[Gastric atresia, diaphragmatic hernia, and gastroesophageal reflux: a rare malformation requiring a multiple approach]. / Atresia del corpo gastrico, ernia diaframmatica laterale sinistra, reflusso gastro-esofageo. Malformazione rara e complessa trattata in più stadi con tecnica mista.

The first cases of atresia or web in the pyloric and prepyloric regions were described in the literature since 1937. To date, only one case of atresia at the junction between the fundus and the body of the stomach has been reported. We want to describe a complex case with incomplete atresia between fundus and gastric body, with left lateral diaphragmatic hernia, treated in several stages by endoscopic, open surgery and minimally invasive surgery

Determination of the anal position in newborns and in children with chronic constipation: comparative study in two European healthcare centres.

INTRODUCTION: The objective of this study was to determine the normal anal position index (API) in neonates and in a group of older children with chronic constipation, and to identify the incidence of anterior ectopic anus (AEA) in the two groups. MATERIALS AND METHODS: A prospective random study was carried out in two European hospitals determining the API in 1,012 neonates (529 in Group A, and 483 in Group B) and in 64 children suffering chronic constipation of ages between 3 months and 12 years (Group C). The API is defined as the ratio between the fourchette-anal and fourchette-coccygeal distances in girls and the scroto-anal and scroto-coccygeal distances in boys. The gestational age, weight, meconium evacuation and anal calibre were recorded in Groups A and B, and age, sex, and API in Group C. Statistical comparisons were made using Student's t test and Welch's t test for independent sample groups. RESULTS: The mean API in Group A was 0.53 ± 0.06 in males and 0.40 ± 0.05 in females, and in Group B 0.51 ± 0.06 in males and 0.39 ± 0.08 in females, with significant differences between the sexes (p < 0.0001) in both groups; 1.7% of the neonates in Group A and 2.4% of Group B presented AEA. 4/13 newborns females with AEA presented with severe constipation during their first months of life. For the 64 patients in Group C: 59.3% were female; the mean API was 0.47 ± 0.1 in males and 0.36 ± 0.1 in females (p < 0.0001). The incidence of AEA was 47% in females and 35% in males. CONCLUSIONS: In the neonates (Groups A and B), the position of the anus in the perineum was more anterior in females than in males (p < 0.0001); 31% of the newborns females with AEA presented with constipation in their first months of life. In the Group C patients, there was a high incidence of AEA, especially in the females, and we consider it to be the probable cause of this defecation disorder.

Anorectal malformations (ARM): quality of life assessed in the functional, urologic and neurologic short and long term follow-up.

UNLABELLED: Imperforate anus represents a wide spectrum of anorectal malformations associated with urologic, neurologic and orthopedic malformations. The outcome from the various corrective measures has improved due to new surgical techniques as well as to a better understanding of the pathology. Other factors which influence the overall outcome include the degree of patient acceptance, family support as well as the ability of the health care structure to support the patient's needs on a clinical, functional and psychologic level. AIM OF THE STUDY: Assess (with the new techniques available) the quality of life in the adult patient with ARM and compare it to that experienced by a younger patient; also we wish to determine the correlation between the observed abnormalities with the functional, neurologic and urologic outcome. MATERIALS & METHODS: Sixty-six patients were subjected to PSARP (36 M; 30 F). Six presented with cloaca and 60 with ARM (23 high and 37 low). All patients underwent the same workup to include L/S MRI diagnostics, evaluation for incontinence (urinary and bowel), a urology screening, and if required, a subsequent urodynamic study with rehabilitation and/or bowel management. All answered questionnaires (AIMAR: Italian parent's association of ARM) in order to assess their satisfaction with the current health condition, with the information received and with the treatment and follow-up sessions. The patients were classified into one of two groups. Group A, totaled 33 patients (4 cloacae) with an age range between 2 and 12 years who were operated after 1995. The second, group B, was made up of 33 patients who had been surgically treated before 1995 (age range 15-41 years), had followed the study protocol and had also a neuropsychiatry consult. RESULTS: Overall fecal continence was 69% and of this number 37% were clean without constipation. Twe2nty-one patients (32%) suffered from some form of constipation. Constipation was the most common functional disorder observed in patients who have undergone PSARP. The highest incidence of constipation was found in the ARM (low type), a favorable prognostic group with 43% constipation. Patient with "high" defects and a cloaca had a lower incidence of constipation (18%). Of the 59 patients evaluated, 85% were urinary continent and 15% were incontinent. All of the incontinent patients were in the unfavorable prognostic group of malformations. Urodynamic studies showed 7 neurogenic bladders (NB) and 2 patients with a neurovescical dysfunction (NVD). Of the 50 "dry" patients. 20 had voiding disturbances due to a voiding dysfunction, in the absence of neurologic abnormalities, and presented occasional daytime or nighttime wetting. There was no correlation between the level of the anatomic defect and the urodynamic patterns in the group. Abnormal MRI findings were observed in thirty out of fifty-two patients evaluated. The MRI findings were classified as follows. Severe abnormalities: 7 patients (13%) presented with a combination of skeletal (sacral/lumbar) and spinal cord anomalies. Only spinal cord abnormalities: 12 patients (21%). Only skeletal abnormalities: 11 (19%) patients. Patients were divided into high, low and cloacal malformations. A high degree of statistical correlation was noted between the patients belonging to the cloacae and high defect groups and the abnormal MRI findings. No significant correlation was found between the low defect group and dysrafism, abnormal MRI results and the severity of the malformation. The incidence of Tethered Cord (TC) in our limited number of patients was limited in our study (9% in the high and 7% in the low defect group) when compared to the current literature. Furthermore there was no statistically conclusive evidence that TC by itself affects the urinary or fecal control in our patients. Our recommendation is nevertheless to obtain an MRI study in all patients with ARM. CONCLUSION: All patients 17 and older reported a "good quality of life". Four are married, two with children. Aclose working relationship with the medical personnel is not only necessary but is also well received by the family particularly when younger patients are involved. The adult patient easily adapts even when information is initially scarce. He quickly reaches autonomy with personalized solutions but prefers a longer follow-up time during which, specialized medical facilities will play an important role in the treatment of ARM. Our findings illustrate the importance of both global disease-specific functioning and perceived psychosocial competencies for enhancing the QL of these patients.

Minding the gap between cortisol levels measured with second-generation assays and current diagnostic thresholds for the diagnosis of adrenal insufficiency: a single-center experience.

PURPOSE: The current cut-offs for the diagnosis of adrenal insufficiency (AI) have been established using outdated immunoassays. We compared the cortisol concentrations measured with Roche Cortisol I (R1), the newly available Roche Cortisol II (R2), and liquid chromatography tandem mass spectrometry (LC-MS/MS), the gold standard procedure to measure steroids in patients undergoing the corticotropin (ACTH) test. METHODS: We enrolled 30 patients (age 47 ± 21 years) referred to undergo the ACTH test (1 or 250 µg). Cortisol was measured at 0, 30, and 60 min after stimulation with R1, R2, and LC-MS/MS. AI was diagnosed for R1-stimulated peak cortisol concentrations < 500 nmol/L. RESULTS: Mean cortisol concentrations measured with R2 and LC-MS/MS were comparable, while mean cortisol concentrations measured by R1 were higher than those of both R2 and LC-MS/MS (respectively, basal 411 ± 177, 287 ± 119, and 295 ± 119 nmol/L; at 30 min, 704 ± 204, 480 ± 132, and 500 ± 132 nmol/L; at 60 min, 737 ± 301, 502 ± 196, and 519 ± 201 nmol/L, p ≤ 0.01 for R1 vs. both R2 and LC-MS/MS at each point). Considering the 500 nmol/L cortisol peak cut-off, AI was diagnosed in 5/30 patients using R1 and in 12/30 using R2 (+ 140%). Based on the correlation between R1 and R2, the threshold of 500 nmol/L became 351 nmol/L (12.7 µg/dL) when cortisol was measured with R2, and 368 nmol/L (13.3 µg/dL) with LC-MS/MS. CONCLUSIONS: The use of more specific cortisol assays results in lower cortisol concentrations. This could lead to misdiagnosis and overtreatment when assessing AI with the ACTH test if a different cut-off for cortisol peak is not adopted.

Relugolix for the treatment of uterine fibroids.

INTRODUCTION: Uterine fibroids (UF) are benign tumors common in premenopausal women, with strong impact on the health-care systems. For many years, surgery represented the only therapy for symptomatic fibroids. However, clinicians are observing a switch from surgery to noninvasive methods; in particular, medical treatment has been shown to be efficacious in obtaining a bleeding reduction and in ameliorating patient conditions. AREAS COVERED: The authors review the current options available for the treatment of women with UF, with a special focus on the newest one, relugolix. It is an orally active non-peptide Gonadotropin-releasing hormone (GnRH)-receptor antagonist recently licensed for women with symptomatic fibroids. Relugolix is a well-tolerated safe drug; it is effective in inducing a dose-dependent decrease in menstrual blood loss, with faster reduction of heavy menstrual bleeding (HMB) and a greater shrinkage in fibroid volume compared to the current standard of GnRH agonist treatment. EXPERT OPINION: Relugolix is a promising drug for the non-surgical treatment of women with UF. To date, the only published data come from a well-selected Japanese female population study while results from worldwide ongoing studies are ongoing in order to confirm the efficacy of this GnRH agonist receptor.

Towards an accurate description of the electronic properties of the biphenylthiol/gold interface: the role of exact exchange.

We investigate the role of the exact exchange in describing the biphenylthiol/gold interface. The study is performed by simulating the electronic properties of mercaptobiphenylthiol and aminobiphenylthiol molecules adsorbed on a Au(23) cluster, using local, semilocal and hybrid functionals and an effective exact exchange method, namely, the localized Hartree-Fock (LHF). We find that the local/semilocal functionals strongly underestimate the charge transfer and the bond dipole at the interface due to the self-interaction-error (SIE), which alters the correct level alignment. On the other hand the LHF method is SIE free and predicts a larger charge transfer and bond dipole. We also found that LHF results can be reproduced using hybrid functionals and that conventional local/semilocal correlation functionals are unable to improve over the exchange-only description.

Visible quantum plasmonics from metallic nanodimers.

We report theoretical evidence that bulk nonlinear materials weakly interacting with highly localized plasmonic modes in ultra-sub-wavelength metallic nanostructures can lead to nonlinear effects at the single plasmon level in the visible range. In particular, the two-plasmon interaction energy in such systems is numerically estimated to be comparable with the typical plasmon linewidths. Localized surface plasmons are thus predicted to exhibit a purely nonclassical behavior, which can be clearly identified by a sub-Poissonian second-order correlation in the signal scattered from the quantized plasmonic field under coherent electromagnetic excitation. We explicitly show that systems sensitive to single-plasmon scattering can be experimentally realized by combining electromagnetic confinement in the interstitial region of gold nanodimers with local infiltration or deposition of ordinary nonlinear materials. We also propose configurations that could allow to realistically detect such an effect with state-of-the-art technology, overcoming the limitations imposed by the short plasmonic lifetime.

Neurosteroids in the retina: neurodegenerative and neuroprotective agents in retinal degeneration.

Steroids may have a powerful role in neuronal degeneration. Recent research has revealed that steroids may influence the onset and progression of some retinal disorders as well as neurodegenerative diseases and, as in brain, they accumulate in the retina via a local synthesis (neurosteroids) and metabolism of blood-circulating steroid hormones. Their crucial role as neurodegenerative and neuroprotective agents has been also upheld in a retinal excitotoxic paradigm. These findings are reviewed especially from the emerging perspective that after an insult local changes in steroidogenic responses and consequent neurosteroid availability might turn out to be offensive or defensive cellular adaptations for the potentiation or prevention of neuronal death.

Neurons and ECM regulate occludin localization in brain endothelial cells.

We report that extracellular matrix and neurons modulate the expression of occludin, one of the main components of tight junctions, by rat brain endothelial cells (RBE4.B). Of the three extracellular matrix proteins which we tested (collagen I, collagen IV, and laminin), collagen IV stimulated at the best the expression of occludin mRNA. The corresponding protein, however, was not synthesized. Significant amounts of occludin accumulated only when RBE4.B cells were cultured on collagen IV-coated inserts, in the presence of cortical neurons, plated on laminin-coated companion wells. Finally, occludin segregated at the cell periphery, only when endothelial cells were co-cultured with neurons for > or = 1 week.

Functional feature of a novel model of blood brain barrier: studies on permeation of test compounds.

Drug delivery to the central nervous system (CNS) is subject to the permeability limitations imposed by the blood-brain barrier (BBB). Several systems in vitro have been described to reproduce the physical and biochemical behavior of intact BBB, most of which lack the feature of the in vivo barrier. We developed a fully formed monolayer of RBE4.B immortalized rat brain microvessel endothelial cells (ECs), grown on top of polycarbonate filter inserts with cortical neuronal cells grown on the outside. Neurons induce ECs to synthesize and sort occludin to the cell periphery. Occludin localization is regulated by both compositions of the substratum and soluble signals released by cortical co-cultured neurons. The observed effects do not require strict physical contact among cells and neurons. To assess the physiological function of the barrier we examined the transendothelial transfer of three test compounds: dopamine, L-tryptophan and L-DOPA. Polycarbonate filter inserts, where ECs were co-cultured with neurons, were assumed as open two compartments vertical dynamic models. Permeation studies demonstrated that the ECs/neurons co-cultures possess permeability characteristics approaching those of a functional BBB: the system behaved as a selective interface that excludes dopamine permeation, yet permits L-tryptophan and L-DOPA to cross. The movement of test compounds from the donor to the acceptor compartment was observed at a distinct time from the start of co-culture. Transfer was determined using standard kinetic equations. Different performance was observed after 5 and 7 days of co-culture. After 5 days dopamine, L-tryptophan and L-DOPA passively permeate through the membrane as indicated by fittings with a first-order kinetic process equation. After 7 days of co-culture, occludin localizes at ECs periphery, dopamine does not cross the barrier to any further extent, while the transfer of L-tryptophan and L-DOPA fits well with a saturable Michaelis-Menten kinetic process, thus indicating the involvement of a specific carrier-mediated transport mechanism. Permeation studies confirmed that culture of ECs in the presence of neurons induces the characteristic permeability limitations of a functional BBB.

Laparoscopic surgery for adolescent varicocele: preliminary report on 80 patients.

Laparoscopic clipping and division of the internal spermatic vessels was performed without complications in 80 adolescents to treat varicocele. In four cases the procedure had to be converted to open surgery. Two of the cases were converted because of technical errors during CO2 insufflation and in two cases because dissection of the vessels was impossible owing to abnormal adhesion of sigmoid colon. At 6 months' follow-up there was only one relapse. Only one hydrocele was noted postoperatively, and testicular size did not decrease in any patient. The authors believe that laparoscopic varicocelectomy is a simple, safe, and effective surgical procedure, which could be proposed as an alternative to open surgical or percutaneous embolization approaches. However, much more experience is needed to obtain a definitive conclusion.

Pneumatosis cystoides intestinalis: a rare cause of nonsurgical pneumoperitoneum in an infant.

The authors describe a 3-year-old boy with pneumatosis cystoides intestinalis (PCI) and associated duodenal stenosis who came to them with abdominal pain, significant abdominal distension, large gastric residue, and pneumoperitoneum. PCI is a rare condition in children characterized by the presence of multiple gas-filled cysts within the wall of some part of gastrointestinal tract that may break and cause pneumoperitoneum without an intestinal perforation. Even if in most cases the standard treatment is surgical, to keep in mind this rare condition could be useful to adopt a most rational treatment approach and avoid unnecessary operation in case of "benign" pneumoperitoneum.

Embryonal rhabdomyosarcoma of the lung arising in cystic adenomatoid malformation: case report and review of the literature.

Rhabdomyosarcoma (RMS) of the lung is a very rare lesion, but the association with cystic adenomatoid malformation (CCAM) is unlikely to be a coincidence. Although the etiologic factors predisposing infants and children to pulmonary neoplasms are unknown, pulmonary developmental abnormalities may play a pathogenetic role. A case of embryonal pulmonary RMS is described, which was discovered within a congenital CCAM in a 22-month-old child. The hypothesis regarding histogenesis of this neoplasm are also briefly discussed. Because of the risk of malignant change, early removal of the congenital cystic lesions of the lung is advisable.

Timing of surgery after acute myocardial infarction.

OBJECTIVE: We wished to determine if timing of surgery, when other co-morbid variables are controlled, influenced outcome after operations for acute myocardial infarction. DESIGN: Between 3/20/1990 and 6/17/1994, data was prospectively collected on 338 patients undergoing operation for either evolving infarcts (n=73) or up to 21 days after infarction (mean 7.9 days). SETTING: Tertiary hospital referral center. PATIENTS: Infarction was diagnosed by CK enzymes or EKG Q-waves preoperatively in 338 patients undergoing surgery. The mean age of the patients was 66.1 years (SD+/-10.5 years), 76 had emergency operations immediately after catheterization (50 following PTCA complications), 223 had urgent operations, and 39 were elective. INTERVENTIONS: Seventy-three had preoperative ballon pumps, and 259 had one or more mammary artery bypasses with a mean of 3.27 (SD+/-1.0) distal anastomoses. RESULTS: In-hospital and 30-day survival rate was 95.6% (323/338). Of the 73 variables evaluated by step-wise logistic regression analysis, the multivariate independent preoperative predictors of death were: aortic valve regurgitation, chronic pulmonary disease, preoperative diuretic administration, preoperative balloon pump, preoperative inotropes, and the need for additional concomitant noncardiac surgery. Including the operative variables, the predictors were: preoperative balloon pump, preoperative inotropes, the presence of left main stenosis, preoperative renal failure, chronic pulmonary disease, valve disease, ischemic arrhythmia, pump perfusion time, valve surgery, and homologous blood transfusion volume required. When the postoperative variables were included, the predictors were: preoperative inotropes, postoperative balloon pump, postoperative epinephrine, postoperative permanent stroke, and postoperative acute renal failure. The time between infarction and operation was not an independent prediction (p>0.4) in any of the logistic regression models. CONCLUSION: Early operation after acute infarction is not in itself a risk factor, rather comorbid disease and preoperative hemodynamic status determine outcome after surgery.

Fertility rates after successful correction of varicocele in adolescence and adulthood.

Vast epidemiologic studies have shown that varicocele becomes manifest at the beginning of sexual maturation and its incidence gradually increases in patients between 10-16 years. This percentage is 16-18% in adolescents and is comparable to that of the adult male population. Since varicocele first appears in early adolescence and its gonadotoxic effect increases with age, the possibility of improved fertility rate with early varicocelectomy has been suggested. We report the results of a comparative follow-up study to value the efficacy of surgical correction in two groups of adolescent and adult patients. Our study shows that early recognition and treatment of a severe varicocele provide a higher fertility rate and can prevent the reduced fertility rate associated with delayed varicocelectomy.

Adolescent varicocele: operative anatomy and tricks for successful correction.

Conventional varicocelectomy is often complicated by high recurrence rate, ranging from 6 to 25% and the persistence usually is due to residual venous communications. We report our experience of 21 years in varicocele correction using 3 different operative techniques on 389 adolescents. In the first 12 years (120 patients) a typical ivanissevich operation was carried out with a recurrence rate of 18%. In the following 4 years (63 patients) a preoperative venography was always carried out and a surgical procedure via an inguinal approach was performed with high retroperitoneal and inguinal ligations of the internal spermatic vein(s) and cremasteric vein(s) as indicated by venography; the recurrence rate was still 8%. In the last 5 years we have been using a personally modified technique characterized by: 1) unique access to all venous areas both in the retroperitoneum and in the inguinal canal with a systematic ligation of the internal and external spermatic veins and the deferential vein when dilated; 2) intraoperative identification of the residual collaterals after venous ligations by injecting some milliliters of a blue-methylene solution. This procedure allowed a varicocele recurrence in only 2 out of 206 consecutive patients (1%). Our results suggest that it may be possible to lessen significantly the postoperative recurrence rate using some simple operative tricks.

[HIV infection: results of 4 years of observation (May 1984-May 1988)- of the admitting department of the V. Cervello Hospital in Palermo]. / L'infezione da HIV: risultati di quattro anni di osservazioni (maggio 1984-maggio 1988) presso il centro operativo dell'Ospedale "V. Cervello" di Palermo.

During a period of four consecutive years (1984-1988) more than one thousand of serum samples were obtained from different "at risk" categories of patients with the aim to investigate on the prevalence of anti-HIV antibodies in these populations. Also HIV antigen and HBV markers were investigated in the same people. Some of them were followed up to monitor the various HIV markers and to cultivate biological material from symptomatic cases. All serological investigations were carried out by means of ELISA methods and the Western Blot technique, to confirm positive results. Data obtained from this study showed that: 1. in our area anti-HIV positive people prevail among intravenous drug addicts (IVDA) (42-48%) in contrast to 3.3% of homosexuals, and in 14-16% of subjects or patients declaring themselves "at risk" without stating what of risk it is. 2. HIV antigen was demonstrated in 5% of symptomatic IVDA patients but only in two cases of anti-HIV negative people. 3. HBV markers were found in all categories examined, prevailing in IVDA subjects (72%). 4. Five percent only of anti-HIV negative people followed up through 2-36 mo. seroconverted while only 39.7% of anti-HIV positive people showed an HIV markers variation (increase, decrease or disappearance) in different periods of time (1-8 mo.). 5. Opportunistic infections were observed in 50% of symptomatic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Primary varicocele: an underestimated pathology in childhood and adolescence]. / Varicocele primitivo: una patologia sottostimata in età pediatrico-adolescenziale.

Idiopathic varicocele is a neglected entity in classic pediatric textbooks. Yet vast epidemiologic studies revealed that the incidence of varicocele gradually increases in patients between 10 and 15 years old and is comparable to that of the adult male population. Clinically, the pediatric varicocele is often associated with smaller and hypotrophic testis; histologically it also is associated with pathological and progressive changes of the testis. We report on the preliminary results of a personal epidemiologic study and a comparative follow-up to value the efficacy of surgical correction in two groups of adolescent and adult patients. Early recognition and treatment of a severe varicocele with testicular hypotrophy may help to prevent in adults the infertility associated with this condition.

[Early decortication in the surgical treatment of pleural empyema in childhood: indications and results]. / La decorticazione precoce nel trattamento chirurgico dell'empiema pleurico in età pediatrica: indicazione e risultati.

Antibiotics and pleural drainage with continuous suction is effective in treatment of childhood pleural empyema. However a recognizable number of childhood pleural empyema fail to improve or to cure after this treatment. This study reviews our experience with 27 children over past 8 years. All patients were treated with antibiotics, seven with only pleural drainage, twenty with pulmonary decortication. Indications for decortication were: clinical and radiological failure after 4-5 days of treatment with pleural drainage and continuous suction; persistent fever; persistent respiratory distress; persistent signs of general illness; persistent loculated pleural effusions; worsening parenchymal disease. The clinical and radiological improvements following decortication were dramatic with immediate lung reexpansion and improvement of clinical course. The chest tubes were removed by the fifth postoperative day and the children were discharged by the seventh-nine postoperative day. There were no complications and no deaths. In our experience pulmonary decortication is a simple and effective treatment of childhood empyema in the advanced fibro-purulent and/or early organizing phase with immediate and long-term excellent results.