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)

An 11-year-old boy with univentricular heart type A-III underwent surgical treatment at age 10 with a modified Fontan operation. Six months postoperatively he developed intermittent periods of cyanosis and fatigue associated with profound sinus bradycardia and nodal escape. After demonstrating normal atrioventricular conduction, a transvenous atrial pacemaker was implanted. This produced a marked clinical improvement. Transvenous atrial pacing is a satisfactory method of treating sinus node dysfunction in patients with univentricular heart following the Fontan operation provided that there is normal AV conduction.
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PMID:Transvenous atrial pacing in the management of sick sinus syndrome following surgical treatment of the univentricular heart: case report and review. 242 87

The slowly developing rate-induced prolongation in atrioventricular nodal conduction time, termed "fatigue," was selectively studied using specifically designed stimulation protocols in isolated rabbit heart preparations. A nodal recovery curve (A2H2 versus H1A2 intervals; nodal conduction time of each premature beat plotted against corresponding recovery time) was obtained before and after a stable and nearly maximum fatigue had been reached by driving the atrium for 5 minutes at a fast rate close to the upper limit of 1:1 nodal conduction. The fatigue uniformly prolonged all A2H2 intervals (12.3 +/- 1.3 msec) and systematically increased the minimum H1A2 interval at which complete nodal block occurred (24.8 +/- 4.0 msec) (p less than 0.01, n = 6). To study the rate and time dependence of fatigue, nodal conduction times were obtained during three rapid 5-minute pacings corresponding to 50%, 75%, and 100% shortening of the pacing interval in the 1:1 nodal conduction range. The respective maximum fatigue-induced increases in conduction time were 5.4 +/- 1.8, 9.0 +/- 2.7, and 12.5 +/- 2.1 msec (p less than 0.01, n = 6). However, the pacing interval had no significant effect on the time required to reach either 50% (17.1 +/- 3.5 seconds) or 90% (92.6 +/- 15.4 seconds) of the fatigue observed after 5 minutes of fast rate. At the termination of any rapid stimulation, the fatigue effect dissipated with a time course that was inverse but symmetrical to that of its induction. These findings support the existence of an independent, slow, nodal memory process by which the conduction time changes according to past events with a long time constant.
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PMID:Selective functional characteristics of rate-induced fatigue in rabbit atrioventricular node. 245 Jun 96

The characteristics and origin of the rate-induced changes in atrioventricular nodal conduction time of premature beats (A2H2 intervals) were studied in isolated rabbit heart preparations. Increasing the basic driving rate during a periodic premature stimulation prolonged (a net inhibitory effect) and shortened (a net facilitatory effect) significantly (p less than 0.01, n = 17) the A2H2 intervals associated with long and short recovery times (H1A2 intervals), respectively. The origin of these responses was sought for by analyzing interactions between facilitation and fatigue. When the fatigue developed at a fast basic rate was estimated from changes in conduction time of basic beats and subtracted from the corresponding A2H2 intervals, the calculated A2H2 intervals showed enhanced facilitation but no fatigue. When independently obtained fatigue and facilitation effects were added to the control A2H2 intervals for corresponding H1A2 intervals, resulting A2H2 intervals correlated strongly with the ones observed at the equivalent fast basic rate (r = 0.99, p less than 0.001). Moreover, changes in the A2H2 intervals of premature beats tested with constant coupling intervals during 5-min fast rates were biphasic, confirming the overlapping and competition between facilitation and fatigue effects. Hence, rate-induced deviations of premature nodal conduction time from that predicted by changes in recovery time are consistent and result from the interaction between the overlapping effects produced by two independent, antagonist, and dynamically distinct nodal properties (facilitation and fatigue).
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PMID:Functional origin of rate-induced changes in atrioventricular nodal conduction time of premature beats in the rabbit. 245 77

Atrioventricular (AV) block occurring in the His-Purkinje system may occur sporadically and can be difficult to document. In this article, we describe two patients with spontaneous episodes of AV block, in whom the use of upright tilt during electrophysiological testing led to a diagnosis of His-Purkinje disease. In both cases, testing in the supine position only uncovered mild or no abnormalities of infra-nodal conduction. In the first case, high grade block distal to the His occurred and the mechanism appeared to be bradycardia-dependent block. In this case, increased sympathetic tone due to upright tilt may have enhanced the slope of phase 4 depolarization in abnormal His-Purkinje cells, leading to block. In the second case, high grade block distal to the His was seen with upright tilt and the mechanism of block appeared to be fatigue phenomenon in the His-Purkinje system. These cases emphasize the elusive nature and varied mechanisms of His-Purkinje block and illustrate the utility of electrophysiological testing in the upright position in patients with suspected conduction system disease.
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PMID:Bradycardia-dependent block and fatigue phenomenon of the His-Purkinje system manifested during upright tilt. 248 Dec 85

Different aspects of the intrinsic regulation of rate-induced variations of functional refractory period of atrioventricular node (FRPN) were studied in isolated rabbit heart preparations. First, the hypothesis that these variations originate from the net interaction between facilitation and fatigue was tested. For a constant fast rate, selective effects of faciliation and of steady-stage fatigue were independently shown to shorten and prolong, respectively, FRPN while their combined effects were shown to result in intermediate changes corresponding to the sum of their individual effects. Second, selective and combined effects on FRPN were shown to start for rates corresponding to the upper half of the 1:1 nodal conduction range and to reach their maximums at the fastest rate tested. Third, the time-courses of fatigue-induced prolongations in nodal conduction time and FRPN were shown to be closely linked. Facilitation effects on conduction time and FRPN were confirmed, as previously shown for in situ dog hearts, to be linked, but time-independent. Fourth, FRPN was shown not to correspond to particular limits in its subintervals, but to be, nevertheless, related to nodal refractoriness. Fifth, it was demonstrated that, in conditions of combined facilitation and transient fatigue such as those prevailing in current endocavitary investigations of nodal function, FRPN could be shortened, left unchanged or prolonged by a constant fast rate depending on its duration. In conclusion, the present study demonstrates the dual origin of rate-induced FRPN variations, their rate and time dependence, their relation to changes in nodal refractoriness, and their involvements in various nodal responses.
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PMID:Origin, domain, and dynamics of rate-induced variations of functional refractory period in rabbit atrioventricular node. 273 33

The goal of the present study was to document the intrinsic origin of atrioventricular nodal functional properties (recovery time, facilitation, and fatigue) in two groups of six superfused isolated rabbit heart preparations. These properties were determined from recovery curves (A2H2 versus H1A2 intervals) obtained with previously defined periodic premature stimulation sequences performed before and after autonomic blockade demonstrated effective with the injection of agonists. In group 1 preparations, the muscarinic cholinergic and beta-adrenergic receptors were blocked with atropine (1 mg/L) and propranolol (1 mg/L), respectively. The blockade reduced the facilitation and increased the fatigue by the direct membranous effect of propranolol. To avoid this effect in group 2 preparations, propranolol was replaced by sotalol (5 mg/L), which in combination with atropine altered neither the presence nor the magnitude of the functional properties. These results show that the origin of the three nodal functional properties is independent from the autonomic nervous system.
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PMID:Intrinsic origin of atrioventricular nodal functional properties in rabbits. 276 3

To further define the clinicopathologic features and determinants of survival, we reviewed the cases of 110 patients with primary hepatic malignancy managed surgically between 1975 and 1986. Presenting signs of symptoms were pain (57%), fatigue (48%), abdominal mass (40%), and weight loss (33%). Twenty-six percent of patients had a history of hepatitis or cirrhosis. Histopathologically, tumors were hepatocarcinoma (72%), fibrolamellar variant (7%), cholangiocarcinoma (9%), mixed (7%), and other (5%). Resectability rate with curative intention was 67%. Exploration and biopsy alone was performed in 27% and palliative resection in 6%. Hospital mortality was 9%, and serious morbidity was 22%. Perioperative morbidity and mortality were significantly associated with operative blood loss. Median survival was 12.6 months, with a 5-year survival of 18%. Median survival after curative resection was 22.8 months, and 5-year survival was 27%. Univariate analysis showed that female sex, normal performance status, well-differentiated tumor, and curative resection were associated with increased survival; cholangiocarcinoma, nodal metastases, cirrhosis, hypocalcemia, prolonged prothrombin time, and increased serum transaminase and alkaline phosphatase were associated with decreased survival. Cox multivariate analysis showed that curative resection, normal performance status, and well-differentiated tumors were associated with increased survival, and prolonged prothrombin time and hypocalcemia were associated with decreased survival.
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PMID:Primary hepatic malignancy: surgical management and determinants of survival. 279 50

Based upon the in vitro synergistic activity of interferon-beta (IFN-beta) and interferon-gamma (IFN-gamma) observed in melanoma cells, we initiated a Phase II trial using the combination to determine the clinical antitumor efficacy in patients with advanced disease. Fifteen patients with metastatic malignant melanoma were given 2,000 micrograms of recombinant IFN-gamma (rIFN-gamma) (Biogen) intravenously (i.v.) over 10 min, followed by a 10 min i.v. injection of 30 million units of recombinant IFN-beta (rIFN-beta ser) (Triton) 3 x/week. Six patients had skin, soft tissue, nodal, or subcutaneous metastases, 6 had visceral disease only, and 3 had both. Seven patients had received prior treatment, including chemotherapy (6), radiotherapy (3), and/or immunotherapy (3). Side effects included typical IFN constitutional symptoms such as anorexia, fatigue, nausea, and myalgias, but were not dose limiting. The mean drop in the white blood cell count (WBC) following 1 month of therapy, compared to baseline, was 3.3 x 10(3)/mm2 (p = 0.002); the mean increase in SGOT was 24.1 U/l (p less than 0.001). One patient had a dose reduction for Grade III anorexia and fatigue which did not resolve with repeated treatment. One patient with liver metastases had radiographical and clinical stabilization of his disease for 1 year. No responses were seen. The median time to progression was 6 weeks. Two patients' tumors were evaluable in the human tumor colony forming assay (HTCFA) and were markedly sensitive to the antiproliferative effects of IFN combinations. Both patients, however, failed to respond clinically.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase II trial of a combination of interferon-beta ser and interferon-gamma in patients with advanced malignant melanoma. 314 69

Natural killer (NK) cell activity and psychological status were measured at baseline and at 3 months into treatment, as part of the National Cancer Institute (NCI) Protocol 79-C-111, randomizing breast cancer patients to lumpectomy/radiation v mastectomy. Patients who were found to have positive axillary lymph nodes also received combination chemotherapy (Adriamycin [Adria Laboratories, Columbus, OH], plus Cytoxan [Mead Johnson Pharmaceuticals, Evansville, IN] or methotrexate, plus 5-fluorouracil [5-FU]). Seventy-five patients were entered onto this behavioral immunology protocol at the time of data analysis. We reported in an earlier publication that NK activity was an important predictor of patient baseline prognosis relevant to nodal status. In that study, by using multiple regression analyses, 51% of the baseline NK activity variance could be accounted for by entering three distress indicators into the equation (patient "adjustment," lack of social support, and fatigue/depression symptoms). On reassessment of NK activity after 3 months, it was found that NK activity was not affected by the interim administration of chemotherapy and/or radiotherapy. However, consistent with our earlier findings, NK activity levels remained markedly lower in patients with positive nodes than in patients with negative nodes (at 60 to 1 effector to target cell [E:T] ratio, mean of 18% lytic activity v mean of 31% lytic activity [t = 1.87, P less than .05]). Even though average levels of NK activity were lower for patients with more tumor burden, there was still a substantial range of NK activity levels within the node positive patient group, as well as within the patient group as a whole. We hypothesized that differences in levels of NK activity could be predicted on the basis of baseline distress factors found to be significant in our earlier report. In fact, we found that we could account for 30% of NK activity level variance at 3 months follow-up on the basis of baseline NK activity, fatigue/depression, and lack of social support. Therefore, although neither radiation nor chemotherapy appeared to affect NK activity, tumor burden was again clearly associated with NK activity levels, and a significant amount of baseline and 3-month NK activity could be predicted on the basis of CNS-mediated effects. At the least, such factors provide a psychological marker of host biological status.
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PMID:Correlation of stress factors with sustained depression of natural killer cell activity and predicted prognosis in patients with breast cancer. 354 12

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administered by a 3-hour infusion causes a rapid decline to and recovery from the hematologic white blood cell nadir. This suggests that biweekly administration of paclitaxel alone or in combination with drugs that have limited hematologic toxicity may be possible. The first study discussed in this report tried to determine the tolerability and activity of biweekly paclitaxel administered in combination with cisplatin in patients with metastatic breast cancer. Subsequently, after an impressive response rate, a second study of biweekly paclitaxel alone was initiated to attempt to discern which activity spectrum and which toxicities were due to paclitaxel and which were due to cisplatin. Patients with metastatic breast cancer who received up to one prior adjuvant chemotherapy regimen were eligible for both studies. Paclitaxel was administered intravenously by a 3-hour infusion followed by intravenous cisplatin biweekly in the ambulatory setting. In the second study, paclitaxel was administered alone. Twenty-nine patients have been entered in the combination study, of whom 27 had received prior adjuvant therapy and 23 had received prior anthracyclines. Dose-limiting toxicity for the phase I study of paclitaxel and cisplatin proved to be a failure to recover neutrophil counts greater than 750 cells/microL by day 14. The maximum tolerated dose was paclitaxel 90 mg/m2 and cisplatin 60 mg/m2 every 2 weeks. Nonhematologic toxicities were mild and included fatigue, arthralgias, and nausea and vomiting. At this time, the 27 patients evaluable for response have achieved an 85% response rate and an 11% complete response rate. Complete responses have been seen in soft tissue, lung, and nodal disease. All patients with complete responses have had previous anthracyclines. The biweekly paclitaxel-alone study is still accruing patients. The current paclitaxel dose level is 150 mg/m2. It is still too early to evaluate response; however, response rates appear to be less impressive than those seen with combined paclitaxel/cisplatin. The final results of these studies are pending.
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PMID:Biweekly paclitaxel in the treatment of patients with metastatic breast cancer. 748 53


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