Flow-independent angiography for peripheral vascular disease: Initial in-vivo results

Flow-independent angiography (FIA), an approach that isolates arterial blood using MR relaxation characteristics rather than flow effects, was evaluated for application in peripheral vascular disease (PVD). First, pilot studies were conducted in which FIA coronal projection images were obtained from controls and symptomatic patients with PVD to assess clinical utility. All control images corresponded to the expected leg arterial anatomy with little interference from deep veins (one of five) and muscle (zero of five). Superficial venous signal was less well suppressed in comparison to deep veins (four of five). Images of symptomatic patients were less consistent with difficulty suppressing muscle and deep venous signal in some cases and edema when present. We then compared T2 values for muscle (T2_m, tibialis anterior), arterial blood (femoral and popliteal arteries), and venous blood (femoral, popliteal, and saphenous veins) in controls (n = 8) and symptomatic patients with intermittent claudication (n = 5) or ischemic rest pain (n = 7). Changes in T2 measurements of various tissues accounted for poorer contrast in symptomatic patients. Patients with ischemic rest pain had significantly higher T2_m compared with controls (T2_m = 39.3 ± 2.1 (1 standard error of the mean [SEM]) versus 30.9 ± .4, P < .01). For all measurements, other than saphenous vein, variances were greater in symptomatic patients. To realize the inherent advantages of FIA for this clinical application, additional work on suppression of signals from muscle, veins, and edema is required. One promising approach involves shifting from projection images to three-dimensional acquisitions for improved tissue suppression.     

The thermal effect on the blood flow response to electrical stimulation.

BACKGROUND: Wounds, especially in the elderly, can be life threatening. One modality which allegedly increases blood flow (BF) as an aid to heal chronic wounds is electrical stimulation. This technique applies electrical current (ES) across wounds. However, while many studies show positive findings, others do not. The purpose of this investigation was to investigate some of this inconsistency in results by determining the effect of environmental temperature on the circulation of the skin which may negate the effects of electrical stimulation in a clinical setting. MATERIAL/METHODS: Ten people with no wounds, controls (C), and 12 people with wounds (W) were examined in a thermally neutral or cool room (20 degrees C) and a warm room (34 degrees C) to observe the effect of reducing sympathetic vasoconstrictor activity on the response to 5 and 15 mA sine wave biphasic ES delivered by 2x2 cm surface electrodes. RESULTS: C and W subjects showed a greater BF in the skin in a warm room. In group C, after 30 minutes of stimulation at a current of 15 milliamps, BF increased significantly (p<0.05) but by an average of only 4 flux in the cool room. In the warm environment, BF increased significantly (p<0.01) by 19.3+/-7 flux and increased further during the 60 minute recovery phase. In the W group, BF during ES increased much more during stimulation in a warm room compared to a cool room. CONCLUSIONS: The results show that local vasoconstriction due to exposure to a warm global temperature greatly increases the response of the skin the ES.     

Diabetes insipidus with impaired osmotic regulation in septo-optic dysplasia and agenesis of the corpus callosum.

The clinical and endocrinological findings in 24 children with septo-optic dysplasia and/or agenesis of the corpus callosum are described with particular reference to posterior pituitary function. Nine had diabetes insipidus. The prevalence of diabetes insipidus was similar in children with complete and incomplete forms of septo-optic dysplasia. Maintenance of normal osmotic balance was very difficult in six of these children, even after the introduction of treatment with vasopressin, either as desmopressin, or lysine vasopressin spray in one of the early cases.     

Synergistic antiviral activity of human interferon combinations in the hepatitis C virus replicon system.

The use of type I interferon (IFN), in combination with ribvirin, to treat chronic hepatitis C virus (HCV) infection has many drawbacks that prevent widespread application, ultimately leading to a significant unmet clinical need. Potential improvements in IFN therapy through targeted delivery, molecular alteration, and combination with other agents are ongoing in an attempt to decrease adverse effects and increase efficacy. In this report, the HCV replicon cell culture system was used to assess potential synergistic antiviral effects of multiple IFN species when administered in combination. Quantitative analysis of HCV replicon RNA by TaqMan (PE Applied Biosystems, Foster City, CA) and qualitative analysis of HCV protein expression were used to measure the antiviral efficacy of individual and combination IFN treatments, and synergistic responses of IFN combinations were determined through statistical analysis of the TaqMan results. We found that when administered simultaneously, type I/II IFN combinations (IFN-alpha2b + IFN-gamma or IFN-beta + IFN-gamma) resulted in dramatic antiviral synergy, whereas a type I/I combination (IFN-alpha2b + IFN-beta) demonstrated a slightly antagonistic profile. The synergistic effect is likely due to differential cell surface receptors and signaling pathways employed by types I and II IFNs. Conversely, all type I IFN species bind the same receptor and signal through similar pathways, possibly accounting for the nearly additive response observed. In support of this hypothesis, IFN treatment resulted in differential induction of Stat1 phosphorylation at Tyr 701. In conclusion, simultaneous type I/II IFN combination treatment may allow an overall decreased effective IFN dose, which may reduce the side effect profiles that hinder current therapy.     

The 3-M syndrome.

Five patients from four families, including two male sibs, are reported with clinical and radiological features of the 3-M syndrome.     

Decreased cortical response to verbal working memory following sleep deprivation

STUDY OBJECTIVE: To investigate the cerebral hemodynamic response to verbal working memory following sleep deprivation. DESIGN: Subjects were scheduled for 3 functional magnetic resonance imaging scanning visits: an initial screening day (screening state), after a normal night of sleep (rested state), and after 30 hours of sleep deprivation (sleep-deprivation state). Subjects performed the Sternberg working memory task alternated with a control task during an approximate 13-minute functional magnetic resonance imaging scan. SETTING: Inpatient General Clinical Research Center and outpatient functional magnetic resonance imaging center. PATIENTS OR PARTICIPANTS: Results from 33 men (mean age, 28.6 +/- 6.6 years) were included in the final analyses. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Subjects performed the same Sternberg working memory task at the 3 states within the magnetic resonance imaging scanner. Neuroimaging data revealed that, in the screening and rested states, the brain regions activated by the Sternberg working memory task were found in the left dorsolateral prefrontal cortex, Broca's area, supplementary motor area, right ventrolateral prefrontal cortex, and the bilateral posterior parietal cortexes. After 30 hours of sleep deprivation, the activations in these brain regions significantly decreased, especially in the bilateral posterior parietal cortices. Task performance also decreased. A repeated-measures analysis of variance revealed that subjects at the screening and rested states had similar activation patterns, with each having significantly more activation than during the sleep-deprivation state. CONCLUSIONS: These results suggest that human sleep-deprivation deficits are not caused solely or even predominantly by prefrontal cortex dysfunction and that the paretal cortex, in particular, and other brain regions involved in verbal working memory exhibit significant sleep-deprivation vulnerability.     

Coronary artery distribution in bonnet monkeys (Macaca radiata)

Full use of nonhuman primates as a model for coronary vascular disease has been hampered by several factors, including the limited availability of detailed coronary anatomic data. This study was undertaken to identify the gross coronary arterial anatomy of the Bonnet monkey (Macaca radiata). The hearts of sixteen adult male Bonnet monkeys were subjected to postmortem coronary angiography and gross morphological examination. The main left coronary artery divided into the left anterior descending coronary artery (LAD) and the left circumflex coronary artery (LCA). The posterior descending coronary artery (PDCA) arose from the LCA in 31% of the cases and from the right coronary artery (RCA) in 56% of the hearts. Hearts from two animals (13%) had paired arteries, arising from the LCA and RCA, located in the posterior interventricular groove. The arterial supply to the sinoatrial node originated from the LCA in 69% of the animals and from the RCA in the remainder. The atrioventricular node was supplied by a branch of the RCA in 69% of the animals and from the LCA in the remainder. The coronary anatomy of the bonnet monkey resembles that of man more closely than does the dog in terms of origin of the PDCA, supply of the sinoatrial and atrioventricular nodes, and perfusion of the interventricular septum. The Bonnet monkey may therefore be a useful model for certain specific pathophysiological studies on the coronary circulation.