bluuebunny/crossref_metadata_2025 huggingface dataset:
Anemia in Chronic Kidney Disease and Congestive Heart Failure
Authors: Silverberg D.S. , Wexler D. , Blum B. , Iaina A.
Published: April 2003

Anemia is seen in chronic kidney insufficiency (CKI), dialysis patients, congestive heart failure (CHF), and renal transplantation. Anemia can lead to progressive cardiac damage as well as progressive renal damage. It is not generally appreciated that CHF itself may be a very common contributor to both the production of anemia as well as to the progression of the renal failure. Correction of the anemia with erythropoietin and, as necessary, intravenous iron, may prevent the deterioration of both the heart and the kidneys. We suggest that there is a triangular relationship, a vicious circle, between CHF, CKI and anemia where each of these three can both cause and be caused by the other. We call this syndrome the cardio-renal anemia (CRA) syndrome. All physicians, especially cardiologists and internists who treat CKI and CHF, should be made aware of the dangers of anemia in CKI and CHF and should work with nephrologists to correct it.
A Kinetic Model of Inorganic Phosphorus Mass Balance in Hemodialysis Therapy
Authors: Gotch Frank A. , Panlilio Froilan , Sergeyeva Olga , Rosales Laura , Folden Tom , Kaysen George , Levin Nathan W.
Published: April 2003

Background: There is growing evidence that inorganic phosphorus (iP) accumulation in tissues (dTiP/dt) is a risk factor for cardiac death in hemodialysis therapy (HD). The factors controlling iP mass balance in HD are dietary intake (GiP), removal by binders (JbiP) and removal by dialysis (JdiP). If iP accumulation is to be minimized, it will be necessary to regularly monitor and optimize GiP, JbiP and JdiP in individual patients. We have developed a kinetic model (iPKM) designed to monitor these three parameters of iP mass balance in individual patients and report here preliminary evaluation of the model in 23 HD patients. Methods: GiP was calculated from PCR measured with urea kinetics; JdiP was calculated from the product of dialyzer plasma water clearance (KpwiP) and time average plasma iP concentration (TACiP) and treatment time (t); a new iP concentration parameter (nTACiP, the TACiP normalized to predialysis CoiP) was devised and shown to be a highly predictable function of the form nTACiP = 1 – α(1 – exp[–βKpwiP· t/ViP]), where the coefficients α and β are calculated for each patient from 2 measure values for nTACiP, KpwiP·t/ViP early and late in dialysis; we measured 8–10 serial values for nTACiP, KpwiP· t/ViP over a single dialysis in 23 patients; the expression derived for iP mass balance is ΔTiP = 12(PCR) – [KpwiP(t) (N/7)][CoiP(1 – α(1 – exp[–β(Kt/ViP)]))] – kb·Nb. Results: Calculated nTACiP = 1.01(measured nTACiP), r = 0.98, n = 213; calculated JdiP = 0.66(measured total dialysate iP) + 358, n = 23, r = 0.88, p < 0.001. Evaluation of 10 daily HD patients (DD) and 13 3 times weekly patients with the model predicted the number of binders required very well and showed that the much higher binder requirement observed in these DD patients was due to much higher NPCR (1.3 vs. 0.96). Conclusion: These results are very encouraging that it may be possible to monitor the individual effects of diet, dialysis and binders in HD and thus optimize these parameters of iP mass balance and reduce phosphate accumulation in tissues.
In vitro Expression of Human Hepatitis B Virus Genomes Carrying Woodchuck Hepatitis Virus Pre-S1 Sequences
Authors: Hourioux Christophe , Kneser Jonas , Bruss Volker
Published: April 2003

Many hepatitis B virus (HBV) in vivo experiments are unfeasible because this virus infects only humans. Former studies demonstrated that the pre-S1 domain of the viral envelope protein L determines host range. Therefore, we tried to generate HBV recombinants which might be able to infect woodchucks by exchanging different portions of the pre-S1 encoding gene with homologous parts from the related woodchuck hepatitis virus (WHV) in a cloned HBV genome. In 6 mutants, 11–92 N-terminal HBV pre-S1 codons were replaced by 20–120 codons from WHV. Four mutants carried C-terminal substitutions. The pre-S1 region overlaps with the viral polymerase gene, which is therefore also affected. After transfection of Huh7 cells, the DNA polymerase activity in cytoplasmic nucleocapsids was found to be only slightly affected. All mutants except for the largest C-terminal substitution allowed virion formation. Only the smallest N- and C-terminal substitutions had a wild-type phenotype. The remaining 7 variants allowed virion yields between 5 and 50% of that of the wild type. This demonstrated that substitution of up to 92 pre-S1 codons in an HBV genome with up to 120 codons from WHV pre- S1 was compatible with DNA replication and virion formation. Some recombinant viruses might be able to grow in woodchucks.
Iron and Ascorbic Acid Concentrations in Human Dermis with Regard to Age and Body Sites
Authors: Leveque Nathalie , Robin Sophie , Makki Safwat , Muret Patrice , Rougier André , Humbert Philippe
Published: April 2003

Background: Reactive oxygen species (ROS) contribute to processes relating to cutaneous aging. Iron catalyses ROS formation whereas ascorbic acid (AA) plays a fundamental role in defending the organism against undesirable ROS action. Objective: The aim of this work was to determine the ex vivo iron and AA concentrations in human dermis from different age groups to better understand their role. Methods: Skin fragments were collected from 66 female patients during surgical operations and were grouped according to age: group I (<15 years, before puberty, n = 12), group II (15–50 years, adults, n = 42), and group III (>50 years, advanced age adults, n = 12). Two sites were investigated: the abdomen (unexposed areas) and face (exposed sites). Iron and AA were collected from human dermis by microdialysis and assessed by atomic absorption spectrometry and gas chromatography mass spectrometry, respectively. Results: Iron concentrations in the dermis were significantly higher in group III (27.4 ± 20.9 µg/l) than in group I (13.8 ± 3.3 µg/l; p< 0.05 ). An inverse correlation between AA dermis levels and increasing age was detected. For groups III and I, iron and AA concentrations were significantly different in dermis from the face compared to that of the abdomen (p < 0.05). Conclusion: This study shows for the first time that there is a direct relationship between iron and AA concentrations in the dermis and aging. Moreover, iron and AA concentrations differed according to body site.
Quantitative EEG Abnormalities and Cognitive Dysfunctions in Frontotemporal Dementia and Alzheimer’s Disease
Authors: Lindau M. , Jelic V. , Johansson S.-E. , Andersen C. , Wahlund L.-O. , Almkvist O.
Published: April 2003

Objective: To investigate the relationship between quantitative EEG (qEEG) measurements in frontotemporal dementia (FTD), Alzheimer’s disease (AD) and healthy controls and to study to what extent qEEG in FTD and AD or neuropsychological test results of FTD and AD patients or a combination of both contribute to classification accuracy. Method: The FTD sample consisted of 19 patients, the AD sample of 16 patients, and the control group of 19 subjects. Groups were matched on the group level with respect to demographic variables. For qEEG the global field power was calculated for six frequency bands: δ (1.0–3.5 Hz), Θ (4.0–7.5 Hz), α (8.0–11.0 Hz), β1 (12.0–15.5 Hz), β2 (16.0–19.5 Hz), β3 (20.0–23.5 Hz), and spectral ratio as the ratio of the sum of fast frequency bands α + β1 + β2 + β3 and slow frequency bands δ + Θ. Results: In comparison to controls FTD patients were marked by an absence of an increase in slow qEEG activities and a decrease in fast activities, whereas AD patients were marked by an increase in slow activities and a smaller decrease in fast activities. According to the Mann-Whitney U test the cognitive functions of attention, visuospatial thinking and episodic memory were significantly better in FTD than in AD. Using logistic regression analysis the best predictors of FTD and AD were in a model using the δ and Θ activities, and high levels of visuospatial ability and episodic memory. Classification accuracy of the model was 93.3%. Conclusion: FTD patients reveal a different pattern of qEEG changes than AD patients. This result demonstrates the importance of qEEG for FTD diagnosis. Cognition is selectively better in FTD than in AD. A combination of qEEG and neuropsychology is recommended for differential diagnoses of FTD and AD.
Animal Models of Inflammatory Bowel Disease: An Overview
Authors: Hoffmann Jörg C. , Pawlowski Nina N. , Kühl Anja A. , Höhne Wolfgang , Zeitz Martin
Published: April 2003

Inflammatory bowel disease (IBD) research has been performed in human in vitro studies and in in vivo studies using appropriate animal models. Such animal models allow both the examination of inflammatory processes (both early and late events) as well as the evaluation of new therapeutic modalities. Since the first description of the immune complex colitis in rabbits in 1961, overall 63 models have been described, most of which within the last decade. These IBD animal models can be divided into 5 different categories: (1) antigen-induced colitis and colitis induced by microbials; (2) other inducible forms of colitis (chemical, immunological, and physical); (3) genetic colitis models (transgenic and knock-out models); (4) adoptive transfer models, and (5) spontaneous colitis models. In spite of the high overall number of models, none of them is the ‘perfect’ model and therefore numerous aspects need to be considered when choosing one model for a particular study. Importantly, most clinical aspects (e.g. extraintestinal manifestations or fistula) have recently been described in one or the other model allowing further studies with relevance for almost all aspects of IBD. So far, IBD animal models have taught us important lessons, e.g. the requirement of T-helper cells in most models, the need of a particular genetic background, and the role of the flora in the initiation of IBD. It is expected that our understanding of IBD will further increase in a number of additional areas using animal models, e.g. exploring the role of the innate immune system in IBD.
Percutaneous Treatment of Varicocele
Authors: Trombetta Carlo , Liguori Giovanni , Bucci Stefano , Ciciliato Stefano , Belgrano Emanuele
Published: April 2003

Varicocele is a common finding in adolescents and adult men. Its association with male infertility has been well documented: varicoceles are reported to be present in 20–40% of infertile men. It has been demonstrated that varicocele correction leads to an improvement in the quality of semen in most cases. Percutaneous sclerotherapy is an established treatment method for varicocele performed on an outpatient basis. In our report we review our experience with venographic study and transcatheter sclerotherapy based on 560 cases of infertile patients with varicocele. Our study confirms that percutaneous therapy of varicocele may lead to improved spermatogenesis in the majority of patients.
Performance of Conventional and New Methods for the Detection of Occlusal Caries in Deciduous Teeth
Authors: Lussi A. , Francescut P.
Published: April 2003

The aim of this study was to compare, in vitro, the performance of different conventional diagnostic techniques with the laser-based device, DIAGNOdent, for diagnosis of occlusal caries in deciduous teeth. 95 deciduous teeth with macroscopically intact occlusal surfaces were selected. All teeth were assessed by the following techniques: visual inspection (VI), visual inspection with magnification (VIM), visual inspection combined with light pressure probing (VIP), bitewing radiography (BW) and the DIAGNOdent (DD). Caries extension was assessed by histology. DIAGNOdent showed, in comparison with the conventional clinical methods, a significantly improved ability (p < 0.05) to detect dentinal lesions (D3 or D4) in deciduous teeth and an overall performance similar to that obtained in previous studies on permanent teeth. There was no statistically significant difference between VIM and DD in detecting caries confined to enamel (D2). DD performed better at D2 level than the other methods. The intraexaminer kappa scores for DIAGNOdent were 0.76–0.86 (D2) and 0.77–0.85 (D3), respectively. It was concluded that DIAGNOdent could be used as an additional tool in the detection of occlusal caries in deciduous teeth and its good reproducibility should enable the laser device to monitor the caries process over time.
Ischemic Optic Neuropathy Associated with Subarachnoid Hemorrhage after Rupture of Anterior Communicating Artery Aneurysm
Authors: Hara Naoto , Mukuno Kazuo , Ohtaka Hironori , Shimizu Kimiya
Published: April 2003

Two clinical cases in which ischemic optic neuropathy (ION) occurred after subarachnoid hemorrhage (SAH) are reported. Hemorrhage in the proximity of the optic chiasm was confirmed in 2 cases following rupture of an anterior communicating artery aneurysm. Optic disk atrophy with excavation and permanent visual field defect (altitudinal superior hemianopia) occurred in both cases. ION seems to occur in association with the optic nerve coincidental with the hyperdensity side of SAH on head CT scan. The incidence of ION appears to be attributable to an insufficient blood supply to arteries distributed in the posterior part of the optic nerve as a result of SAH.
Expression of Substance P and Its Neurokinin-1 Receptor on Thymocytes: Functional Relevance in the Regulation of Thymocyte Apoptosis and Proliferation
Authors: Santoni Giorgio , Amantini Consuelo , Lucciarini Roberta , Pompei Pierluigi , Perfumi Marina , Nabissi Massimo , Morrone Stefania , Piccoli Mario
Published: April 2003

Herein, we provide evidence of the expression and function of substance P (SP) and neurokinin-1 receptor (NK-1R) in the rat thymus. In situ hybridization evidenced NK-1R mRNA mainly in the thymic medulla, and Northern blot analysis of mRNA from FACS-sorted thymocytes identified NK-1R on CD4+, CD8+ and double-positive subpopulations. With flow cytometry, it could be seen that NK-1R was expressed on the majority of CD5+ thymocytes, and it was identified by Western blot analysis as two bands migrating at 44 and 54 kD. SP administration rescues thymocytes from spontaneous and NK-1R antagonist (SR140333)-induced apoptosis and stimulates concanavalin A (ConA)-induced thymocyte proliferation, CD25 expression and IL-2 production, whereas SR140333 exerts inhibitory effects on these functions. We also demonstrated the expression of mRNA for the SP precursor preprotachykinin-A in the thymic medulla and purified CD5+ thymocytes. SP protein was detected on 40% of CD5+ thymocytes and identified as a band of 1.3 kD by Western blot analysis. Finally, thymocytes spontaneously released SP, which was increased upon ConA or CD3 stimulation.
Calcitonin Receptor-Like Receptor Is Expressed on Gastrointestinal Immune Cells
Authors: Hagner Stefanie , Knauer Jens , Haberberger Rainer , Göke Burkhard , Voigt Karlheinz , McGregor Gerard Patrick
Published: April 2003

Background/Aims: Pharmacological and morphological studies suggest that the gut mucosal immune system and local neuropeptide-containing neurones interact. We aimed to determine whether gut immune cells are targets for calcitonin gene-related peptide (CGRP), which has potent immune regulatory properties. Methods: Using density gradient centrifugation, rat lamina propria mononuclear cells (LP-MNCs) and intra-epithelial lymphocytes (IELs) were isolated. RT-PCR was employed for the detection of mRNA of rat calcitonin receptor-like receptor (CRLR), which is considered to represent the pharmacologically defined CGRP receptor-1 subtype, as well as mRNA of the receptor activity-modifying proteins, which are essential for CRLR function and determine ligand specificity. A radioreceptor assay was employed for the detection of specific CGRP binding sites. Results: RT-PCR and DNA sequencing showed that LP-MNCs and IELs express CRLR. Incubation of isolated LP-MNCs with radiolabelled αCGRP revealed the existence of specific binding sites for CGRP. Conclusion: These novel data indicate that mucosal immune cells of the rat gut are a target for CGRP and provide significant evidence that CGRP functions as an immune regulator in the gut mucosa.
Gelatin Prepared from Tuna Skin: A Risk Factor for Fish Allergy or Sensitization?
Authors: André Françoise , Cavagna Sylvie , André Claude
Published: April 2003

Background: Although fish gelatin may represent a useful alternative to bovine or porcine gelatins, the clearly recognized high prevalence of fish allergy could increase the risk of anaphylaxis to gelatin. The rationale for investigating tuna gelatin rather than gelatins from more allergenic fishes is the availability of an industrial gelatin under development. The infrequent occurrence of tuna allergy should influence the safety of a derived product. The present study investigated IgE antibodies to tuna-skin-derived gelatin in adults and children with documented fish allergy or sensitization. Methods: Serum samples were taken from 100 consecutive patients with fish allergy or sensitization and tested for IgE antibodies against hydrolyzed or nonhydrolyzed gelatin extracted from tuna skin as compared to extracts from tuna flesh, tuna skin as well as bovine or porcine gelatins. Patients with tuna allergies or sensitization were sensitive to the same tuna species (yellowfin) as that from which the gelatin was obtained. IgE antibodies to these various extracts were analyzed using SDS-PAGE and immunoblotting. Results: Only 3 of the 100 serum samples tested gave evidence of reactivity to gelatin extracted from tuna skin. Cross-reactivity between bovine/porcine and fish gelatins was not observed. Conclusion: The risk of adverse reactions to tuna skin gelatin seems to be significantly lower than the risk of fish allergy. Fish gelatin may represent a valuable alternative to bovine or porcine gelatins.
Cloning and Molecular Characterization of a cDNA from Blomia tropicalis Homologous to Dust Mite Group 3 Allergens (Trypsin-Like Proteases)
Authors: Flores Idhaliz , Mora Carlos , Rivera Elizabeth , Donnelly Robert , Montealegre Federico
Published: April 2003

Background: Exposure to the house dust mite Blomia tropicalis is increasingly being implicated as a major risk factor for asthma exacerbations in sensitized individuals. The objective of this study is to clone and characterize B. tropicalis allergens in order to better define their role in allergic asthma. Methods: A λgt22A cDNA library was constructed from B. tropicalis mRNA and screened using specific DNA probes. A full-length cDNA (Bt2-3) was isolated, subcloned, and sequenced. Results: Sequence analysis showed that clone Bt2-3 encodes the full-length serine protease preproenzyme from B. tropicalis. The predicted Bt2-3 protein consists of a 15-amino-acid signal peptide, a 20-amino-acid propeptide and a mature protein of 231 amino residues. BLAST analysis of the deduced amino acid sequence showed high homology (48–54%) between clone Bt2-3 and serine proteases (group 3 allergens) from domestic dust mites. Both the serine active site (DACQGDSGGPVA; amino acids 214–225) and the histidine active site (LTAAHC; amino acids 71–76) of serine proteases were highly conserved. The estimated molecular weight of the preproenzyme is 27.5 kD and its theoretical pI is 8.7. The mature protein contains a putative tyrosine kinase phosphorylation site (amino acids 24–31) and several N-myristoylation sites. Sequence alignment shows that the serine protease active sites are highly conserved among the clinically important mite species, including B. tropicalis. Conclusion: We report the cloning and molecular characterization of a B. tropicalis cDNA clone encoding a trypsin-like protease, with a possible major role as an allergen. Expression and further characterization of the recombinant product will help determine the role of proteolytic enzymes in the pathophysiology of allergic asthma.
Metoclopramide-Induced Hyperprolactinemia Affects Mouse Endometrial Morphology
Authors: Rossi Alexandre G.Z. , Soares Jr. José M. , Motta Eduardo L.A. , Simões Manuel J. , Oliveira-Filho Ricardo M. , Haidar Mauro A. , Rodrigues de Lima Geraldo , Baracat Edmund C.
Published: April 2003

Information about the effects of pituitary hyperprolactinemia on endometrium, especially in levels coexisting with absence of amenorrhea in women, is scarce. The interference of high prolactin levels on endometrial morphology was thus investigated in young post-pubertal and adult mice rendered hyperprolactinemic by long-term treatment with metoclopramide (MC). No remarkable differences have been noticed upon light microscopy examination of the endometria comparing young to adult cycling MC-treated mice, except on the max/min diameter ratio, which in young animals was lower than in adults (ANOVA, p < 0.01). Both young and adult MC-treated mice presented an increased number of endometrial glands than their respective controls (ANOVA, p < 0.01). However, young MC-treated animals showed the highest values of endometrial thickness index compared to other groups (ANOVA, p < 0.01). Our results indicate that MC-induced hyperprolactinemia causes mouse endometrium proliferation, mainly in young animals.
Explaining Variation in Affiliative Relationships among Male White-Faced Capuchins (Cebus capucinus)
Authors: Jack Katharine M.
Published: April 2003

Relationships among coresident male white-faced capuchins are highly variable, ranging from affiliative to aggressive. In this paper I examine the affiliative relationships of all adult and subadult males residing in four social groups in Santa Rosa National Park, Costa Rica. Relationships among males in two study groups were neutral and tolerant, while in the remaining two groups males were highly affiliative. Male-male dyadic affiliative interactions were examined to determine which variables (group size, sex ratio, age relationship, relationship duration, and rank distance) influence the quality of male relationships within the study groups. Group size explained much of the variation, with males in small groups being more affiliative. However, the duration and history of the relationship among coresident males appears to be the most important variable in understanding male-male relationships within social groups.
Microvenular Hemangioma
Authors: Kim Y.-C. , Park H.-J. , Cinn Y.-W.
Published: April 2003

Microvenular hemangioma is a rare, slowly growing, benign vascular tumor. It usually presents as a solitary, asymptomatic, purple to red papule or plaque in young to middle-aged adults. Histologically, the tumor is composed of irregular, branching venules with inconspicuous lumina with a lack of endothelial atypia. We describe a case of microvenular hemangioma in a 40-year-old female. The lesion was slightly tender unlike that of previously reported cases. In the context of the histological similarity to a low-grade malignant tumor, Kaposi’s sarcoma, the awareness of microvenular hemangioma, a benign vascular tumor, is important.
Transient Global Amnesia: A Clinical and Sonographic Study
Authors: Maalikjy Akkawi N. , Agosti C. , Anzola G.P. , Borroni B. , Magoni M. , Pezzini A. , Rozzini L. , Vignolo L.A. , Padovani A.
Published: April 2003

Background: The aetiology of transient global amnesia (TGA) is still unknown. The aim of this study was to identify potential risk factors for TGA, vascular risk factors, the role of patent foramen ovale (PFO) and of retrograde jugular venous flow. Methods: 138 subjects entered the study, including 48 patients with TGA, 42 age-matched patients with transient ischaemic attack (TIA) and 48 controls. PFO was studied by contrast transcranial duplex sonography. Retrograde jugular venous flow was tested with air contrast ultrasound venography (ACUV). Results: TGA patients and controls showed a lower prevalence for vascular risk factors than TIA patients. No statistical difference was found between the 3 groups with regard to PFO. ACUV detected jugular valve incompetence in 72.9% TGA, 35.7% TIA and 39.5% controls (TGA vs. TIA and TGA vs. controls p < 0.01). Conclusions: TGA patients have fewer vascular risk factors than TIA patients. Paradoxical embolism due to PFO as a cause of TGA is not confirmed in our study. Cerebral venous hypertension due to incompetence of the internal jugular valve may play a role in the pathogenesis of TGA.
Early Prediction of Neurological Outcome after Cardiopulmonary Resuscitation: A Multimodal Approach Combining Neurobiochemical and Electrophysiological Investigations May Provide High Prognostic Certainty in Patients after Cardiac Arrest
Authors: Zingler Vera Carina , Krumm Bertram , Bertsch Thomas , Fassbender Klaus , Pohlmann-Eden Bernd
Published: April 2003

A reliable and reproducible method for precisely predicting the neurological outcome of patients with hypoxic-ischemic encephalopathy after cardiac arrest is urgently needed in neurological intensive care units. We prospectively investigated the predictive power of serum concentrations of neuron-specific enolase (NSE) and protein S-100B (S-100B) measured on days 1, 2, 3 and 7 as well as somatosensory-evoked potentials (SEPs) recorded within 48 h and on day 7 after cardiopulmonary resuscitation (CPR) in 27 patients (14 females, 13 males; mean age 61.3 ± 17.3 years) with hypoxic-ischemic encephalopathy. During the first 7 days after CPR, median values of NSE and S-100B were increased in patients who remained unconscious after CPR compared to those patients who regained consciousness (significance up to ≤0.001). The best predictor of negative outcome was an NSE cutoff point ≧43 µg/l on day 2; this had a sensitivity of 90.9% and a specificity of 100%. Additional use of S-100B on day 2 did not increase sensitivity, but this could be markedly increased by combining NSE and S-100B on days 1, 3 and 7. SEPs showing bilateral loss of cortical responses identified patients who did not regain consciousness with a specificity of 100%.
Survival of Cardiac Function after Brain Death in Patients in Kuwait
Authors: Al-Shammri S. , Nelson R.F. , Madavan R. , Subramaniam T.A. , Swaminathan T.R.
Published: April 2003

Background: Persistent cessation of all cerebral and brainstem function (brain death) is accepted in most countries as legal evidence of death. It is presumed that cardiac function will cease within a short time after brain death has occurred. In some countries, such as Kuwait, tradition and practice discourage application of the brain death criteria despite legal acceptance. Objective: The study was designed to assess the duration of persistence of cardiac function in patients after the diagnosis of brain death had been made on the basis of generally accepted criteria. Methods: We evaluated how long cardiac function persisted after brain function had ceased in 40 patients in Kuwait who were admitted to hospital and died during the 10-year period 1992–2001. Results: It was found that the mean persistence of cardiac function after brain death was 8.20 days and the median survival time was 6 days. Two thirds of the patients survived longer than a week, but none had cardiac function for longer than 30 days. Conclusion: The study confirms that brain death is not automatically followed immediately by cessation of all other body functions. It may be speculated therefore that whole-body homeostasis is not as intimately associated with brain function as has hitherto been thought.
Stroke: Trial by Jury
Authors: Lees Kennedy R.
Published: April 2003

Trials of pharmacological intervention for acute stroke show several points of similarity with legal trials by jury. The relationships between sponsoring organisation and regulatory authorities and the roles of the many other participants are described. Only through a partnership can the common aim of developing improved treatment for patients with stroke be realised. Excellent structures and procedures have recently developed which minimise the risk of undertaking impractical, invalid or unreported trials. This will lead to greater confidence in our ability to identify a successful treatment and to discount worthless approaches.
Phenotyping Renal Leukocyte Subsets by Four-Color Flow Cytometry: Characterization of Chemokine Receptor Expression
Authors: Vielhauer Volker , Anders Hans-Joachim , Pérez de Lema Guillermo , Luckow Bruno , Schlöndorff Detlef , Mack Matthias
Published: April 2003

To investigate mechanisms of cell-mediated injury in renal inflammatory disease it is critical to determine the surface phenotype of infiltrating renal leukocyte subsets. However, the cell-specific expression of many leukocyte receptors is difficult to characterize in vivo. Here, we report a protocol based on flow cytometry that allows simultaneous characterization of surface receptor expression on different subsets of infiltrating renal leukocytes. The described technique combines an adapted method to prepare single cell suspensions from whole kidneys with subsequent four-color flow cytometry. We recently applied this technique to determine the differential expression of murine chemokine receptors CCR2 and CCR5 on infiltrating renal leukocyte subsets. In this article, we summarize our current findings on the validity of the method as compared with immunohistology and in situ hybridization in two murine models of nonimmune (obstructive nephropathy) and immune-mediated (lupus nephritis) inflammatory renal disease. Flow cytometry analysis revealed an accumulation of CCR5-, but not CCR2-positive lymphocytes in inflamed kidneys, compared to the peripheral blood. Particularly renal CD8+ cells expressed CCR5 (79% in obstructed kidneys, 90% in lupus nephritis). In both models, infiltrating renal macrophages were positive for CCR2 and CCR5. These data corresponded to immunohistological and in situ hybridization results. They demonstrate that flow cytometric analysis of single cell suspensions prepared from inflamed kidneys is a rapid and reliable technique to characterize and quantify surface receptor expression on infiltrating renal leukocyte subsets.
Comparison of Antiallergic Drugs in an Experimental Model of Ocular Anaphylaxis
Authors: Bayer Atilla , Uludağ H. Avni , Sobacı Güngör , Mutlu Fatih Mehmet
Published: April 2003

Purpose: To compare the efficacy of antiallergic drugs in an experimental ocular anaphylaxis model. Materials and Methods: Fifty-two rats were divided into 8 groups. Dithiothreitol and ovalbumin (OVA) were applied to both eyes of previously OVA-inoculated rats in groups 1–5 and 7. In groups 1–5, antiallergic efficacy of the drugs (lodoxamide, sodium cromoglycate, levacobastine, cimetidine, and diclofenac sodium) instilled on the right eyes were compared with the buffer instilled on the left eyes, measuring the amount of extravasated Evans blue (EB) dye by spectrophotometric analysis. Group 6 served as a control of EB dye extravasations in nonimmunized eyes. Histopathologic examinations for anaphylaxis and controls were done in groups 7 and 8. Results: Only levacobastine and lodoxamide decreased vascular permeability at a significant ratio (46%, p < 0.01 and 31%, p < 0.05, respectively). Conclusion: Levacobastine and lodoxamide but none of the three other drugs mentioned above were found to be effective in decreasing vascular permeability.
The Effect of N-Acetyl Serotonin on Ultraviolet-Radiation-Induced Cataracts in Rats
Authors: Yildirim Nilgün , Özer Ahmet , İnal Mine , Angin Kemal , Yurdakul Sumru
Published: April 2003

Aims: To investigate the effects of ultraviolet radiation (UVR) on cataract development in rat lenses and whether or not N-acetyl serotonin has an effect on changes in these lenses. Material and Methods: The study was performed using 5 groups of Sprague-Dawley albino rats, with each group consisting of 15 rats. The 5th group being the control group did not receive any applications, whilst the other 4 groups received a daily dose of 0.2 J/cm2/day UVR (305 nm wavelength) for 60 days. A dose of 4 mg/kg/0.1 ml N-acetyl serotonin was injected intraperitoneally to group 1 and group 2 every day and on alternate days, respectively. Group 3 received an intraperitoneal injection of 0.1 ml phosphate buffer solution every day, whilst group 4 received no injection. On the 60th day, an intracardiac withdrawal of blood was performed, after the rats had been anesthetized with ether. Following the withdrawal of blood, the rats were killed using a high dose of ether and their eyes were enucleated. The lens fresh weights, plasma malondialdehyde (P-MDA), erythrocyte glutathione peroxidase (E-GSHPx), erythrocyte glutathione reductase, blood reduced glutathione (B-RGSH), erythrocyte catalase (E-CAT), lenticular malondialdehyde, lenticular superoxide dismutase (L-SOD), lenticular glutathione peroxidase (L-GSHPx) and lenticular glutathione (L-GSH) levels were all assessed. Results: The lens fresh weights were determined to be lower in group 1 and in the control group in comparison with the other groups (p < 0.01). Whilst the P-MDA level was found to be lower (p < 0.001), the E-GSHPx level was higher (p < 0.01) in the control group than in the other groups. The E-GSHPx level was higher in groups 1 and 2 than in groups 3 and 4 (p < 0.01). The B-RGSH level was higher in the control group than in the other groups (p < 0.001). The E-CAT level was higher in both the control group and group 1 than in groups 2, 3 and 4 (p < 0.01), whilst it was higher in group 2 when compared to groups 3 and 4 (p < 0.01). The L-SOD levels were found to be higher in the control group and group 1 than in groups 2, 3 and 4 (p < 0.001). Whilst the L-GSHPx levels were determined to be higher only in the control group (p < 0.001), the L-GSH levels were higher in the control group and group 1 than in the other groups (p < 0.001). Conclusions: In recent years, the depletion of the atmospheric ozone layer has resulted in the penetration of more UVR to the earth, which causes various effects on different tissues of organisms. N-acetyl serotonin, a melatonin precursor, may well be effective in the prevention of the negative effects induced by the UVR upon the lens tissue, in which case the capability of melatonin to capture free radicals as well as its antioxidative properties should be taken into consideration.
Topographic Mapping of Retinal Function with the SLO-mfERG under Simultaneous Control of Fixation in Best’s Disease
Authors: Rudolph Gunther , Kalpadakis Petros
Published: April 2003

Purpose: To introduce the scanning laser ophthalmoscope-evoked mfERG (SLO-mfERG) as a new method to measure focal retinal function. Methods: Sixty-two healthy individuals and 12 patients with Best’s disease were examined. mfERGs were recorded using a scanning laser ophthalmoscope as a stimulator and trigger device (He-Neon 632.8 nm) as well as a fundus-monitoring system (Infrared 730 nm). Results: Amplitudes in the central concentric area were found to be significantly lower in patients with Best’s disease than in healthy controls, while no significant differences were found for the more peripheral areas. Conclusion: SLO-mfERG is a reliable new technique for topographic mapping of retinal function under simultaneous control of fixation.
Expression of p16 Protein and Hypermethylation Status of Its Promoter Gene in Adenoid Cystic Carcinoma of the Head and Neck
Authors: Maruya Shin-Ichiro , Kurotaki Hidekachi , Shimoyama Norihiko , Kaimori Mitsuomi , Shinkawa Hideichi , Yagihashi Soroku
Published: April 2003

Reduced expression of the p16 gene product (protein), an inhibitor of cyclin-D-dependent protein kinase which regulates cell cycle at the G1/S boundary, is implicated in tumor progression in various neoplasms. Hypermethylation of the p16 promoter gene has recently been suggested to be one of the reasons for the reduced protein expression. To explore the role of p16 in the biological behavior of adenoid cystic carcinomas (ACC), we investigated the immunohistochemical expression of p16 protein in 38 ACC tumors (32 primary, 3 recurrent, and 3 metastatic tumors) and the methylation status of its promoter gene. We also examined their relationships to the histological grade of malignancy. Positive reaction of p16 protein was demonstrated in the nuclei of luminar cuboidal cells in areas with tubular patterns. The reactions were reduced in the areas with solid or large cribriform patterns. The levels of p16 expression correlated with the histological grade of malignancy. Recurrent or metastatic tumors did not differ with respect to histological grades from the original tumor except for 1 case, in which p16 expression was reduced compared to the primary tumor. Methylation-specific PCR demonstrated the hypermethylation status of the p16 promoter gene in 4 of 22 primary tumors (21%), all of which showed negative or low expression of the p16 protein. The study indicated that p16 expression was reduced in ACC cases of higher histological grade of malignancy and that hypermethylation of its promoter gene may be involved in its process in some cases.
New Interdisciplinary Approach for Removing Large Clivus and Upper Cervical Spine Tumors
Authors: Okamura Hiro-oki , Nishimura-Ogino Eriko , Shinomiya Kenichi , Komori Hiromichi , Haro Hirotaka , Kishimoto Seiji
Published: April 2003

We have developed a new interdisciplinary approach for removing large clivus and upper cervical spine tumors. This approach is a combination of the Le Fort I osteotomy, midfacial degloving, and median labiomandibular glossotomy. Our approach gives an excellent, wide surgical field from the nasopharynx, including the base of the skull, to the base of the tongue and permits sufficiently safe extirpation of clivus and upper cervical spine tumors that may not be removed by transoral or transcervical approaches. Our approach not only incorporates the merits of each approach but also creates a larger surgical field that may be modified or expanded to accommodate the removal of more bulky tumors in this region. This novel approach will facilitate more successful resection of tumors arising between the nasopharynx, including the skull base, and the retropharyngeal area.
Effects of the Intravenously Administered Anaesthetics Ketamine, Propofol, and Thiamylal on the Cortical Renal Blood Flow in Rats
Authors: Shiga Yousuke , Minami Kouichiro , Uezono Yasuhito , Segawa Kayoko , Nagaoka Etsuko , Shiraishi Munehiro , Noguchi Takashi , Shigematsu Akio
Published: April 2003

Intravenous anaesthetics such as ketamine, propofol, and thiamylal are widely used, although the direct effects of these anaesthetics on the renal blood flow (RBF) have not been well elucidated. In this study, we examined the effects of bolus and continuous administrations of ketamine, propofol, and thiamylal on cortical RBF and the effects of noradrenaline (NA) on RBF under continuous administration of these anaesthetics. We used laser Doppler flowmetry to measure the effects of bolus injection and continuous infusion of ketamine, propofol, and thiamylal on cortical RBF in male Wistar rats. We also examined the effects of the anaesthetics on mean arterial blood pressure (MAP) and heart rate (HR). Bolus injections of ketamine, propofol, or thiamylal (1–8 mg/kg each, n = 10) at clinically relevant concentrations did not affect MAP, HR, or RBF. Continuous administration of ketamine, propofol, or thiamylal (1–8 mg/kg/h each, n = 10) did not affect MAP, HR or RBF. Exogenous NA (2 µg/kg) caused an increase in MAP and a decrease in RBF and HR. In experiments with continuous infusions of propofol or thiamylal (1–8 mg/kg/h each, n = 10), similar results were observed without infusion of any anaesthetics. However, bolus injection of NA did not result in a decrease in RBF during continuous ketamine infusion (98.8 ± 6.7% of control, n = 6, p < 0.05), while ketamine did not affect the NA-induced increase in MAP. In conclusion, bolus and continuous administrations of ketamine, propofol, and thiamylal did not affect the RBF. From our present findings, ketamine would be useful for maintaining the RBF.
Laterality of Brain Tumors
Authors: Inskip Peter D. , Tarone Robert E. , Hatch Elizabeth E. , Wilcosky Timothy C. , Selker Robert G. , Fine Howard A. , Black Peter McL. , Loeffler Jay S. , Shapiro William R. , Linet Martha S.
Published: April 2003

Tumor laterality was evaluated with respect to presenting symptoms and demographic factors among 489 adults with histologically confirmed glioma (354 high-grade, 135 low-grade), 197 with meningioma, and 96 with acoustic neuroma. The ratio of left-sided to right-sided tumors did not differ significantly from 1.00 for any of the major tumor types. Low-grade glioma and meningioma occurred nonsignificantly more often on the left side, whereas high-grade glioma and acoustic neuroma occurred nonsignificantly more often on the right side. Aphasia or mental status changes were significantly more common among glioma patients with tumors on the left side than among those with tumors on the right side. Associations between tumor laterality and symptoms may influence the probability or timing of diagnosis, possibly differentially by marital status.
Total Calcium Content of Sacs Associated with Inguinal Hernia, Hydrocele or Undescended Testis Reflects Differences Dictated by Programmed Cell Death
Authors: Tanyel F. Cahit , Ulusu N. Nuray , Tezcan E. Ferhan , Büyükpamukçu Nebil
Published: April 2003

Introduction: Inguinal hernia and hydrocele are suggested to result from the persistence of smooth muscle (SM) which should undergo programmed cell death (PCD) after presenting transiently to propel the testis. Since Ca2+ is involved in PCD, the Ca2+ contents of the peritoneum and sacs associated with undescended testis, inguinal hernia and hydrocele were determined and compared. Materials and Methods: Sacs were obtained from boys with undescended testis (n = 11), inguinal hernia (n = 22) and hydrocele (n = 10), and girls with inguinal hernia (n = 7). The calcium content of the sacs and peritoneal samples (n = 6) was determined through atomic absorption spectrophotometry. Calcium contents were compared according to their sources using the Mann-Whitney U test and p values of <0.05 were considered significant. Results: While revealing similar Ca2+ contents as the peritoneum, sacs associated with undescended testis and hydrocele contained more Ca2+ contents than the sacs of boys and girls with inguinal hernia (p < 0.05). Conclusions: Sacs associated with inguinal hernia, which are known to contain SM all around the mesothelial layer, contain the least Ca2+. Despite the decrease in SM, sacs associated with hydrocele contain more Ca2+. Since PCD is associated with Ca2+ overload and inhibition of Ca2+ load inhibits PCD, differences in Ca2+ content may reflect the inhibition of PCD at different stages and for different reasons in inguinal hernia or hydrocele of childhood.
Mortality in Alzheimer’s Disease
Authors: Bonsignore Marzia , Heun Reinhard
Published: April 2003

Objective: This study examines the relevance of variables suspected to influence mortality in Alzheimer’s disease (AD). Methods: 172 subjects with AD recruited through a family study were followed up for a mean of 4.7 ± 2.6 years. Their survival was compared with that of matched control subjects using Kaplan-Meier and log-rank statistics. Variables determining mortality were examined with the Cox proportional hazards model. Results: Survival in subjects with AD depended on age, the severity of cognitive decline and on the incidence of hospitalisation. Gender, the duration of the illness, the velocity of cognitive decline, the allele E4 of the apolipoprotein E genotype and the presence of other lifetime psychiatric diagnoses did not influence mortality. Conclusion: Mortality in AD depended mainly on the subjects’ age and the severity of the disorder.
Cardiovascular Effects of Donepezil in Patients with Dementia
Authors: McLaren A.T. , Allen J. , Murray A. , Ballard C.G. , Kenny R.A.
Published: April 2003

Heart rate variability is used to assess cardiovascular autonomic function. The cholinesterase inhibitor donepezil potentially affects parasympathetic activity. Twenty participants with Alzheimer’s disease or dementia with Lewy bodies were treated with donepezil in a pilot study. Power spectral analysis was used to analyse 5 min of beat-to-beat RR interval data in 15 cases. Heart rate variability was significantly reduced following treatment with donepezil; mainly for high frequency (median changed from 581 to 78 ms2; p = 0.001) but also for total power (median changed from 1,563 to 844 ms2; p = 0.047). Donepezil may adversely influence cardiovascular autonomic control. These results indicate the need for larger controlled trials to further investigate the cardiovascular effects of donepezil.
Recurrent Erythematous Dermatitis artefacta in the Face Induced by Benzyl Nicotinate
Authors: Thiele Jens J. , Kaatz Martin , Schmidt Silke , Heinemann Christian , Elsner Peter
Published: April 2003

Dermatitis artefacta may mimic a number of common skin disorders. We report an example of an unusual and treatment-resistant erythematous facial dermatosis in an adolescent girl imitating a number of dermatological disorders which led to a delay in the diagnosis of dermatitis artefacta induced by benzyl nicotinate. Cutaneous factitious disease should be included in the differential diagnosis of recurrent lesions, particularly in facial skin if signs and symptoms, history, laboratory results and dermatopathology findings are inconclusive.
Ultrasound Shear Wave Propagation in Caucasian Hair
Authors: Piérard-Franchimont C. , Goffin V. , Uhoda E. , Piérard G.E.
Published: April 2003

Background: The aspect of hair depends on the spatial organization of the hair shafts and on their chemical, physical and structural integrity. Some genetic disorders and exogenous influences may affect it. Aims: In vivo objective assessments are welcome in order to compare the consequences of hair damage and to assess the kinetics of the changes occurring in time after damaging or attempting to repair the hair structure. Method: Ultrasound shear wave propagation measured on hair is introduced as an objective non-invasive method with in vitro and in vivo applications. Results: With multiple measurements made on the scalp of 72 Caucasians, hair felting following damage appeared to be associated with an increase in the coefficient of variation of the shear wave velocity measurements. Maximum hydration of hair locks increased the shear wave velocity in vitro and decreased the intra-individual range of data. The relevance of the method and reproducibility of data were influenced by the experimentalist’s skill. Conclusion: Ultrasound shear wave propagation on hair is influenced by the physical integrity of the hair shafts and their three-dimensional arrangement.