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[A comparative study of epinephrine injection and beta 2-agonist inhalation in the treatment of childhood asthma].

A total of 29 cases were enrolled in this study and divided randomly into Group I (traditional epinephrine injection) and Group II (terbutaline nebulizer inhalation). If patients did not respond well to the initial therapy. a crossover therapeutic regimen was assigned and their pulmonary function, peak expiratory flow rate (PEFR) was measured every 10 minutes for half an hour. Both groups of patients revealed significant improvement post initial treatment P less than 0.0001). Within group difference was analysis by Wilcoxon signed rank test. All subgroups at 10 minutes, 20 minutes, and 30 minutes were compared in terms of their baseline pulmonary function, epinephrine group P value showed 0.0059, 0.0038, 0.0025; and terbutaline nebulizer inhalation group P value showed as 0.0007. 0.0003, 0.0003 respectively. An analysis of the group with an initial PEFR below 40% of the normal predicted or the more severely ill childhood acute asthmatic patients, the ten minutes post-treatment PEFR value of the epinephrine group showed P = 0.059; a significant P value of 0.0038 was noted for the terbutaline inhalation group, but both group P value was less than 0.05 at 20.30 minutes post-treatment, respectively. Between-group difference was analysed by Mann Whitney U test. Although all time interval mean data showed higher for the terbutaline inhalation group, statistically it showed P greater than 0.05. The above data suggest terbutaline inhalation therapy at the dosage noted will have early onset of action and better early clinical improvement than the traditional epinephrine injection regimen. There seemed to be no difference in degree of improvement between the two regimens. Observation of crossover treatment found a 50% re-response rate in both group of of patients who did not respond well to their initial regimen, and post crossover treatment PEFR all showed statistically significant improvement. However, still there was no significant difference between the two groups. This suggests that the terbutaline nebulizer inhalation method can not totally replace the more traditional method of acute asthma management, and emphasizes that a crossover therapeutic regimen should be kept in mind because the re-response rate is still encouraging. According to the variance analysis, the most important factor influencing the final outcome was the degree of severity of the initial asthmatic attack. The lower in initial PEFR value. The worse the clinical response. Other factors like age, sex, duration of asthma (year) and time interval between onset to arrival at the emergency room, showed as neither significant nor important.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗

Use of hyperbaric oxygen to enhance auricular composite graft survival in the rabbit model.

OBJECTIVE: To evaluate the efficacy of using hyperbaric oxygen to enhance auricular composite graft survival via a prospective, randomized, placebo-controlled, double-blind study. DESIGN: Eighteen New Zealand White rabbits were randomly assigned to treatment (n = 9) and control (n = 9) groups after amputation and reattachment of 20 x 10-mm auricular composite grafts. The treatment group received twice-daily hyperbaric oxygen treatments for 5 days. The control group received twice-daily hyperbaric room-air treatments for 5 days. After 21 days, digital photographs of the composite grafts were taken and compared with photographs taken on the day of surgery. From these photographs, digital imaging software was used to calculate the percentage of graft survival. RESULTS: The treated group (18 ears) had a mean +/- SD graft survival area of 80.67% +/- 19%, whereas the control group (18 ears) had a mean +/- SD graft survival area of 26.33% +/- 29%. Variance analysis with the Snedecor test allowed the comparison of the groups. The paired, 2-tailed t test proved a significant difference (P<.001) between groups. CONCLUSION: Hyperbaric oxygen therapy is an effective way to enhance the survival of 2-cm auricular composite grafts.

Animals↗

Brain morphometric analysis in neurofibromatosis 1.

RATIONALE AND OBJECTIVES: To investigate the relationships between brain and skull base growth in patients with neurofibromatosis 1 (NF1) compared with healthy control subjects using brain magnetic resonance imaging (MRI) for morphometric analysis. METHODS: Evaluated patients included children who underwent T1- and T2-weighted or dual-echo proton density axial and T1-weighted sagittal brain MRI from January 1, 1988, to December 31, 1995. Study subjects (n = 27) received a diagnosis of NF1 by accepted National Institutes of Health clinical criteria and were compared with an age- and sex-matched control group (n = 43). Twenty-four predetermined ventricular and brain parenchymal dimensions and area calculations were evaluated. Data were analyzed using 2-tailed t tests, chi2 analysis, analysis of variance, and analysis of covariance adjusted for age and sex. Correlational analyses with respect to subject type and age were performed separately. RESULTS: There were 27 patients (20 boys, aged 1.0-17.7 years; mean age, 8.8 years) and 43 controls (22 boys, aged 0.1-17.7 years; mean age, 5.9 years). The mean ages between groups (boys, girls, and totals) were not statistically different. Significant differences were appreciated for 6 of 24 measures. Patients with NF1 had a significantly larger bicaudate width (P = .002), biatrial width (P<.001), and biparietal diameter (P = .003), but not hemispheric length. They also had significantly increased iter measures (P = .004), descending sigmoid sinus (P<.001), and an age-specific increase in brainstem height (P = .03) not seen in controls. CONCLUSIONS: Patients with NF1 experience dynamic changes in brain morphometry, resulting in a predominant lateral volume expansion of the supratentorial compartment and an increasing velocity of brainstem growth as they age. These data underscore brain-region-specific parenchymal overgrowth potential.

Adolescent↗

Synaptic recruitment during long-term potentiation at synapses of the medial perforant pathway in the dentate gyrus of the rat brain.

Long-term potentiation (LTP) in synapses of the medial perforant pathway of the rat dentate gyrus has been studied using the whole-cell voltage clamp technique and a standard hippocampal slice preparation. The rate of LTP induction by 2-4 brief trains of stimuli at 100 Hz, paired with postsynaptic depolarization to -20 mV, in individual granule neurons was only 42% but the average magnitude was large. In a representative series of nine experiments the average potentiation was 339% (s.d. 255%). The variable magnitude of LTP appeared to be related to the relative size of the NMDA receptor dependent current in individual neurons. LTP was further characterized by the selective enhancement of the AMPA (but not the NMDA) component in the excitatory synaptic responses. This selective enhancement of the AMPA component and a graphical variance analysis suggest that the large magnitude of LTP in dentate gyrus can be best explained by recruitment of previously silent synapses by a combination of pre- and post-synaptic mechanisms.

Afferent Pathways↗

Sealant bond strengths of CO(2) laser-etched versus acid-etched bovine enamel.

BACKGROUND AND OBJECTIVE: The purpose of this study was to evaluate sealant shear bond strength on bovine enamel with standard acid etching compared with CO(2) laser etching. STUDY DESIGN/MATERIALS AND METHODS: Bovine enamel was prepared either by acid or laser etching and divided into four experimental groups, either acid or laser-etched teeth with or without a primer. A gelatin capsule was used to place the sealant on the prepared enamel surface and the bond tested in shear. Also surface roughness was evaluated by using a surface analyzer and an atomic force microscope. RESULTS: Shear bond strength results were the following: acid etch = 8.8 +/- 3.8 MPa, acid etch with primer = 10.3 +/- 5.5 MPa, laser etch = 4.0 +/- 1.1 MPa, and laser etch with primer = 6.2 +/- 2.3 MPa. Analysis of variance statistical analysis found no significant difference in bond strength between the acid-etched groups. However, the laser-etched groups had significantly lower bond strengths from the acid-etched teeth. In addition, a significant difference was observed between the laser-etched groups, where the use of the primer helped to increase the bond strength of the sealants. The surface roughness was significantly greater on the laser-etched teeth at the microm level (by using a surface analyzer) from the acid-etched and the control specimens. No difference in roughness (by using an atomic force microscope) was observed at the nanometer level between the laser and acid-etched teeth. CONCLUSION: For these particular settings, the laser-etched teeth resulted in lower bond strengths to enamel and the use of a primer increased the bond strength for laser-etched teeth only.

Acid Etching, Dental↗

Genetic basis of hair medulla by twin study.

Data on the incidence of medulla of human head hair based on 9,600 strands examined from 48 pairs of zygosity--determined German twins were quantified as medullary ratio and subjected to variance analysis to give information about genetic significance of the character concerned. The results of F test and heritability estimate yielded significant values indicating the presence of a strong genetic component of variability in the incidence of medulla of human head hair. Sex influence upon the character is found to be absent.

Female↗

South Amerindian craniofacial morphology: diversity and implications for Amerindian evolution.

The most compelling models concerning the peopling of the Americas consider that modern Amerindians share a common biological pattern, showing affinities with populations of the Asian Northeast. The aim of the present study was to assess the degree of variation of craniofacial morphology of South American Amerindians in a worldwide context. Forty-three linear variables were analyzed on crania derived from American, Asian, Australo-Melanesian, European, South-Saharan African, and Polynesian regions. South America was represented by seven Amerindian samples. In order to understand morphologic diversity among Amerindians of South America, variation was estimated using regions and local populations as units of analysis. Variances and F(ST) values were calculated for each unit, respectively. Both analyses indicated that morphologic variation in Southern Amerindians is extremely high: an F(ST) of 0.01531 was obtained for Southern Amerindians, and values from 0.0371-0.1205 for other world regions. Some aspects linked to the time and mode of the peopling of the Americas and various microevolutionary processes undergone by Amerindians are discussed. Some of the alternatives proposed to explain this high variation include: a greater antiquity of the peopling than what is mostly accepted, a peopling by several highly differentiated waves, an important effect of genetic drift, and gene flow with Paleoamericans. A combination of some of these alternatives explains at least some of the variation.

Biological Evolution↗

Effects of long-term estrogen replacement therapy on osteoarthritis severity in cynomolgus monkeys.

OBJECTIVE: To determine the effects of long-term estrogen replacement therapy (ERT) on the severity of osteoarthritis (OA) of the knee joint in surgically postmenopausal (bilaterally ovariectomized) female monkeys. A secondary aim was to evaluate the effect of soy phytoestrogen (SPE) treatment on the severity of OA. METHODS: Feral adult female cynomolgus macaques were ovariectomized bilaterally and then randomly divided into 3 age- and weight-matched treatment groups. For 3 years, the first group received ERT with conjugated equine estrogens, the second group received SPE, and the third group received no treatment (controls). At necropsy, histologic lesions of OA were graded, and the area and thickness of cartilage and subchondral bone were measured. The data were summarized by principal components analysis, and the resulting factors and individual variables were compared using analysis of variance and analysis of covariance (age and weight as covariates). RESULTS: Cartilage lesions of OA were significantly less severe in the animals given ERT compared with those in the control group. This treatment effect remained significant when adjusted for age and weight. The factor representing subchondral bone was significantly higher, but the number of osteophytes was lower, in the ERT group compared with the control group. SPE treatment had no significant effect on cartilage or bone lesions of OA. CONCLUSION: These results demonstrate that long-term ERT significantly reduces the severity of OA lesions in this animal model.

Animals↗

Purification of plasmid DNA with polymer-salt aqueous two-phase system: optimization using response surface methodology.

An experimental design was used to optimize plasmid purification from an alkaline lysate of Escherichia coli cells using PEG-sodium citrate aqueous two-phase systems (ATPS), and to evaluate the influence of pH, PEG molecular weight, tie line length, phase volume ratio, and lysate load. To build the mathematical model and minimize the number of experiments for the design parameters, response surface methodology (RMS) with an orthogonal rotatable central composite design was defined based on the conditions found for the highest purification by preliminary tests. The adequacy of the calculated models for the plasmid recovery and remaining RNA were confirmed by means of variance analysis and additional experiments. Analysis of contours of constant response as a function of pH, PEG molecular weight, tie line length, and cell lysate load for three different phase volume ratios revealed different effects of these five factors on the studied parameters. Plasmid recovery of 99% was predicted for a system with PEG 400, pH 6.9, tie line length of 38.7%, phase volume ratio of 1.5, and lysate load of 10% (v/v). Under these conditions the predicted RNA removal was 68%.

Citrates↗

The development and evaluation of a clinical test of surgical resident proficiency.

The two purposes of this study were to develop a clinical test of surgical resident proficiency and to compare this clinical test with currently applied methods of resident evaluation. Appendicitis is a common surgical disease, and its accurate diagnosis depends largely on clinical acumen. Ten third-year surgical residents prospectively evaluated 107 patients admitted because of suspected appendicitis. After taking a history, performing a physical examination, and reviewing laboratory data, these residents were asked to state, as a percentage, the likelihood that each patient had appendicitis. Sixty-three patients had appendicitis documented by pathologic inspection after appendectomy. Forty-four patients did not have appendicitis, as was determined by operation (17) or by in-house observation and resolution of abdominal pain (27). These outcomes were used to calculate a diagnostic ability score (DAS) for each resident. Residents were evaluated by standard methods including in-service examinations and monthly evaluations by the attending staff. Residents were also evaluated by nonstandard, but potentially useful, neuropsychologic and psychologic tests, including the trail making test, the Ravens progressive matrices test, the paced auditory serial addition test (PASAT), the grooved pegboard test of manual dexterity, and the profile of mood states (POMS) psychologic questionnaire. Cumulative scores were calculated and compared by multiple regression with coefficient variance analysis. The correlation (R2) of DAS with standard evaluation techniques was as follows: In-service (0.055), faculty (0.508), trails (-0.293), Ravens (0.028), PASAT (0.251), dexterity (0.432), POMS (0.381). We found that (1) the DAS is a discriminating clinical test; (2) the DAS correlates with subjective faculty evaluation; and (3) the DAS does not correlate with in-service examination scores. We conclude that faculty evaluation remains the best currently applied test of surgical resident clinical proficiency as measured by the DAS.

Adult↗

Acebultolol: basis for the prediction of effect on exercise tolerance.

Twelve unselected males suffering from documented coronary insufficiency and moderately severe angina submitted to graded multistage treadmill exercise testing on 3 separate days, 3.5 hr after a single dose of 0,200, or 400 mg of acebulolol, a cardioselective beta blocker. Control measures included random allocation of 2 patients to each of 6 balanced sequences of administration, standardized double-blind conditions, and variance analysis for Latin-square design with repeated measures on each subject. Performance was evaluated by measuring time elapsed until anginal pain, peak heart rate, peak product of heart rate and blood pressure, and peak oxygen consumption. Mean values for all criteria were significantly atered by 400 mg of acebutolol. Seven out of twelve patients were classified as responders (i.e., exercise duration increased 100% or more). The response after acebutolol was correlated with the performance on placebo in the base of exercise duration, peak heart rate, and peak product of heart rate and blood pressure. It is concluded that: (1) performance criteria are useful predictors of response to beta blockade and (2) acebutolol is a potent antianginal agent when judged by an objective treadmill exercise test.

Acebutolol↗

Efficacy and safety of donepezil in patients with more severe Alzheimer's disease: a subgroup analysis from a randomized, placebo-controlled trial.

BACKGROUND: There have been very limited investigations of cholinesterase inhibitor therapy in more advanced stages of Alzheimer's disease (AD). The efficacy and safety of donepezil were evaluated in post hoc analyses of a subgroup of patients with more severe AD (standardized Mini-Mental State Examination [sMMSE] score 5-12) within a randomized, placebo-controlled trial in moderate to severe AD (MSAD study). Additional analyses examined whether donepezil's treatment effects were consistent across the full range of baseline AD severity studied (sMMSE score 5-17). METHODS: Patients with moderate to severe AD (n = 290) who were living in the community or in assisted living facilities received donepezil or placebo for 24 weeks; n = 145 in the more severe AD subgroup. The primary outcome measure was the Clinician's Interview-Based Impression of Change (CIBIC-plus) with secondary outcomes including the sMMSE, Severe Impairment Battery, Neuropsychiatric Inventory, and Disability Assessment for Dementia. Analysis of Variance and Analysis of Covariance models tested for treatment x disease severity interaction in the full MSAD study sample. RESULTS: CIBIC-plus scores for donepezil patients were significantly improved compared with placebo for each time-point, with a 0.70 mean treatment difference at Week 24 last observation carried forward (LOCF; p = 0.0002). Significant differences favoring donepezil were noted at Week 24 LOCF for all secondary measures. There were no treatment x severity interactions for any of the efficacy measures. CONCLUSIONS: In this analysis, donepezil had significant benefits over placebo on global, cognitive, functional, and behavioral measures in a subgroup of patients with more severe AD. Furthermore, the treatment effects of donepezil were not driven by a particular stratum within the moderate to severe dementia range.

Aged↗

Assessment of hepatic phagocytic activity by in vivo microscopy after liver transplantation in the rat.

Phagocytic activity of sinusoidal lining cells was studied in 32 livers of male Lewis rats by in vivo fluorescence microscopy with epiillumination. Normal livers (group 1, n = 8) were compared with orthotopic syngeneic liver grafts 90 min after reperfusion after a period of cold storage in University of Wisconsin solution for 17 hr (group 2, n = 10) or 24 hr (group 3, n = 14). After bolus injection of fluorescence-labeled latex particles (3 x 10(8)/kg; diameter = 1.1 micron), zonal distribution and kinetics of adherence of latex beads were quantified by off-line video analysis. Hepatocellular function was estimated by the rate of bile production and biliary concentrations of bile acids. In normal livers 50%, 37% and 13% of injected latex beads adhered in zones 1, 2 and 3, respectively, whereas in transplanted livers a more homogeneous distribution was found (group 2: 37%, 41%, 22%; group 3: 37%, 39%, 24%; p less than 0.01 vs. controls by analysis of variance). Kinetic analysis of phagocytic activity showed no significant difference between group 1 (88% adherence of visible latex beads 3 min after injection) and group 2 (90% adherence). However, after long-term preservation in group 3, sinusoidal adherence was significantly faster (96.4% adherence; p less than 0.001). Bile secretion in group 2 was lower than in controls and severely depressed in group 3 (group 1: 1.1 +/- 0.07 microliter/min/gm liver [mean +/- S.E.M.]; group 2: 0.8 +/- 0.07; group 3: 0.1 +/- 0.04; p less than 0.001) without significant changes in bile acid concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Formation of DNA adducts and water-soluble metabolites of benzo[a]pyrene in human monocytes is genetically controlled.

Formation of DNA adducts and of water-soluble metabolites was studied in monocytes of 86 first-degree relatives of 15 families. Tests were performed with blood monocytes using (G-3H)-benzo[a]pyrene as a model pro-carcinogen. Variance analysis revealed significantly higher inter-familial than intra-familial variations. From these data we conclude that the formation of DNA adducts is genetically controlled. Therefore the enhanced formation of benzo[a]pyrene DNA adducts in lung cancer patients found in earlier studies may reflect a genetic predisposition for lung cancer in some patients.

Adolescent↗

Investigation of the relationship between nitric oxide metabolites' levels and adenosine deaminase activity in 7,12-dimethylbenz[a]anthracene induced mouse liver.

7,12-Dimethylbenz[a]anthracene (7,12-DMBA) is a member of the polycyclic aromatic hydrocarbons with a severe carcinogenic effect. In this study, nitrate levels and ADA (Adenosine deaminase) activity in the liver homogenates of mice were measured and the effect of free radicals induced by 7,12-DMBA on inducible nitric oxide synthase (iNOS) and ADA activity were investigated. Antioxidant effects of melatonin were also compared. Three groups of mice were included in the study. The first served as control, the second was treated only with 7,12-DMBA and the third was treated with 7,12-DMBA + melatonin. Spectrophotometric methods were used at all measurements. Data were analyzed using Kruskal-Wallis Variance Analysis Test and Mann-Whitney U Test that were applied to the groups. The nitrate concentrations of mouse liver were as follows: 4.98 +/- 0.63 micro mol/L in the control group (n = 10), 8.23 +/- 1.58 micro mol/L (higher than control group, p < 0.05) in the 7,12-DMBA-treated group (n = 10), and 6.43 +/- 0.57 micro mol/L (lower than 7,12-DMBA-treated group, p < 0.05) in the 7,12-DMBA + melatonin-treated group (n = 10). Liver ADA activities were measured to be 4.14 +/- 0.674 U/L in the control group, 6.25 +/- 1.261 U/L (higher than control group, p < 0.05) in the 7,12-DMBA-treated group, and 4.93 +/- 0.916 U/L (lower than 7,12-DMBA-treated group, p < 0.05) in the 7,12-DMBA+melatonin-treated group. Differences between free nitrite levels were no significantly. Results demonstrated that nitrate levels and ADA activities were increased by means of free radicals induced by 7,12-DMBA. Melatonin inhibited the 7,12-DMBA induced increase that was observed in the activities of ADA enzyme and nitrate levels. It is concluded that determination of ADA activity and nitrate levels can be useful in the assessment of liver damage caused by toxic chemicals.

9,10-Dimethyl-1,2-benzanthracene↗

Effects of corticosterone and 5 alpha-dihydrocorticosterone on brain excitability in the rat.

The effects of corticosterone (B) and its reduced metabolite 5 alpha-dihydrocorticosterone (DHB) on CNS activity in the rat were examined. Two indices of brain excitability were evaluated: 1) amplitude of population responses (evoked potentials [EP] to sciatic nerve stimulation) and 2) changes in the rate of firing of tonically discharging neurons--both at pontine brainstem regions of the reticular formation. Experiments were carried out in adrenalectomized rats, and recordings were obtained from animals under urethane anesthesia. Steroids were dissolved in a 4:1 saline:Cremophor-El (Sigma) solution and doses of 750 micrograms/0.5 ml were injected (IV). The effects of B on EPs were bidirectional. Increases (8 animals) and decreases (6 animals) of the amplitude responses in different animals were observed. In 4 animals, no changes were detected. In contrast, injection of DHB produced a consistent and significant reduction of brainstem sciatic evoked potentials in 10 of 12 animals tested; 2 animals did not respond to the steroid. At the neuronal level, the effects of the steroids were evaluated by the changes they induced in the mean firing frequency (P less than 0.01) measured during 5-min intervals as determined by a one-way analysis of variance and analysis with a test of multiple comparisons. Only cells that fired in a stationary mode for 15 min before the steroid injection were studied. A more consistent pattern of responses to B was observed at the single-cell level. From 31 neurons that responded to the hormone, of 76 examined, 27 showed an increase in their firing rate and only 4 neurons showed a decrease. The increase in firing rate had an onset latency of 2-5 min (means = 3.5, SE 0.43) with a duration of 16-25 min (means = 17.5, SE 2.7). Of 69 neurons that were tested with DHB, 51 showed a significant decrease in their mean firing frequency. Onset latency of the effect was 2-8 min (means = 4.0, SE 1.21) and the duration of the induced changes was 16-40 min (means = 30.0, SE 3.47). Central interactions of DHB and B when sequentially administered were examined in 28 neurons. Of these, 21 responded to DHB administration with a significant decrease in their firing rates. In 11 of these neurons, injection of B, 5 min after DHB, was followed by a rapid (1-2 min) return of the neurons to baseline firing rates.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

In vivo proton MR spectroscopy of human gliomas: definition of metabolic coordinates for multi-dimensional classification.

Several multi-dimensional statistical evaluation methods were applied to single-voxel proton MR spectra of glial brain tumors and of healthy volunteers. Metabolic coordinates with histological relevance for future diagnosis were found by which spectra from controls, low-grade tumors, and high-grade tumors were completely separated. Significant differences between low-grade and high-grade glioma patients and controls were found for several metabolic ratios by variance analysis. Cluster analysis both with and without principal component analysis was applied. The outcome of these two approaches depended mainly on the lipid-to-creatine ratio. Two other approaches, discriminant factor analysis and the orthonormal discriminant vector method were then used to find discriminatory metabolic coordinates. It turned out that a linear combination of all evaluable metabolic ratios made it possible to separate the three groups completely. On the basis of these results, a classification method that uses the entire proton MRS spectrum is proposed.

Adult↗

Analgesic and hepatotoxic effects of Ononis spinosa L.

The present study investigated the analgesic and hepatoprotective activities of a water extract of Ononis spinosa L. (OS) in mice. Analgesic activity was based on the pain thresholds measured with the tail-flick test before administration at 30, 90 and 150 min. The results were analysed with one-way variance analysis. The extract of Ononis spinosa showed analgesic activity equivalent to aspirin at 30 and 90 min and even higher than aspirin with the 50 mg/kg dose. At a dose of 100 mg/kg OS showed an analgesic effect equivalent to aspirin at all time points.The hepatoprotective influence of OS on carbon tetrachloride (CCl(4))-induced acute liver toxicity was also studied. The extract had no significant effect on the increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin in CCl(4) treated animals (p > 0.05). Thus, the results reveal that the extract of OS had no hepatoprotective effect on CCl(4)-induced acute liver toxicity.

Alanine Transaminase↗