Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
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Trospectomycin sulfate is a novel aminocyclitol antibiotic. This study evaluated the tolerance and the pharmacokinetics of multiple, intravenous doses of trospectomycin (TRO) in healthy male volunteers. Three groups of 10 volunteers were studied. Eight volunteers in each group were studied in a parallel design to receive trospectomycin (Group 1 = 250 mg, Group 2 = 500 mg, Group 3 = 750 mg) while 2 volunteers received placebo (normal saline). Drug doses were administered in 30 ml volumes over 30 min every 8 h for 7 days (i.e. 21 total doses). Evaluations of vital signs, side effects, and safety laboratory tests were made at regular intervals during the study. The most frequent medical events observed in the volunteers receiving trospectomycin were perioral/facial paresthesias (54%), pain at the i.v. infusion site (46%), dizziness/lightheadedness (58%), and GI symptoms (38%). A statistically significant dose response relationship was observed for the incidence of perioral/facial paresthesias and pain at the i.v. infusion site (i.e., increased incidence with increased dose). All the medical events were mild or moderate in severity and reversible following drug discontinuation. In the 500 and 750 mg trospectomycin groups, standing systolic blood pressure decreased significantly with the first dose of study drug. Elevated levels of SGPT were observed in 9 volunteers (1 in placebo, 3 in 250 mg, 1 in 500 mg, and 4 in 750 mg dose groups). This study demonstrates that multiple intravenous trospectomycin doses up to 750 mg are reasonably well tolerated in healthy male volunteers. The concentration of trospectomycin in serum, measured with a sensitive HPLC assay, was less than 3 mcg/ml at 8 h postinfusion for all dose levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Multiple-dose, double-blind, placebo controlled intravenous tolerance and pharmacokinetic study of trospectomycin sulfate (U-63, 366F) in healthy male volunteers. 214 31

In this study, local and systemic tolerance and pharmacokinetics of trospectomycin sulfate in human beings were evaluated for the first time. Trospectomycin sulfate (U-63,366F; trospectomycin) or sterile saline was administered to 96 healthy male volunteers in doses ranging from 0.25 ml (75 mg) to 3.3 ml (1,000 mg) in a single intramuscular injection in a double-blind, randomized design. Volunteers were screened to establish baseline vital signs and laboratory test values. Pain and tenderness at the injection site, which occurred at doses of 450 mg and above, were the most common side effects; they were mild in severity and transient. Adverse drug experiences reported by subjects included nausea, dizziness, light-headedness, diaphoresis, costal pain, and perioral numbness. The perioral numbness (paresthesia) experienced at doses of 750, 900, and 1,000 mg was probably drug related. No Clostridium difficile toxin was detected in fecal samples. Pharmacokinetic calculations based on data obtained by high-performance liquid chromatography showed that after a 1,000-mg intramuscular dose of trospectomycin (3.3 ml), the serum mean half-life was 1.85 h (1.70 to 2.02 h), mean area under the serum concentration-time curve was 140.2 micrograms.h/ml and was linear with dose, mean peak concentration was 28.3 micrograms/ml (20.4 to 34.7 micrograms/ml), mean time to maximum concentration was 71 min (30 to 120 min), and the elimination rate constant was 0.307 h-1. The elimination rate constant and half-life did not vary with dose. Little trospectomycin was detected in 2-day fecal collections. A few randomly occurring abnormal clinical laboratory test values and vital signs were observed. For the trospectomycin-treated group, creatinine phosphokinase increased substantially for 24 h after injection and then decrease through day 5, while serum glutamic oxalacetic transaminase and lactate dehydrogenase increased slightly.
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PMID:Human safety and pharmacokinetics of a single intramuscular dose of a novel spectinomycin analog, trospectomycin (U-63,366F). 215 Sep 7

The Isoparaffins covered in this manuscript are branched aliphatic hydrocarbons with a carbon skeleton length ranging from approximately C10 to C15. They are used in the manufacture of liquid imaging toners, paint formulations, charcoal lighter fluid, furniture polishes and floor clearners. Potential exposure exists in the petroleum, printing and paint industries. Isoparaffins have a very low order of acute toxicity, being practically non-toxic by oral, dermal and inhalation routes. However, aspiration of liquid isoparaffins into the lungs during oral ingestion could result in severe pulmonary injury. Dermally, isoparaffins have produced slight to moderate irritation in animals and humans under occluded patch conditions where evaporation cannot freely occur. However, they are not irritating in non-occluded tests, which are a more realistic simulation of human exposure. They have not been found to be sensitizers in guinea pig or human patch testing. However, occasional rare idiosyncratic sensitization reactions in humans have been reported. Instillation of isoparaffins into rabbit eyes produces only slight irritation. Several studies have evaluated sensory irritation in laboratory animals or odor or sensory response in humans. When evaluated by a standard procedure to assess upper airway irritation, isoparaffins did not produce sensory irritation in mice exposed to up to 400 ppm isoparaffin in air. Human volunteers were exposed for six hours to 100 ppm isoparaffin. The subjects were given a self-administered questionnaire to evaluate symptoms, which included dryness of the mucous membranes, loss of appetite, nausea, vomiting, diarrhea, fatigue, headache, dizziness, feeling of inebriation, visual disturbances, tremor, muscular weakness, impairment of coordination or paresthesia. No symptoms associated with solvent exposure were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Toxicology update isoparaffinic hydrocarbons: a summary of physical properties, toxicity studies and human exposure data. 219 78

Headache is a common symptom following head trauma and not related to the degree of trauma. The term post-head-trauma syndrome is used to denote a group of symptoms following head trauma. Dizziness, vertigo, perceptual changes, memory loss, paresthesias, and tinnitus have been reported as well as psychological disturbances. Pathophysiology of headache and other symptoms in the syndrome are believed to relate to vascular and neuronal disturbances. Imaging techniques may provide objective evidence of changes in the brain. Often diagnostic studies do not reveal an abnormality. Treatment consists of diagnosing the type of headache and targeting appropriate therapy. Long-term prognosis is good, the majority of patients recovering after 1 year.
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PMID:Headache and head trauma. 252 Mar 90

In 984 patients with generalized anxiety disorder who received buspirone in double-blind studies, the incidence of drowsiness (9 percent) did not differ significantly from that (10 percent) reported in 334 patients who received placebo. A probability value of p less than or equal to 0.10 was the criterion for significance. The incidence of drowsiness in buspirone-treated patients was significantly less than that in each of the groups receiving diazepam (32 percent), clorazepate (26 percent), lorazepam (58 percent), or alprazolam (43 percent). The side effects that did occur significantly more frequently in the buspirone group than in the placebo group were dizziness (9 percent versus 2 percent), headache (7 percent versus 2 percent), nervousness (4 percent versus 1 percent), light-headedness (4 percent versus less than 1 percent), diarrhea (3 percent versus less than 1 percent), paresthesia (2 percent versus less than 1 percent), excitation (2 percent versus less than 1 percent), and sweating/clamminess (1 percent versus 0 percent). The severities of these effects were predominantly rated as only mild or moderate. Fatigue occurred less frequently in buspirone-treated patients than in those receiving any of the benzodiazepines, and weakness occurred more frequently in diazepam-treated patients. Depression occurred less frequently in buspirone-treated patients than in those receiving clorazepate, diazepam, or lorazepam. Impotence occurred only in clorazepate- and lorazepam-treated patients. Decreased libido occurred more frequently in diazepam-treated patients, whereas increased libido was more frequent in clorazepate-treated patients. Nausea was reported more frequently in buspirone-treated patients than in those receiving clorazepate, diazepam, or alprazolam; diarrhea occurred more frequently in the buspirone group than in the diazepam group. The mean daily doses of the various treatments were buspirone, 20 mg; diazepam, 20 mg; clorazepate, 24 mg; lorazepam, 3 mg; and alprazolam, 1.5 mg. In an open-field study in West Germany involving 5,414 patients, gastrointestinal-related complaints were the most frequently reported side effects.
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PMID:Review of the side-effect profile of buspirone. 287 Jun 41

Blood pressure, which ist the product of cardiac output and peripheral vascular resistance is regulated by a complex feedback mechanism involving the sympathetic and parasympathetic systems and hormones. An acute disturbance of regulation may lead to a life-threatening increase in blood pressure. Diagnosis is based upon a careful measurement of blood pressure, which must be performed under internationally standardized conditions. Hypertensive crisis refers to a rapid blood pressure increase greater than 30 mmHg above the age-related 95th percentile. The main causes of hypertension in childhood are renal diseases, which may be aggravated by additional conditions either by the clinician himself (e.g. cyclosporin, steroids) or by the patient (lack of compliance). Crisis affects the brain (hypertensive encephalopathy), the heart (left ventricular insufficiency), the retina (visual disturbances) and the mucous membranes (epistaxis). Hypertensive encephalopathy is induced by a break-through of the autoregulation of brain flow, leading to hyperperfusion and, thus to cerebral oedema. The clinical manifestations are characterized by restlessness, severe and diffuse headache, vomiting, nystagmus, impaired vision, dizziness, paraesthesia, seizures and palsies, which may lead - if untreated - to coma and death. The course is usually prolonged and reversible by adequate treatment. The morphological consequences are purpura cerebri, fresh retinal haemorrhages and papillary oedema, apart from left ventricular dilatation and hypertrophy. The diagnostic procedure rests on the quick realization of essential anamnestic (blood pressure, renal disease, drugs), clinical (oedema, cardiac action, central nervous system, fundus) and laboratory parameters (serum creatinine, electrolytes, glucose, blood count, urine). Treatment should start before the manifestation of clinical signs (hypertensive emergency) with rapidly acting antihypertensive drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The hypertensive crisis in childhood]. 305 87

Intravenous flecainide acetate (2 mg/kg) was administered to 40 patients undergoing routine electrophysiological evaluation for the investigation of recurrent paroxysmal tachycardias. Ten patients had recurrent atrial flutter, 11 patients had recurrent atrial fibrillation, one of whom also had paroxysmal left atrial tachycardia, and 19 patients had recurrent ventricular tachyarrhythmias (17 with recurrent ventricular tachycardia and 2 with recurrent fascicular tachycardia). Flecainide was administered during tachycardia (over 5 to 10 minutes) to all patients with atrial flutter, to 10 patients with atrial fibrillation, and to 17 patients with ventricular tachyarrhythmias. In the remaining 3 patients with ill-sustained arrhythmias flecainide was administered during sinus rhythm and reinitiation of tachycardia was then attempted. Flecainide restored sinus rhythm in only 2 patients with atrial flutter (20%), in 9 patients with atrial fibrillation (90%), in 12 patients with ventricular tachycardia (80%), and in one of the 2 patients with fasicular tachycardia. Flecainide also successfully terminated the left atrial tachycardia. Two patients experienced proarrhythmic side effects during flecainide administration, one of whom required intervention by cardioversion. Minor dose effects included oral paresthesia, transient drowsiness or dizziness, and occasional visual blurring. Flecainide acetate is an effective antiarrhythmic agent for the acute termination of recent onset paroxysmal atrial and ventricular tachyarrhythmias.
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PMID:Intravenous flecainide acetate for the clinical management of paroxysmal tachycardias. 310 95

Seventy-four patients with chest pain and no prior history of organic heart disease were interviewed with a structured psychiatric interview immediately after coronary arteriography. The majority of patients with both negative and positive coronary angiographies had undergone previous exercise tolerance tests, but the patients with angiographic coronary artery disease were significantly more likely to have had positive results on a treadmill test. Patients with chest pain and negative coronary arteriograms were significantly younger; more likely to be female; more apt to have a higher number of autonomic symptoms (tachycardia, dyspnea, dizziness, and paresthesias) associated with chest pain, and more likely to describe atypical chest pain. Patients with chest pain and normal coronary arteriographic results also had significantly higher psychologic scores on indices of anxiety and depression and were significantly more likely to meet criteria of the Diagnostic and Statistical Manual of Mental Disorders, third edition, for panic disorder (43 percent versus 6.5 percent), major depression (36 percent versus 4 percent), and two or more phobias (36 percent versus 15 percent) than were patients with chest pain and a coronary arteriography study demonstrating coronary artery stenosis.
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PMID:Chest pain: relationship of psychiatric illness to coronary arteriographic results. 333 15

Although much research has focused on the pathophysiology of panic attacks, little work has been done to describe the phenomenon itself. Twenty-one patients with panic attacks were asked to sequence the panic-related symptoms during an attack in an attempt to clarify the phenomenon. Overall, panic symptoms could be grouped into three categories: early symptoms--consisting of dyspnea, palpitations, chest discomfort, and hot flashes; intermediate symptoms--including shaking, choking, feelings of unreality, sweats, faintness, and dizziness; late symptoms-consisting of fear and paresthesias. Based on symptom clustering and temporal relationships, this study describes the panic phenomenon.
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PMID:The sequence of panic symptoms. 333 5

A clinicopathological study was performed on 46 patients with chronic myeloproliferative diseases (CMPD) showing a thrombocythemia in excess of 1,000 x 10(9)/liter. When applying rigid diagnostic criteria only 23 patients were compatible with the initially suspected diagnosis of primary thrombocythemia (PTH). Comparison of PTH with the other entities of CMPD (CGL, 10, AMM, 6, and polycythemia, 7 cases) revealed a sustained elevation of the platelet count observable over a period of 2 to 8 years, no marked leukocytosis or abnormalities of the differential blood count, and a normal score of the leukocyte alkaline phosphatase. Episodes of hemorrhage and thrombosis as well as neurological symptoms (paresthesias, dizziness, headache), were encountered frequently as clinical manifestations in PTH. Survival time in PTH was significantly longer than in CGL with accompanying thrombocythemia. In a consecutively biopsied population of patients with CMPD, incidence of PTH was about 8%. In PTH the characteristic histopathology of the bone marrow consisted of an isolated (monolinear) proliferation of the megakaryocytes (density 127 +/- 47/mm2) without gross abnormalities of this cell lineage or a conspicuous increase in neutrophilic granulo- or erythrocytopoiesis. These lesions are significantly different from the morphological findings in the other CMPD with extreme thrombocytosis.
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PMID:Chronic myeloproliferative diseases with an elevated platelet count (in excess of 1,000,000/microliter): a clinicopathological study on 46 patients with special emphasis on primary (essential) thrombocythemia. 350 37


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