Antihypertensive therapy and diabetic microvascular disease

Hypertension is commonly associated with diabetes and may represent either a manifestation or a cause of diabetic vascular injury. The following series of studies have explored the role of hypertension in accelerating diabetic microvascular injury. In addition, the role of various classes of antihypertensive agents in preventing or reversing diabetic vascular abnormalities in the presence and absence of systemic hypertension was assessed in both the experimental and clinical context. The induction of streptozotocin diabetes in SHR leads to accelerated development of nephropathy as assessed by both functional and structural parameters. ACE inhibitors but not dihydropyridine calcium channel blockers favourably influence the progression of experimental diabetic nephropathy even in the setting of a normal blood pressure. More recent studies have shown that the trophic changes in the mesenteric arteries from diabetic rats are also attenuated by ACE inhibition. Preliminary results from the Melbourne Diabetic Nephropathy Study Group suggest that the ACE inhibitor, perindopril, is more effective than the dihydropyridine calcium channel blocker, nifedipine, in retarding the rise in urinary albumin excretion in normotensive insulin and noninsulin dependent diabetic patients with microalbuminuria. In conclusion, ACE inhibitors appear to be the drugs of choice in prevention and treatment of diabetic renal disease and may also act as protective agents at other sites of vascular injury.     

Gene therapy for cerebrovascular disease

OBJECTIVE: To review the principles of and the experimental and clinical results of gene therapy for cerebrovascular disease. METHODS: Literature review. RESULTS: Vectors for gene transfer into the brain or into the cerebral vasculature include naked plasmid deoxyribonucleic acid, cationic liposomes, and viruses such as adenovirus, retrovirus, adeno-associated virus, and herpes simplex virus. Experiments using these vectors showed that intra- or perivascular application to systemic arteries can lead to transfection and expression of a foreign transgene in the adventitia and the endothelium. Intrathecal administration can lead to transfection and foreign transgene expression in leptomeningeal cells as well as in fibroblasts of blood vessel adventitia. Biological effects demonstrated thus far include increased nitric oxide production by transfection of cerebral arterial adventitia with adenovirus expressing nitric oxide synthase. Adenoviruses carrying foreign genes have been used to decrease neuronal damage in cerebral ischemia and to decrease blood pressure in spontaneously hypertensive rats. Vectors and therapeutic applications for gene therapy are evolving rapidly. CONCLUSION: Gene therapy for cerebrovascular disease is likely to have clinical application in the near future and will have a major impact on neurosurgery. Neurosurgeons will need to be aware of the literature in this area.     

Antihypertensive drug therapy and coronary heart disease risk

Coronary heart disease (CHD) is the major cause of death in the United States. Major modifiable risk factors for CHD are hypertension, hypercholesterolemia, and cigarette smoking, with concomitant risk factors, especially left ventricular hypertrophy, that act synergistically to significantly increase overall risk. Antihypertensive therapy, while reducing the incidence of stroke, has not consistently reduced the incidence of CHD. This may be a result, in part, of adverse effects on the metabolic profile, especially on blood lipids, which are induced by diuretics and certain beta-blockers. Other antihypertensive agents appear to be either lipid neutral, such as calcium channel blockers and angiotensin-converting enzyme inhibitors, or lipid positive, such as selective alpha 1-blockers. The choice of initial antihypertensive therapy should be made with all of a patient's risk factors in mind. In addition to the drugs recommended in the 1988 Guidelines of the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure, selective alpha 1-blockers should also be considered since they improve the lipid profile as well as reduce blood pressure.     

Ischemic cerebrovascular disease in patients with atrial fibrillation

The purpose of this retrospective study was to elucidate 1) which subgroups are prone to have ischemic cerebrovascular disease (CVD) among patients with atrial fibrillation (Af), 2) vulnerable period of CVD after the diagnosis of chronic Af and 3) the clinical efficacy of antiplatelet therapy in chronic nonvalvular Af patients. During 9 years, a total of 479 patients included 124 cases with paroxysmal Af, 30 cases with paroxysmal Af initially which later changed to chronic Af and 325 cases with chronic Af were enrolled. Among these 355 cases with chronic Af, 57 cases had valvular heart disease (VHD). The results were as follows: 1) The high risk subgroups (incidence rate/100 person-years is more than 6) were chronic Af with VHD or hypertension. The low risk subgroups (less than 2) were paroxysmal Af under 60 years of age, chronic Af with mitral valve prolapse syndrome or with hyperthyroidism. 2) There was no vulnerable period for occurrence of CVD during 9 years' follow-up from the onset of Af. 3) No significant difference in the incidence of CVD was seen in the groups with antiplatelet therapy and without.     

Coronary artery bypass grafting in patients with cerebrovascular disease

The incidence of carotid artery disease in patients undergoing coronary artery bypass grafting appears to be increasing as our population ages. The optimal treatment for these high-risk patients with concomitant carotid and coronary artery disease remains controversial. This review focuses on the management of patients with coexistent carotid and coronary arteriosclerosis. The significance and management of the patient with an asymptomatic carotid stenosis in patients undergoing coronary artery bypass grafting and the role of combined coronary artery bypass grafting and carotid endarterectomy in these patients will be discussed.     

Lipids and lipoproteins in a group of patients with ischemic cerebrovascular disease

OBJECTIVE: To study the blood levels of a group of lipids and lipoproteins in patients with ischemic cerebrovascular disease which was not secondary to cardiac embolic disease. PATIENTS AND METHODS: We assessed 40 patients of an average age of 64.5 years. Of these, 26 had cerebral infarcts due to disease of the great vessels and 14 had lacunar infarcts. Forty persons with no cerebrovascular disease were used as controls. We excluded patients diagnosed as having renal failure, liver, hematological, neoplastic and acute febrile disorders. Plasma was analyzed for total cholesterol, triglycerides, lipoproteins (a), HDL, LDL, VLDL and apoprotein B between 3 weeks and 6 months after the initial stroke. RESULTS AND CONCLUSIONS: Levels of triglycerides and of lipoprotein (a) were significantly greater in patients than in controls. We found no differences between the levels of total cholesterol, HDL, LDL, VLDL in the three groups studied. However, apoprotein B was greater in the controls than in the patients. There were no significant differences between the groups with lacunar ictus and those with infarcts secondary to disease of the great vessels.     

Assessment of thalamic regional cerebral blood flow in patients with cerebrovascular disease

The thalamus is believed to play an integrative role in the central nervous system. In the present study, thalamic rCBF was measured in 65 CVD patients and 15 normal volunteers by stable Xe/CT scanning. ROIs were chosen in the thalamic slice at a level 5cm over the OM line, and mean CBF was 7 cm over the OM line. The clinical factors focused on in multiple regression analysis were: age (A), sex (Se), stage from onset (St), lesion side (Sd); unilaterality or bilaterality, size (Sz) thalamic lesion (Tl). GCS (G), HDS-R (H); Hasegawa dementia score (revised), symptoms (Ss) such as anxiety, dizziness, head-headed feeling and headache, and neurological deficits (N). Each factor was graded and scored. Statistically, there was a significant correlation between thalamic rCBF (Y) and mean CBF (X) in the less affected hemisphere: Y = 1.82X + 2.2, r = 0.801, p < 0.001, n = 65. Multiple regression analysis of the thalamic rCBF revealed that the Sz factor was significant (p < 0.0001) on the lesion side: Y = 76.7-10.2Sz, r = 0.644, p < 0.001, n = 51, while the Se, Sd and St factors were significant (p < 0.005) on the less affected side: Y = 71.9 + 9.7Se-6.8Sd-5.0St, R = 0.585, p < 0.001, n = 65. The thalamic index (X), an indicator of thalamic atrophy, and thalamic rCBF were significantly correlated: Y = 28.7X + 10.2, r = 0.386, p < 0.001, n = 80. In conclusion, thalamic rCBF appeared to reflect the degree of organic changes and time course in the cerebral hemisphere, because factors such as size, sex and stage were statistically significant.     

Stain therapy and reduced incidence of stroke. Implications of cholesterol-lowering therapy for cerebrovascular disease

Three recent large clinical trials-the West of Scotland Coronary Prevention Study, the Scandinavian Simvastatin Survival Study, and the Cholesterol and Recurrent Events Trial-have all confirmed that cholesterol lowering with HMG-CoA reductase inhibitors is safe and effective therapy to prevent an initial or recurrent coronary event in patients at high risk for coronary heart disease. However, a number of questions related to the treatment of lipid disorders and risk reduction for coronary heart disease remain, including the cholesterol concentration at which treatment would best be initiated, the optimal cholesterol reduction or goal to be attained, and the mechanisms by which HMG-CoA reductase inhibitors reduce the risk for clinical events.     

Association of Helicobacter pylori infection with cardiovascular and cerebrovascular disease in diabetic patients

We present the case of 44-yr-old man who presented syncope with ventricular tachycardia in the setting of Brugada syndrome. In addition to the electrocardiographic evidence of the syndrome and the absence of apparent structural heart disease, clear defects of myocardial neuronal metaiodobenzylguanidine (MIBG) uptake on MIBG SPECT imaging also were found in inferior, apical and septal walls. Thallium-201 SPECT distribution was homogeneous along the left ventricle. Thus, cardiac MIBG scintigraphy provides information about left ventricular dysinnervation in a patient with Brugada syndrome, enhancing the clinical utility of myocardial MIBG SPECT imaging in life-threatening ventricular arrhythmias.     

The effect of mesoglycan in patients with cerebrovascular disease: a psychometric evaluation

Mesoglycan is a preparation of natural glycosaminoglycans, containing mainly heparan sulphate and dermatan sulphate. A clinical trial was conducted to evaluate the efficacy and the tolerability of once-daily mesoglycan in 30 patients with clinical evidence of cerebrovascular insufficiency. Clinical effectiveness was assessed using psychometric and neurological scales: Sandoz Clinical Assessment for Geriatric Patients (SCAG); Parkside Behaviour Rating Scale Modified; Geriatric Depression Scale; and Anxiety Evaluation. Mesoglycan was given as a single oral once-daily dose of 100 mg for a period of 6 months. This treatment was shown to have positive effects on the cognitive and behavioural parameters evaluated. The effects on SCAG were already evident after 3 months' treatment and a significant improvement was observed after 6 months in those patients with a moderate to severe disease. During the treatment period only one patient suffered an adverse reaction attributed to the drug investigated.     

STAR MR angiography for rapid detection of vascular abnormalities in patients with acute cerebrovascular disease

BACKGROUND AND PURPOSE: We undertook to investigate the usefulness of signal targeting with alternating radiofrequency magnetic resonance angiography (STAR MRA) in the diagnosis of acute cerebrovascular disease. The potential advantage of the technique is that angiographic images can be acquired in less than 1 minute. METHODS: We studied 19 patients (11 men and 8 women, ranging in age from 36 to 84 years [mean age, 66 years]) presenting with signs and symptoms of acute stroke. Patients underwent STAR MRA and three-dimensional fast imaging with steady-state precession (3D FISP) MRA. The MRAs were analyzed as to image quality and vascular abnormalities in the vascular territory of stroke as defined by diffusion-weighted imaging abnormalities and compared using a Wilcoxon signed-rank test. RESULTS: STAR MRAs had slightly inferior image quality compared with 3D FISP MRA (P < .05). STAR MRA and 3D FISP MRA agreed in 18 of 19 cases regarding vascular abnormalities in the territory of the infarct (occlusion, n = 8; stenosis, n = 4; no abnormality, n = 6). In one patient, the techniques disagreed, when 3D FISP MRA was normal and STAR MRA demonstrated a vessel occlusion in the vascular territory of a stroke as defined by diffusion-weighted imaging abnormalities (P > .05). CONCLUSIONS: Despite slightly inferior image quality compared with 3D FISP MRA, STAR MRA is comparable with 3D FISP MRA in depicting abnormalities in the proximal parts of the cerebral arteries corresponding to ischemic regions on diffusion-weighted imaging, in a strikingly shorter acquisition time. Further studies are necessary to confirm that the smaller branches are better shown by using longer inversion times.     

Thrombosis and cerebrovascular disease

Strokes are heterogeneous not only with respect to their presentation, but more importantly in terms of the underlying pathology. There are now a number of choices available for the treatment of ischemic stroke, and the causative mechanisms responsible for each individual stroke must be considered in choosing an appropriate form of treatment. This article explores the underlying pathophysiological mechanisms responsible for the major categories of stroke and also examines the reasons why strokes worsen or evolve.     

Antihypertensive therapy in type 2 diabetes mellitus

Fifty-seven patients with failed sclerotherapy received a mesocaval interposition shunt with an externally supported, ringed polytetrafluoroethylene prosthesis of either 10 or 12 mm diameter. Thirty-one patients had Child-Pugh grade A disease and 26 grade B; all had a liver volume of 1000-2500 ml. Follow-up ranged from 16 months to 6 years 3 months. Three patients (5 per cent) died in the postoperative period. There were two postoperative recurrences of variceal haemorrhage and one recurrent bleed in the second year after surgery. The cumulative shunt patency rate was 95 per cent and the incidence of encephalopathy 9 per cent; the latter was successfully managed by protein restriction and/or lactulose therapy. The actuarial survival rate for the whole group at 6 years was 78 per cent, for those with Child-Pugh grade A 88 per cent and for grade B 67 per cent. Small-lumen mesocaval interposition shunting achieves portal decompression, preserves hepatopetal flow, has a low incidence of shunt thrombosis, prevents recurrent variceal bleeding and is not associated with significant postoperative encephalopathy.     

New interventions in cerebrovascular disease: the role of thrombolytic therapy and balloon angioplasty

The use of thrombolytic agents (plasminogen activators) in the early moments of ischemic stroke to achieve recanalization and potential neurologic improvement has been actively studied over the past 10 years. In the same period, endovascular techniques for cerebral revascularization have evolved significantly. Recent phase III studies, following angiography-based phase I and II studies of plasminogen activators in stroke, have described evidence of clinical benefit and contributors to morbidity (i.e., symptomatic hemorrhage) and mortality that limit the applicability of this approach. The limited formalized experience with percutaneous transluminal balloon angioplasty and stent placement in the carotid artery and cerebral circulation has given rise to concerns about the safety and appropriateness of the procedures in this territory. However, several prospective series support the feasibility of well-designed clinical trials.     

Thyroxine suppressive therapy in patients with nodular thyroid disease

PURPOSE: To review evidence about thyroxine suppressive therapy in patients with thyroid nodules, including the clinical importance and natural history of nodules and the effects and potential side effects of thyroxine therapy. DATA SOURCES: English-language articles published from 1986 to December 1996 were identified through searches of the MEDLINE database, selected bibliographies, and personal files. DATA EXTRACTION: Randomized, controlled trials and nonrandomized trials of thyroxine suppressive therapy for solitary and predominantly solid thyroid nodules were reviewed. In most studies, nodule cytology was evaluated by fine-needle aspiration biopsy. Therapy was considered suppressive if suppression was documented by thyroid-stimulating hormone-releasing hormone tests or sensitive thyroid-stimulating hormone assays. Response was defined as a decrease of 50% or more in nodule size or volume; most recent studies measured nodule size by ultrasonography. DATA SYNTHESIS: The evidence suggests that thyroxine suppressive therapy fails to shrink most nodules: Only 10% to 20% of nodules responded to this treatment. Fine-needle aspiration biopsy is more reliable in distinguishing benign from malignant nodules. Recent studies suggest that spontaneous decrease in size with complete disappearance of thyroid nodules is not uncommon. No data show that thyroxine therapy arrests further growth in most existing nodules or prevents the emergence of new nodules. Postoperative thyroxine therapy does not seem to prevent recurrence of thyroid nodules except in patients with a history of radiation therapy. Potential adverse effects of long-term suppressive therapy include osteoporosis and heart disease. CONCLUSIONS: Patients with cytologically benign nodules are best followed without thyroxine treatment. Most benign nodules remain stable in size and remain benign when monitored for a long time. For nodules that increase in size, biopsy should be done again or surgery should be performed.     

Transient ischemic attacks in Chilean patients and their relationship with the country''s pattern of cerebrovascular disease

For the globular proteins with known three-dimensional structures, an ellipsoid model of each protein was constructed with least volume and its dimensions were derived. The spatial arrangements were made for the C alpha and side chain atoms of that protein within that ellipsoid. This new spatial representation shows the residue position from the centroid, as well as the depth from the surface. The average spatial parameters were then calculated. The correlations between these new spatial parameters and the existing parameters of the amino acid residues were then derived.