Is the ABCB1 gene associated with the increased risk of gastric cancer development?--preliminary research.

One of the most common malignant diseases, both worldwide and in Poland, is gastric cancer. The pathogenesis of gastric cancer development is not entirely clear. Next to the environmental risk factors, such as Helicobacter pylori infection or dietary habits, the host genetic factors as predispositions to gastric cancer development are discussed. A transmembrane protein that could be associated with predisposition to cancer development is P-glycoprotein (P-gp). Physiologically, P-gp is present in normal tissue of the gastrointestinal tract, where it plays a protective role by transporting xenobiotics from a cell into extracellular environment. P-gp is encoded by the highly polymorphic ABCB1 gene. The most frequent polymorphisms at positions 1236, 2677, and 3435 may affect both the function and amount of protein, thereby leading to a loss of its physiological function, which could increase the predisposition to development of many diseases, including cancer. In this study, the potential significance of the ABCB1 gene in the development and progression of gastric cancer was evaluated. In 19 tissue samples collected from patients with gastric cancer, the ABCB1 gene polymorphisms were identified at positions 1236 and 2677 by automated sequencing and SNP 3435 by the RFLP method. The relative level of ABCB1 expression was measured in 10 samples of gastric cancer and morphologically normal tissues by real-time PCR. For SNPs at positions 1236, 2677, and 3435, no statistically significant differences in genotype frequencies between gastric cancer patients and healthy individuals were found. However, genotype TT for all studied polymorphisms occurred more frequently in the group of gastric cancer patients (31.6, 26.3, 42.1%, respectively) than in the group of healthy individuals (14.6, 13.5, 21.9%, respectively). The lowest relative expression levels of ABCB1 mRNA were observed for genotypes CC of SNP 1236, CC of SNP 3435, and GG of SNP 2677 (median: 0.215, 0.160, 0.160, respectively). There was a tendency that mutant homozygote TT for SNPs at positions 1236, 2677, and 3435 occurred more frequently in the subgroup of patients with Tis or stage I of TNM classification (SNP 1236 p = 0.0760; SNP 2677 p = 0.0813; SNP 3435 p = 0.0760) than in the subgroup of patients with stage II or III. Also the expression levels were lowest (median 0.740) in the group of patients with the less advanced clinical stage of cancer (Tis or I). Preliminary research showed that the ABCB1 gene polymorphisms at positions 1236, 2677, and 3435 were not related to an increased susceptibility of gastric cancer development. However, they may be associated with the inhibition of gastric cancer progression.

Neurocognition of centenarians: neuropsychological study of élite centenarians.

OBJECTIVE: The aim of this study was to evaluate the cognitive state of highly selected Polish centenarians and analyze the mechanisms of their functioning. METHODS: The selected centenarian group (10 persons) and a reference group (20 persons) who started aging (65 years) were examined with a sensitive set of neuropsychological tests and tasks in clinical-experimental assessment. RESULTS: As expected, the centenarians' cognitive functions were different from those of the subjects who started aging, however, not in all aspects. For instance, the former scored significantly lower in the area of linguistic functions but the ability to plan and controlled perform complex visuospatial task with use of simultaneous and sequential strategies was preserved despite unfavorable symptoms of natural aging such as permanence attention as well as prolonged action time. CONCLUSIONS: The results suggest that the studied centenarians show a dominant right-hemispheric pattern functioning not only in relation to perception, but also to planning and executing complex activities. The study and description of preserved neurocognition of centenarians was possible due to introducing a special procedure sensitive to the preserved functions.

The rate of conversion of mild cognitive impairment to dementia: predictive role of depression.

BACKGROUND: Mild cognitive impairment (MCI) is a condition referring to the persons with cognitive deficits measurable in some form or another, but not meeting criteria for dementia, and who have an increased risk of becoming demented. OBJECTIVE: To establish the rate of progression to dementia in MCI, to investigate the risk of conversion for amnestic vs multiple-domains subtypes, and to identify the predictors of progression. METHODS: MCI (n = 105) individuals enrolled in a longitudinal study received annual clinical and psychometric examinations for up to a mean of 3 years. The diagnosis of MCI according to Mayo Clinic Petersen's Criteria was conducted by a panel of specialists. RESULTS: After 3 years of follow-up, 23 of 105 subjects with MCI were diagnosed with dementia. 40 showed cognitive decline not dementia, 34 were stable and showed no cognitive decline or improvement, while eight showed cognitive improvement. CONCLUSIONS: We conclude that conversion rate from MCI to DSM-IIIR dementia was 21.9% over a period of 3 years. The occurrence of depressive symptoms may constitute a predictor for those who are more likely to progress to dementia. The risk of conversion to dementia was higher among the subjects with an evidence of impairment extending beyond memory than with those who suffered only from memory deficits, and the subjects who converted to dementia in this subtype had significantly higher baseline plasma total homocysteine levels than non-converters.

Prion protein gene M129 allele is a risk factor for Alzheimer's disease.

Prion protein gene polymorphism M129V represents a known risk factor for Creutzfeldt-Jakob disease. Recently, the meta-analysis revealed that homozygosity at codon 129 is connected with increased risk of Alzheimer's disease (AD). To determine whether M129V polymorphism is a risk factor for AD we analyzed a group of early-onset, and late-onset Polish AD patients. We observed that in LOAD patients there is a statistically significant increase of MM (p=0.0028) and decrease of MV (p=0.0006) genotype frequency, as compared to controls. When both groups were stratified according to APOE4 status, increase of MM and decrease of MV genotype frequency were significant in the LOAD subgroup with no APOE4 (p=0.017, and p=0.018, respectively). In the subgroup with APOE4 allele, only MV genotype frequency was significantly lower, as compared to controls (p=0.035). However, no interaction was found between APOE4 status and M129V polymorphism. We conclude that MM genotype increases LOAD risk in Polish population independently from the APOE4 status.

Hyperhomocysteinemia and methylenetetrahydrofolate reductase polymorphism in patients with Parkinson's disease.

Elevated levels of homocysteine have been observed in Parkinson's disease (PD) patients treated with levodopa. However, it is not studied if duration of PD or PD per se is associated with hyperhomocysteinemia. In the present study, the levels of homocysteine in 99 levodopa-treated PD patients, 15 untreated PD patients and 100 controls were examined. We focused on the influence of levodopa dose, duration of therapy and disease as well as genetic (C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism) and environmental factors. We found that levodopa-treated PD patients had elevated homocysteine plasma levels as compared to controls (p < 0.05), but the levels did not depend on levodopa doses. Another factor influencing homocysteine level was the duration of PD (p < 0.001). The frequency of allele C677T of MTHFR gene did not differ between PD and controls. In conclusion, hyperhomocysteinemia is associated with the duration of PD and levodopa treatment and possibly also with PD per se.

[The influence of ischemia provoked by dobutamine and exercise on presence of late potentials in patients after myocardial infarction]. / Wplyw przejsciowego niedokrwienia prowokowanego testem dobutaminowym i wysilkowym na obecnosc póznych potencjalów komorowych u chorych po zawale serca.

UNLABELLED: The aim of this study was to examine the influence of transient exercise- and dobutamine-induced myocardial ischemia on time domain parameters of signal-averaged ECG (SAECG) and presence of late potentials (LP) in patients after myocardial infarction (MI). The investigation covered 85 patients after healing of MI, divided into two groups. Group I (24 males and 2 females, mean age 56.8 +/- 6.4 yrs) had exercise-induced ischemia and group II consisted of 59 patients (51 males and 8 females, mean age 58.3 +/- 8.5 years) with ischemia provoked by the intravenous dobutamine stress-testing. In each patient 2-D echocardiography, 24-h ambulatory Holter ECG, coronary arteriography were performed before stress testing. The ischemia was proven by using Tc-99m MIBI myocardial perfusion and standard 12-lead ECG monitoring. Recordings of SAECG were registered at rest and during ischemia under influence of stress-testing. The following time-domain parameters of SAECG were analysed: the root-mean-square voltage of the last 40 and 50 ms of the filtered QRS complex (RMS40, 50), total time duration of filtered QRS (t-QRS) and duration of signal lower than 40 muV (LPD). LP were detected when two or three of following criteria's had been registered: RMS 40 < 20 muV, t-QRS > 114ms, LPD > 38s. There was no statistically significant differences in all time domain parameters of SAECG between records at the baseline and during ischemia in each study group. At the baseline LP have been registered in 11.5% and in 15% patients, respectively of group I and group II. On the top of ischemia during treadmill exercise stress-testing LP have been recorded in 27% subjects. Under influence of dobutamine-provoked ischemia LP have been registered in 25% patients. CONCLUSIONS: Exercise- and dobutamine-induced ischemia triggers development of LP in small grade in post-infarction patients.

[The influence of exercise and dobutamine-induced ischemia on the presence of late potentials in patients after myocardial infarction]. / Wplyw przejsciowego niedokrwienia mienia serca prowokowanego testem dobutaminowym i wysilkowym na obecnosc póznch potencjalów komorowych u chorych po zawale serca.

UNLABELLED: The aim of this study was to examine the influence of transient exercise- and dobutamine-induced myocardial ischemia on time domain parameters of signal-averaged ECG (SAECG) and presence of late potentials (LP) in patients after myocardial infarction (MI). The investigation covered 85 patients after healing of MI, divided into two groups. Group I (24 males and 2 females, mean age 56.8 +/- 6.4 yrs) had exercise-induced ischemia and group II consisted of 59 patients (51 males and 8 females, mean age 58.3 +/- 8.5 years) with ischemia provoked by the intravenous dobutamine stress-testing. In each patient 2-D echocardiography, 24-h ambulatory Holter ECG, coronary arteriography were performed before stress testing. The ischemia was proven by using Tc-99m. MIBI myocardial perfusion and standard 12-lead ECG monitoring. Recordings of SAECG were registered at rest and during ischemia under influence of stress-testing. The following time-domain parameters of SAECG were analysed: the root-mean-square voltage of the last 40 and 50 ms of the filters QRS complex (RMS40, 50), total time duration of filtered QRS (t-QRS) and duration of signals lower than 40 microV (LPD). LP were detected when two or three of following criterias had been registered: RMS 40 < 20 microV, t-QRS > 114 ms, LPD > 38 s. There was no statistically significant differences in all time domain parameters of SAECG between records at the baseline and during ischemia in each study group. At the baseline LP have been registered in 11.5% and in 15% patients, respectively of group I and group II. On the top of ischemia during treadmill exercise stress-testing LP have been recorded in 27% subjects. Under influence of dobutamine-provoked ischemia LP have been registers in 25% patients. CONCLUSION: Exercise- and dobutamine-induced ischemia triggers development of LP in small grade in post-infarction patients.

[The effect of long term use of amiodarone hydrochloride on time and frequency domain parameters of signal averaged electrocardiogram in patients with ischemia heart disease]. / Wplyw przewlekle stosowanego chlorowodorku amiodaronu na parametry czasowe i czestotliwosc elektrokardiogramu wysokiego wzmocnienia u chorych na chorobe niedokrwienna serca.

The aim of this study was to assess the influence of amiodarone hydrochloride on time- and frequency-domain parameters of signal-averaged electrocardiogram (SAECG) in patients with ischaemic heart disease (IHD). The study population consisted of 33 patients (18 female and 15 male), mean age 59.2 +/- 7.7. Amiodarone hydrochloride was orally used in the initial dose 600 mg/day for 10 days, and subsequently 200 mg/days for 6 weeks. Recording of SAECG and ambulatory Holter monitoring were made at baseline and in 10 day and after 6 weeks of therapy. The following time-domain parameters were analyzed: the root mean square voltage of the last 40 and 50 ms of the filtered QRS (RMS40 i RMS50), total time duration of filtered QRS (t-QRS) and duration of low amplitude signals < 40 microV in the terminal part of QRS (LPD). Late potentials (LP) were recognized when at least two from three criteria were fulfilled: 1) RMS40 < 20 microV, 2) t-QRS > 114 ms, 3) LPD > 38 ms. Frequency analysis of SAECG allowed to calculate the following parameters in logarithmic scale: energy spectrum > -60 dB (A) and decibel drop at 40Hz (Dd) and also in linear scale: area ratio 20-50/0-20Hz (Ar) and magnitude ratio (MR1-7). The values of RMS40 and RMS50 did not significantly change during amiodarone therapy. The obtained values of t-QRS were significantly longer after antiarrhythmic therapy, respectively 97.8 +/- 9.1 ms at the baseline, 102.1 +/- 10 ms after 10 days (p < 0.05), and 104.1 +/- 10.4 ms after 6 weeks (p < 0.005). Moreover the values of LPD did not significantly change after amiodarone treatment. At the baseline the presence of LP were observed in 3 (9%), after 10 days were recorded in 8 (24%), and after 6 weeks in 7 (22%) cases. Only in one case the LP were observed during the whole antiarrhythmic therapy. Moreover, amiodarone hydrochloride did not statistically significant change frequency-domain parameters in logarithmic scale and in linear scale.

[Cigarette smoking and alcohol abuse effects on stroke development]. / Wplyw palenia papierosów i naduzywania alkoholu na wystepowanie udarów mózgu.

Cigarette smoking, alcohol abuse and stroke--the material consisted of 272 patients (169 men and 103) women aged between 25-65 years. There were 221 patients with ischemic stroke and 51 patients with haemorrhagic stroke. The control group consisted of 400 healthy subject of the same age and sex. In the stroke group excessive consumption of alcohol was reported by 61 patients (5 women and 56 men). Excessive smoking was reported by 130 patients (41 women and 89 men). It was found in both types of stroke alcohol was not an independent risk factor. In addition, the study revealed that alcohol and cigarette smoking did not increase the risk of developing stroke in patients with diabetes and hypertension. Excessive cigarette smoking was found however, to be an independent risk factor in haemorrhagic stroke.

[Computerized tomography of the head in patients with epilepsy]. / Tomografia komputerowa glowy u chorych na padaczke.

A detection of structural changes in the brain of epileptic patients is of importance to the choice of therapeutical management. Incidence and character of lesions in CT-scans of the skull were analysed in the random group of epileptic patients. Normal areas in CT-scans were prevailing in young patients. Atrophic lesions to the brain increased with the patients' age and duration of the disease. Normal results were obtained in post-traumatic epilepsy and that of unknown etiology similarly to atrophic lesions whereas localized lesions were found in all patients with cerebral tumors. Partial epilepsy, especially of short duration, was characterized by high incidence of localized lesions. Normal EEG records were rare in patients with localized lesions detected with CT-scans whereas normal CT-scans may be related to abnormal EEG record. Presence of the localized lesions in some patients and atrophic areas did not limit clinical results of monitored therapy. CT-scanning of the skull should be performed in case of all patients with epilepsy even if there are no significant changes in EEG records or clinical status.