b 2, N-terminal sequencing was performed on a fragmented peptide common to the separated isoenzymes. Results: Basic β-1,3-glucanase was subdivided into two glycosylated isoenzymes (GI and GII) and one non-glycosylated isoenzyme (GIII). IgE antibodies in latex-positive sera chiefly recognized the glycosylated isoenzymes. Inhibition ELISA supported the significance of the carbohydrate epitopes for the IgE recognition and cross-reactivity. However, non-glycosylated GIII, as well as GI and GII, produced positive results in a skin prick test. The three β-1,3-glucanase isoenzymes shared a partial sequence in common with Hev b 2. Conclusions: Our results suggest that the carbohydrate epitopes in Hev b 2 homologues are relevant to an in vitro diagnosis of latex allergy and the accompanying cross-reactivity. Carbohydrate epitopes do not necessarily provoke allergic symptoms. Therefore, the actual allergenicity of Hev b 2 and its homologues should be carefully evaluated not only by in vitro IgE tests but also by in vivo tests.
Hemostasis and Fibrinolysis Factors in First-Degree Relatives of Patients with Type 2 Diabetes without Hypertension
Authors: Trifiletti A. , Lasco A. , Scamardi R. , Cincotta M. , Gaudio A. , Barbera N. , Frisina N.
Published: April 2003

First-degree relatives of type 2 diabetic patients with or without a family history of hypertension are at increased risk for cardiovascular diseases. The aim of this study was to verify some possible hemostatic alterations in first-degree relatives of type 2 diabetic, normotensive and hypertensive patients. In 78 non-diabetic, normotensive first-degree relatives of type 2 diabetic patients (47 without a family history of hypertension and 31 with a family history of hypertension) and in 36 normoglycemic, normotensive subjects with no family history of hypertension, we evaluated plasma levels of fasting glucose and insulin, tissue-type plasminogen activator (t-PA), plasminogen activator-inhibitor (PAI-1), D-dimer (DD) and prothrombin fragment 1 + 2 (F1+2). Insulin resistance, calculated by the HOMA model, and plasma levels of t-PA and PAI-1 were significantly higher in relatives of diabetics compared to controls. As far as the thrombin activation indexes are concerned, we detected a significant increase in DD and F1+2 in relatives of diabetics with hypertension compared to other study subjects. In conclusion, our data indicate that familial predisposition may influence the hemostatic system in first-degree relatives of diabetic and/or hypertensive patients.
Prospective Assessment of a Nomogram for the Initiation of Oral Anticoagulation Therapy for Outpatient Treatment of Venous Thromboembolism
Authors: Kovacs M.J. , Anderson D.A. , Wells P.S.
Published: April 2003

Venous thromboembolism is a common medical problem. Recently, the emphasis has been on a switch to outpatient low molecular weight heparin therapy. Previous warfarin nomograms have been developed only for inpatients. We prospectively assessed a warfarin initiation nomogram in 105 consecutive outpatients; the nomogram requires International Normalized Ratio (INR) testing on only days 3, 5, and 8. Eighty-three percent had a therapeutic INR by day 5 and 98% by day 8. There were no major bleeds and only 6 instances of INR >4.5. This outpatient warfarin nomogram appears to be safe and efficacious in obtaining timely therapeutic levels of warfarin and deserves further study.
Abnormally Short Activated Partial Thromboplastin Times Are Related to Elevated Plasma Levels of TAT, F1+2, D-Dimer and FVIII:C
Authors: ten Boekel Edwin , Bartels Piet
Published: April 2003

Abnormally short activated partial thromboplastin times (APTTs) are associated with an increased risk of thrombotic disorders. We have examined the status of coagulation activity in subjects with short APTTs. In addition, the presence of the thrombotic risk factors G1691A-factor V, G20210A-prothrombin gene mutation and factor VIII coagulant activity (FVIII:C) was determined. Plasma levels of TAT, F1+2, D-dimer and FVIII:C were markedly higher in subjects with short APTTs compared with subjects with normal APTTs. APTTs were inversely related to TAT, F1+2, D-dimer and FVIII:C levels. The prevalence of G1691A-factor V and G20210A-prothrombin gene mutation between the group with short APTTs and the control group was not significantly different. Hence, these gene polymorphisms do not contribute to the increased risk of thrombosis associated with short APTTs. In conclusion, short APTTs are indicative of marked coagulation activity and elevated FVIII:C levels. Elevated FVIII:C levels may play a pathogenic role in the increased risk of thrombosis associated with abnormally short APTTs.
Quantification of Antithrombin Isoform Proportions in Plasma Samples of Healthy Subjects, Sepsis Patients, and in Antithrombin Concentrates
Authors: Römisch Jürgen , Dönges Reiner , Stauss Harald , Inthorn Dietrich , Mühlbayer Dieter , Jochum Marianne , Hoffmann Johannes N.
Published: April 2003

Antithrombin (AT) circulates in plasma in two isoforms, AT-α (90–95%) and AT-β (5–10%). AT isoform proportions were measured in plasma samples of 17 healthy subjects and 26 posttraumatic or postoperative septic patients, as well as in 4 commercially available AT concentrates. Total AT was immune-purified from plasma and concentrates. Micellar electrokinetic chromatography was used to analytically separate and quantify the isoforms. Compared with plasma samples of healthy donors, septic plasmas revealed significantly reduced AT activity (p < 0.001) and β-isoform content (p < 0.05). AT-β correlated inversely with urea and creatinine serum concentrations (p < 0.01), indicating a relationship between better renal function and higher β-isoform content. β-Isoform neither correlated with age, gender, and 28-day mortality, nor with plasma concentrations of various inflammatory and organ function parameters. The commercial AT concentrate, which is equivalent to the current WHO standard, had an AT-β content close to that found in plasma of healthy subjects. The availability of this novel quantitative AT isoform assay allows, for the first time, a closer look at the role of AT isoforms in hemostasis and sepsis pathophysiology.
Labetalol-Induced Hyperkalemia in Renal Transplant Recipients
Authors: McCauley Jerry , Murray Joan , Jordan Mark , Scantlebury Velma , Vivas Carlos , Shapiro Ron
Published: April 2003

Background: Labetalol is a commonly used agent for perioperative hypertension in renal transplant recipients. A previous report suggested that labetalol may cause life-threatening hyperkalemia after renal transplantation. Methods: We performed a retrospective review of 103 consecutive renal transplants to determine whether labetalol was an independent predictor of hyperkalemia treatment. Thirty-eight patients (36.9%) received labetalol, and 65 patients (63.1%) had no labetalol medication. Results: Of the 103 patients, 24 (23.3%) required treatment for hyperkalemia. Thirteen (34.2%) of the patients who had labetolol medication and 11 (16.9%) of the patients who did not receive labetalol were treated for hyperkalemia (p = 0.045). Factors considered for a logistic regression model included: the use of labetalol, cold ischemia time, diabetes, and dialysis method; intake of tacrolimus, beta blockers, angiotensin-converting enzyme inhibitors, or other antihypertensives prior to admission; the mannitol dose given intraoperatively, and the 24-hour urine output postoperatively. Intravenous labetalol (odds ratio OR = 4.52, confidence interval CI = 1.33–15.28; p = 0.02), 24- hour urine output (OR = 4.4, CI = 0.97–20.1: p = 0.47), increasing cold ischemia time (OR = 1.09, CI = 1.01–1.17; p = 0.02), and continuous ambulatory peritoneal dialysis (OR = 0.17, CI = 0.29-0.98; p = 0.036) were independent predictors. Conclusion: Labetalol appears to increase the risk of hyperkalemia in patients after renal transplantation.
Can Atherosclerosis Regress?
Authors: Kunz J.
Published: April 2003

Background: Previous extensive clinical studies, using angiography or ultrasound, investigated the influence of alimentary, medicamentous and other antiatherosclerotic measures on the degree of atherosclerosis. The following signs of regression were found: clinical improvement, changes in tonus of vascular walls, formation of collateral vessels or reduced occurrence of circulatory disturbances. Evidence of a diminution of plaque size was hardly ever produced from appropriate procedures in human pathology. A clear differentiation of regression and stop of progression was generally not possible. Objective: Causes of the difficulties arising in the evaluation of the atherosclerotic process are analyzed based on a review of the current literature. Prospects of regression in different forms of atherosclerosis were discussed. Conclusions: The strength of imaging diagnostics is limited above all by the remodeling of vascular walls, interfering age-related changes in arteries and the heterogeneity of atherosclerotic lesions in addition to the extremely protracted course of atherosclerosis matched by a corresponding extremely slow regression. Early lesions up to the preatheroma as classified by Stary et al. [Arterioscler Thromb Vasc Biol 1995;15:1512–1531] are considered reversible. Advanced lesions can probably be stabilized by antiatherosclerotic measures. Knowledge of collagen composition, proteoglycans, matrix metalloproteinases and other constituents of the vascular extracellular matrix as well as the histoarchitecture of atherosclerotic plaques using magnetic resonance tomography opens up new prospects for the assessment of regression of atherosclerosis.
Aging and Salivary Cytokine Concentrations as Predictors of Whole Saliva Flow Rates among Women
Authors: Streckfus Charles , Bigler Lenora , O’Bryan Tanya
Published: April 2003

Introduction: How aging influences the secretion of saliva is not entirely clear. Postmortem studies have demonstrated that, with age, the parenchyma of the salivary glands is gradually replaced by fat, connective tissue, and oncocytes. However, functional studies among healthy individuals indicate that aging per se does not lead to a diminution in the capacity of these glands to produce saliva. To date, the ambiguity between the morphometric and the clinical evidence cannot be explained. The purpose of this study was to determine if there was any relationship between the cytokine concentrations, salivary flow rates and aging. Methods: The study group consisted of 50 racially mixed women between the ages of 18 and 90. SWS were collected for 5 min using a 1-cm3 cube of paraffin as a stimulant. The samples were aliquoted, then frozen until assayed. Cytokine concentrations were determined using ELISA kits. The statistical analysis consisted of descriptive statistics, mean comparisons, and regression analyses. Results: The results suggest a reduction in SWS in association with an increase of salivary TGF-β1 concentrations. The overall model demonstrated an ability of the independent variables to predict the dependent variable (SWS) at the R2 = 0.53 level. The addition of the salivary cytokines to the model suggests that TGF-β1 (p < 0.045) and a near significant IL-2 (p < 0.07) concentration best explain the decrease in salivary function. The statistical relationship is supported by the physiological relationship between TGF-β1, IL-2, apoptosis, and aging. Conclusion: The results suggest a reduction in SWS flow in association with an increase of salivary TGF-β1 concentrations. This reduction concurs with the histomorphometric investigations, which indicate an age-related reduction of acinar cells in salivary gland tissues.
Influence of the Visual Environment on the Postural Stability in Healthy Older Women
Authors: Brooke-Wavell K. , Perrett L.K. , Howarth P.A. , Haslam R.A.
Published: April 2003

Background: A poor postural stability in older people is associated with an increased risk of falling. It is recognized that visual environment factors (such as poor lighting and repeating patterns on escalators) may contribute to falls, but little is known about the effects of the visual environment on postural stability in the elderly. Objective: To determine whether the postural stability of older women (using body sway as a measure) differed under five different visual environment conditions. Methods: Subjects were 33 healthy women aged 65–76 years. Body sway was measured using an electronic force platform which identified the location of their centre of gravity every 0.05 s. Maximal lateral sway and anteroposterior sway were determined and the sway velocity calculated over 1-min trial periods. Body sway was measured under each of the following conditions: (1) normal laboratory lighting (186 lx); (2) moderate lighting (10 lx); (3) dim lighting (1 lx); (4) eyes closed, and (5) repeating pattern projected onto a wall. Results: Each measure of the postural stability was significantly poorer in condition 4 (eyes closed) than in all other conditions. Anteroposterior sway was greater in condition 3 than in conditions 1 and 2, whilst the sway velocity was greater in condition 3 than in condition 2. Lateral sway did not differ significantly between different lighting levels (conditions 1–3). A projected repeating pattern (condition 5) did not significantly influence the postural stability relative to condition 1. Conclusions: The substantially greater body sway with eyes closed than with eyes open confirms the importance of vision in maintaining the postural stability. At the lowest light level, the body sway was significantly increased as compared with the other light levels, but was still substantially smaller than on closing the eyes. A projected repeating pattern did not influence the postural stability. Dim lighting levels and removing visual input appear to be associated with a poorer postural stability in older people and hence might be associated with an increased risk of falls.
Aggressive Antihypertensive Treatment and Serum Lipid Lowering Therapy Are Necessary to Prevent Deterioration of the Renal Function Even in Elderly Type 2 Diabetic Patients with Persistent Albuminuria
Authors: Narita Takuma , Kakei Masafumi , Ito Seiki
Published: April 2003

Background: In elderly patients with diabetic nephropathy, clinical information aiming at preventing a decline of the renal function is limited. Objective: To clarify factors that could be related to changes in renal function in elderly diabetic patients with persistent albuminuria. Methods: We studied the relationships between the declining rate of creatinine clearance (Ccr) and other clinical features – glycemic control, blood pressure (BP), the degree of albuminuria, and other confounding factors – retrospectively in elderly diabetic patients with persistent albuminuria. Results: We analyzed 17 elderly diabetic patients with persistent albuminuria (4 men and 13 women, mean age 68.0 ± 5.7 years at the beginning of the observation period) for 3.7 ± 1.5 (SD) years. We found that the last value of the urinary albumin excretion (UAE) of the observation period and the individual mean values of systolic BP, mean BP, and serum cholesterol closely correlated with the rate of decline in Ccr estimated by Cockcroft’s formula. The last UAE closely correlated with the individual mean values of systolic BP and mean BP. For patients such as the present subjects, adequate retardation of decline in renal function requires that the estimated goal of antihypertensive treatment should be a BP below 130/70 mm Hg. The level of glycemic control and the use of angiotensin-converting enzyme inhibitors did not correlate with the rate of decline in Ccr. Conclusion: Aggressive antihypertensive treatment and serum lipid lowering therapy may be necessary to prevent deterioration of the renal function in elderly type 2 diabetic patients with persistent albuminuria.
Characteristics and Outcome of Acute Stroke Patients Not Investigated with Computerised Tomography Scan
Authors: Sharma Jagdish , Fletcher Sally , Vassallo Michael , Butcher Clive , Ross Ian
Published: April 2003

Background: It is desirable that all acute stroke patients are investigated with a computerised tomography (CT) scan, but there may be situations when this is not possible. Objective: To investigate the characteristics and outcome of acute stroke patients not investigated with a CT scan and whether ‘not performing a CT scan’ influences mortality. Methods: Consecutive acute stroke patients admitted to a general hospital were studied for baseline characteristics, previous stroke, pre-stroke Rankin score, post-stroke neurological details, functional disability, complications and acute phase and 3-month mortality. Patients were categorised into two groups depending on whether or not they were investigated with a CT scan. χ2 and regression analysis were performed to study characteristics and mortality. Results: Ninety-four of the 296 patients did not undergo investigation with a CT scan. These patients were older (p = 0.001), had suffered previous strokes and had a poorer general health prior to admission (p < 0.001). Although there was no difference in clinical stroke syndromes and immediate post-stroke functional impairment, they had a greater impairment of level of consciousness (p = 0.003) and had a higher acute phase and 3-month mortality (p = 0.001). Not being investigated with a CT scan had an adverse influence on 3-month mortality independent of other variables. Conclusion: Whilst not investigating with a CT scan in acute stroke patients carries a poor prognosis, a group of patients may be managed without this investigation because of their poor pre-existing general health. These facts may be considered when preparing local guidelines for brain imaging for acute stroke patients.