bluuebunny/crossref_metadata_2025_split huggingface dataset:
Putative Role of Dihydropyrimidine Dehydrogenase in the Toxic Side Effect of 5-Fluorouracil in Colorectal Cancer Patients
Authors: Katona Csilla , Kralovánszky Judit , Rosta András , Pandi Erzsébet , Fónyad Gábor , Tóth Katalin , Jeney András 
Published: April 2003

Dihydropyrimidine dehydrogenase (DPD) is the first and rate limiting enzyme in the catabolism of 5-fluorouracil (5-FU). It has been reported from various laboratories that the plasma concentration of 5-FU was influenced by DPD activities in various normal human organs (e.g. liver or lymphocytes). Since the congenital deficiency in DPD caused severe, in some cases lethal, FU-related toxicity, it was decided to collect data about the DPD activity in colorectal cancer patients in order to investigate the possible correlation between the enzyme activity and appearance of the side effects of 5-FU. Assuming that DPD activity in lymphocytes represents the 5-FU catabolic capacity of the organism, DPD activity was determined in the lymphocytes of 48 patients with colorectal cancer after surgery during the therapeutic course with 5-FU and folinic acid. On the basis of the enzyme activity, patients were divided into three categories: low (DPD <5.03 pmol/min/10<sup>6</sup> lymphocytes); medium (DPD = 5.04–13.25 pmol/min/10<sup>6</sup> lymphocytes), and high (DPD > 13.26 pmol/min/10<sup>6</sup> lymphocytes) activity groups. By evaluating the toxic side effects during the 5-FU + folinic acid treatment, the following results were obtained. In the low DPD activity group, 9 of 11 patients had 5-FU-related side effects (mucositis, diarrhea, myelotoxicity, angina pectoris, hypertension). In 3 patients, no change of the therapy was needed, in 3 patients symptoms could be reversed by dose reduction of 5-FU while in 3 patients interruption of 5-FU therapy was needed. In the medium DPD activity group, mild toxicity (diarrhea, transitory hypertension) occurred in 5 of 29 and in the high activity group (diarrhea) in 1 of 8 patients, respectively. In these last two groups, no dose reduction of 5-FU was necessary. The present study furnished further evidence for the possible correlation between the 5-FU side effects and DPD function. Consequently, it is recommended to measure DPD activity prior to 5-FU based chemotherapy, which might be helpful in avoiding drug-related toxicity by adjusting the dose of 5-FU individually.
Residual Disease and Presence of Human Papillomavirus after Conization
Authors: Kanamori Yasunobu , Kigawa Junzo , Minagawa Yukihisa , Irie Takashi , Oishi Testuro , Itamochi Hiroaki , Cheng Xiusi , Terakawa Naoki 
Published: April 2003

The objective of this study was to evaluate the incidence of residual disease and the presence of human papillomavirus (HPV) after conization. Data on 53 patients with carcinoma in situ or microinvasive carcinoma who underwent hysterectomy less than 2 months after conization were examined. Seven of 53 patients (13%) had positive margins. In 4 of these 7 patients (57%), residual disease was found in the postconization hysterectomy specimen. Two of 46 patients (4%) with negative margins also had residual disease. HPV DNA was detected by PCR in 27 of 53 conization specimens and in 2 postconization hysterectomy specimens. Of 2 patients, 1 did not have residual disease. Residual disease could be present even with a negative conization margin, and HPV DNA may be found in a histologically normal cervix after conization.
Mitomycin C, Vinorelbine, Carboplatin plus Granulocyte-Macrophage Colony-Stimulating Factor for Treatment of Advanced Non-Small Cell Lung Carcinoma
Authors: Hejna M. , Kornek G.V. , Raderer M. , Marosi L. , Schneeweiss B. , Greul R. , Weinländer G. , Valencak J. , Huber H. , Scheithauer W. 
Published: April 2003

<b>Background:</b> The therapeutic potential of chemotherapy in the treatment of recurrent or metastatic non-small cell lung carcinoma (NSCLC) seems modest. Thus, the search for novel agents and combination regimens with a superior therapeutic index has a high priority. The present combination regimen consisting of mitomycin C, vinorelbine, carboplatin and granulocyte-macrophage colony-stimulating factor (GM-CSF) was chosen because of the known activity of these agents in NSCLC and their potential drug synergism without (nonhematologic) cross-toxicity. To prevent/counteract neutropenia that was assumed to represent the dose-limiting toxicity, the hematopoietic growth factor GM-CSF was routinely adminstered. The objective of our trial was to determine the antitumor efficacy and tolerance of this combination regimen in patients with advanced NSCLC. <b>Patients and Methods:</b> Forty consecutive patients with nonresectable, measurable NSCLC (stage IIIB, 7; stage IV, 33) were treated with an intravenous combination chemotherapy regimen consisting of mitomycin C 8 mg/m<sup>2</sup> on day 1, vinorelbine 40 mg/m<sup>2</sup> on days 1 and 21, and carboplatin 250 mg/m<sup>2</sup> on days 1 and 21; GM-CSF 5 µg/kg was administered subcutaneously on days 2–8 and 22–28. Treatment cycles were repeated every 6 weeks. All patients are evaluable in terms of toxicity and response assessment. A total of 123 courses was administered. <b>Results:</b> Objective tumor response was notes in 16 patients (40%; 95% confidence interval 24.9–56.7%), including 3 (7.5%) complete and 13 partial responses. There was no change in 12 (31.5%) patients, and 12 had progressive disease. Median duration of response was 6 (range 3–15) months, the median time to progression for all patients was 6.2 (range 1–17.5) months, and the projected median survival time was 8.7 (range 1–23.3) months; the 1-year survival rate was 27.5%. Myelosuppression was the most frequently encountered adverse reaction; WHO grade 3 or 4 granulocytopenia and/or thrombocytopenia occurred in 42.5 and 12.5%, respectively. Other toxicities were generally mild to moderate, and always fully reversible. <b>Conclusion:</b> With a 40% major response rate and disease stabilization in one additional third of our patients, this drug combination seems to have significant activity against advanced metastatic NSCLC. Due to its subjective tolerance and ease of administration, further investigation of this regimen in the palliative-intent care setting seems warranted.
Lack of p53-Mediated G1 Arrest in Response to an Environmental Carcinogen
Authors: Khan Qasim A. , Vousden Karen H. , Dipple Anthony 
Published: April 2003

The environmental carcinogen, 5-methylchrysene, is a component of cigarette smoke. Its reactive metabolite, <i>anti</i>-5-methylchrysene-1,2-dihydrodiol-3,4-epoxide (5-MeCDE) mainly reacts with the N<sup>2</sup>-position of guanine residues in the DNA molecule. In this study, we demonstrate that the tumor suppressor protein p53 is stabilized in response to DNA damage by 5-MeCDE but fails to induce the cells’ protective mechanism of G1 arrest in the human breast carcinoma cell line, MCF-7. In contrast, actinomycin D treatment of these cells did lead to G1 arrest. Western analyses revealed that, though both actinomycin D and 5-MeCDE treatment stabilized p53, only trace levels of p21<sup>waf1/cip1</sup> were seen in the latter case. This lack of p21<sup>waf1/cip1</sup> expression in 5-MeCDE-treated cells is attributed to a stealth characteristic of this environmental carcinogen that allows it to damage DNA and still escape the p53-mediated cellular defense mechanism of G1 arrest.
Evaluation of the Therapeutic Effect of Transcatheter Arterial Embolization for Hepatocellular Carcinoma
Authors: Okusaka Takuji , Okada Shuichi , Ueno Hideki , Ikeda Masafumi , Yoshimori Masayoshi , Shimada Kazuaki , Yamamoto Junji , Kosuge Tomoo , Yamasaki Susumu , Iwata Ryoko , Furukawa Hiroyoshi , Moriyama Noriyuki , Sakamoto Michiie , Hirohashi Setsuo 
Published: April 2003

Transcatheter arterial embolization (TAE) has been widely performed for patients with hepatocellular carcinoma (HCC). However, the method of evaluating the therapeutic effect of TAE has not been established. We examined the rate of necrotic area to whole tumor (TN) by CT, the tumor regression rate (TR) and the reduction rate in serum α-fetoprotein (AFP) levels in patients with HCC who received hepatic resection within 3 months after TAE. In the evaluation of TN, the lipiodol accumulation in tumor was regarded as being necrotic. Rates of necrotic area, which were also examined pathologically (PN) in resected tumors, were compared with TN, TR and AFP reduction rates, respectively. Eighty-eight patients were enrolled in this study, and there was a significant positive correlation between TN and PN (r = 0.80, p < 0.001). Although TR significantly correlated to PN (p = 0.001), the correlation coefficient between them was low (r = 0.34). The correlation coefficients between AFP reduction rate and PN was 0.76 (p < 0.001) in 26 patients (30%) with an AFP level ≥200 ng/ml before TAE. The evaluation method using lipiodol accumulation in CT is the most useful for assessing the therapeutic effect of TAE, particularly when a sufficiently long interval exists between TAE and the evaluation, because of the highest correlation coefficient between TN and PN, and the availability of TN for all patients. The reduction rate in serum AFP levels was also useful in patients with AFP levels >200 ng/ml before treatment.
Aminopeptidase A Expression in Cervical Neoplasia and Its Relationship to Neoplastic Transformation and Progression
Authors: Fujimura Hidehiko , Ino Kazuhiko , Nagasaka Tetsuro , Nakashima Nobuo , Nakazato Hiroshi , Kikkawa Fumitaka , Mizutani Shigehiko 
Published: April 2003

Aminopeptidase A (AP-A) is a cell surface metallopeptidase which specifically cleaves the amino-terminal acidic residue from peptide substrates such as angiotensin II. AP-A is identical to the differentiation-related antigen, murine BP-1 or human kidney gp160, and is involved in regulating cell differentiation and/or neoplastic transformation of certain normal and transformed cells. We examined expression of AP-A in premalignant and malignant lesions of the uterine cervix, and investigated whether its expression was related to disease progression and neoplastic transformation. Formalin-fixed, paraffin-embedded tissue sections including 14 cervical intraepithelial neoplasms (CIN) and 23 invasive squamous cell carcinomas (SCC) were immunohistochemically evaluated. AP-A was localized in the basal cell layer in normal squamous epithelium. In CIN, AP-A expression was found on dysplastic cells, and increased with the severity of the precancerous lesions. In invasive cancer, 18 of 19 non-keratinizing-type SCCs and none of 4 keratinizing-type SCCs expressed AP-A. In addition, AP-A immunoreactivity was significantly correlated with proliferating cell nuclear antigen expression in both CIN and SCC cases. Furthermore, angiotensin II type 1 receptor was present in all AP-A-positive SCCs. These results indicate that AP-A is upregulated as the lesion progresses toward carcinoma in the cervical epithelium, and suggest that AP-A may play a regulatory role in neoplastic transformation and disease progression in cervical neoplasms and may serve as a potential tumor marker during cervical neoplasia development.
Olive Oil Supplementation in Healthy Adults: Effects in Cell Membrane Fatty Acid Composition and Platelet Function
Authors: Vicario Isabel M. , Malkova Dala , Lund Elizabeth K. , Johnson Ian T. 
Published: April 2003

Ten healthy volunteers were given a daily supplement of 30 g olive oil for 6 weeks in order to evaluate how it would affect cell membrane composition and ultimately platelet function. Fasting blood and cheek cell samples were taken before commencing the study, after 21 and 42 days of supplementation and also at 30 days after finishing the supplement (washout). C18:1<i>n</i>-9 was significantly increased (p < 0.01) in platelet and cheek cell phospholipids. Erythrocytes were not good markers for C18:1<i>n</i>-9 intake and no significant change was found in this tissue. There was a small nonsignificant decrease in platelet phospholipid 20:4<i>n</i>-6 after the supplementation, in accordance with previously published results. C18:1<i>n</i>-9 did not persist in platelet membranes after the volunteers stopped consuming the olive oil supplement, but in erythrocytes a significant increase (p < 0.05) was found after the washout period. None of these changes in fatty acid composition in the different tissues were related to significant changes in serum cholesterol-related variables or in clotting factors or adenosine diphosphate-induced platelet aggregation.
Australian Food Sources and Intakes of Omega–6 and Omega–3 Polyunsaturated Fatty Acids
Authors: Ollis Tennille E. , Meyer Barbara J. , Howe Peter R.C. 
Published: April 2003

<i>Background/Aims:</i> Both ω–6 and ω–3 polyunsaturated fatty acids (PUFAs) are recognised as essential nutrients in the human diet, yet we have little information on the extent to which different food sources contribute to their intake. The aim of the present study was to ascertain the daily intakes and food sources of ω–6 and ω–3 PUFAs in our local community. <i>Methods:</i> Three-day food records were obtained from 83 healthy adults living in the Illawarra region of New South Wales. The PUFA composition of the foods which they consumed was derived from food composition tables and recently published food analysis data. <i>Results:</i> Polyunsaturated margarine, nuts/seeds, bread, snacks/desserts and takeaway foods were important sources of ω–6 PUFAs, while canola oil and margarine, takeaway foods, snacks/desserts and bread were sources of α-linolenic acid (LNA), an ω–3 PUFA. As expected, fish was the main source of the very long chain (VLC) ω–3 PUFAs, i.e. eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA), to which significant health benefits are attributed. An unexpected finding, however, was that, due to the large amount eaten, meat was also a major contributor (29%) to the dietary intake of VLC ω–3 PUFAs. Median intakes of ω–6 and ω–3 PUFAs were 9.9 and 1.2 g/day, respectively, resulting in a dietary ω–6:ω–3 ratio of 8:1. The median intake of VLC ω–3 PUFA was 0.18 g/day. <i>Conclusion:</i> We have identified food sources and intakes of PUFAs for an Australian subpopulation differentiating between ω–6 and ω–3 PUFAs. Whilst canola and fish were the primary sources of LNA and VLC ω–3 PUFAs respectively, we found that meat made a significant contribution to VLC ω–3 PUFA intake.
Eicosapentaenoic Acid Inhibits Mitogen-Induced Endothelin-1 Production and DNA Synthesis in Cultured Bovine Mesangial Cells
Authors: Nitta Kosaku , Uchida Keiko , Tsutsui Takaaki , Honda Kazuho , Kawashima Akira , Yumura Wako , Nihei Hiroshi 
Published: April 2003

The present study was designed to examine whether eicosapentaenoic acid (EPA) inhibits the production of basal or stimulated endothelin (ET)-1 by platelet-derived growth factor (PDGF)-BB or epidermal growth factor (EGF), and DNA synthesis in cultured bovine mesangial cells. PDGF-BB and EGF stimulated ET-1 secretion in a dose-dependent fashion in these cells. EPA (10–100 µ<i>M</i>) exhibited dose-related inhibition of PDGF-BB- and EGF-stimulated ET-1 secretion. EPA had no inhibitory effects on basal ET-1 secretion in these cells. Moreover, 50 µ<i>M</i> EPA significantly attenuated PDGF-BB- and EGF-stimulated [<sup>3</sup>H]thymidine incorporation into mesangial cells. Receptor-binding experiments showed that EPA competitively inhibited <sup>125</sup>I-PDGF-BB or <sup>125</sup>I-EGF binding to mesangial cell surface receptors. Scatchard analysis for PDGF-BB receptor or EGF receptor revealed a linear regression fit and one binding site. Pretreatment with 50 µ<i>M</i> EPA suppressed the number of maximum binding sites, but did not affect the K<sub>d</sub> values. These results indicate that EPA potentially inhibits mesangial cell ET-1 production, when stimulated by PDGF-BB or EGF. This inhibitory effect of EPA could be related to the attenuation of mesangial cell proliferation via inhibition of the binding of PDGF-BB or EGF to their receptors due to alteration of the physicochemical characteristics of the cell membrane.
A Cluster of Bloodstream Infections and Pyrogenic Reactions among Hemodialysis Patients Traced to Dialysis Machine Waste-Handling Option Units
Authors: Jochimsen Elise M. , Frenette Charles , Delorme Monique , Arduino Matthew , Aguero Sonia , Carson Loretta , Ismaïl Johanne , Lapierre Stephen , Czyziw Elizabeth , Tokars Jerome I. , Jarvis William R. 
Published: April 2003

From June 17 through November 15, 1995, ten episodes of <i>Enterobacter cloacae</i> bloodstream infection and three pyrogenic reactions occurred in patients at a hospital-based hemodialysis center. In a case-control study limited to events occurring during October 1–31, 1995, seven dialysis sessions resulting in <i>E. cloacae</i> bacteremia or pyrogenic reaction without bacteremia were compared with 241 randomly selected control sessions. Dialysis machines were examined, dialysis fluid and equipment were cultured, and <i>E. cloacae</i> isolates were genotyped by pulsed-field gel electrophoresis. Each dialysis machine had a waste-handling option (WHO) through which dialyzer-priming fluid was discarded before each dialysis session; in 7 of 11 machines, one-way check valves designed to prevent backflow from the WHO into patient bloodlines were dysfunctional. In the case-control study, case sessions were more frequent when machines with ≥1 dysfunctional check valves were used. <i>E. cloacae</i> with identical pulsed-field gel electrophoresis patterns were isolated from case patients, dialysis fluid, station drains, and WHO units. Our investigation shows that bloodstream infections and pyrogenic reactions were caused by backflow from contaminated dialysis machine WHO units into patient bloodlines. The outbreak was terminated when WHO use was discontinued, check valves were replaced, and dialysis machine disinfection was enhanced.
Improvement of Myocardial Fatty Acid Metabolism through <i>L</i>-Carnitine Administration to Chronic Hemodialysis Patients
Authors: Sakurabayashi Tai , Takaesu Yoshiji , Haginoshita Susumu , Takeda Tetsurou , Aoike Ikuo , Miyazaki Shigeru , Koda Yutaka , Yuasa Yasuko , Sakai Shinji , Suzuki Masashi , Takahashi Sachio , Hirasawa Yoshihei , Nakamura Takamichi 
Published: April 2003

The concentration of carnitine, which is essential to fatty acid metabolism, can decrease markedly in patients on long-term hemodialysis coincident with life-threatening cardiac damage. However, administration of <i>L</i>-carnitine improves the myocardial function of these patients. To evaluate the underlying events of this phenomenon, we used recently developed technology, <sup>123</sup>I-labeled β-methyl-<i>p</i>-iodophenyl-pentadecanoic acid (BMIPP) myocardial scintigraphy, as a test of myocardial fatty acid metabolism. Our results showed that the free carnitine concentration (19.2 ± 6.5 μmol/l) was lower in 11 chronically dialyzed patients than in 8 healthy controls (49.3 ± 7.7 μmol/l, p < 0.0001). Additionally the heart to mediastinal ratio (H/M) of BMIPP was higher for these patients than for the controls (1.91 ± 0.19 vs. 1.52 ± 0.24, p < 0.005), and the patients’ washout rate (WOR) of BMIPP was lower (17.2 ± 6.0 vs. 22.8 ± 4.2%, p < 0.05). After <i>L</i>-carnitine was administered orally to the patients at doses of 1 g/day for 1 month and 0.5 g/day for the following month, the concentration of free carnitine in their sera increased to 85.4 ± 27.0 μmol/l (p < 0.0001). Although the H/M ratio did not change (1.89 ± 0.20) with this treatment, their WOR increased to 21.9 ± 6.6% (p < 0.001), similar to that of controls. The left ventricular end-diastolic dimension and left ventricular fractional shortening remained unchanged, as shown by echocardiography. The results presented here denote that a carnitine deficiency in chronically hemodialyzed patients disrupts their myocardial fatty acid metabolism, which is improved by <i>L</i>-carnitine supplementation.
Dialysis-Associated Renal Cystic Disease Resembling Autosomal Dominant Polycystic Kidney Disease: A Report of Two Cases
Authors: Bakir Asad A. , Hasnain Mohammed , Young Stephanie , Dunea George 
Published: April 2003

Acquired renal cystic disease is common in patients receiving dialysis. Characteristically, the kidneys are small or, less often, normal in size, and the cysts are usually less than 0.6 cm in diameter. We present here 2 patients who, after 5 and 7 years on hemodialysis, developed marked renal enlargement, with large cysts in the kidneys and, in 1 patient, in the liver as well; the appearance on ultrasonography and computed tomography was indistinguishable from autosomal dominant polycystic kidney disease. Before starting dialysis the first patient was a 19-year-old man who developed renal shutdown from crescentic glomerulonephritis, and the second patient was a 33-year-old man who developed end-stage renal failure from malignant hypertension. Neither patient had renal cysts at the onset of end-stage renal failure.
<i>Staphylococcus lugdunensis</i> Pulmonary Valve Endocarditis in a Patient on Chronic Hemodialysis
Authors: Kamaraju Sailaja , Nelson Karin , Williams David N. , Ayenew Woubeshet , Modi Kulwant Singh 
Published: April 2003

We describe a case of <i>Staphylococcus lugdunensis</i> pulmonary valve endocarditis in a 65-year-old woman on chronic hemodialysis and provide a review of previously reported cases. The patient presented with fever and altered mental status, but had no other localizing symptoms or signs; coagulase-negative staphylococcus (subsequently identified as <i>S. lugdunensis</i>) was isolated from two sets of blood cultures. Transthoracic and transesophageal echocardiograms showed a large (2.3 × 3.1 cm) vegetation on the pulmonary valve with moderate valvular insufficiency. The patient was treated with 6 weeks of antibiotic therapy and is stable 4 months following the completion of therapy; no surgical intervention was performed. Of the 28 previously reported cases of <i>S. lugdunensis</i> endocarditis, only 1 had previously survived with medical therapy alone. This is the 3rd case report of <i>S. lugdunensis</i> endocarditis in a patient on hemodialysis; the presumed portal of entry in this and previously reported cases was the vascular access device. Endocarditis due to this organism is characterized by a high mortality, rapid tissue destruction, and a predilection for native valves. Because the clinical outcome is much more favorable with valvular replacement, speciation of the organism assumes great importance in defining the therapeutic approach.