Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is commonly overlooked or misdiagnosed owing to its recent identification. It is characterized clinically by recurrent cerebral infarcts, usually appearing between the ages of 30 and 50 years, subcortical dementia, and pseudobulbar palsy. It begins with migraine with aura in approximately one-third of patients. The pathological hallmark of angiopathy is the presence of characteristic granular osmiophilic material (GOM) within the basal lamina of smooth muscle cells. The defective gene in CADASIL is Notch3, which encodes a large transmembrane receptor, and 70% of missense mutations are in exons 3 and 4. Each gene defect leads to either a gain or loss of a cysteine residue in the extracellular N-terminal domain of the molecule. We report the case of a 53-year-old woman admitted to the hospital for transient ischemic attack and stroke-like episodes recurrent since age 43 years. The patient had pseudobulbar palsy, pyramidal signs, and cognitive impairment but not frank dementia. Cerebral MRI showed periventricular diffuse and confluent ischemic lesions. Ultrastructural study revealed an abnormal deposition of granular osmiophilic material (GOM) within the basal lamina in skin capillaries. Direct sequence analysis of the Notch3 gene was performed. Since no mutation was detected in exons 3 and 4, the remaining exons were sequenced and a missense mutation, CGC-TGC in codon 1006 of exon 19 was found. The mutation led to a gain of a cysteine residue. This is the first missense mutation in codon 1006 of exon 19 of the Notch3 gene to be described in Italy and the second reported in the literature.
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PMID:An Italian case of CADASIL with mutation CGC-TCG in codon 1006, exon 19 Notch3 gene. 1476 86

Over a 5-year period, we investigated 77 consecutive patients (36 males, 41 females, mean age 40.9 years) referred to our hospital with the diagnosis of CNS vasculitis. Extensive workup including MRI, echocardiography, laboratory tests, angiography ( n=53), and biopsies at appropriate sites ( n=26) was performed based on individual history and symptoms. Prominent symptoms were stroke ( n=61), encephalopathy ( n=14), and headaches ( n=2). Vasculitis was finally diagnosed in 13 patients (17%) including isolated angiitis of the CNS ( n=3), giant cell arteritis ( n=4), and septic arteritis ( n=3). Thirty-two patients (42%) presented noninflammatory vasculopathies including moyamoya ( n=6), Sneddon's syndrome ( n=5), dissection ( n=4), CADASIL ( n=2), and collagen vascular disease ( n=9). Coagulopathy was found in 14 cases (18%) including antiphospholipid syndrome ( n=8) and APC resistance ( n=4). Other causes were cardiogenic embolism ( n=8), multiple sclerosis ( n=5), and migraine stroke ( n=3). Only a minority of patients referred for evaluation of suspected CNS vasculitis actually present with inflammatory vascular disease. Main differential diagnosis includes noninflammatory vasculopathies, coagulopathies, and cardiac disease. Since septic processes may be responsible for the symptoms, "blind" treatment with immunosuppressive agents should be strictly avoided.
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PMID:[Diagnosis and differential cerebral vasculitis diagnosis]. 1477 Feb 79

Stroke from reversible cerebral arterial vasoconstriction has been described in a variety of conditions, including migraine, pregnancy, puerperium (postpartum angiopathy), use of vasoconstrictive drugs, Call-Fleming syndrome, and benign angiopathy of the central nervous system. Although vasoconstriction is an important cause of ischemic and hemorrhagic stroke in young individuals, vasoconstriction syndromes have not been well characterized and remain under-recognized. Misdiagnosis is common because the clinical and radiological features can overlap with conditions such as primary cerebral vasculitis. With the advent of newer, noninvasive angiography techniques and the escalating use of vasoactive drugs, it is likely that clinicians will encounter more patients with vasoconstriction-induced stroke. This article reviews the history, clinical and radiological characteristics, differential diagnosis, and management of cerebral vasoconstriction syndromes.
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PMID:Cerebral vasoconstriction syndromes. 1511 61

Migraine headaches affect 12% of the adult population in the United States and cause a significant economic loss due to decreased workplace productivity Although interactions between pharmacists and individuals with headache are common, few pharmacists receive adequate training regarding migraine therapy. We refute several misconceptions that hinder effective care, such as that migraine is a vascular disease, triptans cause rampant cardiacrelated morbidity and even mortality, a best oral triptan exists, sinus and tension headaches are prevalent, and migraine is a minor economic problem. Our pathophysiologic understanding demonstrates that migraine is a neurologic process of the trigeminovascular system, of which vascular effects are secondary. This process can result in a myriad of clinical signs and symptoms, often leading to a misdiagnosis of sinus or tension headache. The last decade's experience with triptans in more than half a billion people worldwide reveals a benign adverse-effect profile, particularly when taken early in an attack. Published reports and real-world experiences illustrate that these drugs do not merit fears of triptan-induced cardiac consequences in appropriately selected individuals. Society's productivity loss due to migraine is measured in billions of dollars. Restoring a patient's ability to function normally is now recognized as the primary treatment goal, not merely relieving pain. Thus, the overreliance on "pain killer" drugs such as butalbital-containing products and the continued underutilization of migraine-specific drugs need to be addressed. Opportunities exist for pharmacists and other health care providers to dispel continually propagated migraine misconceptions and familiarize themselves with advances in therapy. Such actions will benefit patients, the health care system, and society as a whole.
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PMID:Migraine headache misconceptions: barriers to effective care. 1516 98

A cerebral arteriopathy with subcortical infarcts and leukoencephalopathy is described with a pedigree suggestive for an autosomal dominant condition. In contrast to the vasculopathy designated with the acronym CADASIL, no deposits of granular osmiophilic material were detected in the vasculature and no point mutations in the NOTCH 3 gene were found. The disease occurred in a family living near Hamburg, Germany, and affected 11 women and 11 men over the last six generations. Onset of the disease was between the age of 12 and 50. Clinical symptoms included gait disturbances, dysarthria, sensomotoric deficits and a progressive dementia. Migraine-like complaints and epileptic seizures were observed in one case each. Cranial computer tomography and magnetic resonance imaging scans showed large confluent areas with decreased density in the white matter and small necroses in the brain stem, the basal ganglia and the white matter. A correlation with factors predisposing for vascular diseases could not be demonstrated. In five cases an autopsy was performed which disclosed an angiopathy affecting predominantly the penetrating arteries with consecutive lacunar infarcts, diffuse demyelination and rarefication of the subcortical white matter and degeneration of the pyramidal tracts. Histologically, the vessels showed concentric and excentric intimal proliferation, an elastosis and hyalinosis, splitting of the lamina elastica interna and a degeneration of the tunica muscularis. Electron microscopy revealed fragmentation and thickening of the basal lamina but electron-dense granules characteristic for CADASIL were not detected.
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PMID:Subcortical angiopathic encephalopathy in a German kindred suggests an autosomal dominant disorder distinct from CADASIL. 1522 37

The purpose of the study was to examine the value of the non-invasive magnet resonance angiography (MRA) in the follow-up of cerebral vasculitis (CV) and vasculitis-like angiopathy. We performed follow-up MRA (TOF 3D), MRI and transcranial doppler ultrasound (TCD) in the patients with isolated angiitis of the CNS (2/6), Crohn-disease-associated CV (1/6), and reversible arterial vasoconstriction (RAV) of the CNS (1 migraine, 1 eclampsia and 1 toxic encephalopathy) (3/6). In all patients with RAV MRA showed a complete remission of the vascular alterations after treatment. In the patients with isolated angiitis of the CNS and Crohn-disease-associated CV, partly regressive and partly progressive changes were demonstrated. The MR-angiographically detectable vascular alterations corresponded to the clinical course of the disease, as well as to TCD in all our patients. Success of therapeutic procedures, the need and the intensity of further drug administration could be estimated. The MRA appears to be a valuable non-invasive method in the follow-up of patients with CV and RAV.
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PMID:Serial magnet resonance angiography in patients with vasculitis and vasculitis-like angiopathy of the central nervous system. 1525 78

Migraine is a common, chronic, multi-factorial, neuro-vascular disorder typically characterised by recurrent attacks of unilateral, pulsating headache and autonomic nervous system dysfunction. Migraine may additionally be associated with aura; those focal neurological symptoms that may precede or sometimes accompany the headache. This review describes the optometric aspects of migraine headache. There have been claims of a relationship between migraine headaches and errors of refraction, binocular vision anomalies, pupil anomalies, visual field changes and pattern glare. The quality of the evidence for a relationship between errors of refraction and binocular vision and migraine is poor. The quality of the evidence to suggest a relationship between migraine headache and pupil anomalies, visual field defects and pattern glare is stronger. In particular the link between migraine headache and pattern glare is striking. The therapeutic use of precision-tinted spectacles to reduce pattern glare (visual stress) and to help some migraine sufferers is described.
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PMID:The optometric correlates of migraine. 1531 51

Grapefruit juice can alter oral drug pharmacokinetics by different mechanisms. Irreversible inactivation of intestinal cytochrome P450 (CYP) 3A4 is produced by commercial grapefruit juice given as a single normal amount (e.g. 200-300 mL) or by whole fresh fruit segments. As a result, presystemic metabolism is reduced and oral drug bioavailability increased. Enhanced oral drug bioavailability can occur 24 hours after juice consumption. Inhibition of P-glycoprotein (P-gp) is a possible mechanism that increases oral drug bioavailability by reducing intestinal and/or hepatic efflux transport. Recently, inhibition of organic anion transporting polypeptides by grapefruit juice was observed in vitro; intestinal uptake transport appeared decreased as oral drug bioavailability was reduced. Numerous medications used in the prevention or treatment of coronary artery disease and its complications have been observed or are predicted to interact with grapefruit juice. Such interactions may increase the risk of rhabdomyolysis when dyslipidemia is treated with the HMG-CoA reductase inhibitors atorvastatin, lovastatin, or simvastatin. Potential alternative agents are pravastatin, fluvastatin, or rosuvastatin. Such interactions might also cause excessive vasodilatation when hypertension is managed with the dihydropyridines felodipine, nicardipine, nifedipine, nisoldipine, or nitrendipine. An alternative agent could be amlodipine. In contrast, the therapeutic effect of the angiotensin II type 1 receptor antagonist losartan may be reduced by grapefruit juice. Grapefruit juice interacting with the antidiabetic agent repaglinide may cause hypoglycemia, and interaction with the appetite suppressant sibutramine may cause elevated BP and HR. In angina pectoris, administration of grapefruit juice could result in atrioventricular conduction disorders with verapamil or attenuated antiplatelet activity with clopidrogel. Grapefruit juice may enhance drug toxicity for antiarrhythmic agents such as amiodarone, quinidine, disopyramide, or propafenone, and for the congestive heart failure drug, carvediol. Some drugs for the treatment of peripheral or central vascular disease also have the potential to interact with grapefruit juice. Interaction with sildenafil, tadalafil, or vardenafil for erectile dysfunction, may cause serious systemic vasodilatation especially when combined with a nitrate. Interaction between ergotamine for migraine and grapefruit juice may cause gangrene or stroke. In stroke, interaction with nimodipine may cause systemic hypotension. If a drug has low inherent oral bioavailability from presystemic metabolism by CYP3A4 or efflux transport by P-gp and the potential to produce serious overdose toxicity, avoidance of grapefruit juice entirely during pharmacotherapy appears mandatory. Although altered drug response is variable among individuals, the outcome is difficult to predict and avoiding the combination will guarantee toxicity is prevented. The elderly are at particular risk, as they are often prescribed medications and frequently consume grapefruit juice.
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PMID:Interactions between grapefruit juice and cardiovascular drugs. 1544 71

Several case-control and cohort studies have suggested an association between migraine and stroke. A significantly higher risk for stroke was found in women under the age of 45 years and for the subgroup with migraine with aura, the posterior circulation being significantly more frequently involved. The link between cardiac diseases and the comorbidity migraine-stroke has been evaluated considering both possible relationships: a higher prevalence of a vascular disease involving both heart and brain in migraineurs, or a cardiac disorder, more prevalent in migraineurs, with a possible aetiological role in migraine attacks.
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PMID:The role of cardiac diseases in the comorbidity between migraine and stroke. 1554 21

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is an autosomal dominant angiopathy characterized by recurrent cerebrovascular events, migraine and dementia. We describe a case of sensorineural hearing loss as the presenting feature of this condition. We have found no previous reports in the world literature of CADASIL presenting with a sudden sensorineural hearing loss. The significance of questioning a patient with regard to family history is exemplified in this case.
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PMID:Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) presenting with sudden sensorineural hearing loss. 1582 71


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