Brain networks associated with cognitive and hedonic responses to a meal.

BACKGROUND: We recently reported interrelated digestive, cognitive, and hedonic responses to a meal. The aim of this study was to identify brain networks related to the hedonic response to eating. METHODS: Thirty-eight healthy subjects (20-38 age range) were evaluated after a 5-hour fast and after ingestion of a test meal (juice and warm ham and cheese sandwich, 300 mL, 425 kcal). Perceptual and affective responses (satiety, abdominal fullness, digestive well-being, and positive mood), and resting scans of the brain using functional MRI (3T Trio, Siemens, Germany) were evaluated immediately before and after the test meal. A high-order group independent component analysis was performed to investigate ingestion-related changes in the intrinsic connectivity of brain networks, with a focus on thalamic and insular networks. KEY RESULTS: Ingestion induced satiation (3.3±0.4 score increase; P<.001) and abdominal fullness (2.4±0.3 score increase; P<.001). These sensations included an affective dimension involving digestive well-being (2.8±0.3 score increase; P<.001) and positive mood (1.8±0.2 score increase; P<.001). In general, thalamo-cortical connectivity increased with meal ingestion while insular-cortical connectivity mainly decreased. Furthermore, larger meal-induced changes (increase/decrease) in specific thalamic connections were associated with smaller changes in satiety/fullness. In contrast, a larger meal-induced decrease in insular-anterior cingulate cortex connectivity was associated with increased satiety, fullness, and digestive well-being. CONCLUSIONS AND INFERENCES: Perceptual and emotional responses to food intake are related to brain connectivity in defined functional networks. Brain imaging may provide objective biomarkers of subjective effects of meal ingestion.

Altered brain responses in subjects with irritable bowel syndrome during cued and uncued pain expectation.

BACKGROUND: A majority of the subjects with irritable bowel syndrome (IBS) show increased behavioral and brain responses to expected and delivered aversive visceral stimuli during controlled rectal balloon distension, and during palpation of the sigmoid colon. We aimed to determine if altered brain responses to cued and uncued pain expectation are also seen in the context of a noxious somatic pain stimulus applied to the same dermatome as the sigmoid colon. METHODS: A task-dependent functional magnetic resonance imaging technique was used to investigate the brain activity of 37 healthy controls (18 females) and 37 IBS subjects (21 females) during: (i) a cued expectation of an electric shock to the abdomen vs a cued safe condition; and (ii) an uncued cross-hair condition in which the threat is primarily based on context vs a cued safe condition. KEY RESULTS: Regions within the salience, attention, default mode, and emotional arousal networks were more activated by the cued abdominal threat condition and the uncued condition than in the cued safe condition. During the uncued condition contrasted to the cued safe condition, IBS subjects (compared to healthy control subjects) showed greater brain activations in the affective (amygdala, anterior insula) and attentional (middle frontal gyrus) regions, and in the thalamus and precuneus. These disease-related differences were primarily seen in female subjects. CONCLUSIONS & INFERENCES: The observed greater engagement of cognitive and emotional brain networks in IBS subjects during contextual threat may reflect the propensity of IBS subjects to overestimate the likelihood and severity of future abdominal pain.

Chronic thromboembolic pulmonary hypertension (CTEPH) - potential role of multidetector-row CT (MD-CT) and MR imaging in the diagnosis and differential diagnosis of the disease.

Chronic thromboembolic pulmonary hypertension (CTEPH) can be defined as pulmonary hypertension (resting mean pulmonary arterial pressure of 25 mm Hg or more determined at right heart catheterization) with persistent pulmonary perfusion defects. It is a rare, but underdiagnosed disease with estimated incidences ranging from 0.5% to 3.8% of patients after an acute pulmonary embolism (PE), and in up to 10% of those with a history of recurrent PE. CTEPH is the only form of pulmonary hypertension that can be surgically treated leading to normalization of pulmonary hemodynamics and exercise capacity in the vast majority of patients. The challenges for imaging in patients with suspected CTEPH are fourfold: the imaging modality should have a high diagnostic accuracy with regard to the presence of CTEPH and allow for differential diagnosis. It should enable detection of patients suitable for PEA with great certainty, and allow for quantification of PH by measuring pulmonary hemodynamics (mPAP and PVR), and finally, it can be used for therapy monitoring. This overview tries to elucidate the potential role of ECG-gated multidetector CT pulmonary angiography (MD-CTPA) and MR imaging, and summarizes the most important results that have been achieved so far. Generally speaking, ECG-gated MD-CTPA is superior to MR in the assessment of parenchymal and vascular pathologies of the lung, and allows for the assessment of cardiac structures. The implementation of iodine maps as a surrogate for lung perfusion enables functional assessment of lung perfusion by CT. MR imaging is the reference standard for the assessment of right heart function and lung perfusion, the latter delineating typical wedge-shaped perfusion defects in patients with CTEPH. New developments show that with MR techniques, an estimation of hemodynamic parameters like mean pulmonary arterial pressure and pulmonary vascular resistance will be possible. CT and MR imaging should be considered as complementary investigations providing comprehensive information in patients with CTEPH.

Effect of hypnotherapy and educational intervention on brain response to visceral stimulus in the irritable bowel syndrome.

BACKGROUND: Gut-directed hypnotherapy can reduce IBS symptoms, but the mechanisms underlying this therapeutic effect remain unknown. AIM: To determine the effect of hypnotherapy and educational intervention on brain responses to cued rectal distensions in IBS patients. METHODS: Forty-four women with moderate-to-severe IBS and 20 healthy controls (HCs) were included. Blood oxygen level dependent (BOLD) signals were measured by functional Magnetic Resonance Imaging (fMRI) during expectation and delivery of high- (45 mmHg) and low-intensity (15 mmHg) rectal distensions. Twenty-five patients were assigned to hypnotherapy (HYP) and 16 to educational intervention (EDU). Thirty-one patients completed treatments and posttreatment fMRI. RESULTS: Similar symptom reduction was achieved in both groups. Clinically successful treatment (all responders) was associated with significant BOLD attenuation during high-intensity distension in the dorsal and ventral anterior insula (cluster size 142, P = 0.006, and cluster size 101, P = 0.005 respectively). Moreover HYP responders demonstrated a pre-post treatment BOLD attenuation in posterior insula (cluster sizes 59, P = 0.05) while EDU responders had a BOLD attenuation in prefrontal cortex (cluster size 60, P = 0.05). Pre-post differences for expectation conditions were almost exclusively seen in the HYP group. Following treatment, the brain response to distension was similar to that observed in HCs, suggesting that the treatment had a normalising effect on the central processing abnormality of visceral signals in IBS. CONCLUSIONS: The abnormal processing and enhanced perception of visceral stimuli in IBS can be normalised by psychological interventions. Symptom improvement in the treatment groups may be mediated by different brain mechanisms. CLINICAL TRIAL NUMBER: NCT01815164.

Randomised clinical trial: symptoms of the irritable bowel syndrome are improved by a psycho-education group intervention.

BACKGROUND: Evidence supports the effectiveness of cognitive behavioural approaches in improving the symptoms of the irritable bowel syndrome (IBS). Duration, cost and resistance of many patients towards a psychological therapy have limited their acceptance. AIM: To evaluate the effectiveness of a psycho-educational intervention on IBS symptoms. METHODS: Sixty-nine IBS patients (72% female) were randomised to an intervention or a wait-list control group. The IBS class consisted of education on a biological mind body disease model emphasising self-efficacy and practical relaxation techniques. RESULTS: Patients in the intervention showed significant improvement on GI symptom severity, visceral sensitivity, depression and QoL postintervention and most of these gains were maintained at 3-month follow-up (Hedge's g = -0.46-0.77). Moderated mediation analyses indicated change in anxiety, visceral sensitivity, QoL and catastrophising due to the intervention had moderate mediation effects (Hedge's g = -0.38 to -0.60) on improvements in GI symptom severity for patients entering the trial with low to average QoL. Also, change in GI symptom severity due to the intervention had moderate mediation effects on improvements in QoL especially in patients with low to average levels of QoL at baseline. Moderated mediation analyses indicated mediation was less effective for patients entering the intervention with high QoL. CONCLUSIONS: A brief psycho-educational group intervention is efficacious in changing cognitions and fears about the symptoms of the irritable bowel syndrome, and these changes are associated with clinically meaningful improvement in symptoms and quality of life. The intervention seems particularly tailored to patients with low to moderate quality of life baseline levels.

Sex-related differences in prepulse inhibition of startle in irritable bowel syndrome (IBS).

Alterations in central networks involved in the regulation of arousal, attention, and cognition may be critical for irritable bowel syndrome (IBS) symptom maintenance and exacerbation. Differential sensitivities in these networks may underlie sex differences noted in IBS. The current study examined prepulse inhibition (PPI), a measure of sensorimotor gating, in male and female IBS patients. Relationships between PPI and symptom severity were examined, as well as potential menstrual status effects. Compared to healthy controls, male IBS patients had significantly reduced PPI; whereas female IBS patients (particularly naturally cycling women) had significantly enhanced PPI suggesting hypervigilance. Considering previously demonstrated sex-related differences in perceptual and brain imaging findings in IBS patients, the current findings suggest that different neurobiological mechanisms underlie symptom presentation in male and female IBS patients. Compromised filtering of information in male IBS patients may be due to compromised top down (prefrontal, midcingulate) control mechanisms while increased attention to threat due to increased limbic and paralimbic circuits may be characteristic of female IBS patients.

Psoriasis patients generate increased serum levels of autoantibodies to tumor necrosis factor-alpha and interferon-alpha.

BACKGROUND: It has been shown in experimental animal models that were extended to humans that during autoimmune conditions, the immune system generates beneficial autoantibody (auto Ab) response to a limited number of inflammatory mediators that drive the pathogenesis of the disease. OBJECTIVE: To investigate the presence of auto Abs to cytokines and chemokines in psoriasis. METHODS: Sera were obtained from patients with psoriasis (n=37), atopic dermatitis (AD) (n=18) and healthy volunteers (n=56). The titers of auto (Abs) to TNF-alpha, interferon-alpha (IFN-alpha), interleukin-17 (IL-17), and chemokines CCL2, CCL3 and CCL5 were determined using enzyme-linked immunosorbant assay. Neutralizing activities of high-titer auto Abs to TNF-alpha and IFN-alpha were determined using functional in vitro assays. RESULTS: Highly significant increased titers of auto Abs to TNF-alpha and IFN-alpha were detected in patients with psoriasis compared with healthy subjects and patients with AD (mean titers more than fourfold). These auto Abs demonstrated some neutralizing activity in vitro, but their serum levels did not correlate with the intensity and duration of the disease and with phototherapy induced remissions. Significantly increased titers albeit to a lesser extent, of auto Abs to CCL3 were detected in AD. CONCLUSIONS: Psoriasis patients produce markedly increased levels of auto Abs to TNF-alpha and IFN-alpha which are two of the key cytokines in this disorder. The presence of these auto Abs which possess some neutralizing activity in vitro, may be an epiphenomenon or might play a role in attempting to suppress the ongoing inflammatory process.

Traditional Chinese medicine based subgrouping of irritable bowel syndrome patients.

Partly from lack of effective conventional therapeutics, patients with irritable bowel syndrome (IBS) turn to complementary and alternative approaches, including Traditional Chinese Medicine (TCM). Key to TCM's approach to IBS is individualized therapies targeted at subgroups. Subgroups represent distinct patterns of dysregulation (e.g. "excess" or "deficiency") identified by both intestinal and extra-intestinal symptoms. Our objective was to identify operational criteria supporting the existence of TCM-based subgroups in IBS and to assess reliability and validity of these criteria. Using TCM principles, items were selected on face validity from conventional questionnaires. TCM practitioners evaluated items for content and face validity. Symptom items and a set of patient cases with item responses were validated by examining patient's pattern of response to items and assessing the consistency with which practitioners diagnosed patients on the spectrum of an "excess" or "deficiency" syndrome. Standard correlation analysis revealed 33 intestinal and extra-intestinal symptom items. There was high degree of practitioner agreement in assessing individual items to particular patterns. External validation by practitioners of cases showed high internal consistency among practitioners (Cronbach's alpha coefficients of 0.91 and 0.87 for excess and deficiency, respectively) and high correlation of average practitioner rating to original questionnaire generated scores (Pearson correlation coefficients of 0.94 and 0.92 for excess and deficiency, respectively). This pilot study provides preliminary support for a methodology to identify novel subgroups of IBS patients related to the TCM classification, which may differ in underlying pathophysiology and treatment responses.

Effects of moderate exercise and oat beta-glucan on lung tumor metastases and macrophage antitumor cytotoxicity.

Both moderate exercise and the soluble fiber beta-glucan can have beneficial effects on the initiation and growth of tumors, but the data are limited, and there is no information on their combined effects. This study tested the independent and combined effects of short-term moderate-exercise training and the soluble oat fiber beta-glucan (ObetaG) on the metatastic spread of injected tumor cells and macrophage antitumor cytotoxicity. Male C57BL/6 mice were assigned to one of four groups: exercise (Ex)-H2O, Ex-ObetaG, control (Con)-H2O, or Con-ObetaG. ObetaG was fed in the drinking water for 10 days before tumor administration and death. Exercise consisted of treadmill running (1 h/day) for 6 days. After rest or exercise on the last day of training, syngeneic B16 melanoma cells (2 x 10(5)) were administered via intravenous injection (n = 8-11 per group). Lungs were removed 14 days later, and tumor foci were counted. Additional mice (n = 8 per group) were killed, and peritoneal macrophages were assayed for cytotoxicity against the same mouse tumor cell line at various effector-to-target ratios. Both moderate exercise and ObetaG decreased lung tumor foci and increased macrophage cytotoxicity. However, there were no differences in lung tumor foci and macrophage cytotoxicity between Ex-ObetaG and either Ex-H2O or Con-ObetaG. These data suggest that, although not additive in their effects, both short-term moderate-exercise training and consumption of the soluble ObetaG can decrease the metatastic spread of injected B16 melanoma cells, and these effects may be mediated in part by an increase in macrophage cytotoxicity to B16 melanoma.

Pure imagery hemi-neglect of far space.

Patients with hemispatial neglect restricted to near (within reaching distance) or to far space (beyond reaching distance) have been described. This constitutes a double-dissociation considered by current neurocognitive thinking as compelling evidence for separate networks. However, a similar double-dissociation exists with respect to perceived as opposed to imagined space. If the organization of represented space was similar to that of perceived space, it should contain a far/near dissociation as well. This paper describes a patient with pure representational neglect restricted to far space.

Representation of anatomical constraints in motor imagery: mental rotation of a body segment.

Classically, the mental rotation paradigm has shown that when subjects are asked to judge whether objects that differ in orientation are spatially congruent, reaction times increase with angular discrepancy, although some reports have shown that this is not always the case. Would similar results be obtained with realistic figures of body segments? In this work, the mental rotation of a hand attached to its forearm and arm in anatomically possible and impossible starting positions is compared with the mental rotation of a hammer. The main results show that reaction times increase monotonically with the angle of discrepancy for both stimuli and that the speed of rotation is higher for anatomically possible orientations in the case of the hand. Thus, mental rotation of body segments follows the same empirical rules as objects of another nature, and biomechanical constraints imposed to the motility of these segments can be considered as attributes of the mental representation.

Hyperbaric oxygen--an effective tool to treat radiation morbidity in prostate cancer.

PURPOSE: We report the results of hyperbaric oxygen therapy (HBO) used in the treatment of radiation cystitis and proctitis following irradiation of prostate cancer. MATERIALS AND METHODS: Between June 1995 and March 2000, 18 men (median age 71 years) with radiation proctitis (n=7), cystitis (n=8), and combined proctitis/cystitis (n=3) underwent HBO therapy in a multiplace chamber for a median of 26 sessions (range 2-60). The treatment schedule (2.2-2.4 atmospheres absolute, 60 min bottom time, once-a-day, 7 days a week) was set at a lower limit of 20 sessions; the upper limit was left open to symptom-related adjustment. Prior to HBO treatment, RTOG/EORTC late genitourinal (GU) morbidity was Grade 2 (n=3), Grade 3 (n=6) or Grade 4 (n=2); modified RTOG/EORTC late gastrointestinal (GI) morbidity was either Grade 2 (n=4) or Grade 3 (n=6). RESULTS: Sixteen patients underwent an adequate number of sessions. RTOG/EORTC late GU as well as modified GI morbidity scores showed a significant improvement after HBO (GI, P=0.004; GU, P=0.004; exact Wilcoxon signed rank test); bleeding ceased in five out of five patients with proctitis and in six out of eight patients with cystitis; one of those two patients, in whom an ineffective treatment outcome was obtained, went on to have a cystectomy. CONCLUSIONS: HBO treatment seems to be an effective tool to treat those patients with late GI and GU morbidity when conventional treatment has led to unsatisfactory results. Particularly in patients with radiation cystitis, HBO should not be delayed too long, as in the case of extensive bladder shrinkage improvement is hard to achieve.

Pure representational neglect after right thalamic lesion.

After a right thalamic stroke, an 86-year-old man presented an acute pure left representational neglect in the absence of any perceptual neglect. On spatial mental imagery tasks, the patient systematically omitted items located on his left side, but only when a vantage point was given. This suggests that (1) pure representational neglect is not just a residual finding after recovery from global (perceptual and representational) neglect; (2) space representation can be coded by two independent processes: in viewer-centered or world-based (allocentric) coordinates; and (3) the right thalamus serves as a relay in the processing of spatial visual imagery.

[Characteristics of behavior of knockout mice with genetic monoamine oxidase A deficiency]. / Osobennosti povedeniia myshei s geneticheskim nokautom monoaminoxidazy tipa A.

The effect of deletion of monoamine oxidase A (MAO A) in the gene encoding on behavior of transgenic Tg8 mice was studied. A decrease in the amplitude of acoustic startle reflex rather than the prepulse inhibition was found in lacking MAO A Tg8 mice, as compared with the control C3H strain. The exploratory activity in the hole-board test in Tg8 was decreased as well as the number of crossed lines in the light-dark test. Tg8 mice showed decreased latency and increased intensity of intermale aggression. At the same time, no difference was found between Tg8 and C3H mice in locomotor activity, in the expression of sexual motivation, and in the behavior in the elevated plus-maze test. No predisposition to catalepsy was shown.

[Reproductive performance and milk production of Israeli-Holstein cows with different supplementation during the dry period]. / Reproduktions- und Milchleistung bei Israeli-Holstein Kühen mit unterschiedlicher Fütterung in der Trockenzeit.

In three field trials comprising 602 Israeli-Holstein dairy cows, the effect of the dry period ration on reproductive performance, culling rate and milk production was investigated. The cows were fed in groups. The basic dry period rations consisted for two herds of medium quality cereal hay and for one herd of corn straw, which were fed ad libitum. In each herd dry cows were assigned to an experimental and control group. Cows of the experimental group were supplemented with 1.5 to 3 kg of lactating cows mixed ration (LMR), whereas in the control group the amount of supplement was increased by the factor two or 3.3. In the experimental group the amount of the supplement was calculated to achieve levels of net energy and of crude protein close to NRC requirements; in the control group the level of net energy and protein was 12 to 18% higher as compared to the experimental group. The amount of LMR supplement in the experimental group of herds A, B, C were 1.5 kg, 1.9 kg, and 3 kg, respectively. In the control groups these amounts were 5 kg, 3.8 kg, and 6 kg, respectively. The groups fed moderate amounts of LMR supplement had a higher conception rate at first insemination, a higher percentage of cows conceiving and fewer cows culled in the consecutive lactation than cows fed increased amounts of LMR supplement. The lactational incidence of reproductive disorders and the milk production were not affected by the differences in feeding during the dry period. Reproductive performance and culling rate appeared to be more favorable for cows fed moderate amounts of supplement during the entire dry period or during the last 3 to 4 weeks of the dry period.

To see better to the left when looking more to the right: effects of gaze direction and frames of spatial coordinates in unilateral neglect.

Unilateral spatial neglect entails a failure to detect or respond to stimuli in the space opposite to a brain lesion. However, the contralesional hemispace can be determined by different frames of spatial coordinates, such as eyes-, head-, body-, or environment-centered coordinates. We observed 2 patients with a right hemisphere stroke whose left spatial neglect was modulated by distinct coordinates systems depending on the task. Four tasks were given in different conditions of central gaze and either the eyes or the head rotated 30 degrees to the right or 30 degrees to the left. While the 2 patients had a retinotopic defect in 1 visual field quadrant that remained the same irrespective of gaze direction (upper or lower quadrant in 1 case each), the other quadranopic field defect improved with eyes rotation to the right but not with head rotation, suggesting a head-centered spatiotopic deficit. Performance on line bisection was influenced both by eyes and head rotation, as well as by the position of the lines with respect to the trunk midline, suggesting the involvement of both head-centered and body-centered coordinates. Visual imagery and auditory extinction were not modified by changing the eyes or head position. These findings suggest that distinct spatial coordinates are brought into play depending on the tasks demands.

Audio and visual stimulation reduces patient discomfort during screening flexible sigmoidoscopy.

OBJECTIVE: Despite current recommendations calling for regular screening flexible sigmoidoscopies over the age of 50, only a small percentage of the population have regular examinations. Improving patient tolerance of flexible sigmoidoscopies could therefore increase patient compliance with these recommended guidelines. The aim of this study was to determine whether audio and visual stimulation reduces discomfort during flexible sigmoidoscopy and whether the effects of the stimulation are secondary to distraction. METHODS: A total of 37 patients undergoing routine screening flexible sigmoidoscopy were randomized to receive no intervention, audio stimulation alone, or audio and visual stimulation. Patient discomfort ratings and affect states were measured prior to and immediately following flexible sigmoidoscopy using a visual analogue scale and the Stress Symptom Ratings (SSR) ratings. RESULTS: Patients receiving audio and visual intervention had lower abdominal discomfort ratings (7.1 +/- 1.4) than patients receiving audio stimulation (9.5 +/- 1.3) or no intervention (10.8 +/- 1.6) (p < 0.05). Patients receiving audio and visual intervention also had higher arousal (7.3 +/- 0.4) and attention (9.2 +/- 0.2) ratings than patients receiving no intervention (6.1 +/- 0.4 and 6.2 +/- 0.7, respectively) (p < 0.05). Anxiety and anger ratings, on the other hand, were significantly lower in patients receiving audio and visual intervention (2.5 +/- 0.4, 1.4 +/- 0.3, respectively) than patients receiving no intervention (4.4 +/- 0.6, 3.6 +/- 0.7). CONCLUSION: Audio and visual stimulation reduces abdominal discomfort associated with flexible sigmoidoscopy. This effect appears to be due to distraction.

High-dose epsilon-aminocaproic acid versus aprotinin: antifibrinolytic efficacy in first-time coronary operations.

BACKGROUND: The antifibrinolytic efficacy of a high-dose regimen of epsilon-aminocaproic acid (epsilon-ACA) was compared with aprotinin in first-time coronary operations. METHODS: In a prospective, double-blinded, randomized study, 20 patients received high-dose epsilon-ACA (10 g both as a loading and cardiopulmonary bypass priming dose, 2.5 g/h until 4 hours after protamine), and another 20 patients received aprotinin (2 x 10(6) KIU [280 mg] for loading and priming, 0.5 x 10(6) KIU/h [70 mg/h]). Ten untreated patients served as controls. RESULTS: Both agents reduced postoperative levels of thrombin/antithrombin III complexes, D-dimers, fibrin degradation products, free plasma hemoglobin (epsilon-ACA versus aprotinin, p = not significant; p < 0.05 versus controls), and amount of retransfused autologous blood (p < 0.001). Epsilon-ACA increased, aprotinin suppressed antiplasmin-plasmin complex generation (epsilon-ACA versus controls, p < 0.02; epsilon-ACA versus AP, p < 0.0001). For 4 hours after discontinuation, more chest drainage occurred with epsilon-ACA than aprotinin (137 +/- 90 mL versus 62 +/- 29 mL; means +/- standard deviation; p < 0.02). Cumulative 12-hour drainage was similar for aprotinin (391 +/- 220 mL) and epsilon-ACA (582 +/- 274 mL), but higher without inhibitor (1,091 +/- 541 mL; p < 0.001 versus drugs). Postoperatively, aprotinin was associated with the lowest autologous retransfusion incidence and highest hematocrits (p < 0.01 versus epsilon-ACA). Homologous transfusion exposures did not differ. CONCLUSIONS: In first-time coronary operations, higher postoperative hematocrit and less shed blood retransfusion constitute only subtle advantages of aprotinin over high-dose epsilon-ACA.

Visionary leadership and the future of VA health system.

As the U.S. Department of Veterans Affairs (VA) makes the change over to Veterans Integrated Service Network (VISNs) the need for new and better leadership is warranted if VA wants to not only survive, but thrive in the emerging twenty-first century healthcare system. VA can prepare for the future and meet the challenges facing them by adopting a system of visionary leadership. The use of scenarios and vision techniques are explained as they relate to VA's efforts to move toward their new system of VISNs. The four scenarios provide snapshots of possible futures for the U.S. healthcare system as well as the possible future role and mission of VA--from VA disappearing to its becoming a premier virtual organization.

Homocysteine and coronary artery disease.

BACKGROUND: Homocystinuria is a rare autosomal recessive disease complicated by early and aggressive occlusive arterial disease. This may be related to the grossly increased homocysteine concentrations seen in this disease. More recently, milder hyperhomocysteinemia has been proposed as an independent risk factor for coronary artery disease. SUMMARY: Many patients with homozygous homocystinuria develop severe premature atherosclerosis and thromboembolism, probably caused by abnormally high concentrations of homocysteine. Homocysteine undergoes metabolism either by remethylation or transsulfuration, and deficiency or dysfunction of any of the substances that regulate these reactions may lead to hyperhomocysteinemia. Homocysteine may have adverse effects on platelets, clotting factors, and endothelial cells. Studies have demonstrated significantly higher plasma homocysteine levels in patients with occlusive arterial disease than in controls. The causes are not clearly understood but may include deficiency of vitamin B6, vitamin B12, and folic acid and heterozygosity for cystathionine synthase deficiency. Vitamin supplementation can lower plasma homocysteine levels. CONCLUSIONS: Whether measuring plasma homocysteine levels in patients with coronary artery disease should be routine and whether treating hyperhomocysteinemia in these patients may reduce the risk of coronary events remains to be determined.