Is prescribing antibiotics by phone for respiratory infections acceptable? This expert says yes!
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Child↗
Biomedical subjects
R J Martin
Publications and source records attributed to R J Martin.
Exogenous surfactant therapy in newborns.
The introduction of surfactant replacement therapy for the management of respiratory distress syndrome (RDS) in the premature infant is one of the major advances in neonatal intensive care. After almost 50 years of intense research, the concerted efforts of basic scientists and clinicians have been rewarded. Despite the remarkable effects of surfactant therapy of RDS, the impact on the incidence of chronic lung disease has been unclear. With the recognition of the role of surfactant inactivation in the pathogenesis of other respiratory disorders of newborns (i.e., meconium aspiration syndrome and pneumonia) newer applications as well as new challenges have emerged. This article provides an overview of the physiology of the surfactant system and the current uses of this therapy in newborns.
Humans↗
Intracerebroventricular (i.c.v.) administration of mouse leptin in rats: behavioral specificity and effects on meal patterns.
Leptin is a protein that is produced primarily in fat tissue and is thought to be a lipostatic feedback signal for the regulation of body fat stores. The purpose of this study was to determine the behavioral specificity of i.c.v.-administered mouse leptin in rats and to assess the effects on meal patterns. Using a modified two-bottle paradigm we examined the putative aversive response to i.c.v. doses of 1, 5, 7, 10, and 30 microg of mouse leptin. Artificial CSF and intraperitoneal lithium chloride served as negative and positive controls, respectively. Saccharin consumption in all leptin treatments was not significantly different from the negative control. Following a recovery period, rats from the same group were used to assess the effects of a 30-microg i.c.v. dose on cumulative food intake and meal patterns using a computer-based system for acquisition of feeding data. Leptin (i.c.v.) significantly increased intermeal interval and decreased meal size. We, therefore, conclude that mouse leptin, at doses up to 30 microg i.c.v., is not aversive in the rat, and that leptin has a multiphasic effect on meal patterns.
Animals↗
Responses of lean and obese Zucker rats to centrally administered leptin.
Obese (Lepr(fa)/Lepr(fa)) Zucker rats have a missense mutation in the leptin receptor gene. One amino acid substitution in the extracellular domain common to all known leptin receptor proteins results from this mutation. Obese Zucker rats are unable to respond behaviorally to leptin which is peripherally administered. However, conflicting reports exist on whether obese Zucker rats can respond to centrally administered leptin. The purpose of this study was to determine whether obese Zucker rats responded behaviorally and metabolically to intracerebroventricularly (i.c.v.) administered leptin and to compare the responses of lean and obese Zucker rats. We found that both lean and obese Zucker rats had similar body weight and food intake responses when administered a single i.c.v. leptin injection in a range of doses (1.25, 2.5, 5, and 10 microg), as well as daily i.c.v. administered leptin for five consecutive days. Both single and daily leptin administration also decreased respiratory quotient (RQ) similarly in lean and obese Zucker rats, indicating mobilization of fat as an energy source for leptin-treated rats. After withdrawal of daily leptin treatment, lean and obese Zucker rats exhibited different recovery responses. It is concluded that obese Zucker rats can respond to exogenous leptin when leptin is delivered into the brain ventricles.
Animals↗
Neuropeptide Y antibody attenuates 2-deoxy-D-glucose induced feeding in rats.
2-deoxy-D-glucose (2-DG) has been shown to induce increased feeding responses in animals. Recent studies suggest the possible involvement of neuropeptide Y (NPY) in 2-DG-induced feeding. The present study examined the effect of immunoneutralization of endogenous NPY on 2-DG-induced feeding. NPY antibody injected into the paraventricular nucleus of the rats significantly attenuated 2-DG-induced feeding, suggesting that hypothalamic NPY may mediate, at least partly, the effect of 2-DG on food intake.
Animals↗
Anthelmintics and ion-channels: after a puncture, use a patch.
Two of three major types of anthelminitic, the avermectins and the nicotinic agonists, exert their therapeutic effect by an action on ligand-gated membrane ion-channels of nematodes. The avermectins, such as ivermectin, open glutamategated chloride channels which have so far been found only in invertebrate preparations; nicotinic anthelmintics, like levamisole, selectively gate nematode nicotinic acetylcholine receptors. We describe recent advances in the knowledge of the molecular structure of these ion-channel receptors in nematodes. Because opening of the ion-channels by these two groups of anthelmintic generates currents across cell membranes of nematodes, we can use electrophysiological methods to examine properties of the channels, the mode of action of the anthelmintics, and changes in the receptors associated with anthelmintic resistance. We illustrate some of our observations on these receptors using a two micro-electrode current-clamp technique to monitor membrane resistance (the puncture); and then some observations using The patch-clamp technique to monitor currents through individual ion-channels (the patch). The receptors for the two major groups of anthelmintics may not be homogeneous. Even in a single membrane patch from one muscle cell, nematode nicotinic acetylcholine receptors show evidence of heterogeneity and the avermectins may have multiple sites-of-action. If separate independent recessive genes are involved in production of different receptor subtypes, and if each subtype has to change to allow the development of resistance by the whole nematode, then the probability of resistance developing would be smaller than for anthelminitics with a single site-of-action. The MISER (multiple independent sites-of-action evading resistance) concept favours the development and use of anthelminitics with more than one site-of-action.
Animals↗
Neonatal apnea, bradycardia, or desaturation: does it matter?
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Apnea↗
Persistence of the biphasic ventilatory response to hypoxia in preterm infants.
OBJECTIVE: To characterize postnatal maturation of the biphasic ventilatory response to hypoxia in order to determine whether it persists beyond the first weeks of life in preterm infants, and the contributions of respiratory frequency and tidal volume to this response. METHODS: Stable preterm infants were studied at two postnatal ages, 2 to 3 weeks (n = 12) and 4 to 8 weeks (n = 12), before hospital discharge at 35 weeks (range, 33 to 38 weeks) of postconceptional age. Infants were exposed to 5 minutes of 15% (or 13%) inspired oxygen; ventilation, oxygen saturation, end-tidal partial pressure of carbon dioxide, and heart rate were simultaneously recorded. RESULTS: Minute ventilation exhibited a characteristic biphasic response to hypoxia at both postnatal ages, regardless of the development of periodic breathing. At both ages there was a transient increase in tidal volume, which peaked at 1 minute, accompanied by a sustained decrease in respiratory frequency as a result of significant prolongation of expiratory time. CONCLUSION: The characteristic biphasic ventilatory response to hypoxia persists into the second month of postnatal life in preterm infants. We speculate that this finding is consistent with the prolonged vulnerability of such infants to neonatal apnea.
Apnea↗
Dietary fat type influences protein consumption in rats given 8-hydroxy-2-(Di-n-propylamino)tetralin.
Our previous work indicates that type and level of dietary fat influences selection of protein and carbohydrate diets. Serotonin (5HT) appears to be involved in this feeding behavior. In the present study, we examined the effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on feeding behavior, and fenfluramine on in vitro 5HT and 5-hydroxyindoleacetic acid (5HIAA) release from the brain in rats fed tallow or corn oil. Male, Sprague-Dawley rats were given a diet containing corn oil or tallow for 2 days. In Experiment 1, rats received an injection of 8-OH-DPAT (a 5HT1A agonist) or saline and were then allowed to select from two diets: low protein/high carbohydrate or high protein/low carbohydrate. Prior exposure to tallow caused an increased intake of protein and 8-OH-DPAT blunted this effect. In Experiment 2, the dorsal raphe from rats fed tallow or corn oil was superfused with fenfluramine or vehicle. Superfusates were collected for analysis of 5HT and 5HIAA. Fenfluramine increased serotonin release in tallow-fed animals as compared to basal. These results suggest that serotonin may be involved in mediating tallow's effect on macronutrient selection.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Role of the medullary raphe nuclei in the respiratory response to CO2.
We characterized the role of neurons within the midline of the medulla oblongata on phrenic and hypoglossal nerve responses to hypercapnia during early-development. Studies were performed on decorticate or anesthetized; vagotomized and mechanically ventilated 14-20 day old piglets. Reversible withdrawal of midline neuronal activity was induced by microinjections of lidocaine (2%, 300 nl; n = 10) and lesioning was caused by microinjections of the neurotoxic agent, ibotenic acid (n = 12), at the same sites. At any given end-tidal CO2, peak phrenic and hypoglossal activities after lidocaine were significantly lower than in the control period (P < 0.01). Similarly, 1-2 h after injections of ibotenic acid, both phrenic and hypoglossal nerve responses to CO2 were significantly lower than in the control period (P < 0.01). The results indicate for the first time that the medullary midline neurons are required for full expression of ventilatory responses to hypercapnia and raise the possibility that dysfunction of these nuclei may contribute to respiratory instability during early postnatal life.
Animals↗
Expression of epithelial markers in nocturnal asthma.
BACKGROUND: Although the airway epithelium participates in inflammation and repair, the circadian expression of epithelial cell markers involved in these processes has not been investigated. OBJECTIVE: We sought to determine whether expression of CD51 (vitronectin and fibronectin receptor), CD54 (intercellular adhesion molecule-1), HLA-DR (activation marker), CD29 (beta1 integrin), CD49b (collagen receptor), and CD11b (complement receptor) exhibit a circadian rhythm in asthma. METHODS: Eleven patients with nocturnal asthma (NA), 9 subjects with nonnocturnal asthma (NNA), and 10 control subjects underwent bronchoscopy at 4 PM and 4 AM in a random order 1 week apart, with brushing of the proximal and distal airways. The percentage of cells staining for a particular marker was determined. RESULTS: At 4 PM, HLA-DR in the proximal airways and CD54 in the distal airways was significantly greater in control subjects as compared with asthmatic subjects (HLA-DR, control subjects: 10.0% [range, 5.0% to 21.0%]; NNA: 8.0% [range, 4.0% to 14.5%] NA: 3.5% [range, 2.0% to 6.0%], P = .01; CD54, control subjects: 17.0% [range, 8.0% to 25.0%], NNA: 8.0% [range, 5.3% to 11.5%], NA: 7.0% [range, 4.0% to 15.0%], P = .O;). At 4 AM, CD51 in the distal airways was significantly greater in patients with NA as compared with patients with NNA and control subjects (control subjects, 23.0% [range, 13.8% to 30.5%]; NNA, 32.0% [range, 13.0% to 35.0%]; NA, 40.0% [range, 23.0% to 50.0%], P = .05). Expression of CD51 in the distal airways correlated with the degree of airway obstruction (r = -0.57, P = .001). Control subjects exhibited significant circadian variation in the expression of HLA-DR in the proximal airways and CD54 in the distal airways. CONCLUSION: The increased CD51 at night in patients with NA may be related to increased airway inflammation and repair processes in response to injury. The circadian changes in CD54 and HLA-DR in control subjects require further study to determine their significance. (J Allergy Clin
Adult↗
The effects of upper respiratory infection on T-cell proliferation and steroid sensitivity of asthmatics.
BACKGROUND: The common cold is a potent trigger for asthma symptoms. Although the mechanisms are not completely understood, inflammatory events may play an important role. OBJECTIVE: We tested the hypothesis that changes in steroid responsiveness are implicated in the relationship between asthma and the common cold. METHODS: We investigated the steroid sensitivity of T cells from 10 patients with asthma (not taking steroids) and 10 control subjects, during upper respiratory infection and at recovery (6 weeks later). We stimulated peripheral blood mononuclear cells with phytohemagglutinin to measure T-cell proliferation, sensitivity to the inhibitory effects of steroids, and cytokine production. RESULTS: During infection compared with recovery, the asthma group exhibited lower responsiveness to dexamethasone at 10(-10) and 10(-9)mol/L and to 10(-10)mol/L hydrocortisone (P <.05) and both groups had decreased T-cell proliferation (P <.05). During recovery, patients with asthma had greater T-cell proliferation than control subjects (P <.02); the values expressed as uptake of [3H]-thymidine were 60119+/-3944 cpm (asthma) and 39078+/-6459 cpm (control subjects). The asthma group had higher TNF-alpha and IFN-gamma production during infection (P <.05); changes in IL-8 and IL-10 levels were not significant, and IL-4 was not detected. CONCLUSION: During infection, asthmatic subjects exhibit decreased T-cell responsiveness to steroids. The T-cell proliferative response to phytohemagglutinin, higher in asthma, is decreased with a common cold. These findings are associated with changes in the cytokine profile. Thus viral-induced upper respiratory infections can produce an inflammatory milieu with altered steroid function and selective increases in cytokines.
Adult↗
Pathophysiology of nocturnal asthma.
LEARNING OBJECTIVES: This article will focus on the pathophysiologic changes underlying the nocturnal worsening of asthma and the therapeutic approach to this disorder. DATA SOURCES: Selected articles appearing since 1985 dealing specifically with the underlying pathologic features and therapy of nocturnal asthma. STUDY SELECTION: Studies that aimed to elucidate the pathologic features, mechanisms, and therapeutic strategies for the treatment of nocturnal asthma are summarized. RESULTS: Nocturnal asthma is associated with significant decline in pulmonary function and increase of airway inflammation at night. The administration of medications must be designed to achieve the maximal effect during the night in nocturnal asthma. CONCLUSIONS: The further elucidation of the reasons underlying nocturnal asthma should lead to more specific therapeutic interventions with maximal effect at night.
Asthma↗
Whole body composition of rats determined by dual energy X-ray absorptiometry is correlated with chemical analysis.
The use of dual energy X-ray absorptiometry (DXA) is increasing in animal research, but data comparing whole body composition by DXA and chemical analysis (CHEM) in rats are limited. Lean and obese Zucker female rats were used to compare DXA (QDR1000W, Hologic, Waltham, MA) values with CHEM data for percent fat (%FATDXA, %FATCHEM), lean body mass (%PROTDXA, %PROTCHEM) and bone mineral content (%BMCDXA, %ASHCHEM). Four groups of rats (n = 9) were tested for differences in body composition due to consumption of a 100 g guar gum supplement/kg to see if DXA was as sensitive as CHEM in detecting body composition differences induced by diet. The study was analyzed using a split-plot ANOVA where the main plot was a 2 x 2 factorial with phenotype (obese or lean) and treatment (guar gum or control) as the effects, and the subplot was method of detecting body composition (DXA and CHEM), which was treated as a repeated measure. Absolute values for percent fat differed significantly (P < 0.0001) between the two methods as %FATDXA was consistently higher than %FATCHEM. There was not a statistically significant difference due to method for %PROT (P = 0.13). Values for %BMCDXA were significantly (P < 0.0049) lower than %ASHCHEM values. The differences in body composition due to diet treatment were detected similarly by DXA and CHEM. Significant correlations were found between the methods (P < 0.0001) for %FAT (r = 0.99), %PROT (r = 0.96) and %BMC or ASH (r = 0.81). Bland-Altman plots showed good agreement between methods, and regression equations were developed to estimate CHEM values from DXA readings. DXA may provide an alternative method for assessing changes in whole body composition.
Absorptiometry, Photon↗
Intracerebroventricular administration of antisense oligodeoxynucleotide against GLUT2 glucose transporter mRNA reduces food intake, body weight change and glucoprivic feeding response in rats.
The GLUT2 glucose transporter, which may play a glucose-sensing role in hepatocyte and islet beta cells because of its low affinity and high Km for glucose, has been identified in some discrete brain areas that are related to feeding behavior and energy metabolism. We tested the hypothesis that brain GLUT2 may play a role in the control of food intake by antisense technology loss-of-function analysis. Antisense oligonucleotides directed against GLUT2 mRNA were administered intracerebroventricularly to eight rats daily for 13 days. Another eight rats were administered intracerebroventricularly with missense oligonucleotides as the control. Food intake was monitored by a computerized feeding system. Data were analyzed using a one-way general linear model or Mann-Whitney U test when appropriate. Cumulative food intake and body weight change in antisense-treated rats were significantly lower (18 and 160%, respectively) in the group treated with antisense oligonucleotides than in the group treated with missense control oligonucleotides. There was no increase in cumulative food intake in response to 2-deoxyglucose challenge in rats treated with antisense oligonucleotide, but in those treated with missense control oligonucleotide, cumulative food intake was fivefold greater in response to 2-deoxyglucose. These data suggest a possible role of brain GLUT2 in the regulation of food intake and body energy stores.
Animals↗
Muscarinic receptor binding sites of the M4 subtype in porcine lung parenchyma.
Muscarinic acetylcholine receptors regulate distal airway resistance and secretion. The subtype expressed in the lung in different species remains uncertain. It has recently become possible to identify the M4 subtype by careful comparison of antagonist affinities. We characterized the binding of [3H]quinuclidinyl benzilate ([3H]QNB) to muscarinic receptors in cell membranes from lung parenchyma of 2-8 week old pigs in comparison to cloned human M3 and M4 receptors expressed in COS cells, to M2 in rat atria and to M4 in bovine adrenal medulla. In porcine lung, [3H]QNB bound with high affinity (Kd = 95 +/- 9 pM) to a single homogeneous population of muscarinic receptor sites (Bmax = 340 +/- 10 fmol/mg protein). Competition studies showed that the affinity (expressed as pKi) of 3 selective blockers was in close agreement between pig lung and cloned human m4 (r = 0.996). A series of 10 blockers showed affinities closely matching reported values for M4 receptors of the adrenal medulla (r = 0.965). Conversely, affinity values in porcine lung differed significantly (P < 0.05, t-test) from those determined in parallel with either human cloned M3 or with rat atria expressing the M2 subtype. We conclude that pig lung muscarinic receptor binding sites most closely resemble the M4 subtype, in contrast to the M3 subtype typical of large airways in this species.
Adrenal Medulla↗
Effect of supplementary dietary biotin on hoof growth and hoof growth rate in ponies: a controlled trial.
The effect of dietary biotin supplementation, at a dose rate of 0.12 mg/kg bwt, on growth and growth rate of the hooves of 8 match-paired poines was investigated in a controlled feeding trial. Treatment animals had a mean hoof growth at the midline dead centre of the hoof capsule of 35.34 mm after 5 months of biotin supplementation compared to control animals 30.69 mm (P < 0.05). Comparison of regression analysis also showed that biotin supplementation produced a significantly higher (P < 0.02) growth rate of hoof horn in this trial. Treatment animals had a 15% higher growth rate of hoof horn and 15% more hoof growth at the midline dead centre, after 5 months of biotin supplementation compared to control ponies. No differences were found between feet for growth of horn, but the older animals in the trial had significantly lower hoof growth (P < 0.05) than the remaining poines.
Analysis of Variance↗
Association of fat cell size and paracrine growth factors in development of hyperplastic obesity.
Inguinal, epididymal, and retroperitoneal adipose tissue from lean and obese Zucker rats, 3-15 wk of age, was used to determine the association among adipocyte size distribution, the presence of paracrine growth factors in adipose tissue, and subsequent changes in adipocyte number. For each specific depot and time point, obese rats had a greater percentage of large adipocytes than did lean rats. A positive correlation (P < 0.02) was found in obese rats between the percentage of inguinal and epididymal adipocytes in the 140- to 180-micrometer size range and the ability of conditioned medium prepared from these depots to stimulate cellular proliferation in a bioassay system utilizing preadipocytes from inguinal fat pads of normal rats. Proliferative activity of the conditioned medium from all depots in obese rats was positively correlated (P < 0.01) to subsequent changes in fat cell number. The data presented here for the inguinal and epididymal depot of obese Zucker rats are consistent with the hypothesis that enlarged adipocytes secrete growth factors that induce preadipocyte proliferation.
Adipocytes↗