Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The appearance of oxygen on earth led to two major problems: the production of potentially deleterious reactive oxygen species and a drastic decrease in iron availability. In addition, iron, in its reduced form, potentiates oxygen toxicity by converting, via the Fenton reaction, the less reactive hydrogen peroxide to the more reactive oxygen species, hydroxyl radical and ferryl iron. Conversely superoxide, by releasing iron from iron-containing molecules, favors the Fenton reaction. It has been assumed that the strict regulation of iron assimilation prevents an excess of free intracellular iron that could lead to oxidative stress. Studies in bacteria supporting that view are reviewed. While genetic studies correlate oxidative stress with increase of intracellular free iron, there are only few and sometimes contradictory studies on direct measurements of free intracellular metal. Despite this weakness, the strict regulation of iron metabolism, and its coupling with regulation of defenses against oxidative stress, as well as the role played by iron in regulatory protein in sensing redox change, appear as essential factors for life in the presence of oxygen.
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PMID:Iron and oxidative stress in bacteria. 1062 Mar 17

On December 29 1995, a 13-year old, male Spanish ibex was easily captured by hand, with depression, weakness and severe tick infestation, mainly in the periocular and auricular regions. Blood and serum samples were collected and haematological analysis and serum iron levels were determined. Red blood cell count, haematocrit, haemoglobin concentration and mean corpuscular haemoglobin concentration (MCHC) were decreased and mean corpuscular volume (MCV) increased (macrocytic-hypochromic anemia). Serum iron and transferrin saturation were decreased and total and unbound iron-binding capacity were increased. Piroplasms were observed within parasitized erythrocytes and presumptively identified as Babesia spp. Ticks were identified exclusively as Ripicephalus bursa. The animal was treated with imidocarb but died after 15 days of capture. Histopathological examination revealed congestion of pulmonary capillaries and spleen, glomerulonephritis, hemoglobinuric nephrosis and generalized hemosiderosis. An indirect fluorescent antibody test was performed using a Babesia ovis isolate of ovine origin as antigen and the animal was positive with a titre of 1:640.
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PMID:Presumptive Babesia ovis infection in a spanish ibex (Capra pyrenaica). 1062 13

CASE. Timmy was born at 32 weeks of gestation after an uncomplicated pregnancy until there was a spontaneous rupture of the membranes and preterm labor associated with chorioamnionitis. A 2-month hospitalization in the neonatal intensive care unit (NICU) was associated with pneumonia, a Grade II intraventricular hemorrhage, chronic lung disease, and a slow weight gain in the nursery. He was discharged to home with plans for ongoing care by his pediatrician. The primary care pediatrician attended a multidisciplinary conference with the NICU staff and Timmy's parents. At the time of discharge from the nursery, at 38 weeks postconceptual age, Timmy still required oral diuretics and supplemental oxygen, as well as other medications such as iron. Timmy's respiratory rates were between 40 and 60 breaths per minute at rest, with mild intercostal retractions. He was discharged with a cardiorespiratory monitor. The discharge examination revealed mild to moderate symmetrical hypotonia with intact deep tendon reflexes, shoulder girdle weakness, and a mild head lag. Timmy would regard a human face and a bright object and would follow them briefly. He became active and would thrash his extremities with minimal tactile, bright light, or auditory stimulation. Typically, he settled slowly with swaddling and a pacifier. Nursing was slow to develop; he was currently receiving one half of his calories at the breast and the remainder of his calories from bottle-feeding of fortified expressed breast milk. As she prepared for the first office visit with Timmy and his parents, the pediatrician asked herself, "What can I do to enhance the developmental outcome for this child?"
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PMID:"What can I do to enhance the development of a premature infant with chronic lung disease?". 1079 83

Hereditary hemochromatosis is the most commonly inherited autosomal recessive disorder. Hemochromatosis is a current or potential progression of abnormally high accumulations of iron in the liver. If left untreated, the condition can lead to chronic or irreversible hepatic fibrosis, cirrhosis, hepatocellular carcinoma, arthritis, and organ failure. Common signs and symptoms seen in the primary care setting include fatigue, weakness, abdominal pain, palpitations, skin pigmentation changes, and arthropathy, but any symptom associated with organ damage may be reported. Because prompt intervention can cease or reverse the debilitating effects of iron overload, prompt disease diagnosis and treatments are imperative.
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PMID:Detecting hereditary hemochromatosis. 1091 30

Many patients with chronic diseases such as chronic renal failure, chronic inflammatory bowel disease and rheumatoid arthritis are anaemic. Recently congestive heart failure (CHF) has also been found to be associated with anaemia. In all these diseases this anaemia or chronic disease is at least partially due to excessive production of cytokines and leukotrines that interfere both with the effect of erythropoietin (EPO) at the bone marrow and the release of stored iron in the reticuloendothelial system. Treating this anaemia with subcutaneous EPO and IV iron improves the weakness, fatigue, cachexia, nutritional state, mood, cognitive function and quality of life. In the case of CHF it also improves cardiac function and patient functional class, prevents deterioration of renal function and markedly reduces hospitalization. Very few agents in medicine improve so many aspects of the patient so well and so quickly. Unfortunately (for the suffering patient) this anaemia is often ignored and goes untreated.
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PMID:The pathological consequences of anaemia. 1142 23

Patients with beta thalassemia major present with severe anemia and need continuous transfusion therapy. The consequent iron overload leads to hemochromatosis. Initial cardiac involvement can be present in thalassemic patients without clinical manifestations of heart failure. The purpose of this study was to assess the contractile reserve of the left ventricle in patients with normal baseline two-dimensional (2-D) echocardiographic findings using low dose dobutamine echocardiography. The underlying hypothesis was that, at an early stage, structural impairment of the myocardial wall due to myocardial iron deposits and/or secondary fibrotic changes could be so subtle so as not to impair resting systolic function, but is severe enough to blunt or even exhaust the contractile response to inotropic stimulation. Twenty-four consecutive patients (13 men and 11 women; ages 18 +/- 3.8 years) with beta thalassemia major undergoing evaluation for bone marrow transplantation entered the study. By selection, all were asymptomatic, without clinical signs of cardiac failure, and had normal regional and global systolic function at baseline echocardiographic study. A control group of 16 age and sex matched subjects was also studied. All underwent baseline, 2-D, and Doppler study, as well as dobutamine stress (up to 5 &mgr;g/kg per min) 2-D echocardiographic study. Patients and controls showed comparable values of indexes of global (ejection fraction: 0.64 +/- 0.06 vs 0.65 +/- 0.05, P = NS) and regional (systolic thickening of posterior wall: 90 +/- 34 vs 91 +/- 34%, P = NS) function at baseline. Left ventricular diastolic filling was evaluated with Doppler echocardiography. Peak flow velocity in early diastole was increased in thalassemic patients compared to controls (114 +/- 16 vs 96 +/- 18 cm/sec, P < 0.01), and flow velocity deceleration time was reduced (139 +/- 17 vs 157 +/- 20 msec, P < 0.01). At peak dobutamine, thalassemic patients showed a blunted contractile response compared to controls for indexes of both global (ejection fraction: 0.62 +/- 0.06 vs 0.69 +/- 0.05, P < 0.01) and regional (% systolic thickening of posterior wall: 91 +/- 36 vs 130 +/- 39%, P < 0.01) function. When individual patient analysis was performed, echocardiographic parameters were beyond the 95% confidence limits obtained from normal controls in 5 (21%) of the 24 study patients by one or more Doppler diastolic indexes, in 6 (25%) by indexes of contractile reserve, and in 11 (46%) by one of either diastolic function or contractile reserve indexes. These data demonstrate that the "iron heart" of asymptomatic thalassemic patients is a weak heart. Even if the regional and global systolic functions are similar to normals under resting conditions, the application of an inotropic challenge unmasks the weakness of these hearts, which can be identified at an earlier stage of their natural history through the blunted contractile response following the infusion of low dose dobutamine. The information on contractile reserve is not redundant, but rather incremental and in addition to that provided by Doppler echocardiographic indexes, which may be abnormal in these patients. (ECHOCARDIOGRAPHY, Volume 13, September 1996)
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PMID:Reduced Left Ventricular Contractile Reserve Identified by Low Dose Dobutamine Echocardiography as an Early Marker of Cardiac Involvement in Asymptomatic Patients with Thalassemia Major. 1144 56

Treatment of iron deficiency anaemia with conventional oral preparations is handicapped by unpredictable haematological response in addition to potential for irritating gastrointestinal adverse events. Iron polymaltose complex (IPC), a novel oral iron formulation with better absorbability, predictable haematinic response and less side effects was compared with oral ferrous fumarate in 100 female patients with documented iron deficiency anaemia. Clinical parameters (pallor, weakness) as well as biochemical parameters (Hb, serum iron, total iron binding capacity) show favourable changes with IPC; the physician and patient assessment also favour IPC over ferrous fumarate.
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PMID:Evaluation of efficacy and safety of iron polymaltose complex and folic acid (Mumfer) vs iron formulation (ferrous fumarate) in female patients with anaemia. 1147 61

A degenerative skeletal muscle disease with vascular, neurologic, and renal lesions and a probable familial distribution was identified in 4-20-month-old purebred Gelbvieh cattle. Thirteen affected animals were confirmed from 6 separate beef herds, with a mortality rate of 100%. Clinical signs in affected animals consisted of ataxia, weakness, and terminal recumbency. Gross and histologic muscle lesions were indicative of nutritional myopathy of ruminants, with a lack of myocardial lesions in most cases and only rare myocardial changes in a few animals. Acute to chronic lesions in most large skeletal muscle groups consisted of degeneration, necrosis, regeneration, fibrosis, and atrophy. Fibrinoid necrosis of arterioles was a common feature in multiple tissues. Lesions in the spinal cord white matter and peripheral nerves consisted of degeneration of the dorsal columns and axons, respectively. Changes in the kidneys consisted of chronic interstitial nephritis with fibrosis, hyaline droplet change and tubular epithelial vacuolar change and were most severe in the older calves. Intracytoplasmic myoglobin and iron were demonstrated within the hyaline droplets in degenerate renal cortical tubular epithelial cells. Vitamin E levels were deficient in most (6/7) of the animals tested. Investigation of the pedigree of affected animals revealed a common ancestry for all but 1 of the animals whose parentage could be traced. This investigation suggests that a hereditary metabolic defect, possibly involving antioxidant metabolism, could be responsible for this condition. Renal disease, possibly secondary to myoglobinuria, may be unique to this bovine condition.
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PMID:A familial degenerative neuromuscular disease of Gelbvieh cattle. 1193 35

We report the muscle pathology in a 43-year-old woman who died of chronic graft versus host disease (GVHD) complicated by myositis and systemic transfusional hemosiderosis, after an allogeneic bone marrow transplantation and a donor leukocyte transfusion for acute myelogenous leukemia. Despite cyclosporin A treatment, fatal ventilatory failure progressed while she was still ambulant. Autopsy revealed the presence of chronic GVHD mildly involving the liver, skin, pericardium, pancreas, and salivary glands, in addition to skeletal muscles. Myopathic changes with mild inflammation and prominent iron deposition were found in the tibialis anterior muscle and, to a lesser degree, in the diaphragm and the intercostal muscle. There were iron deposits in both macrophages and sarcoplasm in the tibialis anterior. The iliopsoas and pectoralis major muscles showed prominent type 2 fiber atrophy; inflammation and iron deposition were minimal in the iliopsoas, but none in the pectoralis. Although we ascribed respiratory failure largely to GVHD myositis, weakness of the lower leg appeared to be aggravated by iron deposition superimposing the underlying GVHD myositis.
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PMID:[Skeletal muscle pathology of chronic graft versus host disease accompanied with myositis, affecting predominantly respiratory and distal muscles, and hemosiderosis]. 1196 47

An unusual cause of upper gastrointestinal bleeding is described in a previously healthy 45-year-old man who was admitted to hospital with weakness and fatigue, and had experienced an episode of melena two days before admission. His medical and surgical history was unremarkable. Upon admission to hospital, he showed evidence of iron-deficiency anemia, with a hemoglobin concentration of 61 g/L (normal range 135 to 175 g/L), a mean corpuscular volume of 73 fL (normal range 85.0 to 95.0 fL) and a ferritin concentration of 1.0 microg/L (normal range in males 15 to 400 microg/L). Upper gastrointestinal endoscopy revealed a 3.5 cm ulcerated submucosal mass in the third portion of the duodenum, for which mucosal biopsies were nondiagnostic. A subsequent endoscopic ultrasound revealed a 2.7 x 4.0 cm hyperechoic, cystic, submucosal tumour in the third portion of the duodenum. Endoscopic ultrasound-guided fine needle aspiration revealed no malignant cells. The patient eventually underwent a resection of the third portion of his duodenum. Surgical pathology revealed that this tumour was a Brunner's gland hamartoma, 4.5 cm in its greatest dimension.
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PMID:Brunner's gland hamartoma: a rare cause of gastrointestinal bleeding -- case report and review of the literature. 1204 80


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