Endotelial activation and flow-mediated vasodilation in young patients with breast cancer.

Endothelial activation and dysfunction may play a significant role in the progression of breast cancer. In our study we examined markers of endothelial activation (soluble ICAM-1, P-selectin, E-selectin) in 98 young patients with breast cancer (< 40 years). In 50 of them (and 20 age-matched controls) we also measured flow mediated vasodilation. Patients with breast cancer had significantly higher serum levels of soluble E-selectin, P-selectin and ICAM-1, P-selectin was higher in patients with larger tumors, node involvement and seemed to be apredictor of poor outcome. We were unable to find significant difference in the parameters of flow mediated vasodilation between patients with breast cancer and healthy subjects, although both peak blood flow (PBF) and flow mediated vasodilation (FMD) seemed to be skewed compared to healthy subjects toward mean and lower levels. Cluster analysis enabled us to distinguish several larger groups of patients with different degree of endothelial activation and function and different outcome. Group of patients with high E-selectin, high ICAM-1 (higher endothelial activation) and low VEGF (putative endothelial damage) had more frequently negative estrogen receptors and had worse outcome compared to the group of patients with lower E-selectin, lower ICAM-1 and mostly positive estrogen receptors. Further studies of larger groups of patients should help to identify the panel of endothelial markers which could help in predicting the outcome of young patients with breast cancer.

Menopause: clustering of metabolic syndrome components and population changes in insulin resistance.

AIM: The incidence of the metabolic syndrome (MS) in women rises rapidly during the menopause, substantially increasing their cardiovascular risk and mortality. The aim of the study was to analyze menopausal changes in individual MS components and the parameter of insulin resistance (HOMA-IR). METHODS: A random population sample of 909 women aged 45-54 years, resident in Prague 4, was examined in an epidemiological study. After excluding women with gynecological hormone therapy or surgical therapy, the two groups of women were compared: women of reproductive age (REPRO, n = 245) vs. naturally postmenopausal women (POSTm, n = 149). RESULTS: The incidence of MS rose significantly in menopause (REPRO/POSTm 22.9 ± 2.6%/38.3 ± 4.0%; p < 0.001). However, a detailed analysis among the five components defining MS showed that increases were only seen in waist circumference (p < 0.0001) and triglycerides (p < 0.001). There was no increase in the other components or HOMA-IR. A detailed analysis showed an increase in HOMA-IR at levels above the median (REPRO/POSTm: low HOMA-IR 0.9/0.9, not significant; high HOMA-IR 1.8/2.1, p < 0.001) and an increase in the incidence of MS just in these high levels of HOMA-IR and those rising during menopause (REPRO/POSTm: low HOMA-IR 13.8%/18.7%, not significant; high HOMA-IR 30.9%/57.3%, p < 0.0001). In menopause, there was an increase in the clustered incidence (accompanying MS) of each of the five MS components at the expense of isolated incidence (not accompanying MS). CONCLUSION: The acceleration of MS incidence at the onset of menopause may be accompanied by an increase in insulin resistance only in the population at highest risk. Reproductive women entering the menopause with an isolated MS component are at high risk for developing additional risk factors during menopause.

An initiator codon mutation in ornithine-delta-aminotransferase causing gyrate atrophy of the choroid and retina.

Gyrate atrophy of the choroid and retina (GA) is an autosomal recessive chorioretinal degeneration caused by deficiency of the mitochondrial matrix enzyme, ornithine-delta-aminotransferase (OAT). To study the molecular basis of the mutations causing GA, we cloned and sequenced the human OAT cDNA and determined the intron-exon arrangement of the structural gene. Using the cDNA template, we synthesized antisense RNA probes and performed RNase A protection experiments with RNA from four Lebanese GA patients. We found a probe-target mismatch at the 5' end of the first coding exon and amplified this region of the patients' genomic DNA using the polymerase chain reaction. Sequence analysis showed a G----A transition, changing the initiator ATG (methionine) codon to ATA. This mutation segregates with the GA allele in both pedigrees. Initiation of translation at the closest in-frame methionine codon would truncate OAT by 138 amino acids, eliminating the entire mitochondrial leader sequence and 113 amino acids of the mature peptide.

Cloning, expression, and functional characterization of rat MIP-2: a neutrophil chemoattractant and epithelial cell mitogen.

Macrophage inflammatory protein-2 (MIP-2) is a member of a family of cytokines that play roles in inflammatory, immune, and wound healing responses. To clone the cDNA for rat MIP-2, RNA was isolated from the lungs of Fischer 344 rats after instillation of lipopolysaccharide. Reverse transcription-polymerase chain reaction was performed by using synthetic oligonucleotide primers designed from the mouse MIP-2 cDNA sequence. A cDNA containing the coding region of rat MIP-2 was cloned and sequenced. Comparison to the mouse MIP-2 cDNA demonstrated 90.3% homology at the nucleotide level and 86% homology at the amino acid level. The rat MIP-2 cDNA was expressed in Escherichia coli and protein evaluated for bioactivity. The recombinant rat MIP-2 was chemotactic for rat neutrophils but did not stimulate migration of rat alveolar macrophages or human peripheral blood eosinophils or lymphocytes. In addition, the recombinant rat MIP-2 and the related rat chemokine, KC/CINC stimulated proliferation of rat alveolar epithelial cells but not fibroblasts in vitro.

Qualitative analysis of green coffee by infrared spectrometry.

Principal component analysis and linear discriminant analysis (LDA) were applied to the mid-infrared spectra for the qualitative analysis of the variety of green coffee (Arabica and Robusta). It is shown that the KBr pellet technique in combination with the LDA method can successfully be used for the identification of sample origin.

Purification of xylenol orange by preparative paper chromatography, and examination of its zirconium complex.

Preparative paper chromatography is proposed as a suitable method for purification of Xylenol Orange (XO). The last three dissociation constants of pure XO have been determined with the aid of the program SPEKTFOT, the values found being pK(9) = 12.34; pK(8) = 10.66; pK(7) = 6.69 (0.1M KNO(3), 20 +/- 0.5 degrees ). The complexation of zirconium with the purified reagent has been studied and the co-existence of ML and M(2) L complexes proved by use of the program DALSFEK. The following conditional stability constants of the complexes and their molar absorptivities were computed: log beta'(ml) 4.58; log beta'(M(2)L) 11.59; (ML) 2.00 x 10(4); (M(2)L) 9.40x 10(4) l.mole(-1).cm(-1) at 550 nm.

The phosphate pool of isolated dog heart during global ischaemia: comparison of two cardioplegic solutions with 31P NMR spectroscopy.

31P NMR spectroscopy was used to study the time course of changes in the concentration of high-energy metabolites and intracellular pH in the dog myocardium during hypothermic ischaemia at 9 degrees C in Bretschneider (HTK-B) and St. Thomas' Hospital (StTH) cardioplegic solutions. It was found that ATP and phosphocreatine degrade slowlier in HTK-B than in StTH, with phosphocreatine depletion occurring within 7.9 +/- 1.4 h in HTK-B and within 6.2 +/- 1.4 h in StTH. The values are virtually identical with the time intervals at which ATP concentration falls below the critical level (60% of initial ATP concentration). In agreement with biochemical analysis, a higher concentration of phosphomonoesters was noted until the 180th minute of ischaemia in HTK-B, a finding suggesting more rapid glycogen degradation in HTK-B. Even though HTK-B contains a high concentration of histidine buffer, higher values of intracellular pH were found during ischaemia in StTH. The effect of extracellular concentration of sodium ions on intracellular pH is discussed.

[Location of the bundle of Kent in patients with Ebstein's anomaly of the tricuspid valve]. / Lokalizace Kentova svazku u pacientu s Ebsteinovou anomálií trikuspidální chlopne.

The prequisite of better therapeutic results in patients with Ebstein's anomaly of the tricuspid valve is more perfect diagnosis not only of the severity of the malformed valve but also of other associated defects incl. the anomalous accessory bundle of Kent which causes the development of dangerous tachydysrhythmias. The authors present their own experience with the localization of the bundle of Kent by mapping the endocardium of the atria in seven children before a cardiac operation. In all ventricular preexcitation type B with the bundle of Kent in the posterior lower portion of the atrial septum was found. In two non-operated patients who died with tachydysrhythmia which could not be controlled, the bundle of Kent was confirmed by histological examination, in three it was severed by operation, two patients are waiting to be operated. The authors recommend interruption of the bundle of Kent always concurrently with operation of the malformed tricuspid valve and other associated cardiac defects.

[Balloon dilatation of subvalvular membranous stenosis of the aorta in an 8-year-old boy]. / Balónková dilatace subvalvární membranózní stenózy aorty u osmiletého chlapce.

Case-history of an eight-year-old boy with subvalvular membranous aortal stenosis where the authors used for treatment percutaneous dilatation by means of a balloon catheter without using surgery. The authors recommend to eliminate the stenosis as soon as possible before serious aortal insufficiency develops.

[Ablation of the accessory bundle of Kent using radiofrequency current in a 17-year-old boy with type A Wolff-Parkinson-White syndrome]. / Prerusení akcesorního Kentova svazku radiofrekvencním proudem u sedmnáctileteho chlapce s WPW syndromem typu A.

The authors describe the in Czechoslovakia so far not used therapeutic catheterization ablation method of the accessory atrioventricular pathway in patients with tachycardia with the Wolff-Parkinson-White syndrome. They performed successful ablation of the accessory bundle of Kent located by electrophysiological examination behind the left atrium and left ventricle in a 17-year-old boy with WPW Syndrome type A. They severed the accessory pathway by radiofrequency current using a catheter inserted from a retrograde approach into the left ventricle beneath the mitral valve. After ablation the boy suffers no longer from tachycardia, the ECG tracing in devoid of preventricular preexcitation, although he has no medicamentous treatment.

[Postoperative atrioventricular and intraventricular block in tetralogy of Fallot. Electrophysiology study]. / Pooperacní sínokomorové a nitrokomorové blokády u Fallotovy tetralogie, elektrofyziologická studie.

One of the causes of the late deaths after operations of the tetralogy of Fallot are dysrhythmias caused by impaired conduction and automatism. To assess the severity and site of the atrioventricular and intraventricular block the authors used in 19 patients after operation of the tetralogy of Fallot an invasive electrophysiological examination. The authors recommend, based on their own experience, to follow-up on a long-term basis all patients with temporary postoperative complete a-v block. The presence of bifascicular or temporary postoperative a-v block alone does not yet imply the need of a permanent pacemaker. If a serious a-v block persists after the third week or if a syncope or cardiac weakness develops, the authors indicate a permanent pacemaker. Also the development of trifascicular block, even in patients with a normal P-Q interval, detected during fever, physical work or during electrostimulation of the atria is an indication for the introduction of a permanent pacemaker.

[Severance of the accessory bundle of Kent in a 13-year-old boy with Ebstein's anomaly of the tricuspid valve]. / Prerusení akcesorního Kentova svazku u 13-letého chlapce s Ebsteinovou anomalií trikuspidální chlopne.

In patients with Ebstein's anomaly of the tricuspid valve combined with WPW syndrome, possibly other cardiac disease, in particular with the repeated occurrence of severe tachydysrhythmias we can foresee cure or at least elimination of complaints by simultaneous surgical treatment of all defects. The author presents experience with the surgical treatment, the first of its kind in this country, in a boy aged 13 years. By better diagnosis it proved possible to locate correctly and to severe by surgery the abnormal accessory bundle between the right atrium and right ventricle, simultaneously with a plastic operation of the insufficient tricuspid valve with closure of the atrial septal defect. Since the operation the patient has no signs of ventricular preexcitation and has no tachydysrhythmias.