Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
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Intermittent hyperthyreosis occurs under various forms of stress, especially heat stress. The clinician may diagnose such cases as masked or apathetic hyperthyroidism or "forme fruste" hyperthyreosis or thyroid autonomy. As most routine and standard tests may here yield inconsistent results, it is the patients' anamnesis which may provide the clue. Our Bioclimatology Unit has now seen over 100 cases in which thyroid hypersensitivity towards heat was the most prominent syndrome: 10-15% of weather-sensitive patients are affected. The patients complain before or during heat spells of such contradictory symptoms as insomnia, irritability, tension, tachycardia, palpitations, precordial pain, dyspnoe, flushes with sweating or chills, tremor, abdominal pain or diarrhea, polyuria or pollakisuria, weight loss in spite of ravenous appetite, fatigue, exhaustion, depression, adynamia, lack of concentration and confusion. Determination of urinary neurohormones allows a differential diagnosis, intermittent hyperthyreosis being characterized by three cardinal symptoms: 1. tachycardia -- every case with more than 80 pulse beats being suspect (not specific); 2. urinary histamine -- every case excreting more than 90 mug/day being suspect. Again the drawback of this test is its lack of specificity, as histamine may also be increased in cases of allergy and spondylitis; 3. urinary thyroxine -- every case excreting more than 20 mug/day T-4 being suspect. This is the only specific test. Therapy should make use of lithium carbonate and beta-blockers. Propyl thiouracil is rarely required.
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PMID:Intermittent hyperthyreosis -- a heat stress syndrome. 5 84

Twenty-three children with advanced cancer refractory to conventional therapy received weekly iv doses of neocarzinostatin for 5 weeks. Doses were escalated from 500 to 6750 units/m2/week. Four types of toxic manifestations occurred: acute reactions consisting of shaking chills with or without fever and cyanosis (rigor), hypersensitivity, vomiting, and marrow depression. Evidence of oncolytic activity was limited to patients with acute leukemia in whom phase II trials at doses between 3000 and 4500 units/m2 appear warranted.
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PMID:Phase I study of neocarzinostatin in children with cancer. 15 67

Between May and September 1973, 68 cases of scrub typhus in Chinese military personnel on the Pescadores Islands were studied. The common symptoms and signs were fever, chills, headache, eschar, myalgia, and lymph node enlargement. Most eschars were located in the axilla, waist, groin and genitals, and neck. These lesions were painless and not noticed by the patients themselves. Regional lymph node enlargement at the site of eschar drainage was common. Relative bradycardia with fever was observed in 40%, a skin rash in 35% of the patients. Leucopenia was noted more frequently in the febrile than in the convalescent stage, but more than half of the patients had a normal count. Lymphocytosis was prominent, especially during the convalescent period. An acceleration of ESR was noted. Instead of depression of the erythroid series in the marrow which was reported previously, 47% of examined patients were found to have erythroid hyperplasia. Two patients showed marked hypocellularity of the marrow in the acute febrile stage; later on became normocellular. Albuminuria was present in 15 and BUN increased in 12 patients. Elevation of serum bilirubin and SGOT was also noted. Biologic false positive VDRL tests were observed in nine patients. In 30 tests elevation of Proteus OX-K titres between 1:160 and 1:640 was noted. A geometric mean OX-K titre rise in the patients is presented; the mean titre reached a peak in the third week of illness, and then fell off. Most of the patients were treated with tetracycline 500 mg every six hours for about nine days. The fever usually subsided within 36 hours. Complications or mortality were not encountered.
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PMID:Clinical observations of scrub typhus on Penghu (the Pescadores Islands). 117 79

Jurors on criminal trials carry a considerable burden of responsibility. They determine the defendant's fate. Additionally, during trials they can be exposed to stressful, frightening, and sordid aspects of life. The stressfulness varies depending upon the nature of the trial, its length, the nature of the testimony and evidence, the jurors' interpersonal relationships, the difficulty establishing guilt or innocence, the public's attitude, etc. These experiences can create psychological and/or physical discomfort that can be transient and mildly or moderately intense, or more serious and constitute illness. The authors have studied juries of four criminal trials--two murder cases, one child abuse case, and one obscenity case. Forty jurors were interviewed. Twenty-seven had one or more discomforting physical and/or physiological symptoms. These involved gastrointestinal distress (10 jurors); generalized nervousness (4 jurors); heart palpitation (6 jurors); headaches (4 jurors); sexual inhibitions (4 jurors); depression (4 jurors); anorexia (4 jurors); faintness (2 jurors); and numbness, lump in throat, chest pain, hives, and flu (1 juror each). Seven of the jurors became clearly ill. Illnesses included: peptic ulcer reactivation and hives, phobic reaction, anxiety state and increased alcohol use, hypertensive episode and visual scotomata, sexual inhibition, chills, fever, and depression, and post-traumatic stress disorder.
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PMID:The occupational hazards of jury duty. 142 62

Forty-three patients with disseminated refractory malignancies each received an individually specified combination of either Adriamycin (n = 24) or mitomycin-C (n = 19) conjugated to a cocktail of murine monoclonal antibodies (mAb). Cancers were typed with both immunohistochemistry and flow cytometry using a panel of antibodies. Cocktails of up to six antibodies were selected based on total binding of greater than 80% of the malignant cells in the biopsy specimen. These mAb cocktails were then drug conjugated, safety tested, and administered intravenously. The Adriamycin immunoconjugates were well tolerated in 22/24 patients, with 17/24 having significant side effects. Fever, chills, pruritus, and skin rash were by far the most common transitory reactions. All were well controlled with premedication. A total of up to 1 g Adriamycin and 5 g mAb were administered to each patient. The limiting factor appeared to be a variable dissociation of active Adriamycin from the antibody that unpredictably caused hemopoietic depression. Similar findings were noted among 19 patients treated with mitomycin-C conjugates. Thrombocytopenia at a 60-mg dose of mitomycin-C in this schedule was dose limiting. Serological evidence suggested that the development of an immunoglobulin M antibody specific against the mouse mAb had the specificity and sensitivity to predict clinical reactions. These antibodies were quantitatively less in mitomycin-C-treated patients. Selected patients were retreated. One patient with chronic lymphocytic leukemia was treated on three occasions with 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. Drug-induced colitis was seen at higher doses with some binding of these conjugates to normal colon epithelium. This study demonstrated the feasibility of preparing individually specified drug immunoconjugate cocktails for patients with refractory malignancies. Cocktail formulation and antibody delivery to the tumor in vivo was accomplished. There was limited antigenic drift among various biopsies within the same patient over time. The major technical hurdle continues to be the selection of effective drug conjugation methods to optimally bind drugs to mAbs for targeted cancer therapy.
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PMID:Custom-tailored drug immunoconjugates in cancer therapy. 176 66

Fluosol, a perfluorcarbon emulsion, has the ability to carry oxygen in solution. In conjunction with oxygen breathing and radiation, Fluosol has been shown in animal models to enhance local tumor control. In September 1985, a Phase I/II Study was instituted to evaluate the effect of this adjuvant therapy with radiation in non small cell carcinoma of the luing. Fifty patients were enrolled in the study which was closed for accrual in November 1987. Five patients were withdrawn prior to the institution of radiation: one patient diagnosed with bone metastasis and four patients withdrawn due to mild to moderate reactions to Fluosol. Of the 49 patients administered Fluosol, 34 mild to moderate adverse reactions were noted in 22 patients to either the test dose/infusion (16 reactions including withdrawn patients) or post infusion (18). Flushing, dyspnea and hypertension (test dose/infusion) and chills and/or fever (postinfusion) were the typical symptoms. Transient elevation of blood chemistries (SGOT, SGPT, alkaline phosphatase, BUN) were noted in some patients. Six patients had transient depression of WBC counts (toxicity scores of 1 or 2) and two patients had transient depression of platelets (toxicity score of 1). None of these altered treatment. Forty-five patients received Fluosol of which 34 completed the planned therapy. Six patients were diangosed with metastatic disease during therapy and three patients died of their disease during treatment. One patient was withdrawn due to ineligibility and one patient withdrawn due to moderate reactions to Fluosol during the 3rd and 4th infusions. The total dose of Fluosol was escalated from 42 mL/Kg to 49 mL/Kg in 5, 6, or 7 weekly infusions. Patients breathed 100% oxygen for a minimum of one-half hr prior to and during radiation treatment. Radiation therapy was administered at a daily fraction of 165 to 200 cGy per fraction to a total dose of 5940 to 6800 cGy. Seventeen of 34 patients (50%) achieved a complete response to treatment and 11 patients (32%) had a partial response. Thirteen patients remain alive (range of 12 to 20 months) including 10 of 17 complete responders, 2 of 11 partial responders, and 1 treated with chemotherapy postradiation. The median absolute survival time of the patients completing therapy was 15.5 months and the 12 and 18 month absolute survival rates were 81% and 74%, respectively. The 45 patients starting protocol therapy had a median absolute survival of 9.2 months with a 12-month and 18-month survival of 45% and 35%, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Fluosol and oxygen breathing as an adjuvant to radiation therapy in the treatment of locally advanced non-small cell carcinoma of the lung: results of a phase I/II study. 216 21

Electrocardiographic (ECG) monitoring was performed on 291 donors during apheresis. Twenty-one donors (7.2%) had clinical symptoms such as discomfort, nausea, chill, numbness, and paresthesia, and 13 of this group exhibited ECG abnormalities, such as tachycardia, bradycardia, and other abnormal wave patterns. The donors with tachycardia and slight bradycardia had no symptoms. Ten donors had moderate to severe bradycardia with pulse rates less than 50 beats per minute; four of them had severe bradycardia (less than 45 beats per minute), and three of the four exhibited severe hypotension, vomiting, fainting, or convulsion. Other abnormal ECG changes, such as supraventricular and ventricular premature contractions, right bundle branch block, ST segment elevation or ST segment depression, and tall, flattened, or inverted T waves were observed in 29 donors (10%). These changes were not associated with symptoms. Only three of these donors complained of discomfort or chest heaviness. The abnormal waves appeared more often in granulocytapheresis donors than in plateletapheresis donors.
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PMID:Abnormal electrocardiographic findings in apheresis donors. 245 70

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.
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PMID:Individually specified drug immunoconjugates in cancer treatment. 250 30

Adult T-cell leukemia (ATL) is one of the most difficult diseases to treat because of severe underlying immune deficiency and metabolic disturbance. Interferon has potent antiviral, antiproliferative, and immunomodulating properties, and therefore, this may be a good agent to treat such immune deficient patients with peripheral T-cell leukemia. During a period from April 1984 to August 1985, six patients were treated with interferon-beta (IFN-beta), and interferon-gamma (IFN-gamma) was given to five patients. Three patients achieved partial remission by IFN-beta administration with a response duration of 1, 1.5, and 12 months respectively, whereas one complete remission and two partial responses were experienced by IFN-gamma treatment with 4, 4, and 2 months of response. Side effects of IFN-beta were similar to those of IFN-gamma including fever, chills, fatigue, mild hematologic depression, and transient hepatic enzyme abnormalities. These promising results warrant further well-designed clinical trials including combination with other agents or modalities of treatment.
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PMID:Recombinant interferon beta and gamma in the treatment of adult T-cell leukemia. 288 Jun 55

Twenty-three patients with disseminated refractory malignancies each received a tailored combination of adriamycin-conjugated murine monoclonal antibodies. Tumors were typed using a panel of antibodies. Cocktails of up to six antibodies were selected based on binding greater than 80% of the malignant cells as tested by immunoperoxidase and flow cytometry. These monoclonal antibodies were then conjugated to Adriamycin and administered intravenously. Seventeen of 23 patients had reactions to the administration of 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 there was limited antigenic drift among various biopsies within the same patient over time. This observation confirms the necessity for the use of a cocktail of antibodies if one wishes to cover all tumor cells. Preliminary serologic 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. 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. In the course of the study free Adriamycin released from the monoclonal antibodies was discovered to be a limiting factor in the amount of antibody that could be administered. Up to 1 g of Adriamycin and up to 5 g of monoclonal antibody were administered. The limiting factor appeared to be a variable dissociation of active Adriamycin from the antibody that unpredictably caused hemopoietic depression. This study demonstrates the feasibility and reviews technical considerations in preparing immunoconjugate cocktails for patients with refractory malignancies. The major technical hurdle appears to be the selection of an effective conjugation method that can be used to optimally bind Adriamycin to monoclonal antibodies for targeted cancer therapy.
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PMID:Adriamycin custom-tailored immunoconjugates in the treatment of human malignancies. 326 48


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