Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two hundred and seventy-three patients with thalassaemia major (TM) were followed in the Ferrara Thalassaemia Centre over a thirty-year period. Forty-two patients had insulin dependent diabetes mellitus (IDDM). The first case was diagnosed in 1973. The incidence of IDDM peaked in 1986 (3.9%), and it was 0.7% at the time of the study (March 1998). The prevalence of IDDM increased progressively over time, reaching 14.2% in 1998. Mean age at diagnosis of IDDM was 18.2 -/+ 3.6 years and this also rose significantly during the study period (p<0.01). Hypogonadism was present in 91% of patients with IDDM, hypothyroidism in 68%, hypoparathyroidism in 21%, and cardiopathy in 69%, all significantly more prevalent than in patients without IDDM. These complications appeared with the same frequency before and after the diagnosis of IDDM. Survival of patients with and without IDDM was similar and no difference in the primary cause of death was found between the two groups. Main risk factors associated with IDDM were poor compliance with desferioxamine (DFO) treatment (p<0.05%), advanced age at the start of intensive chelation therapy (p<0.001), liver cirrhosis or severe fibrosis (p<0.0001, odds ratio 9.5, CI 95% 2.8-32.6). Prevalence of impaired glucose tolerance (IGT) was highest in 1981, 1984, and 1985 when the incidence of IDDM was increasing; in 1995 the prevalence of IGT in patients aged 16-20 years was lower in comparison with that observed in 1975 (17% vs. 59%, p<0.01). Risk factors associated with IGT were: male sex (p<0.05), poor compliance with DFO therapy (p<0.05) and liver iron concentration 4 times above the normal value. In conclusion, our longitudinal study confirms that the incidence of IDDM and prevalence of IGT have been decreasing over the course of the last decade, appearing at a more advanced age, although some differences have not reached statistical significance. Iron overload and liver disease were the main associated risk factors, while positive family history for diabetes did not influence glucose metabolism in our patients.
 ...
PMID:Diabetes mellitus and impaired glucose tolerance in thalassaemia major: incidence, prevalence, risk factors and survival in patients followed in the Ferrara Center. 1646 13

The objective of the study is to determine the proportion and different types of birth defects among the children born in Hospital Kuala Lumpur. A cross-sectional study was conducted for a period of 18 months where all consecutively born infants, dead or alive were included. There were total of 34,109 births recorded during this period. The proportion of birth defects in Hospital Kuala Lumpur was 3.1% (n = 1056). The commonest involved were the hematology system, (157.7 per 10,000 births), the central nervous system, genitourinary system and chromosomal anomalies. The proportion was significantly higher in males and in the Chinese (p < 0.001). The commonest abnormalities are Glucose 6 Phosphate Deficiency (157.7/10000), Down's syndrome (12.6/10000), thalassaemia (8.8/10000), cleft lip and/or palate (7.6/10000) and anencephaly (7.3/10000). Neural tube defect is common and ranked second after G6PD deficiency. There is a need for a birth defect registry to assess the extent of the problem in Malaysia.
 ...
PMID:Audit of birth defects in 34,109 deliveries in a tertiary referral center. 1657 Jul 8

Glycolysis is for some cells, such as erythrocytes, neutrophil granulocytes and many cancer cells, the only or most important source of energy (ATP) production. Based on previous studies we developed an isotachophoretic (ITP) method which allows, in principle, the simultaneous determination of all metabolites of glycolysis. Since glucose metabolites are small anions, mobility of some of them may overlap in isotachophoresis and, therefore, partial mixed zones are generated. By variation of the leading/terminating system, however, it is possible to separate the compounds of interest. In this communication, we describe a method for analysis of glucose metabolites in erythrocytes from healthy donors during storage in blood bags, and from patients with thalassemia, with special respect to intracellular 2,3 bisphosphoglycerate, lactate and ATP/ADP. The well known characteristic changes of glycolysis in erythrocytes during blood storage and in erythrocytes from thalassemia patients, which are often analysed by separate enzymatic assays, could be confirmed with this isotachophoretic procedure. The method is currently adapted for analysis of glycolysis in neutrophil granulocytes and cancer cells which requires some modifications of sample preparation and performance of the isotachophoretic analysis.
 ...
PMID:Determination of glucose metabolites in stored erythrocytes and in erythrocytes from patients with thalassemia by analytical isotachophoresis. 1661 75

Recently introduced chelation regimens that combine deferoxamine (DFO) and deferiprone have been shown to have greater efficacy in promoting iron excretion than either chelator alone and have been associated with rapid reduction of the iron load in the heart and liver, and with reversal of cardiac dysfunction. It is unclear whether this combined therapy could be associated with a reduction in iron load or decline in the severity of iron-induced endocrinopathies. Starting in January 2001, 42 patients with beta-thalassaemia major, previously maintained on subcutaneous DFO only, were switched to combined treatment with DFO and deferiprone. The primary endpoint was to investigate the effects of this therapy on the glucose metabolism characteristics of this population. Combination therapy markedly decreased ferritin levels (638 +/- 1345 vs. 2991 +/- 2093 microg/l, P < 0.001). Glucose responses were improved at all times during an oral glucose tolerance test, particularly in patients in early stages of glucose intolerance. Glucose quantitative secretion also decreased significantly with combined therapy, while no significant change occurred in insulin levels in any group. Insulin secretion, according to the homeostasis assessment model, markedly increased in all groups, while overall reduction in insulin sensitivity did not reach statistical significance. This study showed that the combination of DFO and deferiprone was associated with an improvement in liver iron deposition and glucose intolerance.
 ...
PMID:Effect of enhanced iron chelation therapy on glucose metabolism in patients with beta-thalassaemia major. 1696 87

Suicidal death of erythrocytes (eryptosis) is characterized by cell shrinkage, membrane blebbing, activation of proteases, and phosphatidylserine exposure at the outer membrane leaflet. Exposed phosphatidylserine is recognized by macrophages that engulf and degrade the affected cells. Eryptosis is triggered by erythrocyte injury after several stressors, including oxidative stress. Besides caspase activation after oxidative stress, two signaling pathways converge to trigger eryptosis: (a) formation of prostaglandin E(2) leads to activation of Ca(2+)-permeable cation channels, and (b) the phospholipase A(2)-mediated release of platelet-activating factor activates a sphingomyelinase, leading to formation of ceramide. Increased cytosolic Ca(2+) activity and enhanced ceramide levels lead to membrane scrambling with subsequent phosphatidylserine exposure. Moreover, Ca(2+) activates Ca(2+)-sensitive K(2+) channels, leading to cellular KCl loss and cell shrinkage. In addition, Ca(2+) stimulates the protease calpain, resulting in degradation of the cytoskeleton. Eryptosis is inhibited by erythropoietin, which thus extends the life span of circulating erythrocytes. Eryptosis may be a mechanism of defective erythrocytes to escape hemolysis. Conversely, excessive eryptosis favors the development of anemia. Conditions with excessive eryptosis include iron deficiency, lead or mercury intoxication, sickle cell anemia, thalassemia, glucose 6- phosphate dehydrogenase deficiency, malaria, and infection with hemolysin-forming pathogens.
 ...
PMID:Mechanisms and significance of eryptosis. 1691 Jul 66

Glucose metabolism disturbances are frequently reported among patients with beta-thalassaemia major on conventional treatment consisted of regular blood transfusions and adequate chelation treatment. Aim of this study was to evaluate the evolution of oral glucose tolerance test (OGTT) in thalassaemic patients in relation to their chelation treatment. Data from two OGTTs performed with an interval of 2 years were studied retrospectively. Patients considered eligible for this study were those who maintained unchanged chelation treatment and did not receive any anti-diabetic agent during the last 2 years. Thirty-one patients (16 M and 15 F) were enrolled with a mean age of 23.73+/-4.23 years at the end of the study. Patients were divided into three groups concerning chelation treatment. First group was receiving deferoxamine (DFO) by an 8-hourly subcutaneous infusion five-six times a week, second group was chelated with deferiprone (DFP) at a daily dose of 75 mg/kg orally and the third group was receiving combined therapy with DFO (3 days/week) and DFP (daily). At the time of the first OGTT, 26 patients (84%) were found to have normal OGTT; three of them showed an impaired glucose tolerance during second test (one was chelated with DFP and two were receiving combined therapy). None of the five patients with impaired glucose metabolism during the first test became diabetic. On contrary, one patient receiving combined therapy managed to normalize his second OGTT. In contrast with the overall trend of a deteriorating glucose tolerance in the whole patient series, the group receiving combined therapy managed to increased beta-cell function index and decreased insulin resistance index, although not statistically significant when compared to other groups. Further studies are needed to support these preliminary results.
 ...
PMID:Evolution of OGTT in patients with beta-thalassaemia major in relation to chelation therapy. 1693 Jul 60

The aetiology of the growth retardation occurring in patients with beta-thalassaemia major is considered to be multifactorial. Although growth hormone (GH) secretion appears to be normal in many thalassaemic patients with short stature, there is evidence indicating impaired GH secretion in approximately 3% of patients. The response to recombinant human GH treatment (rHGH) is not predictable, based on either the parameters known to affect the response to treatment or the type of defect in the GH-insulin-like growth factor (IGF-1) axis. The wide variation in growth velocity observed during rHGH treatment suggests that treatment with the usual dose of rHGH (0.6 U/kg/week) cannot be considered effective in all patients, although rHGH has been successful in some patients. Therefore further studies are required in order to evaluate the effects of supraphysiological doses of rHGH on growth. Since these patients are prone to develop abnormal glucose homeostasis, oral glucose tolerance tests must be performed periodically during rHGH treatment.
 ...
PMID:Clinical experience with growth hormone treatment in patients with beta-thalassaemia major. 1803 Nov 17

In general, in women with transfusion-dependent thalassemia, during pregnancy, iron chelation therapy is ceased. We report a splenectomized patient, who was an excellent complier with chelation therapy, who before embarking on a pregnancy showed no evidence of iron overload, with normal cardiac, thyroid function and glucose metabolism. Laboratory findings showed ferritin 67 microg/L, myocardial T(2)* of 34 ms and liver magnetic resonance imaging (MRI) liver iron concentration of 1 mg/g dry weight. She became pregnant by in vitro fertilization in October 2006, delivery occurred in June 2007. She breast fed for 2 months. After 12 months without iron chelation, ferritin was 1583 microg/L. Quantitative MRI showed myocardial T(2)* of 27 ms, that the liver iron concentration had increased to 11.3 mg/g dry weight, indicative of moderate to heavy iron load. This case demonstrates that iron overload can develop rapidly and that physicians caring for patients with transfusion-dependent thalassemia should be particularly alert to any discontinuation of chelation therapy over time.
 ...
PMID:Rapid iron loading in a pregnant woman with transfusion-dependent thalassemia after brief cessation of iron chelation therapy. 1846 51

In beta-thalassemia (beta-thal) major, the pathogenetic mechanisms leading from siderosis to diabetes are poorly understood. We assessed the glycometabolic status in transfusion-dependent Egyptian beta-thal patients and evaluated their possible risk factors for abnormal glucose tolerance (AGT). An oral glucose tolerance test (OGTT) was done on 54 multi-transfused patients and 28 age-matched normal controls, measuring their serum insulin levels at 0 and 120 min. Insulin sensitivity and insulin release indices were calculated. Indicators of iron overload and liver status were recorded. Thirteen patients (24.1%) had AGT. Cases with AGT had significantly higher mean postprandial insulin, fasting insulin resistance index (FIRI) and homeostasis model assessment (HOMA) insulin resistance (IR), p = 0.0001 for all, and significantly lower mean HOMA beta cell, p = 0.007, when compared with normal glucose tolerance (NGT) cases. Abnormal glucose tolerance is common in multi-transfused beta-thal major patients and could be attributed to early impaired beta-cell function with increasing IR.
 ...
PMID:Abnormal glucose tolerance in beta-thalassemia: assessment of risk factors. 1937 85

Optimum glycemic control is extremely important in patients with diabetes mellitus to avoid long-term complications. Glycemic control relies mainly on the use of hemoglobin A1c, which unfortunately showed inaccurate results in patients with hemoglinopathies. The authors describe a case of beta-thalassemia with poorly controlled diabetes mellitus that has misleading low levels of HbA1c. The use of a continuous glucose monitoring system was useful in documenting her poor glycemic control, with prolonged periods of hyper- and hypoglycemia. Based on these results, her insulin regimen was adjusted and the blood glucose levels were greatly improved throughout and the patient was able to meet her target blood glucose range (72-140 mg/dL [4-7.8 mmol/L]) in 70% of the time.
 ...
PMID:Case Study: using a continuous glucose monitoring system in a patient with diabetes and beta-thalassemia hemoglobinopathy. 1986 7


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>