Immediate and Catastrophic Antibody-Mediated Rejection in a Lung Transplant Recipient With Anti-Angiotensin II Receptor Type 1 and Anti-Endothelin-1 Receptor Type A Antibodies.

Preexisting donor-specific anti-HLA antibodies (DSAs) have been associated with reduced survival of lung allografts. However, antibodies with specificities other than HLA may have a detrimental role on the lung transplant outcome. A young man with cystic fibrosis underwent lung transplantation with organs from a suitable deceased donor. At the time of transplantation, there were no anti-HLA DSAs. During surgery, the patient developed a severe and intractable pulmonary hypertension associated with right ventriular dysfunction, which required arteriovenous extracorporeal membrane oxygenation. After a brief period of clinical improvement, a rapid deterioration in hemodynamics led to the patient's death on postoperative day 5. Postmortem studies showed that lung specimens taken at the end of surgery were compatible with antibody-mediated rejection (AMR), while terminal samples evidenced diffuse capillaritis, blood extravasation, edema, and microthrombi, with foci of acute cellular rejection (A3). Immunological investigations demonstrated the presence of preexisting antibodies against the endothelin-1 receptor type A (ETA R) and the angiotensin II receptor type 1 (AT1 R), two of the most potent vasoconstrictors reported to date, whose levels slightly rose after transplantation. These data suggest that preexisting anti-ETA R and anti-AT1 R antibodies may have contributed to the onset of AMR and to the catastrophic clinical course of this patient.

Multisensory perception constrains the formation of object categories: a review of evidence from sensory-driven and predictive processes on categorical decisions.

Although object categorization is a fundamental cognitive ability, it is also a complex process going beyond the perception and organization of sensory stimulation. Here we review existing evidence about how the human brain acquires and organizes multisensory inputs into object representations that may lead to conceptual knowledge in memory. We first focus on evidence for two processes on object perception, multisensory integration of redundant information (e.g. seeing and feeling a shape) and crossmodal, statistical learning of complementary information (e.g. the 'moo' sound of a cow and its visual shape). For both processes, the importance attributed to each sensory input in constructing a multisensory representation of an object depends on the working range of the specific sensory modality, the relative reliability or distinctiveness of the encoded information and top-down predictions. Moreover, apart from sensory-driven influences on perception, the acquisition of featural information across modalities can affect semantic memory and, in turn, influence category decisions. In sum, we argue that both multisensory processes independently constrain the formation of object categories across the lifespan, possibly through early and late integration mechanisms, respectively, to allow us to efficiently achieve the everyday, but remarkable, ability of recognizing objects. This article is part of the theme issue 'Decision and control processes in multisensory perception'.

Surgical correction of Peyronie's disease via tunica albuginea plication: long-term follow-up.

Peyronie's disease (PD) is an acquired connective tissue disorder of the tunica albuginea with fibrosis and inflammation that lead to palpable plaques formation, penile curvature, and pain during erection. Patients report negative effects on main domains such as physical appearance and self-image, sexual function, and performance. The aim of this study was to evaluate plication of the albuginea outcomes after a long-term follow-up period. Between 1998 and 2006, a total of 204 patients with PD underwent surgical correction with albuginea plication technique. We obtained complete long-term follow-up data in 187 cases. The follow-up data included evaluation of curvature correction, penile shortening, sexual function, complications, and patient satisfaction. After a mean follow-up of 141 months, the most common postoperative complications were: loss of length (150 patients had a minimal penile shortening ≤1.5 cm, 37 patient between 1.5, and 3 cm, none >3 cm), recurrent or residual penile curvature (15 patients, without impairing sexual intercourse), erectile dysfunction (15 patients had IIEF-5 < 10 at 5 years of follow-up vs. 28 patients at 10 years), change in penile sensation (37 patients experienced paresthesia of the glans 1 year after surgery, 28 at 5 years, and 15 at 10 years); painful or palpable suture knots (in 20 cases) spontaneously healed in 3 months. Overall, 77% of the patients and partners were completely satisfied, 14% partially satisfied, and 9% unsatisfied. Plication procedure is safe and simple to be performed compared with the classical Nesbit's procedure. It has a shorter surgical time, lower costs, and could be successfully performed by less experienced surgeons too. It has a minimal risk of de novo erectile dysfunction, injury to the dorsal neurovascular bundle. Results are good in terms of patient satisfaction according to anatomical outcome and functional correction.

An update on xenotransplantation.

Xenotransplantation is one of the possible avenues currently being explored to address the shortage problem of human organs. With this in mind, this article will briefly review the current situation with respect to the immunological, physiological and biosafety aspects related to the transplantation of pig organs into primates. Acute humoral xenograft rejection (AHXR) currently remains the central immunological obstacle and the development of strategies for both a better control of the elicited anti-pig humoral immune response or the prevention of the onset of coagulation disorders that accompany AHXR are the two primary focuses of research. To date, porcine xenografts have been shown to sustain the life of nonhuman primates for several months. Such preclinical studies have also demonstrated the absence of insurmountable physiological incompatibilities between pig and primate. In addition, reassuring findings regarding biosafety aspects have been generated and pro-active research aimed at the identification of an organ source with a higher safety profile is also underway. These advancements, in conjunction with ongoing research in pig genetic engineering, immunosuppression and tolerance are expected to further extend the survival of porcine xenografts transplanted into primates. However, until further physiological, efficacy and safety data are generated in relevant primate models, clinical xenotransplantation should not be considered.

Does site of specimen extraction affect incisional hernia rate after robot assisted laparoscopic radical prostatectomy?

BACKGROUND: Robot assisted laparoscopic radical prostatectomy (RALP) spread in the last decade as a minimally invasive alternative to open radical prostatectomy for men with localized prostate cancer. It is associated with excellent surgical, functional and oncological results with less postoperative pain and shorter convalescence. Anyway, the development of an incisional hernia (IH), may negate known benefits as it can lead not only to bothersome symptoms but also to severe complications, such as bowel obstruction, strangulation and perforation. Port-site or extraction site hernias, whose incidence rate is underdiagnosed, have become more commonly after minimally invasive surgery; but IH rate after robot-assisted radical prostatectomy has not been well characterized. This study aimed to evaluate the impact of extraction-site location (vertical supra-umbilical incision versus an off-midline incision) on incisional hernia rates in robotic prostatectomy. MATERIALS AND METHODS: We included in the study 800 patients undergone RALP, 400 with a supra-umbilical incision for specimen extraction and 400 with off-midline incision. All were followed up for at least 3 years. The main study end point was IH occurrence at the extraction site (midline versus off-midline). RESULTS: IH rate for the entire series was 4.75%, in particular 5% for the midline group and 4.5% for the off-midline group. The hernias were diagnosed at a mean of 20.2 and 18.2 months after surgery, respectively in the two groups. There was no statistically significant differences in baseline characteristics; anyway larger prostate weight, wound infection and history of prior cholecystectomy were associated with higher proportion of IH. CONCLUSION: Extraction site hernias are a rare but a potentially serious complication following RALP. In our series, the midline extraction doesn't result in a significantly higher IH rate in comparison with the off-midline extraction site.

Thulium laser enucleation (ThuLEP) versus transurethral resection of the prostate in saline (TURis): A randomized prospective trial to compare intra and early postoperative outcomes. / Enucleación con láser de tulio (ThuLEP) frente a resección transuretral de la próstata en solución salina (TURis): un ensayo prospectivo aleatorizado para comparar resultados intra y postoperatorios tempranos.

OBJECTIVE: To compare clinical intra and early postoperative outcomes between thulium laser transurethral enucleation of the prostate (ThuLEP) and transurethral bipolar resection of the prostate (TURis) for treating benign prostatic hyperplasia (BPH) in a prospective randomized trial. METHODS: The study randomized 208 consecutive patients with BPH to ThuLEP (n=102) or TURis (n=106). For all patients were evaluated preoperatively with regards to blood loss, catheterization time, irrigation volume, hospital stay and operative time. At 3 months after surgery they were also evaluated by International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), and postvoid residual urine volume (PVR). RESULTS: The patients in each study arm each showed no significant difference in preoperative parameters. Compared with TURIS, ThuLEP had same operative time (53.69±31.44 vs 61.66±18.70minutes, P=.123) but resulted in less hemoglobin decrease (0.45 vs 2.83g/dL, P=.005). ThuLEP also needed less catheterization time (1.3 vs 4.8 days, P=.011), irrigation volume (29.4 vs 69.2 L, P=.002), and hospital stay (1.7 vs 5.2 days, P=.016). During the 3 months of follow-up, the procedures did not demonstrate a significant difference in Qmax, IPSS, PVR, and QOLS. CONCLUSION: ThuLEP and TURis both relieve lower urinary tract symptoms equally, with high efficacy and safety. ThuLEP was statistically superior to TURis in blood loss, catheterization time, irrigation volume, and hospital stay. However, procedures did not differ significantly in Qmax, IPSS, PVR, and QOLS through 3 months of follow-up.

Molecular cloning of a recombinant retrovirus carrying a mutated envAKR-mycMH2 fusion gene immortalizing cells of the monocytic-macrophage lineage.

The VN-11 recombinant retroviruses, originally generated by co-transfection of the avian MH2 and AKRv viral genomes, were molecularly cloned from an infected mouse cell line named N11. The analysis of the proviral genome sequence from one of these recombinants showed a possible envAKR-mycMH2 fusion. Point mutations were also found in this envAKR-mycMH2 gene. The cloned viral genome was co-transfected with the neo gene into the psi 2 packaging cell line. Selected clones were shown to transcribe the viral genome and supernatants from these cultures, containing C-type particles, were used to infect primary cultures from mouse lymphoid tissues and brain. Proliferating macrophages and microglial cell clones were obtained, indicating that various types of cells of the mouse monocytic-macrophage lineage can be immortalized in spite of the absence of selection or special growth conditions.

Effect of clot-detection methods and reagents on activated partial thromboplastin time (APTT). Implications in heparin monitoring by APTT.

Two automatic coagulometers, ACL 810 (Instrumentation Laboratory), a laser-nephelometric centrifugal analyzer, and KoaguLab 40 A (Ortho Diagnostics), an optical automatic coagulometer, were compared with the manual tilt-tube method for the performance of activated partial thromboplastin time (APTT). Seven commercial APTT reagents were used for duplicate determinations in 30 normal controls, 26 patients with liver disease, and 33 patients on full-dose heparin treatment. Clotting times were longer with the manual method than with ACL 810 and, to a lesser extent, with KoaguLab 40 A. Average imprecision of duplicate determinations (coefficient of variation [CV]) was less with ACL 810 (less than 1.5%) than with KoaguLab 40 A (2.9%) and the manual method (2.4%). Differences in slope of the regression curves of clotting times obtained with the coagulometers over the tilt-tube method were observed with all the reagents tested (P less than 0.01). Transformation of clotting times of controls, patients with liver disease, and patients on heparin therapy to APTT ratios did not eliminate the bias resulting from the different reagents (P less than 0.001) and clot-detection methods (P less than 0.001); in controls, significant (P less than 0.001) reagent-method interaction was also observed. The in vitro heparin sensitivity differed with the APTT reagents evaluated and was influenced by the clot-detection method used. Transformation of APTT ratios of anticoagulated patients to apparent plasma heparin levels--as derived from in vitro dose-response curves--effectively eliminated the bias resulting from the different clot-detection methods but had no effect on the bias resulting from the different APTT reagents. In vitro heparin activity curves thus have little, if any, relevance for the ex vivo monitoring of heparin treatment.

Comparison of two automated coagulometers and the manual tilt-tube method for the determination of prothrombin time.

Two automatic coagulometers--ACL 810 (Instrumentation Laboratory), a laser-nephelometric centrifugal analyzer, and KoaguLab 40 A (Ortho Diagnostics), an optical automatic coagulometer--were compared with the manual tilt-tube method for the performance of prothrombin time (PT). Seven ISI- (International Sensitivity Index) calibrated commercial thromboplastin reagents were used for duplicate determinations in 30 normal subjects, 30 patients with liver disease, and 30 patients receiving stabilized oral anticoagulation. Clotting times were longer with the manual method than with ACL 810 and, to a lesser extent, with KoaguLab 40 A. Average imprecision of duplicate determinations (CV) was less than 1% with ACL 810; KoaguLab 40 A and the manual method had similarly higher imprecisions (2.8% and 2.7%). Differences in origin and slope of the regression curves of clotting times obtained with the coagulometers over the tilt-tube method were observed with all the reagents tested. Transformation of clotting times to PT ratios did not eliminate the bias resulting from the different clot-detection methods. A higher percentage of patients with liver disease had abnormal PT ratios when their plasma was tested with the coagulometers than with the manual method. Transformation of PT ratios to International Normalized Ratios effectively eliminated the bias resulting from the different thromboplastin reagents but had no effect on the bias resulting from the different clot-detection methods. A significant proportion of patients appeared excessively anticoagulated (INR greater than 4.5) with the coagulometers but not with the manual method. These results highlight the need for standardization of both instrumentations and reagents to improve monitoring of oral anticoagulant treatment.

Tetanus and botulinum neurotoxins: turning bad guys into good by research.

The neuroparalytic syndromes of tetanus and botulism are caused by neurotoxins produced by bacteria of the genus Clostridium. They are 150 kDa proteins consisting of three-domains, endowed with different functions: neurospecific binding, membrane translocation and specific proteolysis of three key components of the neuroexocytosis apparatus. After binding to the presynaptic membrane of motoneurons, tetanus neurotoxin (TeNT) is internalized and transported retroaxonally to the spinal cord, where it blocks neurotransmitter release from spinal inhibitory interneurons. In contrast, the seven botulinum neurotoxins (BoNT) act at the periphery and inhibit acetylcholine release from peripheral cholinergic nerve terminals. TeNT and BoNT-B, -D, -F and -G cleave specifically at single but different peptide bonds, VAMP/synaptobrevin, a membrane protein of small synaptic vesicles. BoNT types -A, -C and -E cleave SNAP-25 at different sites within the COOH-terminus, whereas BoNT-C also cleaves syntaxin. BoNTs are increasingly used in medicine for the treatment of human diseases characterized by hyperfunction of cholinergic terminals.

Prediction of the progression of renal failure in adult and in pediatric patients with malignant focal glomerulosclerosis.

A retrospective analysis of the progression of renal failure was performed in 6 children and 5 adults with idiopathic nephrotic syndrome unresponsive to steroids and immunosuppressants and with histological findings of focal glomerulosclerosis. We analyzed the linear regression of Ccr and of their logarithmic transformation vs time (months) starting from the time when the first abnormal value was observed (t = 0). The regression analysis was performed at three different times, when Ccr was: 30-20, 20-25 and 10-15 ml/min/1.73 sqm. Extrapolation of each of these lines on the x axis predicted when renal function would be zero. The difference in months, between the predicted and actual time of starting dialysis was prediction error. "r" values were always elevated and statistically significant for both linear and logarithmic regression; there was a large intersubject variability in the rate of loss of renal function but the mean prediction error at various levels of Ccr was within limits clinically acceptable. Moreover its magnitude did not significantly decrease by prolonging the time of observation. This indicates that in this disease the decay of Ccr enters a track which proceeds linearly or logarithmically after the onset of renal failure and no major deviation from the predicted line is to be expected. The good predictability in our study may be attributed to the fact that our patients were homogeneous for a number of factors which may be relevant to progression of the disease. It confirms the view supported by Gretz et al. [1983] that there is a need for stratification of patients in large cohort studies on the predictability of loss of renal function.

Coagulation abnormalities in patients with head injury.

The Authors have studied five coagulation parameters (platelets count, prothrombin time, activated partial thromboplastin time, fibrinogen and fibrinogen degradation products) in 60 head traumatized patients. These parameters were alterated in a high percentage of patients. Moreover 5 patients presented laboratory values indicative of disseminated intravascular coagulation (DIC). DIC could be an important factor of mortality in the head traumatized patients. So coagulation system must be carefully evaluated in any patient with head injury.

Validation of a prognostic system in severe brain-injured patients.

Seventy-six patients with severe isolated head trauma (GCS score of 7 or less) were prospectively studied in order to valuate the prognostic power of the APACHE II system. In nonsurvivor patients the APACHE II score was higher than in survivor patients (24.7 +/- 3.2 (SD) vs 18.7 +/- 3.1; p less than .001). With an APACHE II cut-off point of 20 the sensitivity was 100% and the specificity was 70% while a cut-off point of 21 the sensibility decreased to 97.2% but the specificity increased to 72.5%. We conclude that the APACHE II is an effective mean to predict the prognosis of severe brain-injured patients.

Effect of dexamethasone on nitrogen metabolism in brain-injured patients.

A randomized prospective clinical trial was conducted to determine the influence of dexamethasone therapy on nitrogen metabolism in patients with isolated head trauma without any pathologies. One group of 12 patients was not given steroids (groups NS). To the 12 patients of the second group, a dose of 0.36 mg/kg/day of dexamethasone was administered for the first nine days of stay (group S) in hospital. At the beginning of the study, between the two groups, there were no differences in age, sex, Glasgow Coma Scale Score, type of injury. In order to avoid bias, phenytoin, barbiturates and muscle-relaxant drugs were not given and the same caloric and protein intake was prefixed for both groups. The urea excretion, nitrogen output, nitrogen balance and cumulative nitrogen balance were not statistically different in the two groups throughout the period of study. Similar were also weight losses, blood glucose, blood urea nitrogen, albumin and creatinine levels. The outcome, evaluated at 3 months, was also similar. The incidence of sepsis, pulmonary and urinary infections, gastric reflux duration and quantity, was not higher in the steroid group compared with non-steroid treated patients.

Effects of acute smoking on the hemostatic system in humans.

Habitual smoking is one of the best established risk factors for cardiovascular disease. The pathogenesis of smoke-induced damage is not so well clarified, but it probably includes--among some other aspects--an activation of the hemostatic system. Recently it has been shown that smoking a single cigarette can significantly decrease the coronary blood flow in coronary patients as well as in normal subjects. We tested the hypothesis that the acute effects of smoke are mediated by the hemostatic system. Seven healthy male volunteers, aged 20-40 years (mean 32 +/- 6 years), entered the study. All were habitual smokers, but had abstained from smoking in the 12 hours preceding the test. After lying in absolute rest for about 30 minutes, each subject smoked a cigarette containing 1.2 mg of nicotine. Immediately before and after smoking, blood was drawn by clear venipuncture for the evaluation of the following hemostatic variables: collagen-induced platelet aggregation by the method of Born; thromboxane B2 (TxB2) production by platelets stimulated with collagen, radioimmunoassay (RIA); plasma beta thromboglobulin (TG) (RIA); plasma fibrinopeptide A (FPA) (RIA); plasma fibrinolytic activity in the euglobulin fraction (NEF) (fibrin plate method). The following results, respectively before and after smoking, were observed: collagen-induced platelet aggregation 55 +/- 3 vs. 57 +/- 6%; TxB2 100.5 +/- 5.9 vs. 90.3 +/- 9.0 ng/10(8) platelets; plasma beta-TG 20.8 +/- 2.2 vs. 19.2 +/- 2.3 ng/ml; plasma FPA 2.3 +/- 0.3 vs. 2.2 +/- 0.1 ng/ml; NEF, lysis diameter 16.8 +/- 1.6 vs. 16.7 +/- 1.7 mm; NEF + C1 inhibitor lysis diameter 8.8 +/- 0.7 vs. 9.1 +/- 0.7 mm.(ABSTRACT TRUNCATED AT 250 WORDS)

Extracorporeal shock wave lithotripsy.

The first clinical application of extracorporeal SWL dates back to 1980. Since then the use of this method has spread widely and its indications have been extended progressively so that it way now be considered the treatment of choice in 80-90% of cases of ureterorenal lithiasis. Treatments without anesthesia or analgesics have been associated with an increase of retreatments from 5-14% (original HM3) to 45-60% (lithotripters not requiring anesthesia or analgesia). However, almost all lithotripter succeed in fragmenting stones sufficiently. The stone free rate varies with different lithotripters in the different series: 90-56% for stones of maximum diameter < 1 cm, 78-30% for stones of maximum diameter of 1-2 cm. and 52.5-10% for stones of maximum diameter of 2-3 cm. (the last figure was obtained with a piezoelectric lithotripter). Extracorporeal lithotripsy as monotherapy of staghorn stones has yelded a stone free rate varying between 31% and 55% with high percentages of residual fragments in about 50% of case of the various series. The stone free rate after treatment varies according to stone site: it is between 75% and 84% of caliceal stones for upper caliceal calculi and falls to under 60% for lower caliceal ones. The frequency of recurrences, that is, of new stones in patients stone free after SWL, is between 4% and 10% annually. Adding the percentage of true recurrences reported by the various authors at 19 to 42 months of follow-up (6.2-13.8%) to the fragment regrowth rate (17.2-22.3%) gives a total new stone rate of 23.4% and 36%. These figures are not greatly different from those reported in a population of untreated stone formers (10-15% per year). Extracorporeal lithotripsy seems thus not to influence lithiasis recurrence significantly.

[Study of the diuretic efficacy and tolerability of therapy with Rocchetta mineral water in patients with recurrent calcium kidney stones]. / Studio sulla tollerabilità e l'efficacia diuretica della idropinoterapia con acqua oligominerale Rocchetta in pazienti con nefrolitiasi calcica recidivante.

The diluition of urine decreases the risk of stone formation by lowering the concentration of calcium, oxalate and uric acid, but involves a simultaneous decrease of the concentration of the inhibitors of crystallization. On the other hand the ion content of the drinking water used for stone prevention could by itself modify urine composition. We tested the effect of the administration of a mild-calcium high-bicarbonate content water on urine composition of a group of calcium renal stone formers. A group of 40 calcium renal stone formers was instructed to drink 3 l/day of a mild-calcium (57 mg/l) and high-bicarbonate (180 mg/l) content water (Rocchetta) for a 7 day period. A 24-h collection was obtained before and after water administration for analyses of calcium, magnesium, oxalate and citrate. Urine volume was significantly increased after water administration (1601 +/- 357 vs 1878 +/- 339). Daily urinary calcium, magnesium and citrate were significantly increased, whereas daily urinary oxalate was unchanged after water administration. In conclusion the mild-calcium high-bicarbonate content water administration seems suitable for stone prevention because of the increased excretion of urinary inhibitors counterbalancing increased urinary calcium excretion.

[Seminal obstructions of the inflammatory origin]. / Ostruzioni seminali di origine flogistica.

Presence of bacteria in the sperm is often associated to a reduction of fertility in relationship with a decrease in number and motility of spermatozoa and with an augmentation of the abnormal spermatic cells. In the most severe cases, chronic and complicated phlogosis may lead to obstruction of seminal pathways with consequent azoospermia. Clinical features of seminal phlogosis are extremely variable both in acute and chronic evolutions. In every case the first diagnostical step is sperm count and seminal complete analysis which can give evidence of phlogistic alteration in quantity and quality of spermatic cells with a typical presence of an excess in white blood cells (leukospermia) as consequence of infection. The great variety in clinical and bacteriological aspects and the particular biological features of the organs involved, as the prostate, makes treatment a difficult problem to solve with particular regard to the choice of an effective antibiotic which pharmacokinetic has to result suitable for the microorganism as well as for the tissue of the infection site. All those efforts are indispensable to reduce the too frequent therapeutical failures in the management of seminal phlogistic pathology with complications of organic but also physiological relevancy for the patient and the partner too, such as azoospermia.

[Treatment of prostatitis with a new laser probe with optic fiber]. / Trattamento delle prostatiti con nuova sonda laser in fibra ottica.

The present treatment of the subacute abatteric prostatitis, prostatodinia, prostatosis (the most common prostatic flogistic diseases) is represented by the transrectal applications of infrared Laser. The concrete opportunity of applying such an energy directly to the prostate in cases of flogistic diseases--a very frequent pathology treated in many different and controversial ways--is a stimulating therapeutical method which we tested and that we presently use in our clinics. The thanks to the realization of an high technology equipment, easy to handle, cheap, safe, perfectly suitable, formed by a new infrared Laser probe, transrectal, atermical, made by a optical fibre, which we present. Micturition, ejaculation, fertility may draw a relevant improvement, provided that the same treatment is performed after a specific medical diagnosis and following a strict protocol.

Perineal biofeedback versus pelvic floor training in the treatment of urinary incontinence.

Perineal floor training and perineal biofeedback allow to reach a good improvement of clinical discomfort in the treatment of stress and urge urinary incontinence. The aim of this study is the real evaluation of the benefit due to a 6 week perineal biofeedback and pelvic floor training (PFT) versus PFT alone. 8 female patients have been treated with a 6 week trial with perineal biofeedback plus PFT trial and 22 with a 3 month PFT alone one. PFT alone, permits a good improvement but 10% less than if associated to perineal biofeedback.