Peripheral artery disease and all-cause and cardiovascular mortality in patients with NAFLD.

PURPOSE: Cardiovascular disease (CVD) is the first cause of death in patients with non-alcoholic fatty liver disease (NAFLD) and risk stratification is recommended by current guidelines. The aim of this study is to assess the prevalence of peripheral arterial disease (PAD) in patients with NAFLD and its association with all-cause and cardiovascular disease (CVD) mortality. METHODS: 9145 participants 40 years or older attended a mobile examination center visit in the 1999-2004 cycles of the National Health and Nutrition Examination Survey. PAD was defined as an ankle-brachial index (ABI) < 0.90 in either of the legs and mortality data through December 2015 were obtained from the National Death Index. NAFLD was defined by a fatty liver index ≥ 60 in the absence of other liver conditions, leading to a final sample of 3094 subjects. RESULTS: The overall prevalence of PAD was 5.9% (95% CI 5.0-6.9). Over a median follow-up of 13 years, 876 participants died, 208 of cardiovascular causes. Incidence rates of all-cause mortality (for 1000 person-years) were 20.2 (95% CI 18.7-21.7) and 70.0 (95% CI 60.1-81.6) for participants without and with PAD, respectively. Multivariable-adjusted Cox proportional hazard models showed that PAD was associated with a higher risk of all-cause (1.8, 95% CI 1.4-2.4) and cardiovascular mortality (HR 2.5, 95% CI 1.5-4.3) after adjustment for potential confounders including prevalent CVD. CONCLUSION: Current guidelines strongly encourage the screening of CVD in patients with NAFLD and the use of the simple and inexpensive measurement of ABI in routine clinical practice may find indication.

[Laparoscopic treatment of UPJ obstruction in ectopic pelvic kidneys in children]. / Trattamento laparoscopico dell'Ostruzione del Giunto Pielo-Ureterale nei reni ectopici in età pediatrica.

AIMS: To assess the feasibility and safety of a laparoscopic approach to UPJ obstruction (UPJO) in ectopic pelvic kidneys. MATERIAL AND METHODS: In a retrospective analysis we selected 14 children, aged 6 months to 17 years, 12 males, 2 females, who had been treated in our Department between January 2004 and June 2011. 9 patients presented ureteropelvic junction obstruction (in 3 cases pelvic stones coexisted) with normal/moderately reduced (> or = 25%) relative function at radionuclide scan (MAG3), 3 nonfunctioning kidneys associated or not to hypertension, 2 congenital hypo-dysplastic kidneys. The evaluation of each patient involved the medical history, ultrasound examination, VCUG, MAG3 diuresis renogram and MRI in some cases. Of the patients presenting UPJO, 5 underwent dismembered pyeloplasty with pyelolithotomy, if required, and 4 pelvic derotation with straightening of the uretero-pelvic junction. A previous cystoscopic placement of a Double J stent was utilized. This facilitated the identification and dissection around the pelvis. With the patient in Trendelenburg position we utilized an umbilical trocar and two trocar in the right and left iliac fossae; an additional trocar, when required, was inserted more cephalad on the midclavear line contralaterally to the lesion. The derotation of ureteropelvic junction was obtained by freeing the kidney's lower pole and by placing intraperitoneally the junction protected with a Double J stent. This was obtained by suturing the peritoneum behind the ureteropelvic junction resulting in a forward rotation of the major axis of the kidney and a straightening of the junction. The 5 patients presenting nonfunctioning ectopic kidneys underwent laparoscopic nephrectomy. While the removal of congenital hypoplasic kidneys resulted easy, the removal of nonfunctioning kidneys was more difficult due to their complex vascular situation and for the embryonic disposition. RESULTS: The operating time varied between 40 to 200 minutes. No patient required conversion to open surgery. The hypertension resolved after nephrectomy in all cases. 2 cases of dismembered pyeloplasty required a placement of Double J stent due the recurrence of symptoms and ! patient is waiting for redo operation. The pelvic derotation showed an improvement of diuretic MAG3 renogram and the function remained stable and patiens are symptoms-free. CONCLUSION: The UPJO in ectopic pelvic kidneys presents a large spectrum of presentation. The laparoscopic approach provides good surgical exposure, and operative times are acceptable compared to those of laparoscopic procedure in anatomically normal kidneys. It has also proved a very useful tool in the non-functioning kidney nephrectomy thank to the help of magnification in the identification of numerous aberrant vessels that are quite often found in the pelvic kidneys. The derotation of the pelvis seems a useful procedure in moderate obstruction even if a longer followup is needed.

Pneumovesicoscopic correction of primary vesicoureteral reflux (VUR) in children. Our experience.

AIM: We report our experience with pneumovesicoscopic cross-trigonal ureteral reimplantation to correct primary vesicoureteral reflux (VUR) in children. MATERIAL AND METHODS: 14 children (10 girls, 4 boys, aged 4 to 12 years) with persistent VUR ≥ grade III (5 bilateral, 19 refluxing ureters) underwent pneumovesicoscopic Cohen's cross-trigonal reimplantation. Under cystoscopic control, a first midline 5-mm trocar was introduced for a 0°\30° telescope at the dome of the bladder, and 2 left and right 3- or 5-mm trocars were inserted through the anterolateral wall. The ureter was freed by creating a sharp plane between the detrusor muscle and the ureteral wall. If necessary, the ureter was tailored outside the bladder. Submucosal tunnel(s) were prepared with the help of scissors and graspers. The detrusor at the site of the ureter mobilization was repaired and ureteroneocystomy was performed using 4-5 interrupted absorbable sutures. A 12-Ch Foley catheter was introduced at the site of the dome port. The urethral and suprapubic catheters were removed 2-3 days after the procedure and the patients were discharged on day 3. RESULTS: One boy developed mild suprapubic emphysema postoperatively. Mean operating time was 136 min (range 80-230 min). No patient required conversion to the open technique. Renal US, VCUG, and MAG3 radionuclide scans were obtained in all patients between 3-6 months postoperatively, and provided evidence of reflux resolution in 13 out of 14 patients. CONCLUSION: Our experience seems to confirm that pneumovesicoscopic cross-trigonal ureteral reimplantation can be performed safely and effectively.

The value of laparoscopy in the management of non-palpable testis.

OBJECT: To retrospectively review the value of laparoscopy in the management of impalpable testis. MATERIALS AND METHODS: In 1993-2006, 182 laparoscopies for impalpable testis were performed for a total of 194 testicular units. Five laparoscopic findings were considered: testicular ectopia, intra-abdominal testis, and cord structures that are blind ending, completely absent (agenesis) or entering the internal inguinal ring. RESULTS: In 62 cases an intra-abdominal testis was found; 18 were classified as high and managed by a laparoscopic Fowler-Stephens procedure. Cord structures entering the inguinal ring were observed in 77 patients and 45 underwent an inguinal exploration: a testis was found in 12 cases and in 33 a remnant was excised. In 35 cases, intra-abdominal blind ending vas and vessels were observed and eight showed testicular agenesis. No major surgical complications were recorded. Follow up ranged from 1 to 3 years. CONCLUSIONS: Our study confirms the value of laparoscopy in the management of non-palpable testis, providing a definitive diagnosis by the direct view of spermatic bundle and testis. Ninety-three patients were managed by laparoscopy only, and in 44 it was essential for the subsequent surgical approach. When the internal inguinal ring is patent and/or normal spermatic vessels are present an inguinal exploration is mandatory.

Effectiveness of botulinum-A toxin for the treatment of refractory overactive bladder in children.

AIMS: We describe our experience with botulinum-A toxin (BTX-A) in children presenting idiopathic overactive bladder (OAB) refractory to anticholinergic drugs. MATERIAL AND METHODS: 21 patients, aged 8-12 years, were treated over a 3-year period. BTX-A was administered at a dosage of 12.5 UI /kg body weight, without exceeding 200 UI, at 20 detrusor sites. To ensure a stable solution, each 100 UI of botulinum toxin was diluted with 5 cc saline solution just prior to performing the cystoscopy. RESULTS: No patient presented with severe systemic complications or urinary retention after injection therapy; 6 patients presented with slight hematuria for 2-3 days. The clinical results were as follows. At 6 months, 8/21 patients (38%) showed full response, 12/21 (57%) had a partial response after a 2 (nd) injection, and 1/21 (4.7%) showed no response after a 2 (nd) injection. At 12 months, 16 patients (76%) had a full response, 4 (19%) showed a partial response after a 3 (rd) injection, and 1 patient (4.7%) still had no response. At 18 months, 18 patients (85%) showed a full response, 2 patients (9.5%) had a partial response, 1 patient (4.7%) had no response. At the end of this study, 8/21 patients (38%) were symptom-free, after only one botulinum detrusor injection, 13/21 patients (61.9%) received a second botulinum injection because of recurrence of urinary incontinence 6-7 months after the initial treatment, and 4/21 patients (19%) received a third injection 12-14 months after the initial treatment, of whom 2 had a full response and 2 had a partial response. Patient no. 20 refused any further botulinum treatment after the 2 (nd) unsuccessful injection series. CONCLUSION: Intravesical BTX-A injection appears to be safe and useful in children presenting with idiopathic overactive drug-resistant bladder.

[Syringocele in children: an unusual presentation as scrotal mass]. / Il siringocele in età pediatrica: una insolita presentazione come massa scrotale.

Syringocele is a cystic dilation of the excretory bulbourethral Cowper gland duct, and is a rather uncommon finding in pediatric age. It is frequently asymptomatic but sometimes may cause voiding symptoms and urinary tract infection (UTI). This case report describes an unusual manifestation of syringocele presenting with hydrocele. The case concerns a 2-year-old boy who was referred to our Clinic with a diagnosis of hydrocele. The patient underwent hydrocelectomy through a bilateral inguinal incision, but no clear communication with the patent peritoneal vaginal ducts could be demonstrated. The histology evidenced an epidermoid cyst. One year later the scrotal mass relapsed. Sonography, voiding cistography (VCG), computed tomography (CT) scan and magnetic resonance imaging (MRI) were performed. VCG, CT scan and MRI demonstrated the communication between the urethra and the scrotal mass. A surgical excision of the syringocele with endoscopic resection of the collar were performed. Syringocele is a rare entity in pediatrics. To this authors' knowledge there are no reports in the literature describing cases presenting with scrotal mass.

Interaction between theory and experiment in the study of sleep physiology: a historical survey of early sleep research.

The interaction between theory and experiment in sleep research was considered on the grounds of a selective historical survey of early sleep studies up to the first half of the twentieth century. The dialectic pair of experimental reductionism and theoretical holism was the motor of progress in sleep research as soon as it was supported by the electroencephalographic technique, a by-product of applied physics. The identification of sleep stages was a turning point in the development of the experimental methodology of sleep research. Also, other scientific disciplines, particularly anatomy and chemistry, provided technical support increasingly suitable for the experimental study of the physiology and pathology of sleep. In general, cognitive advances depended on a research methodology (theoretical and experimental) free from the influence of cultural prejudices and supposedly indisputable scientific paradigms.

Unexpected finding of laparoscopic appendectomy: appendix MALT lymphoma in children.

Mucosa-associated lymphoid tissue (MALT) lymphomas comprise a group of indolent B-cell non-Hodgkin lymphomas (NHL), which are rare in pediatric age. The clinical presentation of MALT lymphomas varies according to the location of the lymphoma. We report on a case of MALT lymphoma involving the appendix in a 6-year-old girl. A 6-year-old girl was referred to our institution in May 2005 with a diagnosis of appendicitis. The abdominal ultrasound showed slight effusion in the pelvic fossa. The patient underwent laparoscopic appendectomy using the three-trocar technique. The appendix appeared moderately hyperaemic with slight enlargement of the two-thirds of the distal portion. The postoperative course was uneventful and the girl was discharged on day 1 without any complication. The morphological and immunohistochemical examination showed typical findings of low-grade MALT lymphoma (positivity for CD20, no immunostaing for CD5 and CD10, positivity for anti-lambda light chain and low positivity for Ki-67). Further extensive examinations (abdominal MRI, gastroscopy, colonscopy and capsule endoscopy of the ileum) revealed that the lymphoma was limited to the distal two-third of the appendix (stage IA) and was not associated with any specific infection. At a recent follow-up the patients appeared to be doing well. Appendiceal MALToma is a rather uncommon pathology and, to our knowledge, there is only one report of appendiceal intussusception associated with appendiceal maltoma. According to our experience, low-grade MALToma can be managed by simple appendectomy. The histological examination should be the rule whenever an appendectomy is performed in children.

REM sleep related increase in brain temperature: a physiologic problem.

The roles of metabolic heat production, arterial blood flow and temperature in the genesis of the brain temperature increase related to REM sleep occurrence in several mammalian species are discussed on the basis of available experimental evidence. The experimental data show that only changes in arterial blood flow and temperature consistently underlie the rise in brain temperature in presence (cat) or absence (rabbit) of the carotid rete. The alteration of cardiovascular regulation in REM sleep is the remote cause of such rise. The proximate causes are decrease in carotid blood supply and increase in vertebral blood supply to the brain and related depression of systemic and selective brain cooling.

[Painful defecation and chronic functional constipation in children: Diagnosis and treatment]. / Defecazione dolorosa e stipsi cronica funzionale nel bambino. Inquadramento diagnostico e terapeutico.

AIM: The aim of this study was to report our results on the treatment of chronic constipation associated with pain during defecation. METHODS: From January 1999 to January 2004, 60 patients (25 females, 35 males; age range, 6 months to 12 years) who met the ROMA II diagnostic criteria for chronic functional constipation associated with pain on defecation were enrolled in the study. All subjects underwent anorectal manometry to determine rectosphincter inhibitory reflex function. A retraining program for daily defecation, a diet high in fiber and lactulose, and local administration of prilocaine/lidocaine were instituted. At rectal anal endosonography, 7 drug-treatment-resistant patients presented with increased thickness of the internal anal sphincter and received botulin toxin A injection at the sphincter. Because symptoms persisted in 2 of these patients, they received a sphincterectomy. RESULTS: At the end of treatment, 40 (71.4%) of the 56 patients who completed the study had a daily bowel movement without pain; 9 experienced a relapse; in the 2 surgical patients the alveus returned to normal function at 2 and 6 weeks, respectively. CONCLUSIONS: Our treatment strategy breaks the vicious circle of spasm-pain-spasm with use of prolonged analgesic treatment and feces softener over the course of the day. In treatment-resistant patients with functioning rectosphincter reflexes and thickened internal anal sphincter, administration of botulin toxin A may be a valuable aid in place of standard sphincterectomy.

[Efficacy of toxin-A Botulinum for treating intractable bladder hyperactivity in children affected by neuropathic bladder secondary to myelomeningocele: an alternative to enterocystoplasty]. / La Tossina A-Botulinica in bambini con vescica neurogena iperattiva secondaria a mielomeningocele refrattaria agli urofarmaci: una alternativa all'enterocistoplastica.

AIM: To verify the efficacy of botulinus toxin A (TB-A) in treating children with neuropathic bladder secondary to myelomeningocele (MMC) with detrusor hyperactivity/low compliance, resistance to pharmacological therapy, and candidates for enterocystoplasty. METHODS: From January 2002 to June 2003, a group of 7 patients was selected (4 females, 3 males, mean age, 9.8 years, age range, 5-17 years) with detrusor hyperactivity, clean intermittent catheterization and resistance to pharmacological therapy. Two patients presented with grade 2-3 monolateral vesicoureteral reflux (VUR). All patients were incontinent despite catheterization. Botulinus toxin A was administered under general or local anesthesia by the injection of 200 IU of toxin diluted in 10 cc of physiologic solution with a metal or a flexible needle (3.7 F/21 GA). The needle was fully inserted into the detrusor muscle in about 20 sites, and 0.5 cc of solution were injected in each site, except the trigonum vesicae. Follow-up included ultrasound examination of the urinary tract and urodynamic studies performed at 6, 12 and 24 weeks and biannually thereafter. Micturition cystography was performed 3 months after the intervention. Urodynamic parameters were leak point pressure (LPP), leak point volume (LPV) and specific volume at 20 cm H2O pressure. The results were analyzed using the Wilcoxon test. RESULTS: A significant increase in LPV (range, 30-108%, mean, 77.6%) and in specific volume at 20 cm H2O pressure (CS 20) was observed in all patients. No significant change in LPP was found. One patient previously treated with the Cohen reimplantation technique experienced transient VUR which resolved spontaneously within 1 month. No major side effects from the injection of TB-A occurred. All patients were hospitalized for 24 hours with catheterization. CONCLUSIONS: The preliminary results in this small sample of patients suggest that the use of TB-A is efficacious in significantly improving urodynamic parameters and urine storage volume at low pressures in patients with neuropathic bladder resistant to pharmacological therapy.

Laparoscopic Fowler-Stephens procedure is contraindicated for intraabdominal testicular major duct anomalies.

The laparoscopic one- and two-stage Fowler-Stephens procedure has gained large popularity in the treatment of the child with a high intraabdominal testis. It is largely debated which technique (e.g., testicular autotransplant or Fowler-Stephens procedure) offers the best results for high intraabdominal testes. We describe a case of a 3-year-old boy for whom previous bilateral inguinal exploration results were negative for testes or testicular remnants. The diagnostic laparoscopy showed two iliac intraabdominal testes with short spermatic vessels, closed inguinal rings, and complete dissociation of didime-epididime. A left open orchidopexy was perfomed, and testicular autotransplant was proposed for the right testes located 4 cm from the internal inguinal ring. Long-term follow-up evaluation (1.8 years) of the left testis showed it in the scrotum with good testicular size (1.5 cm). We believe that there are two main reasons to contraindicate the Fowler-Stephens technique: associated malformation that does not permit the development of the collateral blood flow via the vasal artery necessary for a viable testis, and previous surgery that represents a risk factor for testicular atrophy. The laparoscopic anatomic classification for the intraabdominal testis is reliable and can disclose the most suitable surgical technique. Laparoscopy is a valuable tool in the diagnosis and treatment of the nonpalpable testicle.

REM sleep enhancement due to rhythmical auditory stimulation in the rat.

From a physiological viewpoint, REM sleep (REMS) is a period during which homeostatic physiological regulations are impaired. In the rat, REMS occurs in two forms respectively characterized by episodes separated by long intervals (single REMS episodes) and by episodes which have short intervals and occur in sequences (REMS clusters). Since the partition of REMS in the form of either single or clustered episodes may reveal how the REMS drive and body homeostatic processes interact in the control of REMS occurrence, we have used this approach to clarify the effects of the rhythmical delivery of an auditory stimulus (1000 Hz, 63 or 88 dB, 50 ms, every 20 s), which has been previously observed by different authors to enhance REMS in the absence of a previous sleep deprivation. Stimuli were delivered to pairs of animals and triggered by the occurrence of REMS in one rat (REMS-selective stimulation), whilst the other animal received the same stimulus irrespectively of the stage of the wake-sleep cycle (REMS-unselective stimulation). The results showed that the REMS-selective stimulation did not change the overall amount of REMS, since an increase in the occurrence of REMS clusters was concomitant with a decrease in the occurrence of single REMS episodes. In contrast, under the REMS-unselective stimulation, the total amount of REMS was increased during the second day of stimulation through an increase in the duration of both types of REMS episodes. Since during the REMS-unselective stimulation 87% of the stimuli fell outside REMS (i.e., during the REMS interval), the results show that the occurrence of REMS is more consistently affected when the stimuli are delivered in a period during which homeostatic physiological regulations are fully operant.

Pattern of REM sleep occurrence in continuous darkness following the exposure to low ambient temperature in the rat.

The occurrence of REM sleep episodes, separated by intervals >3 min (single episodes) and < or =3 min (sequential episodes), was determined in the rat during the recovery (ambient temperature (Ta) 23 degrees C, L period of the LD [12 h:12 h]-cycle), which followed the exposure to low Ta (0 and -10 degrees C) during the D period of the previous LD-cycle, either in normal light (DL) or in continuous darkness (DD). Both exposures were characterized by an almost complete disappearance of REM sleep, whilst the recoveries showed an increase in the amount of REM sleep in the form of sequential episodes, which in DD was particularly prominent and concomitant with a decrease in the amount of REM sleep in the form of single episodes. The initial 2 h-rate of REM sleep occurrence was lower following the exposure to Ta -10 degrees C, than to Ta 0 degrees C. In DD, such an effect was due to the large reduction in the occurrence of sequential REM sleep episodes. A functional correlate of this finding is that the accumulation capacity of a second messenger (cAMP) was found to be lower at the end of the exposure to Ta -10 degrees C, with respect to both the control (Ta 23 degrees C) and the end of exposure to Ta 0 degrees C, in the preoptic-anterior hypothalamus, but not in the cerebral cortex.

Behavioral state-dependent thermal feedback influencing the hypothalamic thermostat.

The experimental evidence on the behavioral state-dependent compartmentalization of temperature in the central nervous system of three homeothermic species has been reviewed to address the question of how selective brain cooling influences hypothalamic temperature regulation.

Influence of the temperature signal on sleep in mammals.

The influence of the temperature signal on sleep may be considered physiologically specific if it entails thermoreceptor activation. Experimental evidence shows that sleep time peaks at neutral ambient temperature.

Changes in REM sleep occurrence due to rhythmical auditory stimulation in the rat.

The effects of the rhythmical delivery of an auditory stimulus (1000 Hz, from 50 to 100 dB, 20 ms, every 20 s) on the pattern of rapid eye movement (REM) sleep occurrence was studied in the rat. The stimulation was simultaneously carried out on pairs of rats over 5 consecutive days (10-h recording sessions), during which a tone of increasing intensity (50, 63, 75, 88, 100 dB) was used. In each experimental session, auditory stimulation was triggered by the REM sleep occurrence of one rat (REMS-selective stimulation) whilst the other rat simultaneously received the same stimuli, but during any stage of the wake-sleep cycle (REMS-unselective stimulation). The results showed that the total amount of REM sleep in the 10-h recording session was increased over the 5 days of stimulation in the REMS-unselective group. This effect was due to an increase in the mean duration of REM sleep episodes. However, no significant changes were observed in animals under REMS-selective stimulation, nor in a third group of animals in which the spontaneous evolution of REM sleep occurrence (REMS-spontaneous) was studied. Since 86% of the stimuli under the REMS-unselective auditory stimulation fell outside REM sleep, the result would suggest that REM sleep occurrence is affected when the stimuli are delivered during a time period (i.e. during wakefulness or non-REM sleep) in which it is well known that physiological regulations are fully operant.

Changes in selective brain cooling across the behavioral states of the ultradian wake-sleep cycle.

In cats, the behavioral state-dependent negative correlation of the pontine-hypothalamic temperature difference, an indicator of selective brain cooling, with the hypothalamic-ear pinna temperature difference, which is an indicator of heat loss from the heat exchangers of the head, is suppressed after bilateral common carotid ligature. Behavioral state-dependent selective brain cooling may underlie a thermal feedback mechanism differentiating the relative influences of hypothalamic and extra-hypothalamic thermoreceptors on the thermoregulatory system during quiet wakefulness and NREM sleep.

Control of REM sleep: an aspect of the regulation of physiological homeostasis.

Since REM sleep is characterized by a suspension of the hypothalamic integration of homeostatic regulations, it has been assumed that the duration of both REM sleep episodes and of the time interval between the end of one episode and the beginning of the following episode may be regulated according to sleep related processes and the homeostatic needs of the organism. A series of studies performed on the rat has shown that REM sleep episodes occur as two basic types: single REM sleep episodes, that are separated by intervals > 3 min and sequential episodes, that are separated by intervals < or = 3 min and appear in a cluster. Moreover, it has been observed that, in this species, a change in REM sleep occurrence is caused by a modification in the number of episodes and not in their duration. With respect to this, sleep deprivation and recovery are characterized by a decrease and an increase, respectively, in the number of sequential REM sleep episodes, but the number of single episodes tends to be kept constant. The central aspects of this kind of regulation have been examined biochemically in the preoptic-anterior hypothalamus, an area involved in the control of autonomic and sleep related processes. The results show that the accumulation of adenosine 3':5'-cyclic monophosphate (cAMP) is impaired, in this region, during sleep deprivation and appears to return to the control levels, during the recovery, with a rate inversely related to the degree of the previous deprivation. Moreover, it has been observed that the systemic administration of DL-propranolol and LiCl reduces cAMP accumulation mainly in the preoptic-anterior hypothalamus; this condition is concomitant with a reduction in REM sleep occurrence.