Showing papers by "Gdańsk Medical University published in 2004"

Postoperative Irradiation With or Without Concomitant Chemotherapy for Locally Advanced Head and Neck Cancer

Abstract: background We compared concomitant cisplatin and irradiation with radiotherapy alone as adjuvant treatment for stage III or IV head and neck cancer. methods After undergoing surgery with curative intent, 167 patients were randomly assigned to receive radiotherapy alone (66 Gy over a period of 6 1 ⁄ 2 weeks) and 167 to receive the same radiotherapy regimen combined with 100 mg of cisplatin per square meter of body-surface area on days 1, 22, and 43 of the radiotherapy regimen. results After a median follow-up of 60 months, the rate of progression-free survival was significantly higher in the combined-therapy group than in the group given radiotherapy alone (P=0.04 by the log-rank test; hazard ratio for disease progression, 0.75; 95 percent confidence interval, 0.56 to 0.99), with 5-year Kaplan–Meier estimates of progression-free survival of 47 percent and 36 percent, respectively. The overall survival rate was also significantly higher in the combined-therapy group than in the radiotherapy group (P=0.02 by the log-rank test; hazard ratio for death, 0.70; 95 percent confidence interval, 0.52 to 0.95), with five-year Kaplan–Meier estimates of overall survival of 53 percent and 40 percent, respectively. The cumulative incidence of local or regional relapses was significantly lower in the combined-therapy group (P=0.007). The estimated five-year cumulative incidence of local or regional relapses (considering death from other causes as a competing risk) was 31 percent after radiotherapy and 18 percent after combined therapy. Severe (grade 3 or higher) adverse effects were more frequent after combined therapy (41 percent) than after radiotherapy (21 percent, P=0.001); the types of severe mucosal adverse effects were similar in the two groups, as was the incidence of late adverse effects. conclusions Postoperative concurrent administration of high-dose cisplatin with radiotherapy is more efficacious than radiotherapy alone in patients with locally advanced head and neck cancer and does not cause an undue number of late complications.

Race-Specific Differences in Endothelial Function Predisposition of African Americans to Vascular Diseases

Abstract: Background— The prevalence of the endothelium-impaired function disorders, such as hypertension and diabetes mellitus, and the severity of their complications are considerably greater in blacks than whites. Evidence has accumulated that superoxide (O2−) production and its interaction with nitric oxide (NO), yielding the strong oxidant peroxynitrite (ONOO−), play central roles in vascular pathophysiology. We hypothesized that the differences in endothelial NO/O2−/ONOO− metabolism may highlight the potential predisposition to endothelial dysfunction and cardiovascular complications prevalent in blacks. Methods and Results— Highly sensitive tandem electrochemical NO/O2−/ONOO− nanosensors were positioned in single human umbilical vein endothelial cells (HUVECs) isolated from blacks and whites, and the kinetics of NO/O2−/ONOO− release were recorded in vitro. HUVECs were also analyzed by Western immunoblotting and enzyme activity assays for NAD(P)H-oxidase and endothelial NO synthase (eNOS). Compared with white...

Independent Association Between Plasma Leptin and C-Reactive Protein in Healthy Humans

Abstract: Background— C-reactive protein (CRP) is synthesized from the liver and is regulated by cytokines, especially interleukin-6. Leptin, the adipocyte-derived protein product of the ob gene, is related ...

Liver transplantation for hepatoblastoma: Results from the International Society of Pediatric Oncology (SIOP) study SIOPEL‐1 and review of the world experience

Abstract: BACKGROUND: For hepatoblastoma (HB) that remains unresectable by partial hepatectomy after chemotherapy, total hepatectomy with orthotopic liver transplantation (LTX) has been advocated as the best treatment option. The role of LTX in the overall management of HB is still, however, unclear. PROCEDURE: The results of LTX from the first study of HB by the International Society of Pediatric Oncology, SIOPEL-1, were analyzed. In addition, the world experience of LTX for HB was extensively reviewed. Twelve patients in the SIOPEL-1 study underwent a LTX. Median (range) follow-up at Dec. 31, 2001 was 117 months (52-125) since LTX. RESULTS: Overall survival at 10 years post-LTX was 85% for the seven children who received a "primary LTX" and 40% for the 5 children who underwent a "rescue LTX" after previous partial hepatectomy. In the world experience (147 cases), the overall survival rate at 6 year post-LTX was 82% for 106 patients who received a "primary LTX" and 30% for 41 patients who underwent a "rescue LTX." Multivariate analysis of patients undergoing primary LTX showed that only macroscopic venous invasion had a significant impact (P-value: 0.045 with a hazard ratio of 2.96) on overall survival. CONCLUSIONS: Orthotopic LTX has added a new dimension to the treatment of HB unresectable by partial hepatectomy. Because of the rarity of the disease and to optimize results, children with extensive HB should be treated in centers with surgical expertise in pediatric major liver resection and LTX, in close collaboration with pediatric oncologists, radiologists, and histopathologists.

Evaluating the cytotoxicity of ionic liquids using human cell line HeLa.

Abstract: This paper presents cytotoxicity data of selected imidazolium ionic liquids evaluated in vitro on the human tumor cell line HeLa. It was found that for 1-n-butyl-3-methylimidazolium entities the toxicity depends strongly on the associated anion; EC50 values are lowest for tetrafluoroborate. No direct dependence of the reduced effect concentration was found on elongating the short, methyl chain to ethyl or n-hexyl. Only for the ionic liquid with an n-decyl chain, the longest one studied, did higher hydrophobicity result in a EC50 one order of magnitude lower than that obtained with the n-butyl entity. The effect concentrations of imidazolium ionic liquids in the HeLa system used are lower than the values obtained for conventional organic solvents such as dichloromethane, toluene or xylene.

The changing pattern of Kaposi sarcoma in patients with HIV, 1994-2003: The EuroSIDA study

Abstract: BACKGROUND The introduction of highly active antiretroviral therapy (HAART) has radically changed the clinical course of human immunodeficiency virus (HIV) infection. The goals of the current study were to assess the change in the incidence of Kaposi sarcoma (KS) among European patients with HIV since the introduction of HAART and to identify the factors associated with the development of KS among patients receiving HAART. METHODS The incidence of KS and the factors associated with the development of this malignancy in patients receiving HAART were evaluated using Poisson regression. Patients examined in the current study were among the 9803 individuals with HIV who were enrolled in the EuroSIDA study, a pan-European multicenter investigation. RESULTS There was an estimated annual reduction of 39% (95% confidence interval [CI], 35–43%; P < 0.0001) in the incidence of KS between 1994 and 2003. The proportion of acquired immunodeficiency syndrome (AIDS) diagnoses made due to KS during prospective follow-up ranged from 4.1% to 7.5%, and there was no significant change over time in this figure (P = 0.97). Four thousand fourteen patients began receiving HAART during prospective follow-up; 41 of these 4014 were subsequently diagnosed with KS (1.0%). After adjustment in multivariate analyses, patients with higher current CD4 counts were found to have a decreased incidence of KS (incidence rate ratio [IRR], 0.60; 95% CI, 0.53–0.68; P < 0.0001), as were those for whom more time had elapsed since the initiation of HAART (IRR, 0.77; 95% CI, 0.60–0.98; P = 0.037). In contrast, homosexual men were found to have a significantly increased incidence of KS (IRR, 2.12; 95% CI, 1.00–4.54; P = 0.050) CONCLUSIONS The current incidence of KS among patients with HIV is less than 10% of the incidence reported in 1994; the proportion of AIDS diagnoses made on the basis of KS diagnoses remains near 6%. Most individuals who developed KS while receiving HAART began treatment with low CD4 cell counts and developed KS within 6 months of the initiation of HAART. There continues to be an increased incidence of KS among homosexual men and a greatly reduced incidence of KS among patients with higher CD4 counts. Cancer 2004. © 2004 American Cancer Society.

Ixodes ricinus as a vector of Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum and Babesia microti in urban and suburban forests.

Abstract: QWKHVXEXUEDQDQGXUEDQIRUHVWVLQWKHFLWLHVRI*GDVN6RSRWDQG*G\QLD (northern Poland), Ixodes ricinus ticks should be considered as the vector of pathogenic microorganisms that may cause significant diseases in wild and domestic animals and humans. These microorganisms include etiologic agents of Lyme disease, human anaplasmosis (HA) and babesiosis: Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum and Babesia microti, respectively. DNA extracts from 701 ticks collected in 15 localities were examined by PCR for the simultaneous detection of these 3 pathogens. Overall, 14% were infected with A. phagocytophilum followed by 12.4% with B. burgdorferi s.l. and 2.3% with B. microti. In total, the percentage of infected females (32.9%) was 2.4 times higher than in males (13.7%) and 3.2 times higher than in nymphs (10.3%). Among adult ticks (n = 303), 8.3% were dually infected with A. phagocytophilum and B. burgdorferi s.l., 2.0% with the agent of human anaplasmosis and B. microti and 0.3% with borreliae and B. microti.

Usefulness of Toxoplasma gondii-Specific Recombinant Antigens in Serodiagnosis of Human Toxoplasmosis

Abstract: Toxoplasma gondii SAG1, GRA1, and GRA7 recombinant antigens may be regarded as tools for the detection of T. gondii immunoglobulin G antibodies in persons with chronic and acute toxoplasmosis. GRA7 is more correlated with acute toxoplasmosis. A combination of these antigens will increase the sensitivity of enzyme-linked immunosorbent assays.

Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia. Multicenter, phase III study

Abstract: To assess the efficacy of an original DAC-7 regimen: daunorubicine (DNR) 60 mg/m2/day, days 1-3; cytarabine (AraC) 200 mg/m2/day, days 1-7; cladribine (2-CdA) 5 mg/m2/day, days 1-5, 400 untreated adult acute myeloid leukemia patients (including 63 with preceding myelodysplastic syndrome), aged 45 (16-60) years were randomized to either DAC-7 (n=200) or DA-7 (without 2-CdA, n=200). The overall CR rate equaled 72% for DAC-7 and 69% for DA-7 arm (P=NS). After a single course of DAC-7 induction, the CR rate equaled 64% and was significantly higher compared to 47% in the DA-7 arm (P=0.0009). Median hospitalization time during the induction was 7 days shorter for DAC-7 compared to the DA-7 group (33 vs 40 days, P=0.002). Toxicity was comparable in both groups. The probability of 3-year leukemia-free survival (LFS) for DAC-7 and DA-7 group equaled 43 and 34%, respectively (P=NS). There was a trend toward higher LFS rate for patients aged >40 years receiving DAC-7 compared with DA-7 regimen (44 vs 28%, P=0.05). This study proves that addition of 2-CdA increases antileukemic potency of DNR+AraC regimen, thus resulting in a higher CR rate after one induction cycle when compared to DA-7, without additional toxicity. It shortens hospitalization time and may improve long-term survival in patients aged >40 years.

Colostrinin (a naturally occurring, proline-rich, polypeptide mixture) in the treatment of Alzheimer's disease.

Abstract: This study was designed to confirm or negate findings from earlier trials demonstrating that Colostrinin, a novel compound derived from ewes' colostrum, has potential in the treatment of mild or moderate Alzheimer's Disease (AD). 105 patients were recruited from six psychiatric centres in Poland. The trial consisted of a 15 week double-blind phase comparing Colostrinin with placebo, followed by a second 15 week open labelled phase when all patients received Colostrinin. The dosage of Colostrinin was 100 microg on alternate days for three weeks followed by two weeks drug-free. This cycle was repeated three times for each phase. The primary outcome measures used were Alzheimer's Disease Assessment Scale-cognitive portion (ADAS-cog) and Clinical Global Impression of Change (CGIC). Secondary outcome measures were Instrumental Activities of Daily Living (IADL); Mini-Mental State Examination (MMSE); ADAS-non cognitive test (ADAS-non cog); and overall Patient Response. The main outcome measures were assessed at week 15 when active was compared with placebo but all parameters were evaluated at baseline, week 15 and week 30. Two separate statistical analyses were undertaken, a Full Sample Analysis (FSA) in which all missing values were replaced with the worst result observed and a Valid for Efficacy (VFE) analysis in which those patients who had serious protocol violations were excluded. This resulted in 14 patients being excluded from the VFE-analysis. The FSA analysis at week 15 showed a stabilizing effect of Colostrinin on cognitive function in ADAS-cog (p = 0.02) and on daily function in IADL (p = 0.02). The overall patient response was also in favour of the active (p = 0.03). Patients graded as mild on entry also showed a superior response of ADAS-cog compared with more advanced cases (p = 0.01). Evidence from this study indicates an early beneficial effect on cognitive symptoms and daily function. Colostrinin has potential value in the treatment AD.

Epidemiology and clinical features of vivax malaria imported to Europe: sentinel surveillance data from TropNetEurop.

Abstract: Plasmodium vivax is the second most common species among malaria patients diagnosed in Europe, but epidemiological and clinical data on imported P. vivax malaria are limited. The TropNetEurop surveillance network has monitored the importation of vivax malaria into Europe since 1999. To present epidemiological and clinical data on imported P. vivax malaria collected at European level. Data of primary cases of P. vivax malaria reported between January 1999 and September 2003 were analysed, focusing on disease frequency, patient characteristics, place of infection, course of disease, treatment and differences between network-member countries. Within the surveillance period 4,801 cases of imported malaria were reported. 618 (12.9%) were attributed to P. vivax. European travellers and immigrants were the largest patient groups, but their proportion varied among the reporting countries. The main regions of infection in descending order were the Indian subcontinent, Indonesia, South America and Western and Eastern Africa, as a group accounting for more than 60% of the cases. Regular use of malaria chemoprophylaxis was reported by 118 patients. With 86 (inter-quartile range 41–158) versus 31 days (inter-quartile range 4–133) the median symptom onset was significantly delayed in patients with chemoprophylaxis (p < 0.0001). Common complaints were fever, headache, fatigue, and musculo-skeletal symptoms. All patients survived and severe clinical complications were rare. Hospitalization was provided for 60% and primaquine treatment administered to 83.8% of the patients, but frequencies varied strongly among reporting countries. TropNetEurop data can contribute to the harmonization of European treatment policies.

Identification of Tissue-Restricted Transcripts in Human Islets

Abstract: The purpose of our study was to identify transcripts specific for tissue-restricted, membrane-associated proteins in human islets that, in turn, might serve as markers of healthy or diseased islet cell masses. Using oligonucleotide chips, we obtained gene expression profiles of human islets for comparison with the profiles of exocrine pancreas, liver, and kidney tissue. As periislet presence of type 1 interferon is associated with the development of type 1 diabetes, the expression profile of human islets treated ex vivo with interferon-2 (IFN2) was also determined. A set of genes encoding transmembrane- or membrane-associated proteins with novel islet-restricted expression was resolved by determining the intersection of the islet set with the complement of datasets obtained from other tissues. Under the influence of IFN2, the expression levels of transcripts for several of the identified gene products were up- or down-regulated. One of the islet-restricted gene products identified in this study, vesicular monoamine transporter type 2, was shown to bind [ 3 H]dihydrotetrabenazine, a ligand with derivatives suitable for positron emission tomography imaging. We report here the first comparison of gene expression profiles of human islets with other tissues and the identification of a target molecule with possible use in determining islet cell masses. (Endocrinology 145: 4513– 4521, 2004)

Determination of pKa by pH gradient reversed-phase HPLC.

Abstract: pH gradient reversed-phase HPLC consists of a programmed increase during the chromatographic run of the eluting power of the mobile phase with regard to ionizable analytes. On the analogy of the conventional organic modifier gradient RP HPLC, in the pH gradient mode, the eluting strength of the mobile phase increases due to its increasing (with acid analytes) or decreasing (with basic analytes) pH, whereas the content of organic modifier is kept constant. We have shown previously that the pH gradient separations are technically possible using standard chromatographic equipment. Here we demonstrate that the method is uniquely suitable to determine pKa values of analytes. A strict theoretical model is proposed to determine pKa values based on the retention data from a pH gradient RP HPLC run. The pKa data so obtained are discussed in relation to the concentration of methanol in the mobile phase, the type of stationary phase, and the duration of the gradient. The pKa values determined by the pH gradient meth...

Prophylactic submucosal saline-adrenaline injection in colonoscopic polypectomy : Prospective randomized study

Abstract: Background Endoscopic polypectomy is a standard method of treatment of gastrointestinal polyps, but is associated with substantial risk of complications The most common is hemorrhage, the rate of which varied between 03%, and 6% Various prophylactic techniques have been used to reduce this incidence The aim of this study was to establish whether the prophylactic injection of adrenaline–saline solution reduces the risk of postpolypectomy bleeding in colonoscopic polypectomy

Endothelial NADH/NADPH-dependent enzymatic sources of superoxide production: relationship to endothelial dysfunction

Abstract: There is growing evidence that endothelial dysfunction, which is often defined as the decreased endothelial-derived nitric oxide (NO) bioavailability, is a crucial factor leading to vascular disease states such as hypertension, diabetes, atherosclerosis, heart failure and cigarette smoking. This is due to the fact that the lack of NO in endothelium-dependent vascular disorders contributes to impaired vascular relaxation, platelet aggregation, increased vascular smooth muscle proliferation, and enhanced leukocyte adhesion to the endothelium. During the last several years, it has become clear that reduction of NO bioavailability in the endothelium-impaired function disorders is associated with an increase in endothelial production of superoxide (O(2)(*-)). Because O(2)(*-) rapidly scavenges NO within the endothelium, a reduction of bioactive NO might occur despite an increased NO generation. Among many enzymatic systems that are capable of producing O(2)(*-), NAD(P)H oxidase and uncoupled endothelial NO synthase (eNOS) apparently are the main sources of O(2)(*-) in the endothelial cells. It seems that O(2)(*-) generated by NAD(P)H oxidase may trigger eNOS uncoupling and contribute to the endothelial balance between NO and O(2)(*-). That is maintained at diverse levels.

Arterial hypertension in Poland in 2002.

Abstract: Arterial hypertension represents a serious medical, social and economic problem in Poland. Owing to a small number of studies concerning HT epidemiology in Poland and large differences in methodology, it is difficult to make an objective verification of the changes regarding principal parameters in our country within the last decade. Important programme for the assessment of the situation in our country is NATPOL PLUS, carried out in the year 2002 on a representative sample of 3051 adult Polish residents aged between 18 and 93 years, using the current diagnostic criteria for arterial hypertension (blood pressure readings obtained at three separate visits in cases of newly detected HT, different cuff sizes for different arm circumference, age range 18-93 years, rejection of first measurement during initial screening visit). Prevalence of HT in Poland is 29%, awareness-67%, and effectiveness of treatment-12%. This means that while HT affects about 8.4 million adult Poles, only 1 million of them get effective treatment. Moreover, as much as 8.7 million Poles have high normal blood pressure and they should apply active prevention. The awareness, detection and control of hypertension is much worse in men than in women. A series of NATPOL studies indicated over the period 1994-2002 a significant and rapid decrease in the awareness of one's own blood pressure among the adult Polish population, especially in small towns and villages, among less educated people, and in males.

A retrospective comparative study of surgery followed by chemotherapy vs. non-surgical management in limited-disease small cell lung cancer

Abstract: Objective: The role of surgery in limited SCLC is still a matter of controversy. Even though the response rates to chemotherapy are very high, prognosis of SCLC patients has remained poor with a median survival of only 12 – 14 months for limited disease. High incidence of local relapses after chemotherapy in limited-stage SCLC led to reassessment of the role of local treatment in the multimodality management of this tumor. Methods: We performed retrospective comparative analysis of survival in a series of 134 limited-stage SCLC patients treated between 1984 and 1996 with either complete resection followed by chemotherapy (67 patients), or with conventional non-surgical management (67 patients). In all patients who underwent resection, the diagnosis of SCLC was established only postoperatively. The control (non-surgical) group was selected using ‘pair-matched case-control’ methodology, out of 176 limited-stage patients potentially suitable for surgery (i.e. with no pleural effusion or other local advancement, no supraclavicular lymph node involvement and good performance status), but treated without resection. The major prognostic factors were well balanced between these two groups. Total series included 109 males and 25 females, 20 patients with T1 and 114 patients with T2 disease, 51 N0, 43 N1 and 40 N2 disease. Results: Median survival in patients treated with and without surgery was 22 months and 11 months, respectively, ðP , 0:001Þ: The two-year and five-year survival probabilities were 43 and 27%, respectively, in the surgical group, and 17 and 4%, respectively, in the non-surgical group. Subset analysis confirmed significantly longer survival with surgery in all T and N categories, except for N2 disease. Local relapse occurred in 15 and 55% of patients treated with and without surgery, respectively, ðP , 0:001Þ: Distant relapse probabilities were similar in both groups (36 and 40%, respectively). The most common site of metastases in the entire series was brain, followed by liver, lymph nodes, bone, lung and skin. Conclusions: Our results suggest a possible role of surgery in limited-stage SCLC. Thus, a randomised study addressing this issue seems to be justified. q 2004 Elsevier B.V. All rights reserved.

Immune consequences of the spontaneous pro-inflammatory status in depressed elderly patients.

Abstract: Introduction. The aim of the study was to describe the interrelationship between senescence, depression, and immunity. Methods. We assessed 10 elderly patients with depression and 10 age- and sex-matched controls: before, at one and at six month intervals after the anti-influenza vaccination. Levels of TNFα, IL6, ACTH, and cortisol, titres of anti-hemagglutinins and anti-neuraminidases, lymphocytes secreting IFNγ, IL2, IL4, and IL10, cytotoxicity of NK and CD3+CD8+IFNγ+ cells, anti-CMV antibodies, and CD28−CD57+ lymphocytes known to be associated with the CMV carrier status were evaluated. Results. Higher levels of anti-CMV, higher percentage of the CD28−CD57+ cells, and elevated levels of TNFα, IL6, and cortisol concomitant with decreased levels of ACTH and insufficient production of IL10 (which increased the IFNγ+/IL10+ ratio) were found in the patients suffering from depression, in comparison to healthy controls. The subjects with depression revealed a low NK cytotoxicity, while a level of CD3+CD8+IFNγ+ cells was comparable between the groups. Although the levels of anti-hemagglutinins and anti-neuraminidases were low in the depressed patients, they reached the protective titres. The majority of these differences disappeared when CMV titres were entered into the analyses as a covariate. Discussion. The results suggest that the elderly depressed patients were characterised by increased exposure to CMV in the past, which could have resulted in a pro-inflammatory profile demonstrated as elevated levels of TNFα, IL6 and deficiency of suppressive IL10+ cells. These changes negatively affect humoral and innate response in the depressed patients.

Peritoneal dialysis with solutions low in glucose degradation products is associated with improved biocompatibility profile towards peritoneal mesothelial cells.

Abstract: Background. In vitro experiments point to a better biocompatibility profile of new pH-neutral peritoneal dialysis fluids (PDFs) containing low levels of glucose degradation products (GDPs). The present study examines the impact on human peritoneal mesothelial cells (HPMCs) of equilibrated dialysates obtained during dialysis with either conventional or new PDFs. Methods. Peritoneal dialysate was collected from 17 patients participating in a randomized, controlled, cross-over trial comparing a pH-neutral low-GDP solution (Balance) to a conventional solution (S-PDF). All patients were treated sequentially for 3 months with both PDFs. At the end of each treatment phase, peritoneal effluent was drained after a timed 10 h dwell. Samples of dialysate were then mixed with standard culture medium and added to in vitro cultures of HPMCs from healthy donors. Cells were assessed for proliferation, viability and cytokine release. Results. Proliferation and viability of HPMCs were better preserved in the presence of effluent obtained during dialysis with Balance (P<0.046 and P<0.035, respectively). The proliferative response of HPMCs correlated with the concentration of fibronectin in dialysates (P ¼ 0.0024). Effluent drained following a 3 month dialysis with Balance contained significantly increased levels of fibronectin (P ¼ 0.004) and CA125 antigen (P ¼ 0.0004) compared with S-PDF. There was no significant difference in constitutive and stimulated cytokine (IL-6, MCP-1, VEGF) synthesis by HPMCs treated with either Balance- or S-PDF-derived effluents. Conclusions. These results suggest that therapy with new pH-neutral low-GDP solutions contribute to an intraperitoneal milieu that improves mesothelial cell proliferation and viability. It may positively impact on the preservation of the peritoneal membrane integrity during long-term dialysis.