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Vascular malformations encompass a wide range of complex vascular lesions. Due to the extreme variability of clinical presentation, classification and their related syndromes presents a challenge. Here we describe a case of a boy presenting with Marfanoid habitus, cutaneous vascular malformations, and severe acute anemia due to ileal venous malformations. Although a panel of genetic markers for the Marfan phenotype was negative, we identified a de novo mutation in the TEK gene in the patient. This case supports expansion of the phenotypic spectrum of TEK-related vascular malformations.

Vascular malformations encompass a wide range of complex vascular lesions. Due to the extreme variability of clinical presentation, classification and their related syndromes presents a challenge. Here we describe a case of a boy presenting with Marfanoid habitus, cutaneous vascular malformations, and severe acute anemia due to ileal venous malformations. Although a panel of genetic markers for the Marfan phenotype was negative, we identified a de novo mutation in the TEK gene in the patient. This case supports expansion of the phenotypic spectrum of TEK-related vascular malformations.

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, disimmune disease of the central nervous system whose etiology and pathogenesis remain poorly understood, due to its complex and multifactorial nature. Evidence of a bidirectional connection linking the gut microbiome with the intestinal barrier and the immune system (the gut-brain axis) may have implications for the pathogenesis of inflammatory demyelinating diseases such as MS. This narrative review summarizes the evidence for the gut-brain axis involvement in the pathogenesis of MS and examines the role of gut-oriented interventions in MS.We reviewed all available studies in PubMed concerning gut-directed interventions and MS. This research was conducted using different combinations of pertinent keywords (multiple sclerosis, immune-mediated inflammatory diseases, autoimmune diseases, first demyelinating event, neurocognition, neurological disorders, neurology practice, risk factors, taxonomic biomarkers, nutrition, diet, dietary additives, complementary treatment, gut bacteria, gut microbiome, microbiome, gut-brain axis, epidemiology, alpha-linolenic acid, fermentative metabolites, fat, saturated fat, monounsaturated fat, polyunsaturated fat, omega-3 fatty acids, calorie restricted diet, fasting, fecal microbiome, fecal microbiota transplantation, animal testing).There is an emerging evidence that alterations in the gut microbiome and increased intestinal permeability may be causative factors in the complex interplay between nutrition, metabolic status and the immune-inflammatory response in patients with MS. This suggests the possibility that modification of lifestyle and the microbiome, for example by specific diets or fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers, may positively influence the pathogenesis of MS.Although the role of nutritional factors in the pathogenesis of MS remains to be established, there is evidence that appropriate gut-directed interventions such as diet, nutritional supplementation or fecal transplantation may modulate the inflammatory response and improve the course of MS as a complementary treatment in the disease.

Genome-wide association studies identified over 200 risk loci for multiple sclerosis (MS) focusing on common variants, which account for about 50% of disease heritability. The goal of this study was to investigate whether low-frequency and rare functional variants, located in MS-established associated loci, may contribute to disease risk in a relatively homogeneous population, testing their cumulative effect (burden) with gene-wise tests. We sequenced 98 genes in 588 Italian patients with MS and 408 matched healthy controls (HCs). Variants were selected using different filtering criteria based on allelic frequency and in silico functional impacts. Genes showing a significant burden (n = 17) were sequenced in an independent cohort of 504 MS and 504 HC. The highest signal in both cohorts was observed for the disruptive variants (stop-gain, stop-loss, or splicing variants) located in EFCAB13, a gene coding for a protein of an unknown function (p < 10–4). Among these variants, the minor allele of a stop-gain variant showed a significantly higher frequency in MS versus HC in both sequenced cohorts (p = 0.0093 and p = 0.025), confirmed by a meta-analysis on a third independent cohort of 1298 MS and 1430 HC (p = 0.001) assayed with an SNP array. Real-time PCR on 14 heterozygous individuals for this variant did not evidence the presence of the stop-gain allele, suggesting a transcript degradation by non-sense mediated decay, supported by the evidence that the carriers of the stop-gain variant had a lower expression of this gene (p = 0.0184). In conclusion, we identified a novel low-frequency functional variant associated with MS susceptibility, suggesting the possible role of rare/low-frequency variants in MS as reported for other complex diseases.

Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is involved in sensorimotor behavior but has not been widely studied within the context of post-stroke upper limb sensorimotor impairment. The hippocampus is vulnerable to secondary degeneration after stroke, and damage to this region could further weaken sensorimotor circuits, leading to greater chronic sensorimotor impairment. The purpose of this study was to investigate the cross-sectional association between non-lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke. We hypothesized that smaller ipsilesional hippocampal volumes would be associated with worse upper-limb sensorimotor impairment.Cross-sectional T1-weighted brain MRIs were pooled from 357 participants at the chronic stage after stroke (>180 days post-stroke) compiled from 18 research cohorts worldwide in the ENIGMA Stroke Recovery Working Group (age: median = 61 years, interquartile range = 18, range = 23-93; 135 women and 222 men). Sensorimotor impairment was estimated from the Fugl-Meyer Assessment of Upper Extremity scores. Robust mixed-effects linear models were used to test associations between post-stroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni-corrected, p-value < 0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. We also performed an exploratory analysis to test whether sex differences influence the relationship between sensorimotor impairment and hippocampal volume.Upper limb sensorimotor impairment was positively associated with ipsilesional (p = 0.005; d = 0.33) but not contralesional (p = 0.96; d = 0.01) hippocampal volume, such that impairment was worse for participants with smaller ipsilesional hippocampal volume. This association remained significant independent of lesion volume or other covariates (p = 0.001; d = 0.36). Evidence indicates an interaction between sensorimotor impairment and sex for both ipsilesional (p = 0.008; d = −0.29) and contralesional (p = 0.006; d = −0.30) hippocampal volumes, whereby women showed progressively worsening sensorimotor impairment with smaller hippocampal volumes compared to men.The present study has identified a novel association between chronic post-stroke sensorimotor impairment and ipsilesional, but not contralesional, hippocampal volume. This finding was not due to lesion size and may be stronger in women. We also provide supporting evidence that smaller hippocampal volume post-stroke is likely a consequence of ipsilesional damage, which could provide a link between vascular disease and other disorders, such as dementia.

Purpose To investigate the radiosensitizing capacity and therapeutic efficacy of the ataxia-telangiectasia mutated (ATM) inhibitor KU60019 on orthotopic glioblastoma (GB) driven by primary glioma initiating cells (GIC) with various p53 statuses. Methods Orthotopic GB have been developed in mice by intracranial injection of different GIC lines. Following tumor development, KU60019 was delivered to the site of the tumor [1] . The irradiation of orthotopic GB was performed by an RS 2000 Biological Irradiator (Rad Source Technologies) whose delivered dose was verified by a RadCal Accu-Gold system (Monrovia) equipped with a 10X6-0.6 High Dose Rate Chamber. The dose was confirmed by radiochromic films (Gafchromic® EBT3) placed over and under the mouse head. The prescription dose ranged 0.5–2.5 Gy. MRI of the orthotopic tumors was performed by a clinical 3T scanner (Signa EXCITE®HDxT, GE, Milwaukee, USA) with mice positioned in a prototype coil (linear birdcage transmit/receive coil, Flick Engineering Solutions BV-General Electric). Tumor volumes were determined by a software for quantitative MRI (GRES) [2] . Results A limited, but significant, elongation of median animal survival was observed after one radiosensitization cycle performed with one KU60019 CED administration followed by three ionizing radiation (IR) fractions as compared to animals treated with vehicle + IR [101 vs 91 days – Hazard Ratio: 4.922]. Other irradiation schedules failed to improve survival of animals bearing orthotopic GBs. Conclusions Further research to determine general and effective conditions for radiosensitization of orthotopic GBs by ATM inhibitors is warranted.

We present our experience with a simplified anastomotic posterior urethroplasty to highlight the necessity and usefulness of ancillary reconstructive maneuvers. We reviewed the records of 46 patients who had undergone anastomotic repair of posterior urethral strictures due to pelvic trauma between 2000 and 2007. Mean patient age at surgery was 43 years. Average stricture length was 2.3 cm. Repair was performed with a progressive perineal anastomotic procedure using flexible cystoscope by means of transcystostomic approach: after mobilization of the bulbo-membranous urethra and the corporal splitting, the prostatic apex is well visualized and the membranous urethra is sectioned proximally; the flexible cystoscope by means of transcystostomic approach facilitates to find the proximal urethral lumen and to perform the bulbo-prostatic anastomosis. Mean follow-up was 32 months. Of 46 cases, 40 (87 %) were successful and 6 (13 %) failed with recurrence of the stricture. Urinary incontinence did not develop in any patients. The operative details and maneuvers facilitate the preparation of the bulbo-membranous urethral tract and prostatic apex, and simplify the performance of the anastomotic repair.

Robustness of a system's behavior to changes in parameter values is a remarkable property of natural systems and especially desirable when designing de novo synthetic gene circuits. Loads on transcription factors resulting from binding to target promoters have been shown to significantly affect the effective time constants of gene transcription networks and to thus alter the overall system's behavior. Here, we employ models that explicitly account for load effects to investigate how these impact the robustness of a stable gene transcription network to parameter perturbations. By employing a combination of sampling-based methods and analytical tools from control theory, we demonstrate that the presence of loading shrinks the region of parameter space where a gene circuit performs the desired function. A number of multi-module synthetic gene circuits are analyzed to demonstrate this point, including an event detector and a molecular signature classifier. These results indicate that for designing genetic circuits that are robust to parameter uncertainty it is highly desirable to find ways to mitigate the effects of transcription factor loading.

IntroductionThere is little research comparing patients’ views with those of their treating psychiatrists. In a survey of patients’ views conducted in 1993 for MIND (UK) by Rogers, Pilgrim and Lacey only 10% saw their problems in terms of mental illness. This highlights the tension between psychiatric codifications of mental abnormalities and explanations provided by patients themselves.AimsThis pilot project explores the perceptions of mental health issues in patients and their psychiatrists in a regional Western Australian setting.MethodsA mixed methods approach including semi-structured interviews of patients and their treating psychiatrists. Recruiting 5 consecutive people in the categories of involuntary in-patients, voluntary in-patients, patients on CTO, community patients and their psychiatrists.Questions asked of the patients were:– Why are you here?– What problems do you have?– What can be done?– What control do you have?– What control do other people have?Psychiatrists were asked similar questions. Responses were recorded, transcribed and thematically analyzed to reveal key themes. Quotations are used to illustrate points participants wished to make.ResultsWe report on differences in understanding in both groups. This study reveals areas for further enquiry.ConclusionsConsiderable diversity is revealed. A key conclusion is that insight is a concept relevant both for treated and treating.Disclosure of interestThe authors have not supplied their declaration of competing interest.

In the surgical treatment of urethral strictures many techniques have been proposed in the last 30 years. Nowadays, only some of them are currently used, because of complications correlated to these surgical procedures. Of course, our School has also changed indications for surgical procedures in urethral strictures. We can use two different kinds of surgical technique; excision of the stricture with an end-to-end anastomosis or urethroplasty. At the Institute of Urology of the University of Milan, 84 patients underwent end-to-end anastomosis: the 12 months follow-up showed 6 relapsed strictures, 1 fistula and 5 penile ventral flexures. In the field of multi-stage urethroplasty our greatest experience is related to the scrotal inlay technique (144 patients: 36 relapsed strictures, 65 phlogoses, 44 stones), while 18 patients underwent the procedure by the use of free epidermal mesh graft (1 fistula, 2 penile flexures, 2 necrosis of the graft). Concerning the one-stage procedures, the bladder mucosa graft seems to be reliable, and the complications observed were the following: 2 relapsed strictures, 3 fistules, 1 penile flexure; the lip mucosa graft represents a possible alternative: using this technique in 8 patients we had 2 recurrent strictures and 1 fistula. Recently we proposed a modified technique using a tubularlzed penile skin flap for complex, recurrent, extended bulbo-membranous strictures. 24 pts. underwent this surgical procedure. Only two stricture relapses have been found. The first four operated pts. had urethrocystograms which revealed a neourethra exceeding the normal caliber and this was resolved in consecutive cases by reducing the size of the flap.

Congenital microphthalmia (CM) is a rare developmental defect of the primary optic vesicle. The estimated incidence is around 1.5–19/10 000 births and it may be unilateral or bilateral, usually associated with other ocular anomalies. The morphogenetic defect can be due to external gestational factors (infection or drugs), or to a primary genetic abnormality, occurring as an isolated finding or as a part of a generalized syndrome. Flash visual evoked potentials (FVEPs) can be useful in assessing acuity and detect any optic nerve dysfunction in patients with CM at an early age. Here we describe the FVEPs findings of five infants of age ranged between birth and 6 months with unilateral CM. The FVEPs were recorded according to ISCEV standard 2010; the amplitude and peak latency of the main P2 wave were matched for postconceptional age and other ocular or systemic morphogenetic defects associated. An isolated microphthalmia was assessed in four patients, while in one case it occurred as a part of Microphthalmia and Skin Linear defect (MSL) Syndrome. Left eye was involved in 4/5 patients (M/F ratio 1/1). All our patients presented asymmetric FVEPs traces with an increased latency of P-2 wave (equivalent to P100) in the affected eye. Binocular stimulation patterns and measurements of peak amplitude of main waves were normal except for two patients, respectively carriers of MSL syndrome and opacities of dioptric media, whose traces revealed a decreased waves’ amplitude. According to our experience, FVEPs can help in distinguishing isolated CM idiopathic cases from those with widespread ocular and/or neurological abnormalities and can provide a reasonable prediction of visual outcome to parents as soon as possible, allowing an appropriate management.

The aim of this study was to evaluate the effect of cloprostenol administration on the blood flow of pre-ovulatory follicle (PF) and corpus luteum (CL), progesterone secretion and pregnancy outcome in buffaloes subjected to AI. The trial was performed on 75 Italian buffaloes at 182 ± 8 days in milk. Synchronized animals were randomly divided into two groups on the day of oestrus: Group T (n = 37) received a 0.524 mg intramuscular injection of cloprostenol and Group C (n = 38) received saline. Ultrasound examinations of the ovaries were performed 5 h after AI on the PF and 10 and 20 days after AI on the CL. Resistive (RI) and pulsatily index (PI) were calculated by colour-Doppler mode in each examination. Blood samples were collected on days 10, 20 and 25 after AI for progesterone assay and 25 days after AI, ultrasonography was performed to assess pregnancy, which was confirmed on day 45. Subjects pregnant on day 25 but not on day 45 were considered to have undergone late embryonic mortality (LEM). Statistical analysis was performed by anova. No differences were found in PF dimensions, CL size and blood flow on day 10 and 20 after AI between treated and control groups. Pre-ovulatory follicle area was higher in buffaloes that resulted pregnant on day 25 after AI compared to those that were non-pregnant (2.13 vs 1.66 cm in pregnant and non-pregnant buffaloes, respectively), while non-pregnant buffaloes showed higher values of RI (0.49 vs 0.30; p0.05) and PI (1.0 vs 0.37; p = 0.07) compared to pregnant subjects. Treatment by cloprostenol did not influence pregnancy rate both on day 25 (31/75; 41.3%) and 45 (27/75; 36.0%), progesterone levels and incidence of LEM (4/31; 12.9%). In conclusion, cloprostenol administration at the time of AI does not seem to affect PF and CL blood flow.

Congenital and especially recurrent complex pathologies of the corpora cavernosa need an integrated surgical approach (urological and plastic surgery). The fields of application of these techniques are: a) correction of congenital pathologies of the male genitalia; b) genital reconstruction after radical pelvic surgery; c) genital reconstruction after trauma. An adequate experience in surgery of flaps, the knowledge of their vascularisation and biology, the observance of particular intraoperative procedures and an accurate postoperative management are mandatory. This is also the case of surgery in female to male transsexuals. Different techniques have been proposed but few of them give aesthetically and functionally satisfactory results. In our experience clitoridal enlargement and urethral transfer, in anatomically selected patients and after substitutive hormonal therapy, give sufficient guarrantee of conservation of sensitivity and erectile capacity and have a positive psychological impact on the patient. When cosmetic dimensional emphasis is required as regards the neophalius the transfer of a rectal abdominal muscle flap with epidermal graft has given, in our experience, satisfactory results.

— Urethro-vaginal fistulas are rare in western countries, but more frequent in under-developed countries. In the latter this pathology is usually due to obstetric causes, whereas in European countries it arises mainly from gynaecological operations (82%). Results differ according to the cause. Almost all authors report a recurrence rate between 3 and 28%. We have chosen transvaginal urethroplasty with overlapping flaps from among the other more complex repair procedures which involve completing the fistulorraphy with myo-lipomatoso-cutaneous flaps. Our case histories (1988–1991) include 19 simple and 6 complex fistulas with the following etiology: gynaecological operation (16), obstetric causes (4), traumas (4). “Simple” fistulas were first treated by urethroplasty with overlapping flaps. Of 24 patients at 8-months follow-up, 82% of those operated once only, and 100% of those operated several times, had fully recovered. There were 2 recurrences due to Infection in the suture and 2 from tissue fibrosis. For “complex” fistulas and re-operations, we modify the Falandry method. We have concluded that transvaginal urethroplasty with several overlapping flaps is a valid procedure for non-recurrent fistulas which are limited in size and with little loss of fluid from ischemic dystrophy, which would otherwise, in our opinion, require the interpositioning of a myo-lipomatoso-cutaneous flap.

The aim in this study was to investigate corpus luteum function and embryonic loss in buffaloes mated by artificial inseminations (AI) during the transitional period from breeding to non-breeding season. The study was carried out using 288 multiparous Italian Mediterranean Buffalo cows at 110 ± 4 days in milk. The buffaloes were mated by AI after synchronization of ovulation by the Ovsynch-TAI protocol 25 days after AI buffaloes underwent trans-rectal ultrasonography to assess embryonic development. Pregnancy diagnosis was confirmed on Days 45 and 70 after AI by rectal palpation. Buffaloes pregnant on Day 25 but not on Day 45 were considered to have undergone late embryonic mortality (LEM), whilst buffaloes pregnant on Day 45 but not on Day 70 were considered to have undergone foetal mortality (FM). Corpus luteum size and blood flow were determined by real-time B-mode/colour-Doppler on day 10 after AI in 122 buffaloes. The resistive index (RI) and pulsatility index (PI) were recorded at the time. Milk samples were collected on Days 10, 20 and 25 after AI in all inseminated buffaloes for the assay of whey P4 concentrations. Data were analysed by anova. Pregnancy rate on Day 25 after AI was 48.6% (140/288) and declined to 35.4% (102/288) and 30.6% (88/288) by Day 45 and Day 70 respectively. The incidences of LEM and FM were respectively 27.1% (38/140) and 13.7% (14/102). Pregnant buffaloes had greater (p 0.01) whey concentrations of P4 from Day 20 onwards than buffaloes which showed LEM, whilst P4 in buffaloes that showed FM did not differ from the other two groups on Day 10 and Day 20. Corpus luteum blood flow on Day 10 after AI showed higher RI (p 0.05) and PI (p = 0.07) values in buffaloes that subsequently were not pregnant on Day 25 compared with pregnant buffaloes. Buffaloes that were not pregnant on Day 45 also had a higher (p = 0.02) RI value on Day 10 than pregnant buffaloes, whilst PI values on Day 10 did not differ for the two groups of buffaloes. It was concluded that blood flow to the corpus luteum on Day 10 after AI influences corpus luteum function as judged by P4 secretion and also embryonic development and attachment in buffaloes.

Amgen has launched darbepoetin alfa, synthetic recombinant novel erythropoiesis stimulating protein (NESP), for the treatment of anemia associated with renal disease. The drug was approved by the European Commission in June 2001, under the tradename Aranesp, for the treatment of anemia in chronic kidney failure including patients on and not yet on dialysis. The company launched the drug on day one of its approval in the following countries: Germany, Sweden, Denmark, Portugal, the Netherlands, the UK and Austria. Roll out of the drug in Italy, Greece and France will follow as soon as pricing and reimbursement issues are resolved [412240], [412357]. By January 2001, the product was still under review and the company anticipated approval during the first half of 2001 in both the US and Europe [396802]. Launch in the US had originally been scheduled for 2000 [387293], [396802] and Japanese launch is planned for 2004 or 2005 [405915]. In January 2001, Amgen reported that the first pivotal trial of darbepoetin alfa in treating oncology patients with anemia was successful [396526], [396802]. The company anticipated a phase III trial in US patients in 2001 for the oncology indication 13977941. In the fourth quarter of 2000, darbepoetin alfa entered phase I trials in Japan. Japanese development of darbepoetin alfa was being conducted by Kirin Brewery (under the research code KRN-321) [396653]. In January 2001, Genesis Pharma licensed the rights to distribute, market and sell darbepoetin alfa for the treatment of anemia, in Greece and Cyprus [396437]. MegaPharm Ltd signed an agreement with Amgen in February 2001, granting MegaPharm certain exclusive rights to distribute, market and sell darbepoetin alfa in Israel [398897]. In February 2000, Merrill Lynch predicted that darbepoetin alfa sales will be in excess of $1.4 billion at maturity [355817]. In October 2000, darbepoetin alfa annual sales were predicted to hit $3 billion [387293].

Background:We have noticed in our clinical practice a few patients with psychoses whose mental health was affected by the use of Benzylpiperazine related compounds. Benzylpiperazine and related compounds were sold legally in the UK until March 2007 when they were declared illegal. They are still legal in New Zealand whilst it is classified as a Class one drug along with LSD, cocaine and cannabis in the USA, Sweden, Denmark and Greece.Aims:To understand the effect of Benzylpiperazine based party pills on the mental health of a patient who already had a diagnosis of Schizophrenia.Methods:We followed up the clinical psychopathology of the patient while he was in our acute Psychiatry ward in 2007 during an admission precipitated by the use of Benzylpiperazine based party pills. Also we went through his previous notes to find out the symptomatology during all his previous admissions and outpatient appointments.Results:Use of Benzylpiperazine based party pills resulted in manic symptoms in this patient with Schizophrenia who did not have these symptoms until he started using the party pills.Comments:Benzylpiperazine based party pills have mood elevating properties and also induce insomnia in users. From our anecdotal experience it is seen that in patients with mental illness this leads to non compliance with medications and may also induce manic symptoms. Benzylpiperazine based drugs of abuse have been less well researched compared to other drugs of abuse.

We present our clinical and metabolic follow-up data of 74 patients submitted to total bladder substitution using an ileal orthotopic neobladder in one group of 64 patients and a continent stomal pouch in another group of 10 patients. In the first group the mean follow-up was 41.5 months. The daytime continence was early achieved in 89% (57/64) and was maintained with time; at 12 month follow-up nocturnal continence was reached in 71% (45/64). Post voiding residual was significant only in 4 patients (2 men and 2 women). No clinical signs of pyelonephritis nor renal scars at IVP was evidenced in all but 7 patients in which a silent uretero-ileal stenosis developed. No severe metabolic acidosis or B 12 deficiency occurred. In the second group (Continent Pouch) the long term 3-Year follow-up shows a complete continence in all patients with an average capacity of 600 cc. No late complications occurred in all patients but one in which self intermittent catheterization was uncomfortable and now he prefer permanent catheter and in another patient with a stone in the Pouch treated with Lithoclast. In conclusion, total bladder substitution after radical cystectomy is now represented by orthotopic neobladder or continent Pouch in men and women. Early and late complication rate is relatively low and continence generally good.

Hysteroscopy is a technique which plays a fundamental diagnostic role in gynecological practice. The possibility of obtaining a direct intracavitary view and performing specific biopsies give it a greater level of diagnostic accuracy than intrauterine curettage. The authors' personal experience of 13,923 case enables the correct method of performing this procedure to be codified in order to avoid the inherent risks and complications. The main indication is abnormal uterine bleeding which is the most frequently observed pathology in gynecological practice. In cases of metrorrhagia in women of child-bearing age benign organic pathology accounts for 45% of patients and malignant pathology 0.3%. Post-menopausal patients reveal an increase in the incidence of organic pathology in general and neoplastic pathologies in particular (8.1%). Complications linked to this type of technique are extremely rare and in overall terms affect 1% of cases. The analysis of results shows that hysteroscopy today represents an extremely reliable and repeatable outpatient procedure. However, in spite of these advantages, including savings in health costs, it is not widely used at a capillary level given that if performed by persons who are not expert it may become traumatic and unreliable. The correct execution of hysteroscopy in fact calls for dexterity acquired over time which is not conditioned by the learning of previous techniques and requires an adequate period of training.

The recent clinical and experimental research innovations in Andrology make possible the following classification of impotence: "Failure to initiate" "Failure to store" "Failure to fill" The last aspect, including veno-occlusive dysfunction, is continuously reevaluated by andrologic studies. The main diagnostic procedure of this complex problem, in constant evolution, is represented by cavernometry. Recently, but with full success, we are utilizing direct radioisotopic penogram in video sexy stimulation: in preselection function but probably in future with substitutive function of the more invasive and traditional cavernometry. In spite of this methodologic progress the findings of cavernometry are in continuous discussion as in tumultuous evolution, in anatomo-physiological environment, is the intracavernous district that, for many aspects, necessity of ulterior histochemical, pharmacodynamic and neurophysiological acknowledgements.

Surgery of hypospadias represents an interesting field of innovatory ideas. Many methods may be suitable and many modifications can be performed. There is no one method for all kinds of hypospadias. It is necessary to find the right method for each patient. The result often depends upon the experience of the surgeon with a particular method. The choice between straightening and urethroplasty in one or two stages depends on cost-benefit ratio and evolution at distance of the straightening must be taken into account as well tissue consumption imposed by the urethroplasty, with one stage straightening that makes reintervention very difficult. In the latter case, a multi-stage operation will be necessary with flaps for urethroplasty after the straightening, or, in a more developed penis, a shortening operation according to Nesbit. With two-stage method, in case of relapsed curvature, this can easily be treated, if tissue is available. For a good result of urethroplasty the ability of surgeon, a constant calibration of the canal, plenty of elastic tissue for the neo-urethra, care not to suture on these planes, are highly important. In our opinion Duplay's method observes these requisites. Two-stages surgery allows easy correction of any eventual relapsing incurvature, with no problems for the following urethroplasty. One-stage surgery allows the problems to be resolved in a single surgical Step, but involves the risk of tissue consumption and proximal stricture.

Veno-occlusive dysfunction (formerly called "venous leakage") is a clinical-radiographic manifestation of a multi-aetiology syndrome, the pathogenesis of which is to be sought in intrinsic damage to the erectile tissue. It has been attributed to psycho-neurogenic, neurovascular and local--physical factors. The unsatisfactory results of the various surgical techniques proposed (venous ligatures, crural plication, corporopexy) can be explained by the formation of vicarious venous circles, a phenomenon which occurs regardless of the type of procedure adopted and which is the direct consequence of the alteration of the occlusive mechanisms intrinsic to the erectile tissue. At the Urological Institute of the University of Milan, a study has been carried out with the aim of experimentally assessing these aetiopathogenetic hypotheses. 48 sexually potent patients were selected from those scheduled for extensive surgical procedures on account of malignant pathologies of the pelvic cavity (urethro-prostato-cystectomy, radical prostatectomy). The protocol included a series of examinations before and after the operation (at three months): computerised recording of nocturnal erections (NPT test, three consecutive nights), dynamic penile Doppler velocimetry, dynamic cavernosometry/graphy, examination of bulbocavernosus reflex. The goal of the study was to evaluate the haemodynamic consequences of the massive venous ligatures effected during these operations (periprostatic plexus, deep dorsal vein, spongio-cavernous connections). There were 28 cases of radical prostatectomy and 20 cases of radical urethro-prostato-cystectomy. Among the cases of radical prostatectomy, the extrafascial retropubic technique was used for 14 patients, the monolateral nerve-sparing procedure was applied for 10 patients (stage B1) and the transperineal approach was used for 4 patients (the most recent).(ABSTRACT TRUNCATED AT 250 WORDS)

The radical surgical option we propose for Peyronie's disease consists in removing the sclero-hyalinotic focus of disease and replacing it by an autologous dermal graft taken from the upper outer thigh area. Between 1981 and 1991, we operated 335 patients with IPP, 152 of whom underwent plaque excision and dermal graft. All could be assessed at two-year follow-up. Two main complications were observed: mild penile flexure due to scar retraction of the graft (35% of cases), and partial erectile deficit with decreased corporal rigidity (17% of cases). The degree of the graft retraction is linked to the individual's histologic response. A mild deviation of the penis can occur some months after surgery and is not a relapse flexure due to disease progression (as it should have evolutive characteristics) but is mere scar retraction and will spontaneously regress. As the patient will date the onset of a postoperative erectile deficit from the time of the operation, it is advisable to assess preoperatively the erectile ability of all patients. Furthermore, an impaired erectile response could result from hypoaesthesia of the glans, post-surgical stress, and fibrosis of the erectile tissue. A retrospective assessment of radical surgery cases involving plaque excision and dermal graft lead us to propose this option where precise indications apply, providing the presence of other alterations of the erectile function are pre-operatively assessed.

The Authors try to show the possibility to combine radical excision with minimal invasiveness in the surgery of penile cancer. The focal point of every therapeutic decision is correct clinical staging. Unfortunately there's some confusion in the two international staging systems (TNM and Jackson's classification). In fact it's not clear the anatomical difference between epithelioma of the glans infiltrating corpus spongiosum and subcoronary epithelioma of the shaft infiltrating the corpora cavernosa. It's obvious that the infiltration of the corpora cavernosa is a far more aggressive oncological manifestation than that of tumour infiltrating the corpus spongiosum. So we consider Jackson's classification more congenial. In terms of surgery this anatomical independence makes it easy to consider the corpora cavernosa as a distinct entity, so they remain perfectly functional when separated from the glandulo-spongio-urethral unit with its vasculo-nervous bundle. This makes conservation of the erectile function, when clinical staging show us that the tumour is not infiltrating the corpora cavernosa. The Authors show their results, which seem to be rather good.

After the remark of the own results on an epidemiological research about andropausal sexual problems, the Authors analyze the alterations of ejaculatory mechanism with elderly, focusing frequency and etiopathogenesis. They underline the need of prevention of ejaculatory disturbances deriving from chronic disease or of iatrogenic origin.

In our opinion, the attempt to save the sexuality and the erectile ability in a patient with a prostate cancer, in the respect of an absolute oncological radicality, should be recommended since potency represents for the patient a primary aspect in the quality of residual life. At the Institute of Urology of the University of Milan a study to identify pathogenetic mechanisms leading to erectile failure in the various phases of a prostate cancer was performed. From January 1988 to December 1993, 36 patients (range 50-60 years old) suffering from prostate cancer B1 stage (14 pts), B2 (20 pts) and C (2 pts) underwent to radical prostatectomy. Out of 24 pts reporting erectile ability before surgery, 10 was in B1 stage and underwent monolateral nerve-sparing technique. Out of these, 6 pts (60%) maintained the erection after the operation. The treatment with LHRH analogues weighted on loss of libido and erectile and erectile potent due to central androgenic delete. At our Institute 87 pts in treatment with LHRH analogues reported loss of erection in 80% of cases. In this group 22 underwent to an andrological examination. The exams (Dynamic penile Doppler, Dynamic Cavernosometry and stimulating test with intracavernous vasoactive drugs) confirm the absence of peripherical damages in the pathogenesis of the erectile dysfunction. Patient underwent radiotherapy develop a secondary impotence due to an obliterant progressive angioitis in a percentage ranging from 30 to 80%.(ABSTRACT TRUNCATED AT 250 WORDS)

After having emphasized the importance of interdisciplinary diagnostic approach to the sexual impotence as a symptom and having made some comments about the erection's physiology, the Authors, according to their experience, take drugs into consideration for elective treatment of sexual intercourse.

In the therapy of vasculogenic impotence, the Vacuum Device has been proposed up to now as an "external" prosthesis device with the aim of obtaining a penile erection of sufficient rigidity for penetration, in patients afflicted by vascular or neurological disorders. In the eighties, the experience gained with the use of Intra Cavernous Injections (C.I.D.) (using papaverine, phentolamine and prostaglandin), demonstrated not to be an exclusively palliative therapy ("pharmacological prosthesis"), but to represent as well a sort of "vasoactive exercise" of the erectile tissue. In the nineties, many wondered what could be a valid alternative to the C.I.D. Taking this into consideration, we modified the method of application of Vacuum Therapy. The device was used once a day without the constrictive band applied to the penis root, in order to generate a passive action on the erectile tissue, a sort of "stretching" for the smooth muscle fibers. From January 1990 to December 1991, we treated 78 pts. afflicted by erectile failure. The patients were divided into 3 groups (26 each) of distinct therapy: the first was treated weekly with only endocavernous papaverine administration (20 mg.), the second underwent daily Vacuum Therapy exclusively (10'-15') and the third received a combined therapy: Vacuum Device, daily and C.I.D. with Papaverine (20 mg.) once a week. The results of this treatment are as follows: the patients who underwent Vacuum Therapy daily (2nd and 3rd groups) showed, at the end of the treatment (6 months), a significant improvement in spontaneous erectile ability (14 Pts.-53.8% in the 2nd group; 17 Pts-65.3% in the 3rd group).(ABSTRACT TRUNCATED AT 250 WORDS)

Background:Fentanyl is a potent Schedule II opioid agonist that has potency more than 80 times that of morphine. A high concentration of Fentanyl is contained in Fentanyl patches (MATRIFEN).They should be used to manage pain for persons with chronic moderate to severe pain who are already physically tolerant to opiates.During the past years there has been an increase in misuse and abuse in the United States of Matrifen that has caused deaths from overdoses.Matrifen can also cause neurological and psychiatric adverse events such as: delirium anxiety, abnormal thinking, abnormal dreams, depersonalization and hostility.In the literature Matrifen have not previously been associated with serious offences such as attempted murder but an association with suicide has been noted.Aims:To describe a previously unreported and serious adverse effect of Fentanyl patches.Methods:We followed up the clinical psychopathology of an elderly gentleman who attempted to murder his wife reportedly due to an altered mental state caused by the application of Fentanyl patch. We searched Pubmed and Google for any reported adverse effect of Fentanyl patches of a similar nature.Results:After ruling out all other Psychiatric, Organic and Forensic causes we came to the conclusion that Matrifen was the cause of altered mental state which led to the attempted murder.Conclusions:Although adverse psychiatric effects of Fentanyl patches have been reported in the past we can add attempted murder to the list. Fentanyl patches can be dangerous particularly in the vulnerable elderly patients where they are most commonly used.

4767 Background: Standard dose (

Recent results showing that a single fibronectin gene can give rise to several different mRNAs by alternative splicing have offered an explanation for fibronectin polymorphism. Here we report on monoclonal antibodies that show specificity for a fibronectin segment (ED) that can be included or omitted from the molecule depending on the pattern of splicing of the mRNA precursors. Using these monoclonals, we have quantitatively analyzed the expression of the ED sequence in human fibronectin from different sources. The results demonstrated that, at the protein level, the ED segment is not expressed in plasma fibronectin and that, in fibronectin from the tissue culture medium of tumor-derived or simian virus-40-transformed human cells, the percentage of fibronectin molecules containing the ED segment is about 10 times higher than in fibronectin from normal human fibroblasts. These results suggest that in malignant cells the mechanisms that regulate the splicing of mRNA precursors are altered.

Pancreatic explants obtained from fetal rats were cultivated over 4 days, then incubated in the presence or absence of glucagon at concentrations between 0.2 and 3.2 μg./ml. Glucagon induced a clear-cut and dose-dependent release of insulin from the explants. This observation in vitro confirms the effect of glucagon reported by Samols et al.3,10 in vivo and may point to a new concept of the physiologic interrelations of the 2 pancreatic hormones.

The need for low-loss, stable, high current density superconducting windings has led to the development of twisted multifilament composite superconductors. For coils with high packing density that are capable of withstanding mechanical loading, the composites are often made rectangular in cross section, and the capability for production of conductors with high aspect ratios has been developed. Tapes of twisted multifilament Nb3Sn composites are in fact now being made in order to reduce the strain in the filaments during winding[1].

The test coil being designed and built by Westinghouse for the Large Coil Program (LCP) utilizes a conductor of forced-flow design having 486 strands of multifilamentary Nb3Sn compacted in a stainless steel conduit.1 The impetus for the present work stemmed from the need for some form of “insulation” on those strands to prevent sintering during reaction and to reduce ac losses. During the course of the LCP design several substances were considered as candidates for strand insulation but were rejected for various reasons.2 However, cuprous sulfide was found to perform well as a protective layer with no deleterious effects on the properties of the conductor.3 The sulfide layer survived the cabling, compacting, and heat-treating processes and effected the required low ac losses. As a result, a good deal of interest has arisen concerning the possible use of cuprous sulfide in other magnet systems. In this paper we describe the continuous process that was developed for applying cuprous sulfide to long lengths of conductor., discuss the properties of the films, and present some encouraging data on test coils that have been wound with sulfide coated conductors.

Three aromatic amines, 2,4 diaminotoluene, aminobenzene and paradimethylaminoazobenzene were examined for their capability of damaging rat liver DNA. Compounds were tested by the "in vivo"/DNA alcaline elution assay. 2,4 diaminotoluene was very positive, aminobenzene weakly positive, paradimethylaminoazobenzene probably negative. All the compounds were tested at doses already clearly toxic.

The affinity between CrIII and purified calf- thymus DNA was studied at neutral pH by competition with ethidium bromide. Competition results indicated an affinity between CrIII and DNA of the order of 10(5) 1/mole. These results are in good agreement with previous results CrIII - DNA affinity was studied by the independent method of equilibrium dialysis and chromium dosage by atomic spectrometry.

Cloricromen is a new drug that inhibits platelet aggregation in man and in experimental thrombosis. Twenty patients with a history of atherothrombotic stroke received cloricromen (100 mg, twice daily) for 30 days in order to evaluate its effects on plasma fibrinogen, antithrombin III, and other variables of the haemostatic system. A statistically significant decrease in the prothrombin time ( P < 0.01) was found only after 30 days of therapy. This decrease was transient and disappeared 15 days after the end of treatment. No statistically significant changes in plasma fibrinogen levels, antithrombin III, partial thromboplastin time, or platelet count were observed compared with baseline values. No side-effects were reported. This study did not reveal an effect of cloricromen on coagulative variables in patients with cerebrovascular occlusive disease.

Percutaneous liver biopsy (PLB) is the golden standard for diagnosing chronic liver disease (CLD) even if it is still debated if and how much a single liver specimen might represent the histological status of the entire liver. A study was conducted to determine the diagnostic value of PLB comparing the histological score of two liver specimens collected in the same patient on the hepatic right and left lobe. The role of PLB for diagnosing CLD is confirmed.