Angiosarcoma of an Arteriovenous Fistula for Hemodialysis in a Kidney Transplant Recipient Affected by Lowe's Syndrome.

Objective/Background. To describe an uncommon, life-threatening condition such as angiosarcoma of a fistula for hemodialysis occurring in a transplant recipient affected by Lowe's syndrome. Summary. We present the case of a 56-year-old male kidney transplant recipient affected by Lowe's syndrome, also known as oculocerebrorenal syndrome, a rare X-linked disorder characterized by congenital cataracts, hypotonia, intellectual disability, and Fanconi-like renal tubular dysfunction, who was diagnosed with angiosarcoma of a functioning arteriovenous fistula for hemodialysis. Conclusion. Angiosarcoma is a rare soft tissue tumor, and only 22 cases of angiosarcoma of arteriovenous fistulae were described so far; although a correlation between Lowe's syndrome and a higher risk of tumor compared to the general population has not been described so far, the mechanisms of disease causation could be an interesting starting point for future studies on a possible connection between the two events.

Indoor and outdoor winter activity of Culicoides biting midges, vectors of bluetongue virus, in Italy.

Indoor and outdoor winter activity of Culicoides spp. (Diptera: Ceratopogonidae) in central Italy was investigated in order to evaluate whether indoor activity might account for the overwintering of bluetongue virus, as has been hypothesized by some authors. Weekly Culicoides collections were performed at three farms over three consecutive winter seasons. At each farm, two black-light traps were operated simultaneously, indoors and outdoors. Culicoides were identified using both morphological and molecular means. The Culicoides obsoletus group accounted for 98.2% of sampled specimens. Within this group, C. obsoletus s.s. accounted for 56.8% and Culicoides scoticus for 43.2% of samples. Nulliparous, parous and engorged females were caught throughout the entire winter, both indoors and outdoors. At times, indoor catch sizes outnumbered outdoor collections. A significant inverse correlation was found between minimum temperature and the proportion of indoor Culicoides of the total midge catch, thus indicating that lower outdoor temperatures drive Culicoides midges indoors. High rates of engorged females were recorded indoors, possibly as the result of the propensity of C. obsoletus females to feed indoors. Higher proportions of parous females were found in indoor than in outdoor catches, indicating higher survival rates indoors and, consequently, higher vectorial capacities of midges sheltering indoors compared with those remaining outdoors.

The legislation on living organ donation in Western Europe: legal and ethical analysis and impact on clinical practice.

In Europe there are various directives on living organ donation (LOD) that are applied differently in member countries. The objectives of this study were as follows: (1) to identify the most relevant normative differences among the countries of Western Europe, and (2) to evaluate the evolution of LOD data in these countries. We performed comparative analysis of national legislations to identify the most significant common and different regulatory elements that were evaluated subsequently from an ethical-legal point of view. For data analysis on LOD, we used the EULOD database of donations in Europe. Relevant legislative differences emerged among European countries. Through legal and ethical analysis, it has possible to delineate two legal guidelines: on the one hand, based primarily on informed consent applying the principle of individual autonomy, and on the other hand, informed consent associated with legal and medical criteria. From 1992 to 2009, countries with standards based primarily on individual informed consent showed an increase in LOD from 5.5% to 25.3%, which was greater than those in countries that had additional legal requirements, namely, from 1.6% to 16.0.%. The distinct transpositions of the European Directives among singles countries related to LOD are based essentially only on the request for informed consent or for additional medical and legal requirements. The former practices which increases LOD, can facilitate "organ tourism."

Ethical evaluation of risks related to living donor transplantation programs.

The shortage of available cadaveric organs for transplantation and the growing demand has incresed live donation. To increase the number of transplantations from living donors, programs have been implemented to coordinate donations in direct or indirect form (cross-over, paired, and domino chain). Living donors with complex medical conditions are accepted by several transplantation programs. In this way, the number of transplants from living has exceeded that from cadaver donors in several European countries. No mortality has been reported in the case of lung, pancreas, or intestinal Living donations, but the perioperative complications range from 15% to 30% for pancreas and lung donors. In living kidney donors, the perioperative mortality is 3 per 10,000. Their frequency of end-stage renal disease does not exceed the United States rate for the general population. However, long-term follow-up studies of living donors for kidney transplantations have several limitations. The frequency of complications in live donor liver transplantation is 40%, of these, 48% are possibly life-threatening according to the Clavien classification. Residual disability, liver failure, or death has occurred in 1% of cases. The changes in live donor acceptance criteria raise ethical issues, in particular, the physician's role in evaluating and accepting the risks taken by the living donor. Some workers argue to set aside medical paternalism on behalf of the principle of donor autonomy. In this way the medical rule "primum non nocere" is overcome. Transplantation centers should reason beyond the shortage of organs and think in terms of the care for both donor and recipient.

Parathyroid-gland ultrasonography in clinical and therapeutic evaluation of renal secondary hyperparathyroidism.

PURPOSE: This study evaluated the relationship between ultrasonographic (US) parameters of parathyroid glands (PTGs) in haemodialysis patients (HDP) and degree of secondary hyperparathyroidism (SHPT), therapeutic responsiveness and type of PTG hyperplasia (diffuse or nodular). MATERIALS AND METHODS: In 85 HDP, we evaluated the following US parameters of all and of the largest PTGs: number, maximum longitudinal diameter (MLD), structural (hypoechoic, heterogeneous, nodular) and vascular (nonhypovascular, intermediate, hypervascular) echo-pattern scores. Sixty-nine HDP underwent medical therapy (vitamin D, 39; vitamin D/cinacalcet, 30) and 16 underwent parathyroidectomy. The 69 HDP were classified as responders [median intact parathyroid hormone (iPTH) ≤300 pg/ml during follow-up) or nonresponders (iPTH >300 pg/ml). RESULTS: Number, MLD and structural and vascular echo patterns of PTGs were significantly correlated with iPTH and calcium concentrations. In the 41 (59%) responders, number (0-1), MLD (<10 mm) and structural and vascular scores (1-2) of the largest PTG were significantly lower than in nonresponders. Receiver operating curve (ROC) curve analysis showed high sensitivity and specificity (90% and 73%, respectively) of the MLD (<10mm) of the largest PTG in the predicting therapeutic outcome. US and histological MLD are significantly correlated and predict the type of hyperplasia. CONCLUSIONS: US parameters of PTGs are correlated to the degree of SHPT and type of hyperplasia and predict responsiveness to medical therapy.

Prediction of resting energy expenditure in severely obese Italian women.

The aims of the present study were to develop and cross-validate new equations for predicting resting energy expenditure (PREE) in severely obese Italian women, and to compare their accuracy with those of the Harris-Benedict, Bernstein, WHO/FAO/UNU, Owen, Mifflin, Nelson, Siervo, Huang and Livingston equations to predict REE, using the Bland-Altman method. One hundred and eighty two women [mean body mass index (BMI) 45.6 kg/m2; 56.7% fat mass (FM)], aged 19 to 60 yr participated in this study. REE was measured by indirect calorimetry and body composition by bioelectrical analysis. Equations were derived by stepwise multiple regression analysis, using a calibration group and tested against the validation group. Two new specific equations based on anthropometric REE=Weightx0.042+Heightx3.619-2.678 (R2=0.66, SE=0.56 MJ) or body composition parameters REE=FFMx0.067+FMx0.046+1.568 (R2=0.63, SE=0.58 MJ) were generated. Mean PREE were no different from the mean measured resting energy expenditure (MREE) (<1%, p>0.800) and REE was predicted accurately (95-105% of MREE) in 60% of subjects. The WHO/FAO/UNU, Harris-Benedict and Siervo equations showed mean differences <2% and PREE was accurate in <44% of subjects. The Huang, Mifflin and Livingston equations showed a mean PREE underestimation (>5.0%, p<0.001) and PREE was accurate in <38% of subjects. The Owen, Bernstein and Nelson equations showed a greater PREE underestimation (>14%, p<0.001) in >90% of subjects. The new prediction equations allow an accurate estimation of REE in groups of severely obese women and result in lower mean differences and lower limits of agreement between PREE and MREE than commonly used equations.

A randomized comparison between rotational and standard coronary angiography.

AIM: Selective coronary angiography is nowadays the gold standard in the definition of coronary anatomy as well as the basis for percutaneous coronary interventions. However, the diagnostic accuracy of coronary angiography can be reduced if the number of angiographic views is inadequate or if the operator does not select appropriate projections. Rotational angiography (RA) has been proposed as an alternative technique in order to provide a more complete definition of coronary anatomy reducing, at the same time, radiation exposure and contrast medium dose. METHODS: We randomly assigned 31 eligible patients, undergoing diagnostic cardiac catheterization, to RA (n=16) and traditional angiography (TA, n=15). Total procedural time, fluoroscopy time, number of cine-runs, X-ray dose and contrast medium volume were recorded in both groups. RESULTS: There were no statistically significant differences between groups in age (59+/-5.8 vs 62.8+/-9.6 years, P=ns), body mass index (26.7+/-3.5 vs 27.1+/-3.4 kg/m2, P=ns), total procedural time (20.6+/-6.6 vs 22.2+/-11.3 min, P=ns) and fluoroscopy time (3.9+/-1.5 vs 4.9+/-1.8 min, P=ns). On the contrary, number of cine-runs, X-ray dose and contrast medium volume were significantly lower in RA patients as compared with TA patients (6.2+/-1.2 vs 9.7+/-2.1, P<0.01; 530.6+/-271.6 vs 831.2+/-343.9 mGy, P<0.05; 76.9+/-22.4 vs 102.9+/-26.4 ml, P<0.01, respectively). CONCLUSIONS: RA is safe and effective in defining coronary anatomy, leading to a significant reduction in radiation exposure and contrast medium volume.

Plasma levels of transforming growth factor-beta1 in renal transplant recipients receiving different immunosuppressive regimens.

Experimental and clinical evidence support the role of transforming growth factor beta-1 (TGF-beta(1)), a cytokine with complex immune and nonimmune effects, on the development of chronic renal allograft nephropathy (CAN). We investigated the effects of different immunosuppressive regimens on circulating TGF-beta(1) plasma levels in stable kidney transplant (KTx) recipients. Two hundred ninety-nine TGF-beta(1) plasma levels were measured in 125 kidney transplant (KTX) recipients exhibiting stable renal function, immunosuppressed with cyclosporine (CsA), tacrolimus (TAC), or sirolimus (SIR), and in 18 normal healthy volunteers (C). Activated immunoreactive TGF-beta(1) was detected in platelet-depleted plasma by an enzyme-linked immunoadsorbent assay. Multivariate analyses correlated immunosuppressive regimens with TGF-beta(1) levels. KTX recipients displayed significantly higher TGF-beta(1) levels compared to C (P =.0005). Patients receiving CsA had significantly higher TGF-beta(1) plasma levels compared to those receiving TAC or SIR (P =.0384). Multivariate analyses showed no correlation between TGF-beta(1) levels and immunosuppressive drug trough blood levels or doses, but only correlations with the main immunosuppressive drug. These data show that: (1) TGF-beta(1) production is activated in kidney transplant recipients; (2) CsA patients display significantly higher plasma TGF-beta(1) levels. Follow-up studies seek to assess the possible relationship with clinical events.

Metabolic effects of biosynthetic growth hormone treatment in severely energy-restricted obese women.

OBJECTIVE: Severe energy restriction in the treatment of obesity is limited by catabolism of body protein stores and, consequently, loss of lean as well as fat tissue. Growth hormone (GH), whose secretion is markedly impaired in obesity, is endowed with both lipolytic and protein anabolic properties. The aim of this study was to verify the effects of GH administration on body composition, plasma leptin levels and energy metabolism in obese patients undergoing severe dietary restriction. DESIGN: Single-blind placebo-controlled study. Twenty obese women were fed a diet of 41.86 kJ/kg ideal body weight (IBW) daily for 4 weeks: 10 of them were randomly assigned to a 4 week treatment with biosynthetic GH (rhGH, Saizen, Serono, Rome, Italy), 1 U/kg IBW/week in daily subcutaneous injections; the other 10 patients, matched for age and BMI, received vehicle only. SUBJECTS: Twenty women with simple obesity (age: 25.4+/-1.07 y, BMI: 35.9+/-0.35 kg/m2). MEASUREMENTS: Plasma IGF-I and leptin, serum markers of bone turnover (serum bone isoenzyme of alkaline phosphatase, osteocalcin and urinary hydroxyproline), nitrogen balance, body composition (by DEXA), and resting energy expenditure (REE, by indirect calorimetry) were evaluated at baseline and after 4 weeks. RESULTS: Mean IGF-I plasma levels, not influenced by energy restriction in patients receiving placebo, displayed a significant increase in the group treated with rhGH. The mean weight reduction and fat mass loss were not significantly different in the two groups (6.0+/-0.51 vs 7.2+/-0.30 kg, NS, and 5.36+/-0.460 vs 4.28+/-0.572 kg, NS, with rhGH and placebo, respectively). Likewise, plasma leptin levels decreased significantly in weight-reduced subjects receiving either rhGH (from 16.2+/-2.37 to 6.4+/-0.39 ng/ml, P < 0.05) or placebo (from 14.3+/-2.55 to 7.7+/-3.77 ng/ml, P < 0.05). On the contrary, the mean decrease of lean body mass (LBM) was significantly lower in the GH-treated patients than in those receiving vehicle (1.52+/-0.60 vs 3.79+/-0.45 kg, P < 0.05). In keeping with these findings, the mean daily nitrogen balance was significantly less negative in the GH-treated subjects than in the vehicle-injected patients (mean of the 4 week daily urine collections -185.7+/-40.33 vs -363.9+/-55.47 mmol/d, P < 0.05, respectively). Further, a significant reduction of mean REE was recorded in the energy-restricted placebo-treated patients (from 8807+/-498 to 7580+/-321 kJ/24 h, P < 0.05), but not in the patients receiving rhGH (from 8367+/-580 to 8903+/-478 kJ/24 h, NS). Actually, when corrected for LBM, REE was even increased by GH administration (from 197.9+/-11.76 to 219.3+/-9.87 kJ/kg LBM/24 h, P < 0.05), whereas it was unchanged in the placebo group (from 201.7+/-13.85 to 190.0+/-9.87 kJ/kg LBM/24 h, NS). A tendency of serum markers of bone turnover to increase was observed in the patients treated with rhGH, however with no changes in bone mineral content and density. CONCLUSION: rhGH treatment, though unable to enhance diet-induced weight and fat mass reduction, was effective in stimulating IGF-I production and conserving LBM and increasing its energy metabolism even in the presence of severe energy restriction.

Abnormal development of the sella turcica and lack of pituitary visualization in a patient with partial hypopituitarism.

We report the case of a 17-year-old girl presenting short stature (height 149 cm, below the 3rd percentile), obesity (weight 83.5 kg, body mass index 37 kg/m2) and secondary amenorrhea, in whom endocrinological evaluation disclosed an absolute lack of GH responsiveness to both suprapituitary challenges and repetitive growth hormone releasing hormone administration together with failure of plasma gonadotropins and PRL, low under basal conditions, to rise in response to GnRH and insulin-hypoglycemia, respectively. In contrast, basal and stimulated TSH and ACTH secretions were normal. Radiological examination of the skull revealed virtual absence of the pituitary fossa due to the lack of sellar cavum and dorsum, while magnetic resonance was unable to detect any pituitary tissue. A mucosal cleft of the nasopharynx, compatible with a pharyngeal hypophysis, was disclosed at endoscopy. This is an unusual case of developmental abnormality including lack of formation of the sella turcica and incomplete caudal migration of the embryonal anterior pituitary, resulting in ectopically located--likely pharyngeal--pituitary tissue. In view of the occurrence of spontaneous menarche and of a growth impairment less severe than one would expect considering the degree of GH deficiency, it is conceivable that the ectopic pituitary tissue has lost, in time, some of its secretory ability.

Epithelial ovarian tumors in young women under 35 years.

The aim of this study was to investigate the clinical-pathological pattern of primary malignant epithelial ovarian tumors in women under 35 years old. We have retrospectively analyzed data from 545 patients with these tumors, identifying 49 patients under age 35. We found a higher frequency of borderline tumors and early-stage tumors in young women than in those over 35. The influence of age as a factor in survival was evaluated by comparing the outcome in young patients and in women over 35. The 5-year survival rate, according to stage and aggressiveness factors, was significantly better in young patients. These findings support the concept of a preclinical phase of epithelial carcinoma and show that young women may be selected for conservative surgery, allowing a good quality of life.

Development of fear-related heart rate responses in neonatal rabbits.

Classical simple conditioning of heart rate (HR) was studied in rabbits between the 1st and 18th neonatal day. An auditory stimulus (1000 Hz, 5 s) served as the conditioned stimulus (CS), and a train of electric impulses (100 Hz, 500 ms, 1-1.5 mA) was used as the unconditioned stimulus (US). HR responses developed during orientation session (CS-alone) as well during acquisition (CS-US paired) were analyzed and compared to those developed by young adult rabbits (3-month-old). In all neonatal animals tested, baseline HR measured during an adaptation session preceding conditioning, was similar though significantly higher than that measured in adult rabbits (Newman-Keuls P < 0.05). Before the 10th neonatal day, the animals did not show either somatomotor or HR orienting responses to the CS-alone presentations. Consequently, since orienting reactions play a necessary role in the formation and manifestation of conditioned reflexes, 1 to 10-day-old infant rabbits were not submitted to the acquisition session. All the other neonatal groups, while showing orienting behaviours similar to those exhibited by adults (head and pinna movement), presented different patterns of HR orienting responses (no response, bradycardia, tachycardia, bradycardia/tachycardia etc.). As for the acquisition session, the first bradycardic response, similar to that developed by adult rabbits, was found in 18-day-old rabbits. However, also in this neonatal group the amplitude of the conditioned response was significantly smaller when compared to that exhibited by young adults (Newman-Keuls P < 0.01). In addition, in some of the 10-day-old neonates, HR appeared very unstable and dropped to very low values (as low as 146 beats/min) early during conditioning, apparently as a consequence of CS-US association. As for the unconditioned response, no differences were found between adult rabbits and the neonatal animals older than 12 days. In contrast, most of the 10-day-old rabbits showed either bradycardia or no response to the unconditioned stimulus. Considering the ability of mammalian infants to learn somatomotor conditioned responses at early stages of maturation, conditioning of HR responses occurs late during ontogeny. Since this incapacity to show HR conditioned responses before the 18th postnatal day cannot be ascribed to their inability to show phasic HR changes nor to a failure in detecting the auditory stimulus, these results suggest the possibility that HR conditioned responses may be mediated by neural structures developing later during maturation.

Surgical strategies in vulvar cancer.

The evolution of surgical strategies in vulvar cancer over thirty years of personal experience is considered. The knowledge of aggressiveness and risk factors of every tumor correlated with the patients' age allows today to perform adequate radical surgery even without the large multilations of the past. 5-year survival rate and incidence of relapses are the same while quality of life is highly improved. The Authors stress the new conservative trend in every field of oncological surgery.

5-year survival of endometrial carcinoma in the experience of the Gynaecological Clinic of Padua University: quality of life.

We have considered 414 cases of endometrial carcinoma from 1963 to 1990, with particular attention to 5-year survival and quality of life. The results show an increase of survival rate and of patients always NED- rate, from the first decades (63-70) to the last period (81-90). Similarly, the percentage of patients treated just with surgical therapies increases too, showing the effectiveness of personalized therapeutical strategies.

Regional coronary hemodynamic effects of diltiazem in man.

We evaluated the changes in regional coronary hemodynamics induced by diltiazem, 0.25 mg/kg intravenously, in nine patients with 75% to 90% diameter stenosis of the left anterior descending coronary artery (LAD) (group 1) and in 10 patients with 100% occlusion of the LAD and collaterals to the distal LAD (group 2). Although diltiazem induced similar changes in systemic hemodynamics in the two groups, a decrease in anterior coronary vascular resistance (ACVR) and an increase in great cardiac vein flow (GCVF) were observed after administration of diltiazem in all patients in group 1 but in only 6 of 10 patients in group 2 (subgroup 2B). ACVR increased and GCVF decreased after administration of diltiazem in 4 of 10 patients in group 2 (subgroup 2A). Clinico-angiographic characteristics, origin of collaterals, and diltiazem-induced changes in systemic hemodynamics were similar in subgroups 2A and 2B. Thus diltiazem increases coronary flow distal to a stenotic coronary artery but can decrease regional coronary flow and increase regional coronary resistance in a minority of patients with an occluded coronary artery supplied by collaterals, probably through a steal mechanism.

Effects of histamine on coronary hemodynamics in humans: role of H1 and H2 receptors.

To evaluate whether histamine exerts a direct effect on coronary hemodynamics in humans, and to investigate the role played by H1 and H2 receptors in this response, intracoronary saline solution or histamine (4 micrograms) was administered in 10 patients with normal coronary arteries during diagnostic cardiac catheterization. Histamine injection was repeated after intravenous cimetidine (400 mg) and diphenhydramine (10 mg). The electrocardiogram, arterial pressure and thermodilution coronary blood flow were continuously monitored during and for 40 seconds after each injection. Immediately after histamine injection there was a significant increase in coronary blood flow (65 +/- 6%) and a decrease in coronary vascular resistance (-40 +/- 3%) (both p less than 0.001), with minor changes in the RR interval and the mean arterial pressure. H2 receptor blockade with cimetidine did not affect these changes, while H1 receptor blockade with diphenhydramine significantly reduced the histamine-induced increase in coronary blood flow and the decrease in coronary vascular resistance (26 +/- 6%, p less than 0.005 and -18 +/- 5%, p less than 0.001, respectively). Twenty to 30 seconds after histamine injection, a significant decrease in mean arterial pressure (-17 +/- 2%, p less than 0.001) and in the RR interval (-4 +/- 1%, p less than 0.01) was observed. These changes persisted after H2 receptor blockade with cimetidine, but were completely abolished after H1 receptor blockade with diphenhydramine. In each case coronary and systemic hemodynamics returned to normal within 40 seconds of the injection.(ABSTRACT TRUNCATED AT 250 WORDS)

[Beneficial effects of diltiazem in exertion stable angina. Evaluation of coronary hemodynamics during cardiac pacing]. / Effetti favorevoli del diltiazem nell'angina stabile da sforzo. Valutazione dell'emodinamica coronarica durante pacing.

We evaluated the protective effect of Diltiazem from pacing-induced myocardial ischemia in 9 patients (pts) with coronary heart disease (CAD) and stable effort angina by studying the changes in systemic and coronary hemodynamics during pacing. Hemodynamic parameters were evaluated at baseline and at peak pacing before and after Diltiazem, 25 mg i.v. Diltiazem prevented angina in 6 of 7 pts who presented angina in the control pacing. This beneficial effect was accompanied at peak pacing rate by a significant fall in ST depression, arterial pressure, rate-pressure product and left ventricular (LV) end-diastolic pressure, while no significant changes were observed in LV dp/dt max, coronary blood flow and coronary vascular resistance. Therefore, Diltiazem exerts a protective effect from pacing-induced myocardial ischemia in pts with CAD and stable effort angina, without impairing LV function. This beneficial effect is due to a reduction in myocardial metabolic requirements, rather than to an improvement of blood supply to the ischemic myocardium.