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)

High-dose therapy with interleukin-2 (IL-2) can produce significant responses in patients with metastatic melanoma (MM) and renal cell carcinoma (RCC). Several studies have shown the benefit of low-dose IL-2 in patients with RCC, but few studies have evaluated low-dose IL-2 in MM. We have used the following regimen: Interferon-alpha 10 million units subcutaneously on days 1, 3, 5, 8, 10, 12, 22, 24, and 26; and IL-2 60,000 IU/kg i.v. every 8 h on days 8-12 and 22-26. Patients had measurable MM or RCC and were excluded for ECOG status > 3, brain metastases, or significant cardiopulmonary or renal dysfunction. Between January 1993 and April 1996, 38 patients with MM and 14 with RCC were treated. In MM, there were six responses (15.7%; 95% confidence interval 4.1-27.3%) (i.e., one complete response and five partial responses). Responses were seen in visceral and nodal disease. Responses were of good duration: 40+, 26+, 13, 6, 4, and 3 months. One response was seen in the 14 RCC patients. Treatment was considerably less toxic than with high-dose IL-2. All treatment was given in a medical or surgical ward with intensive care necessary in only two patients. More than 80% of patients received > 80% of the predicted dose of IL-2. Dose-limiting toxicity consisted mainly of mild confusion or fatigue. In summary, this regimen is better tolerated and produces response rates within the range reported for high-dose IL-2 for patients with MM.
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PMID:Low-dose intravenous bolus interleukin-2 with interferon-alpha therapy for metastatic melanoma and renal cell carcinoma. 945 37

We report a family in which the mother and her three sons suffered sick sinus syndrome and strabismus. Two members had a persistent left superior vena cava with drainage into coronary sinus. The illness in all members of this family was oligosymptomatic, and well tolerated with mild symptoms like dizziness, fatigue and exercise dyspnea associated with nodal rhythm. Three of them, had episodes of paroxysmal atrial fibrillation. All patients remain asymptomatic after pacemaker implantation.
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PMID:[Familial sick sinus syndrome associated to strabismus and persistent left superior vena cava]. 1097 40

Ajmaline is a well-known atrioventricular (AV) node depressant agent, but its effects on functional properties of the AV node and on experimental AV re-entrant tachycardia have not been explored. The aims of the present study were (1) to determine whether ajmaline administration modifies the rate-dependent properties of the AV node and (2) to correlate these changes with the actions of ajmaline on an in vitro model of AV re-entrant tachycardia. Selective stimulation protocols and mathematical formulations were used to quantify independently AV node recovery, facilitation, and fatigue in 10 isolated rabbit AV nodes. Ajmaline decreased facilitation and fatigue and had no significant effect on AV node recovery. The most important effect of ajmaline was rate-induced prolongation of AV node effective refractory period, resulting in a greater increase in tachycardia cycle length. AV re-entrant tachycardia was sustained when AV effective refractory period divided to tachycardia cycle length was less than 1, ajmaline suppressed AV re-entrant tachycardia by increasing the slope of the AV effective refractory period divided to tachycardia cycle length versus tachycardia rate relation, causing the critical ratio of 1 to be attained at a slower rate. A mathematical model incorporating quantitative descriptors of recovery, facilitation, and fatigue accounted for changes in nodal conduction time, AV effective refractory period, tachycardia cycle length, and AV effective refractory period divided to tachycardia cycle length under all conditions. It can be concluded that (1) ajmaline increases AV conduction time, decreases AV node fatigue, and facilitation, without altering AV node recovery. (2) Ajmaline significantly prolongs AV effective refractory period in a rate-dependent manner. (3) These changes play a role in ajmaline's actions on experimental AV re-entrant tachycardia. Ajmaline's ability to terminate re-entrant supraventricular tachycardia may be due, at least in part, to its ability to amplify the rate-induced prolongation of the nodal refractory period.
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PMID:Effects of ajmaline on rate-dependent atrioventricular node properties. Potential role in experimental atrioventricular re-entrant tachycardia. 1116 39

Twenty-three adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or prolymphocytic leukemia (PLL) were treated for up to 12 weeks with the anti-CD52 monoclonal antibody alemtuzumab. Patients were a median of six years from diagnosis and had been treated with a median of four chemotherapy regimens (median of 24 total cycles) prior to enrollment. Fourteen patients (61%) had received prior monoclonal antibody therapy with rituximab. Adverse symptoms were primarily mild to moderate fever, rigor/chills, nausea/vomiting, or fatigue/malaise in up to 86% of patients. Patients with low blood counts at the initiation of alemtuzumab tolerated therapy well. A total of 17 patients were evaluable for disease response. Nine patients (53%) responded with complete remissions in the peripheral blood. Of these nine, five were evaluated by bone marrow biopsy with four complete responses (CR) and one partial response. Six of the nine presented with nodal disease at the start of alemtuzumab therapy with three CRs and three partial responses. Alemtuzumab is a monoclonal antibody that offers effective treatment for chemotherapy refractory CLL and PLL and is generally well tolerated in the outpatient setting.
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PMID:Alemtuzumab in relapsed or refractory chronic lymphocytic leukemia and prolymphocytic leukemia. 1214 79

A 75-year-old man was admitted to our hospital complaining of gastric fatigue. Endoscope and CT scan revealed type 3 gastric cancer with paraaortic lymph nodal metastasis. Histological examination of the endoscopic biopsy revealed poorly differentiated adenocarcinoma. A blood examination and bone marrow biopsy revealed DIC causing bone marrow carcinosis. Chemotherapy with sequential therapy consisting of MTX and 5-FU was performed. Stretch of the fold and flatness of the ulcer were obtained against the gastric primary lesion observed endoscopically. Complete response was obtained against the lymph node around the abdominal aorta. Reduction of low back pain and DIC were observed. He was thus able to be discharged and sequential therapy was performed again over 2 months in outpatient care.
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PMID:[A case of advanced gastric cancer with DIC treated by sequential MTX and 5-FU]. 1504 48

A few series in the literature were published before 1987 on syndrome of inappropriate antidiuretic hormone secretion (SIADH) in small cell lung cancer (SCLC). This study examines the outcome in more recent era. From 1981-1998, there were 1417 new cases of SCLC diagnosed in the provincial registry, of which 244 were of limited stage (LS). A chart review and statistical analyses were performed using Mann-Whitney test, chi-square test and Kaplan-Meier method. Fourteen LS patients (group A) had SIADH at presentation. Group B consisted of 230 LS patients without SIADH. There were more patients with poorer performance status (ECOG 2-4) in group A than B (28.6% versus 7.8%, P=0.03). Otherwise, sex, age at diagnosis, nodal spread, pleural effusion, bronchial obstruction, superior vena cava obstruction, performance status, weight loss, and lactic dehydrogenase at presentation, were comparable between the two groups. Treatments given, e.g., extent of surgical resection (if performed, whether complete/incomplete), total number of chemotherapy cycles, radiotherapy doses, were comparable (P>0.05). The response to chemo-radiation was not significantly different (P=0.7). Five-year overall survival (8% versus 19%, P=0.08), and cause-specific survival (16% versus 20%, P=0.13) showed that group A patients had a worse outcome, though of borderline significance. Symptoms related to SIADH included: weakness, 4 patients; tiredness, 3; change in level of consciousness, 1; seizure, 1. The range of lowest sodium level was 110-129. Two patients also had paraneoplastic myopathy. SIADH resolved in 12 patients at 1.6-44.7 weeks (median: 4.3). Among the 14 patients who initially presented with SIADH and recurred later, 10 had recurrence of SIADH at the time of tumor recurrence. Serum sodium was useful for post-treatment surveillance in SCLC patients who presented with SIADH, with 71% (10/14) developing SIADH again at the time of recurrence. SIADH is a poor prognostic factor for LS SCLC.
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PMID:Syndrome of inappropriate antidiuretic hormone secretion (SIADH) in patients with limited stage small cell lung cancer. 1678 84

A healthy 59-year-old man, a retired general practitioner, suffered from increasing palpitations, fatigue and postural dyspnoea: bending over led to a significant increase in his shortness of breath. Cardiological and pulmonological examination, performed at regular intervals, showed occasional supraventricular arrhythmia and nodal tachycardia but did not yield a satisfactory explanation for the symptoms. In the years that followed, the physical impairment became a considerable handicap. Finally, the patient himself suggested a possible explanation on the basis of an Internet search: his pectus excavatum. A literature search confirmed this hypothesis. A lateral chest X-ray in bending position and a CT-scan of the chest revealed compression of the heart by the sternum. Ten years after the onset of symptoms, a modified Ravitch operation finally brought nearly complete recovery.
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PMID:[Cardiac symptoms due to pectus excavatum in a man over the age of 55]. 1832 16

The present study was undertaken to evaluate the role of Na(+)/K(+) pump dysfunction in the development of diabetic neuropathy (DN). Nerve excitability techniques, which provide information about membrane potential and axonal ion channel function, were undertaken in 15 patients with established DN and in 10 patients with diabetes who had no evidence of neuropathy (DWN). Excitability parameters were recorded at baseline, and then before and after 1 min of maximal voluntary contraction (MVC) of abductor pollicis brevis. Compared to controls, CMAP amplitude was significantly decreased in DN patients with associated reductions in strength-duration time constant and refractoriness, consistent with a reduction in nodal Na(+) conductances. Following MVC for 1 min, there was an increase in normalized threshold in all diabetic patients and controls, consistent with axonal hyperpolarization. When compared to control values, the increase in threshold following MVC was significantly less in DN patients (DN group 13.1 +/- 2.2%; controls 20.4 +/- 1.9%; P < 0.05) and the rate of recovery was slower (P < 0.01). In DWN patients, CMAP amplitude was preserved, and excitability values following MVC were not significantly different to control values. The reduced threshold change and slower recovery in DN patients following MVC are likely to be secondary to Na(+)/K(+) pump dysfunction. Alteration in Na(+)/K(+) pump function, coupled with reductions in nodal Na(+) currents, may be sufficient to trigger conduction failure in DN patients and are likely to contribute to the clinical symptoms of weakness and fatigue.
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PMID:Activity-dependent excitability changes suggest Na+/K+ pump dysfunction in diabetic neuropathy. 1836 98

It is known that adrenal insufficiency is one of the complications in primary adrenal lymphoma, especially those with bilateral adrenal involvement. A 73-year-old man was referred for general fatigue and high fever to the nearest hospital. The patient was transferred to our hospital for evaluation of bilateral adrenal tumors and hyponatremia. He was diagnosed as having non-Hodgkin's lymphoma (NHL) with primaries arising in both adrenal glands. Primary adrenal lymphoma (PAL) is a rare extra-nodal NHL. Although an appropriate treatment of this disease has not been established, our case has demonstrated that the combination of rituximab and THP-COP chemotherapy could be administered, and that it improved clinical manifestations. This case raises the suggestion that malignant lymphoma should be suspected in patients with bilateral adrenal tumors that present with progressive adrenal insufficiency.
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PMID:A case of non-Hodgkin's lymphoma primary arising in both adrenal glands associated with adrenal failure. 1900 13

Conjugated organic molecules with photochromic properties are being extensively studied as prospective optical switching and data storage materials. Among different photochromic compounds, diarylethenes demonstrate thermal stability, fatigue resistance, and high quantum yield. The mechanism of photoswitching in diarylethenes involves a symmetry-allowed conrotatory electrocyclic reaction, initiated by UV light. Replacement of one UV photon with two near-IR ones would offer a number of practical advantages, including drastic increase in storage capacity via three-dimensional multilayer design. For this purpose we designed a prototype molecule with a two-photon absorbing (2PA) pendant substituent, attached to the photochromic diarylethene moiety. However, this molecule was experimentally shown to have lost the photoswitching properties. We analyze reasons for this loss using quantum chemistry tools. Analysis of the nodal structure of the frontier Kohn-Sham orbitals, allowed us to trace the route of the problem to the lone pair orbital of the 2PA substituent falling within the HOMO-LUMO (highest occupied molecular orbital-lowest unoccupied molecular orbital) gap of the photoreactive diarylethene moiety. We suggest a chemical modification of the 2PA substituent in order to restore the order of the orbitals. Potential energy plots along the reaction coordinate at the M05-2X/6-31G* theory level for the prototype 2PA photochromic molecule before and after the modification confirm the predictive capability of the proposed orbital approach. The Slater transition state method was used to obtain geometries along the reaction pathway by the constrained optimization of excited states, whereas potential energy curves were plotted using the recently proposed (Mikhailov, I. A.; Tafur, S.; Masunov, A. E. Phys. Rev. A 2008, 77 (1), 012510) a posteriori Tamm-Dancoff approximation to the time-dependent density functional theory in second order of the external field. We show that this combination is able to produce accurate potential surfaces for 1B and 2A excited states, as compared to available experimental data and results of high-level multireference wave function theory methods.
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PMID:DFT-based methods in the design of two-photon operated molecular switches. 1948 Apr 2


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