Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

New serotonin reuptake inhibitors are available for the treatment of affective disorders and sleep dysfunction in traumatic brain injury (TBI) patients. Commonly reported serotonergic side-effects include nausea, headache, dizziness, nervousness and orthostatic hypotension. Trazodone, a non-selective serotonin reuptake inhibitor, is often used in conjunction with fluoxetine, a selective serotonin reuptake inhibitor, in order to combat the insomnia associated with fluoxetine. Successful use of this combination is generally limited by the cumulative serotonergic side-effects of the two medications. This paper describes the first reported case of speech dysfunction as a complication of combined trazodone and fluoxetine use. A 43-year-old male suffered bilateral wrist fractures and a moderate TBI during a fall. Within 1 week of adding fluoxetine to trazodone the patient developed new-onset dysarthria and speech blocking. Upon discontinuation of fluoxetine, speech returned to normal. Possible mechanisms include inhibition of hepatic metabolism, unmasking of caudate nucleus injury, increased noradrenergic activity or previously unreported serotonergic effects. This case illustrates the importance of monitoring drug combinations for unexpected side-effects in the TBI population.
 ...
PMID:Speech dysfunction due to trazodone--fluoxetine combination in traumatic brain injury. 913 3

The objectives of this study were to determine the dose limiting toxicity (DLT) and other major toxicities, the maximum tolerated dose (MTD) and the human pharmacokinetics of N1N11 diethylnorspermine (DENSPM), a new polyamine analog which in experimental systems inhibits the biosynthesis of intracellular polyamines and promotes their degradation by inducing the enzyme spermine/spermidine N-acetyl transferase. These objectives were incompletely achieved because of the occurrence of an unusual syndrome of acute central nervous system toxicity which forms the basis of the present report. Fifteen patients with advanced solid tumors were entered into a phase I study of DENSPM given by a 1 h i.v. infusion every 12 h for 5 days (10 doses). The starting dose was 25 mg/m2/day (12.5 mg/m2/dose) with escalation by a modified Fibonacci search. Doses of 25 and 50 mg/m2/day were tolerated with only minor side effects of facial flushing, nausea, headache and dizziness (all grade I). At doses of 83 and 125 mg/m2/day, a symptom complex of headache, nausea and vomiting, unilateral weakness, dysphagia, dysarthria, numbness, paresthesias, and ataxia, was seen in 3 patients, one after 2 courses of 83 and 2 after 1 course of 125 mg/m2/day. This syndrome occurred after drug administration was complete and the patients had returned home. Lesser CNS toxicity was seen in 2 other patients at lower daily doses. Preliminary pharmacokinetics of DESPM measured in plasma by HPLC in 8 patients showed linearity with dose and a rapid plasma decay with a t1/2 of 0.12 h. We conclude that great caution is warranted in administering DENSPM on this schedule at doses of > or = 83 mg/m2/day.
 ...
PMID:Unusual central nervous system toxicity in a phase I study of N1N11 diethylnorspermine in patients with advanced malignancy. 938 45

Two siblings (one man, one woman), presenting with diarrhea, severe weight loss peripheral neuropathy, ophthalmoparesis, asymptomatic leukoencephalopathy were diagnosed as a new cases of Mitochondrial Neuro Gastro Intestinal Encephalomyopathy syndrome (MNGIE). Hirano (1994) defined four criteria for the diagnostic: peripheral neuropathy, ophthalmoparesis, gastro intestinal dysmotility, muscle biopsy with histologic features of mitochondrial myopathy (ragged-red fibers, muscle fibers with increased succinate deshydrogenase stain or ultra structurally abnormal mitochondria). In a review of the literature, we found 31 cases with MNGIE. With our two cases, we study this group of 33 patients. First symptoms begin about 13.5 years with a median of 10 years and extremes for 1 to 32 years. The first signs are gastro intestinal symptoms (recurrent nausea, vomiting or diarrhea with intestinal dysmotility) in 22 cases, an ophthalmoparesia in 4 cases, intestinal and ocular signs in 1 case, gait ataxia or peripheral neuropathy in 3 cases, hearing loss in 1 case, gait ataxia or peripheral neuropathy in 3 cases, hearing loss in 1 case. During the evolution, besides the cardinal signs, the following features have been observed with a variable frequency: hearing loss, short stature, facial palsy, dysphonia, dysarthria, sweating, orthostatic hypotension, bladder dysfunction, hepatomegalia, The laboratory features are: abnormal Nerve Condition Studies/EMG compatible with a sensory motor neuropathy, lactic acidosis, mitochondrial respiratory chain defect (essentially complex IV deficiency, complex I deficiency or multiple complex defect), MRI leukodystrophy, elevated CSF protein, heart block, ragged-red fibers or increased SDH stain. The prognosis is poor, due to a severe weight loss bordering on cachexia 13 patients died with a mean age of 28.5 years (median 24 years, extreme 3 years to 51 years). The prognosis seems to be worsened by a young age of onset. The 33 patients belong to 19 families with 7 cases of consanguinity. 25 patients had a brother, a sister or a cousin affected. The study of these families is compatible with an autosomic recessive transmission, suggesting a pathology of the nuclear genomi, probably impliying the control of the mitochondrial DNA replication. In fact, in 13 cases, a study of the mt DNA was realized: multiple deletions were founded in 6 cases, multiples mutations in one case, unique mutation in 1 case. In 5 cases ther was no evidence of abnormality. These precise etiology and pathophysiologic significance of the mt DNA deletions, and the heterogeneity of the modifications of the mt DNA remain unknown. However, the possibility of various phenotypes for a same genotype or inversely is known in mitochondriopathies.
 ...
PMID:[MNGIE syndrome in 2 siblings]. 968 18

We present a case of right middle cerebral artery occlusion after a controlled ovarian hyperstimulation regimen and cryopreserved embryo transfer (ET) in a previously healthy 22-year-old woman. The patient suffered from nausea and progressive abdominal distension 8 days after ET. Under the diagnosis of ovarian hyperstimulation syndrome, she was treated with hypertonic solution, albumin infusion, and paracentesis, with some improvement. Left hemiparesis and dysarthria occurred suddenly on the fourth day of hospitalization, 11 days after ET. The neurologic deficits progressed to complete hemiplegia within a few hours. Computed tomography of the head showed infarction in the territory of the right middle cerebral artery. Magnetic resonance angiography revealed occlusion of the main trunk of the right middle cerebral artery. Laboratory studies showed leukocytosis with neutrophil predominance and a hypercoagulable state. The pregnancy was terminated because of progressive tachycardia, dyspnea, and increased abdominal girth despite supportive treatment. The neurologic deficits remained stationary at the time of discharge. This case emphasizes that the recent advent of ovulation induction and assisted reproductive techniques is a newly recognized cause of devastating cerebral infarction in otherwise healthy women.
 ...
PMID:Ischemic stroke in a young woman with ovarian hyperstimulation syndrome. 970 Feb 49

Unilateral cerebellar infarcts in the territory of the superior cerebellar artery (SCA) have been studied in recent years to delineate the clinical presentation and stroke mechanism, but most studies excluded bilateral infarctions. We have studied patients with bilateral SCA infarctions to provide data on clinical findings, stroke distribution and outcome. We collected data of 8 patients with bilateral SCA infarctions recognized by computed tomography and/or magnetic resonance imaging. The most common clinical presentation of patients with bilateral SCA infarctions were nausea, vomiting or vertigo (6 patients), often associated with ataxia and dysarthria (5 patients). Further symptoms were variable and depended on additional infarcts in other vascular territories. Infarcts were often partial or scattered with equal distribution between the medial and lateral branches of the SCA. Complete infarction within the SCA area occurred in less than half of the cases. Clinical outcome was either benign (full recovery in 3 patients) or fatal (5 patients). Predictors for a good clinical recovery were young age, few vascular risk factors, only partial involvement of the SCA territory without involvement of other vascular territories, and absent limb weakness on clinical presentation.
 ...
PMID:Presentation and prognosis of bilateral infarcts in the territory of the superior cerebellar artery. 1054 90

We report on a 35 year old female with a 26 day history of an intermittent cerebellar syndrome (dysarthria, ataxia of extremities, gait and trunk, nystagmus), mild meningism, cephalgia, recurrent emesis and nausea. Symptoms developed after typically chickenpox exanthema. Examination of the liquor showed mild pleocytosis, elevated protein and increased albumin quotient. Virus was not found by EIA or PCR. There were elevated levels of IgM- and IgG-antibodies to VZV. The EEG showed mild general changes, compatible with an encephalitis. Neuroradiological examinations were unremarkful. The neurological deficits partly regressed in the follow-up of two months. To the best of our knowledge we are the first that describe the paradox of an intermittent cerebellar syndrome after infection with chickenpox without detection of the virus in the liquor. This phenomenon can be related to the unusual combination of cerebellar ataxia and the later occurrence of mild encephalitis.
 ...
PMID:[Cerebellar syndrome after varicella infection without virus identification in cerebrospinal fluid--an important differential ataxia diagnosis]. 1059 44

We describe a case of unilateral IX, X and XI cranial and upper cervical nerve palsies involving zoster sine herpete (ZSH). A 63-year-old man experienced nausea, loss of appetite and general fatigue. On 4 days of illness, dysphagia, dysarthria and difficulty in elevation of his right arm appeared. Neurological examination showed the right curtain sign, a nasal voice and a decreased right gag reflex. He could hardly elevate his right arm laterally. Needle electromyography revealed positive sharp waves in his right trapezius muscle. Although no skin lesion was detected, anti-varicella-zoster virus antibodies were positive in both serum and cerebrospinal fluid. Acyclovir and a steroid were ineffective for these symptoms. Although case reports of unilateral IX, X and XI cranial nerve palsies with ZSH is very rare, ZSH should be kept in mind in the differential diagnosis of multiple cranial nerve palsies.
 ...
PMID:[A case of zoster sine herpete with involvement of the unilateral IX, X and XI cranial and upper cervical nerves]. 1061 62

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)
 ...
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

Spontaneous dissection of the intracranial vertebral artery has been increasingly recognized as a cause of vertebrobasilar ischemic stroke. However, little is known about its natural history and clinical course. The authors report a young patient with repeated cerebral infarction in the posterior cerebral circulation caused by dissection of the vertebral artery, which was not detected on the first angiogram. The otherwise healthy 22-year-old male suddenly developed visual disturbance. Neuroradiological examination revealed right occipital infarction, but cerebral aniography revealed no caliber change or other pathological findings. He was treated with antiplatelet therapy. Two years later, he suffered vertigo, nausea, and dysarthria due to newly developed left cerebellar and medullary infarction. Cerebral angiography revealed left vertebral artery occlusion. T1-weighted MR image demonstrated Gadlinium-enhanced intramural hematoma in the occluded left vertebral artery, which was compatible to the arterial dissection. The present case argues serial neuroimaging studies especially in young patients with vertebrobasilar stroke in order to rule out the arterial dissection, even if initial angiography failed to demonstrate any radiographical evidence.
 ...
PMID:[Repeated vertebrobasilar ischemic stroke caused by an intracranial vertebral artery dissection not detected on the initial angiogram: a case report]. 1151 95

We report a Japanese family with acetazolamide-responsive episodic ataxia. The proband was a 41-year-old woman with interictal nystagmus. She experienced recurrent attacks of loss of equilibrium and loss of coordination of the extremities accompanied by dysarthria and nausea beginning at about 10 years old. These episodes usually lasted for several hours two or three times a week. Direct sequence of CACNA1A demonstrated a novel insertion mutation in the patient and her father. This mutation is estimated to cause early stop of the gene transcription, producing a truncated protein. This is the first report of episodic ataxia type 2 of which the mutation was identified in a Japanese family.
 ...
PMID:A novel insertion mutation of acetazolamide-responsive episodic ataxia in a Japanese family. 1273 95


<< Previous 1 2 3 4 5 6 7 Next >>