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Alanine aminopeptidase and beta 2-microglobulin excretion in patients receiving vancomycin and gentamicin.

The effects of vancomycin, gentamicin, and combination vancomycin-gentamicin treatments on alanine aminopeptidase (AAP) and beta 2-microglobulin (beta 2M) elimination in 30 hospitalized patients were assessed and compared with elimination in a control group. Twenty-four-hour urine excretion values for AAP and beta 2M were determined on treatment day 1 and day 5 for patients receiving the three treatment regimens and for the control group. AAP excretion values for the vancomycin-treated group were not found to be statistically different from those of the control group. Both the gentamicin and the vancomycin-gentamicin groups had statistically higher AAP excretion values on treatment day 1 as well as on treatment day 5 when compared with the vancomycin and control groups. AAP excretion on day 5 of treatment was highest for the vancomycin-gentamicin group. Overall, beta 2M elimination was variable in all treatment groups. Although the beta 2M values were elevated as early as day 1 in all treatment groups, they were significantly elevated only in the vancomycin-gentamicin group on day 1 and only in the gentamicin group on day 5 compared with the vancomycin and the control groups. AAP appears to be a sensitive indicator of renal tubular damage. The combination of vancomycin and gentamicin results in greater AAP excretion than does either agent alone.

Adolescent↗

A novel dispersin protein in enteroaggregative Escherichia coli.

Enteroaggregative Escherichia coli (EAEC) is a diarrheal pathogen defined by its characteristic aggregative adherence (AA) to HEp-2 cells in culture. We have previously shown that EAEC strains secrete a 10-kDa protein that is immunogenic in a human EAEC challenge model. We report here that this protein is encoded by a gene (called aap) lying immediately upstream of that encoding the AggR transcriptional activator, and that aap is under AggR control. The product of aap has a typical signal sequence and is secreted to the extracellular milieu, where it remains noncovalently attached to the surface of the bacterium. EAEC aap mutants aggregate more intensely than the wild-type parent in a number of assays, forming larger aggregates and fewer individual bacteria. Infection of colonic biopsies with wild-type EAEC strain 042 and its aap mutant revealed more dramatic autoagglutination of the mutant compared with the wild-type parent. Our data suggest that the aap gene product participates in formation of a surface coat that acts to disperse the bacteria, thus partially counteracting aggregation mediated by aggregative adherence fimbriae. We have therefore named the aap gene product "dispersin," and we propose that it may be representative of a functional class of colonization factors. Since dispersin is expressed in vivo, is highly immunogenic, and is present in most EAEC strains, it holds considerable promise as an EAEC immunogen.

Agglutination↗

Clinical applications of the Adelaide Activities Profile.

OBJECTIVE: The Adelaide Activities Profile (AAP) was developed from the Frenchay Activities Index, and has been shown to be a valid measure of the lifestyle activities of elderly people. The goals of the current study were to illustrate the value of applying the AAP in the clinical setting, and to demonstrate the relationship of the AAP to the use of formal services. DESIGN: Data were collected as part of the Australian Longitudinal Study of Ageing (ALSA). A community sample, stratified by age and sex, was chosen to be representative of the elderly population of Adelaide, South Australia. PARTICIPANTS: A sample of 1799 community-dwelling people aged 70 years and over. MEASURES: Lifestyle activities were assessed with the AAP, which provides measures of activity on four scales: domestic chores, household maintenance, service to others, and social activities. Participants were defined as users of formal services if they were active clients of any of the Domiciliary Care and Rehabilitation Services, Meals-on-Wheels, or the Royal District Nursing Society. RESULTS: Age and sex norms for the AAP were provided, and the clinical value of using these norms was illustrated by two contrasting case studies. Users of formal services had lower activity levels than nonusers for all AAP scales, particularly household maintenance and domestic chores. CONCLUSIONS: The AAP is a valuable addition to the standard battery of instruments used in the assessment of elderly people, and has clinical application as both a health outcome measure and an indicator of the need for intervention.

Activities of Daily Living↗

Atypical antipsychotic agents and increased risk of diabetes: class action or differential action?

Atypical antipsychotic (AAP) agents are useful in treating patients with schizophrenia and other psychosis. Their advantages are the low incidence of extrapyramidal side effects, and possible amelioration of negative, cognitive and mood symptoms. Occurrence of diabetes after AAP drug administration is of concern as patients do not often recognise their symptoms, physicians may fail to diagnose early, with consequent morbidity and mortality. The symptoms of psychosis, including lack of insight and motivation, may decrease the ability of schizophrenic patients to communicate potential health problems. Whether or not AAP drugs induce diabetes and, if they do, if it is a class action or a differential action, is often debated. Clinical evidence on AAP drug-induced diabetes is mounting. With their discontinuation, the diabetes often dissipates, but reappears when they are started again, thereby implicating the AAP drugs in the development of diabetes. There is still dispute regarding the differential effect of the various AAP drugs in their ability to produce diabetes. Although not scientifically proven, available evidence seems to indicate that clozapine and olanzapine may have a higher propensity to induce diabetes compared with other AAP drugs.

Antipsychotic Agents↗

Effects of phenobarbital on aniline metabolism in primary liver cell culture of rats with ethionine-induced liver disorder.

In experiment 1, the amount of aniline (AN) metabolites in the primary cell culture medium of the liver cells obtained from ethionine (ET)-treated rats was compared with that of the control (normal) rats. Although the metabolites detected in both groups were p-aminophenol (p-AP), N-acetyl-p-AP (AAP), acetoanilide (AAN), AAP-glucuronide (AAPG), phenylhydroxylamine sulfate (PHAS) and p-AP-glucuronide (p-APG), the amount of AAP was lower and that of p-APG was markedly higher in the ET-treated rats than in the control rats. In experiment 2, phenobarbital (PB) was orally administered to the ET-treated and control rats at a dose of 100 mg/kg. The time course changes in AN metabolites in the primary cell culture medium of liver cells obtained at 2 or 48 hr after PB treatment were compared with those without PB treatment. In the ET-treated rats, the amount of PHAS was slightly higher at 2 hr after PB treatment, and that of AAP was lower and that of p-APG was higher at 48 hr after PB treatment as compared with those without PB treatment. In the control rats, the amounts of AAP, AAN, p-AP and p-APG at 2 hr after PB treatment remained lower than those without PB treatment, and that of AAP was markedly lower and that of p-APG was higher at 48 hr after PB treatment as compared with those without PB treatment. These findings indicated greater detoxication in the primary liver cell culture in the ET-treated rats than in the control rats. Furthermore, detoxication was greater in the primary cell culture of liver cell obtained from the ET-treated rats after PB treatment than from those without PB treatment, because the production of acetylates (AAP) decreased and p-APG increased (induction of conjugated enzyme) in the PB treatment group.

Acetaminophen↗

In which journals will pediatricians find the best evidence for clinical practice?

OBJECTIVE: The objective of this study was to identify the journals that contain the best evidence relating to clinical pediatric practice, thus enabling general pediatricians and pediatric trainees to identify the best quality evidence more efficiently and to select journals for general reading more judiciously. METHODS: In the first of three strategies, journal citations from completed systematic reviews using topic headings of pediatric(s), child, infant(s), newborn, neonate(s), neonatology, and adolescent(s) in the Cochrane Database of Systematic Reviews (CDSR) in the 1997, Issue 4, Cochrane Library were collected. In the second strategy, journal citations from American Academy of Pediatrics' (AAP) policy statements from 1994 to 1996 found in the AAP policy reference guide were collected. In the third strategy, journal citations from the Canadian Paediatric Society (CPS) statements from 1990 to 1997 found in Pediatrics and Child Health were collected. Topics related to tertiary neonatology, nonphysician health care professionals, public health policy, ethics, and nonjournal citation sources were excluded. All statements with no references were excluded. Journal citations in CDSR with no pediatric subjects and citation of AAP policy statements cited in AAP policy statements were excluded. The number of citations from the journal cited most frequently, from journals that represented approximately 10% of all citations and from the 10 journals cited most frequently were expressed as a percent of total citations and a 95% CI was calculated. RESULTS: Using all three strategies (CDSR, AAP, and CPS), the journal cited most frequently was Pediatrics. Using the CDSR strategy (n = 234), citations from Pediatrics represented 6.0% of the total (95% CI: 3.0%, 9.0%), using the AAP strategy (n = 930), citations from Pediatrics represented 11. 4% of the total (95% CI: 9.4%, 13.4%), and using the CPS strategy (n = 873), citations from Pediatrics represented 11.9% of the total (95% CI: 9.8, 14.1). Using the CDSR strategy, citations from the 10 journals cited most frequently made up 38.9% of the total citations (95% CI: 32.7%, 45.1%), using the AAP strategy, citations from the 10 journals cited most frequently made up 42.3% of the total citations (95% CI: 39.3%, 45.3%), and using the CPS strategy, citations from the 10 journals cited most frequently made up 60.6% of the total citations (95% CI: 57.4, 63.8). In the CPS strategy, citations from the Journal of Pediatrics represented 10.2% of the total citations (95% CI: 8.2, 12.2) and citations from New England Journal of Medicine represented 9.5% of the total citations (95% CI: 7.6, 11.5). A total of 7 journals were found to be among the 10 cited most frequently using all three strategies (in alphabetical order): Archives of Diseases in Childhood, British Medical Journal, Journal of the American Medical Association, Journal of Pediatrics, Lancet, New England Journal of Medicine, and Pediatrics. CONCLUSIONS: This study provides the general pediatrician and pediatric trainee with a strategy to identify efficiently a significant proportion of the best evidence on pediatric practice by restricting searches and reading to a limited number of journals. It also highlights the fact that the best quality evidence on pediatric practice is found in a large number of medical journals.

Canada↗

Well-child visits in the video age: pediatricians and the American Academy of Pediatrics' guidelines for children's media use.

OBJECTIVES: The goal of this study was to evaluate awareness of, agreement with, and implementation of the American Academy of Pediatrics (AAP) media use guidelines among pediatricians. Pediatricians' beliefs about several media effects were also measured, as was their own media use. Pediatricians were also asked about how often they make media recommendations as part of anticipatory guidance during well-child visits, as well as the perceived efficacy of and barriers to making such recommendations. DESIGN: A cross-sectional survey mailed to all members of the Minnesota chapter of the AAP. PARTICIPANTS: A total of 365 pediatricians completed the survey. MEASURES: The 58-item survey assessed familiarity with, agreement with, and implementation of each of 3 AAP recommendations, to limit children's media time, to discourage television (TV) viewing among children <2 years of age, and to encourage alternative entertainment for children. Pediatricians were also asked about the perceived effectiveness of and barriers to guideline implementation. In addition, pediatricians were asked to report their own TV viewing habits and their opinions about how much media affect children's health and behavior. RESULTS: Most pediatricians were familiar with and also agreed with the 3 AAP recommendations. Their agreement may stem from the fact that pediatricians almost universally believe that children's media use negatively affects children in many different areas, including children's aggressive behavior, eating habits, physical activity levels, risk for obesity, high-risk behaviors, and school performance. Pediatricians were most likely to have encouraged alternative entertainment and were least likely to have discouraged TV viewing for children <2 years of age. The majority of pediatricians provided all 3 recommendations to parents at least sometimes. Most pediatricians reported that their recommendations were at least a little effective when they did make them. The most frequent barrier pediatricians reported facing was a lack of parental motivation or support for the recommendations, with approximately one-third of pediatricians also citing a lack of time and a sense of futility in affecting patients' media habits as barriers. Finally, pediatricians who watched the greatest amounts of TV were significantly more likely than those who watched less to think that the AAP recommendation to limit children's total media time to no more than 1 to 2 hours per day is unrealistic, whereas those who watched less were more likely to agree with the recommendation. CONCLUSIONS: Results suggest that the efforts of the AAP in reaching pediatricians have been largely successful, with the majority of pediatricians in Minnesota being aware of and agreeing with the 3 major recommendations suggested by the AAP policy statement on children, adolescents, and television. However, implementation of the recommendations could be improved, especially because pediatricians usually think that the recommendations are at least a little effective when made. Strategies for overcoming barriers to making recommendations need to be addressed, including the sense of futility in affecting media use that some pediatricians may feel.

Adolescent↗

Diagnostic value of plain abdominal radiographs in acute appendicitis in children.

OBJECTIVE: The plain film of the abdomen (PAX) is still utilised in the diagnosis of acute appendicitis (Aap). Aim of this study was to evaluate the value of PAX in the diagnosis of Aap in children, since it continues to be a controversial subject. DESIGN: A retrospective study. SETTING: Department of Paediatric Surgery, Gazi University Medical School. PATIENTS: The histopathological diagnoses and PAX of 213 children (mean age 9-6 years) operated for acute right-lower quadrant pain were evaluated retrospectively. There were 181 patients with Aap and 32 with normal appendix. METHODS: The rate of detection of overall thirteen roentgenographic criteria defined in various reports in medical literature as indicating appendicitis were noted and compared with histopathological diagnoses. The PAX which revealed one or more of these signs in combination was considered to be positive for Aap. Data was analysed statistically and sensitivity, specificity and positive and negative predictive values of PAX in the diagnosis of Aap were determined. RESULTS: Roentgenographic sign(s) were detected in 170 (79%) cases, 18 without Aap. The most frequent were lumbar scoliosis with left-sided convexity (50%) and small intestinal air-fluid levels (32%). In 39 cases, 25 with Aap, no sign(s) was detected. In all of the perforated cases, at least one of the determined criteria was seen. The percentage of roentgenographic signs found in cases with and without appendicitis was different significantly (p<0.01). The negative predictive value of PAX in the diagnosis of acute appendicitis was 32.5% and positive predictive value was 89%. CONCLUSION: PAX could he helpful in diagnosis in children with suspected acute appendicitis.

Acute Disease↗

Community Access to Child Health (CATCH) in the historical context of Community Pediatrics.

OBJECTIVES: As part of the evaluation of the American Academy of Pediatrics (AAP) Community Access to Child Health (CATCH), to 1) identify, retrospectively, the actual chronology of activities undertaken through CATCH, and 2) review its antecedents within the AAP, and its predecessor program-Healthy Children. METHODS: Key informant telephone interviews with 14 national leaders in CATCH were conducted. Relevant program and administrative files and other documents were reviewed. AAP staff assisted the authors in preparing a detailed chronology of Healthy Children and CATCH activities and events from spring 1988 through summer 1996. RESULTS AND CONCLUSIONS: A decade of change in the AAP, under the acronym CATCH began in the late 1980s. The formation of the AAP's Partnership for Children and the Access to Care for Children Initiative, combined with the decision by the Robert Wood Johnson Foundation to transfer the funding of Healthy Children to the AAP, underpinned the changes. The Foundation's decision provided the resources and stimulus for the expansion and increased recognition of Community Pediatrics at the national AAP office, culminating in the establishment of the Department of Community Pediatrics in mid-1994. A national program of pediatrician-led, community-based programs and supportive services was launched, other resources were attracted, and a philosophical shift in defining the role of the pediatrician was put forward. A responsibility toward all children within the community was included in the role of the pediatrician, as well as caring for the individual child within a community context.

Child↗

Characterization of high affinity binding between laminin and Alzheimer's disease amyloid precursor proteins.

BACKGROUND: In vivo amyloid formation apparently involves several extracellular matrix components that are usually found associated with basement membranes. These include laminin, heparan sulfate proteoglycan, collagen type IV, and entactin. These components have also been found in neuritic plaques. We have therefore been examining interactions between extracellular matrix components and the Alzheimer's amyloid precursors (AAPs). EXPERIMENTAL DESIGN: Binding interactions of laminin with AAP-695, -751, and -770 were examined using a solid phase enzyme-linked immunosorbent assay technique. RESULTS: Objective, quantitative analyses of the laminin AAP-695, -751, and -770 binding data reveal two binding sites for laminin, with Kd values of 1 x 10(-10) M and 1 x 10(-8) M. Zinc and dithiothreitol profoundly stimulate laminin binding to AAPs. Furthermore, zinc fingers were found in the laminin amino acid sequences. Previous binding studies of AAPs with the basement membrane heparan sulfate proteoglycan revealed similar affinities. A particular order of addition of laminin and heparan sulfate proteoglycan to AAPs can be demonstrated. CONCLUSIONS: These avid interactions with extracellular matrix proteins likely reflect normal functions of the AAPs and may be involved in nucleation events in Alzheimer-type amyloid formation.

Alzheimer Disease↗

Treatment of infants with acute diarrhea: what's recommended and what's practiced.

In 1985, the American Academy of Pediatrics (AAP) published a policy statement on the treatment of infants with acute diarrhea complicated by mild to moderate dehydration. To determine how closely physicians in the United States follow the AAP's treatment guidelines, a questionnaire was sent to 457 pediatricians and 360 family practitioners. The questionnaire presented a hypothetical infant with acute diarrhea complicated by mild to moderate dehydration and included questions regarding the number of such patients seen yearly, length of time used to rehydrate the infant, and how formula or solids are introduced following rehydration. Complete responses were received from 53% of pediatricians and 40% of family practitioners. The number of patients with acute diarrhea seen per year did not affect physician's treatment. Pediatricians and family practitioners responded similarly to most questions. Contrary to the AAP's guidelines to rehydrate in 4 to 6 hours, 62% of responding physicians extend the rehydration period to 12 to 24 hours. Also contrary to the AAP's recommendations, 62% of pediatricians and family practitioners use a lactose-free formula. The majority of responding physicians do follow the AAP's treatment guidelines to initiate feedings with diluted formula. Significantly more pediatricians than family practitioners advance to a full-strength formula within 1 day (P = .011). Fewer than 50% of physicians polled started solids within 24 hours as suggested by the AAP. Overall, the findings suggest that very few pediatricians and family practitioners follow all aspects of the AAP's treatment guidelines for infants with acute diarrhea complicated by mild to moderate dehydration.

Acute Disease↗

High affinity interactions between the Alzheimer's beta-amyloid precursor proteins and the basement membrane form of heparan sulfate proteoglycan.

High affinity interactions were studied between the basement membrane form of heparan sulfate proteoglycan (HSPG) and the 695-, 751-, and 770-amino acid Alzheimer amyloid precursor (AAP) proteins. Based on quantitative analyses of binding data, we identified single binding sites for the HSPG on AAP-695 (Kd = 9 x 10(-10) M), AAP-751 (Kd = 10 x 10(-9) M), and AAP-770 (Kd = 9 x 10(-9) M). It is postulated that the "Kunitz" protease inhibitor domain which is present in AAP-751 and -770 reduces the affinity of AAPs for the HSPG through steric hindrance and/or conformational alteration. HSPG binding was inhibited by heparin and dextran sulfate, but not by dermatan or chondroitin sulfate. HSPG protein core, obtained by heparitinase digestion, also bound to the beta-amyloid precursor proteins with high affinity, indicating that the high affinity binding site is constituted by the polypeptide chain rather than the carbohydrate moiety. The effects of various cations on these interactions were also studied. Our results suggest that specific interactions between the AAP proteins and the extracellular matrix may be involved in the nucleation stages of Alzheimer's disease type amyloidogenesis.

Alzheimer Disease↗

Effect of potassium ethylxanthogenate on the acetaminophen hepatotoxicity in mice.

The effects of potassium ethylxanthogenate (PEX), acetaminophen (AAP) and their combination on the activity of serum transaminases, liver glutathione level and the activity of some drug metabolizing enzyme systems in male albino mice are studied. PEX (80 mg/kg p. o.), applied one hour before AAP (737.5 mg/kg p. o.) or simultaneously with it, prevents the AAP-induced rise in transaminases. PEX reduces significantly the AAP-induced depletion of the liver glutathione. Eighteen hours after the administration of a hepatotoxic dose of AAP, there is a statistically significant decrease of the activity of aniline hydroxylase, ethylmorphine demethylase, uridine diphosphoglucuronyl transferase, glutathione-S-transferase, NADPH-cytochrome-c-reductase, the P-450 content and a 5-fold increase of TBA-reactive products. PEX, introduced one hour before AAP or simultaneously with it, prevents these changes. The basic mechanism through which PEX reduces the liver toxicity of AAP is assumed to be the decrease in the amount of toxic metabolite formed.

Acetaminophen↗

Protection of acetaminophen-induced hepatocellular apoptosis and necrosis by cholesteryl hemisuccinate pretreatment.

This study of acetaminophen (AAP) hepatotoxicity examined whether some aspects of the highly integrated process of drug-induced toxicity involves apoptosis, in addition to necrosis in vivo; and if so, whether cholesteryl hemisuccinate (CS) pretreatment would selectively interfere with apoptotic or necrotic liver cell death. We have previously demonstrated that CS preexposure in vivo, protects hepatocellular necrosis and necrosis-related events induced by carbon tetrachloride (CCl4) administration. Our study demonstrates that administration of hepatotoxic doses of AAP (350-500 mg/kg, i.p.) to ICR mice (CD-1) results in severe liver injury leading to cell death both by necrosis and apoptosis. AAP-induced cell death was preceded by massive elevation in serum alanine aminotransferase coupled with rapid loss of large genomic DNA (2-24 hr), fragmentation of DNA in the form of a ladder (2-24 hr), apoptotic nuclear condensation at early hours (2-6 hr) followed by massive fragmentation and margination of heterochromatin at later (6-24) hours and a near total loss of glycogen in pericentral areas. Although CS (100 mg/kg, i.p.) alone had no noticeable biochemical or morphological effects, its administration before AAP (350-500 mg/kg, i.p.) abrogated histological and biochemical diagnostics of both apoptosis and necrosis. These include near total absence of loss of large genomic DNA and glycogen, and dramatic protection from escalating levels of liver injury. CS pretreatment also arrested AAP-induced ultrastructural changes typical of both apoptosis and necrosis. Histopathological examination of periodic acid-Schiff stained liver sections mirrored the biochemical and ultrastructural findings. In conclusion, this study for the first time establishes that apoptosis, in addition to necrosis, significantly contributes to AAP hepatotoxicity in vivo, and preexposure of mice to CS prevents AAP-induced hepatic apoptosis and necrosis.

Acetaminophen↗

Differential biochemical response of freshly isolated rat hepatocytes to paracetamol, carbon tetrachloride and D-galactosamine toxicity.

Differential response of freshly isolated rat hepatocytes to paracetamol (acetaminophen, AAP), carbon tetrachloride (CCl4) and D-galactosamine (GalN) was examined. The viability of the cells in suspension culture was not altered for 4 hr when incubated in Hank's balanced salt solution (HBSS) supplemented with 4.2 mM NaHCO3, 10 mM HEPES buffer and 0.5% bovine serum albumin. AAP induced time and dose dependent depletion of GSH as an early manifestation of AAP toxicity. Hepatocytes exposed to AAP exhibited lower lactate dehydrogenase (LDH) activity released into the medium than in controls. This was due to the interaction of a reactive metabolite of AAP, i. e. N-acetyl p-benzoquinoneimine (NAPQI) with cell proteins. Hepatocytes isolated from rats pretreated with 3-methylcholanthrene expressed higher sensitivity to AAP toxicity at least by a factor of 5. Furthermore, AAP-induced toxicity was not found to be related to any lipoperoxidative stress. CCl4 on the other hand elicited a highly lipoperoxidative response in hepatocytes and consequent leakage of cellular enzymes with lengths of incubation. Again the sensitivity of the response to CCl4 was enhanced remarkably in hepatocytes isolated from phenobarbital- pretreated rats; LDH leakage increased by 3-fold and thio-barbituric acid reactive substances by 25-fold. Unlike the two toxicants, galactosamine depleted UDP-glucuronic acid in a concentration and time-related manners. The differential biochemical response of hepatocytes to three hepatotoxicants investigated may prove useful as rapid in vitro screen for selection of compounds of hepatoprotective potentials.

Acetaminophen↗

[A comprehensive approach to the treatment of popliteal artery aneurysms--personal experience].

UNLABELLED: During a five-year retrospective follow-up period the authors treated a group of 46 patients with the diagnosis of aneurysm of the popliteal artery (AAP). The group comprised 42 men (91%) and 4 women (9%). The mean age was 62 years. In 32 patients (69%) AAP was on both lower extremities, in the remaining 14 (31%) it was unilateral. Forty-one patients (90%) had surgery and a total of 48 AAP were operated. The remainder was treated by conservative methods (10%). The first symptoms of AAP in the investigated group were: claudication in 17%, thromboembolic complications in 46%, rupture of the AAP in 4%. An asymptomatic aneurysm was detected in 33%. RESULTS: The authors did not record any death or occlusion of the reconstruction during hospitalization. When using a vein the primary patency is 100%. When a prosthesis (PTFE) is used the results are worse but still satisfactory and the five-year secondary patency is 85%. Five patients with thromboembolic complications of AAP were successfully treated by i.a. fibrinolysis. In all exclusion of the aneurysm and revascularization of the extremity followed. In the conclusion the authors emphasize the necessity of early surgical treatment as soon as the condition is detected, before the development of thromboembolic complications of AAP. If they develop it is essential to attempt local fibrinolysis and in the second stage revascularization of the extremity, if possible by a vein.

Adult↗

Tuberculosis testing. Physician attitudes and practice.

OBJECTIVE: To assess physician agreement with and adoption of American Academy of Pediatrics' (AAP) recommendations on tuberculosis screening in children. DESIGN AND PARTICIPANTS: Survey of a random sample of 1272 community pediatricians and family physicians (excluding academic institutions) in 4 mid-Atlantic states and the District of Columbia. RESULTS: The response rate was 66%. Seventy-five percent of the respondents were aware of the 1994 AAP screening recommendations. Most (64%) test children at low risk periodically (at age 1 year, preschool age, and adolescent age), and 81% test children at high risk annually. Eighty-one percent of the respondents estimated that 10% or less of their patients were at high risk for tuberculosis. Most use patient-specific factors, geographic or community prevalence, or both as principal criteria to determine risk. Eighty-seven percent used multiple-puncture tests in 1993; this declined to 55% in 1994. Multiple-puncture tests are still used exclusively by 29% of the respondents. Ninety-one percent of those using multiple-puncture tests and 19% of those using the Mantoux test allow parents to read the test reaction. Forty-six percent of the respondents believed that if a return visit was required for reading the test reaction, 50% or less of their patients would return. Only 22% of the respondents adhere to the 1994 AAP recommendations regarding frequency, testing method, and reading the test reaction. Factors associated with adherence to AAP recommendations included physician and practice characteristics and knowledge of AAP recommendations. CONCLUSIONS: Physician practice of tuberculosis testing varies widely; most do not adhere to the 1994 AAP recommendations. Most physicians vary the frequency and testing method based on a patient's risk status. The use of multiple-puncture tests has declined, although they are still widely used. Accurate reading of screening tests remains a major concern.

Adolescent↗

Carbon monoxide-mediated alterations in paracellular permeability and vesicular transport in acetaminophen-treated perfused rat liver.

This study aimed to examine whether acetaminophen (AAP), an anti-inflammatory agent producing hepatocellular damages with its overdose, evokes hepatocellular dysfunction through mechanisms involving carbon monoxide (CO) generated by heme oxygenase (HO). In perfused rat livers, CO and bilirubin were determined in venous perfusate and bile samples as indices of heme degradation. Biliary excretion of transportally injected horseradish peroxidase was also determined to assess paracellular junctional permeability and vesicular transport across hepatocytes. AAP at 20 mmol/L induced a transient choleresis, followed by a reduction of bile output. Under these circumstances, the release of CO and bilirubin IXalpha, terminal products of the HO-mediated heme degradation, became 2. 5-fold greater than the control. The rate of CO production appeared stoichiometric to the degradation rate of microsomal cytochrome P-450. Mechanisms for the AAP-induced cholestasis involved an increase in the junctional permeability that coincided with a reduction of vesicular transport across hepatocytes. Clotrimazole, a cytochrome P-450 inhibitor, or zinc protoporphyrin IX, an HO inhibitor, but not copper protoporphyrin IX, which did not inhibit HO, attenuated these AAP-induced changes. Furthermore, administration of CO at concentrations comparable with those induced by AAP elicited a marked elevation of the paracellular junctional permeability concurrent with a reduction of transcellular vesicular transport, mimicking effects of the AAP administration. Thus, CO serves as a putative regulator of hepatocellular function that is overproduced through acute heme degradation during xenobiotic transformation.

Acetaminophen↗