Arkadiusz Jawień

Persistent oxidative stress in colorectal carcinoma patients

We examine whether the level of 8‐oxo‐2′‐deoxyguanosine (8‐oxodGuo) in lymphocytes DNA is higher in colon cancer when compared to the control group. Factors that may influence oxidative stress such as antioxidant vitamins and uric acid were also determined. Blood samples were obtained from a control group of 55 healthy persons and 43 colon cancers. 8‐OxodGuo level and the vitamins concentration were measured by high‐performance liquid chromatography. The levels of 8‐oxodGuo were significantly higher whereas the concentrations of the vitamins and uric acid were significantly lower in colon cancer patients than in control group. Therefore, the decreased concentration of antioxidant vitamins together with lower amount of uric acid may be responsible for the formation of pro‐oxidative environment in blood of colorectal carcinoma patients.

8-Oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine levels in human urine do not depend on diet.

In the present study, we used the method involving HPLC pre-purification followed by gas chromatography with isotope dilution mass spectrometric detection for the determination of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) and 8-oxo-7,8-dihydroguanine (8-oxoGua) in human urine. The mean levels of 8-oxoGua and 8-oxodGuo in the urine samples of the subjects on unrestricted diet were respectively 1.87 nmol/kg 24 h (±0.90) and 0.83 nmol/kg 24h (±0.49), and in the case of the groups studied, they did not depend on the applied diet. The sum of the amounts of both compounds in urine can give information about the formation rate of 8-oxoGua in cellular DNA. It is also likely that the levels of modified nucleo-base/side in urine sample are reflective of the involvement of different repair pathways responsible for the removal of 8-oxodGuo from DNA, namely base excision repair (BER) and nucleotide excision repair (NER).

The level of 8-oxo-7,8-dihydro-2′-deoxyguanosine is positively correlated with the size of the labile iron pool in human lymphocytes

Abstract. It appears that the labile iron pool (LIP, low molecular weight iron) presence in cells can result in the production of reactive oxygen species (ROS). ROS may be responsible for the formation of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) in cellular DNA. In the present study we report on the relationship between LIP and the endogenous level of 8-oxodGuo in human lymphocytes. Good correlation has been determined between LIP and the oxidatively modified nucleoside. This in turn points out the possibility that under physiological condition there is the availability of LIP for catalyzing Fenton-type reactions in close proximity to cellular DNA. Electronic supplementary material to this paper can be obtained by using the Springer Link server located at http://dx.doi.org/10.1007/s00775-001-0335-x.

Heteroplasmic substitutions in the entire mitochondrial genomes of human colon cells detected by ultra-deep 454 sequencing

Mitochondrial DNA (mtDNA) heteroplasmy has been widely described from clinical, evolutionary and analytical points of view. Historically, the majority of studies have been based on Sanger sequencing. However, next-generation sequencing technologies are now being used for heteroplasmy analysis. Ultra-deep sequencing approaches provide increased sensitivity for detecting minority variants. However, a phylogenetic a posteriori analysis revealed that most of the next-generation sequencing data published to date suffers from shortcomings. Because implementation of new technologies in clinical, population, or forensic studies requires proper verification, in this paper we present a direct comparison of ultra-deep 454 and Sanger sequencing for the detection of heteroplasmy in complete mitochondrial genomes of normal colon cells. The spectrum of heteroplasmic mutations is discussed against the background of mitochondrial DNA variability in human populations.

Comparison of the effectiveness of compression stockings and layer compression systems in venous ulceration treatment

Introduction The aim of the research was to compare the dynamics of venous ulcer healing when treated with the use of compression stockings as well as original two- and four-layer bandage systems. Material and methods A group of 46 patients suffering from venous ulcers was studied. This group consisted of 36 (78.3%) women and 10 (21.70%) men aged between 41 and 88 years (the average age was 66.6 years and the median was 67). Patients were randomized into three groups, for treatment with the ProGuide two-layer system, Profore four-layer compression, and with the use of compression stockings class II. In the case of multi-layer compression, compression ensuring 40 mmHg blood pressure at ankle level was used. Results In all patients, independently of the type of compression therapy, a few significant statistical changes of ulceration area in time were observed (Student’s t test for matched pairs, p < 0.05). The largest loss of ulceration area in each of the successive measurements was observed in patients treated with the four-layer system – on average 0.63 cm2/per week. The smallest loss of ulceration area was observed in patients using compression stockings – on average 0.44 cm2/per week. However, the observed differences were not statistically significant (Kruskal-Wallis test H = 4.45, p > 0.05). Conclusions A systematic compression therapy, applied with preliminary blood pressure of 40 mmHg, is an effective method of conservative treatment of venous ulcers. Compression stockings and prepared systems of multi-layer compression were characterized by similar clinical effectiveness.

Mitochondrial DNA Polymerase γ Mutations and Their Implications in mtDNA Alterations in Colorectal Cancer

Mitochondrial DNA was found to be highly mutated in colorectal cancer cells. One of the key molecules involved in the maintenance of the mitochondrial genome is the nuclear‐encoded polymerase gamma. The aim of our study was to determine if there is a link between polymorphisms within the polymerase gamma gene (POLG) and somatic mutations within the mitochondrial genome in cancer cells. We investigated POLG sequence variability in 50 colorectal cancer patients whose complete mitochondrial genome sequences were determined. Relative mtDNA copy number was also determined. We identified 251 sequence variants in the POLG gene. Most of them were germline‐specific (∼92%). Twenty‐one somatic changes in POLG were found in 10 colorectal cancer patients. We have found no association between the occurrence of mtDNA somatic mutations and the somatically occurring variants in POLG. MtDNA content was reduced in patients carrying somatic variants in POLG or germline nucleotide variants located in the region encoding the POLG polymerase domain, but the difference did not reach statistical significance. Our findings suggest that somatic mtDNA mutations occurring in colorectal cancer are not a consequence of somatic mutations in POLG. Nevertheless, POLG nucleotide variants may lead to a decrease in mtDNA content, and consequently result in mitochondrial dysfunction.

Knowledge of symptoms and diagnostic possibilities of cancer diseases

Introduction The aim of the present study was to analyse patients’ knowledge in the field of neoplastic prophylaxis. Material and methods The research was carried out between 2007 and 2008 in the Provincial Hospital in Bydgoszcz (i.e. general surgery, gynaecology and obstetrics, urology, breast surgery and thoracic surgery). Altogether 300 patients (of whom 250 were hospitalized) as well as 50 healthy subjects forming the control group were invited to participate in the study. A proprietary questionnaire containing eight multiple choice and another twelve open-ended questions was used for the purpose of the study. Results Prostate and lung cancer patients were more aware of their diseases compared to the control group, but the differences were not significant (p = 0.85 and p = 0.53 respectively). In the field of screening the patients’ knowledge, it was significantly higher in breast cancer subjects (p = 0.0008) while there was no difference compared to the control group in the remaining groups of cancer patients (i.e. colorectal, prostate or uterus cancer). Those most aware of their condition were patients from small towns (below 50,000), while subjects living in villages were the least aware. Conclusions Patients showed the greatest amount of knowledge regarding breast cancer and the least amount regarding prostate cancer. Oncological awareness in cancer patients was found to be related to variables such as education, age and residence. No difference was found between patients and controls, comparing their knowledge of disease symptoms as well as screening possibilities.

Randomized study assessing the influence of supervised exercises on ankle joint mobility in patients with venous leg ulcerations

Introduction The aim of the study was to assess the influence of a supervised programme of exercises on ankle joint mobility in patients with venous leg ulcerations. Material and methods The study was carried out between 2008 and 2009 at the Venous Ulcer Treatment Outpatient Clinic and Clinic of General and Vascular Surgery of the Dr Jan Biziel University Hospital no. 2 in Bydgoszcz. It was a randomized control study in which 32 patients with venous leg ulcerations were qualified. Patients with ulcerations were randomized to 2 groups – 16 patients were included in the group with a supervised programme of exercises and the other 16 patients were included in the control group performing physical exercises by themselves, without supervision. The ranges of ankle joint mobility were assessed before, during and after the end of the 9-week exercise programme. A 32 cm goniometer with a scale from 0° to 180° with accuracy to 1° was used for measurements. Results In both groups a substantial increase of ankle joint mobility (p < 0.05) was observed. The total ankle joint mobility after completion of the exercises was significantly higher in the group performing exercises under the supervision of a nurse. Having a significant effect on the mobility of the ankle were the ulceration area, the extent of lipodermatosclerosis, and the intensity of symptoms and signs of CVI (p < 0.05). Conclusions Supervised physical exercises broaden the range of ankle joint mobility. They should constitute an integral part of a holistic model of care for patients with venous leg ulcerations.

Usefulness of CEA Concentration Measurement and Classic Colonoscopy in Follow-Up After Radical Treatment of Colorectal Cancer

UNLABELLED There is always a certain rate of recurrence after radical treatment for cancer and to get on it an early detection of disease set back is crucial. MATERIAL AND METHODS Medical data of patients operated on for primarily detected colorectal cancer in years 1993-2002 was retrospectively reviewed. Usefulness of follow-up means such as physical examination, or CEA and endoscopic surveillance was analyzed. All mentioned above were applied to scheduled follow-up (in 3, 6 and 12 month intervals following an operation and annually after that by the year 5). RESULTS Complete and reliable data was obtained from 340 out of 502 follow-up intended subjects (67.7%). Elevated CEA was the most frequent predictor of recurrence within non-symptomatic subjects meeting follow-up appointments (60%). The cancer set back diagnosed by means of either physical or endoscopic examinations was the case only in one out of five patients (20.75% and 18.87% respectively). Clinical onset of recurrence making patients meet an unscheduled appointment was found increasing relative risk of nothing-but-palliative option either for them with local set back, or meta-static spread. Relative risk of onset of meta-chronous colonic cancer was significantly higher in patients being affected by synchronous advanced adenoma at time of surgery compared to those with one-fold changes. CONCLUSIONS CEA scheduled follow-up after treatment for colorectal cancer CRC seems adequate to provide a good outcome of treatment for recurrent tumors. CRC patients presenting with synchronous advanced adenomas at time of surgery are probably to be under more intensive endoscopic surveillance.

Diabetes mellitus increases the risk of ruptured abdominal aortic aneurysms

The publication is a polemical response to reports that present data that diabetes reduces the risk of rupture of abdominal aortic aneurysm (AAA). The study analyzed all cases of developing AAA in patients with and without diabetes in 2012 in Poland. Data for the analysis were obtained with a unique and complete resources of the National Health Fund (NFZ) and population data from the Central Statistical Office (GUS). In Poland during 2012 2,227,453 patients with diabetes were treated, 975,364 males and 1,252,089 females. The incidence of AAA without rupture in patients without diabetes calculated per 100,000 of the non-diabetes general population was 25.0 +/– 9.0 in males and 5.6 +/– 2.3 in females. The incidence of ruptured AAA in the general population without diabetes was 3.6 +/– 0.9 in males, and 0.6 +/– 0.3 in females calculated per 100,000 of inhabitants without diabetes. The incidence of AAA without rupture in patients with diabetes was 184.897 +/– 70.653 in males and 35.364 +/– 24.925 in females calculated per 100,000 of patients diagnosed with diabetes. The incidence of ruptured AAA in patients with diabetes was 21.090 +/– 6.050 in males and 5.170 +/– 3.053 in females calculated per 100,000 of patients diagnosed with diabetes. The incidence rate for ruptured AAA in 2012 in Poland is statistically higher both in females and males in the population with diabetes. The incidence rate for AAA without rupture in 2012 in Poland is statistically higher in patients diagnosed with diabetes.