Clinical outcome of transfusions with extended red blood cell matching in ß-thalassemia patients: A single-center experience.

BACKGROUND: The development of alloantibodies may complicate the management of patients with ß-thalassemia. An extended antigenic matching may reduce the risk of alloimmunization. Our previous study showed that the introduction of molecular red blood cell (RBC) typing allows finding suitable blood units for multi-transfused patients. The aim of this study was to evaluate the benefit of RBC transfusion with extended antigenic match. MATERIALS AND METHODS: At the University of Campania "L. Vanvitelli", we selected ß-thalassemia major patients (age ≤23 years), without preformed alloantibodies. Data of patients receiving transfusion of leukoreduced RBC units for a period of one year with partial better match (PBM) including ABO, RhD, C/c, E/e, K/k antigens and consecutive one year with extended match (EM) including ABO, RhD, C/c, E/e, K/k, Fya/Fyb, Jka/Jkb, M/N, S/s antigens, were compared. RESULTS: Eighteen patients, 8 males and 10 females with a mean age of 15.4 years (6.4 SD) received a mean number of 41.2 (6.0 SD) RBC units transfused with PBM and 41.8 (6.2 SD) with EM protocols. After two years of RBC transfusions with both antigen matching protocols, no new alloantibodies were developed in patients. No significant differences in Hb concentration and volume of RBC transfused were found between PBM and EM protocols. CONCLUSIONS: Thalassemia patients may benefit from receiving RBC transfusions based on extended antigen matching as demonstrated by the lack of new alloantibodies. However, our data show a high concordance between PBM and EM protocols considering pre-transfusion Hb, increment of Hb and volume of RBC transfused.

Apoptosis of bovine granulosa cells: Intracellular pathways and differentiation.

Follicular atresia in granulosa and theca cells occurs by apoptosis through weak hormonal stimulation. We have previously proposed an in vitro model to study this process by inducing apoptosis in BGC-1, a bovine granulosa cell line, and in primary cultures from ovaries with or without corpus luteum (CPGB+ and CPGB-, respectively), with different doses of gonadotropin releasing hormone (GnRH) analogs (leuprolide acetate (LA) as agonist and antide as antagonist). BGC-1 represent immature granulosa cells, whereas CPGB represent different degrees of luteinization. Our aim was to evaluate the intracellular pathways involved in the GnRH regulation of apoptosis in BGC-1. Treatment with LA 100nM but not with antide led to an increase in BAX over BCL-2 expression, showing antagonism of antide. All treatments inhibited phospholipase-D (PLD) activity compared to control, implying agonist behavior of antide. Progesterone in vitro production and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) expression revealed different degrees of luteinization: BGC-1 were immature, whereas CPGB+ were less differentiated than CPGB-. We concluded that LA-induced apoptosis in BGC-1 occurs by activation of the mitochondrial pathway and by inhibition of PLD activity and that antide might work both as an antagonist of the intrinsic pathway and as an agonist of the extrinsic protection pathway by inhibiting PLD activity.

Is there still a role for computed tomography and bone scintigraphy in prostate cancer staging? An analysis from the EUREKA-1 database.

PURPOSE: According to the current guidelines, computed tomography (CT) and bone scintigraphy (BS) are optional in intermediate-risk and recommended in high-risk prostate cancer (PCa). We wonder whether it is time for these examinations to be dismissed, evaluating their staging accuracy in a large cohort of radical prostatectomy (RP) patients. METHODS: To evaluate the ability of CT to predict lymph node involvement (LNI), we included 1091 patients treated with RP and pelvic lymph node dissection, previously staged with abdomino-pelvic CT. As for bone metastases, we included 1145 PCa patients deemed fit for surgery, previously staged with Tc-99m methylene diphosphonate planar BS. RESULTS: CT scan showed a sensitivity and specificity in predicting LNI of 8.8 and 98 %; subgroup analysis disclosed a significant association only for the high-risk subgroup of 334 patients (P 0.009) with a sensitivity of 11.8 % and positive predictive value (PPV) of 44.4 %. However, logistic multivariate regression analysis including preoperative risk factors excluded any additional predictive ability of CT even in the high-risk group (P 0.40). These data are confirmed by ROC curve analysis, showing a low AUC of 54 % for CT, compared with 69 % for Partin tables and 80 % for Briganti nomogram. BS showed some positivity in 74 cases, only four of whom progressed, while 49 patients with negative BS progressed during their follow-up, six of them immediately after surgery. CONCLUSIONS: According to our opinion, the role of CT and BS should be restricted to selected high-risk patients, while clinical predictive nomograms should be adopted for the surgical planning.

The importance of psychosexual counselling in the re-establishment of organic and erotic functions after penile prosthesis implantation.

Although many studies about penile prosthesis implantation (PPI) have been published so far, only a small amount of them take into account patients and partners outcome in terms of satisfaction and erotic function. The aim of this study is to explore the value of psycosexual counselling in and the sexual and erotic function of penile prosthesis recipients. Thirty patients and their partners were randomised into two groups. In arm A (case group) patients and their partners underwent a multistep psychosexual counselling before and after surgery. In arm B (control group) surgery was performed without the specific psychosexual counselling scheme. Specific questionnaires (International Index of Erectile Function (IIEF) and the Sexual Daydreaming Scale (SDS)) were administered before surgery and 12 months afterwards. Twenty-four months postoperatively patients were asked to complete the Global Assessment Questions (GAQ) and the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), while their partners were asked to answer to the EDITS partner's section. Between January 2009 and October 2011, we enrolled 30 patients undergoing PPI in our institution (15 in each arm). Twenty-four months postoperative follow-up is available for all of them. No significant differences between the two groups in terms of baseline questionnaires scores were observed. Mean IIEF score was significantly higher in case group (arm A 68.3, arm B 53.4, P-value<0.001). At 12 months after PPI the improvement of erotic function according to SDS was significantly higher in the study group for both patients and their partners. Improvement in satisfaction rates were confirmed at 24 months, with statistically significant scores for EDITS in arm A patients and partners as compared with arm B. PPI with a pre- and postoperative psychosexual counselling scheme resulted in better postoperative sexual activity and erotic function for both patients and partners than PPI alone.

Vitamin D levels in a paediatric population of normal weight and obese subjects.

BACKGROUND: Vitamin D exerts pleiotropic effects and few studies are available in the Italian population. AIM: Aim of our study was to evaluate vitamin D status in children living in Northern Italy. METHODS: We studied vitamin D levels in a population of 113 normal weight (NW) and 444 obese (OB) children, prepubertal and pubertal. We considered vitamin D levels >20 ng/ml as normal, but also measured percentage of children with vitamin D levels higher than a cutoff of 30 ng/ml. RESULTS: 68.2 % of NW children showed normal levels of vitamin D, while 31.8 % showed a clear vitamin D deficiency. Only 28.3 % showed vitamin D levels higher than 30 ng/ml. Obese children showed 55.6 % of subjects with normal levels of vitamin D and 44.4 % of subjects a status of vitamin D deficiency. Only the 18.9 % showed vitamin D levels higher than 30 ng/ml. Mean vitamin D levels in NW children (27.3 ± 1.2 ng/ml) were higher than in OB children (21.8 ± 0.6 ng/ml). No differences have been found between prepubertal and pubertal children in terms of vitamin D levels. CONCLUSIONS: Our paediatric population demonstrates a low percentage of vitamin D sufficiency. In particular, obese children show only 19 % of subjects with normal levels while almost half of this population shows a clear deficiency. Further studies are needed to support these results and to evaluate the possible metabolic consequences.

[Craniopharyngioma in children: importance of a multidisciplinary approach and therapeutic strategies in the treatment of relapsing]. / Craniofaringioma in età pediatrica: importanza di un approccio multidisciplinare e strategie terapeutiche nel trattamento della forme recidivanti.

The craniopharyngioma is a benign intracranial nonglial tumor derived from a malformation of the embryonic tissue. Represents approximately 6-9% of brain tumors in children. It grows close to the optic nerve, hypothalamus and pituitary. The most frequent histological variety in children is adamantinomatous. The initial symptoms of intracranial hypertension is headache and nausea, followed by visual disturbances, impaired hormonal changes such as the secretion of GH, gonadotropins, TSH and ACTH and central diabetes insipidus. We present the clinical case of MD, 5yrs at age, which shows signs of intracranial hypertension syndrome: neuroradiological findings raise the diagnosis of adamantinomatous craniopharyngioma for which the child underwent to sub-total surgical removal of the lesion and radiosurgery treatment. During the disease develops visual impairment, and secondary diabetes insipidus, hypothyroidism hipocotisolism that takes therapy with desmopressin (Minirin), Cortone acetate and L-tiroxine. For the failure of previous therapies, the child has performed chemotherapy with cisplatin (30 mg/sqm/day) and Etoposide (150 mg/mq/day). A year after the end of the last cycle of chemotherapy was detected new progression of the lesion with the appearance of worsening headache and vomiting in the upright position. TC notes the expansion of the third ventricle and the patient undergoes surgery craniotomy. This clinical case underlines the difficulties in treatment of recurrent craniopharyngioma in situations where the anatomical location do not permit aggressive radical surgery. Anyway, new studies are needed to evaluate the effectiveness of systemic chemotherapy as a method of experimental treatment that could reduce the progression of disease.

Iliac artery-ureteral fistula: a fatal hemorrhage in a man with ureterocutaneostomy.

Primary and secondary artery-ureteral fistulas are a rare condition. In this case report we describe a case of misunderstood iliac artery-ureteral fistula, with negative radiological preoperative imaging, which occurred in a man as late complication of ureterocutaneostomy.

[Neuroendocrine bladder cancer: oncological emergency?].

Neuroendocrine bladder cancer is extremely rare, with an estimated incidence of 0.5%- 0.7%. In bladder cancers there is no evident connection between the neuroendocrine phenotypic expression and the clinical history. However, prognosis is usually poor and the survival rate at 5 years does not exceed 8%, if untreated. METHODS. We are here describing three case reports of bladder carcinoma with neuroendocrine differentiation, which is extremely aggressive and leads rapidly to death. At the present time, the local control of these tumors is achieved by radical cystectomy and radiotherapy; they can be both associated to chemotherapy. However, since these lesions are fairly rare, there is no gold standard therapy and there are no prospective studies on the management of these tumors. CONCLUSIONS. Considering the quick evolution and progression of any variant of the neuroendocrine tumors of the bladder, urologists and anesthetists should see them as real oncological emergencies. A prompt intervention through radical surgery with cystectomy and linfadenectomia, and the anathomo-pathologist's systematic investigation of the scraps could make the approach therapeutic and not only palliative. Prospective studies on neo-adjuvant chemotherapy as well as experimental studies about target therapies may yield new guidelines on the tumor management.

Effect of gestational hypercholesterolaemia on omental vasoreactivity, placental enzyme activity and transplacental passage of normal and oxidised fatty acids.

OBJECTIVE: Maternal hypercholesterolaemia during pregnancy increases lipid peroxidation in mothers and fetuses and programs increased susceptibility to atherosclerosis later in life. The objective of this study was to elucidate the role of the placenta in mediating oxidative stress from mother to offspring. DESIGN: Comparison between normo- and hypercholesterolaemic mothers (n = 36 each) and their children. SETTING: Obstetric wards, hospitals of the University of Naples and Regione Campania. POPULATION: Healthy primiparas delivering by caesarean section. METHODS: Biochemical measurements of oxidative stress and serum leptin in cord plasma and placenta, immunochemistry of placenta microvessels, and vasoreactivity studies were performed. MAIN OUTCOME MEASURES: Oxidative status (i.e. lipid composition and content of oxidised fatty acids, activity of pro- and antioxidant enzymes, immunohistochemical presence of oxidation-specific epitopes) in maternal and cord blood and in placental tissue, as well as vascular reactivity in omental arteries. RESULTS: Hypercholesterolaemia during pregnancy was associated with extensive changes in fatty acid composition of both maternal and cord blood lipids, sufficient to alter vasoreactivity of omental vessels. Results also indicated that the placenta is not only subject to substantial oxidative stress, but that it may further increase fetal oxidative stress through changes of pro- and antioxidant enzyme activities. CONCLUSIONS: The placenta plays an important role in both transmitting and enhancing pathogenic effects of gestational hypercholesterolaemia.

In vivo veritas: thrombosis mechanisms in animal models.

Experimental models have enhanced our understanding of atherothrombosis pathophysiology and have played a major role in the search for adequate therapeutic interventions. Various animal models have been developed to simulate thrombosis and to study in vivo parameters related to hemodynamics and rheology that lead to thrombogenesis. Although no model completely mimics the human condition, much can be learned from existing models about specific biologic processes in disease causation and therapeutic intervention. In general, large animals such as pigs and monkeys have been better suited to study atherosclerosis and arterial and venous thrombosis than smaller species such as rats, rabbits, and dogs. On the other hand, mouse models of arterial and venous thrombosis have attracted increasing interest over the past two decades, owing to direct availability of a growing number of genetically modified mice, improved technical feasibility, standardization of new models of local thrombosis, and low maintenance costs. To simulate rupture of an atherosclerotic plaque, models of arterial thrombosis often involve vascular injury, which can be achieved by several means. There is no animal model that is sufficiently tall, that can mimic the ability of humans to walk upright, and that possesses the calf muscle pump that plays an important role in human venous hemodynamics. A number of spontaneous or genetically engineered animals with overexpression or deletion of various elements in the coagulation, platelet, and fibrinolysis pathways are now available. These animal models can replicate important aspects of thrombosis in humans, and provide a valuable resource in the development of novel concepts of disease mechanisms in human patients.

A study of low-nutrient diets used for aging studies in the rat.

The effects of diets of low caloric value on rats used in aging studies were investigated. Groups of 85 Sprague-Dawley rats were fed ad libitum from 3 months of age on three different diets containing 8 or 10 Megajoule (MJ) of metabolizable energy and 80 or 100 g of crude protein/kg. Body weights, food consumption, and morphological and biochemical parameters were monitored throughout life. Kidneys were examined histologically. Rats given the diet with highest energy and protein ate less food, attained greater weights, and had larger abdominal fat deposits than those on the lower energy diets. They had a raised proteinuria, and nearly half developed glomerulosclerosis and tubulo-interstitial damage by 26 months. There was no significant difference in mortality between the groups, and no other serious abnormalities were observed. It is concluded that rats can be maintained into old age with no signs of nutritional inadequacy on diets with lower energy and protein contents than those in general use.

Hematologic and biochemical profiles of selectively bred WHHL rabbits.

In Watanabe heritable hyperlipidemic (WHHL) rabbits, hypercholesterolemia and hypertriglyceridemia develop from birth, because of a deficiency of low-density lipoprotein receptors, and are followed by a consequent early development of aortic atherosclerosis. This closely resembles human familial hypercholesterolemia. Starting in 1984, we have developed a closed colony by breeding two male and two female homozygous WHHL rabbits, obtained from Japan (Dr. Watanabe, Kobe University). In our facility, the application of a selective breeding program, strictly based on mating parents that both have high serum lipid concentrations, has produced markedly elevated cholesterol (701 +/- 172 mg/dl, mean +/- SD) and triglyceride (780 +/- 325 mg/dl) concentrations in weaning rabbits. Clinical chemical analysis revealed no kidney or liver function abnormalities even in animals with extremely high lipid concentrations, and hematologic profiles were very similar in WHHL and age-matched New Zealand White rabbits, with the exception of platelet count, which was significantly higher in WHHL rabbits. Platelet aggregation induced by collagen and platelet-activating factor was significantly reduced in WHHL rabbits, whereas thrombin and prothrombin times appeared normal when compared with those in New Zealand White rabbits.

General toxicity and peripheral nerve alterations induced by chronic vincristine treatment in the rabbit.

The effects of five 0.3 mg/kg intravenous administrations of vincristine (VCR) at weekly intervals were studied in the rabbit. Body weight gain was impaired starting from the first injection, while gross signs of motor paralysis and hair loss initiated from the third week. At the end of the observation period blood analysis revealed normocytic normochromic anemia, elevated serum creatine kinase, and low serum alkaline phosphatase, whereas all the tested parameters related to liver and kidney functions where within normal limits. The decreased number of red blood cells was the consequence of a complete, although reversible, blockade of staminal hematopoietic activity. Two important indexes of peripheral nerve function were clearly altered at the end of the treatment: (i) the sciatic nerve conduction velocity in vitro was 27% reduced and (ii) the latency between sciatic nerve stimulation and extensor digitorum longus (EDL) twitch in vivo was 34% prolonged. The usefulness of the rabbit as an animal model to study side-effects of VCR treatment is discussed.