Attention-deficit/hyperactivity disorder: diagnostic criteria, epidemiology, risk factors and evaluation in youth.

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in childhood with persistence into adulthood. It has a multifactorial etiology. Its chronicity, if diagnosis is missed or delayed, will result in significant negative impact on the individual's overall functioning and development. With the revised diagnostic criteria released in 2013 by the American Psychiatric Association, established standards of clinical practice continue to be applicable and valuable in the diagnosis and management of ADHD. In older children and adolescents, it is important to differentiate what is developmentally appropriate from problematic as ADHD has high correlation with poor outcomes, comorbidities, and low quality of life.

Hydrosalpinx in Postmenarchal Nonsexually Active Girls: A Review of 6 Cases in a Children's Hospital.

BACKGROUND: The objective of the study was to identify the presence of hydrosalpinx in postmenarchal nonsexually active girls in a children's hospital and to review the available literature on hydrosalpinx in this population. CASES: In a tertiary care children's hospital, we performed a retrospective review of charts from January 1, 2000 to December 31, 2014 and identified six cases of hydrosalpinx in postmenarchal nonsexually active female adolescents ranging in age from 12 to 19 years old. The diagnosis of hydrosalpinx was made using imaging studies. Four of six patients were symptomatic at presentation, and two patients were diagnosed when seen for unrelated reasons. Five of these six girls had previous abdominopelvic surgery. Four girls were given empiric antibiotic treatment for presumed pelvic inflammatory disease related to hydrosalpinx. Two patients required surgical intervention that resulted in complete resolution of the hydrosalpinx. The oldest patient in the series underwent ultrasound-guided drainage of the pyo- and/or hydrosalpinx with subsequent recurrence with tubal ovarian abscess five months later. SUMMARY AND CONCLUSIONS: The presence of hydrosalpinx might be discovered in the workup of pelvic pain in nonsexually active adolescents or on routine follow-up in patients with previous abdominal surgery, some of whom are asymptomatic. The underlying pathophysiology for hydrosalpinx in this population remains unclear. Among our cases, postsurgical adhesions appeared to be the most likely predisposing factor for tubular obstruction. Early detection and prompt diagnosis will allow for appropriate conservative or definitive treatment.

Gender- and age-related differences in muscular and nerve-mediated responses in human colon.

BACKGROUND: Gender- and age-related differences in muscular and nerve-mediated responses in human colon are poorly characterized. We studied carbachol-induced motor responses and electrically evoked contractions in sigmoid circular muscle from adult and elderly patients of different gender. METHODS: Sigmoid colon segments were obtained from 24 men and 16 women undergoing left hemicolectomy for colon cancer. Isometric tension was measured on muscle strips exposed to increasing carbachol concentrations. The effects of atropine, guanethidine, L-nitro arginine methyl ester (L-NAME), and tetrodotoxin on electrically evoked contractions were also studied. RESULTS: Female patients showed higher maximal response to carbachol than male patients, elderly females being the most sensitive to carbachol among all patient groups. Electrically evoked contractions were linearly related to stimulation frequency and abolished by tetrodotoxin. Electrically evoked contractions were significantly more pronounced in elderly male patients; they were reduced by atropine and guanethidine and increased by L-nitro arginine methyl ester in the presence of atropine and guanethidine (P < 0.05). The effect of L-NAME was most marked in elderly male patients and least pronounced in elderly females. CONCLUSIONS: The response to carbachol and the role of nitrergic pathways differ according to age and gender; this may depend on muscarinic receptor upregulation or humoral factors affecting nitric oxide release, respectively.

A nationwide audit of the use of radiotherapy for rectal cancer in Italy.

BACKGROUND: There is good evidence that radiotherapy is beneficial in advanced rectal cancer, but its application in Italy has not been investigated. METHODS: We conducted a nationwide survey among members of the Italian Society of Colo-Rectal Surgery (SICCR) on the use of radiation therapy for rectal cancer in the year 2005. Demographic, clinical and pathologic data were retrospectively collected with an online database. Italy was geographically divided into 3 regions: north, center and south which included the islands. Hospitals performing 30 or more surgeries per year were considered high volume. Factors related to radiotherapy delivery were identified with multivariate analysis. RESULTS: Of 108 centers, 44 (41%) responded to the audit. We collected data on 682 rectal cancer patients corresponding to 58% of rectal cancers operated by SICCR members in 2005. Radiotherapy was used in 307/682 (45.0%) patients. Preoperative radiotherapy was used in 236/682 (34.6%), postoperative radiotherapy in 71/682 (10.4%) cases and no radiotherapy in 375 (55.0%) cases. Of the 236 patients who underwent preoperative radiotherapy, only 24 (10.2%) received short-course radiotherapy, while 212 (89.8%) received long-course radiotherapy. Of the 339 stage II-III patients, 159 (47%) did not receive any radiotherapy. Radiotherapy was more frequently used in younger patients (P < 0.0001), in patients undergoing abdominoperineal resection (APR) (P < 0.01) and in the north and center of Italy (P < 0.001). Preoperative radiotherapy was more frequently used in younger patients (P < 0.001), in large volume centers (P < 0.05), in patients undergoing APR (P < 0.005) and in the north-center of Italy (P < 0.05). CONCLUSION: Our study first identified a treatment disparity among different geographic Italian regions. A more systematic audit is needed to confirm these results and plan adequate interventions.

Colonic smooth muscle responses in patients with diverticular disease of the colon: effect of the NK2 receptor antagonist SR48968.

BACKGROUND: Little is known about the pathophysiology of diverticular disease. AIM: To compare passive and active stress and the response to carbachol of colonic smooth muscle specimens from patients with diverticular disease and patients with colon cancer. The effect of the NK2 receptor antagonist, SR48968, on electrically evoked contractions of circular muscle was also investigated. PATIENTS: Sigmoid colon segments were obtained from 16 patients (51-83 years) undergoing elective sigmoid resection for diverticular disease and 39 patients (50-88 years) undergoing left hemicolectomy for non-obstructive sigmoid colon cancer. METHODS: Isometric tension was measured on circular or longitudinal taenial muscle. Strips were stretched gradually to Lo (length allowing the development of optimal active tension with carbachol) and were also exposed to increasing carbachol concentrations. The effects of atropine, tetrodotoxin and SR48968 on electrically evoked (supramaximal strength, 0.3 ms, 0.1-10 Hz) contractions of circular strips from 8 patients with diverticular disease and 19 patients with colon cancer were also studied. RESULTS: Both passive and active stress in circular muscle strips obtained from patients with diverticular disease was higher than in patients with colon cancer (P < 0.05). Electrically evoked contractions were significantly reduced by atropine in all preparations and were virtually suppressed by combined SR48968 and atropine. Tetrodotoxin suppressed electrically evoked contractions only in patients with colon cancer, whereas a tetrodotoxin-resistant component was identified in patients with diverticular disease. CONCLUSIONS: The changes in both passive and active stress in specimens from patients with diverticular disease may reflect circular smooth muscle dysfunction. Acetylcholine and tachykinins are the main excitatory neurotransmitters mediating electrically evoked contractions in human sigmoid colon circular muscle.

Persistent dyspepsia after laparoscopic cholecystectomy. The influence of psychological factors.

BACKGROUND: Many patients with gallstone disease continue to report gastrointestinal symptoms after cholecystectomy, but the predictive value of preoperative factors is not well understood. We aimed to investigate whether psychological symptoms can be associated with poor outcome after cholecystectomy in patients with gallstones and dyspepsia. METHODS: A sample of 52 consecutive patients with uncomplicated gallstone disease and dyspepsia (conceived in a broader sense to include symptoms of the whole digestive tract) were assessed for psychological (revised 90-item Hopkins Symptom Checklist) and gastrointestinal symptoms (Gastrointestinal Symptom Rating Scale). One year after laparoscopic cholecystectomy, patients rated their gastrointestinal symptoms and were divided into improved and unimproved on the basis of the change in symptoms. RESULTS: Twenty-one (40.4%) patients did not improve after surgery. Improved and unimproved patients did not differ in terms of sex, age, education or illness duration. Unimproved patients showed significantly higher psychological and dyspeptic symptoms than improved patients before surgery. Logistic regression showed that psychological factors were significantly associated with unimprovement after surgery. CONCLUSIONS: Patients with gallstone disease and dyspeptic symptoms are unlikely to improve 1 year after surgery if they show psychological distress before surgery. Psychological symptoms were strongly associated with poor post-cholecystectomy outcome, thus highlighting the clinical relevance of joint assessment of psychological and gastrointestinal symptoms before surgery.

Increased farnesyltransferase activity in human colorectal cancer: relationship with clinicopathological features and K-ras mutation.

BACKGROUND: The enzyme farnesyltransferase has emerged as an important target for anti-cancer therapies. Farnesyltransferase inhibitors have been introduced in clinical trials of subjects with colorectal cancer. We investigated Farnesyltransferase activity, beta-subunit Farnesyltransferase protein expression and its mRNA in patients with colorectal cancer and its relationship with clinicopathological features and K-ras mutation. METHODS: Farnesyltransferase activity was determined by Farnesyltransferase [3H] SPA enzyme assay. Beta-subunit Farnesyltransferase protein expression was investigated by Western blotting and its mRNA by reverse transcriptase-polymerase chain reaction. K-ras mutation was detected by polymerase chain reaction amplification and restriction enzyme analysis. Multiple linear regression analysis was used to analyse relationships among age, sex, site of tumour, Dukes' stage, histological differentiation, K-ras mutation and Farnesyltransferase activity in normal mucosa and cancer. RESULTS: The levels of Farnesyltransferase activity and beta-subunit Farnesyltransferase protein expression were significantly higher in cancer than in normal mucosa. Moreover, tumours located on the right side, with mucinous histological differentiation and with K-ras mutation showed higher levels of Farnesyltransferase activity. CONCLUSIONS: Our findings suggest that Farnesyltransferase activity may be a potential marker of tumourigenicity. The differences in Farnesyltransferase activity in relation to histological grading, tumour location and K-ras mutation described here may constitute a starting point for investigating the causes of this variation within the large bowel.

K-ras and p53 mutations in DNA extracted from colonic epithelial cells exfoliated in faeces of patients with colorectal cancer.

BACKGROUND: Exfoliated colonic epithelial cells in faeces provide a source of human DNA which may be analysed for the presence of tumour-induced modification. AIM: In the present study we investigated K-ras and p53 mutations in faeces of patients with colorectal carcinoma, to verify whether analysis of these mutations might identify a high percentage of patients with colorectal cancer. PATIENTS AND METHODS: Faeces, tumour and normal mucosa samples were taken from 26 patients. Polymerase chain reaction amplification and restriction enzyme analysis were performed to detect K-ras mutations; p53 gene mutations were identified by using polymerase chain reaction amplification and single strand conformation polymorphism. RESULTS: We were able to amplify the K-ras gene and exons 5-9 of the p53 gene in 100% of the faecal samples studied. K-ras and p53 gene mutations were detected in faeces in 26.9% and 50% of the cases, respectively. The two mutations were present together in 5 out of 26 patients. There was full agreement between the K-ras and p53 pattern observed in faecal DNA and that in tumour tissue DNA. CONCLUSIONS: Application of K-ras and p53 mutation gene analysis in the faeces may have clinical applications in the future. Since this genetic analysis is able to detect only 57.7% of patients with colorectal cancer, the study of other genes involved in colorectal carcinogenesis is necessary.

Duodenogastric reflux and gastric mucosal polyamines in the non-operated stomach and in the gastric remnant after Billroth II gastric resection. A role in gastric carcinogenesis?

BACKGROUND: The relationship between bile reflux and gastric cancer is not defined. In order to verify whether a relationship exists, we evaluated the duodenogastric reflux and the mucosal polyamines concentration, polycation compounds actively involved in cell proliferation, in the non-operated stomach and in gastric remnant after Billroth II gastric resection, a precancerous condition. MATERIALS AND METHODS: The study was performed on three groups of subjects: A) 43 subjects with slight dispeptic symptoms, never operated on; B) 54 cholecystectomized subjects; C) 38 subjects operated on Billroth II gastric resection for duodenal ulcer. Duodenogastric reflux was assessed by measuring the concentration of bile acids in gastric juice and expressed as Fasting Bile Reflux in micromol/hour. Gastric mucosal polyamine concentration was assessed by High Performance Liquid Chromatography and expressed in nmol/mg of proteins. RESULTS: The lowest levels of Fasting Bile Reflux (7.95 micromol/hour) and polyamines (7.09 nmol/mg proteins) were observed in subjects never operated on. The middle values were present after cholecystectomy (Fasting Bile Reflux = 18 micromol/hour; polyamines = 8.14 nmol/mg proteins). The highest values were observed after Billroth II gastric resection (Fasting Bile Reflux = 830 micromol/hour; polyamines 11.74 nmol/mg proteins) (Kruskal-Wallis test, p = 0.0001). There was a positive correlation between Fasting Bile Reflux and polyamines (Spearman's rank = 0.33; p = 0.0008). CONCLUSIONS: High levels of duodenogastric reflux observed after Billroth II gastric resection are associated with high polyamine concentration in the gastric mucosa. Bile reflux can be considered an important causal factor of the increased risk of gastric stump cancer after Billroth II gastric resection.

Involvement of PTEN mutations in the genetic pathways of colorectal cancerogenesis.

So far, somatic mutations of the PTEN gene have been found in several different neoplasms but not in colorectal tumours. As exons 7 and 8 of the PTEN coding sequence contain an (A)(6)repeat and mononucleotide repeat sequences are targets for mutations in tumours with microsatellite instability (MI), we screened a panel of sporadic colorectal tumours exhibiting MI to test whether PTEN gene repeats are frequently mutated in MI(+)colorectal cancers. Of 32 cases studied, seven mutations were found in six (18.75%) patients, as a PTEN biallelic frameshift mutation was observed in one case, with consequent loss of function of the gene. Loss of heterozygosity, evaluated in the remaining five cases using the microsatellite marker D10S541, was detected in two of three informative samples. To further address the role of the PTEN gene in MI(+)colorectal cancer, in the six patients with mutated PTEN, we analysed the mononucleotide repeats of six other genes: BAX, hMSH3, hMSH6, TGFbRII, IGFIIR and APC. In two of these six patients, mutations of the TGFbRII gene only were present, indicating that PTEN may have a role in the mutator pathway of colorectal tumorigenesis. Overall, these results indicate that PTEN mutations are selected for during tumorigenesis in MI(+)colorectal tumours. The mutation of both PTEN alleles and evidence that the PTEN protein is expressed in normal colon suggest that loss of function of this gene could play a direct role in tumorigenesis.

Role of intraoperative ultrasound in the screening of liver metastases from colorectal carcinoma: initial experiences.

The aim of this study was to assess the utility of intraoperative ultrasound (IOUS) in the diagnosis and management of liver metastases from colorectal carcinoma. IOUS was performed on a consecutive series of 70 patients undergoing surgery for colorectal carcinoma, with follow-up ranging from 6 to 24 months. In ten cases (14.3%), 13 metastatic tumours were diagnosed; only six of these had been found by preoperative workup and/or surgical inspection. Seven (53.9%) small metastatic liver lesions were identified only by IOUS. None of the lesions diagnosed by IOUS was palpable, and they were all extremely small--ranging from 4 x 6 to 12 x 16 mm. Seventy-three locations were examined in order to compare the results of IOUS with those of other methods. The sensitivity of the former proved to be higher (P less than .05) than that of conventional pre- and intraoperative screening.

[Screening for liver metastases of colorectal carcinoma by the routine use of intraoperative echography]. / Screening di metastasi epatiche da carcinoma colorettale tramite l'uso routinario dell'ecografia intraoperatoria.

The detection and distribution of liver metastases from colorectal carcinoma is an important problem for the therapeutic approach and prognosis. In this study we evaluated the diagnostic accuracy and technical utility of intraoperative ultrasonography (I.O.U.) in the treatment for liver metastases from colorectal carcinoma. I.O.U. has been routine performed in 70 patients. 13 metastatic lesions have been diagnosed in 10/70 patients with colorectal carcinoma (14.3%). Only 6 of 13 lesions (sensitivity of 46.1%) have been diagnosed preoperatively and/or by surgical exploration. Instead 7 small intrahepatic metastatic lesions (53.9%) have been diagnosed exclusively by I.O.U. It has not been possible to detect this lesions by surgical exploration; the size of these metastatic tumor ranged from 0.4 x 0.6 to 1.2 x 1.6 cm. I.O.U. has been useful for its high sensitivity, for the study of anatomic relation between metastatic lesions and vascular and biliary hepatic structure (good guidance for surgical hepatic resection) and for the possibility of performing deep ultrasound guided biopsies of hepatic lesions.

Asymptomatic hepatocellular carcinoma in Child's A cirrhosis. A comparison of natural history and surgical treatment.

The present study deals with the natural history of 37 asymptomatic patients with cirrhosis and hepatocellular carcinoma, 25 with 2-9-cm tumors who were not surgically treated (first group) and 12 with tumors smaller than 4 cm who underwent resection (second group). All patients were in Child's A class. Two-year survival (according to life-table analysis by the Kaplan-Meier method) was 50% in the first group and 39% in the second group. This difference was not significant. In the first group no relation was found between survival and initial tumor size or alpha-fetoprotein levels. Ultrasound examinations at 3-mo intervals revealed the following patterns of tumor growth: (a) no significant growth during the follow-up (9 patients); (b) significant growth (tumor size at least doubling) only in the final stage of the disease (11 patients); (c) initial significant growth followed by a period of no increase in size (5 patients). These findings show that in our geographical area (a) 2-yr survival of untreated asymptomatic patients with hepatocellular carcinoma associated with cirrhosis does not differ from that of similar patients undergoing resection and (b) the tumor can exhibit long periods of no growth alternating with periods of exponential growth.

Therapeutic efficacy of the transplantation of isolated hepatocytes in rats with surgically induced acute hepatic failure: a study of the mechanism.

In this study, the beneficial effect of intrasplenic transplantation of hepatocytes or splenocytes was shown in animals with 75% hepatectomy and portacaval shunt but not in animals with total dehepatization by hepatic vascular exclusion. No enhancement of the phagocytic activity was observed in the animals with 75% hepatectomy and portacaval shunt after injection of hepatocytes or splenocytes. This study confirms the efficacy of hepatocytes for the treatment of experimental liver failure but shows that nonhepatic cells may be equally as effective. Metabolic activity of the transplanted cells and stimulation of the phagocytic activity of the reticuloendothelial system probably do not explain the therapeutic effect of the transplanted cells.

Transplantation of hepatocytes for treatment of surgically induced acute hepatic failure in the rat.

Efficacy of transplanted hepatocytes was evaluated in rats with a surgically induced acute hepatic failure. After 75% liver resection and portacaval shunt, the intrasplenic or intraperitoneal injection of 20 million isolated fresh hepatocytes was shown to significantly reduce the mortality rate. These results confirm that the transplantation of isolated hepatocytes may prevent death in rats with acute hepatic failure, and suggest that hepatocyte transplantation acts by a mechanism of hepatic support.