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

Castanospermine (1,6,7,8-tetrahydroxyoctahydroindolizine), an inhibitor of glycoprotein processing, has been shown to inhibit the human immunodeficiency virus type 1 (HIV-1) with acceptable toxicity in cultured cells. In contrast to reverse transcriptase inhibitors, castanospermine targets host enzymes. We have analyzed castanospermine in murine systems, using cultured cells as well as live animals. Plaque formation by Rauscher murine leukemia virus (RLV) was inhibited with a median inhibitory concentration (IC50) of 2 micrograms/ml. RLV-exposed BALB/c mice treated with a 20 day course of castanospermine starting 4 h postinoculation showed a dose-dependent inhibition of splenomegaly. Oral castanospermine therapy given to chronically RLV-infected mice prolonged median survival from 36 to 94 days when compared to untreated controls (p = 0.007). Castanospermine was better tolerated orally than intraperitoneally at the same dose. Toxic effects included weight loss, lethargy, and dose-dependent thrombocytopenia. At the highest intraperitoneal dose, lymphoid depletion occurred in thymus, spleen, and lymph nodes. We conclude that castanospermine is an active antiviral agent in animals and that prolonged oral administration is tolerable; however, when compared to 3'-azido-3'-deoxythymidine in the same murine system, castanospermine was less active and more toxic.
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PMID:In vivo analysis of castanospermine, a candidate antiretroviral agent. 249 48

A phase II trial of ifosfamide (isophosphamide, NSC 109724) and mesna (2-mercaptoethane sodium sulfonate, NSC 113891) in women with advanced or recurrent mixed mullerian tumors of the uterus was conducted by the Gynecologic Oncology Group. The starting dose of ifosfamide was 1.5 gm/m2 daily, intravenously, for 5 days. The starting dose of ifosfamide was reduced 1.2 gm/m2 daily in patients who had received prior radiotherapy. Mesna was given intravenously immediately and at 4 and 8 hours after the administration of ifosfamide. Each mesna dose was 20% of the total daily dose of ifosfamide. Twenty-nine patients are evaluable for toxicity, and 28 patients are evaluable for response. Twenty-one patients had received prior abdominal hysterectomy, and eight patients had prior radiotherapy. Thirteen tumors were homologous and 15 heterologous. Gynecologic Oncology Group grade 3 or 4 granulocytopenia occurred in seven (25%) patients and two (7.1%) had grade 3 or 4 thrombocytopenia. Two patients (7.1%) had grade 3 or 4 neurotoxicity. One patient experienced lethargy and confusion that responded to discontinuation of the ifosfamide. A second patient developed progressive cerebellar dysfunction, left hemiparesis, and coma. This patient died after 3 days of therapy. Complete responses were seen in five (17.9%) patients and partial responses occurred in four (14.3%) patients for a total response rate of 32.2%. These results indicate that ifosfamide is an unusually active drug in patients with advanced or recurrent mixed mullerian tumors of the uterus. Studies with combination regimens incorporating ifosfamide are warranted. The toxicity of ifosfamide in Gynecologic Oncology Group studies is being evaluated retrospectively.
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PMID:Phase II trial of ifosfamide and mesna in mixed mesodermal tumors of the uterus (a Gynecologic Oncology Group study). 254 82

Scrub typhus (tsutsugamushi disease) is an acute infectious disease caused by Rickettsia tsutsugamushi transmitted through the bite of larvae of certain trombiculid mites. Geographical distribution in Asian-Pacific region is much of the roughly triangular area bounded by Japan, Pakistan and Australia. It is an endemic illness in the Pescadores Islands, but has scarcely been reported in central Taiwan. An eleven-year-old boy was admitted to Changhua Christian Hospital with the chief complaints of fever, lethargy and skin rash for seven days. On physical examination, he was found to have painless eschar, conjunctivitis, meningoencephalitis, pneumonitis, ascites, jaundice, hepatomegaly, liver function impairment and thrombocytopenia. His Proteus OX-K agglutinin titer increased from 1:160 in the acute sera to 1:640 in the convalescent sera. A greater than four-fold rise (greater than 1:640) in antibody titers to Karp, Gilliam, Kato strains of R. tsutsugamushi between acute and convalescent sera were demonstrated by immunofluorescent antibody. The patient was treated with minocycline and chloramphenicol and was completely recovered.
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PMID:[Scrub typhus--one case report]. 263 64

The diagnosis of adrenal haemorrhage complicating heparin therapy is often delayed, despite computed tomography (CT). Moreover, its pathogenesis is not clear. Adrenal haemorrhages are often seen in cases where there is no unduly excessive anticoagulation, and can be accompanied by a paradoxical thrombosis of the central adrenal vein. Symptoms usually occur within the first 8 to 12 days after starting heparin. The difficulty in establishing the diagnosis stems from the fact that symptoms are rather nonspecific: abdominal pain and backache, nausea, vomiting, lethargy, weakness, hypotension, hyperpyrexia. To confirm the diagnosis, both hormonal proof of adrenal failure and anatomic evidence of haemorrhage must be found. Early CT scans may show the haemorrhage. Several possible causes have been put forward to account for these adrenal haemorrhages. The degree of anticoagulation did not seem to be a prerequisite, 30 to 50% of patients showing no evidence of other bleeding or coagulation tests outside the therapeutic range. Capillary fragility of old age might be a factor. Stress would seem to be an important factor predisposing to adrenal haemorrhage. Many authors consider the paradoxical central vein thrombosis as a result of the haemorrhage rather than its cause, whereas other conclude the opposite. Unfortunately, to date coagulation studies are often incomplete; platelet counts were missing in most reports published before 1985. Since that date, a heparin induced thrombosis-thrombocytopaenia syndrome (HITTS), in which thrombosis may occur in any vascular bed, has been recognized with increasing frequency. Nine cases of adrenal haemorrhage associated with HITTS have been reported. It seems highly likely that a proportion of cases of heparin-related adrenal destruction are due to HITTS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Hematoma of the adrenal glands and heparin]. 269 74

A 32-year-old black man from rural southeastern Texas had headache, fever, chills, bronchopneumonia, and an atypical rash, complicated by hypotension, lethargy, confusion, liver dysfunction, thrombocytopenia, and acute renal failure. The diagnosis of Rocky Mountain spotted fever (RMSF) was not suspected until eight days after the onset of symptoms. He was subsequently treated with chloramphenicol, followed by hemodialysis and aggressive supportive therapy. He recovered uneventfully with complete return of renal function. This case emphasizes that RMSF should be considered in the differential diagnosis of any obscure febrile illness even in nonendemic areas.
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PMID:Viscerotropic Rocky Mountain spotted fever in southeastern Texas: report of a survivor with atypical manifestations and multiple organ failure. 271 89

Sixty cats with hematologic abnormalities indicative of non-lymphoid hematopoietic neoplasia were classified into two groups, myelodysplastic syndromes (MDS) and acute myelogenous leukemias (AML), using criteria developed for human patients with similar diseases. Cats with myeloblast counts in bone marrow of less than 30% were classed as MDS and cats with myeloblast counts of 30% or greater were classed as AML. The clinical, laboratory, and postmortem findings in each group were described and compared. Clinical signs of disease were similar in both groups, the most common being inappetance, lethargy, and weakness. Non-regenerative anemia, macrocytosis, neutropenia, and thrombocytopenia were frequent hemogram abnormalities in both groups. Diagnostically useful differences in physical and peripheral blood findings were a higher prevalence of splenomegaly and/or hepatomegaly, thrombocytopenia, and severe anemia in the AML group. Circulating myeloblasts were found only in cats in the AML group. Outcome of disease was similar in both groups; 85% of the cats in each group died or were euthanatized within one week of diagnosis. In cats that were necropsied, extramedullary leukemic infiltrates were found in all cats in the AML group and in none of the cats in the MDS group.
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PMID:Non-lymphoid hematopoietic neoplasia in cats: a retrospective study of 60 cases. 282 80

In the course of a prospective immunoepidemiological study of homosexual men in Sydney, seroconversion to the AIDS-associated retrovirus (ARV) was observed in 12 subjects. Review of the clinical files defined an acute infectious-mononucleosis-like illness in 11 subjects. The illness was of sudden onset, lasted from 3 to 14 days, and was associated with fevers, sweats, malaise, lethargy, anorexia, nausea, myalgia, arthralgia, headaches, sore throat, diarrhoea, generalised lymphadenopathy, a macular erythematous truncal eruption, and thrombocytopenia. In 1 subject an incubation period of 6 days after presumed exposure to ARV was determined and in 3 subjects seroconversion took place 19, 32, and 56 days after onset. Comparison of T-cell subsets before and after the acute illness showed inversion of T4:T8 ratio in 8 subjects, due to increased numbers of circulating T8+ cells. These findings support the notion of an acute clinical, immunological, and serological response to infection with ARV which should be considered in the differential diagnosis of mononucleosis-like syndromes in groups at high risk for the development of AIDS.
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PMID:Acute AIDS retrovirus infection. Definition of a clinical illness associated with seroconversion. 285 99

A clinical phase I-II evaluation of 2-amino-1,3,4-thiadiazole (A-TDA) administered daily, twice a week, or weekly was undertaken, in which 71 patients were treated with a range of doses from 2 mg/m2 to 200 mg/m2. Pharmacokinetic studies employing high-performance liquid chromatography (HPLC) demonstrated a terminal (beta) serum half-life of 2.19 h. Stomatitis, dermatitis, nausea, vomiting, and lethargy were observed. No significant leukopenia or thrombocytopenia, however, was noted. A-TDA administration led to hyperuricemia, which was adequately controlled with concurrent administration of allopurinol. Antitumor responses included one partial response in a patient with large cell carcinoma of the lung and three objective responses (2 non-small cell lung and 1 squamous cell carcinoma of the esophagus). Two patients with adenocarcinoma of the lung had a marked improvement of psoriasis during A-TDA therapy. Further phase II studies in patients with cancer and trials in patients with psoriasis are recommended.
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PMID:Clinical and clinical pharmacologic studies of 2-amino-1,3,4-thiadiazole (A-TDA:NSC 4728). 293 41

The traditional treatment of African sleeping sickness (trypanosomiasis) with central nervous system involvement is an organic arsenical compound, melarsoprol, which is associated with severe and even life-threatening side effects. A polyamine biosynthesis inhibitor, eflornithine (chemical name, DL-alpha-difluoromethylornithine, supplied as monohydrochloride monohydrate), was used to treat a 3 1/2-year-old child with newly diagnosed severe trypanosomiasis that had been acquired more than two years previously in Zaire or the Congo. Treatment consisted of 300 to 400 mg/kg/d of eflornithine by continuous intravenous infusion for 25 days followed by 300 mg/kg/d of eflornithine by mouth divided in four equal doses daily for 17 days. The child's recovery was dramatic, with eradication of blood and cerebrospinal fluid parasites in the first week. Cerebrospinal fluid pleocytosis resolved completely. Her generalized adenopathy and fever gradually resolved. Severe ataxia, inability to walk or to change posture on her own, marked language regression, and lethargy all improved during and after her therapy. The drug was well tolerated; the only noted adverse effect was transient thrombocytopenia during the fourth week of therapy. Eflornithine was a safe and effective agent for treatment of trypanosomiasis with central nervous system involvement in this child.
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PMID:African sleeping sickness in the United States. Successful treatment with eflornithine. 312 3

The clinical symptoms and signs were assessed in 20 consecutive patients developing infection with the human immunodeficiency virus (HIV). All were male homosexuals and all presented with a glandular-fever-like illness. Changes in laboratory values were compared with findings in 40 HIV negative male homosexual controls. In the 10 patients for whom date of exposure to the virus could be established the incubation period was 11-28 days (median 14). One or two days after the sudden onset of fever patients developed sore throat, lymphadenopathy, rash, lethargy, coated tongue, tonsillar hypertrophy, dry cough, headache, myalgia, conjunctivitis, vomiting, night sweats, nausea, diarrhoea, and palatal enanthema. Twelve patients had painful, shallow ulcers in the mouth or on the genitals or anus or as manifested by oesophageal symptoms; these ulcers may have been the site of entry of the virus. During the first week after the onset of symptoms mild leucopenia, thrombocytopenia, and increased numbers of banded neutrophils were detected (p less than 0.0005). The mean duration of acute illness was 12.7 days (range 5-44). All patients remained healthy during a mean follow up period of 2.5 years. Heightened awareness of the typical clinical picture in patients developing primary HIV infection will alert the physician at an early stage and so aid prompt diagnosis and help contain the epidemic spread of AIDS.
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PMID:Clinical picture of primary HIV infection presenting as a glandular-fever-like illness. 314 67


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