Blood flow and metabolism in locally advanced breast cancer: relationship to response to therapy.

Unlabelled: Locally advanced breast cancer (LABC) is commonly treated with neoadjuvant chemotherapy followed by definitive surgery. The factors influencing the response of LABC to presurgical chemotherapy are incompletely understood. To characterize in vivo tumor biology in patients with LABC, we measured pretherapy blood flow and glucose metabolism in LABC, compared measurements with clinical and pathologic parameters, and examined blood flow and response to subsequent neoadjuvant chemotherapy.

Detection of locoregional and distant recurrences in breast cancer patients by using FDG PET.

Cases of recurrence of breast cancer can pose considerable diagnostic and therapeutic challenges for the oncologic team. The prognosis and management decisions are based on knowledge of the true extent of disease. Conventional staging methods, including physical examination, assessment of levels of tumor markers, cross-sectional imaging, and bone scintigraphy, may not reliably demonstrate the extent of disease in all cases.

Single nucleotide polymorphism array analysis of flow-sorted epithelial cells from frozen versus fixed tissues for whole genome analysis of allelic loss in breast cancer.

Analysis of allelic loss in archival tumor specimens is constrained by quality and quantity of tissue and by technical limitations on the number of chromosomal sites that can be efficiently evaluated in conventional analyses using polymorphic microsatellite markers. Newly developed array-based assays have the potential to yield genome-wide data from small amounts of tissue but have not been validated for use with routinely processed specimens. We used the Affymetrix HuSNP assay, composed of 1494 single nucleotide polymorphism sites, to compare allelic loss results obtained from both formalin-fixed and frozen breast tissue samples.

Internal mammary lymph node drainage patterns in patients with breast cancer documented by breast lymphoscintigraphy.

Background: Metastases to internal mammary lymph nodes (IMN) may occur in patients with breast cancer and may alter treatment recommendations. The purpose of this study was to identify the frequency of IMN drainage in patients undergoing breast lymphoscintigraphy and sentinel lymph node dissection (SLND).

Methods: The combined technique of peritumoral injection of radiocolloid and Lymphazurin blue for SLND was performed on 220 patients.

NMR characterization of a novel bile acid sequestrant, DMP 504.

DMP 504, a potential bile acid sequestrant for the treatment of hypercholesterolemia, is a highly insoluble, cross-linked polymer which does not lend itself to ordinary means of characterization used for drug substances in the pharmaceutical industry. Therefore, alternative characterization techniques have been sought. As part of an effort into extensive characterization of DMP 504 drug substance, nuclear magnetic resonance (NMR) was employed to provide insight into details of the DMP 504 polymer structure.

Low-frequency respiratory rhythms in infants during the first six months of life.

The aim of the study was to investigate characteristics of low-frequency components in respiration. Sixteen healthy term infants were examined from the first day up to the 6th month of life. The respirogram, instantaneous respiratory frequency and respiratory amplitude of undisturbed segments of quiet sleep phases and periodic breathing (PB) were analysed via fast Fourier transformation.

Single nucleotide polymorphisms (SNPs) in the estrogen receptor gene and breast cancer susceptibility.

In order to evaluate the role of inherited variation in the estrogen receptor (ESR1) gene in human breast cancer, we determined intronic sequences flanking each ESRI exon; identified multiple SNPs and length polymorphisms in the ESR1 coding sequence, splice junctions and regulatory regions; and genotyped families at high risk of breast cancer and population-based breast cancer patients and controls. Of 10 polymorphic sites in ESR1, four are synonymous SNPs, two are nonsynonymous SNPs and four are length polymorphisms; five are novel. No ESR1 polymorphisms were associated with breast cancer, either in the high-risk families or the case-control study.

Inherited breast cancer: an emerging picture.

A role for BRCA1 and BRCA2 in the control of genome integrity easily fits a tumor suppressor model. It is well established that mutations in DNA repair genes lead to genomic instability (138). Genomic instability may directly lead to tumorigenesis by allowing for the accumulation of mutations in key cell cycle regulators (139).

Detection and characterization of two cytotoxins produced by Campylobacter jejuni strains.

Campylobacter jejuni strains are able to produce at least two different cytotoxins called "cytolethal distending toxin" (CLDT) and "cytolethal rounding toxin" (CLRT). In this study, we investigated the corresponding changes in CHO-K1 cells using the cell counter and analyzer system CASY 1. Determination of the cell volume after toxin treatment of the cells is a useful criterion for differentiation between the cytotoxic activities produced by Campylobacter strains.

Haplotype and phenotype analysis of nine recurrent BRCA2 mutations in 111 families: results of an international study.

Several BRCA2 mutations are found to occur in geographically diverse breast and ovarian cancer families. To investigate both mutation origin and mutation-specific phenotypes due to BRCA2, we constructed a haplotype of 10 polymorphic short tandem-repeat (STR) markers flanking the BRCA2 locus, in a set of 111 breast or breast/ovarian cancer families selected for having one of nine recurrent BRCA2 mutations. Six of the individual mutations are estimated to have arisen 400-2,000 years ago.

A splicing mutation in RB1 in low penetrance retinoblastoma.

The pediatric eye-tumor retinoblastoma is widely held as a paradigm of human cancer genetics and has been a model system for both the two-hit hypothesis of dominantly inherited cancer as well as for the concept of tumor-specific loss of constitutional heterozygosity to achieve expression of the tumorigenic phenotype. Familial retinoblastoma is usually inherited as an autosomal dominant disease with high penetrance and expressivity. In a small but significant number of families, however, retinoblastoma is inherited with greatly reduced penetrance and expressivity.

Linear and nonlinear properties of heart rate control in infants at risk.

The aim of this study was to test whether the heart rate (HR) control in infants at risk differs in comparison with healthy infants. Twelve former preterm infants suffering from bronchopulmonary dysplasia and 18 control infants, matched for their postconceptional age, were examined polygraphically during quiet and active sleep. HR, low-frequency (LF) power, high-frequency (HF) power, total power, and the ratio of LF to HF power (LF/HF) of the instantaneous HR spectra were calculated for linear analysis.

BRCA2 in American families with four or more cases of breast or ovarian cancer: recurrent and novel mutations, variable expression, penetrance, and the possibility of families whose cancer is not attributable to BRCA1 or BRCA2.

In order to evaluate the role of inherited BRCA2 mutations in American families--particularly the appearance in America of European founder mutations--the BRCA2 coding sequence, 5' UTR, and 3' UTR were screened in 22 Caucasian American kindreds with four or more cases of breast or ovarian cancer. Six mutations were found that cause a premature-termination codon; four of them have been reported elsewhere, and two are novel. In the four families with previously seen mutations, the distinct lineages at high risk of cancer were of Dutch, German, Irish, and Ashkenazi Jewish ancestry; mutations in Europe reflect these ancestries.

BRCA1 and BRCA2 mutations in Ashkenazi Jewish families with breast and ovarian cancer.

The strongest risk factors currently known for inherited predisposition to breast and ovarian cancer are mutations in BRCA1 and BRCA2. Two mutations in BRCA1 and one mutation in BRCA2 have been identified that are present to a particularly high degree in the Ashkenazi Jewish population due to ancient founder effects. To clarify the role of ancient and novel BRCA1 and BRCA2 mutations in the Ashkenazi Jewish population, families with a strong history of breast and ovarian cancer were examined.

Wakefulness and arousal in neonates born to women with schizophrenia: diminished arousal and its association with neurological deviations.

Arousal at 3-4 days of age was blindly assessed during the course of a standardized neurological examination of offspring born to index women with schizophrenic (n = 20), schizo-affective (n = 12), affective (n = 19) and unspecified functional (n = 4) psychoses, as well as 70 offspring born to control women with no history of psychosis. The offspring of women with schizophrenia was the only index group to differ from controls in showing significantly reduced arousal. Among the offspring of schizophrenics, reduced arousal was associated with neurological abnormality and deviant sensitivity to stimulation but not with obstetric complications.

Development of heart rate power spectra reveals neonatal peculiarities of cardiorespiratory control.

Postnatal adaptation should be associated with changes in cardiac rhythmic behavior. To examine the development of heart rate variability, instantaneous heart rate (IHR) and the corresponding breathing signals of 16 healthy infants were analyzed. This was pursued by use of fast Fourier transformation beginning with the 1st day until the 6th mo of life.

Developmental aspects of the interaction between the controls of heart rate and respiratory rhythm--linear and nonlinear components of diverse activity states in childhood.

Heart beat and respiration are rhythmical phenomena with separate intrinsic frequencies which necessarily have to be effectively tuned by a network of interactive processes. Their linear and nonlinear components may ripen in different ways during childhood thus leading to unstable transitions or risk of dangerous events. This study investigates the development from newborns to children mainly between sleep and wakefulness.

Interaction of heart-rate fluctuations and respiration in 12 to 14-year-old children during sleeping and waking.

Our study was designed to investigate and quantitatively characterise the interaction of breathing and instantaneous heart rate. Comparisons were made during consciousness at rest, and during non-REM sleep. 31 12-14-year-old healthy children were subjected to a 24-h polygraphic electrocardiogram, respirogram, electrooculogram and actogram measurements.

Linear and non-linear properties of heart rate in postnatal maturation.

Objective: An investigation was made of how postnatal maturation of cardiac control can be described by linear and non-linear methods of time series analysis.

Methods: Sixteen healthy and term newborns were studied during their first 6 months of life. Power spectrum analysis including total power (TP), low frequency power (LF), high frequency power (HF) and LF/HF ratio were performed on the instantaneous heart rate (IHR) time series and mean heart rate (HR) was derived.

A previously unknown polymorphism located within the RB1 locus only present in Asian individuals.

Although the retinoblastoma susceptibility locus (RB1) spans some 180 kb in the human and has been fully sequenced, few polymorphisms within the locus have been identified and none have been shown to vary in allelic frequency in different populations. We have identified a previously unknown polymorphism within intron 18 of the retinoblastoma susceptibility gene that is present in Asians but not in the other ethnic groups examined. This polymorphism eliminates a Tsp5091 restriction enzyme site, making it easily detectable for use in linkage analysis and genetic population studies.

[Sleep structure in relation to respiration and heart rate in children in puberty].

The different expression of respiratory sinus arrhythmia in REM- versus nonREM-sleep indicates a dependence of cardiorespiratory interaction on patterns of sleep. Investigations of the intensity of respiratory entrainment on heart rhythmicity during various stages of sleep will provide an insight into the coupling of cardiorespiratory interaction and sleep patterns. 42 healthy children (12 to 15 years old) were polygraphically investigated over 24 h.

[Nonlinear dynamics in regulation of heart rate in healthy infants].

The aim of this study was to investigate qualitatively and quantitatively non-linear and linear characteristics of heart rate identifying their connection to sleep states during the first 6 months of life. 16 newborns were examined polygraphically in a longitudinal study (first day, first and sixth month). After R-peak detection of a limb lead ECG and R-R interval calculation, time series of the instantaneous heart rate (IHR) were constructed.

The theory of and experimentation into respiratory gas exchange--Carl Ludwig and his school.

Investigations of respiratory functions progressed considerably in the middle of the 19th century. Motive forces for this were the improvement of basic medical sciences due to the progress in science politics, the evolution of exact measuring methods owing to the improvement of natural sciences and the origin of the ideology of antivitalism and organic physics, revealed by the striving of their leading scientists including Carl Ludwig. Formerly, exchange of O2 and CO2 was related merely to the lungs without exact knowledge of data or mechanisms.