Gene/Protein Disease Symptom Drug Enzyme Compound
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 21,692 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytomegalovirus (CMV) infection is one of the most important opportunistic infections in AIDS. The most common manifestation of neurological CMV disease in HIV infection is retinitis followed by encephalitis, polyradiculopathy, and multifocal neuropathy. Untreated necrotizing retinitis proceeds to blindness but can readily be diagnosed by ophthalmological examination. CMV polyradiculopathy presents as subacute leg weakness, paraesthesia, and urinary retention. Untreated patients develop ascending paralysis and die within weeks. Multifocal neuropathy commonly affects the radial, ulnar, and peroneal nerves but cranial nerves may also be involved. Confusion, cranial nerve palsies, and hyperreflexia are signs of ventriculoencephalitis, whereas the presentation of diffuse micronodular encephalitis is often asymptomatic. The diagnostic approach relies on the detection of CMV DNA in the cerebrospinal fluid for polyradiculopathy, encephalitis, and neuropathy. Neuroimaging can exclude other causes of encephalitis and polyradiculopathy. Ganciclovir, foscarnet, and cidofovir monotherapy are current medical treatment options. Intraocular administration can be used for refractory retinitis, but additional systemic prophylaxis is required to suppress extraocular disease. Ganciclovir and foscarnet have improved the prognosis of multifocal neuropathy and polyradiculopathy, but response rates for encephalitis are low. However, despite therapy survival of central nervous CMV disease is still limited to months. Recently highly active antiretroviral therapy (HAART) has decreased the overall incidence of CMV disease in AIDS. Furthermore (HAART) has become a mainstay for CMV therapy by improving the patient's immunocompetence against CMV.
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PMID:Neurological manifestations of cytomegalovirus infection in the acquired immunodeficiency syndrome. 1034 Jan 95

Ultimately traceable to neural glucose deprivation, symptoms of hypoglycemia include neurogenic (autonomic) and neuroglycopenic symptoms. Neurogenic symptoms (tremulousness, palpitations, anxiety, sweating, hunger, paresthesias) are the results of the perception of physiologic changes caused by the autonomic nervous system's response to hypoglycemia. Neuroglycopenic symptoms (confusion, sensation of warmth, weakness or fatigue, severe cognitive failure, seizure, coma) are the results of brain glucose deprivation itself. Glycemic thresholds for symptoms of hypoglycemia shift to lower plasma glucose concentrations following recent episodes of hypoglycemia, leading to the syndrome of hypoglycemia unawareness--loss of the warning symptoms of developing hypoglycemia. Thus, patients with recurrent hypoglycemia (e.g., those with tightly controlled diabetes or with an insulinoma) often tolerate abnormally low plasma glucose concentrations without symptoms.
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PMID:Symptoms of hypoglycemia, thresholds for their occurrence, and hypoglycemia unawareness. 1050 Sep 27

Six studies are cited to demonstrate that topiramate is effective as adjunctive therapy for refractory partial-onset seizures in adults. Subsequent studies indicate that topiramate is also effective as monotherapy in adults and as adjunctive therapy for partial-onset seizures in children, tonic-clonic seizures of nonfocal origin in children and adults, and drop attacks in Lennox-Gastaut syndrome. Adverse effects for adults and children included dizziness, fatigue, ataxia, confusion, somnolence, nephrolithiasis, paresthesia, and weight loss. More adverse effects were observed at higher doses. Topiramate exhibits rapid absorption, long duration of action, and minimal interaction with other antiepileptic drugs.
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PMID:Topiramate. 1053 Jun 97

R115777 is a nonpeptidomimetic enzyme-specific inhibitor of farnesyl protein transferase (FT) that was developed as a potential inhibitor of Ras protein signaling, with antitumor activity in preclinical models. This study was a phase 1 trial of orally administered R115777 in 35 adults with poor-risk acute leukemias. Cohorts of patients received R115777 at doses ranging from 100 mg twice daily (bid) to 1200 mg bid for up to 21 days. Dose-limiting toxicity occurred at 1200 mg bid, with central neurotoxicity evidenced by ataxia, confusion, and dysarthria. Non-dose-limiting toxicities included reversible nausea, renal insufficiency, polydipsia, paresthesias, and myelosuppression. R115777 inhibited FT activity at 300 mg bid and farnesylation of FT substrates lamin A and HDJ-2 at 600 mg bid. Extracellular signal-regulated kinase (ERK), an effector enzyme of Ras-mediated signaling, was detected in its phosphorylated (activated) form in 8 (36.4%) of 22 pretreatment marrows and became undetectable in 4 of those 8 after one cycle of treatment. Pharmacokinetics revealed a linear relationship between dose and maximum plasma concentration or area under the curve over 12 hours at all dose levels. Weekly marrow samples demonstrated that R115777 accumulated in bone marrow in a dose-dependent fashion, with large increases in marrow drug levels beginning at 600 mg bid and with sustained levels throughout drug administration. Clinical responses occurred in 10 (29%) of the 34 evaluable patients, including 2 complete remissions. Genomic analyses failed to detect N-ras gene mutations in any of the 35 leukemias. The results of this first clinical trial of a signal transduction inhibitor in patients with acute leukemias suggest that inhibitors of FT may have important clinical antileukemic activity. (Blood. 2001;97:3361-3369)
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PMID:Clinical and biologic activity of the farnesyltransferase inhibitor R115777 in adults with refractory and relapsed acute leukemias: a phase 1 clinical-laboratory correlative trial. 1136 25

Peripheral nerve entrapment is a rare, but important, cause of foot and ankle pain that often is underdiagnosed and mistreated. A peripheral nerve may become entrapped anywhere along its course, but certain anatomic locations are characteristic. Clinically,nerve entrapment is divided into three stages: in stage I patients feel rest pain and intermittent paresthesias which are worse at night; in stage II, continued nerve compression leads to paresthesias, numbness, and, occasionally, muscle weakness that does not disappear during the day, and in stage III, patients describe constant pain, muscle atrophy, and permanent sensory loss. Diagnostic confusion abounds because of the multiple etiologies of peripheral nerve entrapments and their complex physical and temporal relation. A thorough understanding of the causes of peripheral nerve entrapments, the anatomic course and variation of the peripheral nerves, the diagnostic modalities, and the treatment options can simplify this complex problem.
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PMID:Peripheral nerve entrapments. 1516 81

Non-ketotic hyperglycaemia (NKH)-related partial seizure disorders are not uncommon in clinical practice but still deserve attention as they significantly affect neurologic outcome if unnoticed. The atypical presentation of sensorimotor symptoms can be seen in this setting, with paroxysmal character as the rule. Atypical manifestations could cause confusion and might lead to improper diagnosis and treatment. We report a case of inadequately controlled diabetes mellitus and NKH presenting as paroxysmal paraesthesia of both hands, which was misdiagnosed as diabetic neuropathy.
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PMID:Non-ketotic hyperglycaemia-related paroxysmal bilateral hand paraesthesia misdiagnosed as diabetic neuropathy. 1689 31

The number of patients submitted to bariatric surgery to treat morbid obesity is increasing, therefore, some nutritional deficiencies, with which many physicians are no longer familiarized, are reappearing. Postoperatively, many nutritional disorders may occur, one of them is thiamine deficiency (beriberi). The thiamine and/or vitamin B12 deficiency can correspond to 40% of the neuropathy cases after bariatric surgery. Two patients with the clinic of peripheral neuropathy and Wernicke-Korsakoff syndrome will be reported. Some months after the surgery, they presented prostration, depression, mental confusion and nystagmus, associated with pain and paresthesia in limbs (especially lower limbs). With the diagnostic hypothesis of beriberi, the treatment with thiamine started. One of the patients presented complete improvement of the neurological symptoms, however the other one remained with motor deficiency, exactly the one who spent a longer period of time between the symptoms appearance and the treatment beginning. These cases serve to alert us about the importance of nutritional vigilance after bariatric surgery.
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PMID:[Beriberi after bariatric surgery: not an unusual complication. Report of two cases and literature review]. 1693 99

A 41-year-old farmer sustained a high-voltage electrical injury resulting in confusion, electrical burns and paroxysmal atrial fibrillation which spontaneously reverted to sinus rhythm after a few hours. Two weeks later he presented with a sudden onset of headache, unsteadiness, horizontal oscillopsia and paraesthesia in the right side of his face. Examination revealed nystagmus to the right, right-sided limb ataxia and a tendency to veer toward the right when walking. An MRI of the brain demonstrated an acute infarct of the right cerebellar hemisphere in the territory of the right posterior inferior cerebellar artery. A transesophageal echocardiogram showed a ruptured mitral valve chordae. This is the first report of a cardio-embolic stroke secondary to mitral valve chordae rupture as a delayed complication of high-voltage electrical injury. Although many mechanisms of direct cerebral electrical injury have been speculated, a cardio-embolic origin should not be overlooked as a cause of stroke secondary to high-voltage electrical injury.
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PMID:Cardio-embolic cerebellar stroke secondary to mitral valve chordae rupture as a delayed complication of a high-voltage electrical injury. 1806 86

We report the case of a 45-year old female multiple sclerosis patient, who accidentally was overdosed with 4-aminopyridine which resulted in dystonic, choreathetoid type abnormal movements in the four limbs, motoric distress, confusion and opisthotonus. There is little known about 4-aminopyridine toxicity. There are only a few reported cases ranging from mild paresthesias to tonic-clonic seizures. 4-aminopyridine enhances neuronal conduction at neuromuscular synapses and is indicated in the treatment of selected neurological disorders including multiple sclerosis (MS) and myasthenia gravis, among others.
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PMID:An unusual case of 4-aminopyridine toxicity in a multiple sclerosis patient: epileptic disorder or toxic encephalopathy? 1940 72

Topiramate is a highly effective drug in migraine prophylaxis and is considered a first-line treatment. The evidence for the efficacy of topiramate is based upon the results of several large, randomized, double-blind, placebo-controlled trials. Adverse events (AEs) are common and require discontinuation of the treatment in about 20-25% of patients, but they are rarely severe. There are reviews regarding topiramate-related AEs representing a large number of patients treated in controlled trials. The most common AEs are weight loss, dizziness, somnolence, abnormal thinking, fatigue, ataxia, confusion, paresthesias, impaired concentration, nervousness, amnesia, and language difficulties. The development of cough has never been reported as an AE during topiramate prophylaxis for migraine. We present 3 cases in which the prophylactic treatment for migraine with topiramate was discontinued due to the onset of primary intractable coughing.
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PMID:Topiramate-induced intractable cough during migraine prophylaxis. 1975 66


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