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)

The aim of this study was assess the activity of thalidomide in patients with progressive relapsed or platinum-refractory germ-cell tumours (GCT). Between April 2002 and January 2003, 15 patients with inoperable progressive GCT were treated with escalated daily doses of 200-600 mg thalidomide. All patients had failed first-line and salvage chemotherapy with a median of 6 (range 4-12) cisplatin-based treatment cycles, 13/15 (87%) patients had received high-dose chemotherapy (HDCT) and 8/15 (53%) patients were considered platinum-refractory or absolute refractory; 8/15 (53%) patients had previously received other palliative chemotherapy regimens. No patient achieved a complete remission (CR) or partial remission (PR). However, 5/15 (33%) patients achieved serological PR and 1 additional patient had stable disease for 3 months. The median duration of remissions was 3 months (range 2-12 months) including 2 patients with a progression-free survival of 9 and 12 months. Responses occurred mainly in patients with a low tumour burden, slow disease progression and alpha-foetoprotein (AFP) elevations. Responses to thalidomide were independent from platinum-sensitivity. Toxicity was mild, with lethargy and constipation in the majority of patients. Skin rash grade II developed in 2 patients and peripheral neurotoxicity grade II/III developed in 4 patients. One responding patient died suddenly from an unknown cause. It is concluded that thalidomide shows single-agent activity in patients with heavily pre-treated GCT, AFP elevations and slowly progressive disease.
 ...
PMID:Activity of thalidomide in patients with platinum-refractory germ-cell tumours. 1676 39

A 47-year-old fishmonger presented with a history of weight loss and lethargy. On investigation he was found to have myeloma. He presented again before follow up, with a 3-day history of fever and a maculopapular rash. He was admitted to the haematology ward and treated with broad-spectrum antibiotics. Blood cultures were found to be positive for Erysipelothrix rhusiopathiae. Penicillin treatment was given, and he made a good recovery. The importance of occupational illness in an already immunocompromised patient and of taking a proper social and occupational history from patients on admission is illustrated through this case.
 ...
PMID:Occupational injury in a fishmonger with a macular rash, hepatosplenomegaly and pancytopenia. 1693 76

We report the case of a 62-year-old woman with rheumatoid arthritis treated with adalimumab, an anti-tumor necrosis factor alpha drug, who presented with 4 weeks of lethargy, upper respiratory tract symptoms, a vasculitic skin rash, and rapidly deteriorating renal function. She had cytoplasmic antineutrophil cytoplasmic antibodies and skin and renal biopsy specimens diagnostic of small vessel vasculitis and necrotizing crescentic glomerulonephritis, respectively. After immunosuppressive therapy and discontinuation of adalimumab therapy, vasculitis resolved and renal function recovered. This is the first report of antineutrophil cytoplasmic antibody associated necrotizing glomerulonephritis with adalimumab.
 ...
PMID:ANCA-associated renal vasculitis following anti-tumor necrosis factor alpha therapy. 1829 46

To evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of the humanised antiepidermal growth factor receptor monoclonal antibody matuzumab combined with epirubicin, cisplatin and capecitabine (ECX) in patients as first-line treatment for advanced oesophagogastric cancer that express epidermal growth factor receptor (EGFR). This was a phase I dose escalation study of matuzumab at 400 and 800 mg weekly and 1200 mg every 3 weeks combined with ECX (epirubicin 50 mg m(-2), cisplatin 60 mg m(-2) on day 1 and capecitabine 1000 mg m(-2) daily). Patients were treated until disease progression, unacceptable toxicity or for a maximum of eight cycles. Twenty-one patients were treated with matuzumab at three different dose levels (DLs) combined with ECX. The main dose-limiting toxicity (DLT) was grade 3 lethargy at 1200 mg matuzumab every 3 weeks and thus 800 mg matuzumab weekly was the maximum-tolerated dose (MTD). Other common toxicities included rash, nausea, stomatitis and diarrhoea. Pharmacokinetic evaluation demonstrated that the coadministration of ECX did not alter the exposure of matuzumab. Pharmacodynamic studies on skin biopsies demonstrated inhibition of the EGFR pathway. Objective response rates of 65% (95% confidence interval (CI): 43-82), disease stabilisation of 25% (95% CI: 11-47) and a disease control rate (CR + PR + SD) of 90% were achieved overall. The MTD of matuzumab in combination with ECX was 800 mg weekly, and at this DL it was well-tolerated and showed encouraging antitumour activity. At the doses evaluated in serial skin biopsies, matuzumab decreased phosphorylation of EGFR and MAPK, and increased phosphorylation of STAT-3.
 ...
PMID:Phase I study of epirubicin, cisplatin and capecitabine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer. 1923 29

Simian varicella virus (SVV; Cercopithecine herpesvirus 9) is a naturally occurring herpesvirus of nonhuman primates. Here we present the clinical, pathologic, and virologic findings from 2 cases of SVV in adult female pigtailed macaques (Macaca nemestrina). The initial case presented with hyperthermia and a diffuse inguinal rash which spread centripetally, progressing to vesiculoulcerative dermatitis of the trunk, face, and extremities. At 96 h after presentation, the animal was anorexic and lethargic and had oral and glossal ulcerations. Euthanasia was elected in light of the macaque's failure to respond to clinical treatment. Seven days after the first case was identified, a second macaque presented with a vesicular rash and was euthanized. Gross necropsy lesions for both cases included vesicular, ulcerative dermatitis with mucocutaneous extension and hepatic necrosis; the initial case also demonstrated necrohemorrhagic gastroenterocolitis and multifocal splenic necrosis. Histology confirmed herpetic viral infection with abundant intranuclear inclusion bodies. Immunofluorescence assays detected antibodies specific for SVV. PCR assays of vesicular fluid, tissue, and blood confirmed SVV and excluded varicella-zoster virus (Human herpesvirus 3). Serology for Macacine herpesvirus 1 (formerly Cercopithecine herpesvirus 1), poxvirus (monkeypox), and rubella was negative. Banked serum samples confirmed SVV exposure and seroconversion. Investigation into the epidemiology of the seroconversion demonstrated a SVV colony prevalence of 20%. The described cases occurred in animals with reconstituted immune systems (after total-body irradiation) and demonstrate the clinical effects of infection with an endemic infectious agent in animals with a questionable immune status.
 ...
PMID:Simian varicella virus in pigtailed macaques (Macaca nemestrina): clinical, pathologic, and virologic features. 1988 33

The World Health Organization (WHO) estimates that there are over 50 million cases of dengue fever reported annually and approximately 2.5 billion people are at risk. Mild dengue fever presents with headache, fever, rash, myalgia, osteogenic pain, and lethargy. Severe disease can manifest as dengue shock syndrome (DSS) or dengue hemorrhagic fever (DHF). Symptoms of DSS/DHF are leukopenia, low blood volume and pressure encephalitis, cold and sweaty skin, gastrointestinal bleeding, and spontaneous bleeding from gums and nose. Currently, there are no therapeutics available beyond supportive care and untreated complicated dengue fever can have a 50% mortality rate. According to WHO DSS/DHF is the leading cause of childhood mortality in some Asian countries. Dendritic cells are professional antigen presenting cells that are primary targets in a dengue infection. Dengue binds to Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN). DC-SIGN has a high affinity for ICAM3 which is expressed in activating T-cells. Previous studies have demonstrated an altered T-cell phenotype expressed in dengue infected patients that could be potentially mediated by dengue-infected DCs.Dengue is enhanced by three interacting components of the immune system. Dengue begins by infecting dendritic cells which in immature dendritic cells is mediated by DC-SIGN. In mature dendritic cells, antibodies can enhance dengue infection via Fc receptors. Downstream of dendritic cells T-cells become activated and generate the very cytokines implicated in vascular leak and shock in addition to activating effector cells. Both the virus and the antibodies are involved in release of complement and anaphylatoxins which can cause or exacerbate DHF/DSS. These systems are inextricable and strongly associated with dengue pathogenesis.
 ...
PMID:The relationship of interacting immunological components in dengue pathogenesis. 1994 67

We report a 14-year-old girl with juvenile dermatomyositis (JDM) complicated by severe inflammatory calcinosis successfully treated with thalidomide. She was diagnosed as JDM when she was 4 years old after a few months of increasing lethargy, muscle pain, muscle weakness, and rash. During three months, clinical manifestations and abnormal laboratory findings were effectively treated with oral prednisolone. However, calcinosis was recognized 18 months after disease onset. Generalized calcinosis rapidly progressed with high fever, multiple skin/subcutaneous inflammatory lesions, and increased level of CRP. Fifty mg/day (1.3 mg/kg day) of oral thalidomide was given for the first four weeks, and then the dose was increased to 75 mg/day. Clinical manifestations subsided, and inflammatory markers had clearly improved. Frequent high fever and local severe pain with calcinosis were suppressed. The levels of FDP-E, IgG, and tryglyceride, which were all elevated before the thalidomide treatment, were gradually returned to the normal range. Over the 18 months of observation up to the present, she has had no inflammatory calcinosis, or needed any hospitalization, although established calcium deposits still remain. Her condition became painless, less extensive and less inflammatory with the CRP level below 3.08 mg/dL. Recent examination by whole-body 18F-FDG-PET-CT over the 15 months of thalidomide treatment demonstrated fewer hot spots around the subcutaneous calcified lesions.
 ...
PMID:Efficacy of thalidomide in a girl with inflammatory calcinosis, a severe complication of juvenile dermatomyositis. 2018 Oct 85

We reported 37 patients with myelodysplastic syndromes (MDS) of refractory cytopenia with multilineage dysplasia or refractory anemia with excess blasts who were treated with cyclosporin A (CyA)/thalidomide combination therapy. Of them, 19 patients (19/37, 51.4%) achieved a hematologic improvement and erythroid response (HI-E); 9 patients (9/29, 31.0%) achieved hematologic improvement and platelet response (HI-P) and 7 patients (7/33, 21.2%) achieved hematologic improvement and neutrophil response (HI-N). 15 of 32 (46.9%) transfusion-dependent patients achieved independence from transfusion. The median response duration of HI-E, HI-P and HI-N were 88 (4-108) weeks, 78 (8-84+) weeks and 78 (10-84+) weeks, respectively. Some patients presented with I or II grade hepatic or nephritic impairment, constipation, lethargy, dizziness, edema, rash or sense of numbness. Therefore, CyA combined with thalidomide appears to be useful and is relatively well-tolerated for patients with MDS.
 ...
PMID:Cyclosporin A and thalidomide in patients with myelodysplastic syndromes: Results of a pilot study. 2059 81

Macrophage activation syndrome is a form of secondary haemophagocytic lymphohistiocytosis seen in the context of rheumatic diseases. It is seen most frequently in association with systemic onset juvenile arthritis or childhood Still's disease. Hemophagocytosis is part of a sepsis-like clinical syndrome caused by hypercytokinemia due to a highly stimulated but ineffective immune response. Coagulopathy and hemorrhages, decreased white cell count, elevated levels of aspartate aminotransferase, fever, rash, hepatosplenomegaly and central nervous system dysfunction are some of diagnostic criteria of macrophage activation syndrome, but it is very difficult to diagnose due to the lack of specific clinical signs. We report a 8-year-old child who was admitted to the ICU with lethargy, fever, acute respiratory failure, coagulopathy, metabolic acidosis and multiorgan failure. Septic shock was suspected, but he was diagnosed with macrophage activation syndrome and treated with corticosteroids and intravenous immunoglobulin and later discharged from the ICU.
 ...
PMID:[Multi-organ failure as first clinical sign of macrophage activation syndrome in childhood Still's disease]. 2064 91

This article describes the case of a 16-month-old Hispanic male toddler with cow's milk allergy living in northern California who was admitted to a children's hospital for weight loss and markedly elevated levels of serum alkaline phosphatase and parathyroid hormone. At a routine outpatient well-child visit, his mother expressed concern about a decrease in his appetite and activity level. A detailed diet history revealed that breast milk was his primary source of nutrition during his first year of life and he had not been given supplemental vitamins. With attempts to introduce cow's milk formula, he had developed a rash and swelling around the mouth. Shortly after his first birthday, his mother weaned him from breast milk and introduced unfortified rice milk as a palatable milk substitute. Upon admission he was pale and lethargic; his laboratory studies were remarkable for elevated serum alkaline phosphatase and parathyroid hormone and low levels of phosphorus, 25-hydroxy-vitamin D, and ferritin. Lower extremity radiographic studies were consistent with rickets. After 5 weeks of therapy with vitamin D(3) and iron, his serum 25-hydroxy-vitamin D level normalized. Within 12 weeks following therapy, the child demonstrated significant clinical improvement, with resolution of growth failure and bone reossification. His activity level had returned to normal. This case emphasizes the importance of adequate vitamin D intake for children with special attention to those who might have nutrition deficiencies attributable to milk allergy.
 ...
PMID:Vitamin D--deficient rickets in a child with cow's milk allergy. 2809 94


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