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)

Human lymphoblastoid interferon-alpha was administered intramuscularly at a dose of 5 x 10(6) units/day to 20 metastatic renal cell carcinoma patients. For potentiating the antitumor effect of interferon, cimetidine was also given to them orally at a dose of 800 mg/day. The combination therapy obtained a complete response in three patients (15%) and a partial response in three (15%). Nine patients (45%) had stable disease and five (25%), progressive disease. All six patients who responded to the combination therapy had been nephrectomized and had pulmonary metastases. Two of them also had metastases to other sites (mediastinal lymph nodes and bone). The pulmonary metastases were significantly more receptive to interferon therapy than those at the other sites. The average times before a response was obtained were 2.2 months for a minor response, 2.7 months for a partial response and 3.0 months for a complete response, and the average duration of response was 26 months. The six patients who responded survived for a significantly longer period than the 14 non-responding patients treated with interferon in combination with cimetidine. The major toxicities encountered were fever, fatigue and anorexia due to interferon, and the combination therapy was well tolerated except in three patients. The results suggest that interferon-alpha and cimetidine combination therapy may be of use in the management of patients with metastatic renal cell carcinoma.
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PMID:Treatment of metastatic renal cell carcinoma with a combination of human lymphoblastoid interferon-alpha and cimetidine. 206 20

The effects of 21 days voluntary leg (plaster) immobilization on the mechanical properties of the triceps surae have been studied in 11 young female subjects, mean age 19.4 years. The results show that during the period of immobilization the mean time to peak tension (TPT) and half relaxation time (1/2RT) and tension (Pt) of the maximal twitch increased significantly (p less than 0.001) but the effects were short lived. Maximal tension and contraction times of the twitch recovered within 2-14 days following the removal of the plaster cast. The electrically evoked tetanic tensions at 10 Hz and 20 Hz did not change significantly (P greater than 0.1) during immobilization, but the 50 Hz tetanic tension (Po50) and maximal voluntary contraction (MVC) were reduced (p less than 0.05). The fall in Po50 and MVC was associated with 10% decrease in the estimated muscle (plus bone) cross-sectional area. The relative (%) change in Po50 and MVC following immobilization was related to the initial physiological status (as indicated by the response of the triceps surae to a standard fatigue test prior to immobilization) of the muscle. The rate of rise and recovery fall of the tetanus were slightly but significantly (p less than 0.01) reduced on day 7 of immobilization, but thereafter remained constant. The isokinetic properties of the triceps surae as reflected in the measured torque/velocity relation of the muscle in 4 subjects did not change significantly if account was taken of the slight degree of atrophy present following immobilization.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Electrically evoked contractions of the triceps surae during and following 21 days of voluntary leg immobilization. 356 38

Electrically evoked mechanical and contractile properties of the triceps surae have been measured in 52 children aged 11 and 14 years, and results compared with previously reported data for adults (Davies and White 1982). The results show that the time to peak tension (TPT), half relaxation time (1/2RT) and supramaximal tension (Pt) of the twitch were not significantly (P greater than 0.1) different in girls and boys and independent of age. The 14-year-old girls and boys were stronger in terms of their supramaximal 10, 20, and 50 Hz tetanic tensions and maximal voluntary contraction (MVC) than their younger counterparts, and both groups of children were significantly (P less than 0.001) weaker than the young adults. However, if standardisation was made for an anthropometric estimate of calf muscle (plus bone) cross-sectional area (CSA), the differences in strength disappeared. Electrically stimulated and voluntary maximal force per unit CSA measured at the knee were 17.1 and 20.5 N X cm2 respectively and independent of sex and age. The loss of force during a 2-min stimulated fatigue test was the same in the children as the adults. The average fatigue indices ranged from 0.52 to 0.72 in the children, compared with 0.68 in the adults. It is concluded that absolute differences in muscle strength in children are a function of muscle mass. The force generating capacity expressed in N X cm2, fatiguability, contraction and relaxation times of the triceps surae would appear to remain unchanged through adolescence and early adulthood.
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PMID:Muscle function in children. 668 19

An experimental study of the fatigue life of cortical bone screws under conditions which stimulated in vivo usage was performed. The two most important factors influencing fatigue life were axial screw tension (the force normal of the plate to bone) and the cyclic shearing load. All screws failed at the root of the thread in the interface between the plate and the bone. A modified screw design effectively resisted fatigue under the described experimental conditions.
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PMID:Fatigue failure of cortical bone screws. 688 32

Stress fractures are ubiquitary and most often caused by the subject's activities. In the past they occurred mostly in recruits, but today they are frequent in sportsmen. Stress fractures most frequently occur in the lower limbs, especially in the distal leg. We reviewed 32 injuries observed January, 1993, to June, 1995, and found that 25% of them had been misdiagnosed as stress fractures: in the cases where the diagnosis was correct, fatigue fractures (32%) were less frequent than insufficiency fractures (68%) and occurred in young subjects (mean age: 24 years), usually sportsmen (2/3 of cases). Insufficiency fractures may occur in people aged 8 to 81 years (mean: 61 years) and in subjects with metabolic disorders (45.5%). Considering the injury biomechanics and the patient history and symptoms, these lesions appear a rather uncommon event, whose radiologic diagnosis must be confirmed by clinical findings, since radiology mostly (81.6% of cases) showed only the repair process, rather than the fracture itself. The radiologic patterns were classified into three groups: the fracture margin was not shown in 70% of cases (group I), where however intraperiosteal reaction and/or soft tissue effusion were found; bone fracture was shown in 3 cases (group II) and fracture sequels in 4 (group III), where bone thickening (3 cases) or abnormal consolidation (1 case) was found. There are several synonyms of "stress fracture" and confusion is increased because stress lines and other not necessarily abnormal signs such as Park or Harris lines, reinforcement or calcification lines, are often grouped together with stress fractures. Only accurate clinical examination and laboratory findings permit to distinguish fatigue from insufficiency stress fractures and the latter are also very difficult to differentiate from pathologic fractures. The differentiation of fatigue from insufficiency fractures, originally made by English speaking authors, may be confusing because the definition "pathologic fractures" should be reserved only to focal injuries while in the past it included also insufficiency fractures. Thus, only (bone) fatigue injuries in patients exercising intensely and constantly should be considered stress fractures. Conventional radiography is an indispensable tool and MRI is used in selected cases where the former method is negative and in the patients needing early mobility to go back to work. If radiographic findings are questionable for metastases, nuclear medicine is the method of choice and CT and/or MRI may be indicated as second-line diagnostic imaging tools.
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PMID:[Clinico-radiologic considerations on "stress fractures" of the leg]. 922 7

Heat-treated bovine cortical bone has been proposed as an alternative to bone grafts and synthetic bone substitutes because it may combine the advantages of allografts (high stiffness and strength) and synthetic materials (abundant supply, reduced risk of rejection and disease transfer). Its mechanical properties and ultrastructure, however, are not well characterized. To address this, we compared the compressive (n = 20, bovine bone) and tensile (n = 26, bovine bone) mechanical properties and the ultrastructure (n = 12, human bone) of intact versus 350 degrees C heat-treated cortical bone. The 350 degrees C heat-treated bone had a mean +/- SD elastic modulus similar to the intact bone for both compression (16.3 +/- 2.2 GPa, pooled; p = 0.68) and tension (16.3 +/- 3.7 GPa, pooled; p = 0.95). It also maintained 63% of the intact strength in compression but only 9% in tension (p < 0.001). Infrared scans and X-ray diffraction patterns showed no differences between the 350 degrees C heat-treated and intact bone but large differences between ashed (700 degrees C) and intact bone. Similarly, heat-treated bone previously has been shown to be biocompatible and osteoconductive. We conclude, therefore, that 350 degrees C heat-treated cortical bone may be an excellent load-bearing bone substitute provided that it is loaded in compression only in vivo and is shown by future work to have acceptable fatigue properties.
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PMID:Characterization of the mechanical and ultrastructural properties of heat-treated cortical bone for use as a bone substitute. 1032 5

Intense remodeling occurs in lamellar bone adjacent to osseointegrated endosseous implants. The purpose of this study was to compare microdamage accumulation subsequent to ex vivo fatigue loading of bone that surrounds an endosseous implant, (a) immediately after placement (nonadapted bone) and (b) following a 12 week healing period after placement (adapted bone). We hypothesize that there is less microdamage in the more compliant adapted bone than in the older nonadapted bone. Nonthreaded titanium plasma sprayed (TPS)-coated endosseous implants were placed into dog mid-femoral diaphyses and allowed to heal for 12 weeks. Block sections of bone, each containing one implant, were cut anteroposteriorly, resulting in an implant containing lateral cortex, and a medial cortex that was used for testing the nonadapted specimens. Control specimens (n = 14 each for adapted and nonadapted) were loaded at 0 N. Experimental specimens (n = 13, adapted; n = 14, nonadapted) were loaded at 100 N in cantilever bending for 150,000 cycles at 2 Hz, at 37 degrees C on a Bionix 858 testing machine. Specimens were bulk stained with basic fuchsin and 120-140 microm sections were obtained. Crack numerical density (Cr.Dn = Cr.N/ B.Ar, #/mm2), crack surface density (Cr.S.Dn = Tt.Cr.Le/ B.Ar, mm/mm2), and percent damage area (Dm.Ar = Cr.Ar x 100/B.Ar, mm2/mm2) were measured at x 250. Statistically significant differences (p < 0.0001) were seen for Cr.Dn, Cr.S.Dn, and Dm.Ar on the compressed cortices suggesting that adapted bone near the implant accumulated significantly less microdamage than nonadapted bone. Also, the adapted nonloaded control specimens had approximately 20-fold less damage than the respective nonadapted specimens. This study suggests that the compliant adapted bone adjacent to endosseous implants is relatively resistant to fatigue loads. The high success rates of endosseous implants may be due to the presence of a rapidly remodeling region that maintains tissue compliance and limits microdamage initiation.
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PMID:Microdamage adjacent to endosseous implants. 1045 88

Multiple myeloma (MM) is a plasma cell malignancy characterized by infiltration of bone marrow, bone destruction, infiltration of soft tissues with plasma cells, and suppression of normal hematopoiesis. The production of monoclonal immunoglobulins with or without light chains is a major feature of the disease. Full spectrum of plasma cell dyscrasias include monoclonal gammapathy of undetermined significance, smouldering myeloma, indolent multiple myeloma, and fully developed, symptomatic multiple myeloma. The usual presenting features of MM include bone pain, weakness, fatigue, fever and infection. Neurologic symptoms are less common but one must not forget that MM may present with a neurologic disease. Careful neurologic history and examination are mandatory in patients with MM. Neurologic symptoms may be a direct manifestation of MM or may be due to the immune effect of monoclonal proteins directed against different neural structures. Finally, metabolic consequences (uremia, hypercalcemia, hyperviscosity) of MM may produce a broad spectrum of different neurologic symptoms including headache, blurring of vision, drowsiness, precoma, coma, vertigo, ataxia, hemiparesis and epileptiform seizures. The most common location of bone changes in MM is the thoracic spine, where it causes osteolytic changes with consequent compressive fractures. The most disastrous sequel is paraplegia. Multiple vertebral involvement with the evidence of osteolytic changes in other bones is usual, but solitary vertebral myeloma may occur. Myeloma usually involves the bone of the vertebral body and then spreads into the extradural space. However, patients with solitary extradural myeloma have been reported. Skull myeloma is frequently asymptomatic. It may grow externally or, rarely, there is intracranial expansion. Involvement of the cranial nerves is not rare, with II, V, VI, VII and VIII cranial nerves being most often affected. Isolated intracerebral plasmacytomas are extremely rare. Diagnostic approach includes plain X-rays of the skeleton, which was found to be the method of choice for demonstration of osteolytic changes, whereas magnetic resonance with gadolinium enhancement most reliably displays the degree of vertebral involvement and demonstrates any associated soft tissue mass. Current treatment of osteolytic changes in multiple myeloma include chemotherapy, radiotherapy in combination with dexamethasone, monthly infusions of bisphosphonates, surgical decompression, and kyphoplasty. Therapeutic approach is dictated by the presenting symptoms. In case of pain as the predominant symptom, treatment with chemotherapy and radiotherapy may be appropriate. Compressive symptoms are relieved with dexamethasone followed by radiotherapy and chemotherapy. Surgical decompression is used in patients with vertebral collapse and vertebral instability. Kyphoplasty is a new method used in the treatment of osteolytic changes of vertebral bodies. A viscous cement is injected into the cavity by a balloon-like inflatable bone tampon. It has been successfully employed to improve the quality of life, to reduce pain, and to increase overall functioning in patients with vertebral compression fractures by restoring most of the original height of the vertebral body. Bisphosphonates reduce pain associated with osteolytic changes in multiple myeloma, but also significantly reduce skeletal events (pathologic fracture, spinal cord compression, surgery or irradiation of bone) via unknown mechanism. It seems that bisphosphonates, by inhibiting bone resorption, alter the microenvironment in which the MM cells grow.
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PMID:[Neurologic sequelae of bone changes in multiple myeloma and its therapy]. 1263 Mar 41

A 56-year-old black woman with diabetes mellitus was admitted for hypoglycemia and confusion. Her past medical history included breast cancer, for which she had undergone a left lumpectomy and then mastectomy for in-breast recurrence. Her oral intake had decreased during the past month because of increasing discomfort from left-sided chest pain. During this period, she continued to take pioglitazone for diabetes at her originally prescribed dose. The patient's mental status improved quickly after taking orange juice and intravenous glucose, but the chest pain persisted. The pain, which was described as an ache along the left costal margin, increased with palpation, deep inspiration, or coughing. She had recently presented with similar complaints at another hospital where she had been prescribed a muscle relaxant that provided no relief from the pain. She also reported a 14-lb weight loss during the previous 3 months, as well as fatigue, weakness, and aches in her legs and arms. She denied fevers, chills, sweats, abdominal pain, nausea, or recent trauma. Laboratory values at the time of admission were: calcium, 11.8 mg/dL; total protein, 11.1 mg/dL; albumin, 3.2 g/dL; creatinine, 1.0 mg/dL; and hematocrit, 29.3%, with a mean corpuscular volume of 89.3. Chest radiography revealed a lytic lesion in the left lateral fourth rib and left humerus (). Serum and urine protein electrophoresis revealed a monoclonal spike in the gamma region consistent with monoclonal gammopathy. The serum spike was quantified at 3.78 g/dL. A skeletal survey showed many small well-defined lytic lesions in the skull (with one 1.5-cm lytic lesion in the upper posterior parietal bone), arms, and legs. A bone scan showed multiple foci of increased uptake in the right and left ribs as well as the proximal portion of the left femur. The peripheral blood smear revealed rouleaux formation () and plasma cells (). What is the diagnosis?
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PMID:Cases from the Osler medical service at Johns Hopkins University. 1275 89

In this issue, we would complete the conclusions of the systematic revision with the results from the major clinical and experimental studies. First of all, we outline that the use of bone mineral density is controversial and opposed of the major studies in the field that show that the bone density is only one of the factors which describe bone resistance, and not the bone quality. In fact, often, a dramatic variation of bone strength is linked to the fact that the newly bone is located in the only in the surfaces where mechanical stress is greatest and this doesn't change completely the density. To study the optimal exercises program we have to remember that the ideal timing in the remodelling unit of the bone was estimated at 4-6 months: therefore any treatment which has the aim of preventing bone loss should last at least 2-3 times this period to ensure that the registered effect on bone density is evaluated in a period of balance. According to Frost, the strength of the bone is determined by 4 factors: the mechanical property characteristic of bony tissue, the amount of micro damage from fatigue, bone mass factors (amount and type of bone in the bone) and the size and shaper of the bone (architectural factors). Moreover, it is very important the role of muscular strength on the bone: the muscles work like a lever in such a manner that to move every kilo of body weight, the muscular force is usually over 2 kg. This explains why strong muscles are usually associated with strong bones. About the specific role of the strain on the bone, from studies of the past 10 years there seems to be more precise and useful information for our queries: new formation of bone took place in rabbits only with dynamic stimuli and not static, and it is very important also the frequency of the stimulus and the speed. Moreover, some authors have shown that the stimuli of ostegoenesis depends on the fluid shear stresses though the lacunar-canalicular network system. So: exercises at high impact which can produce significant deformation of the bone matrix, better carry the fluid through the canalicular network and furthermore the strains applied at high frequency stimulate in a effective manner osteogenesis. Therefore, the mechanical strain necessary to begin osteogenesis decreases with the increase of the frequency of the strain. Rubin and Lanyon have shown that the prolongation of the stimulation with strain the osteogenic response did non increase if the regimen is prolonged more. In fact, Turner demonstrated that the bone presents a phenomenon of desensitisation following a prolonged strain stimulus. He proposed the osteogenic index of exercises like the osteogenic response to exercise which could be increased in a regimen of exercises which foresee also a period of rest between brief sessions of significant strain. So, concerning the effects of exercises, the stimulus produced by the strain must be such that it exceeds a threshold of a minimum effective stimulus, must be applied in a intermittent and dynamic manner, should produce a stimulus which is distributed differently to the norm, should be applied with high speed and few repetitions.
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PMID:The conclusions of the systematic revision with the results from the major clinical and experimental studies. 1617 92


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