bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Sildenafil Citrate an Alternative Agent in the Evaluation of Penile Vascular System with Color Doppler Ultrasound?
Authors: Erdoğru Tibet , Usta Mustafa F. , Çeken Kağan , Köksal Türker , Ates Mutlu , Kabaalioğlu Adnan , Baykara Mehmet
Published: April 2003

Introduction: The ideal diagnosis and therapeutic agent for erectile dysfunction (ED) would be an oral drug taken prior to color Doppler ultrasound (CDU) examination and sexual intercourse. In the present study we have investigated if the efficacy of oral sildenafil is optimal in the diagnosis of underlying pathology of ED. Material and Methods: The study group comprised of 41 patients with ED. Firstly, all patients underwent CDU examinations after the combined intracavernosal injection of 60 mg of papaverine and sexual stimulation (CIS). Secondly, these patients were examined after taking 50 mg of oral sildenafil citrate combined with self-manual and visual sexual stimulation. Results: The differences of peak systolic velocity values were statistically significant between CIS and sildenafil (right: 40.7 ± 2.9 vs. 28.7 ± 3.3; left: 41.2 ± 3.3 vs. 25.7 ± 2.4; p < 0.001) in patients with normal penile vascular system. However, end-diastolic velocity and resistance index values were not significant between the same groups. In addition, there were not significant differences for peak systolic and end-diastolic blood flow velocities and resistances index with CIS and sildenafil in cases with vasculogenic ED. Conclusions: Sildenafil citrate plus visual sexual stimulation is not reliable as CIS to make accurate interpretation of penile vascular status using CDU. On the other hand, in some cases suspected of psychogenic ED after detailed sexual history, sildenafil might be tried as an initial step of the functional evaluation with CDU in order to prevent prolonged erection risk with intracavernosal injection of vasoactive agents.
Habitual Intake of Lactic Acid Bacteria and Risk Reduction of Bladder Cancer
Authors: Ohashi Yasuo , Nakai Satoshi , Tsukamoto Taiji , Masumori Naoya , Akaza Hideyuki , Miyanaga Naoto , Kitamura Tadaichi , Kawabe Kazuki , Kotake Toshihiko , Kuroda Masao , Naito Seiji , Koga Hirofumi , Saito Yutaka , Nomata Koichiro , Kitagawa Motoaki , Aso Yoshio
Published: April 2003

Introduction: A kind of lactic acid bacteria, Lactobacillus casei strain Shirota, shows antitumor activity in experimental animals. One clinical trial using L. casei showed a significant decrease in the recurrence of superficial bladder cancer. So, to assess the preventive effect of the intake of L. casei, widely taken as fermented milk products in Japan, against bladder cancer, we conducted a case-control study. Methods: A total of 180 cases (mean age: 67 years, SD 10) were selected from 7 hospitals, and 445 population-based controls matched by gender and age were also selected. Interviewers asked them 81 items. The conditional logistic regression was used to estimate adjusted odds ratios (OR). Results: The OR of smoking was 1.61 (95% confidence interval: 1.10–2.36). Those of previous (10–15 years ago) intake of fermented milk products were 0.46 (0.27–0.79) for 1–2 times/week and 0.61 (0.38–0.99) for 3–4 or more times/week, respectively. Conclusion: It was strongly suggested that the habitual intake of lactic acid bacteria reduces the risk of bladder cancer.
Analysis of the Trace Element Contents of Inner Nucleus and Outer Crust Parts of Urinary Calculi
Authors: Perk Hakki , Serel T. Ahmet , Koşar Alim , Deniz Nuri , Sayin Adnan
Published: April 2003

In this study, the lead, cadmium, nickel, and aluminum concentrations were analyzed in inner nucleus and outer crust parts of various kinds of urinary calculi, and the results obtained were statistically compared. Significant differences were found among the element concentrations in the different stone groups. In general, higher element concentrations were found in the nuclei as compared with the crust parts. In addition, some significant intra- and intercorrelations were established among the elements analyzed. The results suggest that some trace elements, including lead, cadmium, nickel, and aluminum, together with other factors may have as yet no clarified functions in the stone precipitation process in the urinary tract.
Successful Surgical Reconstruction of Ruptured Renal Pelvis following Blunt Abdominal Trauma
Authors: Bogdanović Jovo , Djozić Jasenko , Idjuški Stevan , Popov Milan , Sekulić Vuk , Stojkov Jovan
Published: April 2003

A 25-year-old man with occult ureteropelvic obstruction presented with abdominal pain 3 h following blunt abdominal trauma. Isolated rupture of the right renal pelvis was promptly diagnosed and the patient underwent immediate pyeloplasty according to the Anderson-Hynes procedure. The patient made an uneventful recovery. One year after surgery, renal function was satisfactory.
Microwave decondensation and codenaturation: a new methodology to maximize FISH data from donors with very low concentrations of sperm
Authors: Ko E. , Rademaker A. , Martin R.
Published: April 2003

To increase analyzable sperm numbers when dealing with semen samples from donors with extremely low quantities of sperm, a microwave decondensation/codenaturation technique for fluorescence in situ hybridization (FISH) was developed and results were compared to those obtained from conventional FISH techniques. There was no significant difference between the frequencies of disomy and diploidy obtained using the two techniques.
Genomic organization of the DCTN1-SLC4A5 locus encoding both NBC4 and p150Glued
Authors: Pushkin A. , Abuladze N. , Newman D. , Tatishchev S. , Kurtz I.
Published: April 2003

In eukaryotes, it is rare for a single gene to encode two functionally unrelated proteins. p150Glued is a component of the dynactin heteromultimeric complex of proteins which is required for dynein-mediated vesicle and organelle transport by microtubules. NBC4 is an electrogenic sodium bicarbonate cotransporter, which regulates intracellular pH. Here we report that NBC4 and p150Glued are encoded by the same locus, DCTN1-SLC4A5. We have characterized the genomic organization of the human DCTN1-SLC4A5 locus which spans ∼230 kilobases on chromosome 2p13 and contains 66 exons. This information should allow the study of potential genomic alterations of DCTN1-SLC4A5 in patients with diseases mapping to this genomic region.
Analysis of chromosomal aberrations involving chromosome 1q31→q53 in a DMBA-induced rat fibrosarcoma cell line: amplification and overexpression of Jak2
Authors: Sjöling Å. , Lindholm H. , Samuelson E. , Yamasaki Y. , Watanabe T.K. , Tanigami A. , Levan G.
Published: April 2003

In a study of DMBA-induced rat fibrosarcomas we repeatedly found deletions and/or amplifications in the long arm of rat chromosome 1 (RNO1). Comparative genome hybridization showed that there was amplification involving RNO1q31→q53 in one of the DMBA-induced rat fibrosarcoma tumors (LB31) and a cell culture derived from it. To identify the amplified genes we physically mapped rat genes implicated in cancer and analyzed them for signs of amplification. The genes were selected based on their locations in comparative maps between rat and man. The rat proto-oncogenes Ccnd1, Fgf4, and Fgf3 (HSA11q13.3), were mapped to RNO1q43 by fluorescence in situ hybridization (FISH). The Ems1 gene was mapped by radiation hybrid (RH) mapping to the same rat chromosome region and shown to be situated centromeric to Ccnd1 and Fgf4. In addition, the proto-oncogenes Hras (HSA11p15.5) and Igf1r (HSA15q25→q26) were mapped to RNO1q43 and RNO1q32 by FISH and Omp (HSA11q13.5) was assigned to RNO1q34. PCR probes for the above genes together with PCR probes for the previously mapped rat genes Bax (RNO1q31) and Jak2 (RNO1q51→q53) were analyzed for signs of amplification by Southern blot hybridization. Low copy number increases of the Omp and Jak2 genes were detected in the LB31 cell culture. Dual color FISH analysis of tumor cells confirmed that chromosome regions containing Omp and Jak2 were amplified and were situated in long marker chromosomes showing an aberrant banding pattern. The configuration of the signals in the marker chromosomes suggested that they had arisen by a break-fusion-bridge (BFB) mechanism.
Where Have All the Young Girls Gone or Where Do All the Men Come from?
Authors: Ødegård Einar , Bretteville-Jensen Anne Line
Published: April 2003

A rough estimate indicates that women amount to one third of the heroin user population in Norway. However, among the youngest users females account and have accounted for a larger proportion. Given this greater representation of females in the younger age groups one would expect that the gender difference in the general population of users would be reduced over time due to a cohort effect. However, the ratio of male to female users has remained stable. The prevailing explanation for this stability is based on the claim that women are more likely to overcome their abuse. This paper addresses both the basis for the assumption of a missing cohort effect and examines an alternative explanation linked to the way into abuse rather than the way out. The study primarily draws upon two distinct data sources. The first body of material consists of interviews carried out in the period 1993–1997 with people attending the only needle exchange service in Oslo. The second data source consists of police records, which provide the number of persons arrested each year in the period 1984–1997 for using, possessing or selling heroin distributed by age and gender. We find that the age of injection debut has increased and that this is especially true for male users. Applying a simple quantitative model, the effect a change in recruitment may have on the male-to-female ratio is analysed. The results indicate that a higher debut age may have contributed to stabilizing the gender gap. The finding suggests that more research is needed on the conditions of recruitment in order to better predict the future population demographics and to avoid hasty and incorrect conclusions.
Modulation of Body Temperature, Interleukin-6 and Leptin by Oral Contraceptive Use
Authors: Salkeld Brittney D. , MacAulay Jannell C. , Ball Richard W. , Cannon Joseph G.
Published: April 2003

Objectives: This study examined the hypothesis that oral contraceptives (OC) influence the production of thermoregulatory cytokines, i.e. interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), soluble glycoprotein 130 (s-gp130) and leptin, and that OC-induced changes in oral temperature (Toral) are associated with changes in plasma concentrations of these cytokines. To determine if increases in Toral are part of a cytokine-driven inflammatory (acute-phase) response, circulating concentrations of the hepatic acute-phase protein C-reactive protein (CRP) were also measured. Methods: Morning Toral were measured and blood samples were collected from 18 women (19- to 22-years-old) on two occasions: Once during active pill usage (quasi-luteal (QL) phase) and once when no active pills were taken (quasi-follicular (QF) phase). Plasma cytokine and CRP concentrations were measured by immunoassay. Results: Toral and plasma leptin were higher during QL phase (36.4 ± 0.1°C, 9.3 ± 1.0 ng/ml) than QF phase (36.1 ± 0.1°C, p < 0.01; 7.5 ± 0.7 ng/ml, p < 0.01). Increases in Toral correlated with increases in plasma leptin (R = 0.55, p = 0.02) and with progestin dose (R = 0.47, p = 0.05) individually as well as with leptin and progestin combined in a multiple regression (R = 0.68, p = 0.01). Plasma IL-6 correlated with progestin dose (R = 0.62, p = 0.006). Although there were no phase-related differences in plasma IL-6, sIL-6R, s-gp130, or CRP, the variation in CRP between individuals correlated with the IL-6 agonist/antagonist ratio combined with progestin dose in a multiple regression (R = 0.71, p = 0.01). Conclusions: These results (a) implicate leptin in basal thermoregulation; (b) indicate that progestins have a significant influence on circulating IL-6 concentrations, and (c) are consistent with the concept that plasma CRP concentrations depend upon combined influences of progestins and bioavailable IL-6.
Cloning, Isolation, and IgE-Binding Properties of Helix aspersa (Brown Garden Snail) Tropomyosin
Authors: Asturias Juan A. , Eraso Elena , Arilla M. Carmen , Gómez-Bayón Nuria , Inácio Filipe , Martínez Alberto
Published: April 2003

Background: Gastropod consumption is quite frequent in the Mediterranean countries and cross-reactivities with crustaceans have been described, but the mechanism of this allergenic cross-reactivity has not been studied in detail. This study aimed to produce recombinant Helix aspersa (brown garden snail) tropomyosin and investigate its implication for cross-reactivity among invertebrates. Methods: A tropomyosin-specific cDNA encoding H. aspersa tropomyosin was synthetized, and recombinant allergen was overexpressed in Escherichia coli as nonfusion protein. IgE-binding reactivity was studied by immunoblotting and immunoblot inhibition experiments with sera from snail-allergic patients. Results: Cloned brown garden snail tropomyosin shares high homology with other edible mollusk tropomyosins (84–69% identity) as well as with those from arthropods (65–62%), and less homology with vertebrate ones (56% identity). Tropomyosin reacted with 18% of the sera from patients with snail allergy. Inhibition experiments, using natural and recombinant tropomyosins, showed different degrees of cross-reactivity between invertebrate tropomyosins. Sera from snail-allergic subjects recognized tropomyosins in both mollusks and crustacean extracts. Conclusions: Tropomyosin represents a minor allergen in snail extracts, but it is clearly involved in invertebrate cross-reactivity.
Trisetum paniceum (Wild Oats) Pollen Counts and Aeroallergens in the Ambient Air of Madrid, Spain
Authors: Cabrera M. , Martínez-Cócera C. , Fernández-Caldas E. , Carnés Sánchez J. , Boluda L. , Tejada J. , Subiza J.L. , Subiza J. , Jerez M.
Published: April 2003

Background: Madrid has a short but intensive grass pollen season, in which 79% of the total grass pollen load is released from the middle of May to the middle of June. The main objectives of this study were to quantify Trisetum paniceum (wild oats) aeroallergen in the atmosphere in Madrid from February to December 1996 and to correlate the aeroallergen concentrations with grass pollen counts. Methods: Two different samplers were used to assess allergen exposure; a Burkard spore trap was used to collect pollen grains and a high-volume air sampler to collect airborne particles. A total of 182 air filters were collected and extracted in 1 ml of PBS and analysed by ELISA inhibition, using pooled sera from highly allergic individuals. Results:T. paniceum aeroallergens were detected not only during the grass pollen season, but also before and after. Wild oat allergens had two main peaks of 1 and 1.9 µg/m3, occurring in late May and July, respectively. The time series analysis established the existence of lags between the two main variables pollen counts and aeroallergen activity. Analysis of the data by the Spearman rank test and linear regression showed a weak correlation between grass allergenic activity and grass pollen counts (Spearman’s rho = 0.29). Data obtained from time series analysis demonstrated that grass allergenic activity correlated strongly with current and 5-week-old grass pollen grain counts (r2 = 0.73). Conclusions: Wild oats allergenic activity was detected during the entire year and not only during the pollen season. This fact is an important aspect to be considered in the clinical follow-up and treatment of grass pollen-sensitised patients in Madrid.
Enhancement of IgE Production in B Cells by Neutrophils via Galectin-3 in IgE-Associated Atopic Eczema/Dermatitis Syndrome
Authors: Kimata Hajime
Published: April 2003

Spontaneous IgE production by B cells from patients with IgE-associated atopic eczema/dermatitis syndrome (AEDS) is enhanced by polymorphonuclear leukocytes (PMN) from patients with AEDS, but not by PMN from non-atopic controls. The enhancement is abolished by preincubation of PMN with lactose, but not with glucose. Anti-galectin-3 serum, but not control rabbit serum, blocked the enhancement. These results indicate that AEDS PMN can enhance IgE production via galectin-3.
Differential Interactions of Urocortin/Corticotropin-Releasing Hormone Peptides with the Blood-Brain Barrier
Authors: Kastin Abba J. , Akerstrom Victoria
Published: April 2003

The two newest members of the urocortin (UCN)/corticotropin-releasing hormone (CRH) family of peptides – UCN II and UCN III – bind to the CRH-2 receptor, suppress feeding, and are expressed in the periphery as well as the brain. We used several sensitive techniques to examine their interactions with the blood-brain barrier (BBB). Of the four known peptides in this family, each interacts with the BBB differently. UCN I barely enters the brain from blood unless its latent saturable influx system is activated by leptin or pretreatment with glucose. However, neither leptin nor glucose affected the entry of intact UCN II. UCN II reached brain paranchyma at a moderate rate that was not self-inhibited or cross-inhibited by UCN/CRH peptides. The apparent, but misleading, rapid influx of UCN III (stresscopin) could be explained by degradation at the BBB itself. Influx of CRH into brain was slower than UCN II but faster than UCN I; it was inhibited by excess CRH but not by excess UCN I, II, III, or leptin. CRH is the only member of this family to have a saturable efflux system out of the brain. Determination of hydrogen bonding, newly applied here to ingestive peptides, was not helpful in explaining these differential interactions of the UCN peptides with the BBB.
Comparison of Different Methods Evaluating the Functional and Structural Abnormalities in Hypertension
Authors: Ficzere Andrea , Csiba László
Published: April 2003

Functional and morphological abnormalities due to hypertension could be detected in neurologically symptom-free patients by CT, MRI, transcranial Doppler ultrasound, PET and SPECT. Neuropsychological tests also provide useful information. Single or combined application of these techniques reveals different aspects of parenchymal or vascular impairment in hypertension. The advantages and disadvantages of the different imaging techniques are reviewed and compared. The relatively simple, non-invasive transcranial Doppler (alone or combined with neuropsychological observations) could be recommended for screening and follow-up of hypertensive patients and seems to be a promising ancillary tool for evaluation of efficacy of antihypertensive therapy, but cannot replace the prospective controlled trials with hard endpoints.
Comparative mapping of CDY and DAZ in higher primates
Authors: Wimmer R. , Kühl H. , Röttger S. , Schempp W.
Published: April 2003

The human male specific expressed gene families CDY and DAZ are known to be repetitively clustered in the Y-specific region of the human Y chromosome. Comparative FISH-mapping of DNA clones specific for CDY and DAZ resulted in a Y-specific but diverse signal pattern within the non-recombining region of the Y-chromosomes of human and great apes. It can be concluded that the non-recombining part of the Y-chromosomes including CDY and DAZ, was exposed to species-specific amplifications, diversifications and rearrangements. Evolutionary fast fixation of any of these variations was possible as long as they did not interfere with male fertility.
Akodon sex reversed females: the never ending story
Authors: Bianchi N.O.
Published: April 2003

The existence of fertile A. azarae females with a chromosome sex pair indistinguishable from that of males was reported more than 35 years ago. These heterogametic females were initially thought to occur due to an extreme process of dosage compensation in which X inactivation was restricted to Xp and complemented by a deletion of Xq (Xx females). Later on, a C-banding analysis of A. mollis variant females showed that these specimens were in fact XY* sex reversed and not Xx females. The finding of positive testing for Zfy and Sry multiple-copy genes in Akodon males and heterogametic females confirmed the XY* assumption. At the present time, XY* sex reversed females have been found to exist in nine Akodon species. Akodon heterogametic females produce X and Y* oocytes, which upon sperm fertilization give rise to viable XX (female), XY* (female), and XY (male) embryos, and to non-viable Y*Y zygotes. Heterozygous females exhibit a better reproductive performance than XX females in order to compensate the Y*Y zygote wastage. XY* sex reversed females are assumed to occur due to a deficient Sry expression resulting in the development of ovaries instead of testes. Moreover, the appearance of Y* elements is a highly recurrent event. It is proposed that homozygosity for an autosomal or pseudoautosomal recessive mutation (s–) inhibits Sry expression giving rise to XY* embryos with ovary development. Location of the Y* chromosome in the female germ cell lineage produces an ovary-specific imprinting of the Sry* gene maintaining its defective expression through generations independently from the presence or absence of s– homozygosity. By escaping the ovary-specific methylation some Y* chromosomes turn back to normal Ys producing Y oocytes capable of generating normal male embryos when fertilized by an X sperm. Fluctuations in the rate of variant females in field populations and in laboratory colonies of Akodon depend on the balance between the appearance of new variant females (s–/s–, XY* specimens) and the extinction of sex reversed specimens due to imprinting escape.
Comparative molecular cytogenetic studies in the order Carnivora: mapping chromosomal rearrangements onto the phylogenetic tree
Authors: Graphodatsky A.S. , Yang F. , Perelman P.L. , O’Brien P.C.M. , Serdukova N.A. , Milne B.S. , Biltueva L.S. , Fu B. , Vorobieva N.V. , Kawada S.-I. , Robinson T.J. , Ferguson-Smith M.A.
Published: April 2003

We have made a set of chromosome-specific painting probes for the American mink by degenerate oligonucleotide primed-PCR (DOP-PCR) amplification of flow-sorted chromosomes. The painting probes were used to delimit homologous chromosomal segments among human, red fox, dog, cat and eight species of the family Mustelidae, including the European mink, steppe and forest polecats, least weasel, mountain weasel, Japanese sable, striped polecat, and badger. Based on the results of chromosome painting and G-banding, comparative maps between these species have been established. The integrated map demonstrates a high level of karyotype conservation among mustelid species. Comparative analysis of the conserved chromosomal segments among mustelids and outgroup species revealed 18 putative ancestral autosomal segments that probably represent the ancestral chromosomes, or chromosome arms, in the karyotype of the most recent ancestor of the family Mustelidae. The proposed 2n = 38 ancestral Mustelidae karyotype appears to have been retained in some modern mustelids, e.g., Martes, Lutra, Ictonyx, and Vormela. The derivation of the mustelid karyotypes from the putative ancestral state resulted from centric fusions, fissions, the addition of heterochromatic arms, and occasional pericentric inversions. Our results confirm many of the evolutionary conclusions suggested by other data and strengthen the topology of the carnivore phylogenetic tree through the inclusion of genome-wide chromosome rearrangements.
Sex-chromosome heterochromatin variation in the wood mouse, Apodemus sylvaticus
Authors: Nová P. , Reutter B.A. , Rábová M. , Zima J.
Published: April 2003

Variation in heterochromatin content, as revealed by G- and C-banding, was studied in the sex chromosomes of the wood mouse, Apodemus sylvaticus. The sex-chromosome heterochromatin was also characterized by DAPI staining. Variation in sex chromatin was recorded in extremely large (giant) sex chromosomes in certain individuals and populations. In some individuals, the Y chromosome was the largest element of the complement. Different variants of both the X and Y chromosomes were found within a single population. The variation is therefore a type of population polymorphism and should not be used for taxonomic discrimination.
Explosive chromosome evolution and speciation in the gerbil genus Taterillus (Rodentia, Gerbillinae): a case of two new cryptic species
Authors: Dobigny G. , Aniskin V. , Volobouev V.
Published: April 2003

The five morphologically sibling gerbil species of the genus Taterillus in West Africa were first identified from karyotypes. These species possess an XX/XY1Y2 sex-chromosome system and are characterized by significant karyotypic reorganization, thus making them a suitable model for studying the role of chromosomal rearrangements in the speciation process. We present here a description of two new cytotypes, Taterillus sp. 1 and Taterillus sp. 2, from the Lake Chad area, the former having a 2n = 22/23, NFa = 40, and the latter 2n = 24/25, NFa = 44. Comparison of their G- and C- banding patterns with those of T. pygargus (2n = 22/23, NFa = 38/40), examined in an earlier paper, revealed that all three species differ from each other by 7 to 11 chromosomal rearrangements, comprising tandem translocations, pericentric inversions, and Robertsonian metacentrics displaying monobrachial homology. Meiotic configurations formed in potential hybrids among any of these three forms would consist of complex rings and chains, alone or in combination, resulting, as expected, in a significant disruption of gametogenesis. These results provide support for assigning Taterillus sp. 1 and Taterillus sp. 2 to two different biological species, which, as demonstrated by our preliminary molecular studies, would have emerged recently. Possible factors responsible for the rapid karyotypic evolution and speciation in this West African gerbil complex are discussed.
Effect of Dietary Fish Oil on Insulin Sensitivity and Metabolic Fate of Glucose in the Skeletal Muscle of Normal Rats
Authors: D’Alessandro M.E. , Lombardo Y.B. , Chicco A.
Published: April 2003

The aim of this work was to study the effect of the administration of cod liver oil on the non-oxidative and oxidative fate of glucose metabolism in the skeletal muscle of normal rats. To achieve this goal, the gastrocnemius was examined regarding glucose oxidation, glycogen synthase activity and glycogen storage both at baseline and during euglycemic hyperinsulinemic clamping. The results show that dietary fish oil decreases plasma insulin levels without alteration in glucose homeostasis (at baseline). In addition, the observed enhancement in whole body glucose utilization during clamping suggests an increased peripheral insulin sensitivity. Furthermore, under insulin-stimulated glucose disposal, an enhancement in the glycolytic pathway (increased levels of muscle glucose-6-phosphate and plasma lactate) rather than changes in the oxidation (pyruvate dehydrogenase complex) and storage components of glucose metabolism was observed in the skeletal muscle of rats fed dietary fish oil. These results coupled with the hypolipidemic effects of fish oil may have implications for the prevention and/or management of some pathological states manifested by insulin resistance with or without dyslipidemia.
Dose-Related Inhibition of Proinflammatory Cytokine Release from Neutrophils of the Newborn by Dexamethasone, Betamethasone, and Hydrocortisone
Authors: Irakam Anitha , Miskolci Veronika , Vancurova Ivana , Davidson Dennis
Published: April 2003

The objective of this study was to determine the doses of dexamethasone (DEX), betamethasone (BET), and hydrocortisone (HC) that effectively inhibit the release of two potent proinflammatory chemokines, interleukin 8 (IL-8) and macrophage inflammatory protein alpha (MIP), from polymorphonuclear neutrophils (PMNs) of the newborn. Human PMNs were isolated from cord blood (n = 18). Chemokines were measured from PMN cell culture supernatants after 18 h of stimulation using tumor necrosis factor (1 ng/ml), with and without pretreatment by DEX (10–10 to 10–6 M) versus HC or BET (10–10 to 10–5 M). Maximal inhibitions of IL-8 release by BET, DEX, and HC were 97, 91, and 91%, respectively. For MIP, the maximal inhibitions by BET, DEX, and HC were 88, 69, and 70%, respectively. The 50% inhibitory concentrations by DEX, BET, and HC for IL-8 release were 3.4 ± (SE) 1.6 × 10–9, 1.8 ± 7.4 × 10–8, and 1.8 ± 0.5 × 10–7 M, respectively. The 50% inhibitory concentrations by DEX, BET, and HC for MIP release were 1.0 ± (SE) 0.5 × 10–8, 3.8 ± 3.1 × 10–8, and 4.8 ± 1.6 × 10–7 M, respectively. In vitro, these corticosteroids effectively inhibited the release of two structurally different chemokines that are found in the airway lavage fluids of infants developing bronchopulmonary dysplasia. When compared to plasma DEX levels previously reported during the treatment of bronchopulmonary dysplasia, our results suggest that the doses of DEX, and potentially BET, needed to treat chronic lung disease may be more than five to ten times lower than those of current DEX regimens.
Detection of a Thrombolysis-Related Reduction in Red Blood Cell Adhesiveness/Aggregation Using a Simple Slide Test
Authors: Mardi Tamar , Aviv Fredy , Rotstein Rivka , Fusman Renato , Roth Arie , Keren Gad , Eldor Amiram , Berliner Shlomo , Zeltser David , Shapira Itzhak
Published: April 2003

Increased red cell aggregability might have unfavorable rheological effects in the microcirculation. It has been suggested that thrombolysis-related hypofibrinogenemia might be associated with a reduced erythrocyte adhesiveness/aggregation. We followed the reduction in erythrocyte adhesiveness/aggregation using a simple slide test and image analysis that measures the spaces that are formed between the aggregated erythrocytes. A significant (p = 0.01) reduction in the degree of erythrocyte adhesiveness/aggregation was noted in patients with acute myocardial infarction who received thrombolysis as opposed to individuals with Braunwald Class IIIB unstable angina who had normal fibrinogen concentrations. No change was found in the Westergren erythrocyte sedimentation rate, which is an indirect method to detect changes in aggregability of red blood cells. The present study shows the superiority of using a direct measurement of red blood cell adhesiveness/aggregation. This extremely rapid, cheap and almost bedside methodology to detect changes in erythrocyte adhesiveness/aggregation might be useful to detect changes of hemorheological relevance following thrombolysis.
Quantification of Corticosteroid-Induced Skin Vasoconstriction: Visual Ranking, Chromameter Measurement or Digital Imaging Analysis
Authors: Smith E.W. , Haigh J.M. , Surber C.
Published: April 2003

Topical corticosteroid formulations have been evaluated by visual grading protocols for many years. Toward a more objective methodology, several instrumental methods have been evaluated for applicability in quantifying the vasoconstriction side-effect that follows corticosteroid application to the skin. Although the chromameter has been adopted by regulatory bodies throughout the world as the current standard for topical bioequivalence determinations, there is considerable criticism of this instrument from several quarters. A preliminary comparison reported here indicates that digital image analysis provides statistically significant results that are similar to those obtained by visual assessment techniques, and shows considerably greater precision than that obtained by the chromameter. Continued evaluation of objective assessment techniques, such as digital imaging, and continued modernisation of regulatory bioequivalence requirements will assist in protecting patients and optimising clinical results.
Sensitization Methodology and Primary Prevention of the Research Institute for Fragrance Materials
Authors: Api Anne Marie
Published: April 2003

The Research Institute for Fragrance Materials Inc. (RIFM) has approached sensitization studies with fragrance materials as primary prevention of sensitization in the healthy, normal population. Secondary prevention, or avoidance of elicitation, most often suggested by dermatologists for patients presenting with dermatitis, has not been part of its program effort. Historically, RIFM evaluated the sensitization potential of fragrance materials using the human maximization test method; no animal models were used. In general, petrolatum was used as the vehicle. This is a harsh procedure whose main use may provide a measure of the uppermost limits of sensitization. Treating skin with sodium lauryl sulfate may be problematic and finding a laboratory to conduct the study may also be difficult. In addition, using a human predictive test method for both hazard and safety assessments is not ideal. The current practice involves a hazard assessment using an animal model, followed by a safety assessment in a human repeated-insult patch test (HRIPT). The animal test method is used to identify the sensitization potential and a no-effect level. Following a review of the no-effect level and the maximum skin level, a safety assessment in humans can be conducted. RIFM also modified the original vehicle used in sensitization testing, since petrolatum presents two major difficulties: solubility and inconsistent effects on skin penetration. Since the greatest exposure to fragrance materials is considered to be from a cologne-type product, ethanol was chosen as a more realistic vehicle. Further modification resulted in combinations of ethanol and diethyl phthalate, due to diethyl phthalate’s use in many perfume formulations as a solvent and fluidizer. Human testing should not be conducted as a hazard assessment. If conducted as a safety study, induction of sensitization should be a rare occurrence. Thus, follow-up studies are not meaningful since the number of sensitized volunteers would be low. However, following a series of the RIPTs with various concentrations of hydroxycitronellal, RIFM identified a group of 41 individuals who became sensitized. An extensive 3-phase use study, with 3 diagnostic patch tests and 4 whole-body dermatological examinations showed that most subjects were able to use a bar soap, a moisurizing lotion and cologne-type products with up to 1% hydroxycitronellal. In subjects where sensitization was induced by predictive testing, no serious recurring adverse dermatological conditions developed.
The Role of Surgery in the Prevention of Familial Cancer Syndromes of the Gastrointestinal Tract
Authors: Koliopanos A. , Wirtz M. , Büchler M.W. , Friess H.
Published: April 2003

Familial predisposition is a well-recognised risk factor in many gastrointestinal cancers. New developments in molecular genetics may contribute to the identification of cancer-prone families. Recognition of familial clustering and genetic testing can identify other members of the family with a high potential risk for cancer development. Appropriate surveillance mechanisms and management protocols may be initiated in order to prevent cancer and/or to detect cancer at an early stage. In the present article, various types of familial cancer of the gastrointestinal tract are reviewed and surgical, diagnostic and therapeutic issues for the management of esophageal, gastric, colorectal, and pancreatic cancer are emphasized.
Molecular Targets for Prevention of Hepatocellular Carcinoma
Authors: Blum Hubert E.
Published: April 2003

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world with an extremely poor prognosis. The major etiologic risk factors for HCC development include toxins (alcohol, aflatoxin B1), androgens and estrogens, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection as well as various inherited metabolic disorders, such as alpha-1-antitrypsin deficiency and hemochromatosis. The molecular pathogenesis of HCC development is very complex and involves alterations in the structure or expression of several tumor suppressor genes, oncogenes and, possibly, mechanisms leading to a genetic instability due to mismatch repair deficiency or chromosomal instability and aneuploidy due to defective chromosomal segregation. Central to the molecular pathogenesis of HCCs are mutations of various genes and a genetic instability which in most cases result from chronic liver disease and the associated enhanced liver cell regeneration and mitotic activity. The prognosis of HCC patients is generally very poor. Most studies report a five year survival rate of less than 5% in symptomatic HCC patients. Furthermore, these tumors have been shown to be quite resistant to radio- or chemotherapy. Investigations of the natural history and clinical course of HCCs revealed long-term survival of patients only with small asymptomatic HCCs that could be treated surgically or by non-surgical interventions. Apart from exploring and refining new HCC treatment strategies, the implementation of existing and the development of novel measures to prevent HCC development are most important. Primary HCC prevention includes among others universal hepatitis B vaccination, antiviral therapy of patients with chronic hepatitis B or C, reduction of food contamination with aflatoxins, elimination of excessive alcohol etc. Also for some genetic diseases there is the potential for HCC prevention by identifying affected family members at risk, such as patients with precirrhotic hemochromatosis. Reduction of iron overload by phlebotomy has been shown to eliminate the progression hemochromatosis to liver cirrhosis and HCC. Preventive measures, therefore, should have a major impact on the incidence of HCCs in patients with acquired and inherited liver diseases. Further, the prevention of a local recurrence or the development of new HCC lesions in patients after successful surgical or non-surgical HCC treatment (secondary prevention) is of paramount importance and is expected to significantly improve disease-free and overall patient survival. Based on rapid scientific advances, molecular diagnosis, gene therapy and molecular prevention are becoming increasingly part of our patient management and will eventually complement and in part replace existing diagnostic, therapeutic and preventive strategies. Overall, this should result in a reduction of the incidence of HCCs, one of the most devastating malignancies worldwide.
Chemoprevention in Colorectal Neoplasias: What Is Practical and Feasible?
Authors: Ricciardiello Luigi , Roda Enrico , Bazzoli Franco
Published: April 2003

Chemoprevention strategies for colorectal cancer have gained increasing attention. Despite contradictory data regarding the use of micronutrients and antioxidant vitamins as chemopreventive tools, the identification of cyclooxygenase 2 (COX-2) upregulation in colorectal adenomas has led to the development of new drugs, named COX-2 inhibitors, that directly target the molecular mechanism of carcinogenesis. Celecoxib, one of the two COX-2 inhibitors available on the market, has been approved for chemoprevention of familial adenomatous polyposis. In the future, we might expect these drugs to be used in the prevention of colon cancer in patients at increased risk, such as those with a positive family history.
Pneumonia Involving Legionella pneumophila and Listeria monocytogenes in an Immunocompromised Patient: An Unusual Coinfection
Authors: Lerolle Nicolas , Zahar Jean-Ralph , Duboc Valerie , Tissier Frederique , Rabbat Antoine
Published: April 2003

Recently, empirical therapy has been recommended for severe community-acquired pneumonia. We report the case of a 68-year-old prednisone-treated man with multiple myeloma who developed a fatal pneumonia due to Legionella pneumophila and Listeria monocytogenes confirmed by immunohistochemistry on postmortem lung sampling. Involvement of the latter bacteria and association of two different pathogens are both highly uncommon features in pneumonia. The route of infection with L. monocytogenes is discussed and the literature on respiratory infections with L. monocytogenes is briefly reviewed. This case highlights the need to consider unusual pathogens when facing pneumonia in immunocompromised patients, and to perform extensive microbiological investigations even if broadspectrum antibiotic therapy is the treatment of choice.
Short-Term Effect of Nasal Intermittent Positive-Pressure Ventilation in Patients with Restrictive Thoracic Disease
Authors: Ergün Pınar , Aydın Gülümser , Yilmaz Turay Ülkü , Erdoğan Yurdanur , Çağlar Atalay , Biber Çiğdem
Published: April 2003

Background: The use of nasal intermittent positive pressure ventilation (NIPPV) would be expected to ameliorate dyspnea, ventilatory capacity and exercise tolerance durably in individuals with hypercapnic respiratory failure secondary to restrictive thoracic disease. Objectives: The purpose of this study was to determine the short-term effect of NIPPV on respiratory muscle endurance, exercise capacity and respiratory functions in patients with chronic respiratory failure due to restrictive thoracic disease. Methods: Twelve patients with chronic ventilatory failure due to restrictive thoracic disease underwent nasal bilevel positive airway pressure (BiPAP) ventilation for 2 h a day during 15 consecutive days. The effects were assessed by spirometry, arterial blood gas analysis, 6-min walking test, sensation of dyspnea according to the American Thoracic Society dyspnea scoring scales (ATS) and surface electromyogram of the diaphragm (EMGdi) before and after the study (on day 15). Results: Nasal BiPAP reduced the ATS dyspnea score from 2.5 ± 0.9 to 1.6 ± 0.4 (p < 0.01). Distances walked in 6 min increased from 320.66 ± 93.56 to 382.41 ± 121.20 m (p < 0.05). Comparison of baseline with levels after nasal BiPAP ventilation showed a statistically significant improvement in PaCO2 (p < 0.05). Forced vital capacity increased from 35 to 50% of the predicted value (p < 0.01). There were no statistically significant reductions in the amplitude of EMGdi after the therapy. Conclusion: These results indicate that NIPPV delivered via nasal BiPAP improves respiratory functions, exercise capacity, and reduces dyspnea in the short term in patients with chronic respiratory failure due to restrictive thoracic disease. Whether such short-term improvements can be sustained merits further study.
An Atypical Pattern of Epstein-Barr Virus Infection in a Case with Idiopathic Tubulointerstitial Nephritis
Authors: Okada Hirokazu , Ikeda Naofumi , Kobayashi Tatsuya , Inoue Tsutomu , Kanno Yoshihiko , Sugahara Souichi , Nakamoto Hidetomo , Yamamoto Takako , Suzuki Hiromichi
Published: April 2003

Recently, Epstein-Barr virus (EBV) received attention because a latent form of its infection in renal proximal tubular epithelial cells was found to cause idiopathic, chronic tubulointerstitial nephritis. In this report, we describe the case of a patient with a replicative form of EBV infection, chronic active EBV infection (CAEBV), who developed acute tubulointerstitial nephritis and minimal change nephrotic syndrome. A renal biopsy revealed papillary infoldings of atypical tubular epithelium and adjacent dense infiltration of lymphocytes. Using in situ polymerase chain reaction methods, we detected the EBV genome in some of the infiltrating lymphocytes, but not in the tubular epithelial cells. EBV-infected T cells are thought to activate other educated T cells, as well as secrete an unrestricted variety of cytokines, thus playing a pivotal role in CAEBV and its end organ disease. Therefore, in our case, the CAEBV activated, educated T cells may have followed the EBV-infected lymphocytes as they infiltrated into the peritubular interstitium, and promoted focal tubular epithelial atypia and minimal change nephrotic syndrome. The long-term observation of such patients is important because CAEBV may progress into lymphoproliferative diseases.
Association between Electrocardiographic Pattern and Level of C-Reactive Protein in Patients with First Anterior Wall Acute Myocardial Infarction
Authors: Adler Yehuda , Wiser Itay , Vaturi Mordehay , Kahana-Duczyminer Malka , Fink Noam , Birnbaum Yochai , Strasberg Boris
Published: April 2003

Background: Studies of prognostic markers after first anterior wall acute myocardial infarction (AMI) have reported an association between persistent ST segment elevation on the electrocardiogram (ECG) and increased levels of C-reactive protein (CRP) and worse outcome. The aim of the present study was to determine the nature of the relationship between these two factors. Methods: Twenty-three consecutive patients admitted with AMI underwent 12-lead ECG on days 1, 2, 3 and 7 and were classified into two groups according to the findings on each day’s recording: pattern A – isoelectric ST segment, or pattern B – ST segment elevation with or without a negative T wave. Serum CRP levels measured on the same days were also compared between the groups. Results: The number of patients classified as pattern A increased over time, from 8 on day 1 after AMI to 11 on day 2, 12 on day 3 and 14 on day 7, with a corresponding decrease in pattern B patients. Most of the patients with pattern B on day 1 showed a persistent pattern on day 7. For each day studied, the pattern A and pattern B patients showed a statistically significant difference in serum CRP levels on the second and third days after AMI, respectively. Values for the day 7 groups were: 3.1 ± 3.4 versus 9.6 ± 3.8 mg% (p = 0.001) (day 2) and 3.1 ± 1.2 versus 7.9 ± 3.6 mg% (p = 0.0005) (day 3). Conclusion: There was a significant association between high CRP levels on the second and third day following first AMI and ECG pattern B (ST elevation). This conclusion strengthens our earlier findings that pattern B is predictive of poor outcome in this patient population.
Predictors of Clinical Recurrence after Successful Electrical Cardioversion of Chronic Persistent Atrial Fibrillation: Clinical and Electrophysiological Observations
Authors: Lin Jih-Min , Lin Jiunn-Lee , Lai Ling-Ping , Tseng Yung-Zu , Stephen Huang Shoei K.
Published: April 2003

Recurrence of atrial fibrillation (AF) after electrical cardioversion of chronic AF is not uncommon. However, it remains unclear which parameter(s) predict clinical recurrence. To assess the potential predictors of clinical recurrence after successful electrical cardioversion, we analyzed clinical, echocardiographic and electrophysiologic parameters in 36 patients (age 63 ± 11 years; 26 males, 10 females) with chronic persistent AF lasting more than 3 months. The dimensions of the left atrium and left ventricular end diastole and end systole were measured by echocardiography. The P wave characteristics from the surface 12-lead electrocardiogram (ECG) were studied in sinus rhythm. Atrial local activations were studied by biatrial basket electrode mapping in AF. With a mean of 7 ± 2 months of follow-up, 17 (47%) patients had AF recurrence despite multiple antiarrhythmic drug therapy. None of the clinical or echocardiographic parameters were relevant to the recurrence. However, among the surface ECG and intraatrial electrophysiological parameters, the mean P wave duration was the only independent predictor of the risk of clinical recurrence after successful electrical cardioversion. The sensitivity and predictive accuracy of recurrence were 82 and 70%, respectively, when the mean P wave duration was more than 125 ms.