Gene/Protein Disease Symptom Drug Enzyme Compound
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 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We conducted a phase I study of CI-898 (trimetrexate), a new diaminoquinazoline antifolate in 22 patients with solid cancer in a multicenter collaborative study. The dosage schedule was single-dose intravenous administration (single treatment), followed by one or two courses of 5-day intravenous administration (5-day treatment) at 3-week intervals. Starting at 2 mg/m2 (1 n), the dose was increased up to 15 mg/m2 (7.5 n) for single treatment and 12 mg/m2 (6 n) for 5-day treatment. Evaluable cases numbered 18 for single treatment and 17 for 5-day treatment. In single treatment, the highest dose of 15 mg/m2 caused no serious side effect and did not reach the maximum tolerated dose (MTD). In 5-day treatment, leukocytopenia and thrombocytopenia were found dose dependently, the dose-limiting factor was bone marrow depression, and MTD was 10 mg/m2/day. The leukocyte and platelet counts reached the nadir in 1-3 weeks after initiation of 5-day treatment. The recovery from the nadir required about one week. Subjective side effects included mucitis (mouth, anus), malaise and gastro-intestinal symptoms (nausea, anorexia, diarrhea). None of alopecia, cardiotoxicity and nephrotoxicity were found. In the present phase I study, a tendency of tumor reduction was found in one case each of breast cancer (adenoma) and lung cancer (squamous cell carcinoma). The plasma concentration of the unchanged compound after single treatment showed a biphasic elimination pattern (t1/2 alpha 0.8-1.4 hr, t1/2 beta 9.4-13.0hr). The urinary excretion of the unchanged compound was 14.7-23.5% of the administered dose. In 5-day treatment, no accumulation was found. From the results of the present study, the recommended dosage of CI-898 in the early phase II study was considered to be 8 mg/m2/day intravenously for 5 days (every 3-4 weeks).
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PMID:[Phase I study of CI-898. CI-898 Study Group]. 183 40

Both cardiologists and psychiatrists have observed that the onset of myocardial infarction is often preceded by feelings of decreasing energy, general malaise, and minor depression. This paper describes these observations and tries to integrate the findings. It is proposed that the mental state preceding myocardial infarction can be best described as 'vital exhaustion'.
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PMID:Mental precursors of myocardial infarction. 224 88

Activity of endothelium-dependent relaxation factor (EDRF) was measured in 139 open ring preparations of fresh human saphenous vein from 85 patients undergoing coronary bypass grafting. The veins were constricted with phenylephrine and relaxed with the EDRF-dependent agents calcium ionophore A23187 or acetylcholine. EDRF activity produced a 36% +/- 4% relaxation of baseline contraction in response to calcium A23187. Vein graft preparation with room-temperature heparinized normal saline and pressurization to 400 mm Hg caused EDRF relaxation to fall to 10.6% +/- 2.0% versus 32.4% +/- 3.4% for control segments (p less than 0.05). Storage alone in room-temperature saline reduced EDRF response to 17.4% +/- 3.9% versus a control of 29.6% +/- 4.7% (p less than 0.05). Storage in heparinized room-temperature blood produced relaxation of 31.4% +/- 4.3% versus 34.1% +/- 5.7% (p less than 0.05). Storage in Plasma-Lyte solution (Travenol Laboratories, Inc., Deerfield, Ill), produced relaxation of 28.4% +/- 6.3% versus 30.1% +/- 5.3% (control) (p greater than 0.05). Veins stored at 2 degrees to 4 degrees C had severe depression of EDRF: 18.2% +/- 4.0% versus 34.0% +/- 5.4% for 37 degrees C storage (p less than 0.05). Pressurization to 400 mm Hg lessened EDRF relaxation: 20% +/- 3% versus 34% +/- 4% (control) (p less than 0.05), and use of nitroglycerin, papaverine, or verapamil produced no improvement. Twenty-eight vein grafts prepared with Plasma-Lyte solution were obtained from 12 patients who died 11.6 days (range up to 66 days) after operation. When compared with control veins prepared with saline and obtained at similar intervals, they had significantly more intact endothelium, less subintimal cellular infiltration, less fibrin deposition, fewer medial inflammatory changes, and less necrosis. Thus EDRF activity is significantly affected by vein graft preparation. Changes in technique to preserve EDRF produced better graft morphology early after operation.
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PMID:Endothelium-dependent relaxation in human saphenous vein grafts. Effects of preparation and clinicopathologic correlations. 212 May 19

Lead (Pb) depresses growth in infants and young children. Our earlier studies using a weanling rat model of Pb exposure suggest that this Pb effect is due to depression of appetite. In the present study we examined whether this depression of appetite is consistent with a down-regulation of the appetite "set point" as described using dietary manipulations following either lesions of certain hypothalamic regions or 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure. Two types of dietary manipulations were employed: (a) consumatory response to hyperalimentation (force-feeding), and (b) consumatory and growth response during the catch-up period following food restriction. In the hyperalimentation experiments, food intake was determined (a) with and without force-feeding, and (b) without Pb and with Pb administered either orally or systemically. Pb exposure reduced food consumption compared to controls. Force-feeding of a liquid diet further reduced food consumption, but only to the level that maintained total caloric intake at, or close to, the level of Pb animals not force-fed. In the food-restriction experiments, weanling rats had their food intake restricted for 4 days and then were provided free access to food, at which time one subgroup of these animals was exposed to Pb. Catch-up of previously food-restricted animals, in terms of food consumption and growth, was the same in the first 2 days, regardless of whether Pb was administered. During the next 10 days, the food intake and growth of the non-Pb-exposed, food-restricted animals gradually converged on the previously free-fed, non-Pb-exposed animals, whereas the food-restricted. Pb-exposed animals converged on the growth-depressed, previously free-fed Pb-exposed animals. All these responses to dietary manipulations are consistent with a reduced set point for appetite rather than with a nonspecific effect of Pb, e.g., aversion to food or general malaise.
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PMID:Lead exposure lowers the set point for food consumption and growth in weanling rats. 212 80

As most patients undergoing pulmonary surgery by postero-lateral thoracotomy have decreased preoperative pulmonary function, efficient postoperative analgesia is mandatory. Nalbuphine, a new agonist-antagonist opioid analgesic, and nefopam were compared in a double blind trial involving 60 patients. Intravenous injections of 0.3 mg.kg-1 of either drug were started when the patient evaluated his pain as being above 60 mm on a visual scale graduated from 0 to 100 mm. Repeated injections were carried out at the same dose, at the patient's request, after a minimal interval of 3 h for nalbuphine, and 6 h for nefopam. Analgesia was assessed by the visual scale, and by the patient's verbal appraisal. The respiratory and cardiovascular repercussions were evaluated clinically, and by monitoring breathing rate, blood gases, systolic and diastolic blood pressures, heart rate, and consciousness. Nalbuphine provided a convenient analgesia to all patients whereas analgesia with nefopam was insufficient in 15 out of 30 patients. No significant respiratory depression with either drug occurred. Nefopam led to a 30% increase in heart rate for one hour (p less than 0.01). Whereas patients given nalbuphine were more drowsy, although easily aroused, (p less than 0.001), nefopam was responsible for adverse effects (sweating, nausea, tachycardia with pallor, vertigo, malaise) requiring the exclusion of 7 patients from the study. Nalbuphine, although not ideal, would therefore seem to be a better analgesic than nefopam in thoracotomy patients.
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PMID:[Analgesic and respiratory effects of nalbuphine during the immediate postoperative period in thoracotomy]. 218 3

Eighty-two patients with either mycosis fungoides (MF) or parapsoriasis en plaques were treated with psoralens ultraviolet A light (PUVA). Clinical and histologic parameters were followed for a period from 6 months to 10 years. Complete clinical clearing of lesions was observed in 51 patients (62%) and most of them were in limited-plaque MF group or parapsoriasis en plaque. The mean total dose of PUVA for complete clearing was less for early MF. Thirty-one patients (38%) relapsed and responded to additional PUVA. Patients in early stages of the disease remained clear for up to 68 months after the first course of PUVA. Post-treatment skin biopsies with early MF showed histologic clearing. A new combination therapy for MF is presented in 15 patients. Recombinant interferon alpha-2a (Roferon-A), administered intramuscularly combined with PUVA were tested in a phase I trial. Interferon doses were from 6-30 million units three times weekly. Disease stages ranged from I-B to IV-B. Complete responses were obtained in 12 of 15 patients, and partial responses seen in 2 of 15 patients, for an overall response rate of 93%. The median duration of response exceeded 23 months (range, 3 to 25 months). All responding patients have been maintained on therapy. The dose-limiting toxicities were constitutional symptoms such as fevers and malaise (93.3%), leukopenias (40.0%), mental status changes consisting of depression and confusion (33.3%), and photosensitivity (26.6%). Interferon plus PUVA appear to be highly effective regimens for the treatment of patients with cutaneous T-cell lymphomas.
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PMID:Photochemotherapy alone or combined with interferon alpha-2a in the treatment of cutaneous T-cell lymphoma. 225 36

Escalating doses of recombinant interferon alfa-2a (Roferon-A), administered intramuscularly three times weekly, combined with psoralen plus ultraviolet light irradiation (PUVA), were tested in a phase I trial for the therapy of patients with cutaneous T-cell lymphomas (CTCL). Interferon doses were escalated in groups of three patients from 6 million to 30 million IUs three times weekly. Disease stages ranged from IB to IVB. Eighty percent of the patients entered in this trial had failed at least one prior therapy. Complete remissions were obtained in 12 of 15 patients, and partial responses were seen in two of 15 patients, for an overall response rate of 93%. The median duration of response exceeded 13 months (range, 3-15+). All patients who responded have been maintained on therapy. The dose-limiting toxic effects were constitutional symptoms such as fevers and malaise (93.3%), leukopenias (40.0%), mental status changes consisting of depression and confusion (33.3%), and photosensitivity (26.6%). These side effects were reversible with a decrement in dose or discontinuation of the interferon. No patient tolerated 30 million IU of the interferon for extended periods; the maximally tolerated dose was 18 million IU. Interferon plus PUVA appears to be a highly effective regimen for the treatment of patients with CTCL. Phase II studies investigating this combination, using 18 million IU of interferon alfa-2a three times weekly, should be undertaken to expand these findings, and to attempt to reduce the toxic effects associated with this therapy.
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PMID:Interferon alfa-2a combined with phototherapy in the treatment of cutaneous T-cell lymphoma. 229 50

The Medical Outcomes Study was designed to (1) determine whether variations in patient outcomes are explained by differences in system of care, clinician specialty, and clinicians' technical and interpersonal styles and (2) develop more practical tools for the routine monitoring of patient outcomes in medical practice. Outcomes included clinical end points; physical, social, and role functioning in everyday living; patients' perceptions of their general health and well-being; and satisfaction with treatment. Populations of clinicians (n = 523) were randomly sampled from different health care settings in Boston, Mass; Chicago, Ill; and Los Angeles, Calif. In the cross-sectional study, adult patients (n = 22,462) evaluated their health status and treatment. A sample of these patients (n = 2349) with diabetes, hypertension, coronary heart disease, and/or depression were selected for the longitudinal study. Their hospitalizations and other treatments were monitored and they periodically reported outcomes of care. At the beginning and end of the longitudinal study, Medical Outcomes Study staff performed physical examinations and laboratory tests. Results will be reported serially, primarily in The Journal.
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PMID:The Medical Outcomes Study. An application of methods for monitoring the results of medical care. 275 93

Twenty-two patients with Stages Ia to IVa cutaneous T cell lymphoma were entered into a controlled trial of interferon alfa-2a (Roferon-A). Patients initially received either 3 million IU interferon alfa-2a, or their dosage was escalated to 36 million IU intramuscularly daily for a 10-week induction period. At the end of induction, 14/22 (64%) of patients had an objective antitumor response: three patients had a complete response, ten patients had a partial response (greater than or equal to 50% resolution of clinical disease), and one patient had a minor response. Responders included those with Stages Ia to IVa cutaneous T cell lymphoma, and remissions have lasted at least 4 to 27.5 months. Three patients progressed from a partial to complete response with further treatment, for an overall complete response rate of 27%. Acute flu-like side effects were generally minor and transient. Malaise/fatigue, depression, anorexia, and weight loss were common chronic dose-related side effects and the most frequent reasons for dose reduction or discontinuation of drug. Leukopenia was the most common laboratory side effect and was also dose-related. Recombinant human leukocyte interferon alfa-2a is an effective and well-tolerated single-agent therapy for early and advanced cutaneous T cell lymphoma.
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PMID:Interferon alfa-2a in the treatment of cutaneous T cell lymphoma. 278 39

The antihistaminic properties of the tricyclic antidepressants have been recognized since these compounds were first developed. Antidepressants, which are equally effective for treating depression or used in the treatment of chronic urticaria, have varying in vitro antihistaminic properties. We compared the duration of H1-receptor blockade by two tricyclic antidepressants, doxepin (the most potent antihistamine) and desipramine (the least potent antihistamine), in a single dose, double-blind, noncrossover study. After baseline prick test with histamine phosphate 1:1000 by Multitest (Lincoln Diagnostics, Decatur, Ill.), the suppression of cutaneous histamine-induced wheal-and-flare responses were measured daily for 7 days in 33 healthy volunteers who were randomly administered a single 25 mg dose of oral desipramine or doxepin. Significant differences in the suppression of the wheal-and-flare responses to histamine between the two drugs were noted (p less than 0.05) during the first 3 days. Desipramine suppressed the wheal for 2 days and flare for 1 day. Doxepin suppressed the wheal for 4 days and flare for 6 days. Our results suggest doxepin should be withheld for at least 7 days before allergy skin testing.
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PMID:Duration of the suppressive effect of tricyclic antidepressants on histamine-induced wheal-and-flare reactions in human skin. 290 76


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