Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We identified 68 patients with clonal T-large granular lymphocyte (T-LGL) proliferations who were seen at the Mayo Clinic between 1984 and 1992. Nineteen (28%) were asymptomatic at diagnosis, while the rest experienced fatigue (60%), B-symptoms (12%), and recurrent infections (15%). Associated comorbid conditions included rheumatoid arthritis (RA) in 26%. Severe anemia (hemoglobin [Hb] < 8g/dL) and neutopenia (absolute neutrophil count [ANC] < 500/microL) were seen in 19% and 40% of patients, respectively. Immunophenotypic studies showed CD3+, CD8+ phenotype in the majority (72%). Twenty-one patients (31%) have required no therapy, and remain relatively stable with a median follow-up period of 50 months. Treatment was required at either diagnosis (36 patients) or at subsequent follow-up (11 patients). Initial response rates were similar in patients treated with cyclophosphamide (CTX) with or without prednisone (69%), or prednisone alone (73%). Overall, 61 patients (90%) are alive with a median follow-up of 44 months. Actuarial median survival of this entire cohort is 161 months. The presence of anemia or symptoms does not appear to correlate with the tumor burden. In patients requiring therapy, a lower ANC and the presence of B-symptoms/infection were independently associated with a significantly lower probability of achieving a molecular or hematologic complete remission (H-CR). Intermittent immunosuppressive therapy is effective in achieving durable responses in a number of patients. T-LGL proliferations are associated with a favorable prognosis and response to therapy. However, significant heterogeneity exists in clinical presentation and associated comorbid conditions. These disorders should be included in the differential diagnosis of patients with unexplained cytopenias, particularly in the setting of RA and other autoimmune disorders. Analogous to the situation with monoclonal gammopathies, a term such as T-cell clonopathy of undetermined significance (TCUS) may be more appropriate to describe these patients.
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PMID:Clinical spectrum of clonal proliferations of T-large granular lymphocytes: a T-cell clonopathy of undetermined significance? 806 51

This case report contains the history of a man's exposure to benzene, trichloroethylene, and toluene. J suffered acutely from classic symptoms of toxic exposure to these compounds, such as fatigue, clumsiness, staggering, and hematopoietic depression. During his medical hospitalization, he was exposed to further organic insults, such as being treated with medications like Cytoxan and medications to treat an abscess in his right parietal lobe. After the acute exposure and after the abscess had resolved, his functioning on neuropsychological testing was still depressed, as he had a Full Scale IQ of 105, whereas at the time of the forensic evaluation he had a Full Scale IQ of 114. It would therefore appear that he did have some mild deficits when originally discharged from the hospital. While he reported having continual mental status changes at the time of the offense and even at the time of the forensic evaluation, it was not felt that these played a significant role in the commission of the offense. Comprehensive forensic evaluation suggested that psychological reactions to his illness and an underlying personality disorder were more direct contributors to the criminal acts. J was therefore recommended and ultimately found to be responsible for his behavior, according to the law.
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PMID:Criminal responsibility and solvent exposure. 893 24

Cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisolone (CHOP) has for many years been the standard chemotherapeutic regimen for patients with aggressive non-Hodgkin's lymphoma. Published data for side effects experienced by patients undergoing CHOP chemotherapy in the treatment of non-Hodgkin's lymphoma are limited and inconsistent. No broad descriptive work appears to have been carried out. This study aimed to describe the range of problems experienced by patients receiving CHOP and to estimate incidence and severity of side effects over the treatment period. Data were collected at each treatment cycle via a 75-item self-report questionnaire, with severity of each side effect graded on a 5-point scale. The instrument has previously been shown to be reliable and valid. Nineteen participants received 99 cycles of CHOP and returned 74 questionnaires (response rate = 75%). Patients reported a total of 80 side effects. Alopecia was the most common problem, with all patients experiencing some hair loss by cycle 3. Fatigue was the second most common side effect (incidence = 77%) and taste change the third (incidence = 74%). Patients judged postchemotherapy nausea to be the "most troublesome" problem, followed by fatigue, taste change, constipation, and difficulty sleeping. Both nausea and fatigue were most problematic in the first part of the treatment course. These results indicate that patients receiving CHOP experience a wide range of problems, many of which merit further investigation.
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PMID:Side effects of CHOP in the treatment of non-hodgkin's lymphoma. 940 65

From June 1984 to October 1995, forty seven consecutive patients (pts) with a confirmed diagnosis of diffuse malignant mesothelioma (MM) of the pleura (41) and peritoneum (6), were treated with cisplatin (CDDP) (24 pts) (Group A), or Doxorubicin (ADM) (14) based chemotherapy (Group B), or a combination of CDDP and ADM (9 pts) (Group C). Chemotherapy for Group A was CDDP 100 mg/m2 Dl with Viblastine 6 mg/m2 Dl, 8 (24 pts) for Group B ADM 40 mg/m2 D I with Vincristine (VCR) 2 mg Dl and DTIC 200 mg/m2 Dl-3 (5 pts) or instead of DTIC Cyclophosphamide 600 mg/m2 Dl instead (pts 4). A Total of 11/47 (23%) of the pts responded to chemotherapy; Group A: I complete and 5 partial responders, Group B: 3 partial responders and Group C: 2 partial responders. Pts with MM of peritoneum showed I complete (Group A) and 4 partial (Group B: 2, Group B: 1, Group C: I) responses, a total of 5/6 (83%). There was no difference in survival time, duration of response and time to progression between the examined groups. A statistically significant difference between responders and non responders in terms of survival was seen: responders 20.8 (3-35), non-responders 5.05 (1-12) months (P = 0.03). Toxicity was acceptable and no treatment-related deaths occurred. Myelo-suppression, mild anemia, nausea-vomiting, anorexia and fatigue were the main toxicities. We conclude that CDDP or ADM-based chemotherapy or a combination of both drugs are equally effective in MM.
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PMID:Combination chemotherapy with cisplatin and/or doxorubicin in malignant mesothelioma. A retrospective study [corrected from prospective]. 942 83

A chemotherapeutic protocol for advanced thymic carcinoma has not been established as yet. We described a case of advanced and relapsed thymic carcinoma that responded remarkably to subsequent chemotherapy with CPT-11. A 61-year-old man was admitted to our hospital because of facial edema and general fatigue. Chest X-ray and CT scan showed anterior mediastinal tumor which involved large vessels and pericardium. CT guided needle biopsy yielded a diagnosis of squamous cell type of thymic carcinoma. The patient was initially treated with ADOC (ADM, CDDP, VCR, CPA) chemotherapy and had successfully controlled for six months. However, the mediastinal tumor recurred and radiotherapy and nedaplatin plus ETP therapy were not effective. Then, CPT-11 chemotherapy (80 mg/m2, 2 weeks) was performed. The patient showed a partial response after two courses of CPT-11 chemotherapy. This case suggests that CPT-11 is a useful chemotherapeutic agent for advanced thymic carcinoma.
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PMID:[A case of relapsed thymic carcinoma that responded remarkably to chemotherapy with CPT-11]. 983 15

Eight years after diagnosis, 40% of MS patients develop a chronically progressive form. Annually we treat approximately 200 patients with progressive MS. Treatment consists of medication, i.e. agents that help to prevent future impairment, or interferon-beta injections, and intervals of mitoxantrone infusions (Novantrone(R)), and in some cases cyclic cyclophosphamide (Endoxan(R)) or nucleoside analogue cladribin (Leustatin(R)). Without clear scientific evidence, we recommend unsaturated fatty acids (thistle or sunflower oil), sufficient protein, and freshly prepared fruits and vegetables as a sound basis for remyelination. Remyelination profits from general prophylaxis in the use of ascorbic acid to help prevent urinary infections via acidification, autogenic training to reduce fatigue, improve ventilation of deeper airways, and stimulate vagotonic regeneration, and prevention of unnecessary immune stimulation caused by insects and some food. We recommend the use of sun hats and disencourage blood donation (Allain 1998). Physiotherapy can improve strength, reduce spasticity, and train the patient to compensate for dysbalance and ataxia; supported by beta blockers and good antispastics, tremor and gait disturbances can be positively influenced. Music and motion, speech therapy, realistic training of daily activities, and prudent psychotherapy complete the range of measurements to reconstitute as much as possible of the patient's individual freedom. In the individual, we eventually provide prudent technical aids and careful prognostic estimations. Cooperating with local and regional patient networks, we reinforce long-term disease management and spread up-to-date medical research results, and finally gather valuable contextual information and clinical data on an increasingly frequent idiopathic disease of the human central nervous system.
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PMID:Medical rehabilitation of chronic progressive disseminated encephalomyelitis (MS). 1087 9

To test the hypothesis that adenosine improves skeletal muscle cell function, we exposed curarized mouse soleus and extensor digitorum longus (EDL) to a range of concentrations of adenosine (10(-9) M to 10(-5) M). Muscles contracted in Krebs-Henseleit bicarbonate buffer (27 degrees C, 95% O2 and 5% CO2) for 500 ms at 50 Hz once every 90 s. Soleus fatigued significantly less with adenosine present at concentrations of 10(-8) M and higher than with the Krebs-Henseleit vehicle control. Adenosine significantly improved force generation or delayed fatigue of EDL only with the initial adenosine challenge. To investigate the receptor population involved, we exposed soleus to agonists specific for A1 receptors (N6-cyclopentyladenosine, CPA), or A2 receptors (CGS 21680 hydrochloride, CGS), or A3 receptors (N6-benzyl-5'-N-ethylcarboxamidoadenosine, BNECA). CPA (A1) significantly decreased fatigue compared with the Krebs-Henseleit vehicle control at concentrations of 10(-9) M and higher. Muscles exposed to the A2 and A3 agonists did not differ from a Krebs-Henseleit plus methanol control. Phenylephrine (10(-6) M), an alpha-adrenergic agonist that increases the concentration of inositol triphosphate (IP3), significantly improved developed force in soleus. Neither a permeable cAMP analog, 8-bromo-cAMP (10(-5) M), nor a beta, agonist, isoproterenol (10(-6) M), had an effect on force generation in the soleus when compared with a saline control. Thus adenosine slowed fatigue in slow-twitch skeletal muscle through A1 receptors.
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PMID:A1 receptor activation decreases fatigue in mammalian slow-twitch skeletal muscle in vitro. 1143 May 87

Dermatomyositis and polymyositis are the two major idiopathic inflammatory myopathies. The Bohan and Peter's criteria are still useful despite the probably different pathogenesis of the two myopathies. Cutaneous manifestations of dermatomyositis include heliotrope rash and Gottron's papules. The heliotrope rash, with or without edema, in a distribution involving periorbital skin is very suggestive of the diagnosis. Papules may be found overlying the "kneedle" of the hand or the elbows, knees, feet. Periungueal erythema with telangiectasis were characteristic but not pathognomonic. Scalp involvement is common. Skin lesions of dermatomyositis may precede the development of the myopathy and may persist after the control of the myositis. Some patients have an amyopathic dermatomyositis with normal muscle-enzyme, magnetic resonance scan and muscle biopsy. Muscle disease affects the proximal muscles, is generally symmetrical and symptoms are fatigue, weakness and sometimes myalgia. Proximal dysphagia reflects an involvement of striated muscle of the pharynx or proximal esophagus. Camptocormia reflects a severe involvement of paravertebral muscle. Other systemic features may be seen: pulmonary involvement (mostly interstitial pneumonitis and hypoventilation), arthralgias or arthritis, cardiac involvement, vasculatis and calcinosis particularly in children or adolescents with dermatomyositis. Malignant disease is associated with idiopathic inflammatory myopathies with a frequency of approximatively 10 to 15% in dermatomyositis and 5 to 10% in polymyositis and is strongly correlated with age, more than 50% of the patient over 65 years old were found to have a cancer. In the absence of malignant disease, the mainstay therapy for dermatomyositis and polymyositis is systemic corticosteroids (mostly 1mg/kg). In the lake of response or high dose dependance, intravenous immunoglobulins or immunosuppressive drugs like methotrexate or azathioprine may be discuss. Cyclophosphamide show some effectiveness in interstitial pneumonitis. Cyclosporin might be effective in children, less in adults. The efficacy of tacrolimus, mycophenolate mofetil, leflunomide and anti-TNF therapy need some prospective studies to determine if there are of value in idiopathic inflammatory myositis.
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PMID:[Dermatomyositis and polymyositis: clinical aspects and treatment]. 1196 87

ASTA Medica is developing retigabine, a carbamic acid ethyl ester and a selective potassium channel opener, for the treatment of complex partial seizures. Phase II trials have commenced [249117], and a multicenter placebo-controlled dosage-finding study has begun in Europe and Australia [392702]. Retigabine is also undergoing phase II testing in Germany, Switzerland, Russia and the US for the potential treatment of epilepsy [323383]. Phase II trials have shown >50% reduction in seizure frequency in 12 of 35 patients with refractory epilepsy [373379]. Phase I clinical trials for epilepsy were successfully completed in Germany in 1995 [180371]. Single and multiple dose trials demonstrated the tolerability and favorable pharmacokinetic behavior of the compound [264306]. The compound showed good compatibility and exhibits an antisense anticonvulsive effect in various preclinical epilepsy models [250565,299344]. Side effects of mild to moderate tiredness, fatigue and nausea were observed [276123]. The spectrum of activity of retigabine resembles that of valproate, but its potency is greater and toxicity is reduced [373379]. The mechanism of action of retigabine is probably multifactorial. Research has shown that retigabine acts as a selective K+ channel opener in neuronal cells and this can be expected to contribute to its anticonvulsant effect [273670]. In addition it demonstrates potentiation of GABA transmission and possibly also weak modulation of sodium and calcium channels [299344]. Retigabine also has neuroprotective activity with potential for the treatment of stroke and neurodegenerative diseases, such as Alzheimer's disease, Huntington's disease and multiple sclerosis [249381]. In February 2000, Lehman Brothers predicted product launch could be as early as 2002 for epilepsy in the US [357788]. In February 1999, Lehman Brothers predicted that the first major launch date of the drug would be 2003, and the year of peak sales to be 2011 [319225].
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PMID:Retigabine (ASTA Medica). 1603 7

There is accumulating evidence that mycophenolate mofetil (MMF), when combined with corticosteroid, is an effective induction treatment for severe proliferative lupus nephritis and is associated with fewer adverse effects compared to cyclophosphamide (CTX), but the quality of life (QOL) associated with these regimens as perceived by the patient has not been compared. This study included patients who had experienced both treatment regimens, for distinct episodes of diffuse proliferative lupus nephritis. QOL parameters during the first six months of each treatment were assessed through SF36 and WHOQOL questionnaires. Twelve patients and 24 episodes of severe lupus nephritis were studied. CTX-treated and MMF-treated episodes showed comparable baseline characteristics and response rate, with complete remission occurring in 83.3%. MMF treatment was associated with higher numerical scores for all domains across both QOL instruments than CTX. MMF treatment was associated with significantly less fatigue, less impediment of physical and social functioning, and better psychological well being compared to CTX. When each patient served as her/his own control, most patients ascribed higher QOL domain scores to the MMF-treated episode. Seventy-five percent of patients found MMF treatment more acceptable and preferred when compared with CTX, and the complications that most concerned them included Cushingoid features, alopecia, menstrual disturbance and infections. These data showed that MMF-based induction immunosuppression for severe lupus nephritis was associated with better QOL than CTX as perceived by patients, which was most likely attributed to the reduced side-effects during MMF treatment.
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PMID:Quality of life comparison between corticosteroid- and-mycofenolate mofetil and corticosteroid- and-oral cyclophosphamide in the treatment of severe lupus nephritis. 1683 Aug 84


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