Hypothalamic TrkB.FL overexpression improves metabolic outcomes in the BTBR mouse model of autism.

BTBR T+ Itpr3tf/J (BTBR) mice are used as a model of autism spectrum disorder (ASD), displaying similar behavioral and physiological deficits observed in patients with ASD. Our recent study found that implementation of an enriched environment (EE) in BTBR mice improved metabolic and behavioral outcomes. Brain-derived neurotrophic factor (Bdnf) and its receptor tropomyosin kinase receptor B (Ntrk2) were upregulated in the hypothalamus, hippocampus, and amygdala by implementing EE in BTBR mice, suggesting that BDNF-TrkB signaling plays a role in the EE-BTBR phenotype. Here, we used an adeno-associated virus (AAV) vector to overexpress the TrkB full-length (TrkB.FL) BDNF receptor in the BTBR mouse hypothalamus in order to assess whether hypothalamic BDNF-TrkB signaling is responsible for the improved metabolic and behavioral phenotypes associated with EE. Normal chow diet (NCD)-fed and high fat diet (HFD)-fed BTBR mice were randomized to receive either bilateral injections of AAV-TrkB.FL or AAV-YFP as control, and were subjected to metabolic and behavioral assessments up to 24 weeks post-injection. Both NCD and HFD TrkB.FL overexpressing mice displayed improved metabolic outcomes, characterized as reduced percent weight gain and increased energy expenditure. NCD TrkB.FL mice showed improved glycemic control, reduced adiposity, and increased lean mass. In NCD mice, TrkB.FL overexpression altered the ratio of TrkB.FL/TrkB.T1 protein expression and increased phosphorylation of PLCγ in the hypothalamus. TrkB.FL overexpression also upregulated expression of hypothalamic genes involved in energy regulation and altered expression of genes involved in thermogenesis, lipolysis, and energy expenditure in white adipose tissue and brown adipose tissue. In HFD mice, TrkB.FL overexpression increased phosphorylation of PLCγ. TrkB.FL overexpression in the hypothalamus did not improve behavioral deficits in either NCD or HFD mice. Together, these results suggest that enhancing hypothalamic TrkB.FL signaling improves metabolic health in BTBR mice.

Probiotic knowledge of adults with cystic fibrosis is limited but is associated with probiotic use: A cross-sectional survey study.

Background: Probiotics are used by people with cystic fibrosis (CF) and other chronic diseases to manage gastrointestinal symptoms. Aim: To describe probiotic knowledge; its relationship with probiotic use, probiotic information sources and factors influencing choice in adults with CF and a general population control group. Methods: A cross-sectional questionnaire study was conducted in adults with CF (n = 205) and Controls (n = 158). Probiotic knowledge was compared between CF and Controls using a knowledge score (maximum 5) based on predefined criteria: (1a) bacteria/microorganism; (1b) live; (2a) administered; (2b) adequate dose and (3) health benefit, using independent samples t-test. Two-way analysis of variance explored knowledge scores between CF and Control and between Ever User and Never User groups. Chi-square and Fisher's exact tests compared knowledge criterion, probiotic sources and influences on probiotic choice between groups. Thematic analysis of open-text responses explored probiotic-related knowledge and influences on probiotic decision making. Results: Knowledge scores (mean ± SD) did not differ between CF (1.70 ± 1.12) and Controls (1.89 ± 0.99), p = 0.13. Probiotic use was associated with knowledge score (p < 0.001). More CF Ever Users than Never Users correctly identified criteria 1a (65% vs. 38%), 1b (16% vs. 0%), 2a (45% vs. 22%) and 3 (73% vs. 42%) (all p < 0.005). CF participants considered 'dairy yoghurt' (69%), 'live cultures' (64%) and 'fermented foods' (37%) as 'all/mostly' probiotic sources. The internet was the commonest source of probiotic-related information. Conclusion: Probiotic knowledge and use were associated in adults with CF. Understanding of probiotic characteristics and sources were limited. Education is needed to help guide patient probiotic decision making.

Hypothalamic AAV-BDNF gene therapy improves metabolic function and behavior in the Magel2-null mouse model of Prader-Willi syndrome.

Individuals with Prader-Willi syndrome (PWS) display developmental delays, cognitive impairment, excessive hunger, obesity, and various behavioral abnormalities. Current PWS treatments are limited to strict supervision of food intake and growth hormone therapy, highlighting the need for new therapeutic strategies. Brain-derived neurotrophic factor (BDNF) functions downstream of hypothalamic feeding circuitry and has roles in energy homeostasis and behavior. In this preclinical study, we assessed the translational potential of hypothalamic adeno-associated virus (AAV)-BDNF gene therapy as a therapeutic for metabolic dysfunction in the Magel2-null mouse model of PWS. To facilitate clinical translation, our BDNF vector included an autoregulatory element allowing for transgene titration in response to the host's physiological needs. Hypothalamic BDNF gene transfer prevented weight gain, decreased fat mass, increased lean mass, and increased relative energy expenditure in female Magel2-null mice. Moreover, BDNF gene therapy improved glucose metabolism, insulin sensitivity, and circulating adipokine levels. Metabolic improvements were maintained through 23 weeks with no adverse behavioral effects, indicating high levels of efficacy and safety. Male Magel2-null mice also responded positively to BDNF gene therapy, displaying improved body composition, insulin sensitivity, and glucose metabolism. Together, these data suggest that regulating hypothalamic BDNF could be effective in the treatment of PWS-related metabolic abnormalities.

Probiotic use in adults with cystic fibrosis is common and influenced by gastrointestinal health needs: A cross-sectional survey study.

BACKGROUND: Cystic fibrosis (CF) primarily affects the lung, however, gastrointestinal disorders and symptoms, including dysbiosis, also impact on morbidity and quality of life. There is interest in strategies to modulate the gastrointestinal microbiota, including probiotics, although the evidence remains inadequate to guide practice, and information on use is limited. The present study aimed to characterise probiotic use, beliefs and experiences of adults with CF. METHODS: A cross-sectional questionnaire study was conducted in adults with CF (n = 205) and a general population Control group (n = 158), recruited from Victoria, Australia. Participants were classified as probiotic 'Ever Users' or 'Never Users'. Outcomes included self-reported probiotic use and factors associated with probiotic use, which were analysed using logistic regression analysis. Open-ended questionnaire responses were thematically analysed. RESULTS: In total, 70% of adults with CF had ever used probiotics (supplements and/or foods), comparable to Controls (80%) (p = 0.03). Key reasons for CF probiotic use were gastrointestinal- and antibiotic-related (75%). Most CF Ever Users (73%) did not discuss probiotic use with CF clinicians and 33% were uncertain if probiotics had been helpful. Female gender (odds ratio [OR] = 2.82; 95% confidence interval [CI] = 1.36-5.87; p = 0.005), university-level education (OR = 2.73; 95% CI = 1.24-6.01; p = 0.01) and bloating on antibiotics (OR = 2.14; 95% CI = 1.04-4.40; p = 0.04) were independently associated with probiotic use in CF; as was female gender in Controls (OR = 2.84; 95% CI = 1.20-6.71; p = 0.02). CONCLUSIONS: Probiotics were used by adults with CF for gastrointestinal- and antibiotic-related reasons often without informing clinicians and despite uncertainty about perceived helpfulness. Further research investigating gastrointestinal outcomes of probiotics will inform practice recommendations guiding their use in CF and other chronic diseases.

NOD2 Influences Trajectories of Intestinal Microbiota Recovery After Antibiotic Perturbation.

BACKGROUND & AIMS: Loss-of-function variants in nucleotide-binding oligomerization domain-containing protein 2 (NOD2) impair the recognition of the bacterial cell wall component muramyl-dipeptide and are associated with an increased risk for developing Crohn's disease. Likewise, exposure to antibiotics increases the individual risk for developing inflammatory bowel disease. Here, we studied the long-term impact of NOD2 on the ability of the gut bacterial and fungal microbiota to recover after antibiotic treatment. METHODS: Two cohorts of 20-week-old and 52-week-old wild-type (WT) C57BL/6J and NOD2 knockout (Nod2-KO) mice were treated with broad-spectrum antibiotics and fecal samples were collected to investigate temporal dynamics of the intestinal microbiota (bacteria and fungi) using 16S ribosomal RNA and internal transcribed spacer 1 sequencing. In addition, 2 sets of germ-free WT mice were colonized with either WT or Nod2-KO after antibiotic donor microbiota and the severity of intestinal inflammation was monitored in the colonized mice. RESULTS: Antibiotic exposure caused long-term shifts in the bacterial and fungal community composition. Genetic ablation of NOD2 was associated with delayed body weight gain after antibiotic treatment and an impaired recovery of the bacterial gut microbiota. Transfer of the postantibiotic fecal microbiota of Nod2-KO mice induced an intestinal inflammatory response in the colons of germ-free recipient mice compared with respective microbiota from WT controls based on histopathology and gene expression analyses. CONCLUSIONS: Our data show that the bacterial sensor NOD2 contributes to intestinal microbial community composition after antibiotic treatment and may add to the explanation of how defects in the NOD2 signaling pathway are involved in the etiology of Crohn's disease.

Association between exposure to air pollution and prefrontal cortical volume in adults: A cross-sectional study from the UK biobank.

Associated with numerous cognitive and behavioral functions and with several diseases, the prefrontal cortex is vulnerable to environmental insult. Among other factors, toxins in air pollution have been associated with damage to the prefrontal cortex in children and older adults. We used data from the UK Biobank to assess further associations between an array of toxins in air pollution and gray matter in the prefrontal cortex including the left and right frontal poles, left and right superior frontal gyri, left and right frontal medial cortex, left and right orbitofrontal cortex, and left and right frontal opercula, using multivariate models adjusted for covariates that possibly could confound the association between air pollution and volume of prefrontal gray matter. The results showed inverse associations between PM 2.5, PM 10, and nitrogen oxides and prefrontal volume in models adjusted for age, sex, education, socioeconomic status, race-ethnicity, self-rated overall health, body mass index, total brain volume, smoking status, and alcohol use frequency. Education appeared to moderate the association between air pollution and prefrontal volume. The data in these analyses came from regions whose mean PM 2.5 was near the upper limit and whose mean PM 10 was under those recommended by the World Health Organization. These findings suggest that comparatively low levels of air pollution might be associated with reduced volume of the prefrontal cortex.

Association between Exposure to Air Pollution and Total Gray Matter and Total White Matter Volumes in Adults: A Cross-Sectional Study.

Total brain gray-matter and white-matter volumes can be indicators of overall brain health. Among the factors associated with gray-matter and white-matter volumes is exposure to air pollution. Using data from the UK Biobank, we sought to determine associations between several components of air pollution-PM2.5, PM2.5-10, PM10, nitrogen dioxide, and nitrogen oxides-and total gray-matter and total white-matter volumes in multivariable regression models in a large sample of adults. We found significant inverse associations between PM2.5 concentration and total white-matter volume and between PM2.5, PM2.5-10, PM10, nitrogen dioxide, and nitrogen oxide concentrations and total gray-matter volume in models adjusted for age, sex, body-mass index, self-assessment of overall health, frequency of alcohol use, smoking status, educational attainment, and income. These findings of pollutant-associated decreases in total gray-matter and total white-matter volumes are in the context of mean PM2.5 concentrations near the upper limit of the World Health Organization's recommendations. Similarly, mean PM10 concentrations were below the recommended upper limit, and nitrogen dioxide concentration was slightly above. Still, there are many areas in the world with much higher concentrations of these pollutants, which could be associated with larger effects. If replicated, these findings suggest that air pollution could be a risk factor for neurodegeneration.

CSF1R inhibitor PLX5622 and environmental enrichment additively improve metabolic outcomes in middle-aged female mice.

As the elderly population grows, chronic metabolic dysfunction including obesity and diabetes are becoming increasingly common comorbidities. Hypothalamic inflammation through CNS resident microglia serves as a common pathway between developing obesity and developing systemic aging pathologies. Despite understanding aging as a life-long process involving interactions between individuals and their environment, limited studies address the dynamics of environment interactions with aging or aging therapeutics. We previously demonstrated environmental enrichment (EE) is an effective model for studying improved metabolic health and overall healthspan in mice, which acts through a brain-fat axis. Here we investigated the CSF1R inhibitor PLX5622 (PLX), which depletes microglia, and its effects on metabolic decline in aging in interaction with EE. PLX in combination with EE substantially improved metabolic outcomes in middle-aged female mice over PLX or EE alone. Chronic PLX treatment depleted 75% of microglia from the hypothalamus and reduced markers of inflammation without affecting brain-derived neurotrophic factor levels induced by EE. Adipose tissue remodeling and adipose tissue macrophage modulation were observed in response to CSF1R inhibition, which may contribute to the combined benefits seen in EE with PLX. Our study suggests benefits exist from combined drug and lifestyle interventions in aged animals.

Perceptions of Missed Care Across Oncology Nursing Specialty Units.

BACKGROUND: An opportunity was identified to compare perceptions of the occurrence and types of missed care at a comprehensive cancer center. PURPOSE: The purpose was to evaluate the difference in perceived occurrence and types of missed care between medical, surgical, and hematologic oncology units in the context of a newly implemented patient care delivery system, Primary Team Nursing (PTN). METHODS: A descriptive, repeated-measures design was used. The MISSCARE survey was distributed electronically to 580 staff members across 6 inpatient units. RESULTS: Frequently perceived elements of missed nursing care were ambulation, turning every 2 hours, and care conference attendance. At the time of study implementation, surgical units reported 0.24 higher scores than medical units (P = .017); hematology units reported 0.26 lower scores than surgical units (P = .005). PTN status did not affect MISSCARE scores (P = .525). CONCLUSIONS: Study findings suggest that perceived missed care in a comprehensive cancer center is similar to that in other hospital settings.

Liposomal bupivacaine versus bupivacaine/epinephrine after video-assisted thoracoscopic wedge resection†.

OBJECTIVES: The purpose of this research is to compare liposomal bupivacaine and bupivacaine/epinephrine for intercostal blocks related to analgesic use and length of stay following video-assisted thoracoscopic wedge resection. METHODS: A retrospective study of patients undergoing video-assisted thoracoscopic wedge resection from 2010 to 2015 was performed. We selected patients who stayed longer than 24 h in hospital. Primary outcomes were length of stay and postoperative analgesic use at 12-h intervals from 24 to 72 h. RESULTS: Intercostal blocks were performed with liposomal bupivacaine in 62 patients and bupivacaine/epinephrine in 51 patients. A Wilcoxon signed-rank test evaluated differences in median postoperative analgesic use and length of stay. Those who received liposomal bupivacaine consumed fewer analgesics than those who received bupivacaine/epinephrine, with a statistically significant difference from 24 to 36 h (20.25 vs 45.0 mg; P = 0.0059) and from 60 to 72 h postoperatively (15.0 vs 33.75 mg; P = 0.0350). In patients who stayed longer than 72 h, the median cumulative analgesic consumption in those who received liposomal bupivacaine was statistically significantly lower than those who received bupivacaine/epinephrine (120.0 vs 296.5 mg; P = 0.0414). Median length of stay for the liposomal bupivacaine and bupivacaine/epinephrine groups were 45:05 h and 44:29 h, respectively. There were no adverse events related to blocks performed with liposomal bupivacaine. CONCLUSIONS: Thoracic surgery patients who have blocks performed with liposomal bupivacaine require fewer analgesics postoperatively. This may decrease complications related to poor pain control and decrease side effects related to narcotic use in our patient population.

Effect of probiotics on respiratory, gastrointestinal and nutritional outcomes in patients with cystic fibrosis: A systematic review.

BACKGROUND: An increasing body of research investigating the use of probiotics to improve health outcomes in patients with cystic fibrosis (CF) prompted the need to systematically assess and summarise the relevant literature. METHODS: An electronic search of five databases and three trial databases was conducted. Studies describing the administration of probiotics to patients with CF older than 2years, with a comparator group on respiratory, gastrointestinal and nutritional outcomes were included. RESULTS: Three pre-post studies and six randomised controlled trials met the inclusion criteria. Overall studies showed a positive effect of probiotics on reducing the number of pulmonary exacerbations and decreasing gastrointestinal inflammation. There was limited effect of probiotics on other outcomes and inadequate evidence for the effects of specific probiotic species and strains. CONCLUSION: The findings suggest that probiotics may improve respiratory and gastrointestinal outcomes in a stable CF clinic population with no reported evidence of harm. There is inadequate evidence at this time to recommend a specific species, strain or dose of probiotic as likely to be of significant benefit.

Efficacy of Sterile Fecal Filtrate Transfer for Treating Patients With Clostridium difficile Infection.

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridium difficile infection (CDI). However, transferring undefined living bacteria entails uncontrollable risks for infectious and metabolic or malignant diseases, particularly in immunocompromised patients. We investigated whether sterile fecal filtrates (containing bacterial debris, proteins, antimicrobial compounds, metabolic products, and oligonucleotides/DNA), rather than intact microorganisms, are effective in patients with CDI. METHODS: We performed a clinical case series to investigate the effects of fecal filtrate transfer (FFT) in 5 patients with symptomatic chronic-relapsing CDI at the Department of Internal Medicine I at the University Hospital Schleswig-Holstein (Kiel, Germany). Patients were followed up for at least 6 months and for up to 33 months. Stool was collected from 5 donors selected by the patients, and fully characterized according to FMT standards. Stool was sterile-filtered to remove small particles and bacteria; the filtrate was transferred to patients in a single administration via nasojejunal tube. Fecal samples were collected from patients before and at 1 week and 6 weeks after FFT. Microbiome, virome, and proteome profiles of donors and patients were compared. RESULTS: In all 5 patients, FFT restored normal stool habits and eliminated symptoms of CDI for a minimum period of 6 months. Proteome analyses of selected FFT filtrates showed no obvious protein candidates associated with therapeutic efficacy. 16S ribosomal RNA gene sequencing detected diverse bacterial DNA signatures in the filtrates. Analysis of virus-like particles from a filtrate found to reduce symptoms of CDI showed a complex signature of bacteriophages. Bacterial phylogeny and virome profile analyses of fecal samples from recipients indicated longitudinal changes in microbial and viral community structures after FFT. CONCLUSIONS: A preliminary investigation of 5 patients with CDI shows that transfer of sterile filtrates from donor stool (FFT), rather than fecal microbiota, can be sufficient to restore normal stool habits and eliminate symptoms. This finding indicates that bacterial components, metabolites, or bacteriophages mediate many of the effects of FMT, and that FFT might be an alternative approach, particularly for immunocompromised patients.

Neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1), previously known as von Recklinghausen disease, is a neurogenetic disorder distinct from neurofibromatosis type 2 (NF2). Approximately 1:2500 to 1:3500 individuals worldwide are affected, regardless of ethnicity or race. The classic manifestations of NF1 include café-au-lait macules, skinfold freckling, neurofibromas, brain tumors, iris hamartomas, and characteristic bony lesions. In addition, patients with NF1 are at increased risk for learning and intellectual disabilities, aqueductal stenosis, pheochromocytoma, vascular dysplasia, scoliosis, and cancer. In this chapter, we discuss the clinical and molecular features of NF1 as well as how insights into its underlying molecular pathophysiology have revealed new targets for therapeutic drug design.

Dietary intake of inulin-type fructans in active and inactive Crohn's disease and healthy controls: a case-control study.

BACKGROUND AND AIMS: Prebiotic inulin-type fructans are widely consumed in the diet and may have contrasting effects in Crohn's disease by stimulating gut microbiota and/or by generating functional gastrointestinal symptoms. The aim of this study was to measure fructan and oligofructose intakes in patients with active and inactive Crohn's disease compared with healthy controls. METHODS: Patients with active Crohn's disease (n = 98), inactive Crohn's (n = 99) and healthy controls (n = 106) were recruited to a case-control study. Dietary intake of inulin-type fructans was measured using a specific food frequency questionnaire and was compared between the three groups and between patients with different disease phenotypes (Montreal classification). Associations between intakes and disease activity (Harvey-Bradshaw Index, HBI) were also undertaken. RESULTS: Patients with active Crohn's disease had lower fructan intakes (median 2.9 g/d, interquartile range [IQR] 1.8) than those with inactive Crohn's (3.6 g/d, 2.1, p = 0.036) or controls (3.9 g/d, 2.1, p = 0.003) and lower oligofructose intakes (2.8 g/d, 1.8) than those with inactive Crohn's (3.5 g/d, 2.2, p = 0.048) or controls (3.8 g/d, 2.1, p = 0.003). There were no differences in intakes related to disease site or behaviour. There were negative correlations between HBI well-being score and fructan intake (ρ = -0.154, p = 0.03) and oligofructose intake (ρ = -0.156, p = 0.028) and for the HBI abdominal pain score and fructan (ρ = -0.164, p = 0.021) and oligofructose intake (ρ = -0.157, p = 0.027). CONCLUSIONS: Patients with active Crohn's disease consume lower quantities of fructans and oligofructose than their inactive counterparts and healthy controls. The impact of lower intakes of prebiotic fructans on gut microbiota is unknown and warrants further research.

Neuropsychological outcomes of stereotactic radiotherapy for cerebral arteriovenous malformations.

To our knowledge, this is the first study to investigate cognitive outcome in patients with large or surgically inaccessible cerebral arteriovenous malformations (AVMs), who were treated with hypo-fractionated stereotactic radiotherapy (HSRT). A sample of 10 patients with AVMs was assessed up to 3.5 years post-HSRT. All patients were treated with HSRT to a total dose of 55 Gy in 11 fractions over a treatment period of 2.5 weeks. Neuropsychological assessments were given prior to radiotherapy and then at three time points following radiotherapy: 6 weeks, 6 months and 2.5-3.5 years post-treatment. The cognitive domains of attention, processing speed, learning, memory, semantic processing, naming, verbal fluency, visuospatial and executive function were assessed. Findings revealed that prior to radiotherapy the patient group was impaired in five of the nine cognitive domains. Post-treatment performances remained stable in the majority of domains; however, there was some fluctuation in semantic processing and memory performances. At 6 weeks post-treatment, a mild decrement was found in semantic processing ability; however, restoration to baseline levels was observed from 6 months onwards. At 2.5-3.5 years post-treatment, improvement was seen in the cohort's ability to remember new information when performances were compared with earlier time points. This study demonstrated improvements in memory several years after HSRT treatment. Further, this form of treatment was not associated with long-term, harmful cognitive side effects for these 10 patients encouraging further study of this treatment method. Further evaluation of the entire cohort is required to assess efficacy in terms of AVM obliteration and other potential side effects.

Clozapine-induced ischaemic colitis.

Ischaemic colitis is a rare side effect of antipsychotics, especially phenothiazines and atypical antipsychotics. The colitis may be precipitated secondary to the anticholinergic effects of such medication rather than a direct cytotoxic effect of the drugs themselves. A 32-year-old man with a history of schizophrenia was admitted to the hospital with a history of diffuse abdominal pain and vomiting. His bloods showed leucocytosis. Sigmoidoscopy demonstrated rectal sparing acute colitis, confirmed on biopsy findings. A CT scan also showed similar findings. After careful drug review, it was decided that clozapine was the cause of colitis and promptly stopped. The patient was managed conservatively on intravenous fluids and antibiotics and made a full recovery. Any patient starting antipsychotics should be counselled on their anticholinergic side effects. Drugs should always be considered as a cause of ischaemic colitis; although an uncommon complication of antipsychotics, it can have a potentially fatal outcome.

Measurement of urinary oxypurinol by high performance liquid chromatography-tandem mass spectrometry.

Oxypurinol is the active metabolite of allopurinol which is used to treat hyperuricaemia associated with gout. Both oxypurinol and allopurinol inhibit xanthine oxidase which forms uric acid from xanthine and hypoxanthine. Plasma oxypurinol concentrations vary substantially between individuals and the source of this variability remains unclear. The aim of this study was to develop an HPLC-tandem mass spectrometry method to measure oxypurinol in urine to facilitate the study of the renal elimination of oxypurinol in patients with gout. Urine samples (50 microL) were prepared by dilution with a solution of acetonitrile/methanol/water (95/2/3, v/v; 2 mL) that contained the internal standard (8-methylxanthine; 1.5 mg/L), followed by centrifugation. An aliquot (2 microL) was injected. Chromatography was performed on an Atlantis HILIC Silica column (3 microm, 100 mm x 2.1mm, Waters) at 30 degrees C, using a mobile phase comprised of acetonitrile/methanol/50 mM ammonium acetate in 0.2% formic acid (95/2/3, v/v). Using a flow rate of 0.35 mL/min, the analysis time was 6.0 min. Mass spectrometric detection was by selected reactant monitoring (oxypurinol: m/z 150.8-->108.0; internal standard: m/z 164.9-->121.8) in negative electrospray ionization mode. Calibration curves were prepared in drug-free urine across the range 10-200 mg/L and fitted using quadratic regression with a weighting factor of 1/x (r(2) > 0.997, n=7). Quality control samples (20, 80, 150 and 300 mg/L) were used to determine intra-day (n=5) and inter-day (n=7) accuracy and imprecision. The inter-day accuracy and imprecision was 96.1-104% and <11.2%, respectively. Urinary oxypurinol samples were stable when subjected to 3 freeze-thaw cycles and when stored at room temperature for up to 6h. Samples collected from 10 patients, not receiving allopurinol therapy, were screened and showed no significant interferences. The method was suitable for the quantification of oxypurinol in the urine of patients (n=34) participating in a clinical trial to optimize therapy of gout with allopurinol.

Long-term cognitive outcome after transcallosal resection of hypothalamic hamartoma in older adolescents and adults with gelastic seizures.

Hypothalamic hamartomas (HHs) are typically associated with pharmacologically intractable gelastic seizures, which often develop into complex partial and/or generalized tonic-clonic seizures. The transcallosal, anterior interforniceal (TAIF) approach to HH resection has been shown to be safe and to result in good seizure frequency reduction. We documented postsurgical cognitive functioning and examined whether using the TAIF approach with older adolescents and adults affected long-term cognitive outcome. Six older adolescents and adults, who had undergone resection of an HH using the TAIF approach, underwent comprehensive neuropsychological assessment at least 2 years postoperatively. Four of these individuals also had neuropsychological evaluation preoperatively. All participants who were assessed pre- and postoperatively demonstrated long-term improvement in perceptual/visuospatial function after surgery. Three of the four participants also demonstrated lasting reduction in memory function postoperatively. The TAIF approach to HH resection is associated with a high risk of long-term memory impairment in older adolescents and adults.

Preoperative skin preparation of cardiac patients.

Nurses at a large southwestern hospital undertook an initiative to optimize the preoperative skin preparation of patients undergoing open heart surgery. After an extensive review of the literature, a proposal was submitted to and accepted by the surgeons and internal review board of the hospital. High-risk patients were identified before surgery and randomized into groups to receive one of four different skin preps. The incidence of infection was lower in the two groups of patients who were prepped with insoluble iodine, indicating that the type of surgical skin prep could affect whether patients develop surgical site infections. The clinical practice of skin preparation in this hospital changed based on the results.

Effectiveness of 0.12% chlorhexidine gluconate oral rinse in reducing prevalence of nosocomial pneumonia in patients undergoing heart surgery.

BACKGROUND: Decreasing the levels of bacteria in the oropharynx should reduce the prevalence of nosocomial pneumonia. OBJECTIVES: To test the effectiveness of 0.12% chlorhexidine gluconate oral rinse in decreasing microbial colonization of the respiratory tract and nosocomial pneumonia in patients undergoing open heart surgery. METHODS: A prospective, randomized, case-controlled clinical trial design was used. Peridex (0.12% chlorhexidine gluconate) was the experimental drug, and Listerine (phenolic mixture) was the control drug. A total of 561 patients undergoing aortocoronary bypass or valve surgery requiring cardiopulmonary bypass were randomized to an experimental (n = 270) or a control (n = 291) group. Nosocomial pneumonia was diagnosed by using the criteria established by the Centers for Disease Control and Prevention. RESULTS: The overall rate of nosocomial pneumonia was reduced by 52% (4/270 vs 9/291; P = .21) in the Peridex-treated patients. Among patients intubated for more than 24 hours who had cultures that showed microbial growth (all pneumonias occurred in this group), the pneumonia rate was reduced by 58% (4/19 vs 9/18; P = .06) in patients treated with Peridex. In patients at highest risk for pneumonia (intubated > 24 hours, with cultures showing the most growth), the rate was 71% lower in the Peridex group than in the Listerine group (2/10 vs 7/10; P = .02). CONCLUSIONS: Although rates of nosocomial pneumonia were lower in patients treated with Peridex than in patients treated with Listerine, the difference was significant only in those patients intubated more than 24 hours who had the highest degree of bacterial colonization.