Magnetic resonance imaging of brain abnormalities in patients with the Nijmegen breakage syndrome

The results of brain MRI are presented in 22 patients with documented Nijmegen breakage syndrome (NBS), aged from 1 and 9/12 to 20 years. T1-, PD or FLAIR and T2-weighted SE/TSE images in three planes were obtained. Twenty-one patients showed microcephaly. Decreased size of frontal lobes and narrow frontal horns of the lateral ventricles was observed in all cases. In 6 patients agenesis of the posterior part of the corpus callosum was found as well as colpocephaly and temporal horn dilatation. In 2 patients callosal hypoplasia was accompanied by other anomalies: abnormal cerebrospinal fluid spaces. Sinusitis was present in all patients as a result of primary immunodeficiency. As in ataxia teleangiectasia and other breakage syndromes, NBS patients show inherited malignancy susceptibility and hypersensitivity to X and gamma radiation. Because of that computed tomography is contraindicated in these patients and MRI should be the method of choice in diagnostic imaging.     

Natural mechanisms protecting against cancer

Carcinogenesis is a multistage process. At each step of this process, there are natural mechanisms protecting against development of cancer. The majority of cancers in humans is induced by carcinogenic factors present in our environment including our food. However, some natural substances present in our diet or synthesized in our cells are able to block, trap or decompose reactive oxygen species (ROS) participating in carcinogenesis. Carcinogens can also be removed from our cells. If DNA damage occurs, it is repaired in most of the cases. Unrepaired DNA alterations can be fixed as mutations in proliferating cells only and mutations of very few strategic genes can induce tumor formation, the most relevant are those activating proto-oncogenes and inactivating tumor suppressor genes. A series of mutations and/or epigenetic changes is required to drive transformation of a normal cell into malignant tumor. The apparently unrestricted growth has to be accompanied by a mechanism preserving telomeres which otherwise shorten with succeeding cell divisions leading to growth arrest. Tumor can not develop beyond the size of 1–2 mm in diameter without the induction of angiogenesis which is regulated by natural inhibitors. To invade the surrounding tissues epithelial tumor cells have to lose some adhesion molecules keeping them attached to each other and to produce enzymes able to dissolve the elements of the basement membrane. On the other hand, acquisition of other adhesion molecules enables interaction of circulating tumor cells with endothelial cells facilitating extravasation and metastasis. One of the last barriers protecting against cancer is the activity of the immune system. Both innate and adaptive immunity participates in anti-tumor effects including the activity of natural killer (NK) cells, natural killer T cells, macrophages, neutrophils and eosinophils, complement, various cytokines, specific antibodies, and specific T cytotoxic cells. Upon activation neutrophils and macrophages are able to kill tumor cells but they can also release ROS, angiogenic and immunosuppressive substances. Many cytokines belonging to different families display anti-tumor activity but their role in natural anti-tumor defense remains largely to be established.     

The striopallidal pathway is involved in antiparkinsonian-like effects of the blockade of group I metabotropic glutamate receptors in rats

The aim of the study was to examine the influence of the blockade of group I metabotropic glutamate receptors (mGluRs) on the haloperidol-induced catalepsy and proenkephalin mRNA expression in the rat striatum. Bilateral, intrastriatal injection of AIDA ((RS)-1-aminoindan-1,5-dicarboxylic acid, 3-15 microg/0.5 microl), a selective antagonist of group I mGluRs, inhibited catalepsy induced by haloperidol (0.5 mg/kg i.p.). Repeated intrastriatal AIDA administrations (3 x 15 microg/0.5 microl, 3 h apart) counteracted the haloperidol-induced (3 x 1.5 mg/kg s.c., 3 h apart) increase in the proenkephalin mRNA expression in that structure. The present study indicates that the blockade of the striatal group I mGluRs may inhibit parkinsonian akinesia by normalizing the function of the striopallidal pathway.     

Assessment of selected co-stimulatory, adhesion and activatory molecules and cytokines of Th(1)/Th(2) balance in acute lymphoblastic leukemia in children

INTRODUCTION: Recent years have seen a rise in the importance of cytokine production and co-stimulatory/activatory molecule expression in the immune response in leukemia. The aim of our study was to assess the function of T lymphocytes in children with acute lymphoblastic leukemia (ALL) during remission induction based on selected cytokine and co-stimulatory/activatory molecule expression. MATERIAL/METHODS: The study group consisted of 50 children with ALL (B cell precursor). Peripheral blood samples were taken before treatment (day 0), after the prednisone prophase (day 8), and during (day 15) and after (day 33) remission induction. The percentages of T cells with interferon (IFN)-gamma (Th(1)), interleukin (IL)-4 (Th(2)) and IL-2 receptor (IL-2R), CD28, CTLA-4, CD38, ICAM-1, and HLA-DR expression were assessed by tricolor flow cytometry. RESULTS: At the time of diagnosis we noted higher percentages of T cells with adhesion molecule ICAM-1, activation molecule CD38 expression, and an increased population of Th(2 )cells (IL-4) compared with the control group. During and after remission induction we observed a decreased population of CD38(+) T cells, elevated percentages of helper T lymphocytes with IL-2R expression, and a rise in helper T lymphocytes producing IFN-gamma (Th(1)). During fever/infection, higher levels of activated T lymphocytes (CD4(+)HLA-DR(+), CD8(+)HLA-DR(+)), a rise in Th1, and no change in Th(2 )populations were observed. CONCLUSIONS: The results suggest T cell activation and Th(2 )predominance at the time of diagnosis and during remission induction in ALL in children. These results confirm the involvement of cellular immunity in the leukemic process and can be used in immune therapy in leukemia.     

Mutation A1298C of methylenetetrahydrofolate reductase: risk for early coronary disease not associated with hyperhomocysteinemia

Diminished activity of 5,10 methylenetetrahydrofolate reductase (MTHFR), a regulatory enzyme of homocysteine metabolism, may predispose to coronary artery disease (CAD). In a case-control study we determined the prevalence of two common MTHFR polymorphisms, C677T and A1298C, in 161 male patients under the age of 50 years with angiographically documented CAD and compared it to that in 211 healthy controls. Genotyping was also performed in a random population sample, consisting of 149 men and 121 women at an average age of 40 years. The studied group had classic risk factors of atherosclerosis but did not differ in fasting plasma homocysteine, folic acid, and vitamin B12 levels in either the control group or population sample. The frequency of the 1298C allele was significantly higher in CAD (0.304) than in controls (0.199) or the population sample (0.235). Allele 1298C showed a significant association with early-onset CAD both in homozygotes and in heterozygous carriers. These findings were further supported by comparisons with the population sample. Homozygosity for allele 677T showed a tendency to associate with CAD. Allele 1298C of MTHFR is associated with early-onset CAD (carriers- RR = 1.71, 95% CI: 1.13-2.59; homozygotes- RR = 3.09, 95% CI: 1.36-7.02), even when blood homocysteine levels are not elevated.     

Prevalence of menstrual pain in relation to the reproductive life history of women from the Mayan rural community

BACKGROUND: The prevalence of menstrual pain in Western societies is relatively high and has been shown to be related to many factors (e.g. age, menarche age, parity, menstrual cycle regularity, cigarette smoking, dietary habits). However, less data are available for traditional societies, within which there are, presumably, not as many potentially disturbing factors that could influence menstrual symptoms as in Western societies. AIM: The study seeks to determine the prevalence of dysmenorrhoea, and the factors related to menstrual pains in women with natural fertility (i.e. without hormonal forms of contraception). SUBJECTS AND METHODS: 177 non-smoking women between 18 and 45 years of age living in one Mayan village (Yaxcaba, Yucatan, Mexico) were the subjects of this study. The method of logistic regression was used with the dichotomous dependent variable being the presence or absence of menstrual pain together with such independent variables as age, age at menarche, number of pregnancies, age when giving birth to the first child, the weight at interview and BMI. RESULTS: The general prevalence of the menstrual pains was 28%. There was only one variable influencing dysmenorrhoea, namely the age at which women give birth to their first children. Those mothers who gave birth to their first child at an earlier age (at mean age of 19.4 vs 21.1 years) had a lower prevalence of dysmenorrhoea. CONCLUSION: In the studied traditional society the main factor related to menstrual pain was the age at which woman first gave birth. It is hypothesized that an earlier start to reproductive life in some way decreases the sensitivity of the uterus to prostaglandins.     

Eosinophilic myocarditis in allergic angiitis and granulomatosis (Churg-Strauss syndrome)

Allergic angiitis and granulomatosis (Churg-Strauss syndrome) is one of the rare form of idiopathic (primary) vasculitis. It is characterized by asthma, blood hypereosinophilia and typical microscopic features: nectrotizing vasculitis, tissue infiltration by eosinophils and extravasal granulomas. We present an autopsy case of 55-years old man with Churg-Strauss syndrome complicated by eosinophilic myocarditis.     

Risk factors for asthma in children in Lódź region

The incidence of asthma and other allergic diseases continues to increase. In addition to genetic factors, environmental influences are thought to play an important role. The aim of this study was to identify factors that influence and drive the atopic march from atopic sensitization to asthma in children from Lód?. METHODS: 800 atopic children, aged 5-18 years, were included to our study. Parents filled in questionnaires and gave interviews about their children's diseases. 405 (43%) children have diagnosis of asthma. RESULTS: A significant association was observed between asthma and male sex, parents' history of atopy, parental highest school grade, maternal smoking during pregnancy, maternal chronic disease (especially chronic renal diseases), maternal allergen-sensitizing diet during breast-feeding, increased exposure to indoor humidity and moulds. Similar effect was seen for episodes of wheeze occurring in the first 3 years of life as followed: wheezing during an airway infection, wheezing not connected with respiratory tract infection, wheezing not related with physical exercise. Child's daycare attendance (nursery school) was associated with decreased risk of asthma.     

Awareness of airflow obstruction together with antismoking advice increases success in cessation smoking

COPD is one of the leading causes of mortality and increased morbidity in developed world. In advanced disease it also imposes an important economic burden on societies. The main etiologic factor for COPD is tobacco smoking. The aim of the study was to asses if the awareness of airflow obstruction combined together with a minimal antismoking advice in middle aged smokers increases the quitting rate. Out of smokers participating in mass spirometric screening for COPD in five polish towns, we invited 734 (300 with airflow limitation and 247 with normal lung function) for a follow-up. During the second visit, at one year, spirometry was performed and smoking status was assessed. Non-smoking was validated with carbon monoxide measurements in exhaled breath. Patients who did not come for the follow-up visit were considered as smokers. Of 734 smokers invited, 543 (74%) presented for the follow-up visit. All smokers tried to modify the habit. Number of cigarettes smoked at one year was reduced by -5.5 (p < 0.001) in patients with airflow limitation and -2.2 (ns) in smokers with normal lung function. One year quit rate in smokers with airflow limitation was 11.1% vs 7.6% in smokers with normal lung function (ns). When the calculation was made for those who had the follow-up the quit rates were 15.1% vs 9.9% (p < 0.05). Cessation of smoking was correlated with lung function. Those smokers who stopped smoking permanently or tried to quit had lower FEV1 (p < 0.01) and FEV1/FVC (p < 0.05), than those who continued to smoke.     

Early detection of COPD by high risk population spirometric screening

COPD is the most frequent chronic lung disease in Poland. The disease is however under-diagnosed, especially at the early stages. The aim of the study was to assess the efficacy of spirometric screening for COPD in middle aged smokers. Informations on causes and symptoms of COPD were disseminated in mass media in 14 large cities. Subject aged over 39 and with smoking history of > 10 packyears were invited for a free spirometry in local chest clinic. However, everyone attending had the spirometry performed. Spirometry was performed according to ATS recommendations. Airway obstruction (AO) was diagnosed when FEV1/FVC < 85% of N and categorised as mild (FEV1 > 70% of N), moderate (FEV1 50-69% of N) or severe (FEV1 < 50% of N). Spirometry was accompanied by an antismoking advice. RESULTS: 12.781 subjects were screened (mean age 52 +/- 12 years, 57% males). In 8.269 subjects who complied with inclusion criteria AO was diagnosed in 29.8% (mild in 10.9%, moderate in 12% and severe in 6.9%). In smokers < 40 years of age and a history of < 10 packyears AO was found in 8.8% (mild in 6.0%, moderate in 1.8% and severe in 1.0%). CONCLUSION: Mass spirometry is an effective and easy method for early detection of COPD.