Inappropriate leptin secretion in thalassemia: a potential cofactor of pubertal timing derangement

The objective of the present study was to gain a better understanding of the role played by scarce leptin production in the deranged sexual development observed in patients with thalassemia. We studied 101 patients at different stages of puberty. Patients of both sexes were divided into three groups according to Tanner stages: T1-2 (20 males and 12 females), T3-4 (9 males and 4 females) and T5 (48 males and 8 females). Serum levels of leptin, ferritin, testosterone and estradiol were assessed. Leptin levels were adjusted for body mass index (BMI) using reference ranges stratified on the basis of gender and pubertal development. Deviations from the mean reference values were evaluated by calculating the standard deviation scores. Mean leptin standard deviation scores were significantly lower than expected in pubertal stage T1-2 and T3-4 in males and T3-4 and T5 in females. The peak leptin level was delayed in boys (13 years). In girls, parallelism between leptin and BMI was present until age 7-10 years; thereafter, although BMI constantly increased, leptin levels fell dramatically. Mean ferritin levels were significantly higher in pubertal stage T1-2 among males and in T5 among females. These findings show that in thalassemia adipose tissue is unable to assure adequate leptin production just when the highest leptin secretion is required and suggest that this inappropriate leptin secretion may be a cofactor of the derangement in pubertal timing observed in patients with thalassemia.     

Expression of alpha2a-2b neuregulin-1 is associated with early peripheral nerve repair along muscle-enriched tubes

Using RT-PCR, we have investigated expression of isoforms beta1 (the axonal isoform) and alpha2a-2b (the mesenchymal isoform) of neuregulin-1, one of the most important known trophic factors for Schwann cells, in the rat sciatic nerve repaired by muscle-enriched non-nervous conduits (made by a vein filled with fresh skeletal muscle). Repaired nerves were harvested 2, 6 and 13 days post-operatively. Results showed that while muscle-vein combined grafts were enriched in mRNA coding for alpha2a-2b since the very early regeneration stages, isoform beta1 mRNA was not detectable inside the tubes at day 2 and 6 post-operatively while its expression at day 13 was very slight. These results suggest that Schwann cell survival and activity inside a fresh muscle-enriched non-nervous conduit graft (a key factor for successful nerve regeneration along the graft) may be supported by the mesenchymal isoform of neuregulin-1 during very early repair phases, i.e. when axons are still not present along the tube.     

Continuous apomorphine infusion and neuropsychiatric disorders: a controlled study in patients with advanced Parkinson’s disease

Abstract. The aim of this study was to asses whether patients with Parkinsons disease (PD) develop cognitive and psychiatric complications more frequently during prolonged therapy with continuous apomorphine infusion compared with standard oral treatment. Thirty consecutive PD patients with severe motor fluctuations were included in the study. Twelve patients accepted the treatment with subcutaneous continuous apomorphine infusion, while the remaining 18 preferred to continue with oral dopaminergic therapy. The two groups were evaluated with neuropsychological, psychiatric, and motor tests at baseline and after 1 year. The off daily duration and the levodopa dosage were significantly reduced in infused patients. The neuropsychiatric assessment did not change in both groups compared with baseline, except for a significant improvement of mood in the apomorphine group.     

Predictors of stroke in the modern era of coronary artery bypass grafting: a case control study

BACKGROUND: Stroke is a rare but devastating complication after coronary artery bypass grafting (CABG) and its prevention remains elusive. We used a case control design to investigate the extent to which preoperative and perioperative factors were associated with occurrence of stroke in a cohort of consecutive patients undergoing myocardial revascularization. METHODS: From April 1996 to March 2001, data from 4,077 patients undergoing CABG were prospectively entered into a database. The association of preoperative and perioperative factors with stroke was investigated by univariate analyses. Factors observed to be significantly associated with stroke in these analyses were further investigated using multiple logistic regression to estimate the strength of the associations with the occurrence of stroke, after taking account of the other factors. RESULTS: During the study period, 4,077 patients underwent CABG and of these 923 (22.6%) had off-pump surgery. Forty-five patients suffered a perioperative stroke (1.1%). Overall there were 46 in-hospital deaths (1.1%), of whom 6 also suffered a stroke. Brain imaging of the stroke patients showed embolic lesions in 58%, watershed in 28%, and mixed in 14%. Multivariate regression analysis identified several preoperative factors as independent predictors of stroke, ie, age, unstable angina, serum creatinine greater than 150 mcg/ml, previous cerebrovascular accident (CVA), peripheral vascular disease (PVD), and salvage operation. When operative risk factors were added to the adjusted model, off-pump surgery was associated with a substantial, but not significant, protective effect against stroke (odds ratio = 0.56, 95% confidence interval 0.20 to 1.55). Survival for stroke patients was 93% and 78% at 1 and 5 years, respectively. CONCLUSIONS: Overall incidence of stroke is relatively low in our series. Age, unstable angina, previous CVA, PVD, serum creatinine greater than 150 mcg/ml, and salvage operation are independent predictors of stroke. These factors should be taken into account when informing each individual patient on the possible risk of stroke and in the decision-making process on the surgical strategy.     

Magnesium-supplemented warm blood cardioplegia in patients undergoing coronary artery revascularization

BACKGROUND: Although there is growing evidence to suggest that the administration of magnesium (Mg2+) to patients undergoing coronary artery bypass grafting (CABG) and to patients after myocardial infarction is beneficial, the addition of Mg2+ to cardioplegic solutions remains controversial. The aim of this study was to compare the effects of intermittent warm blood cardioplegia with and without Mg2+ supplementation on the early postoperative clinical outcomes in patients undergoing both elective or urgent CABG. METHODS: Four hundred patients undergoing CABG were prospectively randomized to receive either blood cardioplegia without Mg2+ (BC, n = 200) or supplemented with Mg2+ (BC-Mg2+, n = 200). Serial plasma Mg2+ concentrations were recorded at base line and postoperatively from days 1 to 4. RESULTS: Patient characteristics were similar and no significant differences were found in early mortality and morbidity in the two groups. Analysis of 178 patients undergoing urgent CABG for unstable symptoms (BC = 95, BC-Mg2+ = 83) demonstrated a significantly lower requirement for internal defibrillation and temporary epicardial pacing in the BC-Mg2+ group. Furthermore, there was a nearly twofold lower incidence of new postoperative atrial fibrillation in the BC-Mg2+ group compared with the BC group (19% versus 34%, p = 0.03). Postoperative plasma Mg2+ levels were consistently lower in those patients who developed new postoperative atrial fibrillation compared with those who did not (p = 0.05). CONCLUSIONS: The addition of Mg2+ to warm blood cardioplegia resulted in a lower incidence of intraoperative and postoperative arrhythmias in patients undergoing urgent CABG for unstable angina.     

Sustained increases of plasma homocysteine,copper, and serum ceruloplasmin after coronary artery bypass grafting

BACKGROUND: Homocysteine (Hcy) is an independent risk factor for coronary artery disease, but there are no reports on Hcy levels in patients undergoing coronary artery bypass graft (CABG) surgery. Interactions between Hcy and copper may mediate the vasculopathic impact of Hcy, and this may play a role in vein graft failure. The aim of this study was to assess the perioperative levels of Hcy, copper, ceruloplasmin (CP), folate, and vitamin B12 in patients undergoing myocardial revascularization surgery. METHODS: Blood samples were taken from 55 consecutive patients undergoing elective conventional CABG (43 male; mean age, 63.2 +/- 5.2 years) 1 day preoperatively and postoperatively at 1 day, 6 days, and 6 weeks. Hcy, copper, CP, red cell folate, vitamin B12, creatinine, and C-reactive protein (CRP) were then measured using standard clinical chemistry methods. The same protocol was applied to 10 patients (7 male; mean age, 63.3 +/- 5.2 years) undergoing off-pump coronary artery bypass (OPCAB) surgery. RESULTS: In the conventional CABG group, there were significant increases in the plasma concentrations at 6 days and 6 weeks postoperatively of Hcy (from 10.1 to 11.6 and 13.5 micromol/L, respectively), plasma copper (from 13.5 to 20.3 and 18.5 micromol/L), and serum ceruloplasmin (from 0.3 to 0.41 and 0.44 g/L). CRP and vitamin B12 were elevated at 6 days but not 6 weeks after the operation. In contrast, red cell folate and creatinine were not significantly changed. The subgroup analysis for the OPCAB patients showed the same trend as for the conventional group. CONCLUSIONS: Coronary surgery precipitates a significant and sustained increase in the blood concentrations of Hcy and copper, which is not due to a decrease in folate and vitamin B12, altered renal function, or inflammation. Further studies are required to establish whether the concomitant increase in Hcy and copper plays an etiological role in vein graft disease.     

Lymphoma of the cecum: a case report

Non-Hodgkin lymphomas present a wider systemic diffusion than Hodgkin lymphomas. Superficial and internal nodes, the tracheobronchial tree, and the digestive tract are almost always affected. The gastrointestinal tract is affected in 50% of the cases; the stomach is the first organ, followed by the small intestine and large intestine. The colon is affected in only approximately 0.4% of cases. The clinical picture of our patient showed abdominal pain, palpable mass, and anemia. Colonoscopy showed a tumor in the cecum (diameter, approximately 10 cm) and the biopsy indicated lymphoma. Through computed tomography, bone marrow biopsy, and measurement of beta2-microglobulin, complete staging was obtained. Right hemicolectomy was immediately performed because the large tumor could determine intestinal occlusion. Definitive diagnosis was non-Hodgkin lymphoma, type mucosa-associated lymphatic tissue B cells with a low grade of malignancy. After surgery the patient underwent six courses of chemotherapy according to the CHOP scheme (750 mg/m2 cyclophosphamide, 1.4 mg/m2 vincristine, 50 mg/m2 adriamicin, and 80 mg prednisone). Two years after surgery the patient shows no sign of the disease.     

Evolution of OPCAB surgery in a single institution

Off-pump coronary artery bypass (OPCAB) grafting is becoming popular worldwide. The development of exposure and stabilization techniques have made this surgery a simple, safe, and routine procedure. The evolution of OPCAB surgery at our institution is presented and discussed.     

Plasma protein oxidation is associated with an increase of procoagulant markers causing an imbalance between pro- and anticoagulant pathways in healthy subjects

The aim of the present study was to investigate whether the overall oxidation state of plasma proteins is associated with changes of circulating pro- and anticoagulant markers in healthy subjects (n = 99, 49 males, 50 females, aged from 6 to 91 yrs.). The carbonyl content of plasma proteins was measured and validated as an ex vivo index of the overall protein oxidation state due to its correlation with the plasma level of o-tyrosine (r = 0.87, P <0.0001), which is a well known oxidized product of L-phenylalanine. Using a multivariate analysis the carbonyl content of plasma protein was positively associated with procoagulant markers such as prothrombin F1 + 2 (r = 0.28, P = 0.0019) and fibrinopeptide A, (FpA) (r = 0.278, P = 0.003), as well as with the soluble derivative of the endothelial protein thrombomodulin (TM) (r = 0.469, P <0.0001). The procoagulant marker of thrombin activity, FpA, was significantly and positively correlated with the anticoagulant product of thrombin, namely the Protein C activation peptide (PCP), only in the tertile with low protein carbonyl content. At higher tertiles this correlation was no longer observed, thus suggesting a detrimental effect of oxidative stress on the TM/Protein C anticoagulant pathway. In 15 subjects with high carbonyl content of plasma protein, treatment for 18 days with 600 mg/d of vitamin E did not substantially modify the protein carbonyl content, the anticoagulant markers APC/PCP, and all procoagulant markers except F1+2, whose value significantly decreased by 25%. In conclusion, the present study shows that a high plasma protein oxidation ex vivo is associated with an overall hemostatic imbalance, which favors procoagulant markers. Vitamin E treatment in vivo restores only in part the equilibrium between pro- and anticoagulant pathways. This may open the way to further studies aimed at elucidating the mechanisms by which the oxidative stress is linked to activation of the coagulation system in atherothrombotic disorders.