Role of pulsatility on particle dispersion in expiratory flows.

Expiratory events, such as coughs, are often pulsatile in nature and result in vortical flow structures that transport respiratory particles. In this work, direct numerical simulation (DNS) of turbulent pulsatile jets, coupled with Lagrangian particle tracking of micron-sized droplets, is performed to investigate the role of secondary and tertiary expulsions on particle dispersion and penetration. Fully developed turbulence obtained from DNS of a turbulent pipe flow is provided at the jet orifice. The volumetric flow rate at the orifice is modulated in time according to a damped sine wave, thereby allowing for control of the number of pulses, duration, and peak amplitude. Thermodynamic effects, such as evaporation and buoyancy, are neglected in order to isolate the role of pulsatility on particle dispersion. The resulting vortex structures are analyzed for single-, two-, and three-pulse jets. The evolution of the particle cloud is then compared to existing single-pulse models. Particle dispersion and penetration of the entire cloud are found to be hindered by increased pulsatility. However, the penetration of particles emanating from a secondary or tertiary expulsion is enhanced due to acceleration downstream by vortex structures.

Trans-ethnic analysis of metabochip data identifies two new loci associated with BMI.

OBJECTIVE: Body mass index (BMI) is commonly used to assess obesity, which is associated with numerous diseases and negative health outcomes. BMI has been shown to be a heritable, polygenic trait, with close to 100 loci previously identified and replicated in multiple populations. We aim to replicate known BMI loci and identify novel associations in a trans-ethnic study population. SUBJECTS: Using eligible participants from the Population Architecture using Genomics and Epidemiology consortium, we conducted a trans-ethnic meta-analysis of 102 514 African Americans, Hispanics, Asian/Native Hawaiian, Native Americans and European Americans. Participants were genotyped on over 200 000 SNPs on the Illumina Metabochip custom array, or imputed into the 1000 Genomes Project (Phase I). Linear regression of the natural log of BMI, adjusting for age, sex, study site (if applicable), and ancestry principal components, was conducted for each race/ethnicity within each study cohort. Race/ethnicity-specific, and combined meta-analyses used fixed-effects models. RESULTS: We replicated 15 of 21 BMI loci included on the Metabochip, and identified two novel BMI loci at 1q41 (rs2820436) and 2q31.1 (rs10930502) at the Metabochip-wide significance threshold (P<2.5 × 10-7). Bioinformatic functional investigation of SNPs at these loci suggests a possible impact on pathways that regulate metabolism and adipose tissue. CONCLUSION: Conducting studies in genetically diverse populations continues to be a valuable strategy for replicating known loci and uncovering novel BMI associations.

The use of phenome-wide association studies (PheWAS) for exploration of novel genotype-phenotype relationships and pleiotropy discovery.

The field of phenomics has been investigating network structure among large arrays of phenotypes, and genome-wide association studies (GWAS) have been used to investigate the relationship between genetic variation and single diseases/outcomes. A novel approach has emerged combining both the exploration of phenotypic structure and genotypic variation, known as the phenome-wide association study (PheWAS). The Population Architecture using Genomics and Epidemiology (PAGE) network is a National Human Genome Research Institute (NHGRI)-supported collaboration of four groups accessing eight extensively characterized epidemiologic studies. The primary focus of PAGE is deep characterization of well-replicated GWAS variants and their relationships to various phenotypes and traits in diverse epidemiologic studies that include European Americans, African Americans, Mexican Americans/Hispanics, Asians/Pacific Islanders, and Native Americans. The rich phenotypic resources of PAGE studies provide a unique opportunity for PheWAS as each genotyped variant can be tested for an association with the wide array of phenotypic measurements available within the studies of PAGE, including prevalent and incident status for multiple common clinical conditions and risk factors, as well as clinical parameters and intermediate biomarkers. The results of PheWAS can be used to discover novel relationships between SNPs, phenotypes, and networks of interrelated phenotypes; identify pleiotropy; provide novel mechanistic insights; and foster hypothesis generation. The PAGE network has developed infrastructure to support and perform PheWAS in a high-throughput manner. As implementing the PheWAS approach has presented several challenges, the infrastructure and methodology, as well as insights gained in this project, are presented herein to benefit the larger scientific community.

Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Multiethnic Cohort Study.

In vitro and in vivo studies have shown that cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of oestrogens. There is evidence that grapefruit, an inhibitor of CYP3A4, increases plasma oestrogen concentrations. Since it is well established that oestrogen is associated with breast cancer risk, it is plausible that regular intake of grapefruit would increase a woman's risk of breast cancer. We investigated the association of grapefruit intake with breast cancer risk in the Hawaii-Los Angeles Multiethnic Cohort Study, a prospective cohort that includes over 50 000 postmenopausal women from five racial/ethnic groups. A total of 1657 incident breast cancer cases were available for analysis. Grapefruit intake was significantly associated with an increased risk of breast cancer (relative risk=1.30, 95% confidence interval 1.06-1.58) for subjects in the highest category of intake, that is, one-quarter grapefruit or more per day, compared to non-consumers (P(trend)=0.015). An increased risk of similar magnitude was seen in users of oestrogen therapy, users of oestrogen+progestin therapy, and among never users of hormone therapy. Grapefruit intake may increase the risk of breast cancer among postmenopausal women.

Do urinary estrogen metabolites reflect the differences in breast cancer risk between Singapore Chinese and United States African-American and white women?

Breast cancer risk is substantially lower in Singapore than in women from the United STATES: Part of the risk discrepancy is probably explained by differences in the production of endogenous estrogens, but differences in the pathway by which estrogen is metabolized may also play a role. We undertook a study to determine whether the ratio of urinary 2-hydroxyestrone (2OHE(1)):16alpha-hydroxyestrone (16alpha-OHE(1)) was higher in Singapore Chinese than in a group of United States (predominantly African-American) women living in Los ANGELES: We also wanted to determine whether any difference in estrogen metabolite ratio between these two groups of women was greater than that in estrone (E(1)), estradiol (E(2)) and estriol (E(3)). The participants in this study were randomly selected healthy, non-estrogen using women participating in the Singapore Chinese Health Study (n = 67) or the Hawaii/Los Angeles Multiethnic Cohort Study (n = 58). After adjusting for age and age at menopause, mean urinary 2-OHE(1) was only 23% (P = 0.03) higher in Singapore Chinese than in United States women, and there were no statistically significant differences in 16alpha-OHE(1) levels or in the ratio of 2-OHE(1):16alpha-OHE(1) between the two groups. The adjusted mean 2-OHE(1):16alpha-OHE(1) ratio was 1.63 in Singapore Chinese and 1.48 in United States women (P = 0.41). In contrast, the adjusted mean values of E1, E2, and E3 were 162% (P < 0.0001), 152% (P < 0.0001), and 92% (P = 0.0009) higher, respectively, in United States women than in Singapore Chinese women. Our study suggests that urinary E1, E2, and E3 reflect the differences in breast cancer risk between Singapore Chinese and United States women to a stronger degree than the estrogen metabolites 2OHE(1) and 16alpha-OHE(1) or the ratio of 2OHE(1):16alpha-OHE(1.)

Can clinical parameters predict fractures in acute pediatric wrist injuries?

OBJECTIVE: Fractures around the wrist are common in pediatric patients presenting to the emergency department (ED). This pilot study was aimed at identifying clinical variables that are most likely to be associated with a fracture. METHODS: This was a prospective blinded case series of patients 3-18 years of age presenting with an acute (<3 days) wrist injury, without obvious deformity. A team of five investigators blinded to the eventual radiographic findings evaluated patients. Physical examination variables included range of motion (ROM), site of maximal tenderness, and functional deficit. The latter was determined objectively, by recording any difference in grip strength between the injured and noninjured hands. Diagnostic radiographs were obtained for all patients. Univariate analysis using Wilks' log likelihood ratio test was performed to identify clinical variables associated with confirmed wrist fractures. Sample size was determined based on the ability to detect a difference of 15 degrees in the ROM variables, 20% point differences in grip strength, and 30% proportion differences in categorical variables using a power of 0.8 and a two-tailed of 0.05. RESULTS: The ROMs were not significantly different between the fracture (Fx) and nonfracture (NFx) group. There was significant change in the grip strength between the Fx and NFx groups (t = 3.3, p = 0.0019). Tenderness over the distal radius was also associated with a greater likelihood of a fracture (G(2) = 5.0, p = 0.02). Sensitivity of clinical prediction was found to be 79%, and specificity was 63%. The false-negative rate was 0.21 and the false-positive rate was 0.37, while the positive predictive value was found to be 0.68 and negative predictive value 0.75. CONCLUSIONS: Distal radius point tenderness and a 20% or more decrease in grip strength were predictive of fractures.

Opportunistic urine ligase chain reaction screening for sexually transmitted diseases in adolescents seeking care in an urban emergency department.

STUDY OBJECTIVE: Neisseria gonorrhoeae and Chlamydia trachomatis are the most common bacterial sexually transmitted diseases (STDs) in sexually active youth and many infections are asymptomatic or unrecognized. This study used ligase chain reaction assays for determination of prevalence of gonococcal and chlamydial infections in adolescents seeking care at an urban emergency department. METHODS: An unlinked prevalence study was performed with ligase chain reaction tests on voided urine specimens from a convenience sample of adolescents 14 years or older who sought care at the Children's Hospital of Alabama ED. Demographic data and data on care provided in the ED were determined from retrospective chart review of those patients whose urine specimens were tested. RESULTS: Of 282 urine specimens screened, 13.5% (38) yielded positive findings on ligase chain reaction testing for either or both pathogens (20 [7%] positive for N gonorrhoeae, 23 [8%] positive for C trachomatis). In the context of acute care, gonorrhea or chlamydial infection was diagnosed in 5 (1.8%). STD prevalence did not vary significantly by age. Only 39% (15/38) of patients with infections detected by ligase chain reaction testing received potentially effective antibiotics as a result of their urgent care evaluation. CONCLUSION: Many adolescents use the ED for nonurgent care and unsuspected STDs are often missed. Urine ligase chain reaction testing is a sensitive, noninvasive means of detecting STDs by which unsuspected adolescent STD cases can be detected in an ED setting.

Identification, cloning, and initial characterization of rot, a locus encoding a regulator of virulence factor expression in Staphylococcus aureus.

A chromosomal insertion of transposon Tn917 partially restores the expression of protease and alpha-toxin activities to PM466, a genetically defined agr-null derivative of the wild-type Staphylococcus aureus strain RN6390. In co-transduction experiments, transposon-encoded erythromycin resistance and a protease- and alpha-toxin-positive phenotype are transferred at high frequency from mutant strains to agr-null strains of S. aureus. Southern analysis of chromosomal DNA and sequence analysis of DNA flanking the Tn917 insertion site in mutant strains revealed that the transposon interrupted a 498-bp open reading frame (ORF). Similarity searches using a conceptual translation of the ORF identified a region of homology to the known staphylococcal global regulators AgrA and SarA. To verify that the mutant allele conferred the observed phenotype, a wild-type allele of the mutant gene was introduced into the genome of a mutant strain by homologous recombination. The resulting isolates had a restored agr-null phenotype. Virulence factor gene expression in mutant, restored mutant, and wild-type strains was quantified by measuring alpha-toxin activity in culture supernatant fluids and by Northern analysis of the alpha-toxin transcript. We named this ORF rot (for repressor of toxins) (GenBank accession no. AF189239) because of the activity associated with rot::Tn917 mutant strains.

Evaluation of emergency department referrals by telephone triage.

OBJECTIVE: Telephone triage programs are becoming very common at children's hospitals across the nation. One of the proposed benefits of these programs is the more efficient use of health care resources by triaging patients to the appropriate level of health care. The purpose of this study is to examine the appropriateness of referrals to a pediatric emergency department (ED) by the Pediatric Health Information Line (PHIL), a hospital-based telephone triage program, versus all other sources of referrals. METHODS: A blinded Delphi rating system was used to review the physician's sheets of 133 consecutive ED referrals by PHIL for medical appropriateness. A total of 260 randomly selected control patients seen in the ED during the same period were similarly reviewed. If 2 of 3 pediatric emergency medicine physicians agreed that an ED visit was appropriate, then it was considered appropriate. A comparison of the 2 groups' ED appropriateness was made using a contingency table chi(2) test. An odds ratio with confidence limits was also calculated. Demographic data were collected for both groups including age, race, gender, and insurance status. RESULTS: The PHIL group had an appropriateness rate of 80.2%, compared with 60.5% for the control group (chi(2) = 14.6369; odds ratio = 2.65; 95% confidence interval [1.5759,4.5008]). CONCLUSIONS: This demonstrated that for the period studied, PHIL referrals to the ED had a 33% higher rate of appropriateness than controls. This evidence supports telephone triage as an efficient gatekeeper for health care resources.

A multiethnic cohort in Hawaii and Los Angeles: baseline characteristics.

The authors describe the design and implementation of a large multiethnic cohort established to study diet and cancer in the United States. They detail the source of the subjects, sample size, questionnaire development, pilot work, and approaches to future analyses. The cohort consists of 215,251 adult men and women (age 45-75 years at baseline) living in Hawaii and in California (primarily Los Angeles County) with the following ethnic distribution: African-American (16.3%), Latino (22.0%), Japanese-American (26.4%), Native Hawaiian (6.5%), White (22.9%), and other ancestry (5.8%). From 1993 to 1996, participants entered the cohort by completing a 26-page, self-administered mail questionnaire that elicited a quantitative food frequency history, along with demographic and other information. Response rates ranged from 20% in Latinos to 49% in Japanese-Americans. As expected, both within and among ethnic groups, the questionnaire data show substantial variations in dietary intakes (nutrients as well as foods) and in the distributions of non-dietary risk factors (including smoking, alcohol consumption, obesity, and physical activity). When compared with corresponding ethnic-specific cancer incidence rates, the findings provide tentative support for several current dietary hypotheses. As sufficient numbers of cancer cases are identified through surveillance of the cohort, dietary and other hypotheses will be tested in prospective analyses.

Calibration of the dietary questionnaire for a multiethnic cohort in Hawaii and Los Angeles.

The performance of the dietary questionnaire used in a multiethnic cohort study in Hawaii and Los Angeles was assessed in a calibration substudy that compared diet reported from the questionnaire with three 24-hour dietary recalls. For the calibration substudy, subjects from each of eight subgroups defined by sex and ethnic group (African-American, Japanese-American, Latino, and White) were chosen randomly from among the cohort members, and each participant's previous day's diet was assessed by telephone recall on three occasions over approximately 2 months. After completing the three 24-hour recalls, each calibration subject was sent a second questionnaire; 1,606 persons completed three recalls and a second questionnaire (127 to 267 per ethnic-sex group). This report describes correlation coefficients and calibration slopes for the relation between the 24-hour recalls and second questionnaire values for a selected set of macro- and micronutrients, as absolute intakes, nutrient densities, and calorie-adjusted nutrients. In all subgroups, estimates of the correlation between the questionnaire and 24-hour recalls were greater after energy adjustment (average correlations ranged from 0.57-0.74 for nutrient densities and from 0.55-0.74 for calorie-adjusted nutrients) than when absolute nutrient values were used (average range 0.26-0.57). For absolute nutrient intakes, the correlations were greatest for Whites, somewhat lower for Japanese-Americans and Latinos, and lowest for African-Americans. After energy adjustment, the difference between subgroups were diminished, and the correlations were generally highly satisfactory.

Pediatric emergency department nurses' perspectives on fever in children.

BACKGROUND: Fever is the most common complaint of children seen in a Pediatric Emergency Department (PED). Since pediatric emergency nurses commonly educate parents on fever management, this study sought to examine their knowledge base regarding fever in children. METHODS: Through convenience sampling, pediatric emergency registered nurses working at one of four PEDs were surveyed using a self-administered questionnaire containing 10 open-ended questions pertaining to fever in children. RESULTS: Eighty-eight pediatric emergency registered nurses (median experience 8.0 years, range 3 months to 28 years) were surveyed. The median temperature considered by pediatric emergency nurses to be a fever was 38.0 degrees C (100.4 degrees F) with a range of 37.2 degrees C (99.0 degrees F) to 38.9 degrees C (102.0 degrees F), while the median temperature considered to be dangerous to a child was 40.6 degrees C (105.0 degrees F) with a range of 38.0 degrees C (100.4 degrees F) to 41.8 degrees C (107.0 degrees F). Eleven percent was not sure what temperature constituted a fever while 31% was not sure what temperature would be dangerous to a child. Fifty-seven percent considered seizures the primary danger to a febrile child while 29% stated permanent brain injury or death could occur from a high fever. Sixty percent chose acetaminophen as first line treatment while 7% stated alcohol or tepid water baths were also acceptable treatment options. Thirty-eight percent stated that a different medication should be added if a child was still febrile 1 hour after initial treatment while 31% would not use additional medication. Eighteen percent stated it was dangerous for a child to leave the PED if still febrile. CONCLUSION: Fever phobia and inconsistent treatment approaches occur among experienced pediatric emergency registered nurses. These phobias and inconsistencies subsequently could be conveyed to parents. In order to assure accurate parental education, PEDs should educate their medical team regarding the management of fever in children.

Effect of ketorolac in pediatric sickle cell vaso-occlusive pain crisis.

BACKGROUND: Ketorolac is a parenteral, nonsteroidal analgesic that does not have a narcotic's risks of respiratory depression, hypotension, or dependence. Its usefulness in providing pain relief in pediatric patients with acute vaso-occlusive crisis of sickle cell disease has not been studied to date. METHODS: Twenty-nine patients with sickle cell disease between the ages of 5 and 18 years who presented to The Children's Hospital of Alabama emergency department (ED) with 41 distinct episodes of acute vaso-occlusive pain crisis were enrolled prospectively and randomized to receive either 0.9 mg/kg intravenous (IV) ketorolac or placebo in a double-blind fashion. All patients also received IV fluids and an initial 0.1 mg/kg of IV morphine. Subsequent standardized doses of morphine were given every 2 hours over a 6-hour observation period based upon severity of pain as scored by a 10-cm linear visual analog scale (VAS). Vital signs and pain severity were recorded initially and assessed hourly. Disposition was made at the end of the observation period. RESULTS: Patients receiving ketorolac and those receiving placebo were of similar age, weight, gender, number of prior ED visits, number of prior hospital admissions, duration of pain prior to presentation, and initial pain score. The total dose of morphine received, reduction in severity of pain as measured by VAS, rate of hospital admission, and rate of return to the ED for discharged patients did not differ significantly between the two groups. CONCLUSION: We were unable to demonstrate a synergistic analgesic effect for ketorolac in the treatment of pain from acute vaso-occlusive crisis in pediatric sickle cell disease. Further investigations involving larger samples of sickle cell patients may be needed to further define a role for ketorolac in the acute management of sickle cell vaso-occlusive pain.

Dissociation of angiotensin II-stimulated activation of mitogen-activated protein kinase kinase from vascular contraction.

Angiotensin II (Ang II) is a potent pressor hormone, a stimulus for vascular smooth muscle hypertrophy and an activator of multiple tyrosine kinases. The physiological effects of Ang II are mediated through activation of AT1 and AT2 receptors, receptors that have been coupled to tyrosine kinase(s) and tyrosine phosphatases, respectively. Agonists of G protein-coupled receptors, of which Ang II is one, have recently been shown to stimulate smooth muscle contraction in part via activation tyrosine kinases. We tested the hypothesis that Ang II-induced contraction in the rat aorta was dependent on activation of tyrosine kinase(s) and specifically investigated the role of the tyrosine kinase mitogen-activated protein kinase kinase (MEK), a kinase important to the mitogen activated protein kinase (MAPK) pathway. Rat thoracic aortic strips denuded of endothelium and cultured aortic smooth muscle cells were used in isolated tissue baths for measurement of isometric contractile force and Western analyses of protein tyrosyl-phosphorylation. Ang II (0.1-100 nM)-induced contraction in the aorta was completely blocked by the AT1 receptor antagonist losartan (1 microM) but unaffected by the AT2 receptor antagonist PD123319 (100 nM) or tyrosine phosphatase inhibitor sodium orthovanadate (1 microM), indicating an AT1 receptor mediates aortic contraction to Ang II. Neither the tyrosine kinase inhibitor genistein (5 microM), inactive tyrosine kinase inhibitor daidzein (5 microM) nor MEK inhibitor PD098059 (10 microM) reduced Ang II-induced contraction; the concentrations of inhibitors used maximally reduced contraction stimulated by other agonists of G protein-coupled receptors such as serotonin. Moreover, Ang II-induced contraction was not altered by the combination of PD098059 and PD123319, indicating that it is unlikely AT2 receptor stimulation masks activation of the MAPK pathway through AT1 receptor activation. The nonflavone tyrosine kinase inhibitor tyrphostin B42 (30 microM) reduced Ang II-induced maximal contraction (to 11.2% control) but, unlike the other tyrosine kinase inhibitors, also reduced KCl-induced contraction (to 55.2% control), indicating a probable nonselectivity of tyrphostin B42. Ang IIinduced maximal contraction was reduced by the L-type voltage gated calcium channel antagonist nifedipine (50 nM), consistent with the activation of calcium channels by Ang II. In cultured rat aortic smooth muscle cells, Ang II (0.1-1000 nM) stimulated concentration-dependent tyrosyl-phosphorylation of the extracellular signal regulated kinase (Erk) mitogen activated protein kinases (maximal stimulation, fold basal: Erk-1 = 17-fold, Erk-2 = 3-fold), indicating that Ang II can activate MEK. Losartan (1 microM) abolished Ang II (10 nM)-induced Erk tyrosyl-phosphorylation and PD098059 (10 microM), which did not diminish Ang II-induced aortic contraction, reduced Ang II (10 nM)-stimulated phosphorylation of Erk-2 by 72%. Finally, Ang II (1 microM) increased tyrosyl-phosphorylation of the Erk proteins in isolated aorta exposed to Ang II for 5 min. Thus, while Ang II can stimulate both MEK activation and vascular contraction via interaction with AT1 receptors, stimulation of MEK does not appear to be important for Ang II-induced contraction. These findings dissociate the process of Ang II-stimulated Erk protein tyrosyl-phosphorylation from Ang II-induced contraction in the rat aorta.

Childhood hypoglycemia in an urban emergency department: epidemiology and a diagnostic approach to the problem.

OBJECTIVE: To 1) determine the prevalence of hypoglycemia in childhood in a pediatric emergency department (ED), 2) determine epidemiology of idiopathic ketotic hypoglycemia (IKH), 3) determine diagnostic yield of the workup of hypoglycemia, and 4) review a diagnostic approach to hypoglycemia. SETTING: Urban pediatric ED of a tertiary level children's hospital. METHODS: Retrospective review of all medical records with a primary or secondary diagnosis of hypoglycemia (ICD-9 code 251.2) seen at the ED between 1/92 and 8/95. RESULTS: Thirty-one patients were identified. Mean blood glucose was 34.2 mg/dl. Prevalence of hypoglycemia among population seeking care in our ED was 6.54/100,000 visits. Eighteen patients were diagnosed with IKH for a prevalence of 3.9/100,000. IKH demographics were: mean age 27.7 months; 12 males, 6 females; 8 white, 9 black, and 1 not available. The weights of five patients were < 25th percentile. Fourteen of the 18 IKH patients had hormone studies done insulin [cost $40], growth hormone [$69], cortisol [$54]. All 14 had appropriately suppressed insulin levels (< 5microU/ml) and high cortisol levels > 22 microg/ml. Thirteen of the 14 had normal or high growth hormone (GH) levels (0.7-6 ng/ml). Four IKH patients had urine drug screens ($280); all were negative. Although no IKH patient was febrile, six had sepsis workups ($380); all were negative. Urine ketones were positive in 15 of the 18 tested (> 3+ in eight patients). Mean anion gap was 20 (range: 16-30). Eight of the 18 IKH patients were discharged from the ED after return to normal status. CONCLUSIONS: IKH is the most common cause of hypoglycemia in children beyond the infancy period. In its typical presentation (previously healthy one- to five-year-old, with normal growth and development, who presents with a first episode of symptomatic fasting hypoglycemia and appropriate degree of ketonuria, without hepatomegaly, and with resolution of symptoms on administration of glucose), an extensive and overzealous workup for endocrinopathy or inborn error of metabolism is not necessary.

Organization of recurrent inhibition and facilitation in motor nuclei innervating ankle muscles of the cat.

The distribution of recurrent inhibition and facilitation to motor nuclei of muscles that act at the cat ankle joint was compared with the locomotor activity and mechanical action of those muscles described in published studies. Emphasis was placed on motor nuclei whose muscles have a principal action about the abduction-adduction axis and the pretibial flexors: tibialis posterior (TP), peroneus longus (PerL), peroneus brevis (PerB), the anterior part of tibialis anterior (TA) and extensor digitorum longus (EDL). Most intracellular recordings in spinalized, unanesthetized decerebrate cats showed only inhibitory or excitatory responses to antidromic stimulation of peripheral nerves, but mixed effects were also seen. Recurrent effects among motor nuclei of ankle abductors and adductors were not distributed uniformly. TP motoneurons received recurrent inhibition from most other nuclei active in stance and stimulation of the TP nerve inhibited these motor nuclei. Although PerB motoneurons are also active during stance, they received primarily facilitation from most motor nuclei. PerL received mixtures of inhibition and facilitation from all sources. Stimulation of the nerves to PerL, PerB, and peroneus tertius (PerT) produced weak recurrent inhibition and facilitation, even in homonymous motoneurons and motoneurons of Ia synergists. The ankle flexors TA and EDL displayed different patterns of recurrent inhibition and facilitation. TA motoneurons received prominent homonymous inhibition and inhibition from semitendinosus (St). EDL, whose activity profile differs from TA and which also acts at the digits, did not receive strong recurrent inhibition from either TA or St, nor did stimulation of the EDL nerve produce much inhibition. The distribution of recurrent inhibition and facilitation is correlated with the pattern of locomotor activity, but with exceptions that suggest an influence of mechanical action, particularly in the antagonistic interactions between TP and PerB. The extended pattern of recurrent inhibition, the reduction or absence of inhibition produced by motor nuclei with individualized functions or digit function and the prevalence of facilitation suggest that the recurrent Renshaw system is organized into inhibitory and disinhibitory projections that participate in the control of sets of motor nuclei engaged in rhythmic and stereotyped movements.

The vascular reactivity of melatonin.

1. Melatonin receptors have been located in the vasculature. The present study investigates the hypothesis that melatonin can alter vascular contraction. 2. Helical strips of endothelium-intact rat thoracic aorta and endothelium-denuded mesenteric and endothelium-denuded caudal arteries were mounted in isolated tissue baths for measurement of isometric contractile force. Melatonin (10(-12)-10(-3) M) did not cause contraction in the thoracic aorta, the mesenteric artery or the caudal artery. In the same arteries contracted with phenylephrine, melatonin (10(-12)-10(-3) M) did not cause direct relaxation. 3. In the rat aorta, a test for inhibition of KCl-induced contraction was conducted. Melatonin (10(-5)-10(-3) M) and the melatonergic agonist N-acetylserotonin (10(-5) M) inhibited contraction to KCl. The percentage inhibition observed at 70 mM KCl were as follows for melatonin: [25.3% (1 x 10(-5) M), 32.0% (1 x 10(-4) M), 26.4% (3 x 10(-4) M), 52.4% (1 x 10(-3) M); N-acetylserotonin 26.7% (1 x 10(-5) M), no inhibition at (1 x 10(-3) M)]. The melatonergic antagonist luzindole (2 x 10(-6) M) did not inhibit the melatonin (10(-3) M)-induced inhibition of KCl contraction in the rat aorta. 4. The possible effect that melatonin may have on endothelial nitric oxide activity also was examined. Melatonin (10(-5) M) did not affect acetylcholine (10(-9)-10(-4) M)-induced relaxation in the rat aorta contracted with a half-maximal concentration of phenylephrine. 5. These data suggest that melatonin can inhibit rat vascular reactivity but does so largely in a non-specific manner.

Use of PRISM scores in triage of pediatric patients with diabetic ketoacidosis.

Triage guidelines are needed to help in the decision process of intensive care unit (ICU) versus non-ICU admission for patients with diabetic ketoacidosis (DKA). Pediatric risk of mortality (PRISM) scores have long been used to assess mortality risk. This study assess the usefulness of the traditional PRISM score and adaptation of that score (PRISM-ED, which uses presentation data only) in predicting hospital stay in pediatric patients with DKA. PRISM and PRISM-ED were tested for correlation with length of stay and length of ICU stay. A medical record review was conducted for patients admitted to The Children's Hospital of Alabama with DKA during an 18-month period (n = 79). Two scores were calculated for each study entrant: PRISM using the worst recorded values over the first 24 hours and PRISM-ED using arrival values. Median scores, median test, and Spearman rank correlations were determined for both tests. Median PRISM scores were PRISM = 11 and PRISM-ED = 12; Median PRISM and PRISM-ED scores for patients admitted to the ICU were less than median scores among floor-admitted patients: [table: see text] Spearman rank correlations were significant for both scores versus total stay: PRISM, rs = 0.29; P = 0.009; PRISM-ED, rs = 0.60, P < 0.001. Also, correlations were significant for both scores versus ICU stay: PRISM rs = 0.22, P = 0.05; PRISM-ED, rs = 0.41, P < 0.001. Triage guidelines for ICU versus floor admission for DKA patients could have significant economic impact (mean ICU charge = $11,417; mean charge for floor admission = $4,447). PRISM scores may be an important variable to include in a multiple regression model used to predict the need for ICU monitoring.

Cancer incidence among Filipinos in Los Angeles County, 1972-1991.

Although Filipinos are the second largest Asian subgroup in the United States, little is known about their patterns of cancer incidence. We have examined cancer incidence rates among Filipinos living in Los Angeles County from 1972 through 1991 and evaluated their risk of non-localized cancer relative to non-Hispanic whites. Although Filipinos have substantially lower cancer rates than non-Hispanic whites in Los Angeles County, their incidence rates of liver cancer, cancer of the nasopharynx and thyroid cancer are higher. Filipino men and women had somewhat more advanced cancer at diagnosis, on average, than non-Hispanic whites, though no statistically significant differences were observed for sites where early detection methods exist. Our data suggest that Filipino-Americans would benefit from increased screening for cervical and breast cancer as well as efforts to interrupt transmission of hepatitis B virus to reduce liver cancer incidence.