An Expert Consensus to Standardize Assessment of Bowel Cleansing for Clinical Trials of Bowel Preparations for Crohn's Disease.

BACKGROUND: Despite regular need for colonoscopy in patients with Crohn's disease (CD), the efficacy and tolerability of bowel preparation (BP) agents is rarely assessed in this population. Assessing BP quality with existing scales may be challenging in CD due to presence of inflammation, bowel resection, and strictures. AIMS: To provide recommendations for assessing BP quality in clinical trials for CD using a modified Research and Development/University of California, Los Angeles appropriateness process. METHODS: Based on systematic reviews and a literature search, 110 statements relating to BP quality assessment in CD were developed. A panel of 15 gastroenterologists rated the statements as appropriate, uncertain, or inappropriate using a 9-point Likert scale. RESULTS: Panelists considered it appropriate that central readers, either alone or with local assessment, score BP quality in clinical trials. Central readers should be trained on scoring BP quality and local endoscopists on performing high-quality video recording. Both endoscope insertion and withdrawal phases should be reviewed to score BP quality in each colonic segment and segments should align with endoscopic disease activity indices. The Harefield Cleansing Scale and the Boston Bowel Preparation Scale were considered appropriate. The final score should be calculated as the average of all visualized segments. Both total and worst segment scores should also be assessed. CONCLUSIONS: We developed a framework for assessing BP quality in patients with CD based on expert feedback. This framework could support the development or refinement of BP quality scales and the integration of BP quality assessment in future CD studies.

A Multicenter Randomized Controlled Trial Comparing Two Bowel Cleansing Regimens for Colonoscopy After Failed Bowel Preparation.

BACKGROUND & AIMS: Failed bowel preparation for colonoscopy occurs commonly, but the optimal regimen for the subsequent attempt is unknown. High-volume preparations often are used but are not well studied. The objective of this study was to compare the efficacy, tolerability, and safety of 2 regimens for use after failed bowel preparation. METHODS: A multicenter, endoscopist-blinded randomized controlled trial was conducted in patients who previously failed bowel preparation despite adequate compliance. Patients were randomized to 1 of 2 split polyethylene glycol (PEG) regimens, preceded by 15 mg bisacodyl: PEG 2 L the evening before and 2 L the day of colonoscopy (PEG 2+2L+bisacodyl), or 4 L and 2 L (PEG 4+2L+bisacodyl). All patients followed a low-fiber diet on both the third and second day before the procedure, followed by a clear fluid diet the day before and the morning of the colonoscopy. The primary outcome was adequate bowel preparation, defined as a Boston Bowel Preparation Scale total score of 6 or higher, with all segment scores of 2 or higher. Secondary outcomes included adenoma detection rate, advanced adenoma detection rate, sessile serrated lesion detection, cecal intubation rate, tolerability, and adverse events. RESULTS: A total of 196 subjects were randomized at 4 academic centers in Canada (mean age, 60.7 y; SD, 11.4 y; 44.9% were women). There were no significant differences between the PEG 2+2L+bisacodyl and the PEG 4+2L+bisacodyl groups in achieving adequate bowel preparation (91.2% vs 87.6%; P = .44). There were no significant differences with regard to mean adenoma detection rate (37.4% vs 31.5%; P = .41), advanced adenoma detection rate (18.7% vs 11.2%; P = .16), sessile serrated lesion detection (8.8% vs 5.6%; P = .41), and cecal intubation rate (96.7% vs 92.1%; P = .19). The 2 regimens were similarly well tolerated, but PEG 2+2L+bisacodyl was associated with a higher willingness to repeat the bowel preparation (91.2% vs 66.2%; P < .001). CONCLUSIONS: Split-dose 4 L-PEG with 15 mg bisacodyl, along with dietary restrictions, has similar efficacy as a higher-volume preparation, and should be considered for patients who previously failed bowel preparation (ClinicalTrials.gov number, NCT02976805).

Reliability of the Endoscopic Ultrasound Ulcerative Colitis (EUS-UC) score for assessment of inflammation in patients with ulcerative colitis.

Background and study aims Endoscopic ultrasound (EUS) may be a useful modality for disease assessment and risk stratification in ulcerative colitis. We assessed the reliability of a newly developed EUS index of inflammation called the EUS-Ulcerative Colitis (EUS-UC) score. Patients and methods The EUS-UC score components include total wall thickness, hyperemia, and depth of inflammation (DOI). Three blinded expert endosonographers assessed EUS videos of 58 patients with UC in triplicate. Intra- and inter-rater reliability of the hyperemia and DOI component scores were estimated using intra-class correlation coefficients (ICCs). Total wall thickness reliability estimates could not be assessed in this study. The ICCs were compared to the original indices from which they were derived. Results For hyperemia, the inter-class ICC was "moderate" at 0.556 (95 % CI = 0.434-0.651) and the intra class ICC was "almost perfect" at 0.884 (95 % CI = 0.835-0.920). The newly defined hyperemia score performed better than the original index from which is was derived. The DOI inter-class ICC was "fair" at 0.335 (95 % CI = 0.201-0.464), and the intra-class ICC was "substantial" at 0.732 (95 % CI = 0.642-0.802). The DOI reliability estimates were similar to the original index from which it was derived. Conclusions The hyperemia component of the EUS-UC score performed significantly better than the original index from which it was derived, but the reliability of the DOI component was suboptimal. Intra-class correlation was excellent for both components. The EUS-UC score is a promising instrument for assessment of UC and further validation is required.

External Validation of the Oakland Score to Assess Safe Hospital Discharge Among Adult Patients With Acute Lower Gastrointestinal Bleeding in the US.

Importance: Lower gastrointestinal bleeding (LGIB), which manifests as blood in the colon or anorectum, is a common reason for hospitalization. In most patients, LGIB stops spontaneously with no in-hospital intervention. A risk score that could identify patients at low risk of experiencing adverse outcomes could help improve the triage process and allow greater numbers of patients to receive outpatient management of LGIB. Objective: To externally validate the Oakland Score, which was previously developed using a score threshold of 8 points to identify patients with LGIB who are at low risk of adverse outcomes. Design, Setting, and Participants: This multicenter prognostic study was conducted in 140 US hospitals in the Hospital Corporation of America network. A total of 46 179 adult patients (aged ≥16 years) admitted to the hospital with a primary diagnosis of LGIB between June 1, 2016, and October 15, 2018, were initially identified using diagnostic codes. Of those, 51 patients were excluded because they were more likely to have upper gastrointestinal bleeding, leaving a study population of 46 128 patients with LGIB. For the statistical analysis of the Oakland Score, an additional 8061 patients were excluded because they were missing data on Oakland Score components or clinical outcomes, resulting in 38 067 patients included in the analysis. The study used area under the receiver operating characteristic curves with 95% CIs for external validation of the model. Sensitivity and specificity were calculated for each score threshold (≤8 points, ≤9 points, and ≤10 points). Data were analyzed from October 16, 2018, to September 4, 2019. Main Outcomes and Measures: Identification of patients who met the criteria for safe discharge from the hospital and comparison of the performance of 2 score thresholds (≤8 points vs ≤10 points). Safe discharge was defined as the absence of blood transfusion, rebleeding, hemostatic intervention, hospital readmission, and death. Results: Among 46 128 adult patients with LGIB, the mean (SD) age was 70.1 (16.5) years; 23 091 patients (50.1%) were female. Of those, 22 074 patients (47.9%) met the criteria for safe discharge from the hospital. In this group, the mean (SD) age was 67.9 (18.1) years, and 11 056 patients (50.1%) were female. In the statistical analysis of the Oakland Score, which included only the 38 067 patients with complete data, the area under the receiver operating characteristic curve for safe discharge was 0.87 (95% CI, 0.87-0.87). An Oakland Score threshold of 8 points or lower identified 3305 patients (8.7%), with a sensitivity and specificity for safe discharge of 98.4% and 16.0%, respectively. Extension of the Oakland Score threshold to 10 points or lower identified 6770 patients (17.8%), with a sensitivity and specificity for safe discharge of 96.0% and 31.9%, respectively. Conclusions and Relevance: In this study, the Oakland Score consistently identified patients with acute LGIB who were at low risk of experiencing adverse outcomes and whose conditions could safely be managed without hospitalization. The score threshold to identify low-risk patients could be extended from 8 points or lower to 10 points or lower to allow identification of a greater proportion of low-risk patients.

Insertion of percutaneous endoscopic gastrostomy tubes with jejunal extensions using the "wedge" technique: a novel method to prevent retrograde tube migration into the stomach.

Background and study aim In percutaneous endoscopic gastrostomy (PEG) with jejunal extension (PEGJ) procedures, retrograde migration of the jejunal extension tube into the stomach during endoscope withdrawal is a frustrating problem. We describe the novel "wedge" technique for inserting the jejunal extension tube, utilizing single-balloon enteroscopy to anchor it in place. Patients and methods Prospective 1-year study of consecutive patients undergoing PEGJ insertion at a single tertiary care center. The primary outcome was number of pyloric intubations required to place the jejunal extension tube. Secondary outcomes included success rate, time, and complications related to jejunal extension tube insertion. Results 17 patients underwent the procedure. The jejunal extension tube was inserted at the first attempt in 15 patients (88.2 %) and 2 required another pyloric intubation. Abdominal X-ray showed that all PEGJ tubes were successfully seated in the proximal jejunum. The mean (SD) time required for jejunal extension insertion was 16.9 (8.6) minutes. Two adverse events occurred due to PEG insertion although none were related to the jejunal extension insertion itself. Conclusions: The "wedge" technique is an effective and easy method for inserting a jejunal extension tube after PEG insertion.

Automated Bone Age Analysis with Lossy Image Files.

BACKGROUND: In our U.S. Department of Defense hospital system, pediatric endocrinology and radiology resources to evaluate bone age radiographs are limited. Our tertiary care center provides expert specialty support to remotely stationed beneficiaries at more than 30 Department of Defense medical facilities using a well-established, asynchronous, Health Insurance Portability and Accountability Act compliant system that allows for physician-to-physician teleconsultation. Up to 14% of these teleconsultations are for endocrinology assessment, many of which include bone age analysis. We sought to evaluate the feasibility of using an automated bone age analysis program using the file format most commonly provided to us, lossy JPEG image files saved at lower quality, to improve access to our consultation services. METHODS: All patients seen in the Tripler Army Medical Center pediatric endocrinology clinic, who were being evaluated for poor growth during the 2-month study period and who had a bone age film performed at Tripler Army Medical Center during that time, were eligible to have their deidentified bone age films analyzed. We imported lossy JPEG bone age image files from our hospital web viewer to BoneXpert, version 2.1, using a fully automated, custom built system that reconstructed each file's true resolution and then packaged the original image into a Digital Imaging and Communications in Medicine header. The original JPEG files were saved at 70% quality. Bone age readings were compared between our pediatric endocrinologists (ENDO), pediatric radiologists (RADS), and BoneXpert (BONE). Additionally, adult height prediction from ENDO and BONE were compared. FINDINGS: 35 bone age images were evaluated over a 2-month period. Most patients were being evaluated for idiopathic short stature or growth hormone deficiency. Analysis of variance showed no significant differences in mean bone age readings between the 3 groups (mean bone age reading = 9.0, 9.1, and 9.1 years for ENDO, RADS, and BONE, respectively, p = 0.827). Mean (SD) differences between physician and software bone age readings were -0.09 (0.89) years (ENDO) and -0.03 (1.01) years (RADS). Mean difference for adult height predictions was only -0.2 cm (p = 0.806). DISCUSSION: Automated analysis of lossy JPEG files of bone age images using the BoneXpert software appears to be feasible and accurate. Larger studies are needed to validate these results.

A giant among dwarfs: a new species of galago (Primates: Galagidae) from Angola.

OBJECTIVES: Based on vocalization recordings of an unknown galago species, our main objectives were to compare morphology and call structure with known closely-related taxa and describe a new species of galago. MATERIALS AND METHODS: We conducted field surveys in three forest habitats along the escarpment region in western Angola (Kumbira Forest, Bimbe Area, and Northern Scarp Forest), and examined galago specimens from museums worldwide. We digitized and analyzed calls using Avisoft SASLab Pro software. We also compared museum specimens from Angola with other Galago and Galagoides specimens, and conducted comparative analyses (ANOVA and between group principle component analysis) based on a set of twelve linear measurements of skulls and teeth. RESULTS: We describe the new species to which we give the name Angolan dwarf galago, Galagoides kumbirensis sp. nov. The new species has a loud and characteristic crescendo call, used by other Galagoides spp. (sensu stricto) in West Africa to attract companions and repel rivals. However, this call shows species-typical differences from its closest relatives. Galagoides kumbirensis sp. nov. is also distinguished by differences in the skull morphology, pelage color and facial markings, as well as a larger body size, similar to that of Galago moholi, which is not known to be sympatric. CONCLUSION: This discovery points to the importance of Angolan forests as refuges for endemic biodiversity. These forests are under severe threat from overexploitation, and there is an urgent need to establish conservation measures and designate protected areas.

Effectiveness and safety of serial endoscopic ultrasound-guided celiac plexus block for chronic pancreatitis.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound - guided celiac plexus block (EUS-CPB) is an established treatment for pain in patients with chronic pancreatitis (CP), but the effectiveness and safety of repeated procedures are unknown. Our objective is to report our experience of repeated EUS-CPB procedures within a single patient. PATIENTS AND METHODS: A prospectively maintained EUS database was retrospectively analyzed to identify patients who had undergone more than one EUS-CPB procedure over a 17-year period. The main outcome measures included number of EUS-CPB procedures for each patient, self-reported pain relief, duration of pain relief, and procedure-related adverse events. RESULTS: A total of 248 patients underwent more than one EUS-CPB procedure and were included in our study. Patients with known or suspected CP (N = 248) underwent a mean (SD) of 3.1 (1.6) EUS-CPB procedures. In 76 % of the patients with CP, the median (range) duration of the response to the first EUS-CPB procedure was 10 (1 - 54) weeks. Lack of pain relief after the initial EUS-CPB was associated with failure of the next EUS-CPB (OR 0.17, 95 %CI 0.06 - 0.54). Older age at first EUS-CPB and pain relief after the first EUS-CPB were significantly associated with pain relief after subsequent blocks (P = 0.026 and P = 0.002, respectively). Adverse events included peri-procedural hypoxia (n = 2) and hypotension (n = 1) and post-procedural orthostasis (n = 2) and diarrhea (n = 4). No major adverse events occurred. CONCLUSIONS: Repeated EUS-CPB procedures in a single patient appear to be safe. Response to the first EUS-CPB is associated with response to subsequent blocks.

A review of factors affecting vaccine preventable disease in Japan.

Japan is well known as a country with a strong health record. However its incidence rates of vaccine preventable diseases (VPD) such as hepatitis B, measles, mumps, rubella, and varicella remain higher than other developed countries. This article reviews the factors that contribute to the high rates of VPD in Japan. These include historical and political factors that delayed the introduction of several important vaccines until recently. Access has also been affected by vaccines being divided into government-funded "routine" (eg, polio, pertussis) and self-pay "voluntary" groups (eg, hepatitis A and B). Routine vaccines have higher rates of administration than voluntary vaccines. Administration factors include differences in well child care schedules, the approach to simultaneous vaccination, vaccination contraindication due to fever, and vaccination spacing. Parental factors include low intention to fully vaccinate their children and misperceptions about side effects and efficacy. There are also provider knowledge gaps regarding indications, adverse effects, interval, and simultaneous vaccination. These multifactorial issues combine to produce lower population immunization rates and a higher incidence of VPD than other developed countries. This article will provide insight into the current situation of Japanese vaccinations, the issues to be addressed and suggestions for public health promotion.

Synthesis and characterization of porous shell-like nano hydroxyapatite using cetrimide as template.

Macromolecules of various surfactants and polymers are being used to prepare nano hydroxyapatites (HAp) of varied morphology. Here we report the successful preparation of shell-like nano HAp spheres with fine morphology, uniform size around 200 nm, and stoichiometry ratio 1.7 with 56% nano- (<5 nm) and 44% mesoporosity using the surfactant tetradecyltrimethylammonium bromide (Cetrimide), which was not reported earlier. The critical micelle concentration (CMC) of Cetrimide was calculated as 3.88 mM at room temperature, and based on that, the other parameters of the experiment were determined. The experiment was conducted at ambient temperature and normal pressure without any temperature control, which was considered a crucial parameter in the earlier works. Thus, this method is suitable to bulk production of HAp. All the inspections confirm the successful preparation of shell-like nano HAp spheres that are suitable for biomedical applications.

Intravascular hemolysis secondary to aorto-atrial fistula presenting as red urine.

Intravascular hemolysis is a rare but potentially life threatening cause of red urine characterized by brisk hemolysis and release of large amounts of hemoglobin into the urine. We present an unusual case of red urine in a 20-year-old male who was subsequently diagnosed with intravascular hemolysis due to an aorto-atrial fistula. Fistula formation was likely secondary to a recently implanted atrial septal occluder, which is a reported but exceedingly rare complication of the device. We discuss the diagnostic approach to hemolytic anemia and conclude with a literature review of other cases of device associated fistula formation and hemolysis.

Deletions of NRXN1 (neurexin-1) predispose to a wide spectrum of developmental disorders.

Research has implicated mutations in the gene for neurexin-1 (NRXN1) in a variety of conditions including autism, schizophrenia, and nicotine dependence. To our knowledge, there have been no published reports describing the breadth of the phenotype associated with mutations in NRXN1. We present a medical record review of subjects with deletions involving exonic sequences of NRXN1. We ascertained cases from 3,540 individuals referred clinically for comparative genomic hybridization testing from March 2007 to January 2009. Twelve subjects were identified with exonic deletions. The phenotype of individuals with NRXN1 deletion is variable and includes autism spectrum disorders, mental retardation, language delays, and hypotonia. There was a statistically significant increase in NRXN1 deletion in our clinical sample compared to control populations described in the literature (P = 8.9 x 10(-7)). Three additional subjects with NRXN1 deletions and autism were identified through the Homozygosity Mapping Collaborative for Autism, and this deletion segregated with the phenotype. Our study indicates that deletions of NRXN1 predispose to a wide spectrum of developmental disorders.

A comparative study of tissue transglutaminase antibodies and endomysium antibody immunofluorescence in routine clinical laboratory practice.

BACKGROUND: The demand for screening for coeliac disease has grown rapidly over the last few years. Laboratories depending on immunofluorescence assays are faced with an increasing workload using a labour-intensive test, and an alternative to this test has been sought. This study compares tissue transglutaminase (TTG) and endomysium antibodies (EMA) in a routine clinical laboratory situation. METHODS: An immunofluorescence IgA EMA test was compared with a guinea pig TTG antibody ELISA for 816 unselected requests for gut antibody screening. Discrepant results were investigated more fully using a variety of human source TTG antigen kits. RESULTS: Guinea pig TTG ELISA and EMA assays showed agreement for 93.6% of samples. Four samples were misclassified and 48 samples gave false positive TTG results. Study of 46 EMA samples (this group included 39 of the 'discrepant' negative EMA/positive guinea pig TTG group) using three different human purified and/or recombinant TTG sources showed that 42 patients had no TTG antibodies using human sources, three were misclassified and one patient had negative EMA and positive TTG results that could not be readily explained. Further study of 32 EMA positive samples showed almost complete agreement between the human source TTG kits. CONCLUSIONS: We can recommend the replacement of EMA with ELISA for TTG antibodies for the routine screening for coeliac disease, but all positive TTG antibodies should still be followed up with IgA EMA and samples should be screened for IgA deficiency.

Acetaminophen-induced hepatotoxicity in mice lacking inducible nitric oxide synthase activity.

We recently reported that nitrotyrosine and acetaminophen (APAP)-cysteine protein adducts colocalize in the hepatic centrilobular cells following a toxic dose of APAP to mice. Whereas APAP-adducts are formed by reaction of the metabolite N-acetyl-p-benzoquinone imine with cysteine, nitrotyrosine residues are formed by reaction of tyrosine with peroxynitrite. Peroxynitrite is formed from nitric oxide (NO) and superoxide. This manuscript examines APAP (300 mg/kg) hepatotoxicity in mice lacking inducible nitric oxide synthase activity (NOS2 null or knockout mice; C57BL/6-Nos2(tm1Lau)) and in the wildtype mice. In a time course the ALT levels in the exposed NOS2 null mice were approximately 50% of the wildtype mice; however, histological examination of liver sections indicated similar levels of centrilobular hepatic necrosis in both wild-type and NOS2 null mice. Serum nitrate plus nitrite levels (NO synthesis) were identical in saline-treated NOS2 null and wild-type mice (53 +/- 2 microM). APAP increased NO synthesis in wild-type mice only. The increases paralleled the increases in ALT levels with peak levels of serum nitrate plus nitrite at 6 h (168 +/- 27 microM). In wild-type mice hepatic tyrosine nitration was greatly increased relative to saline treated controls. Tyrosine nitration increased in NOS2 null mice also, but the increase was much less. APAP increased hepatic malonaldehyde levels (lipid peroxidation) in NOS2 null mice only. The results suggest the presence of multiple pathways to APAP-mediated hepatic necrosis, one via nitrotyrosine, as in the wild-type mice, and another that is not dependent upon inducible nitric oxide synthase activity, but which may involve increased superoxide.

Western blot analysis for nitrotyrosine protein adducts in livers of saline-treated and acetaminophen-treated mice.

The hepatic centrilobular necrosis produced by the analgesic/antipyretic acetaminophen correlates with metabolic activation of the drug leading to its covalent binding to protein. However, the molecular mechanism of the toxicity is not known. Recent immunohistochemical analyses using an antinitrotyrosine antiserum indicated that nitrotyrosine protein adducts co-localized with the acetaminophen-protein adducts in the centrilobular cells of the liver. Nitration of proteins is believed to occur by peroxynitrite, a substance formed by the rapid reaction of superoxide with nitric oxide. Nitric oxide and superoxide may be formed by activated Kupffer cells or by other cells. Because we were unable to successfully utilize the commercial antiserum in Western blot analyses of liver fractions, we developed a new antiserum. With our antiserum, liver fractions from saline-treated control and acetaminophen-treated mice were successfully analyzed for nitrated proteins. The immunogen for this new antiserum was synthesized by coupling 3-nitro-4-hydroxybenzoic acid to keyhole limpet hemocyanin. A rabbit immunized with this adduct yielded a high titer of an antiserum that recognized BSA nitrated with peroxynitrite. Immunoblot analysis of nitrated BSA indicated that nitrotyrosine present in a protein sample could be easily detected at levels of 20 pmoles. Immunohistochemical analyses indicated that nitrotyrosine protein adducts were detectable in the centrilobular areas of the liver. Immunoblot analysis of liver homogenates from both saline-treated and acetaminophen-treated mice (300 mg/kg) indicate that the major nitrotyrosine protein adducts produced have molecular weights of 36 kDa, 44 kDa, and 85 kDa. The 85-kDa protein stained with the most intensity. The hepatic homogenates of the acetaminophen- treated mice showed significantly increased levels of all protein adducts.

Pretreatment of mice with macrophage inactivators decreases acetaminophen hepatotoxicity and the formation of reactive oxygen and nitrogen species.

Hepatotoxic doses of acetaminophen to mice produce not only acetaminophen-protein adducts in the centrilobular cells of the liver, but nitrotyrosine-protein adducts in the same cells, the site of the necrosis. Nitration of tyrosine occurs with peroxynitrite, a species formed by reaction of nitric oxide (NO.) with superoxide (O2. -). Because NO. and O2.- may be produced by activated Kupffer cells and/or infiltrated macrophages, we pretreated mice with the macrophage inactivators/depeleters gadolinium chloride (7 mg/kg, intravenously [iv]) or dextran sulfate (10 mg/kg, iv) 24 hours before administration of acetaminophen (300 mg/kg). Mice treated with acetaminophen plus gadolinium chloride, or acetaminophen plus dextran sulfate, had significantly less evidence of hepatotoxicity as evidenced by lower serum alanine transaminase (ALT) levels (28 +/- 1 IU/L and 770 +/- 240 IU/L, respectively) at 8 hours compared with acetaminophen (6,380 +/- 408 IU/L). Analysis of hepatic homogenates for acetaminophen-protein adducts at 2 hours, a time of maximal covalent binding and before hepatocyte lysis, indicated that these pretreatments did not decrease covalent binding. Western blot analysis for the macrophage marker protein F4/80 in homogenates revealed not only the expected decrease by the macrophage inactivators/depleters, but also an apparent increase in acetaminophen-only-treated mice. At 8 hours nitrotyrosine-protein adducts were present in the acetaminophen-only-treated mice, but not in the acetaminophen plus gadolinium chloride-treated mice, or acetaminophen plus dextran sulfate-treated mice. High levels of heme-protein adducts, a measure of oxidative stress, were detected in livers of the 8 hour acetaminophen-only-treated mice. These data suggest that acetaminophen hepatotoxicity is mediated by an initial metabolic activation and covalent binding, and subsequent activation of macrophages to form O2.-, NO., and peroxynitrite. Nitration of tyrosine correlates with toxicity.

Preventive care in diabetes mellitus. Current practice in urban health-care system.

Early identification and treatment of complications of diabetes mellitus may reduce the severity of the complications. As part of a program to reduce these complications in the Denver Department of Health and Hospitals patient population, our study determined how frequently preventive care, e.g., fundoscopic examinations, referral to an ophthalmologist, foot examinations, and assessment of cardiovascular risk factors, was provided to diabetic patients. With the use of billing records to identify a large sample of diabetic patients, a chart review of 544 patients was conducted. During the study year, the mean +/- SE number of visits to primary-care clinics was 5.7 +/- 0.22, with 86.4% having at least one visit. Most diabetic patients were seen by primary-care physicians; only 9% received care in a specialized diabetes clinic. Despite frequent primary-care visits, most diabetic patients in this county health-care system did not have documentation of care to detect complications of diabetes mellitus, and referral services for detection and treatment of these complications were infrequently used. Moreover, among patients seen on greater than or equal to 10 occasions in a primary-care setting, preventive care was not provided to 30% of the patients. Preventive care does not appear to be a regular part of a primary-care visit for most of the diabetic patients in this study.