Biomedical subjects
Publications and source records attributed to J M Davis.
We describe an immunocompetent adolescent who presented with exceptionally severe Bordetella holmesii infection, including previously undescribed manifestations. Sequelae included a severe restrictive lung defect due to pulmonary fibrosis.
It has previously been shown that hyperoxia induces nonapoptotic cell death in cultured lung epithelial cells, whereas hydrogen peroxide (H(2)O(2)) and paraquat cause apoptosis. To test whether pathways leading to oxidative apoptosis in epithelial cells are sensitive to molecular O(2), A549 cells were exposed to 95% O(2) prior to exposure to lethal concentrations of H(2)O(2). The extent of H(2)O(2)-induced apoptosis was significantly reduced in cells preexposed to hyperoxia compared with room-air controls. Preexposure of the hyperoxia-resistant HeLa-80 cell line to 80% O(2) also inhibited oxidant-induced apoptosis, suggesting that this inhibition is not due to O(2) toxicity. Because hyperoxia generates reactive oxygen species and activates the redox-sensitive transcription factor nuclear factor kappa B (NF-kappa B), the role of antioxidant enzymes and NF-kappa B were examined in this inhibitory process. The onset of inhibition appeared to be directly related to the degradation of I kappa B and subsequent activation of NF-kappa B (either by hyperoxia or TNF-alpha), whereas no significant up-regulation of endogenous antioxidant enzyme activities was found. In addition, suppression of NF-kappa B activities by transfecting A549 cells with a dominant-negative mutant construct of I kappa B significantly augmented the extent of H(2)O(2)-induced apoptosis. These data suggest that hyperoxia inhibits oxidant-induced apoptosis and that this inhibition is mediated by NF-kappa B.
Maternal anxiety and pain prolong labor and contribute to fetal distress. Hydrotherapy during labor may promote relaxation and decrease pain without the risks caused by other treatments. In this pilot study the psychophysiological effects of hydrotherapy on maternal anxiety and pain during labor were examined. Using a randomized, pretest-posttest control group design with repeated measures, 18 term parturients were assigned to a control or an experimental group. Experimental subjects were placed in a tub of 37 degrees C water for 1 hr during early labor. The Wilcoxon two-sample test revealed statistically significant effects. At 15 min bathers' anxiety and pain scores were decreased compared to nonbathers. At 60 min bathers' pain scores were decreased compared to nonbathers. After 15 min of immersion, bathers had a significantly greater increase in plasma volume than nonbathers. No significant differences were found in urine catecholamines or maternal-fetal complications. The small sample limits conclusions, but the findings offer preliminary support for the therapeutic effects of bathing in labor for acute, short-term anxiety and pain reduction.
BACKGROUND: Free oxygen radicals have been implicated in the pathogenesis of chronic lung disease in preterm infants. Superoxide dismutase is a naturally occurring enzyme which provides a defence against such oxidant injury. Exogenously administered superoxide dismutase has been tested in clinical trials to prevent chronic lung disease in preterm infants. OBJECTIVES: To determine if exogenously administered superoxide dismutase is efficacious in the prevention of chronic lung disease in preterm infants who are mechanically ventilated, and efficacious in decreasing the following outcomes: bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, necrotizing enterocolitis, patent ductus arteriosus and mortality. To determine the frequency and nature of adverse effects of superoxide dismutase. SEARCH STRATEGY: We searched Medline (1966 - 2000) and the Cochrane Controlled Trials Register (CCTR) using the following keywords: [bronchopulmonary dysplasia OR chronic lung disease] AND superoxide dismutase, limited to human studies in newborn infants (infant, newborn). We hand searched the reference lists of articles located and the abstracts of the Society for Pediatric Research (USA) (published in Pediatric Research) from 1980 - 2000. SELECTION CRITERIA: Randomized controlled trials where subjects were preterm infants who had developed or were at risk of developing respiratory distress syndrome requiring assisted ventilation and who were randomly allocated to receive either superoxide dismutase (in any form, by any route) or placebo or no treatment. We included studies which reported any of the following outcomes: chronic lung disease, bronchopulmonary dysplasia, any intraventricular hemorrhage, intraventricular hemorrhage grades III/IV, patent ductus arteriosus, periventricular leukomalacia, retinopathy of prematurity, necrotizing enterocolitis, neonatal mortality, death prior to discharge and neurodevelopmental outcome. DATA COLLECTION AND ANALYSIS: We extracted and assessed separately all data for each study and entered final data into RevMan. We did not perform subgroup analyses (which were originally planned) because only two studies were eligible for inclusion. We assessed the methodological quality of the studies by assessing the risk for bias. We pooled the outcomes of infants who had developed bronchopulmonary dysplasia at 28 days with those who had died at 28 days to derive the combined outcome of bronchopulmonary dysplasia or death at 28 days. Similarly we pooled the outcomes of infants who had respiratory problems after discharge with those who had died prior to discharge to derive the combined outcome of respiratory problems after discharge or death. We used the standard method of the Cochrane Neonatal Review Group for statistical analysis, using a fixed effect model. MAIN RESULTS: Two randomized controlled trials were included for analysis. No differences were found in either study or in the pooled data in death prior to discharge, oxygen dependency at 36 weeks corrected age, oxygen dependency at 28 days of life or in other outcomes. In one study (Rosenfeld 1984), survivors who had been treated with superoxide dismutase had a shorter duration of continuous positive airway pressure (4.9 vs 9.7 days), a lower frequency of respiratory problems after discharge (relative risk 0.33, 95% confidence limits 0.11, 0.96) and a lower frequency of chest radiograph abnormalities (relative risk 0.30, 95% confidence limits 0.11, 0.87) compared to survivors who received placebo. A third study was available only in abstract form and will be evaluated for inclusion after publication. REVIEWER'S CONCLUSIONS: Based on currently available published trials, there is insufficient evidence to draw firm conclusions about the efficacy of superoxide dismutase in preventing chronic lung disease of prematurity. Data from a small number of treated infants suggest that it is well tolerated and has no serious adverse effects.
A quantitative theory of plate number N in capillary electrophoresis was developed for buffers containing neutral cyclodextrins (CDs) capable of forming inclusion complexes. In the theory, N was modeled by longitudinal diffusion, injection extent, width of the detection window, and the detector time constant. The apparent mobility was modeled as a weighted sum of the mobilities of the free-solution analyte and the inclusion complex. The apparent diffusion coefficient was modeled as a similarly weighted sum. Both the apparent mobility and diffusion coefficient were corrected by functions that compensated for increases of buffer temperature caused by Joule heat. The experimental N's and apparent mobilities of neutral thiourea and of the anions, dansyl D- and L-leucine, dansyl D- and L-aspartic acid, benzoate, and 4-nitrophenolate, were determined in buffers containing from 0 to 15 mM beta-CD. The binding constants, and mobilities and diffusion coefficients of the free-solution analyte and inclusion complex, were calculated as regression coefficients by fitting theory to these determinations. The regression coefficients were shown to have physicochemical meaning, as assessed by literature values, independent measurements, and theoretical predictions. The assessment showed the Nernst-Einstein equation does not relate mobilities and diffusion coefficients at the electrolyte concentration used. The interdependence of mobilities, diffusion coefficients, binding constants, and other dispersion sources was interpreted to evaluate the factors affecting the variation of N with CD concentration. From the interpretation, an approximate equation for N in low-concentration CD buffers was derived. The equation depends on free-solution and inclusion-complex mobilities and diffusion coefficients, the binding constant, the potential difference over the effective capillary length, and the number of plates in a CD-free buffer.
The purpose of this research was to describe further the effects of exercise-induced muscle damage on reflex sensitivity. The subjects were eight physically active, but untrained males, between the ages of 18 and 29 years. The effects of eccentric and concentric exercise on patellar tendon reflex responses were determined. The 8 week experiment consisted of two, 5 day, test protocols with a 6 week wash-out period between test protocols. Each 5 day test protocol consisted of the following six test sessions: (1) day 1--baseline, (2) day 2 baseline, (3) day 2--immediate post-exercise, and (4-6) days 3-5: 24, 48, and 72 h post-exercise. On day 2, the subjects made either 100 fatiguing concentric or eccentric isotonic contractions using the right leg at 75% of the corresponding repetition maximum values. During each test session, the electromyogram (EMG) and force-time characteristics of basic and conditioned patellar tendon reflex responses were measured. The reflex amplitudes of basic and conditioned patellar tendon reflex responses were decreased following fatiguing concentric exercise. There were no immediate effects of fatiguing eccentric exercise on the basic and conditioned patellar tendon reflex responses, but the EMG amplitudes of these reflex responses were reduced on the days following eccentric exercise. The amount of conditioned patellar tendon reflex facilitation was decreased following the concentric exercise protocol and at 48 h post-eccentric exercise. Our conditioned reflex data suggest that post-exercise changes to the physiological mechanisms that modulate the recruitment gain of the alpha-motoneuron pool may depend upon the type of fatiguing exercise.
BACKGROUND: We investigated the structure of manic episodes by determining whether there was evidence for distinct groups of patients differing in clinical characteristics and course of illness. METHODS: The subjects were 162 patients hospitalized for manic episodes who underwent comprehensive evaluations of behavior, symptoms, and history before a treatment study. Pretreatment behavior ratings (Schedule for Affective Disorders and Schizophrenia, rated by clinicians, and Affective Disorder Rating Scale, rated by nurses) entered a principal components factor analysis, followed by a cluster analysis of the subjects based on their factor scores. Members of the resulting clusters were compared with respect to clinical characteristics and history of illness. RESULTS: The six factors were impulsivity, hyperactivity, anxious pessimism, distressed appearance, hostility, and psychosis. The four clusters were characterized as depressive, with high anxious pessimism (n=22), delusional, with high psychosis (n=39), classic (n=72), and irritable, with high distressed appearance and hostility (n=29). Depressive manics had the earliest onset of illness and the highest density of episodes/year, while irritable manics had later onset and the fewest previous episodes. LIMITATIONS: The number of subjects was smaller than ideal for multivariate analysis, subjects were limited to those able to consent and meet criteria for a randomized clinical trial, and course of illness was determined retrospectively. CONCLUSIONS: Manic episodes have a dimensional structure but appear to fall naturalistically into types that differ with respect to previous history, symptoms, and clinical characteristics. Whether these are distinct clinical subtypes will require further research.
Sapphyrin was the first expanded porphyrin to be reported in the literature and remains among the most extensively studied. Much of the interest in this macrocycle reflects its ability to bind anions, a phenomenon that has been examined in solution and in the solid state by a wide range of experimental techniques. In this Account, we summarize these studies while also outlining strategies that may be used to synthesize sapphyrins.
Exercise can increase plasma inflammatory cytokine concentrations in humans, but tissue responses are not well studied. We examined plasma concentrations and tissue expression of TNFalpha, IL-1beta, and IL-6 following treadmill running in mice. C57B1/6 mice were randomly assigned to: non-exercise control (CON), sacrifice at 0 or 1.5 h after 60 min running (MOD0, MOD 1.5), sacrifice at 0, 1.5, or 3 h after fatiguing running (approximately 3 h) (EX0, EX1.5, EX3), or lipopolysaccharide (25 microg) with no exercise (LPS). Lung, liver, muscle, and brain mRNA expression was analyzed (n = 4-6/group) using reverse transcriptase-rapid polymerase chain reaction (RT-RPCR). Plasma cytokine concentrations were determined (n =4-10/group) by ELISA. Plasma IL-6 was higher in EX1.5, and lung TNFalpha mRNA was higher in EX1.5 and EX3 compared to CON (P < 0.05). No significant increases in plasma cytokine concentrations or tissue cytokine expression were found in other EX groups. LPS significantly increased these cytokine measures in tissues and plasma, with the exception of plasma IL-1beta which was undetectable. The source of the plasma IL-6 following exercise does not appear to be lung, liver, muscle, or brain tissue, and remains to be determined. These data also suggest that tissue level cytokine expression may not necessarily lead to increased plasma cytokine concentrations.
A summary is given of the pathology results after long-term inhalation in rats of insulation wool representing the new biosoluble types. The pathology results are compared with previously conducted long-term inhalation study with MMVF21 (traditional stone wool). The biosoluble fiber MMVF34/HT (HT) is characterized by a relatively high content of aluminum and a relatively low content of silica compared to the older MMVF21. HT has a high in vitro dissolution rate at pH 4.5, and a relatively low dissolution rate at pH 7.5. Male Fischer 344 rats were exposed at one exposure level of 30 mg/m(3) by nose-only inhalation of a well-characterized fiber test atmosphere. The fibers had been size selected to be largely rat respirable. The negative control group was exposed to filtered air. The exposure duration was 6 h/day, 5 days/wk for 104 wk, with a subsequent nonexposure period lasting until approximately 20% survival in the air control group. Interim sacrifices were performed at wk 13, 26, 52, 78, and 104 to monitor the progression of pulmonary change and fiber numbers. Effectively the main protocol for the previously conducted chronic study with MMVF21 was the same, except that there were three concentration levels (3, 16, and 30 mg/m(3)). In addition to the endpoints measured in the previous study, slides from both studies were evaluated for collagen deposition using a quantitative morphometric method. The results of the comparative study clearly showed a marked difference in the pulmonary pathogenicity of the MMVF21 and HT in terms of their fibrogenic potential. MMVF21 caused pulmonary fibrosis, but the HT fiber did not. The incidence of tumors for both the HT and the MMVF21 fiber was comparable to the control groups.
A widely used gasoline additive, methyl tertiary butyl ether (MTBE), has been controversial, in part because of concerns about potential inhalation health effects and more recently because of added concerns about water contamination. Although many of the issues related to MTBE have not been fully resolved, several apparent paradoxes can be discerned, including the fact that something intended to improve air quality is now seen as a threat to water quality. Among the lessons that can be derived from the MTBE experience is the value of a comprehensive understanding of the potential risk-benefit tradeoffs of different fuels and fuel additives.
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The relative efficacy and safety of risperidone versus haloperidol in the treatment of schizoaffective disorder was studied. Sixty-two patients (29 depressed type; 33 bipolar type) entered a three-site, randomized, double-blind, 6-week trial of risperidone (up to 10 mg/day) or haloperidol (up to 20 mg/day). Trained raters assessed baseline, weekly, and end-of-study levels of psychopathology with the Positive and Negative Syndrome Scale (PANSS), the 24-item Hamilton Rating Scale for Depression (HAM-D-24) and the Clinician-Administered Rating Scale for Mania (CARS-M). The authors were unable to statistically distinguish between risperidone and haloperidol in the amelioration of psychotic and manic symptoms. In addition, there was no difference in worsening of mania between the two agents in either subgroup (i.e., depressed or bipolar subgroups). For the total PANSS, risperidone produced a mean decrease of 16 points from baseline compared with a 14-point decrease with haloperidol. For the total CARS-M scale, risperidone and haloperidol produced mean change scores of 5 and 8 points, respectively, and for the CARS-M Mania subscale, 3 and 7 points, respectively. Additionally, risperidone produced a mean decrease of 13 points from the baseline 24-item HAM-D, compared with an 8-point decrease with haloperidol. In those patients who had more severe depressive symptoms (i.e., HAM-D baseline score >20), risperidone produced at least a 50% mean improvement in 12 (75%) of 16 patients in comparison to 8 (38%) of 21 patients receiving haloperidol. Haloperidol produced significantly more extrapyramidal side effects and resulted in more dropouts caused by any side effect. There was no difference between risperidone and haloperidol in reducing both psychotic and manic symptoms in this group of patients with schizoaffective disorder. Risperidone did not demonstrate a propensity to precipitate mania and was better tolerated than haloperidol. In those subjects with higher baseline HAM-D scores (i.e., >20), risperidone produced a greater improvement in depressive symptoms than haloperidol.
OBJECTIVE: To compare elder patients' and their informants' ratings of the elder's physical and mental function measured by a standard instrument, the Medical Outcomes Study Short Form 12 (SF-12). METHODS: This was a randomized, cross-sectional study conducted at a university-affiliated community teaching hospital emergency department (census 65,000/year). Patients >69 years old, arriving on weekdays between 10 AM and 7 PM, able to engage in English conversation, and consenting to participate were eligible. Patients too ill to participate were excluded. Informants were people who accompanied and knew the patient. Elder patients were randomized 1:1 to receive an interview or questionnaire version of the SF-12. The questionnaire was read to people unable to read. Two trained medical students administered the instrument. The SF-12 algorithm was used to calculate physical (PCS) and mental (MCS) component scores. Oral and written versions were compared using analysis of variance. The PCS and MCS scores between patient-informant pairs were compared with a matched t-test. Alpha was 0.05. RESULTS: One hundred six patients and 55 informants were enrolled. The patients' average (+/-SD) age was 77 +/- 5 years; 59 (56%; 95% CI = 46% to 65%) were women. There was no significant difference for mode of administration in PCS (p = 0.53) or MCS (p = 0.14) scores. Patients rated themselves higher on physical function than did their proxies. There was a 4.1 (95% CI = 99 to 7.2) point difference between patients' and their proxies' physical component scores (p = 0.01). Scores on the mental component were quite similar. The mean difference between patients and proxies was 0.49 (95% CI = 3.17 to 4.16). The half point higher rating by patients was not statistically significant (p = 0.79). CONCLUSIONS: Elders' self-ratings of physical function were higher than those of proxies who knew them. There was no difference in mental function ratings between patients and their proxies. Switching from informants' to patients' reports in evaluating elders' physical function in longitudinal studies may introduce error.
The influence of carbohydrate (1 l/h of a 6% carbohydrate beverage), gender, and age on pro- and anti-inflammatory plasma cytokine and hormone changes was studied in 98 runners for 1.5 h after two competitive marathon races. The marathoner runners were randomly assigned to carbohydrate (C, n = 48) and placebo (P, n = 50) groups, with beverages administered during the races in a double-blind fashion using color codes. Plasma glucose was higher and cortisol was lower in the C than in the P group after the race (P < 0.001). For all subjects combined, plasma levels of interleukin (IL)-10, IL-1 receptor antagonist (IL-1ra), IL-6, and IL-8 rose significantly immediately after the race and remained above prerace levels 1.5 h later. The pattern of change in all cytokines did not differ significantly between the 12 women and 86 men in the study and the 23 subjects > or =50 yr of age and the 75 subjects <50 yr of age. The pattern of change in IL-10, IL-1ra, and IL-8, but not IL-6, differed significantly between the C and the P group, with higher postrace values measured for IL-10 (109% higher) and IL-1ra (212%) in the P group and for IL-8 (42%) in the C group. In conclusion, plasma levels of IL-10, IL-1ra, IL-6, and IL-8 rose strongly in runners after a competitive marathon, and this was not influenced by age or gender. Carbohydrate ingestion, however, had a major effect in attenuating increases in cortisol and two anti-inflammatory cytokines, IL-10 and IL-1ra.
To determine whether overexpression of antioxidant enzymes in lung epithelial cells prevents damage from oxidant injury, stable cell lines were generated with complementary DNAs encoding manganese superoxide dismutase (MnSOD) and/or catalase (CAT). Cell lines overexpressing MnSOD, CAT, or MnSOD + CAT were assessed for tolerance to hyperoxia or paraquat. After exposure to 95% O(2) for 10 d, 44 to 57% of cells overexpressing both MnSOD and CAT and 37 to 47% of cells overexpressing MnSOD alone were viable compared with 7 to 12% of empty vector or parental cells (P < 0.05). To assess if viable cells were capable of cell division after hyperoxic exposures (up to 5 d), a clonogenicity assay was performed. The clonogenic potential of cells overexpressing MnSOD + CAT and MnSOD alone were significantly better than those expressing CAT alone or empty vector controls. In addition, 54 to 72% of cells overexpressing both MnSOD and CAT survived in 1 mM paraquat compared with 58 to 73% with MnSOD alone and 27% with control cells. Overexpression of CAT alone did not improve survival in hyperoxia or paraquat. The combination of MnSOD + CAT did not provide additional protection from paraquat. Data demonstrate that overexpression of MnSOD protects cells from oxidant injury and CAT offers additional protection from hyperoxic injury when co-expressed with MnSOD.
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BACKGROUND: The choice of drug to treat a patient with schizophrenia is one of the most critical clinical decisions. Controversy exists on the differential efficacy of olanzapine. DATA SOURCES AND STUDY SELECTION: Raw data from all 4 registrational double-blind, random-assignment studies of olanzapine compared with placebo or haloperidol were obtained from Eli Lilly and Company for this meta-analysis. METHOD: Analysis of covariance of the intent-to-treat last-observation-carried-forward endpoint scores was used to assess efficacy on Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Syndrome Scale (PANSS) total scores and the 5 factors derived by factor analysis (negative symptoms, positive symptoms, disorganized thoughts, impulsivity/hostility, and anxiety/depression). RESULTS: Olanzapine produced a statistically significantly greater reduction in schizophrenic symptoms than haloperidol (p < .05) on total scores on the BPRS and PANSS on each of the 5 factors as well as on almost all items. Olanzapine induced a response at a rate equal to that induced by haloperidol in the first few weeks, but by the end of the study produced a greater percentage of responders. Compared with haloperidol, olanzapine produced a somewhat greater response on symptoms responsive to haloperidol, but a markedly better response on symptoms unresponsive to haloperidol. This difference favoring olanzapine occurred to an equal degree in all subgroups examined. The incidence of parkinsonism or akathisia following olanzapine treatment was extremely low and not statistically distinguishable from placebo. CONCLUSION: Olanzapine produced a greater improvement than haloperidol particularly by benefiting a much larger number of items or factors. Extrapyramidal side effects and akathisia during olanzapine treatment were statistically indistinguishable from effects seen with placebo.