A patient with abnormalities of the coronary arteries and non-compaction of the left ventricular myocardium resulting in ischaemic heart disease symptoms.

Left ventricular non-compaction (LVNC) is a rare cardiomyopathy that results from unsettled embryogenesis of myocardium. It is morphologically characterised by the presence of non-compacted, this is hypertrabeculated, myocardium of the left ventricle with deep endocardial recesses. The clinical spectrum of symptoms is very wide - from asymptomatic patients through the cases of heart failure to the patients requiring heart transplantation. The diagnosis is most frequently based on the echocardiography. LVNC is often coexisted with other heart defects and coronary artery abnormalities. We described a case of a 58-year-old man with LVNC and coronary artery anomalies.

Transcription activity of MMP-2 and MMP-9 metalloproteinase genes and their tissue inhibitor (TIMP-2) in acute coronary syndrome patients.

BACKGROUND: Acute coronary syndromes (ACS) are a consequence of coronary vessel atherosclerosis and they are a leading cause of death in industrialized countries. One of the ACS causative factors is the deranged ratio equilibrium of the matrix metalloproteinase/tissue inhibitor of metalloproteinases (MMPs/TIMPs). AIMS: Assessment of transcriptional activity of metalloproteinase genes using Human Genome-U133A oligonucleotide microarrays and selection of candidate genes differentiating ACS patients from healthy subjects and finally, QRT-PCR (quantitative real time polymerase chain reaction) confirmation of the results. SETTINGS AND DESIGN: The study involved 67 ACS patients, admitted on a consecutive basis, to the Cardiology Clinic as well as 24 healthy subjects (control). MATERIALS AND METHODS: Ribonucleic acid isolated from peripheral blood mononuclear cells was analyzed by QRT-PCR. Transcriptional activity of the analyzed gene was assessed with TaqMan gene expression assays. STATISTICAL ANALYSIS: U Mann-Whitney test was used to compare the results. RESULTS: Homogeneity of the investigated group was assessed through hierarchical clusterization whereas the nine genes differentiating ACS patients from healthy persons were selected using the Bland-Altman technique. Among these genes three (platelet derived growth factor D, NUAK family SNF1-like kinase 1 and peroxisomal biogenesis factor 1) showed decreased transcriptional activity whereas the remaining six genes (MMP-2 and MMP-9, CDK5RAP3, transmembrane BAX inhibitor motif containing 1, adenylate cyclase-associated protein 1 and TIMP-2) were increased. MMP-2, MMP-9 and TIMP-2 were further characterized by QRT-PCR. CONCLUSIONS: The obtained results permit to conclude that the increased expression of MMP-2 and MMP-9 metalloproteinases and their tissue inhibitor (TIMP-2) is responsible for disturbed equilibrium of the metalloproteinase/tissue inhibitors system and as a consequence, for destabilization of atherosclerotic plaque and occurrence of the acute coronary syndrome in the investigated group of patients.

Transcriptional activity of tumour necrosis factor α (TNF-α) in patients with subclinical coronary atherosclerosis - preliminary results.

UNLABELLED: The most frequent cause of ischaemic heart disease is coronary arteriosclerosis. This study was aimed at assessing gene expression of TNFA and its two receptors (TNFR1, TNFR2), as well as determining coronary artery calcium score (CACS) in the context of occurrence of classical risk factors in patients with subclinical atherosclerosis of coronary vessels. The study involved 47 subjects with complaints of chest pain and suspicion of acute coronary syndrome or stable coronary disease. Additionally, CACS was assessed by 64-slice computerized tomography. QRT-PCR molecular studies were performed using RNA isolated from peripheral blood mononuclear cells. Preliminary results of molecular studies on patients with subclinical coronary atherosclerosis revealed a significantly lower numbers of TNFR1 and TNFR2 gene copies as compared with healthy subjects. In addition, it can be demonstrated that among classical risk factors hypertension is of substantial importance in the progression of coronary arteries' calcification, and that in the examined group CACS increases together with the rising number of classical risk factors involved. No correlation was observed, however, between expression of TNFA, TNFR1 and TNFR2 genes and the value of CACS. CONCLUSIONS: 1. The occurrence of hypertension facilitates initiation and progression of arteriosclerotic lesions in blood vessels including the coronary ones; the raised number of circulatory disease classical risk factors involved correlates with elevated calcification of coronary arteries as shown by 64-slice computerized tomography scans. 2. Significantly decreased numbers of TNFR1 and TNFR2 gene copies observed in the investigated group may play a significant role in initiation and progression of arteriosclerosis.

Expression of genes encoding kinin receptors in peripheral blood mononuclear cells from patients with acute coronary syndromes.

BACKGROUND: Inflammation plays a critical role in all stages of atherogenesis, including plaque destabilization leading to the rupture and local thrombosis, clinically manifested as unstable angina (UA) or myocardial infarction (MI). Recent data report enhanced expression of numerous pro-inflammatory genes in patients with acute coronary syndrome (ACS) both in plaque and in inflammatory cells. Kinins are peptides involved in vasodilation, vascular permeability, pain and inflammation. Their effects are mediated by two receptors, B1 and B2. As the role of kinins in ACS is not clear, the aim of the study was to assess the expression of the genes encoding kinin receptors in patients with ACS. METHODS: The study was carried out on 40 patients with ACS and 10 age-matched healthy subjects (control (C)). To evaluate gene expression of B1 and B2 kinin receptors, total mRNA was extracted from peripheral blood mononuclear cells and the number of mRNA copies was assessed by quantitative reverse transcriptase-polymerase chain reaction. RESULTS: In patients with MI and UA, the B1 receptor (B1R)/B2 receptor (B2R) ratio was inversed compared with healthy subjects (C group) (MI vs C: 1.54 +/- 0.39 vs 0.36 +/- 0.04; P < 0.01; UA vs C: 2.13 +/- 0.98 vs 0.36 +/- 0.04; P < 0.05 respectively). B2R gene mRNA level was markedly lower in MI group versus C group (24 216 +/- 5409 copies/microg vs 39 908 +/- 5309 copies/microg; P < 0.05). The difference in B1R gene expression between MI and C group was negligible. We have not observed differences in studied genes expression between UA and C groups. CONCLUSION: Patients with ACS show inverted B1R/B2R ratio. Such disturbance in kinin signalling may reflect increased activation of circulating mononuclears, which are important participants of atherosclerotic plaque development and eventually rupture.

Percutaneous coronary intervention with stent implantation in haemophilic A patient with unstable angina.

The prevalence of coronary artery disease (CAD) and acute coronary syndromes in patients with haemophilia is much lower than in general population and there is a lack of information regarding safe interventional or surgical treatment of CAD in haemophiliacs. This report presents a case of patient with moderate haemophilia A and unstable angina pectoris, who underwent successful coronary angioplasty. The patient was pretreated with factor VIII (before and after the procedure) and the incision site was sealed with vessel closure device. Additionally, the article discusses the issue of the safety of standard, postpercutaneous coronary intervention antiplatelet therapy in patients with haemophilia.

Preliminary report of expression of bax in oral cavity pathologies.

Bax is considered one of major effectors of apoptosis--programmed cell death. Immunohistochemical analysis of in vitro patterns of bax expression was mostly investigated in mammalian cell lines and tissues. The present study is the first in vivo molecular analysis of bax expression in oral cavity pathologies. The study population consisted of 45 patients with hyperplasia, neoplasm in situ malignancy, and carcinoma. Biopsies were taken from incision line, tumour section, and healthy tissue. bax expression was investigated depending on the site of biopsy material sampling and final histopathology result. No statistically significant difference was demonstrated in bax expression between four hyperplasia subgroups. However, statistically significant differences in bax expression were found between the three basic study groups (P = 0.001). Statistically significant differences in bax expression were demonstrated depending on tissue collection site (P = 0.0002). We conclude that differences in bax expression may play a role in the pathogenesis of neoplastic disease.

Comparative study of neutrophil activities in adults and full-term neonates in relation to the method of delivery.

The aim of this study was to compare the markers of neutrophil activity in healthy adults with those in healthy neonates in relation to the method of delivery. The following parameters were studied: absolute neutrophil count, neutrophil adherence to nylon fiber, NBT reduction, and neutrophil phagocytosis of latex particles. The study has shown that the method of delivery significantly affects the markers of neutrophil activity measured in umbilical cord blood. The levels of these markers were higher in neonates born by elective cesarean section than in adults, neonates born vaginally or those born by emergency cesarean section. This comparative study of defensive functions of neutrophils from adults and neonates indicates that the conflicting results of other studies may be caused not only by differences in investigative methodology but also by the fact that the eligibility criteria used in these studies did not include the method of delivery, which can affect the markers of neutrophil activity via triggering a stress response.

[Comparison study of some neutrophils indices in neonates and adults]. / Próba porównania wybranych wskazników granulocytarnych u noworodków oraz u osób doroslych.

The purpose of this study was to estimate the difference in a range of number values, function and metabolism of neutrophil granulocyte sampled from umbilical cord of healthy and full-term newborns and healthy adults. The following indices were measured: total neutrophils number, neutrophil adherence to fibre, nitrobluetetrazolium reduction ability, phagocytic activity, alkaline phosphatase activity and lysozyme activity in serum. Results of the study showed that neutrophils from healthy newborns, when compared with neutrophils from adults, demonstrated the increase of oxidation-reduction processes, the increase of alkaline phosphatase activity in these cells and lysozyme activity in serum. It was associated with the increase of count of neutrophils what resulted from the decrease of their adherence.

A high resolution PIXE measurement for blood plasma ultrafiltrate. Application to loosely bound copper.

A new technique for investigation of elemental concentrations in subfractions of blood plasma is presented. The method is composed of the ultrafiltration of plasma in the presence of ethylenediaminetetraacetic acid (EDTA) and the measurement of the elemental composition by proton-induced X-ray emission (PIXE). The blood samples were collected from both healthy persons and patients suffering from breast cancer. The main emphasis in this study was on the determination of loosely bound copper (Cu) in plasma subfractions containing substances with molecular mass under 10,000, but zinc (Zn) and iron (Fe) contents of these fractions were also determined. The detection limits obtained with this method for Cu, An and Fe were approximately 10 ppb (wet wt).

Early breast cancer, diet, and plasma copper fractions.

In a study of diet and early breast cancer, blood plasma copper has been analyzed by Proton Induced X-ray Emission analysis as both total copper (P-Cu) and that ultrafiltrable from plasma (P-edu-Cu) through membranes with a cut-off at molecular mass 10,000 after equilibration with disodium ethylene diamine tetraacetic acid (EDTA) at 4 degrees C. Ceruloplasmin (P-cer) was also measured using nephelometry of anticeruloplasmin monoclonal antibody-ceruloplasmin complexes. Dietary copper intake per day (D-Cu) was assessed over a five-day dietary record period and calculated from dietary components using a computer program. P-edu-Cu correlated significantly with both D-Cu and ceruloplasmin while P-Cu correlated only with ceruloplasmin. Further, ceruloplasmin did not significantly correlate to D-Cu. Hence, P-edu-Cu better reflects copper status than do P-cer or P-Cu as it relates to both the major copper enzyme in plasma and to daily copper intake. This may be important in drawing conclusions about the significance of copper in disease states where copper fractions other than ceruloplasmin may be most important owing, for example, to oxidative properties. Categorization as cancer or normal, by copper parameters (D-Cu, P-edu-Cu, P-Cu, P-cer), was studied in multiple correlation. In particular, the ratio P-cer/P-Cu and the ratio P-edu-Cu/D-Cu were significantly related to disease. Irrespective of age (pre- and post-menopausal), highly significant differences between normals and early stage breast cancer patients were seen with p < 0.0001 to p < 0.01. The precise role played by plasma and dietary copper fractions deserves continued attention in view of the present and earlier results in cancer studies.

[Comparison of selected indices of nonspecific immunity estimated in peripheral blood of patients with untreated duodenal ulcer and after treatment with ranitidine]. / Porównanie wybranych wskazników odpornosci nieswoistej ocenianych we krwi obwodowej pochodzacej od chorych z nieleczonym wrzodem dwunastnicy i po leczeniu ich ranitydyna.

In 20 patients (8 women and 12 men) aged of 20-56 years (38 years on the average) with the yet untreated duodenal bulb ulcer selected indices of nonspecific immunity in peripheral blood (total leukocytes number and absolute neutrophils (N) number, N adherence to fibre, spontaneous leukocytes migration in a 3 hour test, N phagocytic activity and bactericidal activity of plasma and leukocytes) were estimated. Those indices were again estimated after two week of treatment with ranitidine, 150 mg every 12 hours. After ranitidine treatment reduction of the total leukocytes number and absolute N number was found, as compared with the pretreatment results. In addition to that treatment an increase of N adherence and their phagocytic activity was observed with unchanged leukocyte capacity for spontaneous migration. No statistically significant difference was observed in bactericidal activity of plasma and leukocytes. The following conclusions were reached. 1. Two-week treatment of duodenal ulcer patients with 150 mg ranitidine every 12 hours was followed by reduction of the total leukocytes and N numbers in peripheral blood, and by augmentation of their adherence and phagocytic activity. 2. Bactericidal activity of plasma and leukocytes and leukocytes capacity for spontaneous migration did not show any changes after two-week ranitidine treatment of duodenal patients.

[Phagocytosis and NBT test and phosphatase activity of peripheral blood neutrophils in patients with untreated duodenal ulcer]. / Fagocytoza i test NBT oraz aktywnosc fosfatazy zasadowej granulocytów obojetnochlonnych krwi obwodowej u chorych z nieleczonym wrzodem dwunastnicy.

In 21 patients with active, endoscopically confirmed untreated duodenal ulcer and in a control group of 20 persons, the studies were carried out of peripheral blood neutrophils which included: 1) test with the assessment of neutrophil phagocytic activity against live bacterial cells of the Staphylococcus aureus Oxford 209P standard strain and against latex particles, 2) test of nitroblue tetrazolium reduction (NBT test) by neutrophils, 3) evaluation of alkaline phosphatase activity in the neutrophils by a cytoenzymatic technique. In the group of patients as compared with the control group a decrease was observed of neutrophil phagocytic activity against live bacterial cells, and absence of similar differences was noted when latex particles were the stimulating factor. In the studied group an increase of the value of the index of spontaneous NBT reduction by neutrophils was observed as well as a decrease of the value of the index of latex-stimulated reduction of this dye. Besides that, higher alkaline phosphatase activity was observed in the neutrophils in patients as compared to the activity of this enzyme in the neutrophils of healthy persons. It may be supposed that in patients with duodenal ulcer, peripheral blood neutrophils reveal changes in the function of membranous structures of these cells, and disturbances of redox processes evaluated in the test with NBT.

[Activity of lysozyme in serum and selected granulocytic cytoenzymatic markers evaluated in patients with duodenal ulcer treated with ranitidine]. / Aktywnosc lizozymu w surowicy i wybrane granulocytarne wskazniki cytoenzymatyczne oceniane u chorych z wrzodem dwunastnicy leczonych ranitydyna.

In 20 patients with active, endoscopically confirmed duodenal ulcer, serum lysozyme activity, metabolic and phagocytic activity of neutrophils using the NBT spontaneous and stimulated test and stimulated test, and cytoenzymatic reaction for alkaline phosphatase were evaluated before treatment and after two weeks of treatment with ranitidine 150 mg every 12 hours. In some of the studies carried out the differences were obtained between the mean results which turned out to be statistically significant. In the group of patients with duodenal ulcer after two weeks of treatment with ranitidine, a statistically significant increase was found of diluted serum lysozyme activity as compared to the activity of this enzyme before the treatment. After the treatment with ranitidine, a statistically highly significant increase was noted of alkaline phosphatase activity in the neutrophils as compared to the activity of this enzyme assessed in patients with untreated duodenal ulcer. On the basis of the obtained results of studies the conclusions were formulated: 1) The increase of diluted serum lysozyme activity in the patients with duodenal ulcer after two weeks of treatment with ranitidine may evidence the presence of inhibitors of the enzyme in the serum of the studied group. 2) In patients with duodenal ulcer after two weeks of treatment with ranitidine the activity increases of cytoenzymatically determined alkaline phosphatase in the neutrophils, while the cytoenzymatically determined values of the markers in the test with NBT remain unchanged.

[Hemolytic microangiopathic anemia occurring in a patient with simultaneous cancer in two organs]. / Niedokrwistosc hemolityczna mikroangiopatyczna skojarzona z jednoczesnym wystepowaniem u chorego raka dwóch narzadów.

A case is described of rarely observed hemolytic microangiopathic anaemia associated with gastric and renal cancer. It is stressed that the diagnosis of this anaemia should be for the doctor an indication for searching for the cause of primary disease in which damage to the small blood vessels develops.

Concentrations of human choriogonadotropin, its beta-subunit, and the core fragment of the beta-subunit in serum and urine of men and nonpregnant women.

Sensitive, specific time-resolved immunofluorometric assays were used to measure the concentrations of human choriogonadotropin (hCG), free beta-subunit (beta-hCG), and the core fragment of beta-hCG (c beta-hCG) in serum and urine of men and nonpregnant women without evidence of cancer. Concentrations of hCG and beta-hCG were measurable in 59-70% of serum samples and in 50-59% of urine samples. c beta-hCG was mostly undetectable in serum but measurable in 81% of urine samples. Concentrations were higher in women than in men, and hCG concentrations increased with age. Therefore, reference ranges based on the 97.5 percentile were calculated separately for women and men and for those < 50 and > 50 years. However, concentrations of hCG correlated much more strongly with those of follicle-stimulating hormone than with age. hCG concentrations in serum were similar to those reported before, but beta-hCG concentrations were below the detection limit of earlier assays, and the upper reference limit was one-fifth to one-tenth the cutoff concentrations used earlier. In urine, hCG and c beta-hCG were the major forms of hCG, and their concentrations were similar to those of hCG in serum.

Evidence for increased non-ceruloplasmin copper in early-stage human breast cancer serum.

We measured total serum copper and ceruloplasmin levels in pre- and postmenopausal Stage I and II breast cancer (BC) patients and omnivorous and vegetarian controls. The omnivorous groups included 14 premenopausal women [33 +/- 6 (SD) yrs] and 11 postmenopausal women (57 +/- 5 yrs), and the vegetarian groups were comprised of 12 premenopausal subjects (34 +/- 7 yrs) and 11 postmenopausal subjects (59 +/- 5 yrs). There were 13 premenopausal BC patients (39 +/- 7 yrs) and 10 postmenopausal BC patients (66 +/- 6 yrs). Fasting serum samples were taken on three consecutive days, typically four times in the year. Serum ceruloplasmin levels (g/l) were measured by nephelometry utilizing monoclonal antiserum, and total serum copper levels (mumol/l) were determined by proton-induced X-ray emission analysis. Premenopausal patients had higher serum copper levels than their controls (mean 18.7 vs. 16.6, p less than 0.03). For ceruloplasmin, the postmenopausal BC patients had significantly lower levels than pooled postmenopausal controls (0.309 vs. 0.370, p less than 0.001). The copper-to-ceruloplasmin ratio was significantly higher in the pooled cancer groups than in the pooled control groups (3.69 vs. 3.21, p less than 0.001), with similar patterns in both pre- and postmenopausal classes. This high serum copper-to-ceruloplasmin ratio in BC patients may reflect disordered copper metabolism in this disease, which could also have implications for the origin of, or the response to, the cancer process.

An emerging view of vitamin D.

Vitamin D3 (D2 is 22-ene,24-methyl D3) is a prehormone which is hydroxylated by mixed function mono-oxygenase NADPH-cytochrome P-450 ferredoxin/ferredoxin reductase systems in liver parenchyma and renal proximal tubular cells to 25-hydroxy, then 1,25-dihydroxyvitamin D, the active hormone. 1,25-dihydroxyvitamin D binds to a mainly intranuclear receptor in target cells [classically, bone, kidney and gut; now shown to be wider including parathyroid cells, endocrine cells generally and many cells of ectodermal (brain, skin) and mesodermal (blood forming cells, lymphnode cells) origin as well as tumour cells (breast, lymphoma, leukaemia)] and activates transcription for products such as calcium binding proteins, its own receptor protein, 24-hydroxylase and non-specific esterase which are active in calcium homeostasis and cell differentiation. Advanced methods for measuring components of the vitamin D endocrine system have been developed and involve column extractions, liquid chromatographic purifications (also HPLC) and protein and receptor binding assays as well as mass spectrometry. These have facilitated elucidation of vitamin D physiology (also in pregnancy and lactation) and of metabolic defects in classical, vitamin D resistant and renal rickets and osteomalacia, in sarcoidosis and in the possible involvement of the vitamin in cell differentiation, e.g. in myeloid leukaemia, and breast cancer.

Trace element studies on whole human cerebrospinal fluid with external beam PIXE.

External beam PIXE analysis with a 2.4 MeV proton beam was used to determine the concentrations of K, Ca, Fe, Cu, Zn and Br in cerebrospinal fluid from patients having various disorders. The obtained total concentration ranges K 34,000-1,079,000, Ca 5300-81,300, Fe 40-1030, Cu 20-1650, Zn 15-1250 and Br 400-43,000 micrograms/kg are compared with the values given in the literature. In certain patients there were very high CSF bromine levels, but this was shown to be the result of taking medications presented as bromide salts. The possibility of using the method in clinical practice for CSF analysis is considered. The new method of preparing self-supporting films of the samples was used. This method was further optimized by investigating in detail the use of EDTA as a homogenizer.