Impact of ß-thalassemia trait carrier state on cardiovascular risk factors and metabolic profile in patients with newly diagnosed hypertension.

Thalassemia minor (Tm), the ß-thalassemia carrier state, is followed by favorable lipidemic profile and seems to protect against myocardial infarction mainly in men. However, the cardiovascular risk factor (CRF) and metabolic profile of these subjects has not been thoroughly addressed, although it is not known whether gender differences are involved. We evaluated CRFs, metabolic parameters and risk-prediction equations along with renal function and selected echocardiographic indices in 23,680 consecutive subjects, that is, 11,192 women and 12,488 men, with newly diagnosed hypertension according to the presence or absence of Tm. Of 23,680 patients, 548 (2.3%) had Tm. Compared with patients without Tm, Tm cases had similar gender distribution, age, body mass index and blood pressure. Besides having a better lipidemic profile, Tm patients were less frequently smokers (25% vs. 32%, P<0.001), had a lower prevalence of metabolic syndrome (26% vs. 39%, P<0.001) and lower HeartSCORE and INTERHEART scores (P<0.001). Tm patients also had lower levels of fibrinogen and plasminogen activator inhibitor-1 (P<0.001), lower serum creatinine and higher estimated glomerular filtration rate (P<0.001), lower prevalence of left ventricular hypertrophy (35% vs. 48%, P<0.001) and higher total and mid-wall fractional shortening (P=0.03 and <0.001, respectively). Most of these differences were consistent in both genders, whereas the HeartSCORE and the echo indices were significantly better in Tm only in women. Among patients with newly diagnosed hypertension, those with Tm have a better overall CRF and metabolic profile, beyond the well-known differences in serum lipids. Compared with men, women seem to be at least equally protected.

Safety issues of iron chelation therapy in patients with normal range iron stores including thalassaemia, neurodegenerative, renal and infectious diseases.

An increased number of thalassaemia patients treated with effective chelation therapy protocols are achieving body iron levels similar to those of normal individuals. Iron chelation therapy has also been recently used in a number of other categories of patients with no excess body iron load such as neurodegenerative, renal and infectious diseases. Chelation therapy in the absence of iron overload in the latter conditions raises many safety issues including chelator overdose toxicity and toxicity related to iron and other essential metal deficiencies. Preliminary preclinical and clinical toxicity evidence suggest that deferoxamine and deferasirox can only be safely used for these non-iron loaded conditions for short-term treatments of a few weeks, whereas deferiprone can be used for longer term treatments of many months. The selection of the chelating drug and appropriate dose protocols for targeting specific organs and conditions is critical for the safety of patients with normal iron stores. Chelation therapy is likely to play a major role as adjuvant, alternative or main therapy in many non-iron loading conditions in the forthcoming years.

Heart disease in thalassemia intermedia.

Thalassemia intermedia (TI) presents with a clinical phenotype ranging between the severe, transfusion-dependent TM and the asymptomatic carrier state. Cardiovascular complications represent the primary cause of mortality both in TM and in TI. Several factors have been reported to interfere in the pathophysiology of cardiovascular abnormalities in TI, including high output state, vascular abnormalities, endothelial dysfunction, elastic tissue disorders, hypercoagulability, valvular abnormalities and, to a less extent, iron overload. These mechanisms end up affecting both left and right heart, hence leading to ventricular remodeling and finally heart failure.

Assessment and treatment of cardiac iron overload in thalassemia.

Cardiac disease remains the major cause of death in thalassemia major and iron overload is involved in heart failure development. Cardiac iron load and heart injury are evaluated by different means, among which CMR measurements remain the best method for estimation. In cases of heart iron overload, chelation treatment should be appropriately tailored in terms of intensification.

Impaired oxygen kinetics in beta-thalassaemia major patients.

AIM: Beta-thalassaemia major (TM) affects oxygen flow and utilization and reduces patients' exercise capacity. The aim of this study was to assess phase I and phase II oxygen kinetics during submaximal exercise test in thalassaemics and make possible considerations about the pathophysiology of the energy-producing mechanisms and their expected exercise limitation. METHODS: Twelve TM patients with no clinical evidence of cardiac or respiratory disease and 10 healthy subjects performed incremental, symptom-limited cardiopulmonary exercise testing (CPET) and submaximal, constant workload CPET. Oxygen uptake (VO2), carbon dioxide output and ventilation were measured breath-by-breath. RESULTS: Peak VO2 was reduced in TM patients (22.3 +/- 7.4 vs. 28.8 +/- 4.8 mL kg(-1) min(-1), P < 0.05) as was anaerobic threshold (13.1 +/- 2.7 vs. 17.4 +/- 2.6 mL kg(-1) min(-1), P = 0.002). There was no difference in oxygen cost of work at peak exercise (11.7 +/- 1.9 vs. 12.6 +/- 1.9 mL min(-1) W(-1) for patients and controls respectively, P = ns). Phase I duration was similar in TM patients and controls (24.6 +/- 7.3 vs. 23.3 +/- 6.6 s respectively, P = ns) whereas phase II time constant in patients was significantly prolonged (42.8 +/- 12.0 vs. 32.0 +/- 9.8 s, P < 0.05). CONCLUSION: TM patients present prolonged phase II on-transient oxygen kinetics during submaximal, constant workload exercise, compared with healthy controls, possibly suggesting a slower rate of high energy phosphate production and utilization and reduced oxidative capacity of myocytes; the latter could also account for their significantly limited exercise tolerance.

New insights into the exercise intolerance of beta-thalassemia major patients.

The purpose of our study was assessment of the relative contribution of the systems involved in blood gas exchange to the limited exercise capacity in patients with beta-thalassemia major (TM) using integrative cardiopulmonary exercise testing (CPET) with estimation of oxygen kinetics. The study consisted of 15 consecutive TM patients and 15 matched controls who performed spirometric evaluation, measurement of maximum inspiratory pressure (Pimax) and an incremental symptom-limited CPET on a cycle ergometer. Exercise capacity was markedly reduced in TM patients as assessed by peak oxygen uptake (pVO(2), mL/kg/min: 22.1+/-6.6 vs 33.8+/-8.3; P<0.001) and anaerobic threshold (mL/kg/min: 13.0+/-3.0 vs 18.7+/-4.6; P<0.001) compared with controls. No ventilatory limitation to exercise was noted in TM patients (VE/VCO(2) slope: 23.4+/-3.2 vs 27.8+/-2.6; P<0.001 and breathing reserve, %: 42.9+/-17.0 vs 29.5+/-12.0; P<0.005) and no difference in oxygen cost of work (peak VO(2)/WR, mL/min W: 12.2+/-1.7 vs 12.2+/-1.5; P=NS). Delayed recovery oxygen kinetics after exercise was observed in TM patients (VO(2)/t slope, mL/kg/min(2): 0.67+/-0.27 vs 0.93+/-0.23; P<0.05) that was significantly correlated with Pimax at rest (r: 0.81; P<0.001). The latter was also significantly correlated to pVO(2) (r: 0.84; P<0.001) and inversely correlated to ferritin levels (r: -0.6; P<0.02). Exercise capacity is markedly reduced in TM patients and this reduction is highly associated with the limited functional status of peripheral muscles.

Hypocalcemic heart failure in thalassemic patients.

Hypocalcemic cardiomyopathy in primary or secondary hypoparathyroidism is usually refractory to conventional treatment of cardiac failure. We report the case of a thalassemic patient with severe cardiac failure that might have been attributed to several factors, such as hemosiderosis, hypomagnesemia, and hypocalcemia, refractory to conventional cardiac therapy. Cardiac echocardiography showed impaired biventricular performance, and laboratory analyses revealed hypoparathyroidism due to hemosiderosis. When concomitant treatment of heart failure and calcium supplementation was initiated, correction of hypocalcemia resulted in clinical and laboratory improvement, providing strong evidence in support of our hypothesis about hypocalcemic myocardiopathy.

Neurophysiological monitoring of brainstem function in a patient with Wallenberg syndrome, using Vestibular Evoked Myogenic Potentials.

PURPOSE: We evaluated the use of Vestibular Evoked Myogenic Potentials (VEMPs) in the assessment of neural function, following medullary lesions. METHODS: A 54-year-old male presented with symptoms and signs typical of right lateral medullary (Wallenberg) syndrome. He underwent brain MRI and three successive neurophysiological investigations, which included VEMPs, Brainstem Auditory Evoked Responses (BAERs) and the blink reflex. RESULTS: VEMPs amplitude on the left (unaffected) side was 256.8 microv in the first investigation and remained approximately equal to that value in the following two ones. Their amplitude on the right (affected) side was 37.9 microv, 154.2 microv and 235.2 microv correspondingly. At the same time vertigo, diplopia and nystagmus gradually improved. Right blink reflex comprised a normal R1, but delayed R2 ipsilateral and R2 contralateral responses, which remained unaltered during the follow-up period. Brain MRI disclosed a right dorsolateral medullary infarct. CONCLUSIONS: VEMPs amplitude progressively increased, parallel to the improvement of vestibular symptoms. The blink reflex evolved differently, while BAERs were not affected. As the three evoked responses are mediated by separate neural circuits, they provide information on different aspects of brainstem function. Thus, VEMPs seem to be a useful method that complements existing ones in the assessment of brainstem lesions.

Systolic and diastolic function in middle aged patients with sickle beta thalassaemia. An echocardiographic study.

OBJECTIVE: To evaluate the right and left ventricular systolic and diastolic function in middle aged patients with sickle beta thalassaemia. METHODS: Forty three patients with sickle beta thalassaemia were recruited for echocardiographic study while 55 controls, matched for age and sex, served as the control group. Parameters measured included: dimensions and wall thickness of left (LV) and right (RV) ventricle and left atrium, LV mass, and cardiac index. LV and RV contractility variables--ejection fraction, circumferential fibre shortening velocity, end systolic stress, end systolic stress/volume index ratio, mitral and tricuspid annulus systolic excursion, and Tei index--were also calculated. The study also evaluated parameters of RV and LV diastolic function including early and late atrioventricular flow velocities (E and A wave respectively), E/A ratio, deceleration time (DT), isovolumic relaxation time (IVRT) as well as pulmonary and hepatic veins systolic to diastolic (S/D) ratio. RESULTS: Chamber enlargement, greater LV mass index, cardiac index, and RV wall thickness were found in the anaemic group compared with controls. The LV and RV contractility variables of the patients were similar to controls. Conversely the LV and RV Tei index was significantly greater in the patient group. Diastolic dysfunction was present in the anaemic patients resulting from the increased LV and RV A-wave, the longer LVIVRT, RVIVRT, and RVDT, as well as the higher hepatic and pulmonary veins S/D ratio. CONCLUSIONS: The results show that in middle aged patients with sickle beta thalassaemia the diastolic function is abnormal in both ventricles but still more in RV, whereas the systolic function remains unchanged.

Transfusional hemosiderosis and combined chelation therapy in sickle thalassemia.

Although the indications for transfusions in sickle cell syndromes are well listed, and chronic transfusion has become practicable since the recent advances in chelation therapy have essentially eliminated the risk of secondary iron overload, multi-transfused, non-compliant to long-term chelation therapy patients confront the complication of iron overload and secondary hemosiderosis. In thalassemia major patients, combined therapy with desferrioxamine and deferiprone has maximized tissue iron removal and may reduce the overall occurrence of hemosiderotic heart failure. Despite this, safety and contradictions of chelating agents are still controversial. The aim of this report is to present the results of this combination in a long-term transfused sickle beta-thalassemic patient suffering from severe heart failure and liver dysfunction.

Management of massive presacral bleeding during low pelvic surgery -- an alternative technique.

Although massive presacral bleeding during rectal mobilization is uncommon, it can rapidly destabilize a patient. So, effective hemostasis is critical in severe presacral hemorrhage due to the fatal course of this complication. Among the reported methods are packing, thumbtacks, inflatable devices, muscle tamponade, muscle fragment welding and application of endoscopic staplers. Local hemostatic agents in conjunction with other methods such as diathermy, cyanoacrylate tissue adhesives and application of bone wax are among other alternatives which may help to treat this serious complication. The aim of this study is to describe the anatomic and physiologic basis of our mode of treatment, which is new in the literature approach, treating two patients with presacral bleeding during low anterior resection for rectal cancer. The technique is the early clamping of the infrarenal aorta and suture ligation of the bleeding points from the presacral plexus.

Retroperitoneal perforation of a duodenal diverticulum with colonic necrosis -- report of a case.

Primary duodenal diverticula are usually asymptomatic. About 115 perforations have been reported, but none with right colon necrosis. We report a 45-year-old woman, with a five days history of high fever along with epigastric and periumbilical pain. Physical examination revealed right upper and lower quadrant tenderness with peritoneal signs. White blood cell count was 11 500/mm (3) while biochemical and hepatic biology tests were normal. Abdominal radiographs showed no pathologic findings. Ultrasound disclosed fluid in the lower pelvis. Computerized tomography revealed fluid collection in the right hepatorenal space. Intraoperative findings included purulent fluid in the lower pelvis, segmental necrotic changes of the right colon, and a perforated diverticulum on the antimesenteric border of the third part of the duodenum. Surgery consisted of right hemicolectomy and ileo-transverse anastomosis, diverticulectomy, and decompressive lateral duodenostomy at the second duodenal portion. The patient had an uneventful postoperative course. A contrast study from the duodenostomy tube on the 6 (th) postoperative day showed no leakage or obstruction. Duodenostomy tube was removed on the 14 (th) postoperative day. Histology confirmed the diagnosis of a primary duodenal diverticulum.

Metformin administration improves endothelial function in women with polycystic ovary syndrome.

OBJECTIVE: The aim of this study was to investigate the endothelial status in young women with polycystic ovary syndrome (PCOS), using a simple and easily reproducible hemodynamic method combined with a biological marker and to evaluate the effect of metformin treatment on these parameters. DESIGN: Descriptive clinical trial. METHODS: Forty young women, 20 with PCOS and 20 normal women of similar age and body mass index were studied. Metformin (1700 mg daily) was administered for 6 months to the PCOS group. The endothelium status and the metabolic and hormonal profile were studied in both groups, as well as after metformin, by flow-mediated dilatation (FMD) on the brachial artery and by measurements of plasma endothelin-1 (ET-1) levels. RESULTS: FMD was impaired in the PCOS group when compared with controls (3.24+/-0.71% vs 8.81+/-1.07% respectively, P<0.0001), but this difference normalized after metformin treatment (PCOS(post-metformin) vs controls: 8.17+/-1.26 vs 8.81+/-1.07%, P = 0.70) since the values significantly improved after metformin treatment (PCOS(pre-metformin) vs PCOS(post-metformin): 3.24+/-0.71 vs 8.17+/-1.26%, P=0.003). ET-1 levels were significantly higher in the PCOS women compared with the control group (7.23+/-0.50 vs 4.99+/-0.69 fmol/l, P=0.01), they improved significantly after metformin treatment (PCOS(pre-metformin) vs PCOS(post-metformin): 7.23+/-0.50 vs 3.57+/-0.60 fmol/l, P<0.0001) and their difference compared with the control group was reversed (PCOS(post-metformin) vs controls: 3.57+/-0.60 vs 4.99+/-0.69 fmol/l, P=0.13). Metformin administration improved hyperandrogenemia. However, in this study, mathematical methods used to assess insulin resistance failed to show any detected alteration after treatment with metformin. CONCLUSIONS: PCOS women were found to exhibit endothelial dysfunction compared with controls, which was reversed 6 months after metformin administration.

Reversal of heart failure in thalassemia major by combined chelation therapy: a case report.

In patients with thalassemia major (TM) who are non-compliant with long-term desferrioxamine (DFO) chelation, survival is limited mainly because of cardiac complications of transfusional hemosiderosis. Combined chelation therapy with DFO and deferiprone has maximized the efficacy of the therapy and reduced cardiological complications. The aim of this report is to present the results of this combination in a desperate case of heart failure.

Waldenström's macroglobulinemia developing in a patient with multiple sclerosis: coincidence or association?

Multiple sclerosis (MS) has been reported in association with haematological abnormalities, including monoclonal gammopathies. We present a 54-year-old male patient with a 30-year history of MS who was admitted to our hospital for investigation of anaemia and increased erythrocyte sedimentation rate. A monoclonal IgM protein was detected by serum protein immunofixation, while bone marrow biopsy indicated a 70% infiltration by small lymphoplasmacytoid cells, in the context of a lymphoplasmacytoid immunocytoma, findings compatible to the diagnosis of Waldenström's macroglobulinemia (WM). To our knowledge, this is the first report of WM in a patient with MS. Further to the coexistence of the two diseases observed in the case presented here, there is additional evidence suggesting that the association of MS with plasma cell dyscrasias may not be coincidental.

Presence of metabolic risk factors in non-obese PCOS sisters: evidence of heritability of insulin resistance.

This study was performed to determine whether phenotypically healthy sisters of women with polycystic ovary syndrome (PCOS) have evidence of insulin resistance. We studied 54 women: 17 with PCOS, 17 sisters of these probands and 20 control women with similar age, body mass index (BMI) and waist-to-hip ratio (WHR). The PCOS sisters had neither clinical nor laboratory evidence of hyperandrogenism. However, estimated insulin resistance indices indicated decreased insulin sensitivity in PCOS sisters compared with the controls. No difference of insulin resistance indices was detected between the PCOS and their sisters. This finding provides additional evidence that there is a hereditary trait regarding insulin resistance in the PCOS families.