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Biomedical subjects

J M Davis

Publications and source records attributed to J M Davis.

At least 19 recordsLinked to original sources

Ovarian hormone status and skeletal muscle inflammation during recovery from disuse in rats.

Resumption of normal muscle loading after a period of disuse initiates cellular processes related to mass accretion. The renewed loading also induces a significant amount of muscle damage and subsequent inflammation. Ovarian hormone depletion delays atrophied myofibre mass recovery. Ovarian hormones are also global regulators of immune system function. The purpose of this study was to determine whether ovarian hormone depletion-induced deficits in myofibre regrowth after disuse atrophy are related to the induction of muscle damage and the associated inflammatory response. We hypothesized that soleus muscle immune cell infiltration and inflammatory gene expression would be both accentuated and prolonged in ovarian hormone-depleted rats during the first week of recovery from disuse atrophy. Intact and ovariectomized (OVX) female rats were subjected to hindlimb suspension for 10 days and then returned to normal ambulation for a recovery period, the rats were killed and the soleus muscle removed for analysis. Although reloading increased both circulating creatine kinase and myofibre membrane disruption, there was no effect of ovarian hormones on these processes during recovery. Muscle neutrophil concentration was increased above baseline regardless of hormone status at days 1 and 3 of recovery; however, this increase was 43% greater at day 3 in the OVX group. Muscle ED1+ and ED2+ macrophage concentrations were increased during recovery in both groups. However, macropage concentrations remained elevated at day 7 of recovery in the OVX group, whereas they returned to control levels in the intact group. Cyclo-oxygenase-2, interleukin-6 and interleukin-1beta muscle mRNA expression increased similarly during recovery, regardless of ovarian hormone status. These results demonstrate that the initial myofibre damage and inflammatory gene expression induced during muscle recovery from disuse atrophy are independent of ovarian hormone status.

Animals↗

Estrogen status and skeletal muscle recovery from disuse atrophy.

Although estrogen loss can alter skeletal muscle recovery from disuse, the specific components of muscle regrowth that are estrogen sensitive have not been described. The primary purpose of this study was to determine the components of skeletal muscle mass recovery that are biological targets of estrogen. Intact, ovariectomized (OVX), and ovariectomized with 17beta-estradiol replacement (OVX+E2) female rats were subjected to hindlimb suspension for 10 days and then returned to normal cage ambulation for the duration of recovery. Soleus muscle mass returned to control levels by day 7 of recovery in the intact animals, whereas OVX soleus mass did not recover until day 14. Intact rats recovered soleus mean myofiber cross-sectional area (CSA) by day 14 of recovery, whereas the OVX soleus remained decreased (42%) at day 14. OVX mean fiber CSA did return to control levels by day 28 of recovery. The OVX+E2 treatment group recovered mean CSA at day 14, as in the intact animals. Myofibers demonstrating central nuclei were increased at day 14 in the OVX group, but not in intact or OVX+E2 animals. The percent noncontractile tissue was also increased 29% in OVX muscle at day 14, but not in either intact or OVX+E2 groups. In addition, collagen 1a mRNA was increased 45% in OVX muscle at day 14 of recovery. These results suggest that myofiber growth, myofiber regeneration, and extracellular matrix remodeling are estrogen-sensitive components of soleus muscle mass recovery from disuse atrophy.

Animals↗

Role of lung macrophages on susceptibility to respiratory infection following short-term moderate exercise training.

Moderate exercise training is associated with a decreased risk for upper respiratory tract infection in human and animal studies, but the mechanisms have not been elucidated. Lung macrophages play an important role in resistance to respiratory infection, and moderate exercise can enhance macrophage antiviral resistance, but no studies have directly tested the role of lung macrophages in this response. This study tested the effect of lung macrophage depletion on susceptibility to infection following short-term moderate exercise training. Mice were assigned to one of four groups: exercise (Ex) and resting controls (Con) with and without clodronate encapsulated liposomes (CL(2)MDP-lip). Ex mice ran for 1 h on a treadmill for 6 days at 36 m/min, 8% grade. Fifteen minutes following exercise or rest on the last day of training, mice were intranasally inoculated with a standardized dose of herpes simplex virus type 1. Clodronate (Ex-CL(2)MDP-lip and Con-CL(2)MDP-lip) or PBS liposomes (Ex-PBS-lip and Con-PBS-lip) (100 microl) were intranasally administered following exercise or rest on the 4th day of training and again on the 4th day postinfection. Morbidity, mortality, and symptom severity were monitored for 21 days. Exercise decreased morbidity by 36%, mortality by 61%, and symptom severity score on days 5-7 (P < 0.05). Depletion of lung macrophages negated the beneficial effects of moderate exercise. This was indicated by no differences between Ex-CL(2)MDP-lip and Con-PBS-lip in morbidity (89 vs. 95%), mortality (79 vs. 95%), or symptom severity. Results indicate that lung macrophages play an important role in mediating the beneficial effects of moderate exercise on susceptibility to respiratory infection.

Animals↗

A study of mixing in thermocapillary flows on micropatterned surfaces.

The recent introduction of actuation mechanisms for microfluidic transport based on free surface flows raises a number of interesting questions involving efficient mixing configurations, especially in systems with small aspect ratios. This work investigates the characteristics of convective and diffusive mixing in continuous-mode streaming of thermocapillary microflows on chemically micropatterned surfaces. Mixing times and mixing lengths relevant to chemical microreactors or gas sensors are investigated for various geometries and parameter ranges. Scaling arguments and full numerical solutions are presented to extract optimal operating conditions. Confocal fluorescence microscopy measurements of the interfacial diffusive broadening in adjacent flowing streams confirm numerical predictions. Three important mixing regimes, based on analogues of purely diffusive dynamics, Rhines-Young shear-augmented diffusion and Taylor-Aris dispersion are identified and investigated for use in free surface flows with large surface-to-volume ratios.

Capillary Action↗

Effects of moderate exercise and oat beta-glucan on lung tumor metastases and macrophage antitumor cytotoxicity.

Both moderate exercise and the soluble fiber beta-glucan can have beneficial effects on the initiation and growth of tumors, but the data are limited, and there is no information on their combined effects. This study tested the independent and combined effects of short-term moderate-exercise training and the soluble oat fiber beta-glucan (ObetaG) on the metatastic spread of injected tumor cells and macrophage antitumor cytotoxicity. Male C57BL/6 mice were assigned to one of four groups: exercise (Ex)-H2O, Ex-ObetaG, control (Con)-H2O, or Con-ObetaG. ObetaG was fed in the drinking water for 10 days before tumor administration and death. Exercise consisted of treadmill running (1 h/day) for 6 days. After rest or exercise on the last day of training, syngeneic B16 melanoma cells (2 x 10(5)) were administered via intravenous injection (n = 8-11 per group). Lungs were removed 14 days later, and tumor foci were counted. Additional mice (n = 8 per group) were killed, and peritoneal macrophages were assayed for cytotoxicity against the same mouse tumor cell line at various effector-to-target ratios. Both moderate exercise and ObetaG decreased lung tumor foci and increased macrophage cytotoxicity. However, there were no differences in lung tumor foci and macrophage cytotoxicity between Ex-ObetaG and either Ex-H2O or Con-ObetaG. These data suggest that, although not additive in their effects, both short-term moderate-exercise training and consumption of the soluble ObetaG can decrease the metatastic spread of injected B16 melanoma cells, and these effects may be mediated in part by an increase in macrophage cytotoxicity to B16 melanoma.

Administration, Oral↗

A GABAergic cortical deficit dominates schizophrenia pathophysiology.

Several lines of evidence support the role of an epigenetic-induced GABAergic cortical dysfunction in schizophrenia psychopathology, which is probably dependent on an increase in the expression of DNA-methyltransferase-1 occurring selectively in GABAergic neurons. The key enzyme regulating GABA synthesis, termed glutamic acid decarboxylase 67 (GAD67) and the important neurodevelopmental protein called reelin are coexpressed in GABAergic neurons. Upon release, GABA and reelin bind to postsynaptic receptors located in dendrites, somata, or the axon initial segment of pyramidal neurons. Because GAD67 and reelin are downregulated in schizophrenia, it is suggested that schizophrenics may express GABAergic deficit-related alterations of pyramidal neuron function. A reduction of dendritic spines is a finding reported in the prefrontal cortex of schizophrenia patients. Because dendritic spines are innervated by glutamatergic axon terminals, very probably this reduction of dendritic spine expression is translated into a functional deficit of glutamatergic transmission. Plastic modifications of neuronal circuits are probably dependent on GABAergic transmitter tone, and it is likely that GABAergic dysfunction is at the root of synaptic plasticity deficits in schizophrenia. Thus, a possible avenue for the treatment of schizophrenia would be to address this GABAergic functional deficit using positive allosteric modulators of the action of GABA at GABAA receptors. Benzodiazepines (BZ) such as diazepam are effective in treating positive and negative symptoms of schizophrenia, but because they positively modulate GABAA receptors expressing alpha1 subunits, these BZs cause sedation and tolerance. In contrast, imidazenil, a full allosteric modulator of GABAA receptors expressing alpha5 subunits may reduce psychotic symptomatology without producing sedation. Hence, imidazenil should be appropriately studied as a prospective candidate for a pharmacological intervention in schizophrenia.

Animals↗

Influence of carbohydrate ingestion on immune changes after 2 h of intensive resistance training.

Thirty strength-trained subjects were randomized to carbohydrate (CHO) or placebo (Pla) groups and lifted weights for 2 h (10 exercises, 4 sets each, 10 repetitions, with 2- to 3-min rest intervals). Subjects received 10 ml x kg(-1) x h(-1) CHO (6%) or Pla beverages during the weight training bout. Blood, saliva, and vastus lateralis muscle biopsy samples were collected before and after exercise. Blood cell counts were determined, and plasma was analyzed for IL-6, IL-10, IL-1 receptor antagonist (IL-1ra), IL-8, and cortisol. Muscle was analyzed for glycogen content and relative gene expression of 13 cytokines (IL-1alpha, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p35, IL-12p40, IL-15, IFN-gamma, TNF-alpha) by use of real-time quantitative RT-PCR. Significant but modest increases were measured for plasma IL-6, IL-10, IL-1ra, and IL-8, but the pattern of increase did not differ between CHO and Pla groups. The rate of decrease in muscle glycogen content did not differ between CHO and Pla (P = 0.463). Muscle cytokine mRNA was detected preexercise for IL-1beta, IL-6, IL-15, IL-8, and TNF-alpha, and of these, IL-1beta, IL-6, IL-8, and TNF-alpha were significantly increased after the 2-h weight training bout. The increase in mRNA (fold difference from preexercise) did not differ between CHO and Pla groups. In summary, CHO vs. Pla ingestion did not alter modest increases measured for plasma IL-6, IL-10, IL-1ra, and IL-8, and muscle gene expression for IL-1beta, IL-6, IL-8, and TNF-alpha in strength-trained subjects lifting weights intensively for 2 h.

Administration, Oral↗

Asking questions can help: development and preliminary evaluation of a question prompt list for palliative care patients.

Question prompt lists (QPLs) have been shown to be an inexpensive and effective communication tool for patients in oncology consultations. We aimed to develop and pilot a QPL for palliative care (PC) patients. In order to identify suitable questions for inclusion in the QPL, we conducted focus groups and individual interviews with 19 patients, 24 carers and 22 PC health professionals. A further 21 health professionals reviewed the draft document. The draft QPL was piloted in 23 patients. In total, 112 questions were identified and grouped into eight categories. All participants felt that the QPL, in booklet form, could be a useful tool. Out of 23 patients in the pilot study, 22 agreed that the QPL was helpful, contained useful questions, was easy to understand and would be useful in the future. State anxiety (STAI) decreased after receiving the booklet and seeing the doctor in 16 out of 19 patients (overall anxiety decreased by a median of 8, IQR 1-13). Participants in the pilot study endorsed the inclusion of end-of-life issues in the QPL, despite some reservations expressed about this by health professionals in the individual interviews. We have identified a specific QPL that might facilitate useful dialogue between PC patients and their doctor. The QPL has strong support from patients, their carers and relevant health professionals.

Adult↗

Effects of moderate exercise and oat beta-glucan on innate immune function and susceptibility to respiratory infection.

Both moderate exercise and the soluble oat fiber beta-glucan can increase immune function and decrease risk of infection, but no information exists on their possible combined effects. This study tested the effects of moderate exercise and oat beta-glucan on respiratory infection, macrophage antiviral resistance, and natural killer (NK) cell cytotoxicity. Mice were assigned to four groups: exercise and water, exercise and oat beta-glucan, control water, or control oat beta-glucan. Oat beta-glucan was fed in the drinking water for 10 days before intranasal inoculation of herpes simplex virus type 1 (HSV-1) or euthanasia. Exercise consisted of treadmill running (1 h/day) for 6 days. Macrophage resistance to HSV-1 was increased with both exercise and oat beta-glucan, whereas NK cell cytotoxicity was only increased with exercise. Exercise was also associated with a 45 and 38% decrease in morbidity and mortality, respectively. Mortality was also decreased with oat beta-glucan, but this effect did not reach statistical significance. No additive effects of exercise and oat beta-glucan were found. These data confirm a positive effect of both moderate exercise and oat beta-glucan on immune function, but only moderate exercise was associated with a significant reduction in the risk of upper respiratory tract infection in this model.

Animal Nutritional Physiological Phenomena↗

Carbohydrate ingestion influences skeletal muscle cytokine mRNA and plasma cytokine levels after a 3-h run.

Sixteen experienced marathoners ran on treadmills for 3 h at approximately 70% maximal oxygen consumption (Vo(2 max)) on two occasions while receiving 1 l/h carbohydrate (CHO) or placebo (Pla) beverages. Blood and vastus lateralis muscle biopsy samples were collected before and after exercise. Plasma was analyzed for IL-6, IL-10, IL-1 receptor agonist (IL-1ra), IL-8, cortisol, glucose, and insulin. Muscle was analyzed for glycogen content and relative gene expression of 13 cytokines by using real-time quantitative RT-PCR. Plasma glucose and insulin were higher, and cortisol, IL-6, IL-10, and IL-1ra, but not IL-8, were significantly lower postexercise in CHO vs. Pla. Change in muscle glycogen content did not differ between CHO and Pla (P = 0.246). Muscle cytokine mRNA content was detected preexercise for seven cytokines in this order (highest to lowest): IL-15, TNF-alpha, IL-8, IL-1beta, IL-12p35, IL-6, and IFN-gamma. After subjects ran for 3 h, gene expression above prerun levels was measured for five of these cytokines: IL-1beta, IL-6, and IL-8 (large increases), and IL-10 and TNF-alpha (small increases). The increase in mRNA (fold difference from preexercise) was attenuated in CHO (15.9-fold) compared with Pla (35.2-fold) for IL-6 (P = 0.071) and IL-8 (CHO, 7.8-fold; Pla, 23.3-fold; P = 0.063). CHO compared with Pla beverage ingestion attenuates the increase in plasma IL-6, IL-10, and IL-1ra and gene expression for IL-6 and IL-8 in athletes running 3 h at 70% Vo(2 max) despite no differences in muscle glycogen content.

Adult↗

Depot risperidone for schizophrenia.

BACKGROUND: Risperidone is the first new generation antipsychotic drug made available in a long acting injection. OBJECTIVES: To examine the clinical effects of depot risperidone for people with schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's Register (December 2002), references of all included studies, and contacted industry and authors of included studies. SELECTION CRITERIA: Randomised clinical trials comparing depot risperidone with other treatments for people with schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: Two reviewers independently inspected citations and/or abstracts, ordered papers, re-inspected and quality assessed the results, and extracted data. For dichotomous data, we calculated the relative risk (RR), the 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT), on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). MAIN RESULTS: One study (n=400) compared depot risperidone with placebo but 56% of people did not complete the three-month study rendering most global and mental state data unusable. Risperidone depot compared with placebo did not affect levels of anxiety (n=400, RR 0.58 CI 0.32 to 1.05) but may decrease agitation (n=400, RR 0.60 CI 0.39 to 0.92). Risperidone depot did not substantially influence hallucinations (n=400, RR 1.23 CI 0.47 to 3.22) but 'psychosis' was reduced (n=400, RR 0.52 CI 0.33 to 0.83, NNT 9 CI 7 to 26). Attrition was higher for the placebo group compared with people allocated risperidone depot (n=400, RR 0.74 CI 0.63 to 0.88, NNT 6 CI 4 to 12). Severe adverse events were common (13% to 23%) but significantly more so in the placebo group (n=400, RR 0.59 CI 0.38 to 0.93, NNT 11 CI 7 to 70). Poor reporting, however, makes these difficult to interpret. Movement disorders were equally common in both groups (n=400, RR 2.38 CI 0.73 to 7.78) although it looks as if there is a trend for the higher depot doses to encourage movement disorders. One study (n=640) compared depot risperidone against oral risperidone for stable people with relatively mild illness. For global outcomes there was no clear difference between the depot group and oral group (n=640, RR 'no global improvement' 1.06 CI 0.92 to 1.22). Mental state measures were also similar across groups. Overall, in this study compliance was good (n=640, RR <4 injections or "major protocol violation" 1.16 CI 0.81 to 1.67). Adverse effects were poorly reported but over half of both groups reported some adverse effect (n=640, RR 1.04 CI 0.91 to 1.18). REVIEWER'S CONCLUSIONS: There is no reliable data to support the claim that depot risperidone is beneficial for people with schizophrenia. For reasonably well, stable people it may mean that the need for regular oral doses can be avoided, but adverse affects are not well reported. For more severely ill people, few benefits are evident although it may increase compliance with injections in comparison with placebo. Use of depot risperidone, especially at the higher doses, is weakly associated with movement disorders. Well designed and reported, randomised studies, firmly grounded in real world clinical practice are needed to fully assess the effects of this new preparation.

Antipsychotic Agents↗

Effects of recombinant human superoxide dismutase during reoxygenation with 21% or 100% oxygen after cerebral asphyxia in newborn piglets.

OBJECTIVE: Superoxide radicals (O2-) are generated during reoxygenation following asphyxia, possibly more when higher concentrations of O2 are used during resuscitation. Superoxide dismutase (SOD) is an antioxidant enzyme, which scavenges O2-. We tested the hypothesis that a single intravenous dose of recombinant human Cu,Zn SOD (rhSOD) could influence microcirculation and biochemical markers of asphyxia in piglets reoxygenated with 21% or 100% O2 after combined cerebral hypoxemia-ischemia-hypercapnia. METHODS: Anesthetized newborn piglets were randomized to asphyxia (n = 40) or control (n = 3). Asphyxia was induced by ventilation with 8% O2, adding CO2, and temporary occlusion of both common carotid arteries. After 20 min, 16 piglets received rhSOD 5 mg/kg intravenously and reoxygenation with 21% O2 (rhSOD, 21%; n = 8) or 100% O2 (rhSOD, 100%; n = 8), and 24 piglets received saline and reoxygenation with 21% O2 (21%, n = 13) or 100% O2 (100%, n = 11). The cortical microcirculation was assessed by laser Doppler flowmetry, and glutamate in the striatum and hypoxanthine in the cortex were measured by in vivo microdialysis. RESULTS AND CONCLUSION: rhSOD peaked in plasma after 5 min. No rhSOD was detected in brain tissue. There were no significant differences between rhSOD and non-rhSOD groups in any measured variable.

Animals↗

Effect of creatine supplementation on cardiac muscle of exercise-stressed rats.

The role of creatine supplementation in altering the physiological parameters regulating cardiac muscle's functional capacity through the initiation of cardiac hypertrophy and altered contractile protein expression has not been determined. The purpose of this study was to determine the effect of creatine supplementation, with and without exercise stress, on physiological parameters regulating functional capacity through alterations in rat cardiac mass and contractile-protein expression. Thirty male Sprague-Dawley rats were subjected to 30 min of exercise stress 5 days/week for 3 weeks with 2% of total body mass attached to the tail. Animals were randomly assigned to one of four treatment groups: group 1 (Con) received (1 ml/day) sucrose water by intubation tube (n=8); group 2 (Cr) received (1 ml/day) sucrose/creatine solution (n=6); group 3 (EX) received 1 ml/day sucrose water and the exercise stimulus (n=8), and group 4 (Cr/EX) received (1 ml/day) sucrose/creatine solution and the exercise stimulus (n=8). At the conclusion of the 21-day exercise-training period, the heart was collected and weighed for determination of wet weight, total protein, total RNA, and myosin heavy chain protein expression. RNA concentration decreased significantly (13%) in the EX group, but not in the CR/EX group, indicating an interactive effect of creatine and exercise. Total RNA significantly decreased (15%) in the EX group. Protein concentration significantly increased (9%) in the exercising treatments, while total protein did not change. Cardiac myosin heavy chain expression significantly shifted towards a predominant expression of the beta-isoform in the Cr/EX group [54.53% (3.42) beta]. These results indicate an interaction of creatine supplementation and swimming exercise stress that potentially alters cardiac protein synthesis and demonstrates a possible mechanism through which the combination of creatine supplementation and swimming stress stimuli act to alter the physiological parameters regulating cardiac functional capacity.

Administration, Oral↗

Effects of granulocyte colony-stimulating factor on hyperoxia-induced lung injury in newborn piglets.

Granulocyte colony-stimulating factor (G-CSF) increases the concentration and activation of neutrophils in the peripheral blood and has been used to prevent late-onset infection in premature infants. However, if G-CSF also augmented the inflammatory response in the lung, the incidence and severity of acute and chronic lung injury might be expected to increase. Using a newborn piglet model of acute lung injury, we examined the effects of rhG-CSF (recombinant-metHuG-CSF) on lung injury. Thirty-three newborn piglets were studied as follows: 1). Unventilated controls; 2). normally ventilated (PaCO2 = 35-45 torr) with room air(RA) for 48 h; 3). normally ventilated with RA for 48 h and received rhG-CSF (10 mg/kg/dose IV) at 0, 12, 24, and 36 h; 4). hyperventilated (PaCO2 = 15-25 torr) with 100% O2 for 48 h; 5) hyperventilated with 100% O2 for 48 h and received rhG-CSF (10 mg/kg/dose IV) at 0, 12, 24 and 36 h. Complete blood counts and and differentials were performed at 0, 24, and 48 h. Animals were sacrificed at 48 h, lungs were removed en bloc, and bronchoalveolar lavage (BAL) was performed. Total blood white blood cells and neutrophil counts increased significantly over 48 h in animals who received rhG-CSF either with normoventilation (p <0.0001) or hyperventilation with 100% O2 (p <0.003), and did not change significantly in the other experimental groups. However, there were no significant differences in BAL total cell counts, neutrophil chemotaxis activity, total protein, or albumin concentrations among the groups. Despite significantly increasing peripheral neutrophil counts, rhG-CSF did not potentiate acute lung injury or inflammation. This suggests that prophylactic administration strategies using rhG-CSF to prevent sepsis in premature infants should not increase the risk for developing acute and chronic lung disease.

Air↗

Change in salivary IgA following a competitive marathon race.

The influence of carbohydrate (1 l/h of a 6 % carbohydrate beverage), gender, and age on salivary IgA (sIgA) changes and incidence of upper respiratory tract infection (URTI) was studied in 98 runners following two competitive marathon races. The pattern of change in sIgA concentration differed significantly between carbohydrate (C) (N = 48) and placebo (P) (N = 50) groups, with higher post-race values measured in P. However, when this was adjusted for saliva protein concentration and saliva secretion rate, no difference between groups was measured. For all subjects combined, sIgA concentration, saliva IgA: protein ratio (spIgA), and sIgA secretion rates fell significantly (21 %, 31 %, and 25 %, respectively) below pre-race levels by 1,5-h post-race (p < 0.001). The pattern of change in all saliva measures did not differ significantly between the 12 women and 86 men in this study, and between the 23 older (> or =50 yr) and 75 younger (< 50 yr) subjects. Ninety-three subjects returned health/sickness logs, and of these, 16 (17 %) reported developing URTI during the 15-d period following the race event. The 1.5-h post-race spIgA concentration, but not sIgA concentration or secretion rate, was lower in runners reporting URTI compared to those who did not (254 +/- 30 and 388 +/- 26 microg*g(-1), respectively, p = 0.002), and this was negatively correlated with the post-race plasma cortisol concentration (r = -0.36, p < 0.001). Of the 16 runners, six were in the C group and 10 in the P group (Chi square = 1.11, p = 0.293). In conclusion, the output of sIgA decreased in runners following a competitive marathon, and this was not influenced by carbohydrate ingestion, age, or gender.

Adult↗

Evaluation of methyl tert-butyl ether (MTBE) as an interference on commercial breath-alcohol analyzers.

Anecdotal reports suggest that high environmental or occupational exposures to the fuel oxygenate methyl tert-butyl ether (MTBE) may result in breath concentrations that are sufficiently elevated to cause a false positive on commercial breath-alcohol analyzers. We evaluated this possibility in vitro by establishing a response curve for simulated breath containing MTBE in ethanol. Two types of breath-alcohol analyzers were evaluated. One analyzer's principle of operation involves in situ wet chemistry (oxidation of ethanol in a potassium dichromate solution) and absorption of visible light. The second instrument uses a combination of infrared absorption and an electrochemical sensor. Both types of instruments are currently used, although the former method represents older technology while the latter method represents newer technology.The percent blood alcohol response curve was evaluated over a breath concentration range thought to be relevant to high-level environmental or occupational exposure (0-361 microg/l). Results indicate that MTBE positively biases the response of the older technology Breathalyzer when evaluated as a single constituent or in combination with ethanol. We conclude that a false positive is possible on this instrument if the MTBE exposure is very high, recent with respect to testing, and occurs in combination with ethanol consumption. The interference can be identified on the older technology instrument by a time dependent post-reading increase in the instrument response that does not occur for ethanol alone. In contrast, the newer technology instrument using infrared and electrochemical detectors did not respond to MTBE at lower levels (0-36 microg/l), and at higher levels (>72 microg/l) the instrument indicated an "interference" or "error". For this instrument, a false positive does not occur even at high MTBE levels in the presence of ethanol.

Air Pollutants↗

A comparative evaluation of three self-rating scales for acute mania.

This study compared the performance of three self-rating mania scales, The Internal State Scale (ISS), the Self-Report Manic Inventory (SRMI), and the Altman Self-Rating Mania Scale (ASRM), in a group of patients with acute mania. Forty-four adult inpatients with bipolar disorder, manic or mixed, completed all scales shortly after admission, and 31 patients completed them again after 4-6 weeks of pharmacotherapy. Patients also were rated by clinicians on the Clinician-Administered Rating Scale for Mania (CARS-M). At baseline, scores on the ASRM and the ISS well-being subscale were significantly correlated with CARS-M scores. Posttreatment scores were significantly decreased for the ASRM, SRMI, and the ISS activation subscale. The sensitivities for each scale to correctly identify patients with acute symptoms was 45% for the ISS, 86% for the SRMI, and 93% for the ASRM. Specificities were 73%, 46.6%, and 33%, respectively. The ASRM and SRMI were more sensitive than the ISS in screening patients with acute mania. All three measures were sensitive to treatment effects; however, the item content of the SRMI and the poor sensitivity of the ISS may limit their utility in inpatient settings.

Acute Disease↗

Recombinant human superoxide dismutase enhances the effect of inhaled nitric oxide in persistent pulmonary hypertension.

We investigated the pulmonary vascular effects of superoxide dismutase (SOD) alone and in combination with inhaled nitric oxide (iNO) in newborn lambs with persistent pulmonary hypertension (PPHN) following prenatal ligation of the ductus arteriosus. In in vitro experiments, pretreatment with SOD significantly enhanced vascular relaxation in response to the NO donor S-nitrosyl-acetylpenicillamine (SNAP) in fifth-generation pulmonary arteries isolated from lambs with PPHN. In vivo treatment of fully instrumented newborn lambs with a single intratracheal dose of recombinant human CuZn SOD (rhSOD; 5 mg/kg) produced selective dilation of the pulmonary circulation. Further studies, of the combination of rhSOD and iNO, showed enhancement of the pulmonary vascular effects of iNO after brief periods of inhalation of 5 ppm and 80 ppm NO. We conclude that rhSOD reduces pulmonary vascular resistance and facilitates the action of iNO in a lamb model of PPHN. This suggests that rhSOD may prove to be an effective adjunctive treatment for newborns with PPHN.

Administration, Inhalation↗