A proof of principle study investigating the effects of supplemental concentrated brewer's yeast on markers of gut permeability, inflammation, and fecal metabolites in healthy non-challenged adult sled dogs.

Yeast-derived ß-glucans impact immunity, though their effects on gut permeability and inflammation are less understood. Most research has investigated other components of the yeast cell wall, such as the prebiotic mannan- and fructo-oligosaccharides. The objective of this study was to assess the effects of feeding a concentrated yeast product on markers of inflammation (serum amyloid A [SAA] and haptoglobin [Hp]) and oxidative status (malondialdehyde [MDA]), fecal products of fermentation, and gut permeability. Nineteen privately owned domestic Siberian huskies, and one Alaskan husky (9 females: 5 intact, 4 spayed; 11 males: 3 intact, 8 neutered), with an average age of 4.8 ± 2.6 yr and body weight (BW) of 25.6 ± 4.1 kg, were used in this study. Dogs were blocked and randomly allocated to one of two diet groups. Ten dogs received a dry extruded diet. The other 10 received the same diet top dressed with yeast for a daily ß-glucan dose of 7 mg/kg BW for 10 wk. Fecal collection, for evaluation of fecal metabolites, and scoring occurred weekly. Gut permeability was assessed using the chromium-labeled ethylenediamine tetra-acetic acid (Cr-EDTA) and iohexol markers prior to the initiation of dietary treatment and after 10 wk of treatment. Blood samples were collected premarker administration and 0.5, 1, 2, 3, 4, 5, and 6 h postadministration. Fasting concentrations of SAA, Hp, and MDA were measured on weeks -1, 2, 4, and 8. Incremental area under the curve (I-AUC) was calculated for serum iohexol and Cr-EDTA concentrations. All data were analyzed using PROC GLIMMIX of SAS with dog as random effect, and week as fixed effect and repeated measure. Dogs receiving treatment tended to have decreased I-AUC of Iohexol (P = 0.10) and Cr-EDTA (P = 0.06) between baseline and cessation of treatment compared to the change over time in I-AUC for control (Ctl) dogs. Treatment dogs had lower Hp concentrations (P ≤ 0.05) than Ctl. There were no differences between treatments for SAA and MDA concentrations (P > 0.05). Fecal arabinose concentrations were greater in treatment (Trt) dogs (P ≤ 0.05) compared to Ctl, though no other fecal metabolites were affected by treatment. There was no difference in the relative frequency of defecations scored at any fecal score between Trt and Ctl dogs, and mean score did not differ between groups (P > 0.10). These data suggest that concentrated brewer's yeast may have the potential to reduce gut permeability without impacting inflammatory status and markers of health in adult dogs.

This study evaluated the effects of concentrated brewer's yeast on gut health in dogs. Nineteen Siberian Huskies and one Alaskan husky were blocked and randomly allocated to one of two groups. Treatment dogs received a yeast supplement for 10 wk, while control dogs received no supplement. Dogs were administered two markers to assess intestinal permeability prior to start of treatment and following 10 wk of treatment. Blood samples were collected and analyzed for markers of inflammatory status (serum amyloid A [SAA] and Haptoglobin [Hp]) and oxidative status (serum malondialdehyde [MDA]). Fecal samples were collected weekly to assess fecal score as well as fecal metabolite concentrations. Intestinal permeability was reduced in treatment dogs following treatment, and no change was observed in the control group. Treatment dogs had lower Hp concentrations than control (Ctl), but there were no differences between treatments for SAA and MDA. Fecal arabinose concentrations were significantly greater in the treatment group when compared to control. There were no differences in the relative frequency of defecations scored at any fecal score between treatment and Ctl dogs, nor did mean score differ between the groups. This study suggests that concentrated brewer's yeast may reduce gut permeability and inflammation without detrimentally impacting markers of health in adult dogs.

Crotonylation at serine 46 impairs p53 activity.

Post-translational modifications (PTMs) play pivotal roles in controlling the stability and activity of the tumor suppressor p53 in response to distinct stressors. Here we report an unexpected finding of a short chain fatty acid modification of p53 in human cells. Crotonic acid (CA) treatment induces p53 crotonylation, but surprisingly reduces its protein, but not mRNA level, leading to inhibition of p53 activity in a dose dependent fashion. Surprisingly this crotonylation targets serine 46, instead of any predicted lysine residues, of p53, as detected in TCEP-probe labeled crotonylation and anti-crotonylated peptide antibody reaction assays. This is further confirmed by substitution of serine 46 with alanine, which abolishes p53 crotonylation in vitro and in cells. CA increases p53-dependent glycolytic activity, and augments cancer cell proliferation in response to metabolic or DNA damage stress. Since serine 46 is only found in human p53, our studies unveil an unconventional PTM unique for human p53, impairing its activity in response to CA. Because CA is likely produced by the gut microbiome, our results also predict that this type of PTM might play a role in early human colorectal neoplasia development by negating p53 activity without mutation of this tumor suppressor gene.

Household energy efficiency and health: Area-level analysis of hospital admissions in England.

INTRODUCTION: Fuel poverty affects up to 35% of European homes, which represents a significant burden on society and healthcare systems. Draught proofing homes to prevent heat loss, improved glazing, insulation and heating (energy efficiency measures) can make more homes more affordable to heat. This has prompted significant investment in energy efficiency upgrades for around 40% of UK households to reduce the impact of fuel poverty. Despite some inconsistent evidence, household energy efficiency interventions can improve cardiovascular and respiratory health outcomes. However, the health benefits of these interventions have not been fully explored; this is the focus of this study. METHODS: In this cross sectional ecological study, we conducted two sets of analyses at different spatial resolution to explore population data on housing energy efficiency measures and hospital admissions at the area-level (counts grouped over a 3-year period). Housing data were obtained from three data sets covering housing across England (Household Energy Efficiency Database), Energy Performance Certificate (EPC) and, in the South West of England, the Devon Home Analytics Portal. These databases provided data aggregated to Lower Area Super Output Area and postcode level (Home Analytics Portal only). These datasets provided measures of both state (e.g. EPC ratings) and intervention (e.g. number of boiler replacements), aggregated spatially and temporally to enable cross-sectional analyses with health outcome data. Hospital admissions for adult (over 18 years) asthma, chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) were obtained from the Hospital Episode Statistics database for the national (1st April 2011 to 31st March 2014) and Devon, South West of England (1st April 2014 to 31st March 2017) analyses. Descriptive statistics and regression models were used to describe the associations between small area household energy efficiency measures and hospital admissions. Three main analyses were undertaken to investigate the relationships between; 1) household energy efficiency improvements (i.e. improved glazing, insulation and boiler upgrades); 2) higher levels of energy efficiency ratings (measured by Energy Performance Certificate ratings); 3) energy efficiency improvements and ratings (i.e. physical improvements and rating assessed by the Standard Assessment Procedure) and hospital admissions. RESULTS: In the national analyses, household energy performance certificate ratings ranged from 37 to 83 (mean 61.98; Standard Deviation 5.24). There were a total of 312,837 emergency admissions for asthma, 587,770 for COPD and 839,416 for CVD. While analyses for individual energy efficiency metrics (i.e. boiler upgrades, draught proofing, glazing, loft and wall insulation) were mixed; a unit increase in mean energy performance rating was associated with increases of around 0.5% in asthma and CVD admissions, and 1% higher COPD admission rates. Admission rates were also influenced by the type of dwelling, tenure status (e.g. home owner versus renting), living in a rural area, and minimum winter temperature. DISCUSSION: Despite a range of limitations and some mixed and contrasting findings across the national and local analyses, there was some evidence that areas with more energy efficiency improvements resulted in higher admission rates for respiratory and cardiovascular diseases. This builds on existing evidence highlighting the complex relationships between health and housing. While energy efficiency measures can improve health outcomes (especially when targeting those with chronic respiratory illness), reduced household ventilation rates can impact indoor air quality for example and increase the risk of diseases such as asthma. Alternatively, these findings could be due to the ecological study design, reverse causality, or the non-detection of more vulnerable subpopulations, as well as the targeting of areas with poor housing stock, low income households, and the lack of "whole house approaches" when retrofitting the existing housing stock. CONCLUSION: To be sustainable, household energy efficiency policies and resulting interventions must account for whole house approaches (i.e. consideration of the whole house and occupant lifestyles). These must consider more alternative 'greener' and more sustainable measures, which are capable of accounting for variable lifestyles, as well as the need for adequate heating and ventilation. Larger natural experiments and more complex modelling are needed to further investigate the impact of ongoing dramatic changes in the housing stock and health. STUDY IMPLICATIONS: This study supports the need for more holistic approaches to delivering healthier indoor environments, which must consider a dynamic and complex system with multiple interactions between a range of interrelated factors. These need to consider the drivers and pressures (e.g. quality of the built environment and resident behaviours) resulting in environmental exposures and adverse health outcomes.

Exploring traditional and complementary medicine use by Indigenous Australian women undergoing gynaecological cancer investigations.

BACKGROUND: Indigenous Australian women experience worse gynaecological cancer outcomes than non-Indigenous women. While traditional and complementary medicine (T&CM) is increasingly used by cancer patients alongside conventional treatments, little is known about T&CM use by Indigenous women. This study aimed to explore the beliefs, attitudes and experiences related to T&CM use and disclosure among Indigenous women undergoing gynaecological cancer investigations. METHODS: A mixed-methods design explored T&CM use among Indigenous women who presented for gynaecological cancer investigation at an urban Queensland hospital (September 2016 and January 2018). RESULTS: Fourteen women participated. The reported use (86%) and perceived value of T&CM was high among the participants, however, women reported major challenges in communicating with healthcare providers about T&CM, commonly associated with trust and rapport. CONCLUSIONS: These findings highlight the need for strategies to facilitate culturally-appropriate doctor-patient communication around T&CM to foster trust and transparency in gynaecological cancer care for Indigenous women.

Increased Effectiveness of Microbiological Verification by Concentration-Dependent Neutralization of Sanitizers Used in Poultry Slaughter and Fabrication Allowing Salmonella enterica Survival.

Sanitizer neutralizers can assist foodborne pathogen detection during routine testing by counteracting sanitizer residues carried over into fluids collected and tested from food samples. This study tested sanitizer-matched neutralizers applied at increasing concentrations to facilitate Salmonella enterica survival following exposure to cetylpyridinium chloride (CPC) or peracetic acid (PAA), identifying minimum required concentrations of neutralizers to facilitate pathogen survival. Salmonella isolates were individually inoculated into a non-selective medium followed immediately by CPC (0.1 to 0.8% v/v) or PAA (0.0125 to 0.2% v/v) application, followed by neutralizers application. CPC was neutralized by lecithin and polysorbate 80, each supplemented into buffered peptone water (BPW) at 0.125 to 2.0X its respective content in Dey-Engley (D/E) neutralizing buffer. PAA was neutralized in BPW supplemented with disodium phosphate, potassium monophosphate, and sodium thiosulfate, each at 0.25 to 3.0X its respective concentration in BPW (phosphates) or D/E buffer (thiosulfate). Addition of neutralizers at 1X their respective concentrations in D/E buffer was required to allow Salmonella growth at the maximum CPC concentration (0.8%), while 2X neutralizer addition was required for Salmonella growth at the maximum PAA level (0.2%). Sanitizer neutralizers can assist pathogen survival and detection during routine food product testing.

A Comparative Study of Natural Antimicrobial Delivery Systems for Microbial Safety and Quality of Fresh-Cut Lettuce.

Nanoencapsulation can provide a means to effectively deliver antimicrobial compounds and enhance the safety of fresh produce. However, to date there are no studies which directly compares how different nanoencapsulation systems affect fresh produce safety and quality. This study compared the effects on quality and safety of fresh-cut lettuce treated with free and nanoencapsulated natural antimicrobial, cinnamon bark extract (CBE). A challenge study compared antimicrobial efficacy of 3 different nanoencapsulated CBE systems. The most effective antimicrobial treatment against Listeria monocytogenes was chitosan-co-poly-N-isopropylacrylamide (chitosan-PNIPAAM) encapsulated CBE, with a reduction on bacterial load up to 2 log10 CFU/g (P < 0.05) compared to the other encapsulation systems when fresh-cut lettuce was stored at 5 °C and 10 °C for 15 d. Subsequently, chitosan-PNIPAAM-CBE nanoparticles (20, 40, and 80 mg/mL) were compared to a control and free CBE (400, 800, and 1600 µg/mL) for its effects on fresh-cut lettuce quality over 15 d at 5 °C. By the 10th day, the most effective antimicrobial concentration was 80 mg/mL for chitosan-PNIPAAM-CBE, up to 2 log10 CFU/g reduction (P < 0.05), compared with the other treatments. There was no significant difference between control and treated samples up to day 10 for the quality attributes evaluated. Chitosan-PNIPAAM-CBE nanoparticles effectively inhibited spoilage microorganisms' growth and extended fresh-cut lettuce shelf-life. Overall, nanoencapsulation provided a method to effectively deliver essential oil and enhanced produce safety, while creating little to no detrimental quality changes on the fresh-cut lettuce.

Inhibition of Bacterial Pathogens in Medium and on Spinach Leaf Surfaces using Plant-Derived Antimicrobials Loaded in Surfactant Micelles.

UNLABELLED: Encapsulation of hydrophobic plant essential oil components (EOC) into surfactant micelles can assist the decontamination of fresh produce surfaces from bacterial pathogens during postharvest washing. Loading of eugenol and carvacrol into surfactant micelles of polysorbate 20 (Tween 20), Surfynol® 485W, sodium dodecyl sulfate (SDS), and CytoGuard® LA 20 (CG20) was determined by identification of the EOC/surfactant-specific maximum additive concentration (MAC). Rheological behavior of dilute EOC-containing micelles was then tested to determine micelle tolerance to shearing. Antimicrobial efficacy of EOC micelles against Escherichia coli O157:H7 and Salmonella enterica serotype Saintpaul was first evaluated by the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Pathogen-inoculated spinach was treated with eugenol-containing micelles applied via spraying or immersion methods. SDS micelles produced the highest MACs for EOCs, while Tween 20 loaded the lowest amount of EOCs. Micelles demonstrated Newtonian behavior in response to shearing. SDS and CG20-derived micelles containing EOCs produced the lowest MICs and MBCs for pathogens. E. coli O157:H7 and S. Saintpaul were reduced on spinach surfaces by application of eugenol micelles, though no differences in numbers of surviving pathogens were observed when methods of antimicrobial micelle application (spraying, immersion) was compared (P ≥ 0.05). Data suggest eugenol in SDS and CG20 micelles may be useful for produce surface decontamination from bacterial pathogens during postharvest washing. PRACTICAL APPLICATION: Antimicrobial essential oil component (EOC)-containing micelles assist the delivery of natural food antimicrobials to food surfaces, including fresh produce, for decontamination of microbial foodborne pathogens. Antimicrobial EOC-loaded micelles were able to inhibit the enteric pathogens Escherichia coli O157:H7 and Salmonella Saintpaul in liquid medium and on spinach surfaces. However, pathogen reduction generally was not impacted by the method of micelle application (spraying, immersion washing) on spinach surfaces.

Interactions between oil substrates and glucose on pure cultures of ruminal lipase-producing bacteria.

The hydrolysis of free fatty acids from lipids is a prerequisite for biohydrogenation, a process that effectively saturates free fatty acids. Anaerovibrio lipolyticus 5s and Butyrivibrio fibrisolvens have long been thought to be the major contributors to ruminal lipolysis; however, Propionibacterium avidum and acnes recently have been identified as contributing lipase activity in the rumen. In order to further characterize the lipase activity of these bacterial populations, each was grown with three different lipid substrates, olive oil, corn oil, and flaxseed oil (3 %). Because different finishing rations contain varying levels of glycogen (a source of free glucose) this study also documented the effects of glucose on lipolysis. P. avidum and A. lipolyticus 5s demonstrated the most rapid rates (P < 0.05) of lipolysis for cultures grown with olive oil and flaxseed oil, respectively. A. lipolyticus, B. fibrisolvens, and P. avidum more effectively hydrolyzed flaxseed oil than olive oil or corn oil, especially in the presence of 0.02 % glucose. Conversely, P. acnes hydrolyzed corn oil more readily than olive oil or flaxseed oil and glucose had no effect on lipolytic rate. Thus, these bacterial species demonstrated different specificities for oil substrates and different sensitivities to glucose.

Antimicrobial efficacy of poly (DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped cinnamon bark extract against Listeria monocytogenes and Salmonella typhimurium.

Nanoencapsulation of active compounds using poly-(d,l-lactide-co-glycolide) (PLGA) is commonly used in the pharmaceutical industry for drug delivery and may have important applications in the food industry. Control of growth of foodborne bacteria with the goals of reducing the number of foodborne illness outbreaks, assuring consumers a safer food supply remains a priority in the food industry. Natural antimicrobials are an excellent way to eliminate pathogens without introducing chemical preservatives that consumers may find undesirable. Cinnamon bark extract (CBE) is an effective pathogen inhibitor isolated from cinnamon spice. PLGA nanoparticles containing CBE were produced using an emulsion-solvent evaporation method and characterized for size, polydispersity, morphology, entrapment efficiency, in vitro release and pathogen inhibition. PLGA with 2 different ratios of lactide to glycolide (65:35 and 50:50) were used to determine how polymer composition affected nanoparticle characteristics and antimicrobial potency. The size of the nanoparticles ranged from 144.77 to 166.65 nm and the entrapment efficiencies of CBE in 65:35 PLGA and 50:50 PLGA were 38.90% and 47.60%, respectively. The in vitro release profile at 35 °C showed an initial burst effect for both types of PLGA followed by a more gradual release of CBE from the polymer matrix. Both types of PLGA nanoparticles loaded with CBE were effective inhibitors of Salmonella enterica serovar Typhimurium and Listeria monocytogenes after 24 and 72 h at concentrations ranging from 224.42 to 549.23 µg/mL. The PLGA encapsulation improved delivery of hydrophobic antimicrobial to the pathogens in aqueous media.

Paranasal sinus surgery through a frontonasal flap in sedated, standing horses.

OBJECTIVE: To report experience with paranasal sinus surgery through a frontonasal flap in sedated, standing horses. STUDY DESIGN: Treatment of 10 horses with naturally occurring paranasal sinus disease through a frontonasal bone flap created with the horses standing. ANIMALS: Ten adult horses. METHODS: After restraint and sedation, local anesthetic was injected subcutaneously along the proposed incision line over the conchofrontal sinus and was instilled into the sinuses through a small hole created in the frontal bone. A 3-sided, rectangular, cutaneous incision that extended through the periosteum was created over the frontal and nasal bones. The incision was extended into the conchofrontal sinus using a bone saw, and the base of the flap, on the midline of the face, was fractured. The sinuses were explored, and the horse was treated for the disease encountered. The flap was repositioned; subcutaneous tissue and skin were sutured separately. RESULTS: The horses had few signs of discomfort during creation of the bone flap and during disease treatment. Diseases encountered included inspissated exudate in the ventral conchal sinus (five horses), feed and exudate throughout the sinuses (one horse), occlusion of the nasomaxillary aperature (one horse), polyp (one horse), osteoma (one horse), and progressive ethmoidal hematoma (one horse). CONCLUSION: In selected cases, surgery of the paranasal sinuses can be performed safely on sedated and standing horses through a frontonasal bone flap. CLINICAL RELEVANCE: Performing surgery through a frontonasal bone flap with the horse standing and sedated, rather than anesthetized, eliminates risks and expense of general anesthesia.

Efficacy and safety of acarbose in metformin-treated patients with type 2 diabetes.

OBJECTIVE: To demonstrate the efficacy, tolerability, and safety of acarbose compared with placebo in patients with type 2 diabetes inadequately controlled with diet and metformin (2,000 or 2,500 mg/day in divided doses). RESEARCH DESIGN AND METHODS: This study had a multicenter randomized double-blind placebo-controlled parallel-group comparison design. The trial lasted 31 weeks and consisted of a 1-week screening period, a 6-week placebo pretreatment period, and a 24-week period of acarbose or placebo, with a forced titration from 25-50 mg t.i.d. and a titration of 50-100 mg tid that was based on glucose control. The primary efficacy variable was the mean change from baseline in HbA1c. Secondary efficacy variables included mean changes from baseline in fasting and postprandial plasma glucose, serum insulin, and triglyceride levels. RESULTS: The addition of acarbose to patients on background metformin and diet therapy showed a statistically significant reduction in mean HbA1c of 0.65%. There were statistically significant reductions in fasting and postprandial plasma glucose and serum insulin levels compared with placebo. Gastrointestinal side effects were more frequently reported in the acarbose-treated patients. No significant differences in liver transaminase elevations were observed between patients treated with acarbose and those treated with placebo. CONCLUSIONS: The results of this study demonstrate that the addition of acarbose to patients with type 2 diabetes who are inadequately controlled with metformin and diet is safe and generally well tolerated and that it significantly lowers HbA1c and fasting and postprandial glucose and insulin levels.

Efficacy and safety of acarbose in insulin-treated patients with type 2 diabetes.

OBJECTIVE: To demonstrate the efficacy, tolerability, and safety of acarbose compared with placebo in patients with type 2 diabetes inadequately controlled with diet and insulin. RESEARCH DESIGN AND METHODS: A multicenter randomized double-blind placebo-controlled parallel-group comparison study was conducted. The trial was 26 weeks with a 2-week screening period and a 24-week period of treatment with acarbose or placebo, with forced titration from 25 mg t.i.d. to 50 mg t.i.d. after 4 weeks, and titration of 50 mg t.i.d. to 100 mg t.i.d. after 12 weeks based on glucose control. The dosage of insulin was to remain stable. The primary efficacy variable was mean change from baseline in HbA1c, and secondary efficacy variables included mean changes in fasting and postprandial plasma glucose and triglyceride levels. RESULTS: The addition of acarbose to the treatment of patients receiving background insulin and diet therapy resulted in a statistically significant reduction in mean HbA1c of 0.69% compared with placebo. There were statistically significant reductions in postprandial plasma glucose and glucose area under the curve, and in postprandial serum triglyceride levels in the acarbose-treated patients. Gastrointestinal side effects were more frequently reported in the acarbose-treated patients. There were no significant differences in hypoglycemic events or liver transaminase elevations between groups. CONCLUSIONS: This study demonstrated that the addition of acarbose to patients with type 2 diabetes who are inadequately controlled with insulin and diet is safe and generally well tolerated and that it significantly lowers HbA1c and postprandial glucose levels.

Outcome after treatment of high-risk papillary and non-Hürthle-cell follicular thyroid carcinoma.

BACKGROUND: Treatment of differentiated thyroid cancer has been studied for many years, but the benefits of extensive initial thyroid surgery and the addition of radioiodine therapy or external radiation therapy remain controversial. OBJECTIVE: To determine the relations among extent of surgery, radioiodine therapy, and external radiation therapy in the treatment of high-risk papillary and non-Hürthle-cell follicular thyroid carcinoma. DESIGN: Analysis of data from a multicenter study. SETTING: 14 institutions in the United States and Canada participating in the National Thyroid Cancer Treatment Cooperative Study Registry. PATIENT: 385 patients with high-risk thyroid cancer (303 with papillary carcinoma and 82 with follicular carcinoma). MEASUREMENTS: Death, disease progression, and disease-free survival. RESULTS: Total or near-total thyroidectomy was done in 85.3% of patients with papillary carcinoma and 71.3% of patients with follicular cancer. Overall surgical complication rate was 14.3%. Total or near-total thyroidectomy improved overall survival (risk ratio [RR], 0.37 [95% CI, 0.18 to 0.75]) but not cancer-specific mortality, progression, or disease-free survival in patients with papillary cancer. No effect of extent of surgery was seen in patients with follicular thyroid cancer. Postoperative iodine-131 was given to 85.4% of patients with papillary cancer and 79.3% of patients with follicular cancer. In patients with papillary cancer, radioiodine therapy was associated with improvement in cancer-specific mortality (RR, 0.30 [CI, 0.09 to 0.93 by multivariate analysis only]) and progression (RR, 0.30 [CI, 0.13 to 0.72]). When tall-cell variants were excluded, the effect on outcome was not significant. After radioiodine therapy, patients with follicular thyroid cancer had improvement in overall mortality (RR, 0.17 [CI, 0.06 to 0.47]), cancer-specific mortality (RR, 0.12 [CI, 0.04 to 0.42]), progression (RR, 0.21 [CI, 0.08 to 0.56]), and disease-free survival (RR, 0.29 [CI, 0.08 to 1.01]). External radiation therapy to the neck was given to 18.5% of patients and was not associated with improved survival, lack of progression, or disease-free survival. CONCLUSIONS: This study supports improvement in overall and cancer-specific mortality among patients with papillary and follicular thyroid cancer after postoperative iodine-131 therapy. Radioiodine therapy was also associated with improvement in progression in patients with papillary cancer and improvement in progression and disease-free survival in patients with follicular carcinoma.

Role of orlistat in the treatment of obese patients with type 2 diabetes. A 1-year randomized double-blind study.

OBJECTIVE: Obesity is an important risk factor for type 2 diabetes. Weight loss in patients with type 2 diabetes is associated with improved glycemic control and reduced cardiovascular disease risk factors, but weight loss is notably difficult to achieve and sustain with caloric restriction and exercise. The purpose of this study was to assess the impact of treatment with orlistat, a pancreatic lipase inhibitor, on weight loss, glycemic control, and serum lipid levels in obese patients with type 2 diabetes on sulfonylurea medications. RESEARCH DESIGN AND METHODS: In a multicenter 57-week randomized double-blind placebo-controlled study, 120 mg orlistat or placebo was administered orally three times a day with a mildly hypocaloric diet to 391 obese men and women with type 2 diabetes who were aged > 18 years, had a BMI of 28-40 kg/m2, and were clinically stable on oral sulfonylureas. Changes in body weight, glycemic control, lipid levels, and drug tolerability were measured. RESULTS: After 1 year of treatment, the orlistat group lost 6.2 +/- 0.45% (mean +/- SEM) of initial body weight vs. 4.3 +/- 0.49% in the placebo group (P < 0.001). Twice as many patients receiving orlistat (49 vs. 23%) lost > or = 5% of initial body weight (P < 0.001). Orlistat treatment plus diet compared with placebo plus diet was associated with significant improvement in glycemic control, as reflected in decreases in HbA1c (P < 0.001) and fasting plasma glucose (P < 0.001) and in dosage reductions of oral sulfonylurea medication (P < 0.01). Orlistat therapy also resulted in significantly greater improvements than placebo in several lipid parameters, namely, greater reductions in total cholesterol, (P < 0.001), LDL cholesterol (P < 0.001), triglycerides (P < 0.05), apolipoprotein B (P < 0.001), and the LDL-to-HDL cholesterol ratio (P < 0.001). Mild to moderate and transient gastrointestinal events were reported with orlistat therapy, although their association with study withdrawal was low. Fat-soluble vitamin levels generally remained within the reference range, and vitamin supplementation was required in only a few patients. CONCLUSIONS: Orlistat is an effective treatment modality in obese patients with type 2 diabetes with respect to clinically meaningful weight loss and maintenance of weight loss, improved glycemic control, and improved lipid profile.

Intramuscular artemether vs intravenous quinine: an open, randomized trial in Malawian children with cerebral malaria.

OBJECTIVES: To compare artemether (by intramuscular injection) and quinine (by intravenous infusion) as treatments for cerebral malaria in African children. METHODS: An open, randomized trial conducted at the Queen Elizabeth Central Hospital in Blantyre, Malawi. This trial was part of a multicentre study designed to determine if treatment with artemether would significantly lower mortality rates compared with quinine. Data from 83 artemether recipients and 81 quinine recipients are reported here. RESULTS: Overall mortality rates and coma resolution times were not significantly different in the two treatment groups. Parasite and fever clearance times were significantly more rapid in the artemether recipients. Analyses which took into account the possible confounding variables did not significantly alter the findings of these unadjusted analyses. CONCLUSION: These results do not suggest that treatment with artemether would confer a survival advantage in children with life-threatening malaria. The power and precision of the estimated treatment effects of artemether would be enhanced by a meta-analysis of all relevant clinical trials.

Artemisinin and the antimalarial endoperoxides: from herbal remedy to targeted chemotherapy.

Artemisinin and its derivatives are endoperoxide-containing compounds which represent a promising new class of antimalarial drugs. In the presence of intraparasitic iron, these drugs are converted into free radicals and other electrophilic intermediates which then alkylate specific malaria target proteins. Combinations of available derivatives and other antimalarial agents show promise both as first-line agents and in the treatment of severe disease.

Permanent tracheostomy in standing horses: technique and results.

Permanent tracheal stomas were created in seven sedated, standing horses with severe upper airway obstruction. After local anesthesia, a 3-cm by 6-cm rectangle of skin was removed from the ventral surface of the neck, 3 cm distal to the cricoid cartilage. The sternothyrohyoideus muscles were clamped proximally and distally, then transected to expose the tracheal rings. The ventral third of four tracheal rings was dissected from the tracheal mucosa that was then incised in a double "Y." Two layers of suture were used to achieve mucocutaneous closure. Stomas healed without serious complications; two mares subsequently foaled, and three horses were used for riding.