Glucose disturbances and regulation with glibenclamide in thalassemia.

Specific laboratory and clinical characteristics indicate that the pathogenesis of diabetes in patients with thalassemia resembles the pathogenesis of maturity-onset diabetes (type II). Thus oral hypoglycemic agents may be used to regulate blood glucose levels by induction of insulin secretion and reduction of insulin resistance. The efficacy of glibenclamide administration in the management of glucose disturbances was evaluated in 33 patients with thalassemia, aged 12-30 years (mean 17.4 +/- 3.7), in whom diet and exercise failed to regulate hyperglycemia. The results were compared to 30 thalassemic patients (mean age 18.4 +/- 4.8 yr), who followed only diet and exercise. Improvement of OGTT was observed in 73% of the treated patients versus 43% of the control group for a mean period of 59 months. Deterioration of OGTT occurred more rapidly (33.7 +/- 26.1 vs 40.7 +/- 34.5 mos), and in more patients of the untreated group (57%) than in treated patients (27%). Among treated patients, effectiveness of oral hypoglycemic agents lasted longer in patients with diabetic (64.1 +/- 40.3 mos) than in patients with impaired curves (54.2 +/- 31 mos).

Growth and management of short stature in thalassaemia major.

UNLABELLED: With modern treatment and longer survival of patients with homozygous beta-thalassaemia endocrine dysfunction assumes greater importance. Short stature, delayed puberty and hypogonadism are major problems in both adolescent and adult patients. Growth failure has been attributed to GH deficiency (hypothalamic or pituitary), hypothyroidism, delayed sexual maturation, hypogonadism, diabetes mellitus, zinc deficit, low Hb levels, bone disorders and desferrioxamine toxicity. The present report concentrates on the incidence of short stature among children aged 7-8 years (n = 50) and young adults aged 20-29 years (n = 93) with blood transfusion dependent homozygous beta-thalassaemia appropriately treated who have entered and completed puberty spontaneously (n = 45) or with treatment (n = 48) and have attained final height. It also concentrates on the role of GH in the growth retardation of 65 blood transfusion dependent thalassaemia major patients, their GH response to provocative stimulation, the effect of rhGH therapy on growth and final height in 13 patients who had GH deficiency and the effect of long acting androgens on growth and final height of 11 short boys with thalassaemia major, delayed puberty and normal GH secretion. CONCLUSION: 8% of young boys with thalassaemia major aged 7-8 years have short stature. 12% of the older boys and 15% of the older girls without endocrinopathies had height < 3rd percentile. This incidence was 29% when endocrinopathies were present. GH deficiency is rare among short blood transfusion dependent thalassaemia major patients (20%) and seems to play a limited role in the etiology of growth retardation. One year treatment with rhGH improved growth rate and predicted height without causing serious metabolic problems. Long term administration of rhGH is also safe and promising. Patients with thalassaemia major can achieve acceptable final heights but below their target heights with rhGH therapy. Low dose long acting sex steroid treatment in boys with delayed puberty, delayed bone age and without GH deficiency for a year or more is safe and can produce similar results to those obtained with rhGH therapy.

Variations of ferritin levels over a period of 15 years as a compliance chelation index in thalassemic patients.

We studied the changing pattern of the distribution of ferritin levels in 430 regularly-transfused patients with thalassemia in an attempt to evaluate compliance of chelation with deferoxamine. The study covered 15 years and was divided in three periods: 1981-1985, 1986-1990, and 1991-1995. The patients were stratified in age-groups. The mean ferritin levels of each period were calculated for each patient individually. The study showed that: (i) When all the patients were compared as a group, there was a significant decrease in mean ferritin between 1981-1985 and 1991-1995, despite a significant change in the patients' mean age; (ii) When patients of same age were compared between periods, there was a decrease in mean ferritin between 1981-1985 and 1991-1995, as well as a decrease in the proportion of patients with ferritin >4000 microg/L, with a parallel increase in the proportion of patients who had ferritin <2000 microg/L; (iii) When the same patients were followed longitudinally, they showed a decrease in their ferritin levels in all age groups with the exception of the late adolescence period. The decrease in iron overload observed in patients on close follow up implies that compliance with chelation therapy has improved with time and therefore, a favourable influence in survival could be expected.

Prevalence of yersinia plasmid-encoded outer protein (Yop) class-specific antibodies in multitransfused Greek patients with thalassemic syndromes.

OBJECTIVE: To evaluate the prevalence of class-specific antibodies (G, A, M) to Yersinia enterocolitica plasmid-encoded outer proteins (Yops), in a closely followed multitransfused population of patients with thalassemia. METHODS: Sera from 408 beta-thalassemic patients and 386 healthy blood donors used as controls were analyzed with the enzyme-linked immunosorbent assay (ELISA) for IgG, IgA and IgM antibodies to yersinia outer proteins. The Yop antigen for the ELISA was prepared using a plasmid-bearing wild-type strain of Y. enterocolitica of serotype O:8. RESULTS: Anti-Yop IgG antibodies were detected in 84 out of 408 beta-thalassemic patients (20.6%) compared with only eight out of 386 (2.1%) healthy blood donors. None of the sera of either group was positive for anti-Yop IgA or IgM antibodies. On evaluating patients with registered clinical and laboratory signs of a previous yersinia infection in the period from 1978 to 1996, we found that those with a positive agglutination test for Y. enterocolitica infection at the time of manifestation showed a higher rate of persisting IgG seropositivity to Yops than those with positive culture and clinical signs only. A significant percentage (9.49%) of the seropositive patients had no registered data of a past Y. enterocolitica infection. There was remarkable persistence of anti-Yop IgG antibodies in the thalassemic population, even in patients infected during the early years of our study period (1978--80). CONCLUSIONS: The results suggest that the determination of class-specific antibodies to Yops, which are specific antigens for the pathogenic yersiniae (Y. enterocolitica, Y. pseudotuberculosis and Y. pestis), in addition to its usefulness in the diagnosis of infection, will be a very sensitive and specific index for epidemiologic studies.