Methylomic profiling and replication implicates deregulation of PCSK9 in alcohol use disorder.

Alcohol use disorder (AUD) is a common and chronic disorder with substantial effects on personal and public health. The underlying pathophysiology is poorly understood but strong evidence suggests significant roles of both genetic and epigenetic components. Given that alcohol affects many organ systems, we performed a cross-tissue and cross-phenotypic analysis of genome-wide methylomic variation in AUD using samples from 3 discovery, 4 replication, and 2 translational cohorts. We identified a differentially methylated region in the promoter of the proprotein convertase subtilisin/kexin 9 (PCSK9) gene that was associated with disease phenotypes. Biological validation showed that PCSK9 promoter methylation is conserved across tissues and positively correlated with expression. Replication in AUD datasets confirmed PCSK9 hypomethylation and a translational mouse model of AUD showed that alcohol exposure leads to PCSK9 downregulation. PCSK9 is primarily expressed in the liver and regulates low-density lipoprotein cholesterol (LDL-C). Our finding of alcohol-induced epigenetic regulation of PCSK9 represents one of the underlying mechanisms between the well-known effects of alcohol on lipid metabolism and cardiovascular risk, with light alcohol use generally being protective while chronic heavy use has detrimental health outcomes.

Panel report: best practices for the surgical treatment of obesity.

BACKGROUND: Bariatric surgery is a rapidly growing field. Advances in surgical technologies and techniques have raised concerns about patient safety. Bariatric surgeons and programs are under increased scrutiny from regulatory agencies, insurers, and public health officials to provide high quality and safe care for bariatric patients at all phases of care. METHODS: During the 2009 annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), a panel of experts convened to provide updated information on patient safety and best practices in bariatric surgery. The following article is a summary of this panel presentation. RESULTS AND CONCLUSIONS: Weight loss surgery is a field that is evolving and adapting to multiple external pressures. Safety concerns along with increasing public scrutiny have led to a systematic approach to defining best practices, creating standards of care, and identifying mechanisms to ensure that patients consistently receive the best and most effective care possible. In many ways, bariatric surgery and multidisciplinary bariatric surgery programs may serve as a model for other programs and surgical specialties in the near future.

Waste management health risk assessment: a case study of a solid waste landfill in South Italy.

An integrated risk assessment study has been performed in an area within 5 km from a landfill that accepts non hazardous waste. The risk assessment was based on measured emissions and maximum chronic population exposure, for both children and adults, to contaminated air, some foods and soil. The toxic effects assessed were limited to the main known carcinogenic compounds emitted from landfills coming both from landfill gas torch combustion (e.g., dioxins, furans and polycyclic aromatic hydrocarbons, PAHs) and from diffusive emissions (vinyl chloride monomer, VCM). Risk assessment has been performed both for carcinogenic and non-carcinogenic effects. Results indicate that cancer and non-cancer effects risk (hazard index, HI) are largely below the values accepted from the main international agencies (e.g., WHO, US EPA) and national legislation (D.Lgs. 152/2006 and D.Lgs. 4/2008).

The role of diagnostic laparoscopy for chronic abdominal conditions: an evidence-based review.

BACKGROUND: Diagnostic laparoscopy is minimally invasive surgery for the diagnosis of intraabdominal diseases. The aim of this review is a critical examination of the available literature on the role of laparoscopy for chronic intraabdominal conditions. METHODS: A systematic literature search of English-language articles on MEDLINE, the Cochrane database of evidence-based reviews, and the Database of Abstracts of Reviews of Effects was performed for the period 1995-2006. The level of evidence in the identified articles was graded. The search identified and reviewed six main categories that have received attention in the literature: pelvic pain and endometriosis, primary and secondary infertility, nonpalpable testis, and liver disease. RESULTS: The indications, contraindications, risks, benefits, diagnostic accuracy of the procedure, and its associated morbidity are discussed. CONCLUSIONS: The limitations of the available literature are highlighted, and evidence-based recommendations for the use of laparoscopy to stage intraabdominal cancers are provided.

The role of staging laparoscopy for intraabdominal cancers: an evidence-based review.

Diagnostic laparoscopy is minimally invasive surgery for the diagnosis of intraabdominal diseases. The aim of this review is a critical examination of the available literature on the role of laparoscopy for the staging of intraabdominal cancers. A systematic literature search of English-language articles on MEDLINE, the Cochrane database of evidence-based reviews, and the Database of Abstracts of Reviews of Effects was performed for the period 1995-2006. The level of evidence in the identified articles was graded. The search identified and reviewed seven main categories that have received attention in the literature: esophageal cancer, gastric cancer, pancreatic cancer, hepatocellular carcinoma, biliary tract cancer, colorectal cancer, and lymphoma. The indications, contraindications, risks, benefits, diagnostic accuracy of the procedure, and its associated morbidity are discussed. The limitations of the available literature are highlighted, and evidence-based recommendations for the use of laparoscopy to stage intraabdominal cancers are provided.

PCB concentrations in some foods from four European countries.

Samples of salmon, butter and cabbage from Belgium, Italy, Spain and Portugal were analysed for their content in total, non-dioxin-like (as represented by the so-called seven indicator-PCBs: congeners 28, 52, 101, 118, 138, 153 and 180) and dioxin-like PCBs (mono-ortho and non-ortho PCBs). Salmon and cabbage from Belgium, and butter from Portugal and Belgium, contained less total and non-dioxin-like PCBs than those from other countries. Samples from Italy had the highest concentrations. Similar patterns were observed for dioxin-like PCBs (as represented by the TCDD-equivalents of toxicity, WHO-TEQs), with the lowest values in Belgium and Portugal for salmon, in Portugal for butter and in Belgium for cabbage. Differences up to five-fold in PCB concentrations and TEQ values were seen among commodities from the four countries. The implication is that it might be worthwhile monitoring, with selection of the least contaminated commodities, to reduce the PCB exposure of the general population. This could have health consequences, because daily intakes are higher than the tolerable levels for a considerable part of the European population.

Laparoscopic resection of curable colon and rectal cancer: an evidence-based review.

The initial enthusiastic application of laparoscopic techniques to colorectal surgical procedures was tempered in the early 1990s by reports of tumor implants in the laparoscopic incisions. Substantial evidence has accumulated, including evidence from randomized controlled trials, to support that laparoscopic resection results in oncologic outcomes similar to open resection, when performed by well-trained, experienced surgeons. This review was developed in conjunction with guidelines published by the Society of American Gastrointestinal and Endoscopic Surgeons. Data from the surgical literature concerning laparoscopic resection of curable colorectal cancer was evaluated regarding diagnostic evaluation, preoperative preparation, operative techniques, prevention of tumor implants, and training and experience. Recommendations are accompanied by an assessment of the level of supporting evidence available at the time of the development of the guidelines.

GC-MS analysis of dichlobenil and its metabolites in groundwater.

We have developed a new method for the determination of the widely used herbicide 2,6-dichlorobenzonitrile (dichlobenil) and its major metabolites 2,6-dichlorobenzamide (BAM) and 2,6-dichlorobenzoic acid (2,6-DCBA) in groundwater samples. The procedure is based on solid phase extraction (SPE) combined with a derivatization procedure before GC-MS analysis in order to quantify analytes simultaneously. This method can be used from regulatory laboratories for monitoring the presence of dichlobenil and its metabolites during testing groundwater samples quality.

[Psychosocial adaptation in adolescents with chronic kidney disease]. / L'adattamento psico-sociale nell'adolescente con nefropatia cronica.

BACKGROUND: Chronic disease represents a very critical experience for personal identity. This is far more true in adolescence when corporeal, emotional, relational and cognitive changes are taking place. The aim of the present study is to draw attention to the social and emotional balance and the psychosocial adaptation in a group of nephropathic adolescents and to formulate a suitable assistance program. METHODS: We studied two adolescent groups, one group of nephropathics and one group of healthy individuals, by administering the MMPI (Minnesota Multiphasic Personality Inventory) personality test. RESULTS: We found significant differences between the mean score of the two groups in the clinical scale for depression, hypochondria and hysteria (p < 0.5); in addition, we observed a statistically significant difference in the emotional balance indicators. CONCLUSIONS: Our experience suggests that nephropathic adolescents require global awareness of their psychological problems through the use of innovative assistance methods. A new strategy involving a more modern approach (i.e., educational camps) and specific psychosocial rehabilitation programs should be introduced to improve the quality of life.

Circumferential mucosectomy with stapled proctopexy is a safe, effective outpatient alternative for the treatment of symptomatic prolapsing hemorrhoids in the elderly.

BACKGROUND: Circumferential mucosectomy with stapled proctopexy (CMSP) was first introduced in 1993 as a less painful and highly effective alternative to traditional operative hemorrhoidectomy. Although CMSP has many advantages over traditional hemorrhoidectomy, some authorities and insurers continue to regard it as an inpatient procedure and others have been slow to adopt this progressive technique. This study documents the safe and effective outpatient nature of this procedure. METHODS: From December 2001 through August 2002, 33 patients with mucosal prolapse and prolapsing internal hemorrhoids were treated using circumferential mucosectomy with stapled proctopexy as outpatients at an ambulatory surgery center. Fourteen (42%) patients were treated using local anesthesia with intravenous sedation, 18 (55%) chose spinal anesthesia, and general anesthesia was used in one patient. Patients were evaluated postoperatively by telephone at 1 and 2 weeks, and seen in clinic at 4 weeks. RESULTS: One patient (3%) required an emergency department visit for minor postoperative bleeding. None of our elderly patients required emergency department evaluation and none reported significant complications. Four patients (13%) required urinary catheter placement prior to discharge from the surgery center due to urinary retention. One patient (3%) developed an uncomplicated urinary tract infection, which resolved with antibiotic treatment. Two patients were seen earlier than 4 weeks at the surgeon's request; one was immunocompromised from chemotherapy for metastatic carcinoid, and one reported persistent pain during initial telephone follow-up. No complications were identified in either patient, and no additional complications have been noted to date. CONCLUSIONS: CMSP is a safe, effective, time-efficient procedure for patients with mucosal prolapse and prolapsing hemorrhoids that can be performed safely in the ambulatory surgery center setting. Age is not a limiting factor in selecting patients for this safe outpatient procedure.

Organic tracers identification as a convenient strategy in industrial landfills monitoring.

Today, a significant environmental problem is due to the presence of industrial landfills, some of them old, which can release toxic compounds into the environment (Chemosphere 42 (2001) 415; Chemosphere 31 (1995) 3455). The identification of directly linked to the leachate tracers of contamination in the wells around the landfills, as early markers of a potential risk for the environment and/or man, is a good strategy for an early evaluation of contamination. Our protocol developed for wells water characterization is based on solid phase extraction combined with GC-MS and HPLC-MS/MS. In this way a list of organic contaminants of a specific industrial landfill is obtained, giving a solid basis also for the risk assessment. Here we present some specific examples and the use of these pollutants for environmental monitoring.

Colonoscopic retrieval of an appendiceal foreign body: prophylaxis for appendicitis?

Management of orally ingested foreign bodies usually consists of endoscopic retrieval while the objects reside within the esophagus or stomach. Although most foreign bodies that pass through the pylorus will be excreted without incident, some may become impacted distally, resulting in obstruction or perforation. Appendiceal foreign bodies have been reported rarely, yet have resulted in the development of acute appendicitis. We report the case of a young male who swallowed a nail that became impacted in the appendiceal lumen and was retrieved colonoscopically before the development of acute appendicitis.

Cryoanalgesic ablation for the treatment of chronic postherniorrhaphy neuropathic pain.

BACKGROUND: Chronic postoperative pain has been reported in as many as 62.9% of patients after inguinal herniorrhaphy. Moderate to severe neuropathic pain requiring intervention develops in 2.2% to 11.9% of patients as a result of ileoinguinal and genitofemoral nerve entrapment. Cryoanalgesic ablation has been successful in treating chronic pain from craniofacial neuralgia, facet joint syndrome, and malignant pain syndromes. We report our experience using cryoanalgesic ablation for chronic ileoinguinal and genitofemoral neuralgia after inguinal herniorrhaphy. METHODS: Ten patients with ileoinguinal, genitofemoral, or combined neuralgia underwent 12 cryoanalgesic ablations between April 1996 and June 2001. These patients were referred from a multidisciplinary pain clinic, and focused low-volume nerve blocks were used to map nerve involvement preoperatively. After surgical exposure, nerves and surrounding tissues were cooled to ?70 degrees C for 3 min using the Lloyd Neurostat. Patients were seen 2 weeks postoperatively and offered monthly follow-up assessments. RESULTS: Nine men and one woman, ages 20 to 54 (mean, 42.6 years) were treated during 58 months, with a mean follow-up period of 8.2 months, for ileoinguinal (n = 4), genitofemoral (n = 1), and combined (n = 5) neuralgia. Patients reported one to five prior herniorrhaphies (mean, 1.8), experienced neuropathic pain 0 to 14 years (mean, 6.3 years), and underwent up to 3 (mean, 1.3) ablative pain procedures before referral. After cryotherapy, patients reported overall pain reduction of 0% to 100% (mean, 77.5%; median, 100%); 80% reported decreased analgesic use, and 90% reported increased physical capacity. Two patients underwent additional cryotherapy, one for incomplete relief and one for recurrent pain, both with 100% efficacy. Wound infection (n = 1) was the only complication. CONCLUSIONS: Cryoanalgesic ablation successfully eliminates ileoinguinal and genitofemoral neuralgia in most patients, and should be considered early in the treatment of patients with postherniorrhaphy neuropathic pain.

Risks and benefits of PVC in medical applications.

The safety of using PVC in the medical field has been recently challenged due to the toxic activity it allegedly exerts on exposed patients. The environmental repercussions of disposing of PVC, once its use has terminated, represent an additional point of debate, used to sustain the advisability of abolishing PVC. The reasons that have led some to request the abolition of PVC involve valid questions of principle, perhaps, but they lack a technical evaluation of the benefit-risk ratio and the possible consequences this action would have on patients and on healthcare personnel. The purpose of this paper is therefore to help bring the terms of the question back into the realm of evidence and proof, attempting to formulate a brief picture of what is known, in terms of PVC uses in the clinical field, evaluating the benefits and risks to human health and to the environment, also in relation to possible alternatives, and discussing the margins of uncertainty that emerge. Evidence supports the conclusion that PVC is an important weapon in the complex arsenal medicine has at its disposal to care for patients and cure diseases. Though its use can be considered safe, recent surveys have identified in some patients possibility of risks associated with DEHP, the principal plasticizer of PVC for medical applications. Studies are in progress to eliminate these margins of risk and increase the safety for patients.

Screening for silent myocardial ischaemia in type 2 diabetic patients with additional atherogenic risk factors: applicability and accuracy of the exercise stress test.

OBJECTIVE: Coronary artery disease (CAD), a major cause of mortality in patients with type 2 diabetes (T2D), is often diagnosed late because of silent myocardial ischaemia (SMI). Exercise electrocardiogram testing (ECG) stress is the most utilized screening test for SMI. Its applicability and accuracy, which have never been reported in asymptomatic high-risk T2D patients, have been investigated in this study. DESIGN: A cross-sectional study with coronary angiography as the gold standard for detecting CAD was used. METHODS: Two hundred and six consecutive T2D patients, without symptoms and resting ECG signs of ischaemia but with peripheral vascular disease (PVD) and/or > or = two atherogenic factors, were studied. Ischaemia at ECG stress was indicated by horizontal or downsloping ST segment depression > or =1 mm at 0.08 s after the J point. CAD was defined by stenosis > or =70%. RESULTS: Only 141/206 (68%) patients had a diagnostic test: 27 (19%) tested positive and 114 (81%) tested negative. Coronary angiography in 71 patients (the 27 who tested positive and 44 randomly selected patients who tested negative) indicated a CAD prevalence of 29% and the ECG stress accuracy was 79%. 'False negative' patients (18%) had a higher prevalence (P<0.01) of long duration of diabetes and PVD. CONCLUSIONS: This is the first study which provides insights into the applicability and accuracy of ECG stress in screening SMI in high-risk patients with T2D. Due to the high prevalence of CAD, alternative screening tests in patients unable to perform the test and in those with a high chance of being 'false negative' should be looked for and validated.

Persistent organic pollutants in food: public health implications.

Persistent organic pollutants are a heterogeneous group of chemicals sharing a number a common properties, including long term persistence and diffusion in the environment, and bioaccumulation through the food chain. Animal experiments and epidemiological studies suggest that the most sensitive adverse effects, such as disturbances on metabolism, development, and reproductive system, may occur in the range of current human exposure. Although the potential cancer risk of persistent organic pollutants remains undefined, the implementation of actions to reduce the exposure to these substances, which mainly occurs through the diet, is important.

Enteroscopic treatment of early postoperative small bowel obstruction.

BACKGROUND: Early postoperative small bowel obstruction (EPSBO) occurs in 1% of patients undergoing laparotomy and has a mortality rate exceeding 17%. Nasogastric (NG) decompression is successful in avoiding reoperation in 73% of patients. Repeat laparotomy has been recommended when obstruction does not resolve after 14 days of NG decompression. We report four patients with EPSBO treated successfully with push enteroscopy after failed NG decompression. METHODS: Four patients who failed NG decompression underwent push enteroscopy instead of repeat laparotomy. EPSBO was diagnosed if obstruction lasting more than 14 days developed after initial resolution of postoperative ileus, high NG output persisted postoperatively for 21 days in the absence of sepsis, or radiographic signs of obstruction persisted. Small bowel series or computed tomography were utilized when radiographic assessment was necessary. The Olympus SIF 100 push enteroscope was introduced with an overtube using topical anesthesia and intravenous sedation. After maximal insertion, the enteroscope was withdrawn without evacuation of insufflated air. NG tubes were placed after enteroscopy and patients were followed clinically. Flatus, defecation, and tolerance of a general diet defined resolution of EPSBO. RESULTS: EPSBO resolved 24 to 36 h following enteroscopy, and all patients were discharged on general diets 48 h after return of bowel function. Readmission has not been necessary during 18- to 30-month follow-up. CONCLUSIONS: Our experience suggests that push enteroscopy is successful in treating EPSBO and should be considered prior to reoperation. Push enteroscopy may eliminate the hazards of repeat laparotomy and reduce the morbidity, treatment cost, and lengthy hospital stays associated with this uncommon surgical complication.

Laparoscopic endobiliary stenting significantly improves success of postoperative endoscopic retrograde cholangiopancreatography in low-volume centers.

BACKGROUND: Occult common bile duct stones (CBDS) discovered during laparoscopic cholecystectomy with intraoperative cholangiography are most often managed by postoperative endoscopic retrograde cholangiopancreatography (ERCP). Expert endoscopists at high-volume centers achieve common bile duct cannulation in nearly all patients undergoing ERCP, but cannulation rates of less than 80% have been observed in low-volume centers. As many as 20% of patients with CBDS referred for postoperative ERCP in low-volume centers may require repeated attempts at ERCP, referral to a high-volume center, percutaneous transhepatic techniques, or reoperation for clearance of CBDS when postoperative ERCP fails. METHODS: Laparoscopic cholecystectomy with intraoperative cholangiography performed in 511 consecutive patients over 80 months at a community hospital showed occult CBDS in 66 patients (12.9%). Laparoscopic endobiliary stent placement was successful in 65 patients (98.5%). As part of an earlier study, 16 patients underwent laparoscopic common bile duct exploration with clearance of CBDS before stent placement. Laparoscopic endobiliary stent placement failed in one patient for whom CBDS were cleared with intraoperative ERCP. RESULTS: Initial postoperative ERCP was successful in clearing CBDS in all 65 patients (100%) with laparoscopically placed stents. During the same period, 611 patients underwent ERCP for various indications including CBDS (43%). Selective cannulation was achieved in 78% of all patients during initial ERCP. CONCLUSIONS: Laparoscopic endobiliary stent placement is an effective adjunct to the management of occult CBDS. Laparoscopic endobiliary stenting ensures selective cannulation during postoperative ERCP and eliminates the need for repeated attempts at ERCP, referral to specialty centers, use of transhepatic techniques, or reoperation for retained CBDS. Laparoscopic endobiliary stent placement for treatment of occult CBDS significantly improves the success of postoperative ERCP in low-volume centers and eliminates the morbidity and expense of repeated procedures.