Validity of prostate-specific antigen as a tumour marker in men with prostate cancer managed by watchful-waiting: correlation with findings at serial endorectal magnetic resonance imaging and spectroscopic imaging

OBJECTIVE: To investigate the validity of prostate-specific antigen (PSA) as a tumour marker in men with clinically localized prostate cancer who have selected watchful waiting, by determining if serial PSA level measurements are correlated with findings of malignancy or benign prostatic hyperplasia (BPH) at serial endorectal magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI). PATIENTS AND METHODS: We retrospectively identified 69 men with biopsy-proven prostate cancer being managed by watchful waiting, who underwent serial endorectal MRI/MRSI and who had contemporaneous serial PSA measurements. The mean (range) follow-up was 392 (294-571) days. A panel of three experienced readers reviewed the initial and follow-up MRI/MRSI studies, and classified findings of prostate cancer as stable or progressive. Another reader assessed BPH by calculating total gland and central gland volumes on all studies. RESULTS: At the follow-up MRI/MRSI, 51, 17 and one patient had stable, progressive, or unevaluable prostate cancer, respectively. The mean PSA velocity was significantly greater in patients with radiologically progressive disease (1.42 vs 0.42 ng/mL/year, P = 0.04). A PSA velocity of >0.75 ng/mL/year identified those with radiologically progressive disease with a true-positive fraction of 0.71 and a false-positive fraction of 0.39. PSA levels were not correlated with changes in total or central gland volumes (P > 0.05). CONCLUSIONS: In men with clinically localized prostate cancer who select watchful waiting, serial PSA levels are correlated with findings of malignancy but not BPH at serial endorectal MRI/MRSI, suggesting that PSA is a useful longitudinal tumour marker in this population.     

Combined time-resolved and high-spatial-resolution 3D MRA using an extended adaptive acquisition

PURPOSE: To combine the benefits of time-resolved dynamic imaging and single elliptical centric acquisitions in a reasonable scan time. MATERIALS AND METHODS: A time series of images with moderate spatial resolution was acquired using the 3D Time-Resolved Imaging of Contrast KineticS (3D TRICKS) technique with elliptical centric encoding during contrast arrival. Following venous opacification, a complete large centrically encoded k-space volume was acquired. The high-spatial-frequency portions of this volume were combined with a 3D TRICKS time frame to form a high-resolution image. An additional single image is formed by suppressing background and signal averaging all acquired data, including post-venous low-spatial-frequency data. For this image, 2D temporal correlation analysis is used to suppress low-spatial-frequency vein contributions. Arrival time and spatial correlations are used to suppress background. RESULTS: The 3D TRICKS time frame may be selected to ensure a combined high-resolution image that has optimal central k-space sampling for any vascular region. The single image formed by signal averaging all acquired data has increased contrast-to-noise (CNR) and signal-to-noise (SNR) ratios. CONCLUSION: The advantages of time-resolved and high-spatial-resolution imaging were combined using an extended dual-phase acquisition. Some SNR and CNR gain was achieved by signal averaging. This process is facilitated by background and vein suppression.     

Exercise training in obesity lowers blood pressure independent of weight change

PURPOSE: We used the rabbit model of obesity and exercise training to determine effects of exercise training during the development of obesity on resting blood pressure and heart rate, ventricular hypertrophy, blood volume, and hormonal profile. METHODS: Female New Zealand white rabbits were assigned to one of four groups: lean sedentary (L-S, N = 17), lean exercise-trained (L-EX, N = 16), obese sedentary (O-S, N = 18), and obese exercise-trained (O-EX, N = 15). Lean rabbits were fed a maintenance diet whereas obese rabbits were fed an ad libitum high fat (10% added fat) diet. Simultaneously, exercise-trained animals underwent a progressive treadmill exercise training protocol for 12 wk. After 12 wk of diet and exercise regimens, resting blood pressure and heart rate were measured from a central ear artery catheter. Ventricular hypertrophy was evaluated using wet ventricular weights. Blood volume was measured using the Evans blue dye procedure; hormonal profile was evaluated from arterial plasma/serum samples. RESULTS: After 12 wk, O-S and O-EX had similar body weights and similar percentage increases in body weight. Despite similar body weights, O-EX had an approximate 6-mm Hg lower mean blood pressure compared with the elevated pressure seen in O-S (P < or = 0.05). Obese rabbits had greater resting heart rate, plasma cholesterol and triglycerides, and plasma renin activity compared with lean rabbits, and these values were unaffected by exercise training. Plasma and blood volumes, as well as plasma insulin, cortisol, and aldosterone were unaffected by exercise training. CONCLUSION: These data suggest that exercise training, in the absence of differences in body weight, may be useful in the reduction of obesity-induced hypertension but that other therapies may be needed in order to control other cardiovascular risk factors.     

Technical developments in MR angiography

CE MRA has evolved rapidly since the early studies by Prince et al [3]. Whereas many of the procedures in clinical use today rely heavily on the use of gadolinium contrast agents and standard. Fourier transform acquisition techniques, advances will have a significant impact on MRA by shortening the acquisition time, improving the reproducibility of the image-acquisition techniques, and improving spatial resolution or SNR. From a technical basis, shorter acquisition times associated with fast gradients are likely to improve spatial resolution and allow for acquisition of MR images over large FOVs. In addition, alternative k-space sampling techniques, such as parallel imaging and PR, are expected to further reduce acquisition time, while maintaining or improving spatial resolution. The approval and subsequent use of new contrast agents will also have a beneficial impact on the image quality of contrast-enhanced MRA applications. It is likely that these contrast agents will be coupled with advanced acquisition techniques to improve spatial resolution and technical success rates of MRA examinations.     

Murine hindlimb reperfusion injury can be initiated by a self-reactive monoclonal IgM

BACKGROUND: Murine hindlimb reperfusion injury (I/R), is initiated by activation of the classical pathway of complement. Complement receptor-2 knockout mice (Cr2-/-) are protected from I/R injury due to defective B-1 cells with a resulting deficient natural immunoglobulin M (IgM) repertoire. Cr2-/- and wild type (WT) mice were studied to isolate the antibody or antibodies responsible for initiation of I/R. METHODS: IgM-secreting B-1 cell clones were produced with hybridoma technology from WT cells. Of 21 clones tested in murine I/R models, only 1 clone, CM22, was found to restore injury in protected mice. Cr2-/- mice reconstituted with IgM from individual clones, WT serum, or saline were subjected to 2 hours hindlimb ischemia and 3 hours reperfusion and compared with WT. RESULTS: Muscle injury in Cr2-/- mice reconstituted with CM22 was similar to injury in WT mice reconstituted with saline and Cr2-/- mice reconstituted with WT serum. This injury was 137% greater (P < .05) than in both Cr2-/- mice reconstituted with saline and those reconstituted with a different IgM clone, CM31. IgM and C3 deposition was found only on injured muscle of WT mice or Cr2-/- mice reconstituted with CM22 or WT serum. CONCLUSION: A single clone of self-reactive IgM, CM22, can initiate complement-dependent I/R injury.     

Lymphokine-induced phagocytosis in angiocentric immunoproliferative lesions (AIL) and malignant lymphoma arising in AIL

A factor that augmented the phagocytosis of IgG-coated ox red blood cells by the human monocyte/macrophage line U937 was identified in cell culture supernatants from two of two patients with angiocentric peripheral T cell lymphomas, three of three patients with angiocentric immunoproliferative lesions that were not frankly malignant, and one of two patients with T lymphoblastic malignancies. The factor was not present in supernatants derived from 14 nonangiocentric peripheral T cell lymphomas of other histologic types nor in ten cases of B cell lymphoma and two cases of Hodgkin's disease. A similar factor was present in the supernatants of concanavalin A (Con A)-stimulated normal peripheral blood mononuclear cells and in the supernatants of IL-2- dependent T cell lines derived from normal peripheral blood. The factor had an apparent mol wt of greater than 50,000 daltons, was heat labile (100 degrees C for two minutes), and stable at pH 2.0. Its stimulation of phagocytosis was independent of any increase in number of Fc receptors. Thus, this factor is probably not gamma-interferon. This factor may play a pathogenetic role in the hemophagocytic syndromes associated with certain T cell malignancies and immunodeficient states.     

Mapping of steroid 21-hydroxylase genes adjacent to complement component C4 genes in HLA, the major histocompatibility complex in man.

The genes for four components (C) of complement in the human major histocompatibility complex (HLA) have been aligned previously in a series of overlapping cosmid cloned inserts. Those inserts, which contained the two C4 genes C4A and C4B, hybridized with human adrenal mRNA, indicating that they contain a gene expressed in the adrenal. The mRNA fraction of 2.4 kilobases (kb) hybridizes with genomic DNA of 4.5 kb, which is duplicated and lies about 1.5 kb 3' of both the C4A and the C4B complement genes. Sequencing of a 430-base section and comparison with the published cDNA sequence of bovine cytochrome P-450 21-hydroxylase, peptide sequences of porcine 21-hydroxylase, and a cDNA sequence of a rat liver cytochrome P-450 identified the gene as coding for human steroid 21-hydroxylase [steroid,hydrogen-donor:oxygen oxidoreductase (21-hydroxylating), EC 1.14.99.10]. Mapping of the gene was helped by use of a synthetic oligonucleotide based on the bovine cDNA sequence.     

Effect of selenium supplementation on selenium balance in the dependent elderly

Although trace minerals are necessary constituents of enzymes, dietary requirements of these nutrients for the elderly are unknown. This study measured selenium balance in six dependent elderly men before and after five weeks daily administration of 200 micrograms organically-bound selenium; dietary selenium intake averaged 62.1 +/- 7 micrograms/day during both study periods. Selenium status was assessed not only chemically but also biologically as red cell and platelet glutathione peroxidase activities. Plasma selenium averaged 8.8 +/- 0.8 micrograms% (normal: 10 +/- 2 micrograms %) when intake derived from dietary sources alone and increased during medicinal supplementation to an average of 12.8 +/- 1.9 micrograms %. The rise in plasma selenium was not associated with an increase in red cell or platelet glutathione peroxidase activity. The effect of selenium supplementation on in vivo platelet aggregability was studied by measuring plasma levels of beta-thromboglobulin and platelet factor 4, two proteins secreted concomitant with aggregation. beta-thromboglobulin diminished 7.5 +/- 11.0 ng/ml and platelet factor 7.6 +/- 11.0 ng/ml during selenium supplementation despite no change in platelet glutathione peroxidase activity. These data support the concept that selenium nutritional status should be assessed not only by blood selenium content but also by selenium-dependent enzyme activity or selenium-dependent biologic effect.     

Adherent and soluble mucus in the stomach and duodenum

Gastroduodenal mucus is present as a water insoluble gel adherent to the mucosal surface and as a viscous mobile solution in the lumen. The protective properties of the mucus against acid (with bicarbonate), pepsin (diffusion barrier) and mechanical damage depend on the quality (structure) and quantity (thickness) of the adherent mucus gel layer. Adherent mucus is a viscoelastic gel which is 95% (v/v) water. It is permeable to ions and smaller molecules (M_r c. 1000), but is impermeable to large proteins (M_r,c. 17,000) including pepsins. However, mucus is solubilized rapidly by pepsin, more slowly (>-1 h) by thiol agents, and is unchanged following exposure to bile, acid and ethanol (<40%). Glycoprotein macromolecules (M_r≥2×10⁶) are the structural components of the mucus gel and have a polymeric, structure of glycoprotein subunits (M_rc. 5×10⁵, for gastric mucus) joined by disulphide bridges between their protein cores. This glycoprotein polymerization, which is essential for gel formation and hence function, is the site of action of proteolytic enzymes and thiol agents. The glycoprotein polymeric structure is deficient in antral mucus from patients with peptic ulcer disease.In vivo, adherent mucus forms a thin but continuous cover of variable thickness (50–450 μm in man, about two-fold less in rat) over the gastroduodenal mucosa. Pepsin in gastric juice will rapidly dissolve this mucus cover and can be active up to luminal pH values of 5. Mucus erosion by pepsin or by abrasion must be balanced by its secretion. Prostaglandins and carbachol stimulate a rapid increase (within minutes) in mucus thickness of up to two-fold. Soluble luminal mucus can be increased by mucus secretagogues, mucosal damaging agents, or peptic degradation of adherent mucus. Increases in luminal mucus can occur independently of increased gel thickness.