Intensive Blood Pressure Management Preserves Functional Connectivity in Patients with Hypertension from the Systolic Blood Pressure Intervention Randomized Trial.

BACKGROUND AND PURPOSE: The Systolic Blood Pressure Intervention (SPRINT) randomized trial demonstrated that intensive blood pressure management resulted in slower progression of cerebral white matter hyperintensities, compared with standard therapy. We assessed longitudinal changes in brain functional connectivity to determine whether intensive treatment results in less decline in functional connectivity and how changes in brain functional connectivity relate to changes in brain structure. MATERIALS AND METHODS: Five hundred forty-eight participants completed longitudinal brain MR imaging, including resting-state fMRI, during a median follow-up of 3.84 years. Functional brain networks were identified using independent component analysis, and a mean connectivity score was calculated for each network. Longitudinal changes in mean connectivity score were compared between treatment groups using a 2-sample t test, followed by a voxelwise t test. In the full cohort, adjusted linear regression analysis was performed between changes in the mean connectivity score and changes in structural MR imaging metrics. RESULTS: Four hundred six participants had longitudinal imaging that passed quality control. The auditory-salience-language network demonstrated a significantly larger decline in the mean connectivity score in the standard treatment group relative to the intensive treatment group (P = .014), with regions of significant difference between treatment groups in the cingulate and right temporal/insular regions. There was no treatment group difference in other networks. Longitudinal changes in mean connectivity score of the default mode network but not the auditory-salience-language network demonstrated a significant correlation with longitudinal changes in white matter hyperintensities (P = .013). CONCLUSIONS: Intensive treatment was associated with preservation of functional connectivity of the auditory-salience-language network, while mean network connectivity in other networks was not significantly different between intensive and standard therapy. A longitudinal increase in the white matter hyperintensity burden is associated with a decline in mean connectivity of the default mode network.

Periodontitis is associated with cognitive impairment among older adults: analysis of NHANES-III.

BACKGROUND: Periodontitis is ubiquitous and associated with serological evidence of exposure to periodontal organisms, systemic inflammation and vascular disease. Dementia is a major public health problem likely related to a complex interaction between genetics and diseases associated with systemic inflammation, including diabetes, smoking and stroke. METHODS: To assess relationships between systemic exposure to periodontal pathogens and cognitive test outcomes, data were analysed from the Third National Health and Nutrition Examination Survey (NHANES-III), a nationally representative cross sectional observational study among older adults. We included 2355 participants >or=60 years who completed measures of cognition and Poryphyromonas gingivalis IgG. Using SUDAAN, logistic regression models examined the association of P gingivalis IgG with cognitive test performance. RESULTS: Poor immediate verbal memory (<5/9 points) was prevalent in 5.7% of patients, and 6.5% overall had impaired delayed recall (<4/9); 22.1% had difficulty with serial subtractions (<5/5 trials correct). Individuals with the highest P gingivalis IgG (>119 ELISA Units (EU)) were more likely to have poor delayed verbal recall (OR 2.89, 95% CI 1.14 to 7.29) and impaired subtraction (OR 1.95, 95% CI 1.22 to 3.11) than those with the lowest (

Adrenocortical tumor with left renal vein, vena cava and intrahepatic venous extension.

A 41 year old white female presented with upper respiratory distress and shortness of breath appeared on initial computed tomography (CT) scan to have a large left retroperitoneal mass with left renal vein extension including a mass up to the level of the atrium. This presentation suggested hypernephroma. She proved, however, to have an adrenal cortical carcinoma which displaced the kidney, exhibiting vascular invasion within the gland and non-adherent extension into the vena cava, atrium, common hepatic vein and left renal vein, where some adherence was present. This unusual tumor required extensive surgery for removal, including use of cardiopulmonary bypass, with good results.

Eosinophilic vasculitis in an isolated central nervous system distribution.

BACKGROUND: Eosinophilic vasculitis has been described as part of the Churg-Strauss syndrome, but affects the central nervous system (CNS) in <10% of cases; presentation in an isolated CNS distribution is rare. We present a case of eosinophilic vasculitis isolated to the CNS. CASE REPORT: A 39-year-old woman with a history of migraine without aura presented to an institution (located in the borough of Queens, New York, USA; no academic affiliation) in an acute confusional state with concurrent headache and left-sided weakness and numbness. Laboratory evaluation showed increased cerebrospinal fluid (CSF) protein level, but an otherwise unremarkable serological investigation. Magnetic resonance imaging showed bifrontal polar gyral-enhancing brain lesions. Her symptoms resolved over 2 weeks without residual deficit. After 18 months, later the patient presented with similar symptoms and neuroradiological findings involving territories different from those in her first episode. Again, the CSF protein level was high. She had a raised C reactive protein level and erythrocyte sedimentation rate. Brain biopsy showed transmural, predominantly eosinophilic, inflammatory infiltrates of medium-sized leptomeningeal arteries without granulomas. She improved, without recurrence, when treated with a prolonged course of corticosteroids. CONCLUSIONS: To our knowledge, this is the first case of non-granulomatous eosinophilic vasculitis isolated to the CNS. No aetiology for this patient's primary CNS eosinophilic vasculitis has yet been identified. Spontaneous resolution and recurrence of her syndrome is an unusual feature of the typical CNS vasculitis and may suggest an environmental epitope with immune reaction as the cause.

Brain Perivascular Spaces as Biomarkers of Vascular Risk: Results from the Northern Manhattan Study.

BACKGROUND AND PURPOSE: Dilated perivascular spaces in the brain are associated with greater arterial pulsatility. We hypothesized that perivascular spaces identify individuals at higher risk for systemic and cerebral vascular events. MATERIALS AND METHODS: Stroke-free participants in the population-based Northern Manhattan Study had brain MR imaging performed and were followed for myocardial infarction, any stroke, and death. Imaging analyses distinguished perivascular spaces from lesions presumably ischemic. Perivascular spaces were further subdivided into lesions with diameters of ≤3 mm (small perivascular spaces) and >3 mm (large perivascular spaces). We calculated relative rates of events with Poisson models and hazard ratios with Cox proportional models. RESULTS: The Northern Manhattan Study participants who had MR imaging data available for review (n = 1228; 59% women, 65% Hispanic; mean age, 71 ± 9 years) were followed for an average of 9 ± 2 years. Participants in the highest tertile of the small perivascular space score had a higher relative rate of all deaths (relative rate, 1.38; 95% CI, 1.01-1.91), vascular death (relative rate, 1.87; 95% CI, 1.12-3.14), myocardial infarction (relative rate, 2.08; 95% CI, 1.01-4.31), any stroke (relative rate, 1.79; 95% CI, 1.03-3.11), and any vascular event (relative rate, 1.74; 95% CI, 1.18-2.56). After we adjusted for confounders, there was a higher risk of vascular death (hazard ratio, 1.06; 95% CI, 1.01-1.11), myocardial infarction (hazard ratio, 2.22; 95% CI, 1.12-4.42), and any vascular event (hazard ratio, 1.04; 95% CI, 1.01-1.08) with higher small perivascular space scores. CONCLUSIONS: In this multiethnic, population-based study, participants with a high burden of small perivascular spaces had increased risk of vascular events. By gaining pathophysiologic insight into the mechanism of perivascular space dilation, we may be able to propose novel therapies to better prevent vascular disorders in the population.

Diltiazem prophylaxis reduces incidence of atrial fibrillation after coronary artery bypass grafting.

AIM: To evaluate the prophylactic effect of diltiazem on the incidence of atrial arrhythmia (fibrillation and/or flutter) following coronary artery bypass grafting (CABG). Data were retrospectively gathered. METHODS: Patients undergoing elective CABG by one surgeon at one institution over a three-year period were considered for inclusion. Those selected were divided into 3 groups: A (patients placed on intravenous diltiazem intraoperatively, then converted to oral diltiazem upon initiation of oral intake); B (patients started on oral diltiazem upon initiation of oral intake without prior intravenous diltiazem); and C (patients receiving no diltiazem). A comparison of postoperative rates of atrial fibrillation was made between the 3 (demographically balanced) groups using logistic regression. RESULTS: Two hundred and eighty seven patients met inclusion criteria. The incidence of postoperative atrial fibrillation in the entire sample was 19.9% (57/287). Incidence of postoperative atrial fibrillation within each group was: A = 16.3% (22/135); B = 12.7% (7/55); C = 28.9% (28/97). Statistical significance was demonstrated for the following comparisons: A versus C (p = 0.0451) and B versus C (p = 0.0065). In an alternate model groups A and B were combined and compared to C (p = 0.0181). CONCLUSIONS: A lower incidence of atrial fibrillation following CABG was observed in patients treated prophylactically with diltiazem. Differences were statistically significant whether the drug was administered intravenously and orally (A) or only orally (B). Diltiazem, which has an established role in the management of atrial fibrillation, may prove to be well suited for prophylaxis due to low cost and relative safety.

Venous bypass of complicated stent placement for recurrent extracranial carotid occlusive disease.

Aim of the study was to to demonstrate a useful solution to carotid angioplasty and stent complications. A 67 year old male had uncomplicated left carotid endarterectomies in 1985 and 1986. A left distal common carotid angioplasty and stent in 1999 was complicated by stenosis. In 2000 a left common carotid bypass from the lower common carotid to the distal internal carotid well above the stent was performed, yielding retrograde filling of the external carotid, distal antegrade filling of the internal carotid, and widely patent vessels in subsequent Doppler studies. He is currently doing well clinically with no recurrent stenosis. In conclusion a second redo carotid operation was deferred in favor of angioplasty and stent, which had complications. Despite prior operations the only difficulty with the reoperation was obtaining control of the distal internal carotid above the stent. The strategy demonstrated here will be useful to correct complications of carotid angioplasty and stenting.

Effects of valproic acid on beta-adrenergic receptors, G-proteins, and adenylyl cyclase in rat C6 glioma cells.

Valproic acid (VPA) is an anticonvulsant drug with demonstrated efficacy in the treatment of mania. In the present study, we found that chronic exposure of rat C6 glioma cells to VPA induces a coordinate decrease in multiple components of the beta-adrenergic receptor- (beta-AR) coupled cyclic adenosine 3'-5'monophosphate (cAMP) generating system. Chronic VPA decreased the number of beta-ARs in a time- and concentration-dependent manner; the decrease of beta-ARs was largely beta 1-AR selective and affected beta-ARs in both the high- and low-affinity states. Chronic VPA also significantly attenuated receptor- and postreceptor-stimulated cAMP production, [3H]forskolin binding sites, immunolabeling of G alpha s 45, and cholera toxin catalyzed ADP-ribosylation of G alpha s 52 and 45. Although the precise underlying mechanisms remain to be elucidated, such profound long-term changes in the functioning of this key signaling pathway may help explain the antimanic effects of chronic VPA treatment and are worthy of further study.

Coronary reserve in volume-induced right ventricular hypertrophy from atrial septal defect.

To assess coronary reserve in patients with right ventricular (RV) hypertrophy secondary to volume overload, the quantitative characteristics of coronary reactive hyperemia were examined in 20 patients with a large atrial septal defect (ASD). The control group consisted of 13 patients who had undergone elective cardiac surgery for abnormalities that did not involve the right ventricle or its blood supply. Coronary blood flow velocity was measured in RV branches of the right coronary artery at cardiac surgery. Echocardiographic measurements of RV diameter in ASD and in control patients (2.3 +/- 0.2 and 1.1 +/- 0.2 cm, respectively, p less than 0.05) documented the presence of substantial RV enlargement in patients with ASD. In patients with ASD and in control subjects, a 20-second coronary occlusion produced maximal coronary dilation. After release of a 20 second coronary occlusion, the peak-to-resting velocity ratio in ASD and in control patients was 3.1 +/- 0.2 and 5.5 +/- 0.1, respectively (p less than 0.05). The 50% decrease in the ratio of peak-to-resting coronary blood flow velocity, a measure of relative coronary reserve, in patients with ASD suggests that coronary reserve is compromised in volume-induced RV hypertrophy. These studies support the concept that in humans, volume-induced RV hypertrophy substantially decreases coronary reserve.

Use of plasma volume expanders in myocardial revascularisation.

The optimal solution for priming cardiopulmonary bypass machines and for postoperative resuscitation following myocardial revascularisation should be inexpensive, free of risk of transmitting disease, and free of other detrimental side effects. Colloid solutions are preferred over crystalloid solutions because of elevations in extracellular sodium and water that occur with cardiopulmonary bypass. Albumin, plasma protein solution, hetastarch (hydroxyethyl starch) and dextran are available for use if blood is not necessary and mediastinal blood is not available. Hetastarch is associated with a lower risk of bleeding and less risk of allergic reaction than dextran, and its cost is substantially less than that of albumin. However, high doses increase the risk of bleeding complications.

Surgical implications of sclerosing mediastinitis. A report of six cases and review of the literature.

Sclerosing mediastinitis is an uncommon disease associated with a multiplicity of clinical syndromes. The cause of this disorder is probably an abnormal fibroproliferative response to an inflammatory stimulus, most commonly a granulomatous infection secondary to Histoplasma capsulatum. The pathophysiology of this disease is predicated on the encasement of mediastinal vital organ structures within a dense fibrotic mass. This mass appears to emanate from an invasive chronic inflammatory process causing erosion as well as external compression of these structures. The following case reports illustrate the diversity of this disease entity, representing a patient population from the Ohio River Valley, endemic for histoplasmosis. The purpose of this report is to elucidate the various clinical manifestations of sclerosing mediastinitis and to correlate the pathologic process with a rational approach to treatment.

Coronary bypass without angiography: an unusual circumstance.

This paper presents an unusual case of an individual with myocardial ischemia, angina pectoris, and myocardial infarction who also had an anaphylactic reaction to angiographic dye. The coronary bypass operation was guided by the use of intraoperative coronary reactive hyperemia assessed by Doppler ultrasound. The patient has had a good response to the operation without additional angina or difficulties.

Measurements of coronary reactive hyperemia with a Doppler probe. Intraoperative guide to hemodynamically significant lesions.

The physiological significance of coronary obstructions of intermediate severity are difficult to assess from the angiogram alone. The hemodynamic significance of clinical coronary stenoses can be readily assessed, however, with a miniaturized Doppler probe developed at The University of Iowa Hospitals and Clinics to measure phasic coronary velocity. No dissection of the coronary vessel is required. The probe is held in place over the coronary vessel with a small suction cup. Reactive hyperemia responses obtained following a 20 second occlusion clearly demonstrate the hemodynamic significance of a coronary stenosis. We have employed this approach in 64 patients with coronary artery disease. In 12 (19%) in whom the degree of stenosis of the vessel was equivocal (diameter narrowing 25% to 70%), the use of the Doppler probe and a 20 second reactive hyperemia curve allowed accurate and immediate assessment of the need for a bypass. Five of these equivocal lesions did not produce any alterations in coronary reserve and, accordingly, the vessels were not bypassed. In seven of them, the reactive hyperemia response was markedly depressed and as a result the vessel in question was bypassed. Thus measurements of coronary reactive hyperemia in vessels with obstruction of intermediate severity can influence the operative plan by assessing the physiological significance of the obstruction.

The cost of simultaneous surgical standby for percutaneous transluminal coronary angioplasty.

From November, 1980, to May 1985, 699 patients have undergone percutaneous transluminal coronary angioplasty of 784 lesions at our institutions. Simultaneous surgical standby was available on all cases. One hundred twenty-four patients (18%) underwent immediate myocardial revascularization; 45 (6%) were operated on because the lesion could not be dilated. Seventy-nine patients (11%) underwent immediate operation for an acute complication of angioplasty: coronary occlusion in 45, dissection in 29, coronary perforation in three, and atrial perforation in one. Fourteen patients (18%) required cardiopulmonary resuscitation en route to the operating room, and 10 patients (20%) had insertion of an intra-aortic balloon pump in the cardiac catheterization laboratory. The average time from complication to reperfusion was 87 minutes, ranging from 40 to 165 minutes. An average of 2.0 grafts per patient (ranging from one to five grafts per patient) were performed. Of those 79 patients who underwent operation for an acute complication, one died (1.3%), 31 patients (39%) had a myocardial infarction according to enzyme criteria (creatine kinase-myocardial band greater than 40 IU), and 17 patients (22%) had new Q waves on the electrocardiogram. Good results are related to minimizing the time the myocardium is ischemic. No patient in whom reperfusion was begun in less than 75 minutes had a Q wave infarction or a creatine kinase-myocardial band level greater than 40 IU. Simultaneous surgical standby is the only method allowing immediate access to surgical facilities. A standby team of eight persons and equipment were immediately available for emergency bypass grafting for an average of 3.6 hours (range 1.3 to 5.4 hours per angioplasty attempt). The patient charges for this simultaneous standby were $632.00 per angioplasty attempt, or $442,278.00 for the entire series. The actual cost of the standby was over $1,700.00 per attempt totaling $1,188,843.00 for the 699 patients. This underestimation of the cost of surgical standby has occurred in other series, because little mention has been made of this cost in the published reports on the cost effectiveness of angioplasty. In terms of time demands, over 2,500 hours were spent by surgeons standing by for the 699 attempts. Simultaneous surgical standby is the most effective means of limiting the time the myocardium is ischemic after an angioplasty complication. However, this method is costly, necessitating more of a financial and time commitment than generally anticipated. Future studies of the cost effectiveness of angioplasty should include the cost of surgical standby with accurate per-patient cost accountability.

Management of of arteriosclerotic aneurysm of the innominate artery.

Arteriosclerotic aneurysm of the innominate artery is an unusual lesion. A review of the literature has revealed many approaches to this problem in the past, but the mortality rate has remained significant and serious complications have been frequent. Computerized axial tomography and noninvasive cerebrovascular methods can be useful in managing this lesion. Vein grafts from the ascending aorta to the common carotid and subclavian arteries were used to revascularize a patient following resection of an innominate aneurysm.

Inferior mesenteric artery aneurysm: case report and discussion.

Although visceral artery aneurysms are uncommon, an isolated inferior mesenteric artery aneurysm is reported. A 55-year-old man underwent aortofemoral reconstruction with resection of the aneurysm and replantation of the artery into the Dacron graft. This unusual entity is discussed.

Successful management of popliteal arterial disruption in Ehlers-Danlos syndrome.

A review of the literature on Ehlers-Danlos syndrome with particular attention to vascular complications enabled us to outline an orderly diagnostic and therapeutic plan which has allowed salvage of an individual with a popliteal false aneurysm. In patients with Ehlers-Danlos syndrome and brachial, superficial femoral, or popliteal arterial disruption, the use of proximal tourniquet control to allow ligation of the disrupted artery under a no-flow, no-pressure situation is recommended. The ligations should be carried out with a large ligature or possibly with large hemoclips and/or reinforced with multiple fine atraumatic vascular sutures distally. These patients may be treated successfully for flexion contractures because of the laxness of their tissues.

The filtration limitations of ultrapore filters.

The filtration effectiveness of four commercially available microaggregate filters was determined using 14-day-old stored human blood in a constant infusion system. All filters significantly reduced the volumes of microaggregates contained in 500 ml. of blood. Three of the filters tested either occluded or failed to effectively remove microdebris from larger volumes of blood. These filters should be employed only for single blood transfusions. A fourth filter--of grid design--was effective in removing microdebris from 2,000 ml. of blood, the limits of the study. When employing microaggregate filters in massive transfusion situations for the prevention of pulmonary dysfunction, filtration characteristics and efficiencies of the filters employed must be known so that inadvertent administration of microdebris to the patient might be prevented.

Adrenergic mechanisms in the cephalic and cerebral circulations of the subhuman primate.

Effects of circulating adrenergic amines on the cerebral circulation remain contraversial. Common carotid (CCF) and internal carotid (ICF) arterial flows were determined electromagnetically in eight lightly anesthetized baboons to evaluate alterations in the cephalic and cerebral vascular beds, respectively. Epinephrine (E), norepinephrine (NE), phenylephrine (PE), and isoproterenol (I) were injected randomly in doses of 10-3, 10-2, 10-1, and 1 mug (base) per kilogram into each carotid artery. Measurements were repeated in four animals after alpha-adrenergic blockade with phenoxybenzamine and in another four animals after beta-adrenergic blockade with propranolol. Baseline CCF was 75 plus or minus 10 (S.E.M.) ml. per minute and ICF was 58 plus or minus 8 ml. per minute. Significant (p smaller than 0.05) CCF changes without arterial pressure alterations occurred with 10-1 mug per kilogram doses. Alpha blockade significantly (p smaller than 0.05) attenuated the effects of E, NE, and PE on CCF while beta blockade significantly (p smaller than 0.05) attenuated the effect of I on CCF. ICF did not change significantly (p greater than 0.05) after injection of any of the vasoactive amines, unless associated with pressure changes at the highest dose. Our data suggest the presence of alpha- and beta-adrenergic receptor sites within the cephalic circulation resulting in significant flow responses to intra-arterial adrenergic amines. The absence of responses in the cerebral circulation suggests that circulating catecholamines do not significantly influence or regulate the cerebral vasculature. In addition the data suggest that use of adrenergic agonists to alter the hemodynamics of the cerebral circulation is limited.

Hemodynamic effects of intra-arterial injection of drugs of abuse.

Acute vascular insufficiency following intra-arterial injection of a variety of drugs has been recognized for many years. The present study addresses the hypothesis that this vascular insufficiency may be due to vasospasm. Intra-arterial injections of logarithmic doses of drugs of abuse from the barbiturate, narcotic, non-narcotic analgesic, and amphetamine groups were studied in baboons. All drugs except amphetamine produced significant increases in femoral flow. Dextroamphetamine produced insignificant alteration in flow. Solid excipients, cornstarch, and talcum powder when injected intra-arterially decreased flow, and vascular obstruction was shown angiographically. These data suggest that vasospasm is not a primary response of intra-arterial injection of drugs of abuse.