Safety, feasibility, and short-term outcomes of laparoscopically assisted primary ileocolic resection for Crohn’s disease

Background  Outcomes of laparoscopic resection for ileocecal Crohn’s disease have been reported previously in smaller studies, suggesting its short-term advantages over open surgery. This study assessed the safety and recovery parameters in the largest, consecutive, single-institution series to date. Methods   Consecutive patients undergoing laparoscopically assisted primary ileocolic resection for Crohn’s disease between 1994 and 2006 were identified in an institutional prospectively collected database. Operative and postoperative outcomes at 30 days were studied. Results  In this study, 109 patients (35 men) with a mean age of 35 ± 14 years and a mean body mass index (BMI) of 25 ± 6 kg/m² were identified. The main indications for surgery were medically refractory disease (63%) and fibrous stenosis (27%). In 41% of the cases, previous abdominal surgery had been performed. The surgery had a mean duration of 150 ± 45 min and a conversion rate of 6%. The overall 30-day morbidity rate was 11%, and the reoperation rate was 1%. The mortality rate was 0%. The median postoperative hospital stay was 4 days (range, 2–15 days). Conclusions   This series, the largest reported to date, concurs with recent metaanalyses findings that laparoscopically assisted primary ileocecal resection for Crohn’s disease is safe and feasible, resulting in better short-terms outcomes than open resection. This operation is therefore the procedure of choice for Crohn’s disease at our institutions.     

A dual benefit of sacral neuromodulation

Sacral neuromodulation is a therapeutic option for women with detrusor overactivity and more recently has been used in patients with fecal incontinence and slow-transit constipation. A 47-year-old woman presented with chronic constipation since childhood. She used multiple laxatives, fiber supplements, and enemas, all without success, and defecated only once per week. Extensive investigations, including barium enema, colonoscopy, defecating proctography, pelvic magnetic resonance imaging, and anorectal manometry all were normal. A transit study showed delayed small-bowel emptying. Colonic transit could not be accurately interpreted because of the marked delayed in proximal transit. An ileostomy was being considered to defunction the colon after the patient become desperate for a better quality of life. She also complained of severe urinary frequency and incomplete emptying. A cystoscopy was normal, and a temporary sacral neuromodulation device was inserted as a staged procedure to improve her urinary symptoms. From the day of device placement and thereafter, the patient defecated without difficulty and has also been free of bladder symptoms. Repeat colonic transit has shown normalization of the stomach, small bowel, and colon.     

Resting electroencephalogram alpha-power over posterior sites indexes baseline visual cortex excitability

Variations of oscillatory brain activity have been related to distinct functional states depending on the frequency of oscillations. In the alpha-band (about 8-14 Hz), decreased oscillatory activity is thought to reflect a state of enhanced cortical excitability, and increased activity to reflect a state of cortical idling or inhibition in which excitability is reduced, but the alpha/excitability link has not been probed directly. Here, we studied the relationship between resting oscillatory activity and visual cortex excitability across participants using electroencephalography and transcranial magnetic stimulation to the occipital pole. We found individual posterior alpha-band power to correlate with the individual threshold for eliciting illusory, transcranial magnetic stimulation-induced visual percepts. This provides direct support for an alpha/excitability link and for baseline states of the visual brain to vary across individuals.     

Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome

Clinical studies with bortezomib have validated the proteasome as a therapeutic target for the treatment of multiple myeloma and non-Hodgkin's lymphoma. However, significant toxicities have restricted the intensity of bortezomib dosing. Here we describe the antitumor activity of PR-171, a novel epoxyketone-based irreversible proteasome inhibitor that is currently in clinical development. In comparison to bortezomib, PR-171 exhibits equal potency but greater selectivity for the chymotrypsin-like activity of the proteasome. In cell culture, PR-171 is more cytotoxic than bortezomib following brief treatments that mimic the in vivo pharmacokinetics of both molecules. Hematologic tumor cells exhibit the greatest sensitivity to brief exposure, whereas solid tumor cells and nontransformed cell types are less sensitive to such treatments. Cellular consequences of PR-171 treatment include the accumulation of proteasome substrates and induction of cell cycle arrest and/or apoptosis. Administration of PR-171 to animals results in the dose-dependent inhibition of the chymotrypsin-like proteasome activity in all tissues examined with the exception of the brain. PR-171 is well tolerated when administered for either 2 or 5 consecutive days at doses resulting in >80% proteasome inhibition in blood and most tissues. In human tumor xenograft models, PR-171 mediates an antitumor response that is both dose and schedule dependent. The antitumor efficacy of PR-171 delivered on 2 consecutive days is stronger than that of bortezomib administered on its clinical dosing schedule. These studies show the tolerability, efficacy, and dosing flexibility of PR-171 and provide validation for the clinical testing of PR-171 in the treatment of hematologic malignancies using dose-intensive schedules.     

Prevalence of hepatitis C virus (HCV) genotypes and increase of type 4 in central Italy: an update and report of a new method of HCV genotyping

Hepatitis C virus (HCV) genotyping is very useful for identifying the patients (type 1 and 4) that need more aggressive management. In recent years, genotype 4 has shown spread in different parts of Europe. The aim of this study was to update on the prevalence of HCV genotypes of 288 patients in Central Italy, to analyze the possible increase of genotype 4 and to evaluate a new simple genotyping method. A line-probe assay (LiPA, Bayer) was used based on the reverse hybridization of HCV genome fragments previously amplified and biotinylated by a polymerase chain reaction (PCR) assay, COBAS System Amplicor HCV monitor version 2.0 (Roche) or previously amplified by COBAS Ampliprep/TaqMan HCV test (Roche). This last method uses non-biotin-labeled primers, therefore we added for each sample 10 microl of amplified HCV products, 10 microl of denaturation solution and 10 microl of biotinylated-nested primers (Bayer) to utilize the genotyping procedure previously used. The results showed that the prevalence of type 1, 2 and 3 (482, 34.6 and 10.5%, respectively) as well as the prevalent subtypes, 1b and 2a/2c (30.7 and 27.2%, respectively) were similar to previous data. Type 1 and 2 were statistically associated with an older group of patients when compared with type 3 and 4 (p < 0.001). Type 3 and 4 showed a significant prevalence of male patients compared to type 1 and in particular to type 2 (p < 0.014). The prevalence of type 4 was 5.6% in 2004, 6.1% in 2005 and 9.9% from January to July 2006. Type 4 showed an increase of male prevalence over a 3-year period (p < 0.001). In conclusion, subtype 1b and 2a/2c showed a very similar prevalence, age and gender distribution in Central Italy. The type 4 patient group was analyzed because an increase of this genotype (1.8 times) was detected.     

Childhood febrile seizures: overview and implications

This article provides an overview of the latest knowledge and understanding of childhood febrile seizures. This review also discusses childhood febrile seizure occurrence, health services utilization and treatment costs. Parental reactions associated with its occurrence and how healthcare providers can assist parents with dealing effectively with this potentially frightening and anxiety-producing event are also discussed.     

40 Hz Auditory Steady-State Response: The Impact of Handedness and Gender

The 40 Hz auditory steady-state response (ASSR) is a periodic response to a periodic stimulation. Its sources are located in the primary auditory cortex and the asymmetry of the planum temporale has previously been associated with hand preference and gender-related differences; thus subject’s handedness and gender could potentially influence ASSRs. Nevertheless, electrophysiological studies of ASSRs are mainly dominated by right-handed participants and the observed findings can only be generalized to the right-handed populations. However, for a potential use of 40 Hz ASSR as a translational biomarker of neuropsychiatric disorders, it is important to investigate the response in association to handedness and gender. We included an equal number of left-handed and right-handed males and females and recorded EEG responses during left-ear, right-ear and both ears stimulation. The results of the study suggest that the processing of 40 Hz auditory stimulation depends on the subjects’ gender and handedness: significantly lower phase-locking and strength of 40 Hz ASSRs were observed in left-handed females as compared to left-handed males, but right-handers did not differ in 40 Hz ASSRs. Our observation of the opposite impact of gender in the examined handedness groups stresses the importance of careful consideration of handedness and gender factors when evaluating the determinants of inter individual variability of 40 Hz ASSRs. This finding is of particular importance for clinical studies in psychiatry and neurology.     

The National Trajectory Project of Individuals Found Not Criminally Responsible on Account of Mental Disorder in Canada. Part 1: Context and Methods

The National Trajectory Project examined longitudinal data from a large sample of people found not criminally responsible on account of mental disorder (NCRMD) to assess the presence of provincial differences in the application of the law, to examine the characteristics of people with serious mental illness who come into conflict with the law and receive this verdict, and to investigate the trajectories of NCRMD–accused people as they traverse the mental health and criminal justice systems. Our paper describes the rationale for the National Trajectory Project and the methods used to collect data in Quebec, Ontario, and British Columbia, the 3 most populous provinces in Canada and the 3 provinces with the most people found NCRMD.