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)

Twenty-one patients with liver metastases of various histologies (predominantly colorectal carcinoma) underwent Infusaid pump implantation for long-term hepatic arterial 5-fluorodeoxyuridine (5-FUdR) infusion. Patients received 5-FUdR infusion on a 2-wk cycle alternating with a 2-wk saline--heparin infusion. A dosage of 0.2-0.3 mg/kg/day (average 0.23 mg/kg/day) was infused for a cumulative 5-FUdR administration of 1940 days. Six patients (29%) responded to therapy (five colorectal, one carcinoid); median response duration was 6 mo. Median survival for the treated group was 17 mo from diagnosis of liver metastases and 13 mo from pump implantation. Median survival among the six responding patients was 15 mo from diagnosis of liver metastases and 11 mo from pump implantation. Comparison of survival from the diagnosis of liver metastases of the treated group to ten patients found ineligible for the study by virtue of extrahepatic metastases revealed no significant difference in median (18 mo for ineligible group) or overall survival. However, median survival for the treated group after pump implantation (13 mo) was significantly better than the median survival of the ineligible group after evaluation for this study (4 mo). Toxicities of therapy included fatigue, anorexia, nausea, vomiting, toxic hepatitis, epigastric pain, and diarrhea. No patients died of toxicity, but six patients required hospitalization for management of pain or vomiting. No serious technical complications developed in any patient except separation of the infusion catheter at its junction with the pump in one patient, necessitating pump replacement for continuation of therapy. These survival data suggest identification of new anticancer agents for hepatic arterial infusion.
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PMID:Long-term hepatic arterial infusion of 5-fluorodeoxyuridine for liver metastases using an implantable infusion pump. 619 74

The prognosis and the quality of life of patients with carcinoid tumors is related either to symptoms from the substances secreted or to progressive tumor growth. Medical treatment with cytotoxic agents is of marginal value for increasing life expectancy and reducing clinical symptoms. Recent studies with interferon have shown interesting results. In the present investigation, 22 patients with carcinoid tumors and syndrome were treated with recombinant interferon alpha-2a (r-IFN alpha-2a) at the dose of 6 x 10(6) IU intramuscularly daily for 8 weeks and three times weekly thereafter. The primary tumor was localized in the foregut (n = 11), midgut (n = 7), hindgut (n = 1), and unknown site (n = 3). Most cases had liver metastasis. Seventeen patients had elevated 5-hydroxyindoloacetic acid (5-HIAA) excretion and 5 had flushing and/or diarrhea as the only clinical manifestation. Six cases presented a complete syndrome (flushing, diarrhea and 5-HIAA excretion). Control of symptoms was obtained in 80% and a 5-HIAA level reduction in 58% of the patients. The interferon treatment was more effective for control of the carcinoid syndrome than for control of tumor growth. The treatment was well tolerated and fever, myalgia, anorexia and fatigue were the most frequent side-effects.
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PMID:Treatment of carcinoid syndrome with recombinant interferon alpha-2a. 768 66

During the past 2 decades, great advances have been made in the treatment of ulcer disease. This has involved the development of new drugs that are not only well tolerated, but are relatively inexpensive. The lack of significant adverse effects has revealed a degree of tolerability that, to write a review of the adverse effects, poses a difficult task. Most of the adverse effects are related to an excessive reaction to the relevant pharmacological characteristic that mediates the therapeutic response. The drug dosage can be reduced, freeing the patient of the adverse reaction, but leaving behind a background activity adequate to produce a therapeutically beneficial effect. The adverse effects of H2-antagonists fall into 2 groups. Firstly, there are poorly defined symptoms that have a prevalence similar to that in the community; these include headache, giddiness, dizziness, fatigue, constipation and diarrhoea. Secondly, they may delay the metabolism of drugs metabolised by the the cytochrome P450 system, and rarely be androgenic. Many antacids and the site-protective agent sucralfate contain aluminium, which can be absorbed, producing elevation of serum aluminium levels. In view of the possible association of aluminium with Alzheimer's disease, anxiety has arisen as to whether aluminium from these sources may, in those on prolonged treatment, cause Alzheimer's disease. However, the evidence so far indicates that aluminium is not a risk factor for Alzheimer's disease. The association of gastric cancer with achlorhydria has led to the fear that long term use of potent acid inhibitors may cause cancer. This fear has been accentuated by the observation that some rats, given omeprazole over their lifetime, developed carcinoid tumours of the stomach. However, enthusiastic research, both clinical and epidemiological, indicates that drug-induced achlorhydria is unlikely to be a problem in humans. Site protective agents have a role in certain conditions such as pregnancy where the systemic effect of a drug may produce adverse effects.
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PMID:A comparative overview of the adverse effects of antiulcer drugs. 776 37

Neuroendocrine gut and pancreatic tumors are neoplasms that present distinct features from other malignant tumors. Firstly, in most patients, tumor growth is rather slow, and even in advanced metastatic disease, there is very little impairment of the general well-being of the individual, e.g. appetite and weight. Secondly, these tumors are known to produce specific peptide hormones which may be factors in some clinical conditions e.g. carcinoid, Zollinger-Ellison and hypoglycemic syndromes. These conditions can be critical to the patients and can occasionally be lethal. Therefore, the treatment of neuroendocrine tumors must control the clinical symptoms related to hormone over-production and prevent further tumor growth. These two features are not always in parallel. Systemic treatment of neuroendocrine tumors mainly consists of chemotherapy, interferon and somatostatin analog administration. Chemotherapy has been used for at least 30 years; the most effective combination has proved to be streptozotocin with 5-fluorouracil or adriamycin. This combination produces biochemical responses in up to 60% of patients with endocrine pancreatic tumors; the results in carcinoid patients are very poor and response rates are < or = 10%. Alpha-interferon (IFN-alpha) produces biochemical responses in approximately 50% of patients with malignant carcinoid tumors, significant reductions in tumor size in 15% and a further 39% of patients have disease stabilization with no further tumor growth. Somatostatin analogs have only been used clinically within the last 10 years, but produce symptomatic improvement in 70% of cases, biochemical responses in 40-60%, but rarely produce any significant reduction in tumor size. These analogs are particularly useful to control severe clinical symptoms and are the first-line therapy for the management of carcinoid patients both peri- and intra-operatively. Patients with endocrine pancreatic tumors, particularly those with glucagon and vasointestinal peptide-producing tumors, benefit most from this type of treatment. Recently, a combination of IFN-alpha and a somatostatin analog has showed an additive effect of these two drugs. The side effects of streptozotocin and 5-fluorouracil are mainly nausea and vomiting which can be controlled with 5-HT3 receptor blocker therapy. Another significant adverse reaction is impaired renal function. The adverse reactions to IFN-alpha are mainly flu-like symptoms, fatigue, mild impairment of liver and bone marrow function and autoimmune reactions in 15% cases. Somatostatin analog treatment causes a low frequency of adverse reactions, those which do occur include gall stone formation and steatorrhea. Future systemic treatment should be based on increased knowledge of the tumor biology, particularly growth-regulatory mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endocrine tumors of the gastrointestinal tract: systemic treatment. 785 82

A 48-year-old woman with type II diabetes developed fatigue, arthralgia and myalgia. A few weeks later she was found to have hepatomegaly. The erythrocyte sedimentation rate was raised (53/93 mm), as were liver enzyme activities (GOT 186 U/l; GPT 240 U/l; gamma-GT 199 U/l), the gamma-globulin levels (40.7%;IgG 4470 mg/dl, IgA 698 mg/dl, IgM 245 mg/dl), antinuclear antibodies and antibodies against double-strand DNA, smooth muscles and actin. Laparoscopy revealed small-nodular liver cirrhosis. The autoimmune hepatitis was treated with prednisolone (initially 60 mg daily, then reduced to 10 mg daily) and azathioprine (initially 100 mg daily, reduced to 50 mg daily). The symptoms markedly improved. But one year later, during follow-up examination, gastric polyps were found, excised and histologically found to be carcinoid. The gastrin level was raised to 765 pg/ml. Another year later the liver cirrhosis had advanced further and the type A gastritis was still present, but there was no sign of carcinoid recurrence.
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PMID:[Autoimmune hepatitis, autoimmune gastritis, hypergastrinemia and stomach carcinoid]. 788 17

A phase I-II trial was initiated to investigate the effects of a combination of alpha- and gamma-interferon in 12 patients with malignant carcinoid tumors. All patients were treated with alpha-interferon at a dose of 5-10 MU, 3-5 times weekly for a median of 22 months and had stable or progressive disease. Gamma-interferon was added at a daily dose of 0.5 MU subcutaneously. After 3 months of treatment 4 patients showed progressive biochemical disease while 8 patients had continuous stable biochemical disease. The dose was escalated to 1 MU daily in 8 patients while 3 continued at lower dose levels. Gamma-interferon was withdrawn from one patient due to mental depression. At 6 months there was 1 partial response, 3 patients with progressive and 7 with stable disease. Half of the patients experienced increased fatigue during the study. Other adverse reactions were skin lesions and myalgia. The combination therapy demonstrated subjective improvement in half of the patients, but lacked antitumoral effects.
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PMID:Combined alpha- and gamma-interferon therapy for malignant midgut carcinoid tumors. A phase I-II trial. 832 62

Amyloid deposition in skeletal muscle is a well-recognized but rare occurrence. Sixteen such cases seen in a 17-year period (1979 to 1996) out of a total of 3,937 muscle biopsy specimens (0.004%) form this study group. Either Congo red or sulfated alcian blue stains were routinely performed in each biopsy to screen for amyloid. Patients in this study (eight men, eight women) ranged in age from 42 to 90 years (mean, 61 years) at initial presentation. The most common symptoms at presentation included weakness/fatigue (n = 10), autonomic symptoms (n = 8), and weight loss/decreased appetite (n = 7). Five patients had a concomitant malignancy (myeloma, n = 3; malignant carcinoid tumor, n = 1; melanoma, n = 1). Two patients had known hereditary forms of amyloidosis. Five patients had amyloid diagnosed on another organ biopsy (excluding peripheral nerve). Histologically, amyloid was deposited in the interstitium or perivascular region in 14 muscles and endomysial region in seven muscles. All cases were confirmed with Congo red staining (apple green birefringence) or by electron microscopic identification of fibrillary amyloid material. Scattered angular atrophic esterase-positive muscle myofibers indicative of acute denervation atrophy were seen in 14 muscles. Eight muscles showed small group atrophy, and seven showed myofiber type grouping. Scattered regenerating muscle fibers were seen in nine cases, degenerating myofibers in six, and foci of chronic endomysial and perivascular inflammation in two. Four muscles showed type II muscle fiber atrophy. A concomitant sural nerve biopsy specimen was evaluated in seven patients; all seven contained amyloid, confirmed either by Congo red staining or electron microscopic examination. In two nerves, there was a mild loss of myelinated axons; four had a moderate loss, and one, severe loss. Six of seven nerves showed predominantly axonopathic changes. In conclusion, (1) the prevalence rate of amyloid myopathy in muscle biopsy specimens was low (in this series, 0.004%); (2) only a minority of patients had multiple myeloma, and most presented with muscle weakness/fatigue or autonomic symptoms; (3) most of the muscles showed neurogenic features histologically; (4) all concomitant sural nerve biopsy specimens contained amyloid, and most showed a predominance of axonopathic changes.
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PMID:Amyloid myopathy: clinicopathologic study of 16 cases. 959 69

We report a 66-year-old patient with previously diagnosed iron deficiency anemia. He complained of fatigue, but had no further symptoms. Hemoglobin was 9.1 g/dl. Test for occult blood in stool was positive, but gastroduodenoscopy and colonoscopy revealed no bleeding source. The man was referred to our department for push-type enteroscopy. By enteroscopy we diagnosed a pedunculated, large polyp in the upper jejunum. The polyp seemed to be submucosal, but had some ulcerations on its surface as the probable bleeding source. In the lower parts of the small intestine no further polyps were detected. After endoscopic doppler examination we injected adrenaline into the base of the polyp to prevent bleeding and the polyp was removed by snare without complications. The polyp was diagnosed to be a carcinoid and was removed in sano.
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PMID:[A rare cause of iron deficiency anemia: recurrent hemorrhage from a carcinoid of the jejunum--diagnosis and therapy with enteroscopy]. 1049 7

An intestinal carcinoid with multiple metastases was identified in a 5-year-old male Shih Tzu with a clinical history of anemia, fatigue, anorexia, vomiting, intermittent diarrhea, intestinal bleeding, and progressive emaciation. There was a yellowish-white mass 15 mm in diameter in the anterior jejunum and white nodules consistent with metastases in many organs. Histopathologically, the mass consisted of neoplastic cells arranged in lobules, trabeculae, or closely interdigitating islands of cells. Neoplastic cells were generally polygonal with round hyperchromatic nuclei, modest amounts of eosinophilic cytoplasm, and eosinophilic cytoplasmic granules. Mitoses were common. Rosette formations of tumor cells were apparent in metastatic tumors. Immunohistochemically, tumor cells stained positive for cytokeratin 13, synaptophysin, protein gene product 9.5, neuron-specific enolase, chromogranin A, calcitonin gene-related peptide, serotonin (5-HT), and Leu-7. Serum 5-HT concentrations for this dog were increased 10-fold compared with those of normal dogs. All findings were consistent with a diagnosis of a malignant intestinal carcinoid.
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PMID:Immunohistochemical evaluation of a malignant intestinal carcinoid in a dog. 1263 63

Type I gastric carcinoid tumors result from hypergastrinemia in 1%-7% of patients with pernicious anemia. We diagnosed pernicious anemia in a 48-year-old female patient with complaint of fatigue for three months. She had no gastrointestinal symptoms. Endoscopic examination ot the upper gastrointestinal tract revealed atrophic gastritis and a polypoid lesion in the corpus of 3-4 mm in size. Endoscopic polypectomy was performed. Histopathological examination of the specimen revealed positive chromogranin A and synaptophysin stainings compatible with the diagnosis of a carcinoid tumor. Serum gastrin level was increased, urinary 5-hydroxyindoleacetic acid was within the normal range. There was no other symptom, sign, or laboratory finding of a carcinoid syndrome in the patient. No metastasis was found with indium-111 octreotide scan, computed tomographies of abdomen and thorax. Type I gastric carcinoid tumors are only rarely solitary and patients with tumors < 1 cm in size may benefit from endoscopic polypectomy.
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PMID:Treatment of solitary gastric carcinoid tumor by endoscopic polypectomy in a patient with pernicious anemia. 1683 Mar 92


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