bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolated Resection of Segment 1 of the Liver – with Invited Commentary
Authors: van Gulik Thomas , Lang Hauke
Published: July 2005

Isolated resection of segment 1 is a parenchyma-sparing technique that can be used for the resection of benign or malignant tumors confined to this segment. The method of resection of segment 1 is described in relation with its complex anatomical features. Special attention is paid to prevention of damage to the hilar bile ducts and major hepatic veins during the procedure.
Ring-Reinforced Prosthesis for Paracolostomy Hernia
Authors: de Ruiter P. , Bijnen A.B.
Published: July 2005

Background: The reported recurrence rate after paracolostomy hernia repair, with or without mesh, varies between 47 and 100%. We developed a polypropylene mesh prosthesis with a central opening, reinforced with a polypropylene ring, that can be implanted suprafascially through a mucocutaneous incision. Methods: The results of a consecutive series of 46 patients with paracolostomy hernia, who were implanted with this prosthesis between October 1988 and November 2000 in 12 hospitals, were analyzed. The mean follow-up was 5 (range 1–13) years. Results: The early infection rate was 4.3%. Two patients were lost to follow-up. The late infection rate was 2.3%. Seven patients (15.9%) developed a recurrent parastomal hernia and were all reoperated. The prosthesis was definitively removed in 10 patients. Conclusion: Although implantation of this new prosthesis is not without complications, it offers the lowest reported recurrence rate until now.
Atherosclerotic Plaque Progression and Vulnerability to Rupture
Authors: Virmani Renu , Kolodgie Frank D. , Burke Allen P. , Finn Aloke V. , Gold Herman K. , Tulenko Thomas N. , Wrenn Steven P. , Narula Jagat
Published: July 2005

Observational studies of necrotic core progression identify intraplaque hemorrhage as a critical factor in atherosclerotic plaque growth and destabilization. The rapid accumulation of erythrocyte membranes causes an abrupt change in plaque substrate characterized by increased free cholesterol within the lipid core and excessive macrophage infiltration. Neoangiogenesis is associated closely with plaque progression, and microvascular incompetence is a likely source of intraplaque hemorrhage. Intimal neovascularization is predominantly thought to arise from the adventitia, where there are a plethora of pre-existing vasa vasorum. In lesions that have early necrotic cores, the majority of vessels invading from the adventitia occur at specific sites of medial wall disruption. A breech in the medial wall likely facilitates the rapid in-growth of microvessels from the adventitia, and exposure to an atherosclerotic environment stimulates abnormal vascular development characterized by disorganized branching and immature endothelial tubes with “leaky” imperfect linings. This network of immature blood vessels is a viable source of intraplaque hemorrhage providing erythrocyte-derived phospholipids and free cholesterol. The rapid change in plaque substrate caused by the excessive accumulation of erythrocytes may promote the transition from a stable to an unstable lesion. This review discusses the potential role of intraplaque vasa vasorum in lesion instability as it relates to plaque rupture.
Combination of Tumor Necrosis Factor-α Ablation and Matrix Metalloproteinase Inhibition Prevents Heart Failure After Pressure Overload in Tissue Inhibitor of Metalloproteinase-3 Knock-Out Mice
Authors: Kassiri Zamaneh , Oudit Gavin Y. , Sanchez Otto , Dawood Fayez , Mohammed Fazilat F. , Nuttall Robert K. , Edwards Dylan R. , Liu Peter P. , Backx Peter H. , Khokha Rama
Published: July 2005

Cytokine and extracellular matrix (ECM) homeostasis are distinct systems that are each dysregulated in heart failure. Here we show that tissue inhibitor of metalloproteinase (TIMP)-3 is a critical regulator of both systems in a mouse model of left ventricular (LV) dilation and dysfunction. Timp-3
−/−
mice develop precipitous LV dilation and dysfunction reminiscent of dilated cardiomyopathy (DCM), culminating in early onset of heart failure by 6 weeks, compared with wild-type aortic-banding (AB). Timp-3 deficiency resulted in increased TNFα converting enzyme (TACE) activity within 6 hours after AB leading to enhanced tumor necrosis factor-α (TNFα) processing. In addition, TNFα production increased in timp-3
−/−
-AB myocardium. A significant elevation in gelatinase and collagenase activities was observed 1 week after AB, with localized ECM degradation in timp-3
−/−
-AB myocardium. Timp-3
−/−
/tnfα
−/−
mice were generated and subjected to AB for comparative analyses with timp-3
−/−
-AB mice. This revealed the critical role of TNFα in the early phase of LV remodeling, de novo expression of Matrix metalloproteinases (MMP)-8 in the absence of TNFα, and highlighted the importance of interstitial collagenases (MMP-2, MMP-13, and MT1-MMP) for cardiac ECM degradation. Ablation of TNFα, or limiting MMP activity with a synthetic MMP inhibitor (PD166793), each partially attenuated LV dilation and cardiac dysfunction in timp-3
−/−
-AB mice. Notably, combining TNFα ablation with MMP inhibition completely rescued heart disease in timp-3
−/−
-AB mice. This study provides a basis for anti-TNFα and MMP inhibitor combination therapy in heart disease.
Neonatal Hypoxia/Ischemia Is Associated With Decreased Inflammatory Mediators After Erythropoietin Administration
Authors: Sun Yun , Calvert John W. , Zhang John H.
Published: July 2005

Background and Purpose—

Erythropoietin (EPO), a hematopoietic growth factor, has been shown to be neuroprotective when administered as either a pretreatment or posttreatment. This study tested the hypothesis that one of the mechanisms of protection afforded by posttreatment with recombinant human EPO (rh-EPO) is an anti-inflammatory effect via inhibition of interleukin (IL)-1β.

Methods—

Seven-day-old rat pups were subjected to unilateral carotid artery ligation followed by 90 minutes of hypoxia (8% O
2
at 37°C). Pups were divided into the following groups: control, hypoxia/ischemia, and hypoxia/ischemia plus rh-EPO. In the rh-EPO–treated pups, rh-EPO (5 U/g body weight IP) was administered starting 24 hours after the insult and then for 2 additional days. Samples were collected at 3, 7, 14, and 21 days after the insult. IL-1β mRNA and protein levels were determined by quantitative real-time reverse transcription–polymerase chain reaction and ELISA. Tumor necrosis factor (TNF)-α mRNA levels were determined by colorimetric microplate assay.

Results—

rhEPO attenuated brain injury, as assessed by brain weight, and attenuated both the hypoxia/ischemia–induced increases in IL-1β mRNA and protein levels. TNF-α mRNA levels did not increase at 3 to 14 days after the hypoxic/ischemic insult.

Conclusions—

Administration of exogenous rh-EPO starting 24 hours after a hypoxic/ischemic insult is neuroprotective in the neonatal rat. This neuroprotective activity prevented the secondary, delayed rise in IL-1β and attenuated the infiltration of leukocytes into the ipsilateral hemisphere.
Daily Functioning and Quality of Life in a Randomized Controlled Trial of Therapeutic Exercise for Subacute Stroke Survivors
Authors: Studenski Stephanie , Duncan Pamela W. , Perera Subashan , Reker Dean , Lai Sue Min , Richards Lorie
Published: July 2005

Background and Purpose—

The ability of therapeutic exercise after stroke to improve daily functioning and quality of life (QOL) remains controversial. We examined treatment effects on these outcomes in a randomized controlled trial (RCT) of exercise in subacute stroke survivors.

Methods—

This is a secondary analysis of a single-blind RCT of a 12-week program versus usual care. Baseline, post-treatment and 6-month post-treatment daily functioning and QOL were assessed by Barthel index, Functional Independence Measure, instrumental activities of daily living, Medical Outcomes Study short-form 36-item questionnaire (SF-36), and Stroke Impact Scale (SIS).

Results—

Of 100 randomized subjects, 93 completed the postintervention assessment, (mean age 70; 54% male; 81% white; mean Orpington Prognostic Score 3.4), and 80 had 6-month post-treatment assessment. Immediately after intervention, the intervention group improved more than usual care in SF-36 social function (14.0 points;
P
=0.0051) and in SIS (strength [9.2 points;
P
=0.0003], emotion [5.6 points;
P
=0.0240], social participation [6.6 points;
P
=0.0488], and physical function [5.0 points;
P
=0.0145]). Treatment was marginally more effective on Barthel score (3.3 points;
P
=0.0510), SF-36 (physical function [6.8 points;
P
=0.0586], physical role function [14.4 points;
P
=0.0708]), and SIS upper extremity function (7.2 points;
P
=0.0790). Effects were diluted 6 months after treatment ended.

Conclusion—

This rehabilitation exercise program led to more rapid improvement in aspects of physical, social, and role function than usual care in persons with subacute stroke. Adherence interventions to promote continued exercise after treatment might be needed to continue benefit.
The Effect of Amniotic Fluid Index on the Accuracy of Sonographic Estimated Fetal Weight
Authors: Durbin Sharon A. , Lee Connie W. , Parker Veronica G.
Published: July 2005

The objective of this study was to investigate whether there is a relationship between the amniotic fluid index (AFI) and the accuracy of the sonographic estimated fetal weight (EFW) as substantiated by the actual birth weight. This is a retrospective study where data of the sonographic estimated fetal weight and the birth weight at delivery were collected to calculate range of error when the amniotic fluid index was indicative of polyhydramnios or oligohydramnios, with normal amniotic fluid volumes as a control group. Results revealed significant, fairly strong to strong correlations between the variables within each group. Further analysis compared the mean scores of the three groups. Although differences in the mean values exist, large overlaps existed. This questions the usefulness of the correlation of the EFW and AFI in clinical use.
Describing Elderly Women in Assisted Living’s Risk for Breast Cancer and Participation in Screening Behaviors
Authors: Evans Kevin D. , Bates R. Cory
Published: July 2005

The purpose of this research was to provide descriptive information on elderly women’s breast cancer risk and their level of participation in breast cancer screening behaviors. Ninety-two women participated in the study; the mean breast cancer risk for five years was 2.4, and the lifetime mean risk was 4.4. An elevated five-year risk is a value greater than 1.7. The participants’ also provided information on their breast cancer screening behaviors. The modal response for participation in obtaining a medical checkup with a physician was six months or less. The modal response for obtaining a clinical breast examination was six months or less. These elderly women indicated a high rate of adopting breast cancer screening activities. Breast sonographers and mammographers have a unique opportunity to raise awareness with their elderly patients about breast cancer. Advocating screening measures and patient education are needed to assist elderly women in managing risk.
Campomelic Dysplasia
Authors: Eger Kristen J.
Published: July 2005

Campomelic dysplasia is a rare congenital skeletal disorder. It is an autosomal dominant condition caused by mutation of the SOX9 gene on chromosome 17. Many different body systems can be harmfully affected, resulting in a variety of skeletal and extraskeletal anomalies attributable to the gene mutation. The most evident characteristics of the condition are symmetrical shortening and anterior bowing of the femurs and tibias. For most affected fetuses, death occurs in the fetal period or in the neonatal period shortly after birth. The primary cause of death is respiratory distress due to many possible factors such as micrognathia and hypoplastic chest cavity, lungs, or airways. Fetal sonography is fundamental in the detection of related defects and the ultimate diagnosis of the disorder.
An Evaluation of the Incidence of Right-Sided Ovarian Cystic Teratoma Visualized on Sonograms
Authors: Ismail Saad Ramzi
Published: July 2005

This study set out to determine the incidence of right-sided ovarian cystic teratoma. The author examined 270 cases of ovarian cystic teratoma. In this series, ovarian dermoids were more frequently found on the right ovary than the left ovary. The primary data were obtained over two decades and include both retrospective and prospective review. The data included the clinical history of each patient, pelvic sonography examination, and microscopic and/or surgical findings reports. Data used were limited to proven cases of ovarian cystic teratoma shown by sonography and confirmed by histology. Results demonstrate that 195 dermoids (72.22%) were located on the right ovary, 47 dermoids were found on the left side (17.41%), and 28 dermoids were found bilaterally (10.37%). The results indicate that the incidence of unilateral dermoids occurs more often on the right side.
G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow
Authors: Semerad Craig L. , Christopher Matthew J. , Liu Fulu , Short Brenton , Simmons Paul J. , Winkler Ingrid , Levesque Jean-Pierre , Chappel Jean , Ross F. Patrick , Link Daniel C.
Published: July 2005

Accumulating evidence indicates that interaction of stromal cell-derived factor 1 (SDF-1/CXCL12 [CXC motif, ligand 12]) with its cognate receptor, CXCR4 (CXC motif, receptor 4), generates signals that regulate hematopoietic progenitor cell (HPC) trafficking in the bone marrow. During granulocyte colony-stimulating factor (G-CSF)–induced HPC mobilization, CXCL12 protein expression in the bone marrow decreases. Herein, we show that in a series of transgenic mice carrying targeted mutations of their G-CSF receptor and displaying markedly different G-CSF–induced HPC mobilization responses, the decrease in bone marrow CXCL12 protein expression closely correlates with the degree of HPC mobilization. G-CSF treatment induced a decrease in bone marrow CXCL12 mRNA that closely mirrored the fall in CXCL12 protein. Cell sorting experiments showed that osteoblasts and to a lesser degree endothelial cells are the major sources of CXCL12 production in the bone marrow. Interestingly, osteoblast activity, as measured by histomorphometry and osteocalcin expression, is strongly down-regulated during G-CSF treatment. However, the G-CSF receptor is not expressed on osteoblasts; accordingly, G-CSF had no direct effect on osteoblast function. Collectively, these data suggest a model in which G-CSF, through an indirect mechanism, potently inhibits osteoblast activity resulting in decreased CXCL12 expression in the bone marrow. The consequent attenuation of CXCR4 signaling ultimately leads to HPC mobilization.
Platelet aggregation induces platelet aggregate stability via SLAM family receptor signaling
Authors: Nanda Nisha , Andre Patrick , Bao Ming , Clauser Karl , Deguzman Francis , Howie Duncan , Conley Pamela B. , Terhorst Cox , Phillips David R.
Published: July 2005

Platelet aggregation is a dynamic entity, capable of directing its own growth and stability via the activation of signaling cascades that lead to the expression and secretion of various secondary agonists. Here we show that the signaling pathways triggered during platelet aggregation include an intrinsic pro-thrombotic activity mediated by 2 homophilic adhesion molecules, CD84 and CD150 (SLAM [signaling lymphocyte activation molecule]), which are tyrosine phosphorylated in a platelet aggregation–dependent fashion. The 2 CD84/SLAM adapter proteins, SAP (SLAM-associated protein) and EAT-2 (EWS-activated transcript-2), were found in platelets; only SAP, however, was found to immunoprecipitate with tyrosine-phosphorylated SLAM. The immobilized extracellular domain of CD84 promoted microaggregate formation, while SAP-deficient platelets demonstrated defective spreading on immobilized CD84, demonstrating a functional role in platelets for SLAM family interactions. Finally, analysis of SLAM-deficient mice revealed an overall defect in platelet aggregation in vitro and a delayed arterial thrombotic process in vivo. The data indicate that signaling of the adhesion molecules in the SLAM family, activated by proximity during aggregation, further stabilize platelet-platelet interactions in thrombosis.
Excessive fluid accumulation during stem cell mobilization: a novel prognostic factor of first-year survival after stem cell transplantation in AL amyloidosis patients
Authors: Leung Nelson , Leung Tessa R. , Cha Stephen S. , Dispenzieri Angela , Lacy Martha Q. , Gertz Morie A.
Published: July 2005

High-dose melphalan followed by stem cell transplantation (HDM-SCT) has become the treatment of choice for patients with immunoglobulin light chain amyloidosis (AL). Unfortunately, treatment mortality can be excessive in certain subpopulations. We have noted that patients who gained more than 2% body weight during mobilization had a poorer outcome following HDM-SCT. Excluding 2 patients for lack of weight record and denial of consent, 126 patients between July 1997 and June 2003 were retrospectively studied. Weight increased more than 2.0% during mobilization in 51.6% of the patients. Patients who accumulated more than 2.0% tended to have more proteinuria, more organs involved, lower serum albumin, more diuretic use, and dosage adjustment during mobilization. First-year mortality was significantly higher in those with more than 2% weight gain (33.9% versus 9.8%, P = .002). Multivariate analysis showed weight gain, glomerular filtration rate, and septal thickness to be independent predictors of first-year mortality. The increase in mortality was noted even after the excess weight was diuresed prior to conditioning. The impact on mortality dissipated after the first year. Weight gain during mobilization appears to be a new marker of adverse outcome following HDM-SCT. Better prognostication may improve the treatment mortality rate of these patients.
CCR2 is required for CD8-induced graft-versus-host disease
Authors: Terwey Theis H. , Kim Theo D. , Kochman Adam A. , Hubbard Vanessa M. , Lu Sydney , Zakrzewski Johannes L. , Ramirez-Montagut Teresa , Eng Jeffrey M. , Muriglan Stephanie J. , Heller Glenn , Murphy George F. , Liu Chen , Budak-Alpdogan Tulin , Alpdogan Onder , van den Brink Marcel R. M.
Published: July 2005

Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HSCT). Migration of donor-derived T cells into GVHD target organs plays a critical role in the development of GVHD and chemokines and their receptors are important molecules involved in this process. Here, we demonstrate in murine bone marrow transplantation models that the expression of the inflammatory CC chemokine receptor 2 (CCR2) on donor-derived CD8+ T cells is relevant for the control of CD8+ T-cell migration and development of GVHD. Recipients of CCR2-deficient (CCR2-/-) CD8+ T cells developed less damage of gut and liver than recipients of wild-type CD8+ T cells, which correlated with a reduction in overall GVHD morbidity and mortality. Assessment of donor CD8+ T-cell target organ infiltration revealed that CCR2-/- CD8+ T cells have an intrinsic migratory defect to the gut and liver. Other causes for the reduction in GVHD could be excluded, as alloreactive proliferation, activation, IFN-γ production and cytotoxicity of CCR2-/- CD8+ T cells were intact. Interestingly, the graft-versus-tumor effect mediated by CCR2-/- CD8+ T cells was preserved, which suggests that interference with T-cell migration by blockade of CCR2 signaling can separate GVHD from GVT activity.
Lung vasodilatory response to inhaled iloprost in experimental pulmonary hypertension: amplification by different type phosphodiesterase inhibitors
Authors: Schermuly Ralph Theo , Inholte Christiane , Ghofrani Ardeschir Hossein , Gall Henning , Weissmann Norbert , Weidenbach Andreas , Seeger Werner , Grimminger Friedrich
Published: July 2005

Inhaled prostanoids and phosphodiesterase (PDE) inhibitors have been suggested for treatment of severe pulmonary hypertension. In catheterized rabbits with acute pulmonary hypertension induced by continuous infusion of the stable thromboxane analogue U46619, we asked whether sildenafil (PDE1/5/6 inhibitor), motapizone (PDE3 inhibitor) or 8-Methoxymethyl-IBMX (PDE1 inhibitor) synergize with inhaled iloprost. Inhalation of iloprost caused a transient pulmonary artery pressure decline, levelling off within <20 min, without significant changes in blood gases or systemic hemodynamics. Infusion of 8-Methoxymethyl-IBMX, motapizone and sildenafil caused each a dose-dependent decrease in pulmonary artery pressure, with sildenafil possessing the highest efficacy and at the same time selectivity for the pulmonary circulation. When combining a per se ineffective dose of each PDE inhibitor (200 μg/kg × min 8-Methoxymethyl-IBMX, 1 μg/kg × min sildenafil, 5 μg/kg × min motapizone) with subsequent iloprost nebulization, marked amplification of the prostanoid induced pulmonary vasodilatory response was noted and the area under the curve of PPA reduction was nearly threefold increased with all approaches, as compared to sole iloprost administration. Further amplification was achieved with the combination of inhaled iloprost with sildenafil plus motapizone, but not with sildenafil plus 8MM-IBMX. Systemic hemodynamics and gas exchange were not altered for all combinations. We conclude that co-administration of minute systemic doses of selective PDE inhibitors with inhaled iloprost markedly enhances and prolongs the pulmonary vasodilatory response to inhaled iloprost, with maintenance of pulmonary selectivity and ventilation perfusion matching. The prominent effect of sildenafil may be operative via both PDE1 and PDE5, and is further enhanced by co-application of a PDE3 inhibitor.
Comparison of codon usage measures and their applicability in prediction of microbial gene expressivity
Authors: Supek Fran , Vlahoviček Kristian
Published: July 2005

Background

There are a number of methods (also called: measures) currently in use that quantify codon usage in genes. These measures are often influenced by other sequence properties, such as length. This can introduce strong methodological bias into measurements; therefore we attempted to develop a method free from such dependencies. One of the common applications of codon usage analyses is to quantitatively predict gene expressivity.

Results

We compared the performance of several commonly used measures and a novel method we introduce in this paper – Measure Independent of Length and Composition (MILC). Large, randomly generated sequence sets were used to test for dependence on (i) sequence length, (ii) overall amount of codon bias and (iii) codon bias discrepancy in the sequences. A derivative of the method, named MELP (MILC-based Expression Level Predictor) can be used to quantitatively predict gene expression levels from genomic data. It was compared to other similar predictors by examining their correlation with actual, experimentally obtained mRNA or protein abundances.

Conclusion

We have established that MILC is a generally applicable measure, being resistant to changes in gene length and overall nucleotide composition, and introducing little noise into measurements. Other methods, however, may also be appropriate in certain applications. Our efforts to quantitatively predict gene expression levels in several prokaryotes and unicellular eukaryotes met with varying levels of success, depending on the experimental dataset and predictor used. Out of all methods, MELP and Rainer Merkl's GCB method had the most consistent behaviour. A 'reference set' containing known ribosomal protein genes appears to be a valid starting point for a codon usage-based expressivity prediction.
QT interval prolongation after sertraline overdose: a case report
Authors: de Boer Rudolf A , van Dijk Tonnis H , Holman Nicole D , van Melle Joost P
Published: July 2005

Background

Selective serotonin reuptake inhibitors (SSRIs) are the most common antidepressants used in first-world countries and are generally well tolerated. Specifically, less cardiovascular toxicity has been reported in comparison with tricyclic antidepressants. Here we report QT interval prolongation after an overdose of the SSRI sertraline.

Case presentation

A previously healthy female patient presented with an attempted suicide with overdoses sertraline (2250 mg), diazepam (200 mg), and temazepam (400 mg). Routine laboratory studies were normal and her ECG upon admission showed a normal QT interval. The next day, her ECG showed prolongation of the QTc interval up to 525 ms. After discontinuation of sertraline the QT interval normalized. Echocardiography and exercise electrocardiography were normal. After hospitalization, the patient resumed sertraline in the normally recommended dose and QT interval remained within normal ranges.

Conclusion

It seems that the SSRI sertraline in overdose may cause QT interval prolongation.
Kocuria kristinae infection associated with acute cholecystitis
Authors: Ma Edmond SK , Wong Chris LP , Lai Kristi TW , Chan Edmond CH , Yam WC , Chan Angus CW
Published: July 2005

Background

Kocuria, previously classified into the genus of Micrococcus, is commonly found on human skin. Two species, K. rosea and K. kristinae, are etiologically associated with catheter-related bacteremia.

Case presentation

We describe the first case of K. kristinae infection associated with acute cholecystitis. The microorganism was isolated from the bile of a 56-year old Chinese man who underwent laparoscopic cholecystectomy. He developed post-operative fever that resolved readily after levofloxacin treatment.

Conclusion

Our report of K. kristinae infection associated with acute cholecystitis expands the clinical spectrum of infections caused by this group of bacteria. With increasing number of recent reports describing the association between Kocuria spp. and infectious diseases, the significance of their isolation from clinical specimens cannot be underestimated. A complete picture of infections related to Kocuria spp. will have to await the documentation of more clinical cases.
Nerve tolerance to high-dose-rate brachytherapy in patients with soft tissue sarcoma: a retrospective study
Authors: Kubo Tadahiko , Sugita Takashi , Shimose Shoji , Matsuo Toshihiro , Hirao Ken , Kimura Hiroaki , Kenjo Masahiro , Ochi Mitsuo
Published: July 2005

Background

Brachytherapy, interstitial tumor bed irradiation, following conservative surgery has been shown to provide excellent local control and limb preservation in patients with soft tissue sarcomas (STS), whereas little is known about the tolerance of peripheral nerves to brachytherapy. In particular, nerve tolerance to high-dose-rate (HDR) brachytherapy has never been properly evaluated. In this study, we examined the efficacy and radiation neurotoxicity of HDR brachytherapy in patients with STS in contact with neurovascular structures.

Methods

Between 1995 and 2000, seven patients with STS involving the neurovascular bundle were treated in our institute with limb-preserving surgery, followed by fractionated HDR brachytherapy. Pathological examination demonstrated that 6 patients had high-grade lesions with five cases of negative margins and one case with positive margins, and one patient had a low-grade lesion with a negative margin. Afterloading catheters placed within the tumor bed directly upon the preserved neurovascular structures were postoperatively loaded with Iridium-192 with a total dose of 50 Gy in 6 patients. One patient received 30 Gy of HDR brachytherapy combined with 20 Gy of adjuvant external beam radiation.

Results

With a median follow-up of 4 years, the 5-year actuarial overall survival, disease-free survival, and local control rates were 83.3, 68.6, and 83.3%, respectively. None of the 7 patients developed HDR brachytherapy-induced peripheral neuropathy. Of 5 survivors, 3 evaluable patients had values of motor nerve conduction velocity of the preserved peripheral nerve in the normal range.

Conclusion

In this study, there were no practical and electrophysiological findings of neurotoxicity of HDR brachytherapy. Despite the small number of patients, our encouraging results are valuable for limb-preserving surgery of unmanageable STS involving critical neurovascular structures.
Cancer incidence in Arkhangelskaja Oblast in northwestern Russia. The Arkhangelsk Cancer Registry
Authors: Vaktskjold Arild , Lebedintseva Jelena A , Korotov Dmitrij S , Tkatsjov Anatolij V , Podjakova Tatjana S , Lund Eiliv
Published: July 2005

Background

Data concerning incidence and prevalence of cancer in the different regions of Russia have traditionally not been provided on a basis that facilitated comparison with data from countries in western parts of Europe. The oncological hospital in Arkhangelsk, in co-operation with Universitetet i Tromsø (Norway), has established a population based cancer registry for Arkhangelskaja Oblast (AO). AO is an administrative unit with 1.3 million inhabitants in northwestern Russia. The aim of this investigation was to assess the content and quality of the AO cancer registry (AKR), and to present the site-specific cancer-incidence rates in AO in the period 1993–2001.

Methods

The population in this study consisted of all individuals registered as residents of AO. All new cancer cases in the period 1993 – 2001, registered the AKR, were included in the study (ICD-10: C00-C95, except for C77-78). The annual gender and age-group-specific population figures were obtained from the AO statistics office.

Results

A total of 34 697 cases of primary cancers were included. The age-adjusted (world standard) incidence rate for all sites combined was 164/100 000 for women and 281/100 000 for men. The highest incidence was for cancer of the trachea, bronchus and lung (16.3% of all cases), whereof 88.6 % of the cases were among men. Among women, cancer of the breast constituted 15.9 percent of all cases. The age-adjusted incidences of the most frequent cancer sites among men were: lung (77.4/100 000); stomach (45.9); rectum (13.4); oesophagus (13.0); colon (12.2); bladder (11.6); and prostate cancer (11.1). Among women they were: breast (28.5); stomach (19.7); colon (12.2); and ovary cancer (9.0).

Conclusion

Our findings confirm and strengthen the indication that the incidences of stomach, larynx, liver, pancreas, prostate, colon, bladder and melanoma cancer are quite different in male populations in Russia compared to many other European countries. Among women, most major cancer types, except stomach, appear to be relatively low in Russian populations. The AKR provides quality data for estimations and insight to the cancer incidence in a northern Russian population, and we consider the reported incidence rates to reflect the cancer situation in AO well.
Application of serum SELDI proteomic patterns in diagnosis of lung cancer
Authors: Yang Shuan-ying , Xiao Xue-yuan , Zhang Wang-gang , Zhang Li-juan , Zhang Wei , Zhou Bin , Chen Guoan , He Da-cheng
Published: July 2005

Background

Currently, no satisfactory biomarkers are available to screen for lung cancer. Surface-Enhanced Laser Desorption/ionization Time-of- Flight Mass Spectrometry ProteinChip system (SELDI-TOF-MS) is one of the currently used techniques to identify biomarkers for cancers. The aim of this study is to explore the application of serum SELDI proteomic patterns to distinguish lung cancer patients from healthy individuals.

Methods

A total of 208 serum samples, including 158 lung cancer patients and 50 healthy individuals, were randomly divided into a training set (including 11 sera from patients with stages I/II lung cancer, 63 from patients with stages III/IV lung cancer and 20 from healthy controls) and a blinded test set (including 43 sera from patients with stages I/II lung cancer, 41 from patients with stages III/IV lung cancer and 30 from healthy controls). All samples were analyzed by SELDI technology. The spectra were generated on weak cation exchange (WCX2) chips, and protein peaks clustering and classification analyses were made using Ciphergen Biomarker Wizard and Biomarker Pattern software, respectively. We additionally determined Cyfra21-1 and NSE in the 208 serum samples included in this study using an electrochemiluminescent immunoassay.

Results

Five protein peaks at 11493, 6429, 8245, 5335 and 2538 Da were automatically chosen as a biomarker pattern in the training set. When the SELDI marker pattern was tested with the blinded test set, it yielded a sensitivity of 86.9%, a specificity of 80.0% and a positive predictive value of 92.4%. The sensitivities provided by Cyfra21-1 and NSE used individually or in combination were significantly lower than that of the SELDI marker pattern (P < 0.005 or 0.05, respectively). Based on the results of the test set, we found that the SELDI marker pattern showed a sensitivity of 91.4% in the detection of non-small cell lung cancers (NSCLC), which was significantly higher than that in the detection of small cell lung cancers (P < 0.05); The pattern also had a sensitivity of 79.1% in the detection of lung cancers in stages I/II.

Conclusion

These results suggest that serum SELDI protein profiling can distinguish lung cancer patients, especially NSCLC patients, from normal subjects with relatively high sensitivity and specificity, and the SELDI-TOF-MS is a potential tool for the screening of lung cancer.
A population-based nested case control study on recurrent pneumonias in children with severe generalized cerebral palsy: ethical considerations of the design and representativeness of the study sample
Authors: Veugelers Rebekka , Calis Elsbeth AC , Penning Corine , Verhagen Arianne , Bernsen Roos , Bouquet Jan , Benninga Marc A , Merkus Peter JFM , Arets Hubertus GM , Tibboel Dick , Evenhuis Heleen M
Published: July 2005

Background

In children with severe generalized cerebral palsy, pneumonias are a major health issue. Malnutrition, dysphagia, gastro-oesophageal reflux, impaired respiratory function and constipation are hypothesized risk factors. Still, no data are available on the relative contribution of these possible risk factors in the described population. This paper describes the initiation of a study in 194 children with severe generalized cerebral palsy, on the prevalence and on the impact of these hypothesized risk factors of recurrent pneumonias.

Methods/Design

A nested case-control design with 18 months follow-up was chosen. Dysphagia, respiratory function and constipation will be assessed at baseline, malnutrition and gastro-oesophageal reflux at the end of the follow-up. The study population consists of a representative population sample of children with severe generalized cerebral palsy. Inclusion was done through care-centres in a predefined geographical area and not through hospitals. All measurements will be done on-site which sets high demands on all measurements. If these demands were not met in "gold standard" methods, other methods were chosen. Although the inclusion period was prolonged, the desired sample size of 300 children was not met. With a consent rate of 33%, nearly 10% of all eligible children in the Netherlands are included (n = 194). The study population is subtly different from the non-participants with regard to severity of dysphagia and prevalence rates of pneumonias and gastro-oesophageal reflux.

Discussion

Ethical issues complicated the study design. Assessment of malnutrition and gastro-oesophageal reflux at baseline was considered unethical, since these conditions can be easily treated. Therefore, we postponed these diagnostics until the end of the follow-up. In order to include a representative sample, all eligible children in a predefined geographical area had to be contacted. To increase the consent rate, on-site measurements are of first choice, but timely inclusion is jeopardised. The initiation of this first study among children with severe neurological impairment led to specific, unexpected problems. Despite small differences between participants and non-participating children, our sample is as representative as can be expected from any population-based study and will provide important, new information to bring us further towards effective interventions to prevent pneumonias in this population.
Intermittent preventive treatment of malaria during pregnancy: a qualitative study of knowledge, attitudes and practices of district health managers, antenatal care staff and pregnant women in Korogwe District, North-Eastern Tanzania
Authors: Mubyazi Godfrey , Bloch Paul , Kamugisha Mathias , Kitua Andrew , Ijumba Jasper
Published: July 2005

Background

Intermittent preventive treatment of malaria during pregnancy (IPTp) is a key intervention in the national strategy for malaria control in Tanzania. SP, the current drug of choice, is recommended to be administered in the second and third trimesters of pregnancy during antenatal care (ANC) visits. To allow for a proper design of planned scaling up of IPT services in Tanzania it is useful to understand the IPTp strategy's acceptability to health managers, ANC service providers and pregnant women. This study assesses the knowledge, attitudes and practices of these groups in relation to malaria control with emphasis on IPTp services.

Methods

The study was conducted in February 2004, in Korogwe District, Tanzania. It involved in-depth interviews with the district medical officer (DMO), district hospital medical officer in charge and relevant health service staff at two peripheral dispensaries, and separate focus group discussions (FGDs) with district Council Health Management Team members at district level and pregnant women at dispensary and community levels.

Results

Knowledge of malaria risks during pregnancy was high among pregnant women although some women did not associate coma and convulsions with malaria. Contacting traditional healers and self-medication with local herbs for malaria management was reported to be common. Pregnant women and ANC staff were generally aware of SP as the drug recommended for IPTp, albeit some nurses and the majority of pregnant women expressed concern about the use of SP during pregnancy. Some pregnant women testified that sometimes ANC staff allow the women to swallow SP tablets at home which gives a room for some women to throw away SP tablets after leaving the clinic. The DMO was sceptical about health workers' compliance with the direct observed therapy in administering SP for IPTp due to a shortage of clean water and cups at ANC clinics. Intensified sensitization of pregnant women about the benefits of IPTp was suggested by the study participants as an important approach for improving IPTp compliance.

Conclusion

The successful implementation of the IPTp strategy in Tanzania depends on the proper planning of, and support to, the training of health staff and sustained sensitization of pregnant women at health facility and community levels about the benefits of IPTp for the women and their unborn babies.
Gastrointestinal autonomic nerve tumours – report of a case and review of literature
Authors: Mulchandani Manoj H , Chattopadhyay Dipankar , Obafunwa John O , Joypaul Vickram B
Published: July 2005

Background

Gastrointestinal autonomic nerve tumours are uncommon stromal tumours of the intestinal tract. They can involve any part of the gastrointestinal system, but are very rarely seen in the rectum.

Case presentation

We report a unique case of rectal schwannoma with associated synchronous adenocarcinoma of the splenic flexure and adenoma of the descending colon. A 70-year-old patient was admitted with complaint of bleeding per rectum and investigations revealed the presence of a large submucosal rectal lesion in addition to the colonic pathologies. Following panproctocolectomy with permanent spout ileostomy, histopathology and immunohistochemistry confirmed the rectal lesion to be a schwannoma.

Conclusion

Literature review of the few reported cases has suggested radical surgical excision to be the best approach. Prognosis tends to be favourable after resection.
Evidence that the p53 negative / Bcl-2 positive phenotype is an independent indicator of good prognosis in colorectal cancer: A tissue microarray study of 460 patients
Authors: Watson Nicholas FS , Madjd Zahra , Scrimegour Duncan , Spendlove Ian , Ellis Ian O , Scholefield John H , Durrant Lindy G
Published: July 2005

Background

Advances in our understanding of the molecular biology of colorectal cancer have fuelled the search for novel molecular prognostic markers to complement existing staging systems. Markers assessed in combination may perform better than those considered individually. Using high-throughput tissue microarray technology, we describe the prognostic value of combined p53 / Bcl-2 status in colorectal cancer.

Patients and methods

Tumour samples from 462 patients who underwent elective surgery to resect a primary colorectal cancer between 1994 and 2000 (mean follow-up of 75 months) were assembled in tissue microarray format. Clinico-pathological data including tumour grade, stage, vascular invasion status along with disease specific survival data has been collected prospectively. Immunohistochemical analysis of p53 and Bcl-2 expression was performed using antibodies DO-7 (p53) and 124 (Bcl-2), and results correlated with known clinico-pathological variables and outcomes.

Results

Abnormal nuclear p53 accumulation and Bcl-2 overexpression were detected in 221/445 (49.6%) and199/437 (45.5%) tumours respectively, with a significant inverse correlation between the two markers (p = 0.023). On univariate analysis no correlations were found between either marker and standard clinico-pathological variables, however nuclear p53 expression was associated with a significantly reduced survival (p = 0.024). Combined analysis of the two markers indicated that 112/432 (24.2%) cases displayed a p53(-)/Bcl-2(+) phenotype, this occurring more frequently in earlier stage tumours. Kaplan-Meier analysis revealed a significant survival advantage in these p53(-)/Bcl-2(+) tumours compared with the remaining cases (p = 0.0032). On multivariate analysis using the Cox proportional hazards model, neither p53 expression nor Bcl-2 expression alone were of independent prognostic significance, however the combined p53(-)/Bcl-2(+) phenotype was significantly associated with a good prognosis in this series (HR 0.659, 95%CI 0.452–0.959, p = 0.029).

Conclusion

Patient stratification by combined p53 / Bcl-2 phenotype provides stage-independent prognostic information in colorectal cancer. Specifically, that up to a quarter of patients display a good prognosis p53(-)/Bcl-2(+) phenotype. This may indicate a more clinically indolent phenotype and a subset of patients for whom less aggressive adjuvant treatment appropriate.
Alternative pre-mRNA processing regulates cell-type specific expression of the IL4l1 and NUP62 genes
Authors: Wiemann Stefan , Kolb-Kokocinski Anja , Poustka Annemarie
Published: July 2005

Background

Given the complexity of higher organisms, the number of genes encoded by their genomes is surprisingly small. Tissue specific regulation of expression and splicing are major factors enhancing the number of the encoded products. Commonly these mechanisms are intragenic and affect only one gene.

Results

Here we provide evidence that theIL4I1gene is specifically transcribed from the apparent promoter of the upstreamNUP62gene, and that the first two exons ofNUP62are also contained in the novelIL4I1_2variant. While expression ofIL4I1driven from its previously described promoter is found mostly in B cells, the expression driven by theNUP62promoter is restricted to cells in testis (Sertoli cells) and in the brain (e.g., Purkinje cells). SinceNUP62is itself ubiquitously expressed, theIL4I1_2variant likely derives from cell type specific alternative pre-mRNA processing.

Conclusion

Comparative genomics suggest that the promoter upstream of theNUP62gene originally belonged to theIL4I1gene and was later acquired byNUP62via insertion of a retroposon. Since both genes are apparently essential, the promoter had to serve two genes afterwards. Expression of theIL4I1gene from the "NUP62" promoter and the tissue specific involvement of the pre-mRNA processing machinery to regulate expression of two unrelated proteins indicate a novel mechanism of gene regulation.
Gait variability: methods, modeling and meaning
Authors: Hausdorff Jeffrey M
Published: July 2005

The study of gait variability, the stride-to-stride fluctuations in walking, offers a complementary way of quantifying locomotion and its changes with aging and disease as well as a means of monitoring the effects of therapeutic interventions and rehabilitation. Previous work has suggested that measures of gait variability may be more closely related to falls, a serious consequence of many gait disorders, than are measures based on the mean values of other walking parameters. The Current JNER series presents nine reports on the results of recent investigations into gait variability. One novel method for collecting unconstrained, ambulatory data is reviewed, and a primer on analysis methods is presented along with a heuristic approach to summarizing variability measures. In addition, the first studies of gait variability in animal models of neurodegenerative disease are described, as is a mathematical model of human walking that characterizes certain complex (multifractal) features of the motor control's pattern generator. Another investigation demonstrates that, whereas both healthy older controls and patients with a higher-level gait disorder walk more slowly in reduced lighting, only the latter's stride variability increases. Studies of the effects of dual tasks suggest that the regulation of the stride-to-stride fluctuations in stride width and stride time may be influenced by attention loading and may require cognitive input. Finally, a report of gait variability in over 500 subjects, probably the largest study of this kind, suggests how step width variability may relate to fall risk. Together, these studies provide new insights into the factors that regulate the stride-to-stride fluctuations in walking and pave the way for expanded research into the control of gait and the practical application of measures of gait variability in the clinical setting.
Genetic characterization of measles viruses isolated in Turkey during 2000 and 2001
Authors: Korukluoglu Gulay , Liffick Stephanie , Guris Dalya , Kobune Fumio , Rota Paul A , Bellini William J , Ceylan Ali , Ertem Meliksah
Published: July 2005

Background

Molecular epidemiologic studies have made significant contributions to measles surveillance activities by helping to identify source and transmission pathways of the virus. This report describes the genetic characterization of wild-type measles viruses isolated in Turkey in 2000 and 2001.

Results

Wild-type measles viruses were isolated from 24 cases from five provinces in Turkey during 2001. The viruses were analyzed using the standard genotyping protocols. All isolates were classified as genotype D6, the same genotype that was identified in Turkey in previous outbreaks during 1998.

Conclusion

Turkey has begun implementation of a national program to eliminate measles by 2010. Therefore, this baseline genotype data will provide a means to monitor the success of the elimination program.