Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Up to 30% of patients with advanced germ cell tumors will fail induction chemotherapy or will relapse. New agents with activity in this still potentially curable subgroup of patients are needed. Edatrexate (10-ethyl, 10-deaza-aminopterin) is a methotrexate analogue that has preclinical and clinical activity in breast, lung, and head and neck cancers, as well as in non-Hodgkin's lymphomas. A phase II trial of edatrexate in relapsed or refractory malignant germ cell tumors was conducted by the Southwest Oncology Group (SWOG). Twenty-five patients were enrolled in the trial. Edatrexate was administered intravenously at a dose of 80 mg/m2 weekly for four weeks followed by a one-week rest period. The treatment course was repeated every five weeks. Among the 23 patients evaluable for response, there were no objective responses with all patients developing progressive disease. Thirteen patients (56%) developed Grade 3-4 toxicities, predominantly stomatitis and malaise/fatigue/lethargy. One patient developed Grade 4 anemia while another developed grade 4 anemia and thrombocytopenia. No patients discontinued treatment due to toxicity nor were there any toxic deaths. Edatrexate administered in this dose and schedule has no antitumor activity and has substantial toxicity in patients with relapsed or refractory germ cell tumors.
 ...
PMID:Phase II trial of edatrexate in relapsed or refractory germ cell tumors: a Southwest Oncology Group study (SWOG 9124). 1042 70

Rathke's cleft cysts are sometimes associated with aseptic meningitis or metabolic encephalopathy due to hyponatremia. We treated such a case manifest by lethargy, fever and electroencephalographic abnormalities. A 68-year-old man was admitted to our ward after experiencing general malaise, nausea and vomiting and then high fever and lethargy. On admission, he was drowsy and had nuchal rigidity and Kernig's sign. Physically, he was pale with dry, thickened skin. He had lost 5.0 kg of body weight in the last month. His serum sodium was 115 mEq/l. He had a low serum osmotic pressure (235 mOsmol/l) and a high urine osmotic pressure (520 mOsmol/l). His urine volume was 1200-1900 ml/24 h with a specific gravity of 1008-1015. The urine sodium was 210 mEq/l. He did not have an elevated level of antidiuretic hormone. Electroencephalograms showed periodic delta waves over a background of theta waves. With sodium replacement, the patient become alert and symptom free, and his electroencephalographic findings normalized. However, the serum sodium level did not stabilize, sometimes falling with a recurrence of symptoms. Magnetic resonance imaging clearly delineated a dumbbell-shaped intrasellar and suprasellar cyst. The suprasellar component subsequently shrunk spontaneously and finally disappeared. An endocrinologic evaluation showed panhypopituitarism. The patient was given glucocorticoid and thyroxine replacement therapy, which stabilized his serum sodium level and permanently relieved his symptoms. A transsphenoidal approach was performed. A greenish cyst was punctured, and a yellow fluid was aspirated. The cyst proved to be simple or cubic stratified epithelium, and a diagnosis of Rathke's cleft cyst was made. The patient was discharged in good condition with a continuation of hormonal therapy. Rathke's cleft cyst can cause aseptic meningitis if the cyst ruptures and its contents spill into the subarachnoid space. Metabolic encephalopathy induced by hyponatremia due to salt wasting also can occur if the lesion injures the hypothalamus and pituitary gland.
 ...
PMID:Hyponatremia-induced metabolic encephalopathy caused by Rathke's cleft cyst: a case report. 1046 7

To study effects of dietary Cu and Fe levels on the onset of hepatitis in Long-Evans Cinnamon (LEC) rats, female rats (40 days old) were fed a semipurified diet containing 0.1 or 10 mg Cu/kg and 1.5 or 150 mg Fe/kg in a 2 x 2 factorial arrangement for 35 days. At 75 days after birth, LEC rats (+Cu-Fe) fed a Cu-sufficient but Fe-deficient diet (Cu, 10 mg/kg; Fe, 1.5 mg/kg) showed jaundice, with lethargy, anorexia, and malaise. The biochemical variables relating to liver function were significantly increased compared to three other groups, a Cu- and Fe-deficient (-Cu-Fe) group, a Cu-deficient but Fe-sufficient (-Cu+Fe) group, and a Cu and Fe sufficient (+Cu+Fe) group. Furthermore, the +Cu-Fe rat liver showed massive necrosis with huge nuclei. The other three groups presented no biochemical and histological findings of hepatitis. Hepatic Cu and metallothionein concentrations were 289 +/- 87 (mean +/- SD) microg/g liver and 8.7 +/- 1.8 mg/g liver, respectively, in the +Cu-Fe rats. However, in the +Cu+Fe group the values were 196 +/- 28 microg Cu/g liver and 10.8 +/- 1.0 mg/g liver. Hepatic Fe deposition was not influenced significantly by the dietary Cu level. The +Cu-Fe group with jaundice showed the highest free Cu concentration in the liver among the four groups, but the hepatic free Fe concentration was similar to those in the -Cu+Fe and +Cu+Fe groups. Our results indicate that an Fe-deficient diet enhances the deposition of hepatic Cu due to increased absorption of Cu from the gastrointestinal tract. This deposition stimulated the onset of hepatitis.
 ...
PMID:An iron-deficient diet stimulates the onset of the hepatitis due to hepatic copper deposition in the Long-Evans Cinnamon (LEC) rat. 1055 Apr 76

We conducted a randomized phase II trial of two different schedules of topotecan in patients with advanced-stage non small lung cancer (NSCLC) without prior cytotoxic chemotherapy. All patients had histologic or cytologic confirmation of stage IV (M1) or III-B NSCLC. Patients were stratified by performance status, stage and weight loss. Patients were randomized to receive topotecan at intravenous doses of 1.5 mg/m(2)/day over 30 min for 5 days every 3 weeks (Arm A) or 1.3 mg/m(2)grade 3 in both arms included leukopenia, thrombocytopenia, malaise, constipation, diarrhea, lethargy, pulmonary, vomiting, infection and myalgia. Severe (> or = grade 3) thrombocytopenia occurred in 15.8% of Arm A patients and 37.8% of Arm B patients and this difference was statistically significant (P=0.03). The median times to progression are 101 and 63 days (P=0. 75) and the median survival times are 257 and 179 days (P=0.83) for Arms A and B, respectively. These differences in time to progression and overall survival are not statistically significant. Topotecan has limited, single agent activity in advanced NSCLC when given as 1. 5 mg/m(2)/day over 30 min for 5 days every 3 weeks. We do not intend to pursue further investigations with topotecan in patients with NSCLC.
 ...
PMID:A randomized phase II trial of two schedules of topotecan for the treatment of advanced stage non-small cell lung cancer. 1071 33

CT-2584 HMS, 1-(11-dodecylamino-10-hydroxyundecyl)-3, 7-dimethylxanthine-hydrogen methanesulphonate, is a modulator of intracellular phosphatidic acid. We treated 30 patients as part of a Phase I and pharmacokinetic study to determine the maximum-tolerated dose of CT-2584 HMS, toxicity profiles, pharmacokinetic profile and antitumour effects at escalating dose levels. CT-2584 HMS was given as a continuous infusion for 6 hours for 5 consecutive days every 3 weeks. Plasma samples for pharmacokinetic studies were analysed using a validated high-performance liquid chromatographic assay. Mean C(max)and AUC values for each dose group were similar on days 1 and 5 and increases in plasma concentration (C(max)and AUC) appeared proportional to the dose. CT-2584 HMS had a mean elimination half-life of 7.3 hours. Values of V(d)and clearance were independent of dose and duration of treatment. Dose escalation was halted at 585 mg/m(2)because of malaise and lethargy, which was sometimes accompanied by nausea and headache. 26 patients were evaluable for response, one patient with pleural mesothelioma achieved a partial response to treatment confirmed by CT scanning. A dose level of 520 mg/m(2)daily x 5 days would be suitable for Phase II testing. Alternative schedules of CT-2584 HMS to overcome the limiting toxicity of malaise would be worthy of examination.
 ...
PMID:Phase I and pharmacologic study of CT-2584 HMS, a modulator of phosphatidic acid, in adult patients with solid tumours. 1110 52

We performed a phase II, Southwest Oncology Group (SWOG) clinical trial of recombinant human interleukin-4 (rhuIL-4) in patients with previously treated non-Hodgkin's lymphoma (NHL). We studied 18 eligible patients with low-grade and 21 patients with intermediate- or high-grade NHL. All patients had received prior chemotherapy. A protocol amendment after the first four patients reduced the frequency of s.c. rhuIL-4 administration from daily to 3 times per week at 3 microg/kg and limited the number of prior chemotherapy regimens allowed. We documented no complete or partial responses in the low-grade NHL group [0%; 95% confidence interval (CI) 0-19%]. One patient in the intermediate/high-grade NHL group developed a partial response lasting longer than 15 months (5%; 95% CI 0-24%). Median survivals for the low- and intermediate/high-grade NHL groups were 15 and 13 months, respectively. Common toxicities included: arhralgia/myalgia, fatigue/malaise/lethargy, fever, headache, nausea and rigors/chills. Cardiac toxicity, gastrointestinal ulceration and nasal congestion due to rhuIL-4 were not prominent toxicities in our patients. Our previously treated NHL patients tolerated s.c. rhuIL-4 at a dose of 3 microg/kg given 3 times per week, but objective response rarely occurred. Further evaluation of rhuIL-4 in these patient populations does not appear warranted.
 ...
PMID:Phase II evaluation of interleukin-4 in patients with non-Hodgkin's lymphoma: a Southwest Oncology Group trial. 1112 30

Cryptococcosis, caused by Cryptococcus neoformans, is the most common life-threatening AIDS-related fungal infection. The infection can occur in any organ of the body, although meningitis is its most frequent form. Symptoms of cryptococcal meningitis appear gradually and generally include headache, fever, or malaise. Symptoms may also include memory loss, lethargy, and personality changes. Isolation of the pathogen is done by using microscopy of the cerebrospinal fluid or by testing the serum antigen titer. Appropriate therapy includes amphotericin B or triazole antifungals. Patients with elevated intracranial pressure may be treated by draining cerebrospinal fluid (about 30 ml) daily. Other antifungal agents are being investigated.
 ...
PMID:Cryptococcosis. 1136 41

Toxoplasma gondii is a unicellular protozoan. The definitive hosts, cats, produce hardy oocysts and sporozoites. Ingestion by a nonfeline leads to the formation of tachyzoites acutely, which cause parasitemia and further dissemination, and bradyzoites, which lead to latent infection with the formation of tissue cysts in skeletal muscle, heart muscle, and central nervous system (CNS) tissue. Toxoplasmosis can be transmitted to humans by ingestion of tissue cysts in raw or inadequately cooked infected meat or in uncooked foods that have come in contact with contaminated meat, by inadvertent ingestion of oocysts and sporozoites in cat feces, or transplacentally. Immunocompetent adults and adolescents with primary infection are generally asymptomatic, but symptoms may include mild malaise, lethargy, and lymphadenopathy. Specific treatment for nonpregnant adults and adolescents is not required. Immunosuppressed patients may experience more severe manifestations, including splenomegaly, chorioretinitis, pneumonitis, encephalitis, and multisystem organ failure. These patients are also prone to reactivation of latent infection involving the CNS. All patients with human immunodeficiency virus infection and CD4 counts <100 cells per cubic millimeter should be treated prophylactically with pyrimethamine-sulfonamide. Congenital toxoplasmosis is marked by the classic triad of chorioretinits, intracranial calcifications, and hydrocephalus. Current studies have determined that prolonged treatment (1-2 years) of neonates with fansidar is important to prevent serious sequelae. Diagnosis of acute toxoplasmosis is mainly by antibody detection and generally only undertaken in pregnant patients with risk factors for transplacental transmission. All positive screening tests in pregnant women must be confirmed at a toxoplasma reference laboratory. Recent studies have shown that polymerase chain reaction testing of amniotic fluid is useful for identification or exclusion of fetal T. gondii infection. Ultrasound can be used as an adjunct to serological screening but cannot itself definitively diagnose disease. Early-first-trimester maternal infections are less likely to result in congenital infection, but the sequelae are more severe. Transplacental passage is more common when maternal infection occurs in the latter half of pregnancy, but fetal injury is usually much less severe. Typically, infected pregnant patients are treated with pyrimethamine-sulfonamide for positive PCR-amniotic-fluid testing and with spiramycin for negative PCR-AF testing.
 ...
PMID:Toxoplasmosis. 1137 31

We report a case of aortic valve endocarditis caused by Bartonella henselae. The patient initially presented to a regional hospital with generalized symptoms including lethargy, malaise and decreased appetite. Transthoracic echocardiogram revealed a large vegetation on the aortic valve and he was treated empirically with broad spectrum intravenous antibiotics. Several blood cultures were obtained which all returned negative results and the white blood cell count was normal. He was transferred to our hospital, with persistence of his initial symptoms and additional low-grade fevers. In light of his negative culture results, serological testing for Bartonella and Chlamydia was performed, which gave a positive result for Bartonella henselae. In view of this result and following development of severe aortic valve insufficiency, he underwent an aortic valve replacement and made a good recovery.
 ...
PMID:Aortic valve endocarditis caused by Bartonella henselae: a rare surgical entity. 1180 50

Primary HIV can be asymptomatic or result in a severe symptomatic illness. Common symptoms are pyrexia, pharyngitis, malaise, lethargy, maculopapular rash, mucous membrane ulceration, lymphadenopathy and headache. It can be reliably diagnosed by a positive virologic test in the absence of HIV-specific antibodies. Progression to late-stage disease is influenced by the severity of the symptoms in primary HIV infection, the duration of the illness, the presence of neurological symptoms and the presence of oral candidiasis. This stage is characterized by a very high viral load and infectiousness. Currently the experimental data are insufficient to recommend whether or not those diagnosed with primary HIV infection should routinely receive antiretroviral therapy.
 ...
PMID:Primary HIV infection. 1183 60


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>