bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrically enhanced transdermal delivery of a macromolecule
Authors: Badkar Advait V , Banga Ajay K 
Published: October 2002

Abstract
The purpose of this study was to establish the delivery parameters for the enhanced transdermal delivery of dextran sulfate (MW 5000 Da). Full-thickness pig skin or epidermis separated from human cadaver skin was used. Silver-silver chloride electrodes were used to deliver the current (0.5 mA cm−2). For electroporation experiments, one or more pulses were given using an exponential decay pulse generator. The correct polarity for iontophoresis and pulsing was first established as cathode in the donor. The amount of drug delivered increased with increasing donor concentration up to a point, but not any further. The amount delivered also increased with pulse voltage, the delivery being twice as much as with iontophoresis alone (144.5 ± 10.35 μg cm−2), when 6 pulses of 500 V were applied at time zero before iontophoresis (276 ± 45.2 μg cm−2). It was observed that the amount delivered was a function of increasing pulse length when the apparent charge delivered was kept constant. Transport through pig skin (107.4 ± 24.4 μg cm−2) was found to be comparable with that through human epidermis (84.9 ± 18.4 μ g cm−2). In conclusion, we have demonstrated the transdermal delivery of a 5000 Da molecular weight dextran sulfate using iontophoresis. It was also seen that iontophoretic delivery could be enhanced by simultaneous electroporation.
Non-specific binding of the experimental anti-cancer drug 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in liver microsomes from various species
Authors: Zhou Shufeng , Kestell Philip , Paxton James W 
Published: October 2002

Abstract
Total (added) drug concentrations other than unbound concentrations have been used to estimate the in-vitro enzyme kinetic parameters for 5,6-dimethylxanthenone-4-acetic acid (DMXAA), an experimental anti-cancer drug. This study aimed to investigate the non-specific binding of DMXAA to liver microsomes from various species and to microsomes from human lymphoblastoid cells expressing drug-metabolising enzymes, and to examine the effect of the binding on the estimation of enzyme kinetic parameters for DMXAA in-vitro. The separation of unbound DMXAA was conducted by ultrafiltration and DMXAA concentrations were determined by validated HPLC. The results indicated that DMXAA was bound to liver microsomes and lymphoblastoid cell microsomes to a small extent (free fraction in microsomes, fu(mic) mostly &gt; 0.85). Correction for the unbound DMXAA concentration resulted in slightly lower apparent Michaelis-Menten constant (Km) values, but with the maximal velocity of reaction (Vmax) unchanged, leading to slightly higher unbound Vmax/Km values. These results indicate that the non-specific binding of DMXAA to microsomes is insignificant and has little impact on the enzyme kinetic estimation in-vitro.
An exponential change of measure for the Feller diffusion and some implications for superprocesses
Authors: Adler Robert J. , Iyer Srikanth K. 
Published: October 2002

Let Xt be a Feller (branching) diffusion with drift αx. We consider new processes, the probability measures of which are obtained from that of X via changes of measure involving suitably normalized exponential functions of with λ > 0. The new processes can be thought of as ‘self-reinforcing’ versions of the old.Depending on the values of α, T and λ, the process under the new measure is shown to exhibit explosion in finite time. We also obtain a number of other results related to the new processes.Since the Feller diffusion is also the total mass process of a superprocess, we relate the finite-time explosion property to the behaviour of superprocesses with local self-interaction, and raise some interesting questions for these.
TM4SF2 gene involvement reconsidered in an XLMR family after neuropsychological assessment
Authors: Gomot Marie , Ronce Nathalie , Dessay Sabine , Zemni Ramzi , Ayrault Anne‐Dominique , Moizard Marie‐Pierre , Nivelon Annie , Gilgenkrantz Simone , Dourlens Julliette , Des Portes Vincent , Chelly Jamel , Moraine Claude 
Published: October 2002

AbstractThe TM4SF2 gene (localized at Xp11.4 between the loci DXS564 and DXS556) has been found to be mutated in one MRX family. In order to define the corresponding behavioral phenotype, global IQ and specific cognitive skills were assessed in seven males and three females of this family, independent of subject status. Mental retardation (MR) was mild in three patients and moderate in three others. Despite the broad variability of severity of MR, a cognitive profile specific to the MR in this family was documented. It was characterized by language disorder that was more marked in the articulatory component and spatial/verbal short‐term memory dissociation with larger mnemonic span for spatial than for verbal cues. Linkage analysis was then performed on the basis of the cognitively determined status. Recombinations were observed with the loci DXS556 at Xp11.4 and DXS441 at Xq13.2 (maximum LOD score = 2.23 at θ = 0 for ALAS2). This localization region does not include the TM4SF2 gene that has been found mutated in both patients with MR and in one non‐MR male subject of this family. The present results suggest two main hypotheses. First, TM4SF2 gene mutation could be involved in MR in this family, therefore representing accentuated intra familial phenotypic variability. Second, the structural particularity detected in the TM4SF2 gene might reflect a rare polymorphism rather than a pathogenic mutation, with the gene responsible for MR in this family being therefore more likely to be searched for in the pericentromeric region of the X chromosome. © 2002 Wiley‐Liss, Inc.
Male limited association of the dopamine receptor D2 gene TaqI a polymorphism and alcohol dependence
Authors: Limosin Frédéric , Gorwood Philip , Loze Jean‐Yves , Dubertret Caroline , Gouya Laurent , Deybach Jean‐Charles , Adès Jean 
Published: October 2002

AbstractAssociation studies of the TaqI A allele of the dopamine receptor D2 (DRD2) gene with alcohol dependence have produced conflicting findings. Although a wide series of clinical features have been considered in the different association studies performed, very few studies specifically analyzed the role of gender. We compared the TaqI A polymorphisms of theDRD2gene in 120 French Caucasian alcohol‐dependent inpatients (62 males and 58 females) and 107 healthy ethnically matched controls (66 males and 41 females). We observed that 55% of alcohol‐dependent males have at least one A1 allele, a prevalence that is significantly above that observed in the control males (38%). On the contrary, no differences were found in females between the alcohol‐dependent inpatients and controls for the A1 allele prevalence. In our sample, this male‐specific association was not explained by gender specificities of alcohol dependence, such as age at onset and severity measures (mean numbers of social, somatic, and withdrawal complications). On the other hand, alcohol‐dependent women with the A1 allele reported more frequently a major depressive disorder (70% vs. 40%,P = 0.03). We thus replicated the allelic association of the A1 allele of theDRD2gene with alcohol dependence, but showed a male‐limited effect of this “vulnerability allele.” Recent evidence for gender difference in dopamine D2‐like receptor levels and affinity may explain this discrepancy. © 2002 Wiley‐Liss, Inc.
Current concepts in radiation enteritis and implications for future clinical trials
Authors: Nguyen Nam P. , Antoine John E. , Dutta Suresh , Karlsson Ulf , Sallah Sabah 
Published: October 2002

AbstractBACKGROUNDRadiation enteritis is one of the most feared complications of abdominal and pelvic radiation. Once its occurs, the process is relentless and may result in the patient's death. Available treatment is only supportive. Recent progress in molecular biology has shed some light on the pathogenesis of radiation enteritis and other diseases that are characterized by excessive fibrosis. New treatment modalities may be devised to improve the outcome of patients who are affected with this complication.METHODSA literature search was used to identify the common denominator between many radiation‐induced fibrotic conditions and other sclerotic diseases. Factors that affect the disease process and possible therapeutic interventions were evaluated.RESULTSThe hyperstimulation of transforming growth factor β1 (TGF‐β1) leads to increased fibrosis and, ultimately, organ failure. Interferon gamma (IFN‐γ) inhibits the effects of TGF‐β1 in the nucleus. The fibrotic process may be reverted by IFN‐γ in various pathologic conditions.CONCLUSIONSRadiation enteritis and other radiation‐induced, long‐term complications are characterized by excessive stimulation of TGF‐β1. Preliminary studies suggest that IFN‐γ may be effective in the treatment of patients with radiation‐induced cutaneous fibrosis. IFN‐γ should be considered in Phase I–II studies to assess its toxicity and efficacy in the treatment of patients with radiation enteritis. Cancer 2002;95:1151–63. © 2002 American Cancer Society.DOI 10.1002/cncr.10766
Validation of a biopsy‐based pathologic algorithm for predicting lymph node metastases in patients with clinically localized prostate carcinoma
Authors: Haese Alexander , Epstein Jonathan I. , Huland Hartwig , Partin Alan W. 
Published: October 2002

AbstractBACKGROUNDThe authors validated an algorithm for the preoperative prediction of lymph node (LN) metastases in patients with clinically localized prostate carcinoma. The algorithm was applied to sextant biopsy material and radical retropubic prostatectomy (RRP) stage obtained from a cohort of men who were treated at the authors' institution.METHODSFour hundred forty‐three patients underwent systematic sextant biopsy and RRP with staging lymphadenectomy. The original algorithm was based on systematic sextant biopsy data and classified patients into three risk groups for LN metastases based on the biopsy result. If ≥ 4 of 6 biopsies contained any Gleason Pattern 4 disease, then the patient was at high risk for LN metastases (45%). Patients with ≥ 1 of 6 biopsies with dominant Gleason Pattern 4 disease (excluding high‐risk patients) had an intermediate predicted risk (19%) of LN metastases. All other patients had a low predicted risk of LN metastases (2.2%). The authors assed the percentage of patients who were positive and negative for LN metastases and calculated the specificity and negative predictive value in the series when patients were classified according to the original algorithm.RESULTSTwenty of 443 patients had intraoperative LN metastases. When applied to the current data, the Hamburg algorithm classified 404 patients in the low‐risk group, 30 patients in the intermediate‐risk group, and 9 patients in the high risk group. The incidence of LN metastases was 2.47% in the low‐risk group, 20% in the intermediate‐risk group, and 44.4% in the high‐risk group. The negative predictive value for the low‐risk group was 97.52%, and the specificity was 94.14%.CONCLUSIONSThe Hamburg algorithm proved a valid tool for the prediction of lymphatic spread in this validation study on data from the authors' institution. The algorithm may serve as a tool to select patients who do not need to undergo pelvic lymphadenectomy at the time they undergo RRP, hence reducing morbidity and expense. More importantly, with the increasing numbers of men undergoing treatment options in whom LN dissection is not performed, this validated algorithm provides an important selection basis regarding the appropriateness of a therapy that does not routinely include LN staging. Cancer 2002;95:1016–21. © 2002 American Cancer Society.DOI 10.1002/cncr.10811
Evidence for a dynamic host‐parasite relationship in e‐negative hepatitis B carriers
Authors: Tedder Richard S. , Ijaz Samreen , Gilbert Nicola , Barbara John A.J. , Corden Sally A. , Gilson Richard J.C. , Boxall Elizabeth H. 
Published: October 2002

AbstractAnti‐hepatitis Be (HBe) carriers are perceived as having low infectivity, with hepatitis B virus (HBV) DNA levels far below those seen in the HBeAg carrier. However, the temporal stability of HBV DNA in anti‐HBe carriers remains poorly characterised. UK Department of Health guidelines use HBV DNA levels to define whether HBV‐infected health care workers may perform exposure‐prone procedures. Two samples separated by 1–23 years available from 147 carriers were analysed for precore variants and HBV DNA levels. Among 15 HBeAg carriers, HBV DNA was maintained at high levels. There was a 5 log10 fold reduction in DNA in 11 individuals who developed anti‐HBe during follow‐up evaluation. Proportional changes in HBV DNA levels in anti‐HBe carriers were similar to those in HBeAg carriers, although there was a trend for changes in viral DNA to be more marked in anti‐HBe carriers followed up for longer periods. Closer sampling in 20 anti‐HBe carriers demonstrated large fluctuations of DNA levels over short periods. Serum transaminases and precore mutant status at the outset failed to predict those in whom HBV DNA levels fluctuated. HBV DNA was below the detection threshold (<400 copies/ml) in 36 anti‐HBe carriers at first sampling and remained so in all but 5 of these carriers. Twelve individuals who were previously viraemic lost detectable HBV DNA during follow‐up evaluation. While HBV DNA levels are found to fluctuate in carriers, our results indicate that once below the threshold of detectability, levels are unlikely to rise. This is an important factor when assessing health care workers for exposure‐prone procedures. J. Med. Virol. 68:505–512, 2002. © 2002 Wiley‐Liss, Inc.
Low hepatitis B prevalence among pre‐school children in Denmark: Saliva anti‐HBc screening in day care centres
Authors: Fisker Niels , Georgsen Jørgen , Stolborg Torsten , Khalil Mohammed Rohi , Christensen Peer Brehm 
Published: October 2002

AbstractAlthough Denmark has a low hepatitis B virus (HBV) prevalence, HBV transmission has been reported in Danish day‐care centres. The aim of this study was to validate saliva anti‐HBc testing as a method for HBV screening, the applicability of saliva sampling to pre‐school children, and to determine the HBV prevalence in Danish day‐care centres with a high proportion of immigrants. For validation, paired saliva and plasma samples were obtained from blood donors and injecting drug users. Employees and children in day‐care centres with a high proportion of immigrant children were offered saliva screening followed by blood test if positive. The specificity and sensitivity of anti‐HBc tests on saliva was 100% (102 blood donors and four injecting drug users) and 85.9% (61 of 71 anti‐HBc‐positive injecting drug users), respectively. In all samples from HBsAg (n = 7) or anti‐HBc IgM‐positives (n = 9), anti‐HBc was detected in saliva. Adequate saliva samples were obtained from 93% (588/634) of children and 100% (166/166) of employees participating in the day‐care centre survey. Among children 55% were of non‐Scandinavian origin and only one (0.2%, 95% CI [0.0; 1.0]) was HBV positive. Among employees the corresponding values were 22% and 7 (4.2%). The positive predictive value of the saliva test was 25% (1/4) among children and 88% (7/8) among adults. In conclusion, saliva testing is feasible for HBV screening among children in low prevalence populations, but any anti‐HBc reactivity should be confirmed by plasma analysis. The HBV prevalence in pre‐school children in Denmark is low even among immigrants from endemic areas. J. Med. Virol. 68:500–504, 2002. © 2002 Wiley‐Liss, Inc.
Mediastinal mass in childhood T‐cell acute lymphoblastic leukemia: Significance and therapy response
Authors: Attarbaschi Andishe , Mann Georg , Dworzak Michael , Wiesbauer Peter , Schrappe Martin , Gadner Helmut 
Published: October 2002

AbstractBackgroundT‐cell acute lymphoblastic leukemia (T‐ALL) accounts for ∼10–13% of childhood ALL cases. Patients with T‐ALL frequently present with unfavorable features at diagnosis and thus are considered to have a higher risk to relapse. Within the last 10 years, the previously dismal prognosis of this ALL subtype has been improved by intensified chemotherapy. However, 30–40% of patients still relapse, so that additional prognostic factors such as the local response of the mediastinal mass to therapy might allow defining the patients at risk in a better manner.ProcedureA retrospective analysis of 116 Austrian patients with T‐ALL was performed to assess whether an initial mediastinal mass (70/116) and its response to chemotherapy as measured by thoracic X‐rays (32/70) might predict outcome.ResultsNeither patients with a mediastinal tumor at the time of diagnosis nor patients with an incomplete response on day 35 or 70 of therapy had a worse prognosis, as compared with the group of patients with no initial tumor and complete regression on day 35 and 70.ConclusionsWe failed to show that in children with T‐ALL residual mediastinal tumors are of prognostic relevance. This might suggest that incomplete local response is not necessarily an indication for treatment intensification such as local irradiation, second‐look operation, or high‐dose chemotherapy with bone marrow rescue. However, due to the relatively small number of patients analyzed, our results have to be validated prospectively on a larger cohort of patients in future clinical trials. Med Pediatr Oncol 2002;39:558–565. © 2002 Wiley‐Liss, Inc.
On the origin of EEG‐slowing and encephalopathy during induction treatment of acute lymphoblastic leukemia
Authors: Korinthenberg Rudolf , Scheuring Bernadette , Boos Joachim , Niemeyer Charlotte 
Published: October 2002

AbstractBackgroundNeurological complications and EEG slowing frequently occur in children undergoing induction treatment for acute lymphoblastic leukemia (ALL). Disease‐related factors and treatment‐related toxicity are believed to play causative roles. We wanted to elucidate the etiology further by serial EEG examinations and parallel CSF amino acid analyses.ProcedureTwenty‐nine children participated in the study. EEG examinations with quantitative computerized analysis were scheduled on day 1, 10, 29, and 59 of protocol I of BFM‐ALL 90 and 95 Study Protocols. CSF analysis for amino acids was carried out on day 1, 15, 29, 45, and 59.ResultsA total of 21 of 25 available EEGs showed slight‐to‐moderate slowing already at diagnosis. The abundance of slow waves was significantly correlated to the white blood count and the CSF glutamine concentration. The EEGs significantly worsened during the first 10 days of treatment with prednisone, VCR, daunorubicin, and intrathecal methotrexate. The following treatment including asparaginase (ASP) gave rise to depletion of CSF from asparagine and a rise of aspartate; glutamine, and glutamate did not follow this pattern. The EEGs remained abnormal, but did not worsen further; the CSF amino acid changes were not related to the EEG. During the subsequent consolidation treatment, the EEGs normalized despite administration of cyclophosphamide, cytara bine, intrathecal methotrexate, and mercaptopurin.ConclusionsThe greater part of EEG changes observed in the early treatment of ALL is due to disease‐related factors. Treatment with prednisone, vincristine, and to a much lesser degree asparaginase aggravates the pre‐existing encephalopathy. Depletion of CSF from asparagine does not give rise to additional changes. In the second month, the EEG normalizes despite ongoing treatment with different cytotoxic drugs. Med Pediatr Oncol 2002;39:566–572. © 2002 Wiley‐Liss, Inc.
Localised Ewing sarcoma/PNET of bone—prognostic factors and international data comparison
Authors: Jenkin R. Derek , Al‐Fawaz Ibrahim , Al‐Shabanah Mohammed , Allam Ayman , Ayas Mouhab , Khafaga Yasser , Memon Muhammad , Rifai Samira , Schultz Henrik , Younge Derek 
Published: October 2002

AbstractBackgroundTo determine if the distribution of prognostic factors accounted for the differences when the outcome for localised Ewing Sarcoma/PNET bone in Saudi Arabia was compared with results from countries with well developed health care systems.ProcedureRetrospective analysis was undertaken of 163 consecutive patients of all ages, treated with radical intent at KFSHRC from 1975 to 1998. Standard chemotherapy was commenced in all patients. The local treatment modality was resection ± radiation in 30% and radiation treatment alone in 67%. Size data were available for 51 patients treated from 1994 to 1998, inclusive. One third of these patients had tumors with volume >500 ml.ResultsThree year survival significantly increased with the year of diagnosis, 1975–1988 45%; 1989–1993 55%; and 1993–1998 63% (P = 0.006). Favorable prognostic factors were age ≤14 (P = 0.07); site, distal extremity, and skull (P = 0.08); and volume ≤ 200 ml (P = 0.06). Secondary prognostic factors were response to induction chemotherapy, both histological, 100% necrosis, (P = 0.04) and clinical CR+PR, (P = 0.02). From 1994 to 1998, 3 year survival for tumors in the distal extremity and skull was 80% and for small tumors, < 200 ml, at any site was 82%. In comparison, the 3 year survival for patients with tumors at any other sites was 60%, and for tumors >200 ml, 55%.ConclusionsOverall survival progressively improved. From 1994 to 1998 the survival of patients with small tumors and/or favorable sites was similar to the best reported results. It was not possible to compare results by tumor size for large tumors, > 500 ml, due to the absence of data from elsewhere. A better staging system is required for the international comparison of results. Med Pediatr Oncol 2002;39:586–593. © 2002 Wiley‐Liss, Inc.
A classification and evaluation of research in operations management
Authors: Chase Richard B. 
Published: October 2002

AbstractIt is important that the first issue of a new journal devoted to research in a given subject area examine the general nature of research in the field at present, and indicate what type of research might be beneficially undertaken in the field in the future. It is also desirable for a new journal to consider the ways in which it will judge the general quality of its articles in the aggregate, relative to established journals in similar disciplines. That is, what criteria can and should be used, say five years hence to determine if the journal is a strong one? It is the purpose of this paper to consider these distinct, but interrelated questions. This will be done by classifying some recent OM research, commenting on what appear to be broad areas where more work might be done, and then suggesting some measures we might want to think about for evaluating papers published by the JOM in the future.