bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between the Engagement of Relatives in a Behavioural Group Intervention for Smoking Cessation and Higher Quit Rates at 6-, 12- and 24-Month Follow-Ups
Authors: Picardi A. , Bertoldi S. , Morosini P.
Published: April 2003

Objective: To assess the effectiveness of a behavioural group intervention for smoking cessation, which included as its most original feature the recommendation to participate with a relative or close friend. Methods: A total of 1,060 subjects entered the programme, which consisted of 9 group sessions over a period of 5 weeks. The intervention consisted of a modified version of the Five-Day Plan, the main differences being the use of behavioural therapy techniques and small group work, and the addition of 4 weekly booster sessions. About two thirds of the participants came with a relative or close friend. Long-term abstinence from smoking was assessed with follow-up telephone interviews. Results: Very few subjects were lost to follow-ups (9.2% at 6 months, 9.7% at 1 year, 10.8% at 2 years). The observed quit rates were 42.6% at 6 months, 35.5% at 1 year and 32% at 2 years. When considering as smokers all subjects who were lost to follow-ups, quit rates were also satisfactory (38.7% at 6 months, 32.1% at 1 year and 28.6% at 2 years). The main predictors of a good outcome were being male, smoking less than 20 cigarettes per day, having started smoking after 18 years of age, having made previous quitting attempts, not having a history of unsuccessful participation to smoking cessation interventions and attending the sessions with a relative or close friend. Discussion: Although some limitations inherent in the design of our study suggest caution in interpreting the results and in making comparisons, the long-term effectiveness of the intervention was satisfactory. The inclusion of a relative or close friend appeared useful. This simple and inexpensive strategy may deserve recommendation, though in the future it should be tested in controlled trials.
Anti-Inflammatory Cytokines: Expression and Action in the Brain
Authors: Vitkovic Ljubisa , Maeda Shigeru , Sternberg Esther
Published: April 2003

Transforming growth factor-β1 (TGF-β1) and interleukin (IL)-10 gene expression is equivocal in normal brain and upregulated in over a dozen central and peripheral diseases/disorders. The patterns of specific expression of cytokines differ in these diseases. Published data indicate that these cytokines are produced by and act on both neurons and glial cells. Although their actions are commonly viewed as ‘anti-inflammatory’, they protect neurons and downregulate the responses of glial cells to diseases/disorders in the absence of inflammation. Their actions counterbalance the actions of elevated IL-1 and/or tumor necrosis factor-α to maintain homeostasis. Their therapeutic potential will be realized by improving our understanding of their place in neural cytokine networks.
Histamine and Serotonin Stimulate Eotaxin Production by a Human Lung Fibroblast Cell Line
Authors: Sato Etsuro , Haniuda Masayuki , Numanami Hiroki , Ushiyama Toshiki , Tsukadaira Akihiro , Takashi Shuji , Okubo Yoshio , Koyama Sekiya
Published: April 2003

Histamine and serotonin are important inflammatory mediators in the pathophysiology of asthma, and asthmatic patients have higher plasma histamine and serotonin levels than nonasthmatic control subjects. Eotaxin, a potent eosinophil-specific chemotactic factor, is increased in the lower respiratory tract of allergic patients. Recently, lung fibroblasts have been reported to produce eotaxin and are suggested to be the major cellular source of eotaxin. We postulated that lung fibroblasts might release eotaxin in response to histamine or serotonin. To test this hypothesis, we evaluated the potential of histamine or serotonin to induce the release of eotaxin by the human fetal lung fibroblast cell line, HFL-1. HFL-1 released eotaxin in response to histamine and serotonin in a dose- and time-dependent manner (p < 0.05). Histamine or serotonin treatment of HFL-1 augmented the expression of eotaxin mRNA. Eosinophil chemotactic activity by HFL-1 supernatant fluids was inhibited by anti-human eotaxin-neutralizing antibody. These findings lead to the hypothesis that lung-fibroblast-derived eotaxin may in part be responsible for the eosinophil infiltration observed in allergic disease of the airways.
Hepatitis B Vaccination and First Central Nervous System Demyelinating Event: A Case-Control Study
Authors: Touzé Emmanuel , Fourrier Annie , Rue-Fenouche Cécile , Rondé-Oustau Véronique , Jeantaud Isabelle , Bégaud Bernard , Alpérovitch Annick
Published: April 2003

Objective: To investigate the relationship between hepatitis B (HB) vaccination and a first central nervous system (CNS) demyelinating event in adults. Methods: In 1998, we conducted a multicentre, hospital-based case-control study which enrolled 402 cases of first CNS demyelinating event occurring between 1994 and 1995 and 722 controls matched for centre, age, sex and date of admission. An independent expert committee validated the diagnoses of cases and controls. Data on vaccinations were obtained from a standardized phone interview. Forty percent of eligible cases and 50% of eligible controls could not be localized or were excluded because they did not satisfy inclusion or matching criteria. Results: Conditional logistic regression performed on 236 and 355 matched controls showed that adjusted odds ratios for the first CNS demyelinating event within 2 months following an injection of HB vaccine were 1.8 [95% confidence interval (CI), 0.7–4.6] in the whole group and 1.4 (95% CI, 0.4–4.5) in the subgroup of cases (n = 152) and controls (n = 253) referring to vaccination certificates during the phone interview. Restricting the analyses to the cases with definite or probable multiple sclerosis, these odds ratios were 2.0 (95% CI, 0.8–5.4) and 1.6 (95% CI, 0.4–5.6), respectively. Odds ratios tend towards 1 for a longer interval between HB vaccine and demyelinating event. Conclusions: This study was sufficiently powerful to rule out a strong association between HB vaccine exposure and a subsequent demyelinating event. However, it could not provide a clear indication of a moderately increased risk of a CNS demyelinating event shortly after HB vaccination in adults.
An Ecologic Study of Geographical Variation in Multiple Sclerosis Risk in Central Sardinia, Italy
Authors: Montomoli C. , Allemani C. , Solinas G. , Motta G. , Bernardinelli L. , Clemente S. , Murgia B.S. , Ticca A.F. , Musu L. , Piras M.L. , Ferrai R. , Caria A. , Sanna S. , Porcu O.
Published: April 2003

We carried out an ecological study in the most archaic area of Sardinia to obtain a reliable estimate of the prevalence of multiple sclerosis (MS) and to investigate the geographical variation in the prevalence across the 100 administrative communes. To estimate the area-specific prevalence rate, we adopted a Bayesian approach that makes it possible to filter out the random variation from the estimates and to obtain a map that reflects the true geographical variation in MS prevalence. 428 resident cases were identified by the case register, including 69 multiplex families. The overall prevalence was 157 per 100,000 inhabitants. The Bayesian area-specific prevalence ranged from 143 to 262/100,000. The high prevalence and its moderate geographical variation in a genetically homogeneous population, as well as the high number of multiplex families observed in the communes with the highest prevalence, could be interpreted as representing a high susceptibility of the population to MS.
Vaccination Strategies in the Treatment of Lymphomas
Authors: Veelken Hendrik , Osterroth Frank
Published: April 2003

Malignant lymphomas are clonal neoplasms of lymphoid origin. By definition, all cells of the malignant clone have undergone the same rearrangement of antigen receptor genes and express identical antigen receptor molecules (immunoglobulin for B cell lymphomas, T cell receptor for T cell lymphomas). The hypervariable stretches within the variable regions of these receptors are considered true tumor-specific antigens (‘idiotypes’). In several animal models, protective humoral or cellular immunity can be induced against the malignant lymphoma by vaccination with the tumor-derived idiotype. Successful experimental immunization strategies in animals include idiotype protein vaccines combined with various adjuvants, genetically or immunologically modified lymphoma cells, idiotype-presenting dendritic cells, idiotype-encoding viral vectors, and DNA immunization. Firm evidence for the induction of lymphoma-specific immunity has also been obtained from human idiotype vaccination trials. Furthermore, some trials have provided strong but hitherto formally unproven evidence for clinical benefit of idiotype-vaccinated patients. Alternative vaccination approaches are based on immunologically modified tumor cells. Current research efforts concentrate on the identification of the most efficacious vaccination route, on definitive proof of clinical efficacy, and on the development of convenient methods to manufacture individual idiotype vaccines.
Evaluation of Intraoperative Intraperitoneal Cytology for Advanced Gastric Carcinoma
Authors: Fujimoto Toshihiro , Zhang Bin , Minami Shuji , Wang Xianghui , Takahashi Yutaka , Mai Masayoshi
Published: April 2003

Objective: We evaluated intraperitoneal cytology during surgery as a significant predictor of survival and tried to establish strategies for preventing peritoneal carcinomatosis. Methods: The study included 236 patients with gastric carcinoma macroscopically invading the serosa who underwent intraperitoneal cytological examination during surgery. In the 215 resected patients, the relationship between cytological positivity for cancer cells and various clinicopathologic features was analyzed. Additionally, postoperative survival was assessed in relation to the positivity of intraoperative cytology. Results: Cancer cells were positive [Cy(+)] in 78 (33.1%) of 236 patients who underwent cytological examinations. Among 73 patients with peritoneal metastases, 53 patients (72.6%) were Cy(+), as were 25 (15.3%) of the 163 patients without peritoneal metastases. Multivariate analysis indicated that peritoneal metastasis (p = 0.0001) and the depth of tumor invasion (p = 0.0069) were significant factors correlated with Cy(+). Among patients with curative surgery, the 5-year survival rate of the Cy(+) group was 22.2%, which was worse (p = 0.0004) compared with that of the Cy(–) group (60.9%). Among Cy(+) patients, the survival rate of the group treated with intraperitoneal administration of mitomycin C (MMC) and OK-432 was better (p = 0.0108) than that of the historical control group. Conclusion: These results suggest that intraperitoneal cytological examination can be a significant prognostic factor for gastric carcinoma with serosal invasion. In addition, dissemination of cancer cells in the peritoneum may be controlled by intraperitoneal immunochemotherapy with MMC and OK-432.
Phase I Study of Paclitaxel (Taxol) and Pegylated Liposomal Doxorubicin (Caelyx) Administered Every 2 Weeks in Patients with Advanced Solid Tumors
Authors: Mavroudis D. , Kouroussis Ch. , Kakolyris S. , Agelaki S. , Kalbakis K. , Androulakis N. , Souglakos J. , Samonis G. , Georgoulias V.
Published: April 2003

Objectives: Paclitaxel and doxorubicin are among the most active chemotherapeutic agents in various types of tumors. Pegylated liposomal doxorubicin (Caelyx) has a more favorable pharmacokinetic and toxicity profile than the free drug. We conducted a phase I study to determine the maximum tolerated doses (MTD) and the dose limiting toxicities (DLT) of the combination administered every 2 weeks in patients with advanced solid tumors. Patients and Methods: Treatment consisted of escalating doses of Caelyx (12.5–17.5 mg/m2) administered as a 30-min intravenous infusion on day 1 and paclitaxel (90–115 mg/m2) as a 3-hour intravenous infusion on day 2 every 2 weeks without growth factor support. One cycle was considered as the administration of two consecutive treatments in 28 days. Twenty-six patients with histologically confirmed advanced stage solid tumors have been enrolled. Treatment was first-line treatment for 38% of patients, second-line for 31% and third-line for 31%. Results: The DLT were evaluated during the first 4 weeks of treatment (2 treatment administrations) and consisted in all but one case of grade 2–3 neutropenia resulting in treatment delay. One patient died of cardiac arrest 1 day after the first treatment. A total of 86 cycles have been administered with only 1 episode of febrile neutropenia. Hematologic toxicity was generally mild. Only 1 patient at the first and another at the highest dose level developed grade 4 neutropenia. At the highest dose level, 3 of 6 patients developed grade 3 neutropenia. Grade 4 anemia or grade 3–4 thrombocytopenia was not observed. Non-hematologic toxicity included grade 2–3 nausea/vomiting in 10%, grade 2–4 diarrhea in 7% and grade 2–3 neurotoxicity in 8% of cycles. Mucositis grade 3 complicated 1 cycle. Palmar-plantar erythrodysesthesia grade 2–3 was observed in 3 patients and was the reason for treatment discontinuation in 1 patient. Cardiotoxicity as the development of congestive heart failure or more than 10% reduction in left ventricular ejection fraction was not observed. The most common non-hematologic toxicity was grade 2–3 asthenia complicating 31% of the cycles. Among 18 evaluable patients, 1 complete and 4 partial responses were observed primarily in patients with breast cancer. The MTD which are the recommended doses for further use in phase II trials were Caelyx 15 mg/m2 on day 1 and paclitaxel 115 mg/m2 on day 2 administered every 2 weeks. Conclusion: The administration of Caelyx and paclitaxel every 2 weeks is a feasible regimen and is associated with acceptable toxicity.
DNA Sequences of the Immunoglobulin Heavy Chain Variable Region Gene in Pyothorax-Associated Lymphoma
Authors: Miwa Hideaki , Takakuwa Tetsuya , Nakatsuka Shin-ichi , Tomita Yasuhiko , Iuchi Keiji , Aozasa Katsuyuki
Published: April 2003

B cell lymphoma develops in the pleural cavity of patients affected by long-standing pyothorax resulting from lung tuberculosis, thus termed pyothorax-associated lymphoma (PAL). PAL usually shows a diffuse large cell morphology, and constantly contains Epstein-Barr virus (EBV) genome. To investigate whether PAL cells proliferate in response to specific antigenic stimuli and its stage in B cell differentiation, immunoglobulin heavy chain gene in 7 cases and 2 cell lines from PAL, all confirmed by histological studies to be EBV-positive diffuse large B cell lymphoma, were examined by using polymerase chain reaction (PCR) method. Clonal rearrangement of the gene was detected in 4 cases of PAL tissues and one cell line. As for the usage of the V region gene (VH), the VH3 family gene was used in 3 of these 5 cases with different homologous germlines, suggesting that the origin of PAL cells from a repertoire of B lymphocytes responsive to specific antigenic epitope was unlikely. Compared to the homologous germline, the mutation frequency of PAL was 9% on average. Only one case might have more replacement mutations in the complementarity-determining regions than expected by chance, thus antigen-selected maturation might not take place in PAL. Intraclonal sequence heterogeneity in the VH gene was found in another case. From these findings, it is concluded that PAL is composed of B lymphocytes at the differentiation stage of the postgerminal center. Antigen-selected maturation might not take place in PAL, which is distinct from the majority of B cell lymphomas.
Immunohistochemically Detectable Bcl-2 Expression in Metastatic Melanoma: Association with Survival and Treatment Response
Authors: Vlaykova Tatyana , Talve Lauri , Hahka-Kemppinen Marjo , Hernberg Micaela , Muhonen Timo , Collan Yrjö , Pyrhönen Seppo
Published: April 2003

Objective: The antiapoptotic protein Bcl-2 is supposed to influence the treatment responsiveness of different malignancies. In the present study the prognostic and predictive significance of Bcl-2 expression for survival and response to an administered therapy was explored in patients with metastatic melanoma. Also, the correlation between Bcl-2 expression and proliferation activity of tumor cells was defined to examine the regulatory role of Bcl-2 in proliferation. Materials and Methods: Sixty metastatic melanomas obtained from patients treated with chemoimmunotherapy were examined by immunohistochemistry with anti-Bcl-2 and anti-Ki-67 (MIB-1) antibodies. Proliferation activity was expressed in percentages as MIB-1 index. Results: The presence of Bcl-2 immunoreactivity was associated with a significantly lower MIB-1 index (p = 0.016), and a longer disease-free survival (p = 0.004). The lack of Bcl-2 expression was related to a higher response rate to therapy in comparison to a diffuse and focal pattern of Bcl-2 expression (p = 0.017). Although the presence of Bcl-2 immunoreactivity as such did not correlate with survival after the initiation of chemoimmunotherapy, the focal Bcl-2 expression pattern was strongly associated with a worse prognosis compared to a diffuse expression or a lack of Bcl-2 staining (p < 0.0001). Conclusions: Our results support the role of Bcl-2 in the regulation of cell proliferation and suggest that an increase of metastatic potential and progression of malignant melanoma is associated with a loss of Bcl-2 expression. The lack of Bcl-2 expression could be a predictor of the response to chemoimmunotherapy, whereas the Bcl-2 expression pattern, possibly indicating the heterogeneity of the tumors, might be a potential prognostic factor for survival after the initiation of therapy.
PAI-1 Promoter Polymorphism Modulates uPA-PAI Complex Accumulation by Breast Cancer Cells
Authors: Alvarez-Millán J.J. , Bocos C. , Ferrín V. , Lucas A.R. , Ruibal A. , Schneider J.
Published: April 2003

Objectives: The uPA-PAI system has been shown to play a role in the development of a more aggressive tumor phenotype. The PAI-1 promoter 4G/5G polymorphism, furthermore, regulates free plasma PAI-1 levels in patients with myocardial infarction. Our aim was to verify if the different polymorphisms in the PAI-1 promoter are also associated with alterations in the intracellular accumulation of uPA-PAI complexes in human breast cancer. Methods: Accumulation of uPA-PAI complexes inside the tumor cells was determined by means of immunohistochemistry, as previously described by our own group, and two extremely different sets of tumors were chosen, one of them with strong uPA-PAI complex reactivity inside more than 50% of tumor cells, the other with no demonstrable reactivity at all. Finally, the 4G/5G polymorphism of the PAI-1 promoter was studied in all of them by means of DNA extraction, PCR amplification of the PAI promoter sequence, and restriction polymorphism typing. Results: Absence of intracellular uPA-PAI complex accumulation was significantly associated with the prevalence of the 4G allele and, conversely, the presence of uPA-PAI complexes inside the tumor cells was significantly associated with 5G/5G homozygosity (logistic regression, p = 0.0128). Furthermore, none of the 7 5G/5G homozygous tumors showed histological grade 3, as did 6/21 tumors in the group where the 4G allele was present. In spite of the low case number, this association of the 5G/5G polymorphism with a less aggressive phenotype almost reached statistical significance (Spearman’s correlation test, p = 0.118). Conclusions: The 4G/5G polymorphism of the PAI-1 promoter seems indeed to be associated with different rates of uPA-PAI complex internalization by breast cancer cells. Complex accumulation inside the tumor cells is significantly related to 5G/5G homozygosity, and this shows a trend towards an association with a less aggressive, better-differentiated tumor phenotype.
Correlation between the Retinal Nerve Fiber Layer Thickness and the Pattern Electroretinogram Amplitude
Authors: Toffoli Giovanni , Vattovani Odilla , Cecchini Paolo , Pastori Giulio , Rinaldi Giorgio , Ravalico Giuseppe
Published: April 2003

Objective: To establish a correlation between the retinal nerve fiber layer (RNFL) thickness measured by a scanning laser polarimeter (GDx) and the pattern electroretinogram (p-ERG) amplitudes in a heterogeneous population sample composed of normal subjects, ocular hypertensive and glaucomatous patients. Methods: 112 subjects were considered: 40 glaucomatous patients, 39 ocular hypertensive and 33 normal subjects. All were examined with the GDx, and the RNFL thickness was measured. A transient p-ERG was then recorded. Results: A statistically significant correlation was observed between the RNFL thickness and the p-ERG amplitudes (p < 0.001) by means of linear regression analysis. Conclusion: We observed a strict correlation between the measurements of the RNFL thickness obtained with the GDx and the amplitude of the p-ERG signal. These techniques represent additional objective tools to detect an early glaucomatous damage.
Detection of Inducible Nitric Oxide Synthase and Vascular Endothelial Growth Factor in Choroidal Neovascular Membranes
Authors: Hattenbach Lars-Olof , Falk Bettina , Nürnberger Frank , Koch Frank Heinz Johannes , Ohrloff Christian
Published: April 2003

Vascular endothelial growth factor (VEGF) is among the cytokines which have been implicated in the pathogenesis of choroidal neovascularization secondary to age-related macular degeneration (ARMD). There is, however, evidence that intercellular signaling molecules, such as nitric oxide (NO), are involved in this process. NO is synthesized via the inducible isoform of NO synthase (iNOS), which is expressed after induction by cytokines. In the current study, we investigated whether VEGF and iNOS are coexpressed in choroidal neovascular membranes (n = 7) from patients with ARMD. Immunohistochemistry was performed on cryosections with anti-iNOS and anti-VEGF. Moderate to intense immunostaining for iNOS and VEGF was observed in retinal pigment epithelial cells, macrophages, and in spatial relation to vessel walls. As scored by light microscopy, we found a significant correlation between immunoreactivity for VEGF and iNOS (p < 0.0341) in vascular endothelial cells. Our study supports a significant role for iNOS in the pathogenesis of neovascularization and membrane growth in ARMD. Moreover, our findings suggest a possible relationship between NO and VEGF in the regulation of pathologic angiogenesis in this disease.
Cold Stress in Captive Great Apes Recorded in Incremental Lines of Dental Cementum
Authors: Cipriano Alessandra
Published: April 2003

Incremental lines in dental cementum of museum specimens of 11 free-ranging great apes were compared to the respective structures in 5 captive specimens of known age-at-death, and with many known life-history parameters. While the dental cementum of the free-ranging apes was regularly structured into alternating dark and light bands, 4 out of 5 captive animals showed marked irregularities in terms of hypomineralized bands which could all be dated to the year 1963. Cementum preservation was insufficient in the fifth specimen and did not permit such a differentiation. All 4 captive apes had been kept in a zoo located in the northern hemisphere, where 1963 was characterized by an extremely cold winter. Since cold stress is a calcium-consuming process, the lack of available calcium in newly forming cementum could be responsible for the observed hypomineralization. The appositional growth characteristics of dental cementum serve as a record for such life-history events.
Origin and evolution of avian microchromosomes
Authors: Burt D.W.
Published: April 2003

The origin of avian microchromosomes has long been the subject of much speculation and debate. Microchromosomes are a universal characteristic of all avian species and many reptilian karyotypes. The typical avian karyotype contains about 40 pairs of chromosomes and usually 30 pairs of small to tiny microchromosomes. This characteristic karyotype probably evolved 100–250 million years ago. Once the microchromosomes were thought to be a non-essential component of the avian genome. Recent work has shown that even though these chromosomes represent only 25% of the genome; they encode 50% of the genes. Contrary to popular belief, microchromosomes are present in a wide range of vertebrate classes, spanning 400–450 million years of evolutionary history. In this paper, comparative gene mapping between the genomes of chicken, human, mouse and zebrafish, has been used to investigate the origin and evolution of avian microchromosomes during this period. This analysis reveals evidence for four ancient syntenies conserved in fish, birds and mammals for over 400 million years. More than half, if not all, microchromosomes may represent ancestral syntenies and at least ten avian microchromosomes are the product of chromosome fission. Birds have one of the smallest genomes of any terrestrial vertebrate. This is likely to be the product of an evolutionary process that minimizes the DNA content (mostly through the number of repeats) and maximizes the recombination rate of microchromosomes. Through this process the properties (GC content, DNA and repeat content, gene density and recombination rate) of microchromosomes and macrochromosomes have diverged to create distinct chromosome types. An ancestral genome for birds likely had a small genome, low in repeats and a karyotype with microchromosomes. A “Fission–Fusion Model” of microchromosome evolution based on chromosome rearrangement and minimization of repeat content is discussed.
High-resolution organization of mouse telomeric and pericentromeric DNA
Authors: Garagna S. , Zuccotti M. , Capanna E. , Redi C.A.
Published: April 2003

We studied the organization of telomeric, major and minor satellite DNA sequences located in the pericentromeric regions of mouse telocentric and Robertsonian metacentric chromosomes by high-resolution fluorescence in situ hybridization. Molecular data have already proved that in telocentrics, from the physical chromosome end, telomeric sequences are followed by minor and then by major satellite DNA. We showed that the three families of repetitive DNA are organized as uninterrupted long-range cluster repeats and that there is no intermingling between telomeric and minor satellite DNA or between the major and the minor tandem repeats or with non-satellite DNA. The pericentromeric region of metacentric chromosomes consists of a small block of minor satellite DNA sandwiched between two blocks of major satellite DNA.
Chromosome painting refines the history of genome evolution in hares and rabbits (order Lagomorpha)
Authors: Robinson T.J. , Yang F. , Harrison W.R.
Published: April 2003

Fluorescence in situ hybridization (FISH) was used to define homologous segments among representatives of 7 of the 11 recognized leporid genera. Chromosome painting using 22 rabbit chromosome-specific paints derived from flow-sorted chromosomes revealed that at least 18 fusions and six fissions differentiate the extant karyotypes from the presumed ancestral state (2n = 48). The riverine rabbit, Bunolagus monticularis, has the most derived karyotype, differing from the ancestor by seven fusions and five fissions, followed by Pronolagus rupestris, with four fusions and one fission. These findings are consistent with the proposed Palaeolaginae/Leporinae dichotomy in the lagomorphs. The molecular cytogenetic data allow for a refinement of the structural changes that have shaped genome evolution in this group of mammals and underscore the rapid radiation of the Leporidae suggested by mitochondrial DNA sequence data.
Mapping the distribution of the telomeric sequence (T2AG3)n in rock wallabies, Petrogale (Marsupialia: Macropodidae), by fluorescence in situ hybridization
Authors: Metcalfe C.J. , Eldridge M.D.B. , Johnston P.G.
Published: April 2003

The distribution of the conserved vertebrate telomeric sequence (T2AG3)n was examined by fluorescence in situ hybridization in the six Petrogale (rock wallabies) taxa of the lateralis complex. As expected, the (T2AG3)n sequence was located at the termini of all chromosomes in all taxa. However, the sequence was also present at several nontelomeric (viz., interstitial and centromeric) sites. The signals identified were associated with either ancient rearrangements involved with the formation of the 2n = 22 plesiomorphic macropodine karyotype or more recent rearrangements associated with karyotypes derived from the 2n = 22 karyotype. Interstitial (T2AG3)n signals identified on chromosomes 3 and 4 in all six species of the lateralis complex and a large centromeric signal identified on chromosome 7 in the five subspecies/races of P. lateralis appear to be related to the more ancient rearrangements. Subsequent chromosome evolution has seen these signals retained, lost, or amplified in different Petrogale lineages. Within the lateralis complex, in two submetacentric chromosome derived by recent centric fusions, the telomeric sequence was identified at or near the centromere, indicating its retention during the fusion process. In the two taxa where chromosome 3 was rearranged via a recent centromeric transposition to become an acrocentric chromosome, the telomeric signal was located interstitially.
Effect of Probiotics on Constipation, Fecal Azoreductase Activity and Fecal Mucin Content in the Elderly
Authors: Ouwehand Arthur C. , Lagström Hanna , Suomalainen Tarja , Salminen Seppo
Published: April 2003

Background: Constipation is a common problem in elderly subjects, probiotics have been suggested to improve intestinal motility and reduce fecal enzyme activity. Methods: Elderly subjects (n = 28) were enrolled in an open parallel study. The subjects were divided into 3 groups: 1 control group receiving juice; 1 group receiving juice supplemented with Lactobacillus reuteri, and 1 group receiving juice supplemented with Lactobacillus rhamnosus and Propionibacterium freudenreichii. During the first 3 weeks all subjects consumed unsupplemented juice. In the subsequent 4 weeks, the subjects received their designated juice. During the last 3 weeks, all subjects again received unsupplemented juice. From the subjects, defecation frequency, laxative use, fecal pH, mucin content and azoreductase activity were assessed during the last week of each period. Results: The subjects receiving the L. rhamnosus/P. freudenreichii-supplemented juice exhibited a 24% increase in defecation frequency. However, no reduction in laxative use was observed. The fecal azoreductase activity was also significantly reduced in this group. No changes in fecal pH or mucin excretion were observed. Conclusion: Some relief from constipation may be observed with the combination of L. rhamnosus/P. freudenreichii. This probiotic combination also reduced fecal enzyme activity. The tested probiotics did not affect the mucosal barrier.
A Caffeine Diet Can Alter the Mechanical Properties of the Bones of Young Ovariectomized Rats
Authors: Ohta Mitsuhiro , Ide Kazuya , Cheuk Gina , Cheuk Shu L. , Yazdani Malektaj , Nakamoto Tetsuo , Thomas Kevin A.
Published: April 2003

The general public widely consumes caffeine which is contained in various foods, beverages, and over-the-counter medications. The relationships between caffeine intake and bone fractures is controversial. Therefore, the aim of the current study was to determine what effects, if any, caffeine intake in early life exerts on mechanical properties and mineral contents of bone in growing ovariectomized rats. A total of 8 dams with pups were divided into two groups. Group 1 was fed a 20% protein diet. Group 2 was fed a 20% protein diet supplemented with caffeine (4 mg/100 g). The respective diets were fed to the dams during lactation and to the pups continuously after weaning on day 22 until the end of the experimental period. On day 32, offspring from both groups were ovariectomized. On day 52, the rats were sacrificed and the femora removed. The biomechanical properties of the femora were determined by three-point bend testing to failure at a rate of 2 mm/min, with continuous data sampling at 10 samples/s. The properties determined included the modulus of elasticity, yield load, yield stress, ultimate load, ultimate stress, and the second moment of area. The caffeine group exhibited a decrease in the various mechanical properties (ranging from approximately 7 to 20%), except for yield strain and moment of inertia. The decreases in maximum stress and elastic modulus values were significant. Calcium, magnesium, and phosphorous values for the caffeine group were significantly decreased. These results suggest that the bone in the caffeine group is weaker and less stiff, with greater deformation under applied loading. It could be concluded that caffeine intake during the early growing period affects the mechanical properties of bone.
Effect of Early Enteral Feeding on Apolipoprotein AI Levels and High-Density Lipoprotein Heterogeneity in Preterm Infants
Authors: Genzel-Boroviczény Orsolya , Göbel Yvonne , Koletzko Berthold
Published: April 2003

Background/Aim: We have previously shown that infants receiving total parenteral nutrition have low apolipoprotein AI levels which are associated with high-density lipoprotein (HDL) class distributions as in lecithin:cholesterol acyltransferase deficiency. This study investigates the influence of early enteral feedings on apolipoprotein AI and HDL subclasses. Methods: Apolipoprotein AI and HDL distributions were determined in 15 total parenterally fed preterm infants (TPN group) receiving early feedings, in 28 enterally fed preterm infants (ENT group), and in 26 term infants at birth and on day 5. The HDL subclasses were determined by gradient gel electrophoresis. Results: In the TPN group, the apolipoprotein AI levels increased significantly postnatally (from 73 ± 16 to 104 ± 23 mg/dl) to levels found in the term and ENT groups on day 5 (88 ± 16 and 96 ± 19 mg/dl). The HDL subclass distributions at birth and on day 5 were similar in both TPN and ENT groups with more large HDL2b and less small HDL3c than in term infants. Whereas the HDL subclass distribution of term infants remained unchanged, in TPN and ENT infants, a shift from HDL2b to HDL3c was observed, with no difference between term and preterm infants on day 5. Conclusion: In contrast to exclusively parenterally fed infants, infants receiving early enteral feedings exhibited a significant rise of apolipoprotein AI and HDL subclass distributions as fully enterally fed preterm infants.
In vitro Removal of Therapeutic Drugs with a Novel Adsorbent System
Authors: Reiter Karl , Bordoni Valeria , Dall’Olio Giuliano , Ricatti Maria Grazia , Soli Maurizio , Ruperti Salvatore , Soffiati Giuliano , Galloni Elisabetta , D’Intini Vincenzo , Bellomo Rinaldo , Ronco Claudio
Published: April 2003

Background/Aim: Substances in the middle molecular weight range have been shown to play a significant pathogenetic role in as diverse disorders as end-stage renal disease and multiple organ failure. To overcome the limitations in the amount removed by hemofilters, new sorbents with a high biocompatibility are actively being developed. Furthermore, biocompatible sorbents by their nonspecific adsorptive behavior could have great impact on detoxification treatment in exogenous intoxications. We performed an in vitro evaluation of a newly developed highly biocompatible sorbent cartridge (Betasorb®), examining its adsorptive capacity concerning therapeutic drugs. Methods: Uremic blood spiked with a range of therapeutic drugs was recirculated for 2 h in an in vitro hemoperfusion circuit containing a Betasorb device for hemoperfusion. The drug concentrations before and after the passage of the cartridge were measured, and the total amount removed was calculated. Results: The sorbent showed effective removal of glycopeptide antibiotics, digoxin, theophylline, phenobarbital, phenytoin, carbamazepine, and valproic acid. Moderate removal could be demonstrated for tacrolimus and cyclosporine A; aminoglycosides were removed to a small extent only. Conclusions: Betasorb hemoperfusion shows a potent adsorptive capacity concerning therapeutic drugs (except aminoglycosides) and could be of major value in the treatment of intoxications. On the other hand, drug monitoring and possible adjustments are necessary during Betasorb hemoperfusion to maintain the therapeutic ranges of the drugs in blood.
An Unusual Case of Genodermatosis with Familial Gastrointestinal Polyposis, Angiomatous Malformation and Ascites
Authors: Neri S. , Bruno C.M. , Mondati E. , Scavo S.
Published: April 2003

Gardner’s syndrome is a familial adenomatous polyposis syndrome with extraintestinal manifestations, characterized by the coexistence of intestinal polyposis with an early risk of malignant degeneration and extraintestinal manifestations mainly involving the skin, eye, bone and thyroid. We describe an unusual case of intestinal adenomatous polyposis, retinal hypertrophy, fibromas of the skin, bone and thyroid tumors accompanied by congenital arteriovenous malformations with lethal complications.
Report of a Case of Schnitzler’s Syndrome Treated Successfully with Interferon Alpha 2b
Authors: Schartz Noël Emile Célestin , Buder Suzanne , Sperl Hans , Audring Heike , Paus Ralph , Tebbe Beate , Krüger Katharina , Sterry Wolfram
Published: April 2003

Schnitzler’s syndrome (SS) is characterized by the association of generalized chronic urticaria, osteocondensation and monoclonal IgM gammopathy. Nonsteroidal anti-inflammatory drugs and systemic steroids are the most promising treatments. In our patient, they were ineffective. By contrast, during the follow-up period of 18 months, interferon α2b therapy (IFN-α) relieved the patient from its urticarial lesions and bone pain. IFN-α was tried to be stopped twice: each time, relapse of urticaria was noticed and, each time, the cutaneous lesions disappeared after IFN-α had been reintroduced. Furthermore, our observation supports the idea of the interleukin (IL)-1-mediated pathogenesis of SS as IFN-α induces high levels of IL-1 receptor antagonists. IFN-α could be an alternative treatment in disabling SS resisting other drugs.
Self-Reported Skin and Respiratory Symptoms Related to Latex Exposure among 5,087 Hospital Employees in Norway
Authors: Holter Gro , Irgens Ågot , Nyfors Allan , Aasen Tor B. , Florvaag Erik , Overå Kari Britt , Elsayed Said , Nærheim Jakob
Published: April 2003

Background: Latex allergy has become prevalent among health care workers. Objectives: To determine the prevalence of self-reported symptoms related to latex exposure among hospital personnel. Methods: Questionnaires addressing symptoms and risk factors for latex allergy were distributed to all employees (n = 5,087) at Haukeland University Hospital. Results: Symptoms associated with latex exposure were reported by 23.8% of the participants. Skin symptoms were most frequently reported – flushing/itching/hives: 21.0%, hand eczema: 11.8% – while systemic and respiratory symptoms were reported by 1.4 and 1.2%, respectively. Approximately twice as many women than men reported symptoms (odds ratio 2.55, confidence interval 2.04–3.18). Symptoms were reported by 33.7% of those with atopy and by 20.0% of those without. The occurrence of symptoms increased significantly with the frequency of use of latex gloves but was unrelated to age, years of exposure or number of surgical procedures. Conclusions: The occurrence of self-reported symptoms was associated with the frequent use of latex gloves, atopy and female gender.
Infantile Multiple Ingrowing Nails of the Fingers Induced by the GraspReflex – A New Entity
Authors: Matsui Tamano , Kidou Masato , Ono Tomomichi
Published: April 2003

Background: A new clinical entity of ingrowing fingernail of infants, which was associated with the grasp reflex, was found. Objective: To define this new disease. Methods: We encountered 26 cases of this disease between 1984 and 1996. We describe the clinical features of this new disease. Results: The median age of the cases was 1 month (from 6 days to 4 months). The main findings were multiple and bilateral paronychia of the fingernails. This disease was observed in some babies only when they had the grasp reflex. Conclusions: The repeated compression of the nail due to the grasp reflex caused the soft tissue swelling at the end of the nail to be penetrated by the edge of the nail plate.
Topical Calcipotriol plus Oral Fumaric Acid Is More Effective and Faster Acting than Oral Fumaric Acid Monotherapy in the Treatment of Severe Chronic Plaque Psoriasis vulgaris
Authors: Gollnick H. , Altmeyer P. , Kaufmann R. , Ring J. , Christophers E. , Pavel S. , Ziegler J.
Published: April 2003

Background: Calcipotriol is an established topical therapy for psoriasis vulgaris. Objective: This study aimed to investigate whether the addition of calcipotriol to fumaric acid ester (FAE) monotherapy had an additive efficacy and an FAE-sparing effect in patients with severe plaque psoriasis. Methods: This multicentre, randomised, double-blind, vehicle-controlled study included 143 patients for up to 13 weeks treatment. Group A received FAE tablets (Fumaderm®) with an increasing daily dosage from 105 to 1,075 mg + ointment vehicle. Group B received FAE tablets + calcipotriol ointment (50 µg/g). Ointments were applied twice daily. Clinical response was assessed using percentage changes in the Psoriasis Area and Severity Index (PASI), from baseline to treatment end. Results: The mean percentage change in the PASI was –76.1% in group B and –51.9% in group A, the difference between treatments was –24.2% (95% CI from –34.2 to –14.2%; p < 0.001). Group B responded more rapidly to treatment. Investigators’ and patients’ overall efficacy assessments were significantly more favourable for group B (p ≤ 0.001). Group B was prescribed less FAE than group A. This difference was greatest at the last visit (mean daily dose 529 and 685 mg, respectively; p = 0.006). Overall adverse events in the two groups were similar. Conclusion: This study shows that the combination of calcipotriol and FAEs is significantly more effective and faster acting than FAE monotherapy in the treatment of severe plaque psoriasis. The combination has a slight FEA-sparing effect and therefore a superior benefit/risk ratio.
Fetal and Neonatal Outcomes in Twin Oligohydramnios-Polyhydramnios Sequence Including Cerebral Palsy
Authors: Matsuda Yoshio , Kouno Satoshi
Published: April 2003

Objective: The purpose of this study was to review consecutive pregnancies complicated by twin oligohydramnios-polyhydramnios sequence (TOPS) and to clarify the probable factors influencing the perinatal outcomes. Methods: Twenty-five pregnancies with a diagnosis of TOPS were treated with and without amniocentesis. A poor perinatal outcome was defined when either perinatal mortality or cerebral palsy was observed. Results: The mean gestational age at the time of diagnosis and of delivery was 27.8 (range 21–34) and 30.7 (range 23–35) weeks, respectively. Tocolytic therapy and therapeutic amniocentesis were done in 16 (64%) and 13 (52%) cases. Hydrops fetalis was present in 10 cases. The survival rate was 72%, and cerebral palsy was diagnosed in 8 of 36 infants (22%). The poor prognostic factors were gestational age at delivery (<30 weeks) and presence of symptomatic preterm labor and hydrops fetalis. Therapeutic amniocentesis did not influence the perinatal outcome. Conclusions: In this observational study, the long-term as well as the short-term perinatal outcome of pregnancy with TOPS seems to be poor. In addition, therapeutic amniocentesis in TOPS does not appear to affect fetal and neonatal outcomes.
Antenatal Sonographic Detection of Vesicoureteral Reflux
Authors: Satoh Shoji , Inatomi Shigeru , Kubota Masayuki , Suita Sachiyo , Nakano Hitoo
Published: April 2003

We report a case with vesicoureteral reflux (VUR), diagnosed antenatally. A 31-year-old Japanese woman was referred at 37 weeks’ gestation because of the fetus having unilateral renal pelvis dilatation. The real-time ultrasound revealed a right renal pyelectasia with periodic changes in size over intervals lasting several minutes. The simultaneous examinations of both anteroposterior dimension of the renal pelvis and the ellipse size of urine-filled bladder area demonstrated that they varied in size in a reciprocal fashion, leading us to diagnose the fetus as having VUR. Postnatally, bilateral VUR was confirmed by the voiding cystogram. This case has typical ultrasonographic findings of fetal VUR, in which both the renal pelvis and urinary bladder dimensions change periodically in a reciprocal manner with each other, when the reflux really occurred.
Sonographic Nuchal Markers for Down Syndrome Are More Common but Less Ominous in Gestations with a Male Fetus
Authors: Drugan A. , Weissman A. , Avrahami R. , Zamir R. , Evans M.I.
Published: April 2003

Objective: A change in the normal male-to-female ratio has been reported in some autosomal trisomies (i.e., trisomy 21 or trisomy 18). The objective of the present study was to evaluate the male-to-female ratio in pregnancies with sonographic nuchal markers for Down syndrome. Methods: The results of amniocenteses performed for isolated nuchal markers for Down syndrome were grouped by fetal sex and by maternal age. The male-to-female ratio in normal and trisomic gestations was compared. Results: 584 fetal karyotypes were available for analysis. A significantly higher male-to-female ratio was observed. More affected gestations were observed in association with a female fetus. These differences were mainly attributed to the group of patients younger than 35 years that represents more than 80% of our study population. No difference was observed in pregnancies of patients older than 35 years of age. Conclusions: In patients younger than 35 years, sonographic nuchal markers for Down syndrome are more frequent (but apparently less ominous) in gestations with a male fetus. If the gender is known, counseling can be modified to include such differential risks.
The Semmelweis University Experience
Authors: Papp Zoltán
Published: April 2003

The author has worked in genetic counseling and prenatal genetic diagnosis and screening since 1966. He has been the Head of the Department of Obstetrics and Gynecology at Semmelweis University of Budapest for 10 years where he founded its center of prenatal genetics. This tertiary center aims to treat as many pregnancies with a prenatal diagnosis or suspicion of fetal anomalies as possible for confirmation, further testing and possible termination of pregnancy. The department is equipped with an in-house cytogenetic, molecular genetic, fetopathological and ultrasound laboratory and deals with the methodological, psychological, ethical, and legal aspects of abortions. Their excellent database facilitates the follow-up of maternal and fetal patients, in order to investigate the efficiency of genetic counseling and diagnosis. As the President of the Hungarian College of Obstetricians and Gynecologists and the Hungarian Society of Ultrasound in Obstetrics and Gynecology, Zoltán Papp oversees the prenatal diagnosis system for the whole of Hungary. He has also developed and now supervises the quality assurance system which ensures effective and reliable ultrasound screening for pregnant women.