Deferiprone chelation therapy for thalassemia major.

Iron overload is one of the major causes of morbidity in patients with thalassemia major. Deferiprone (DFP), an orally active iron chelator, emerged from an extensive search for new drugs to treat iron overload. Comparative studies have shown that at comparable doses the efficacy of DFP in removing body iron is similar to that of desferoxamine (DFO). In retrospective and prospective studies, DFP monotherapy was significantly more effective than DFO in the treatment of myocardial siderosis in thalassemia major. DFP can be used in combination with DFO in the management of severe iron overload. This chelation regimen is tolerable and attractive for patients unable to comply with standard DFO infusions or with inadequate response to DFP monotherapy. DFP has a well-known long-term safety profile. Agranulocytosis is the most serious side effect associated with its use, occurring in about 1% of the patients. More common but less serious side effects are gastrointestinal symptoms, arthralgia, zinc deficiency, and fluctuating transaminase levels.

Clinical and molecular analysis of haemoglobin H disease in Sardinia: haematological, obstetric and cardiac aspects in patients with different genotypes.

In this study, 251 Sardinian patients (187 adults and 64 children) with haemoglobin (Hb) H disease were evaluated. Two-hundred and sixteen patients (86%) had the deletional type (- -/-alpha) and 36 (14%) patients had the non-deletional type (- -/alpha(ND)alpha). A clear genotype-phenotype correlation was found, with the non-deletional type more severe than the deletional type. Diagnosis of Hb H disease was incidental in about 60% of cases. Aplastic crises due to B19 parvovirus infection were found in five patients (2.1%), while 23 patients (9.6%) experienced one or more haemolytic crises. Nineteen patients with Hb H received sporadic red blood cell transfusions and three patients were repeatedly transfused. Forty-seven of 61 married women (77%) had 82 pregnancies. In children, mean serum ferritin was 87 +/-92 mug/l and in adults, was 192 +/- 180 mug/l in females and 363 +/- 303 mug/l in males. For the 98 male patients, a significant correlation was found between ferritin values and age (r2 = 0.33, P < 0.0001). In the Sardinian population, Hb H disease needs regular monitoring for early detection and treatment of possible complications, such as worsening of anaemia that may require red cell transfusion, cholelithiasis and iron overload.

The euglycemic clamp in patients with thalassaemia intermedia.

In order to evaluate the influence of haemosiderosis on the glucose metabolism we studied tissue sensitivity to insulin and the metabolic clearance rate (M.C.R.) of this hormone by means of euglycemic clamp technique using an artificial endocrine pancreas in 8 patients with thalassaemia intermedia and 8 control subjects. During the steady-state of euglycemic-hyperinsulinemic clamp (40 mU/m2/min) plasma insulin values were significantly lower and the insulin M.C.R. was significantly higher in thalassaemic patients compared to the controls. To achieve a comparable steady-state insulin concentration to the controls, we performed for a second time the euglycemic clamp in the thalassaemic patients increasing the insulin infusion rate to 80/mU/m2/min. The insulin M.C.R., the M index and the M/IRIs-s ratio were significantly higher in the thalassaemic patients compared to the controls. These results are indicative of an increased tissue peripheral sensitivity to insulin as well as the metabolic clearance rate of this hormone.

Systolic function of the hypertrophied left ventricle.

The effects of left ventricular hypertrophy (LVH) on systolic function were studied by echocardiography in 61 hypertensive patients. LV mass index (LVMI) and relative wall thickness (h/r ratio) were used together as LVH indices, and three patterns of LV adaptation to the pressure overload were observed: 13 patients had normal LVMI and h/r ratio (no LVH); 32 patients had increased h/r ratio, with normal or increased LVMI (concentric LVH); 16 patients had increased LVMI and normal h/r ratio (eccentric LVH). Cuff arterial pressure was lower in patients without LVH than in those with LVH, but both LVH indices correlated weakly with systolic, diastolic, and mean blood pressure (r = 0.22 to 0.33). Eccentric LVH showed peculiar hemodynamics, characterized by high cardiac output (CO) and normal total peripheral resistance (TPR), whereas CO was normal and TPR moderately and severely increased in patients without LVH and with concentric LVH, respectively. In the group without LVH, peak systolic stress (PSS) and systolic blood pressure/end-systolic volume index (SBP/Ves) were increased, whereas end-diastolic diameter (EDD), end-systolic stress (ESS), and fractional shortening (FS) were normal; thus, the ejective performance was preserved by increased contractility. The group with concentric LVH had normal PSS, ESS, EDD, and FS and increased SBP/Ves, showing that systolic function was normal or supernormal in the presence of adequate LVH. The group with eccentric LVH had increased PSS, ESS, and EDD, whereas FS and SBP/Ves were both normal; thus, the ejective performance was preserved--in spite of an inadequate LVH and increased afterload--through the action of preload reserve.(ABSTRACT TRUNCATED AT 250 WORDS)

Massive haemorrhagic pericardial effusion in beta-thalassaemia major.

The case of a child with beta-thalassaemia major who developed a massive haemorrhagic pericardial effusion is reported and in whom the clinical picture completely resolved after pericardiocentesis. Possible causes are discussed and the role of echocardiography in the follow-up of thalassaemic patients is emphasized.

Diagnostic and prognostic value of TPA in breast cancer.

Serum tissue polypeptide antigen (TPA) was measured by RIA in 151 female patients who had had mastectomies for breast cancer, in 30 patients with benign breast disease, and in 30 normal controls. The marker was elevated in 52 neoplastic patients (25 with metastases) and in six cases of benign breast disease. At the time of our observation 15 cancer patients were at stage I, 53 at stage II, 48 at stage III, and 35 at stage IV, the prevalence of high TPA values significantly correlated with staging gradually increasing from 0 to 71.4% from stage I to IV. In patients with breast cancer TPA was significantly higher in the subgroup with metastatic disease compared to patients with apparently inactive disease. Nineteen patients without (group A) and 35 with metastases (group B) were monitored with serial measurements of TPA for 8-24 months. Group B was receiving either hormone or chemotherapy. In 10 group A patients TPA was either higher or rose 1-7 months prior to the clinical detection of metastases. Twenty-two patients from Group B had disease progression: In 20 of them TPA rose further. The remaining 13 patients had an apparent disease regression, and in 11 instances TPA either fell or remained normal. Thus TPA can detect early recurrence of breast cancer before clinical and instrumental methods; moreover, it might prove important in evaluating tumor response to treatment and in follow-up of patients with metastatic disease. Finally, serial measurements of TPA could identify previous false-positive results, thus improving the specificity of the test.

Systolic time intervals in hyperthyroidism.

PEPI (pre-ejection period index), QS2I (total electromechanical systolic index), LVETI (left ventricular ejection time index), and PEP/LVET ratio were measured in 35 thyrotoxic patients. None of the patients had clinical evidence of heart disease nor received drugs which might have affected the systolic time intervals. the hyperthyroid subjects showed significant shortening of PEPI and significant reduction of PEP/LVET, which returned within normal limits when the patients became euthyroid during treatment. No correlation could be found between T3, T4, FTI and PEPI or PEP/LVET. However, serial measurements indicated that the fall toward the normal range of PEPI parallelled that of T3; the latter is considered the most important index of thyroid function. Our study suggests that PEPI and PEP/LVET ratio may be of great usefulness in detecting hemodynamic alterations in subjects with uncomplicated hyperthyroidism. Moreover, these methods may facilitate the diagnosis in unusual types of hyperthyroidism occurring in the absence of clinical signs of toxicosis. In addition, PEPI and PEP/LVET appear to be useful in detecting T3 toxicosis. Finally, serial controls of PEPI could represent a useful index to monitor the response to therapy.

Alteration of thyroid function in the early stage of subacute thyroiditis.

Measurement of serum triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyroxine-binding-globulin (TGB), antithyroglobulin antibodies (anti-hTg), thyroid 131I uptake and scanning was performed on 12 patients during the early phase of subacute thyroiditis. Serum thyrotropin (TSH) was measured during baseline conditions and following administration of synthetic thyrotropin-releasing-hormone (TRH). The stimulation with exogenous TSH was performed on 7 subjects. 131I uptake was depressed in all patients including those with solitary nodules. Free and total hormone concentrations were elevated in the three cases with diffuse gland involvement, whereas an increase of T3 alone was present in 3 patients with unilobar involvement. In the latter group and in the 2 patients with a nodular form T4, FT3 and FT4 levels were within normal limits. Interruption of the pituitary-thyroid feed-back mechanism with absence of thyrotropin response to TRH occurred in 11 patients, independent of whether thyroid hormone concentrations were elevated or normal. In one patient only with unilateral involvement, TSH responsiveness to TRH was normal while 131I uptake was not raised by exogenous TSH, indicating diffuse cellular damage. The normal values of FT3 and FT4 found in patients with normal T3 and T4 levels seem to exclude the possibility that the free hormones are responsible for the interrupted feed-back which represents the main cause of suppressed iodine uptake. However, it is possible that the pituitary-thyroid axis is responding to transient or light increases of free and total T3 and T4 still within their 'normal range'.