Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
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Target Concepts:
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Query: UMLS:C0011570 (
depression
)
172,036
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The membrane protein bacteriorhodopsin was imaged in buffer solution at room temperature with the atomic force microscope. Three different substrates were used: mica, silanized glass and lipid bilayers. Single bacteriorhodopsin molecules could be imaged in purple membranes adsorbed to mica. A
depression
was observed between the bacteriorhodopsin molecules. The two dimensional Fourier transform showed the hexagonal lattice with a lattice constant of 6.21 +/- 0.20 nm which is in agreement with results of electron diffraction experiments.
Spots
at a resolution of approximately 1.1 nm could be resolved. A protein, cationic ferritin, could be imaged bound to the purple membranes on glass which was silanized with aminopropyltriethoxysilane. This opens the possibility of studying receptor/ligand binding under native conditions. In addition, purple membranes bound to a lipid bilayer were imaged. These images may help in interpreting results of functional studies done with purple membranes adsorbed to black lipid membranes.
...
PMID:Imaging the membrane protein bacteriorhodopsin with the atomic force microscope. 227 63
Quinidine, procainamide and disopyramide are antiarrhythmic drugs in the class 1A category. These drugs have a low toxic to therapeutic ratio, and their use is associated with a number of serious adverse effects during long term therapy and life-threatening sequelae following acute overdose. Class 1A agents inhibit the fast inward sodium current and decrease the maximum rate of rise and amplitude of the cardiac action potential. Prolonged Q-T interval and, to a lesser extent, QRS duration may be observed at therapeutic concentrations of quinidine. With increasing plasma concentrations, progressive
depression
of automaticity and conduction velocity occur. 'Quinidine syncope' (a transient loss of consciousness due to paroxysmal ventricular tachycardia, frequently of the torsade de pointes type) occurs with therapeutic dosing, often in the first few days of therapy. Extracardiac adverse effects of quinidine include potentially intolerable gastrointestinal effects and hypersensitivity reactions such as fever,
rash
, blood dyscrasias and hepatitis. Procainamide produces electrophysiological changes that are similar to those of quinidine, although Q-T interval prolongation with the former is less pronounced at therapeutic concentrations. Hypersensitivity reactions including fever,
rash
and (more seriously) agranulocytosis are associated with procainamide, and a frequent adverse effect requiring cessation of therapy is the development of systemic lupus erythematosus. Of the 3 drugs, disopyramide has the most pronounced negative inotropic effects, which are especially significant in patients with pre-existing left ventricular dysfunction. As with quinidine, unexpected 'disopyramide syncope' at therapeutic concentrations has been described. Anticholinergic side effects are common with this drug and may require cessation of therapy. Disopyramide therapy may unpredictably induce severe hypoglycaemia. Severe intoxication with the class 1A agents may result from acute accidental or intentional overdose, or from accumulation of the drugs during long term therapy. Acute overdose can result in severe disturbances of cardiac conduction and hypotension, frequently accompanied by central nervous system toxicity. Decreased renal function can cause significant accumulation of procainamide and its active metabolite acecainide (N-acetyl-procainamide), resulting in severe intoxication. Mild to moderate renal dysfunction is less likely to lead to quinidine or disopyramide intoxication, unless renal failure is severe or concurrent hepatic dysfunction is present. Management of acute intoxication with class 1A drugs includes gut decontamination with provision of respiratory support and treatment of seizures as needed. Hypertonic sodium bicarbonate, by antagonising the inhibitory effect of quinidine on sodium conductance, may reverse many or all manifestations of cardiovascular toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Poisoning due to class IA antiarrhythmic drugs. Quinidine, procainamide and disopyramide. 228 95
Eosinophilia-myalgia syndrome (EMS) is a newly recognized illness characterized by intense eosinophilia, debilitating myalgia, and absence of any condition that could account for the eosinophilia or myalgia. The disorder has previously been associated with ingestion of capsules containing the amino acid L-tryptophan. In 1989, the Wisconsin Division of Health began surveillance for EMS. Each of 25 persons reported with the illness and meeting a standardized case definition were using L-tryptophan when their symptoms began, between June 1989 and January 1990. The median age of the patients was 43 years (range 26-82 years); 92% were female, and 96% were white. The majority of patients reported were using L-tryptophan for insomnia (36%), premenstrual syndrome (28%), or
depression
(20%). Common signs and symptoms in these cases included cough or dyspnea (60%), arthralgia (44%), edema of the extremities (44%), fever (36%), and
rash
(32%). Other epidemiologic investigations to date suggest that EMS may be associated with a product contaminant.
...
PMID:Eosinophilia-myalgia syndrome in Wisconsin. 229 89
Plasma phenytoin and phenobarbitone levels were estimated in 123 adult Ethiopian epileptics by gas-liquid chromatography. Thirty four (38.2%) of the patients on phenytoin, and 52 (52%) of those on phenobarbitone, had plasma levels in the conventional therapeutic ranges of 10-20 micrograms/ml and 10-30 micrograms/ml respectively. Of the 89 patients who were taking phenytoin either singly or combined with phenobarbitone, motor disturbances (ataxia and nystagmus) were seen in 31 (34.8%) and dysmorphic and idiosyncratic side effects including gum hypertrophy, hirsutism, acne and skin
rash
in 37 (41.6%). Subnormal serum calcium levels were noted in 15 (30.6%) and high alkaline phosphatase was found in 13 (26.5%). Phenobarbitone was found to be an effective anticonvulsant (78.1% seizure control rate), with adverse effects of sedation and intellectual
depression
. Seizure control was achieved in 77.1% of patients on a single drug as opposed to 55.6% on combination of phenytoin and phenobarbitone (p less than 0.05). The overall seizure control rate was 66%.
...
PMID:Plasma level distribution, effect and toxicity of antiepileptic drugs among Ethiopian epileptics. 230 55
Pneumocystis carinii pneumonia (PCP) is the most common opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS). Eflornithine is an antiprotozoal agent active against P. carinii. It acts by inhibiting ornithine decarboxylase, an enzyme that is essential for cellular function. The drug is initially administered intravenously, followed by oral therapy. Eflornithine has been used on a compassionate basis in AIDS patients with PCP who were intolerant of or unresponsive to traditional agents. Overall, the response rate has been about 35%; however, conclusions are difficult to make since patients had different stages of disease and received treatment for varying periods of time. Side effects include
depression
of bone marrow function, diarrhea, hearing loss, seizures, alterations in liver function tests, and
rash
. While the need for safer and more efficacious antipneumocystis drugs grows, widespread use of seemingly promising agents should be based on well-conducted clinical trials.
...
PMID:Eflornithine for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome: a preliminary review. 249 38
Forty-three patients with disseminated refractory malignancies each received an individually-specified combination of either Adriamycin (24 patients) or mitomycin-C (19 patients) conjugated murine monoclonal antibodies. Tumors were typed using a panel of antibodies with both immunohistochemistry and flow cytometry. Cocktails of up to six antibodies were selected based on binding greater than 80% of the malignant cells in the biopsy specimen. These monoclonal antibody cocktails were drug conjugated and administered intravenously. Seventeen out of twenty-four patients had reactions to the administration of Adriamycin immunoconjugates, but these were tolerable in all but two patients. Fever, chills, pruritus and skin
rash
were by far the most common transitory reactions. All were well controlled with premedication. In several patients it was demonstrated that there was limited antigenic drift among various biopsies within the same patient over time. Up to 1 gram of Adriamycin and up to 5 grams of monoclonal antibody were administered. The limiting factor appeared to be a variable dissociation of active Adriamycin from the antibody which unpredictably caused hemopoietic
depression
. Similar findings were noted in 19 patients with mitomycin-C conjugates. Thrombocytopenia at a 60mg dose of mitomycin-C in this schedule was dose limiting. Preliminary serological evidence suggests that the development of an IgM antibody which is specific against the mouse monoclonal antibody has the specificity and sensitivity to predict clinical reactions. These antibodies were quantitatively less in mitomycin-C patients. Selected patients were re-treated. One patient with chronic lymphocytic leukemia had re-treatment on three occasions and demonstrated regression of peripheral lymph nodes. Two patients with breast carcinoma had definite improvement in ulcerating skin lesions and two patients with tongue carcinoma had shrinkage of their lesions. No responses were seen with mitomycin-C conjugates but binding was noted to tumors and colon with likely drug induced colitis seen after colon binding. This study demonstrates the feasibility and illustrates technical considerations in preparing drug immunoconjugate cocktails for patients with refractory malignancies. Cocktail formulation and antibody delivery was accomplished. The major technical hurdle appears to be the selection of effective conjugation methods that can be used to optimally bind drugs to monoclonal antibodies for targeted cancer therapy.
...
PMID:Individually specified drug immunoconjugates in cancer treatment. 250 30
Sixty-five cases of mental
depression
were treated with maprotiline (Ludiomil), including 46 cases of endogenous depression, 18 cases of neurotic depression and 1 case of
depression
in association with hypertension and cerebral arteriosclerosis. Ludiomil of 50-200 mg/d was given for 4 weeks and clinical pictures evaluated weekly. Clinical results showed complete recovery in 33 cases (50%), improvement in 22 cases (34%), fair in 7 cases (11%) and poor in 3 cases (5%). Dry mouth, constipation and faintness were the commonest side effects. Seizure occurred in 1 case and skin
rash
in 3 cases. The authors suggest that Ludiomil at a maximal dosage of 150 mg/d can be considered a relatively safe and effective antidepressant.
...
PMID:Maprotiline (Ludiomil) treatment of mental depression--a clinical report of 65 cases. 259 36
Thirty-two patients (14 women and 18 men) whose age ranged between 15 and 76 were admitted on an emergency and anesthetized with propofol in view of various surgical interventions (9 appendectomies, 9 fractures, 5 wound healing, 6 abscess incisions, 2 corneal grafts and one complex trauma surgery) undergone 24 hours after their admission. Premedication included hydroxyzine 1.5 mg.kg-1, atropine sulfate 0.5 to 0.75 mg and pethidine 1 mg.kg-1 according to pain intensity and initial pathology. Narcosis was induced by 2.5 mg.kg-1 propofol injected intravenously. Propofol was then administered continuously at a dose of 9 mg.kg-1 in the first hour and of 4.5 mg.kg-1.h-1 in the following hours for 28 of the patients. Four patients undergoing short operations were given additional injections of one third of the initial dose. Analgesia and myorelaxation were obtained with fentanyl (0.16 +/- 0.06 mg) and vecuronium (9.3 +/- 4 mg). Narcosis proved to be very efficient. The side effects observed (13% myoclonia, 6%
rash
, 6% bradycardia, 0.3% pains at the time of injection) were similar to those quoted in the literature. Blood pressure stabilized after a short slight
depression
(13% to 18% of the standard values). Pulse remained regular. We can thus say that propofol is a good hypnotic drug for emergency anesthesia provided that its contra-indications especially shocks of cardiac or septic origin and hypovolemia, are carefully respected.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:[Propofol in emergency anesthesia]. 278 40
After a controlled, double blind multicenter trial of D-penicillamine in the treatment of rheumatoid arthritis, 148 patients were followed for an additional year in an open label trial. Complications of longterm D-penicillamine included
rash
, gastrointestinal manifestations, proteinuria, bone marrow
depression
, myasthenia gravis, myositis, acute febrile reaction and pemphigus foliaceus. With the exception of one patient with myasthenia gravis, all adverse reactions resolved after withdrawal of D-penicillamine. While the complications of D-penicillamine therapy are usually dose related, these reactions can occur at any time and at any dose. Continued and frequent longterm monitoring of D-penicillamine therapy is required.
...
PMID:Toxicity of longterm low dose D-penicillamine therapy in rheumatoid arthritis. Cooperative Systematic Studies of Rheumatic Disease Group. 295 97
Interleukin 2 (IL-2) therapies have antitumor activities against several neoplasms. In vitro these activities are enhanced by beta-interferon (IFN-beta). Therefore, we initiated a Phase I trial with a combination of IL-2 and IFN-beta three times weekly. The IFN-beta was administered i.v. Initially, the IL-2 was administered s.c. However, neutralizing antibody to the IL-2 developed in five patients, and the route of administration of the IL-2 was changed to i.v. Forty-seven patients were entered on the study. The maximum tolerated doses for the combination given i.v. were 5 x 10(6) units/m2 of IL-2 and 10 x 10(6) units/m2 of IFN-beta. Dose-limiting toxicities were profound fatigue/decreased performance status, anorexia/weight loss,
depression
, and arthralgias. Hypotension, exfoliative skin
rash
, thrombocytopenia, diarrhea, temperature greater than 40.6 degrees C, and peripheral edema were rarely dose limiting. Thirty-two patients were evaluable for response. After 4 weeks of treatment, 21 patients had stable disease, three patients had a minor response, and one patient had a partial response. Significant lymphokine-activated killer cell (LAK) activity was seen in seven patients (22%) and required 5 x 10(6) units/m2 of IL-2. Those who had progressive disease had significantly less LAK activity than those with either stable disease or a response. This therapy also induced more than 60 units/ml of endogenous gamma-interferon 4 h after the i.v. IL-2 administration. This study demonstrates that (a) intermittent i.v. bolus IL-2 therapy can generate LAK activity, (b) LAK activity may be associated with an antitumor response, (c) significant levels of gamma-interferon are induced by this therapy, and (d) IL-2 and IFN-beta given three times weekly i.v. is both tolerable and biologically active. The recommended Phase II dose is 5 x 10(6) units/m2 of IL-2 plus 6 x 10(6) units/m2 of IFN-beta.
...
PMID:A phase I study of recombinant interleukin 2 plus recombinant beta-interferon. 313 24
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