Regional aortic compliance studied by magnetic resonance imaging: the effects of age, training, and coronary artery disease.

Arterial compliance was measured in 70 healthy volunteers, 13 athletes, and 17 patients with coronary artery disease. Magnetic resonance images were acquired at end diastole and end systole through the ascending aorta, the aortic arch, and the descending thoracic aorta. Regional compliance was derived from the change in luminal area in a slice of known thickness and from the pulse pressure. Total arterial compliance was also measured from the left ventricular stroke volume and the pulse pressure. In the volunteers, mean (SD) regional compliance (microliters/mm Hg) was greatest in the ascending aorta (37 (18], lower in the arch (31 (15], and lowest in the descending aorta (18 (8], and it decreased with age. Compliance in the athletes was significantly higher than in their age matched controls (41 (16) versus 22 (11) microliters/mm Hg). In the patients with coronary artery disease it was significantly lower (12 (4) v 18 (10] than in age matched controls. Total arterial compliance also fell with age in those with coronary artery disease although there was more variation. The results suggest a possible role for compliance in the assessment of cardiovascular fitness and the detection of coronary artery disease.     

Hyperprolactinemia--a review of recent clinical advances

Since the radioimmunoassay for serum prolactin became available eight years ago, prolactin has become a hormone of considerable clinical interest. An elevated serum prolactin concentration is the most frequent hormone marker for pituitary tumors. Secreted in excess, prolactin causes dysfunction of the hypothalamic-pituitary axis, the gonads, and the adrenal cortex. In women, menstrual disturbances, galactorrhea, infertility, and hirsutism result. Impotence, oligospermia, and decreased libido are common in men. These metabolic abnormalities attributed to prolactin excess are corrected when prolactin concentrations are lowered by either medical or surgical therapy. The availability of effective therapy mandates early recognition and proper management of the patient with hyperprolactinemia.     

Do patients with moderately impaired gastrointestinal function requiring enteral nutrition need a predigested nitrogen source? A prospective crossover controlled clinical trial.

This prospective double blind randomised seven day crossover controlled clinical trial was carried out to determine whether enterally fed patients with moderately impaired gastrointestinal function require a predigested nitrogen (N) source compared with whole protein. Twelve malnourished patients with varying gastrointestinal abnormalities, who required enteral feeding, received 2.25 l of one of two isocaloric isonitrogenous enteral diets (1 kcal/ml, 4.8 g nitrogen/l) containing either predominantly medium chain peptides (tetra or higher peptides) or whole protein as the nitrogen source. Nitrogen absorption and balance were calculated from dietary intake and analysis of 24 hour total urinary and faecal nitrogen for the last five days of each study period. There was no significant difference in either stool weight (110 (SEM) (49) v 111 (32) g/d), nitrogen absorption (91 (2) v 89 (2)%) or nitrogen balance (+1.0 (1.3) v +0.6 (1.4) g nitrogen/d) between the peptide and whole protein nitrogen sources when all patients are considered. There was, however, evidence to suggest a nutritional advantage from administering an enteral diet whose nitrogen source comprises oligopeptides, rather than whole protein, to a subgroup of patients with small bowel disease.     

Habituation of the corticosterone response of ducks (Anas platyrhynchos) to daily treadmill exercise

The habituation of the corticosterone response of ducks to treadmill exercise (1.1 km/hr 0 degrees incline for 60 min) has been determined over a 28-day period. In untrained birds 30 min of treadmill exercise resulted in a marked (P less than 0.001) increase in the basal plasma corticosterone level. After 60 min of exercise the corticosterone concentration remained elevated (P less than 0.001) in comparison with basal and control (nonexercised) levels but was less (P less than 0.01) than that at 30 min. Following exercise the concentration declined to basal levels within 60 min. After 7 days of daily training the peak (30 min) corticosterone response to exercise diminished by greater than 50% and was absent in birds trained for 21 days. This habituation of the corticosterone response may be due to adrenocortical stimulation by pituitary adrenocorticotrophin (ACTH) being reduced. As the stimulatory effect of ACTH administration (8 IU/kg) on corticosterone secretion does not habituate in birds treated daily (for 28 days), the reduced corticosterone response to exercise may be due to decreased ACTH release rather than to a reduction in adrenal ACTH sensitivity.     

Immunohistochemical localization of relaxin, prolactin and prostaglandin synthase in human amnion, chorion and decidua

Relaxin, prolactin and prostaglandin synthase were localized by the avidin-biotin immunoglucose oxidase method in human amnion, chorion and decidua. Specimens from ten normal spontaneous deliveries and four elective Caesarean section deliveries with no labour were compared. Relaxin was found more consistently in the cells of the chorionic cytotrophoblast than in the cells of the parietal decidua adherent to the fetal membranes. Only half the tissues after spontaneous delivery contained positive relaxin-stained cells, whereas all the tissues from elective Caesarean sections contained cells positively stained with antiserum to relaxin. In both series of tissues prolactin was localized predominantly in the parietal decidual cells and was very infrequently found in the chorionic cytotrophoblast. Polyclonal antiserum to prostaglandin synthase was used to identify those cells producing prostaglandin in amnion, chorion and decidua. The cells of the amnion and chorion showed positive immunolocalization with no differences between tissues collected before or after labour. Double immunostaining using avidin-biotin immunoperoxidase for prolactin, followed by avidin-biotin immunoglucose oxidase for prostaglandin synthase, produced identical results in the same series of tissues examined with the single-staining method.     

Microarray analysis reveals a major direct role of DNA copy number alteration in the transcriptional program of human breast tumors

Genomic DNA copy number alterations are key genetic events in the development and progression of human cancers. Here we report a genome-wide microarray comparative genomic hybridization (array CGH) analysis of DNA copy number variation in a series of primary human breast tumors. We have profiled DNA copy number alteration across 6,691 mapped human genes, in 44 predominantly advanced, primary breast tumors and 10 breast cancer cell lines. While the overall patterns of DNA amplification and deletion corroborate previous cytogenetic studies, the high-resolution (gene-by-gene) mapping of amplicon boundaries and the quantitative analysis of amplicon shape provide significant improvement in the localization of candidate oncogenes. Parallel microarray measurements of mRNA levels reveal the remarkable degree to which variation in gene copy number contributes to variation in gene expression in tumor cells. Specifically, we find that 62% of highly amplified genes show moderately or highly elevated expression, that DNA copy number influences gene expression across a wide range of DNA copy number alterations (deletion, low-, mid- and high-level amplification), that on average, a 2-fold change in DNA copy number is associated with a corresponding 1.5-fold change in mRNA levels, and that overall, at least 12% of all the variation in gene expression among the breast tumors is directly attributable to underlying variation in gene copy number. These findings provide evidence that widespread DNA copy number alteration can lead directly to global deregulation of gene expression, which may contribute to the development or progression of cancer.     

Serum thyroglobulin measurements with a high sensitivity enzyme-linked immunosorbent assay: is there a clinical benefit in patients with differentiated thyroid carcinoma?

Serial serum thyroglobulin (Tg) measurements with a highly sensitive enzyme-linked immunosorbent assay (ELISA; functional sensitivity 0.03 ng/mL) in 126 patients (Tg autoantibody negative) with treated differentiated thyroid cancer (DTC) are described. At the beginning of the retrospective study, all 126 patients were in remission and Tg was detectable by ELISA in 92 (73%; range, 0.03-0.8 ng/mL). Over the following 4-year period, Tg levels remained essentially unchanged (i.e., any increases were less than 2 times the Tg level at the start of the study) in 121 of 126 (96%) and all 121 patients remained well. In 5 patients, Tg levels increased to more than 2 times the starting Tg level over the study period and in 4 of these 5, there was recurrence of DTC. The fifth patient in this group remains well as evidenced by extensive diagnostic imaging, although his serum Tg level continues to increase and can be stimulated by thyrotropin (TSH). Our results suggest that serial measurements of low levels of Tg by ELISA in treated patients with DTC enable detection of recurrence (without using TSH stimulation) 6-12 months earlier than would have been possible using a conventional Tg immuno-radiometric assay (IRMA). A prospective study is now needed to confirm these observations.