Variability in tracheal mucociliary transport is not controlled by beating cilia in lambs in vivo during ventilation with humidified and nonhumidified air.

Mucociliary transport in the respiratory epithelium depends on beating of cilia to move a mucus layer containing trapped inhaled particles toward the mouth. Little is known about the relationship between cilia beat frequency (CBF) and mucus transport velocity (MTV) in vivo under normal physiological conditions and when inspired air is dry or not fully humidified. This study was designed to use video-microscopy to simultaneously measure CBF and MTV in the tracheal epithelium through an implanted optical window in mechanically ventilated lambs. The inspired air in 6 animals was heated to body temperature and fully saturated with water for 4 hours as a baseline. In another series of experiments, 5 lambs were ventilated with air at different temperatures and humidities and the mucosal surface temperature was monitored with infrared macro-imaging. In the baseline experiments, during ventilation with fully humidified air at body temperature, CBF remained constant, mean 13.9 ± 1.6 Hz but MTV varied considerably between 0.1 and 26.1 mm/min with mean 11.0 ± 3.9 mm/min, resulting in a maximum mucus displacement of 34.2 µm/cilia beat. Fully humidified air at body temperature prevented fluctuations in the surface temperature during breathing indicating a thermodynamic balance in the airways. When lambs were ventilated with dryer air, the mucosal surface temperature and MTV dropped without a significant change in CBF. When inspired air was dry, mainly latent heat (92%) was transferred to air in the trachea, reducing the surface temperature by 5 °C. Reduced humidity of the inspired air lowered the surface temperature and reduced MTV in the epithelium during ventilation.

Haemodynamic effects of parenteral vs. enteral paracetamol in critically ill patients: a randomised controlled trial.

Paracetamol is a commonly used drug in the intensive care unit. There have been reports in the literature of an association with significant hypotension, a potentially important interaction for labile critically ill patients. Route of administration may influence the incidence of hypotension. This single-centre, prospective, open-label, randomised, parallel-arm, active-control trial was designed to determine the incidence of hypotension following the administration of paracetamol to critically ill patients. Fifty adult patients receiving paracetamol for analgesia or pyrexia were randomly assigned to receive either the parenteral or enteral formulation of the drug. Paracetamol concentrations were measured at baseline and at multiple time points over 24 h. The maximal plasma paracetamol concentration was significantly different between routes; 156 vs. 73 micromol.l(-1) [p = 0.0005] following the first dose of parenteral or enteral paracetamol, respectively. Sixteen hypotensive events occurred in 12 patients: parenteral n = 12; enteral n = 4. The incident rate ratio for parenteral vs. enteral paracetamol was 2.94 (95% CI 0.97-8.92; p = 0.06). The incidence of hypotension associated with paracetamol administration is higher than previously reported and tends to be more frequent with parenteral paracetamol.

Hypertriglyceridemic waist and newly-diagnosed diabetes among remote-dwelling Indigenous Australians.

AIMS: Hypertriglyceridemic waist (HTgW) is predictive of cardiovascular disease. The HTgW relationship with diabetes is little studied. METHODS: This study analysed data from diabetes and cardiovascular risk factor screening programmes in remote Indigenous Australian settlements. Elevated waist girth (EW) was defined as ≥90 cm for men (n = 1134) or ≥80 cm for women (n = 1313). Hypertriglyceridemia (ETg) was defined as ≥1.7 mmol/L. Diabetes was defined as fasting plasma glucose ≥7.0 mmol/L. Body mass index (BMI) was categorised as <22, 22-24.9 and >25.0 kg/m(2). Logistic regression was used to analyse the odds of newly-diagnosed diabetes for individuals with either HTgW, ETg or EW, relative to individuals with values below cut-offs. RESULTS: The prevalence of HTgW was 33.2% for men and 34.8% for women. Accounting for age-group and gender, newly-diagnosed diabetes was associated (odds ratio (OR) (95% confidence interval)) with HTgW: 9.6 (6.6, 13.8). The relationship remained strong after accounting for the covariates BMI and smoking (OR = 4.9 (2.7, 8.8)). In BMI-stratified analyses the strongest odds were observed for the lowest category (<22 kg/m(2): OR = 12.9 (4.0, 41.7)). CONCLUSIONS: HTgW has a high prevalence and is associated with newly-diagnosed diabetes in Indigenous people, particularly those with BMI <22 kg/m(2), whom clinicians might not normally consider for screening.

The binding site of human adenosine deaminase for CD26/Dipeptidyl peptidase IV: the Arg142Gln mutation impairs binding to cd26 but does not cause immune deficiency.

Human, but not murine, adenosine deaminase (ADA) forms a complex with the cell membrane protein CD26/dipeptidyl peptidase IV. CD26-bound ADA has been postulated to regulate extracellular adenosine levels and to modulate the costimulatory function of CD26 on T lymphocytes. Absence of ADA-CD26 binding has been implicated in causing severe combined immunodeficiency due to ADA deficiency. Using human-mouse ADA hybrids and ADA point mutants, we have localized the amino acids critical for CD26 binding to the helical segment 126-143. Arg142 in human ADA and Gln142 in mouse ADA largely determine the capacity to bind CD26. Recombinant human ADA bearing the R142Q mutation had normal catalytic activity per molecule, but markedly impaired binding to a CD26(+) ADA-deficient human T cell line. Reduced CD26 binding was also found with ADA from red cells and T cells of a healthy individual whose only expressed ADA has the R142Q mutation. Conversely, ADA with the E217K active site mutation, the only ADA expressed by a severely immunodeficient patient, showed normal CD26 binding. These findings argue that ADA binding to CD26 is not essential for immune function in humans.

Effect of collagen packing and moisture content on leather stiffness.

Applications for skin derived collagen materials, such as leather and acellular dermal matrices, usually require both strength and flexibility. In general, both the tensile modulus (which has an impact on flexibility) and strength are known to increase with fiber alignment, in the tensile direction, for practically all collagen-based tissues. The structural basis for flexibility in leather was investigated and the moisture content was varied. Small angle X-ray scattering was used to determine collagen fibril orientation, elongation and lateral intermolecular spacing in leather conditioned by different controlled humidity environments. Flexibility was measured by a three point bending test. Leather was prepared by tanning under biaxial loading to create leather with increased fibril alignment and thus strength, but this treatment also increased the stiffness. As collagen aligns, it not only strengthens the material but it also stiffens because tensile loading is then applied along the covalent chain of the collagen molecules, rather than at an angle to it. Here it has been shown that with higher moisture content greater flexibility of the material develops as water absorption inside collagen fibrils produces a larger lateral spacing between collagen molecules. It is suggested that water provides a lubricating effect in collagen fibrils, enabling greater freedom of movement and therefore greater flexibility. When collagen molecules align in the strain direction during tanning, leather stiffens not only by the fiber alignment itself but also because collagen molecules pack closer together, reducing the ability of the molecules to move relative to each other.

Perinatal delta-9-tetrahydrocannabinol exposure disrupts social and open field behavior in adult male rats.

Marijuana is the most frequently used illegal drug among women of reproductive age, but little is known about the consequences of using marijuana during pregnancy. Delta-9-tetrahydrocannabinol (Delta9-THC), one of the active chemicals in marijuana, has been shown to cross the placental barrier easily. In this study, pregnant Long Evans rats were assigned to one of three treatment groups (Delta9-THC-exposed, vehicle control, and non-treated control) on day 1 of gestation. Drug exposure consisted of 2 mg/kg of natural Delta9-THC, administered twice daily by subcutaneous (s.c.) injection, from gestational day 1 through 22. Pups continued to receive drug exposure via s.c. injection from postnatal day 2 through 10. Male rats from each group were tested starting on postnatal day 90 in a battery of tests which included open field activity, active social interaction, and the forced swim test. There were no significant differences in weight gained by dams or weight of offspring when compared to controls. Delta9-THC-exposed rats showed decreased time in the inner part of the open field and an increase in investigation time in the test of social interaction compared to both control groups. There were no differences among groups in the forced swim test. Perinatal Delta9-THC exposure may result in increased susceptibility to anxious behavior and alter social functioning in adult offspring.

Data on collagen structures in leather with varying moisture contents from small angle X-ray scattering and three point bend testing.

The data presented in this article are related to the research article entitled "Effect of collagen packing and moisture content on leather stiffness" (Kelly et al., 2018). This article describes how moisture content affects collagen packing and leather stiffness. Structural changes were experimentally introduced into ovine leather through biaxial strain during tanning (׳stretch tanning׳). Leather samples produced normally without strain (׳non-stretch tanned׳) and those produced by stretch tanning, were conditioned in a range of relative humidity environments and then analysed by small angle X-ray scattering and three point bend testing. The collagen D-spacing, lateral intermolecular spacing and flexural properties were measured under these varying moisture contents.

An increase in tryptophan in brain may be a general mechanism for the effect of stress on sensitivity to pain.

The role of the stress-induced increase in the uptake of tryptophan in brain in opioid-induced analgesia was investigated by modifying the uptake of amino acid in brain with injections of competing amino acids. Blockade of analgesia by valine (200 mg/kg, i.p.) alone, and by valine and tyrosine (100 mg/kg, i.p.), but not by valine and tryptophan (100 mg/kg, i.p.), was taken to indicate that an increase in the uptake of tryptophan in brain was involved in opioid-induced analgesia. Morphine-induced analgesia exhibited by rats that were habituated to the laboratory and not restrained did not involve an increase in the uptake of tryptophan in brain. However, a mild form of restraint, or exposure to a novel environment interacted with morphine to induce analgesia which involved an increase in the uptake of tryptophan in brain. These stressors did not affect sensitivity to pain in the absence of morphine. Analgesia induced by 3 hr of restraint, which was preventable by naltrexone (1 mg/kg, s.c.) but not reversible by naloxone (1 mg/kg, s.c.), also involved an increase in the uptake of tryptophan in brain. It is concluded that the endogenous opioid-induced analgesia that is induced by stress alone and analgesia induced by stress interacting with morphine, both depend on an increase in the uptake of tryptophan into the brain.

Effect of transfer RNA from various sources on placental messenger RNA translation.

Poly(A+)-containing mRNA from human term placenta was used to direct protein synthesis in a nuclease-treated rabbit reticulocyte lysate, which is dependent on mRNA and tRNA for maximal activity. The major protein product was human pre-placental lactogen (hPL). Addition of tRNA from rabbit liver, rabbit reticulocyte, human first trimester and term placenta, human liver and yeast resulted in 2-5-fold stimulation of [35S]methionine incorporation into total protein. Although all mammalian tRNA increased hPL synthesis, the relative synthesis as compared to endogenous globin was markedly different and most efficient with tRNA from term placenta. Addition of yeast tRNA increased total incorporation 3-fold but decreased incorporation of [35S]methionine into pre-hPL. These results suggest that the population of isoacceptor tRNAs may influence the expression of hPL in term placenta. Results are discussed by showing codon bias and usage of mRNA coding for hPL, alpha- and beta-hCG, rabbit globin and yeast alcohol dehydrogenase I.

Percutaneous needle aspiration biopsy of chest lesions. New instrument and new technique.

From March 1986 to April 1987, 70 percutaneous needle aspiration (PCNA) procedures were performed in 66 consecutive patients. Seven immunocompromised patients had the procedure performed to obtain culture material from the lung, and 59 patients with chest lesions were analyzed. This includes 49 patients with either a lung nodule or mass. In the remaining ten patients, there were three chest wall or pleural lesions, two aortic pulmonary window lesions, two right hilar lesions, and three anterior mediastinal lesions. Forty of these 59 patients were ultimately proven to have a malignancy. The diagnostic yield for malignant disease by cytology and histology of PCNA was 97.5 percent (39 of 40). Twelve patients had a final diagnosis of benign disease. The diagnostic yield in benign diseases by PCNA was 91.6 percent (11 of 12). The remaining seven patients do not yet have a final diagnosis, though the clinical course favors benign disease in six of these patients. We attribute the major reason for this high specific diagnostic yield in both malignant and benign diseases to the ability of obtaining histologic specimens for interpretation.

Effects of colchicine on IgE-mediated early and late airway reactions.

BACKGROUND: The pathogenesis of bronchial asthma is thought to involve elements of both acute and chronic inflammation. Hence, there is growing interest in the potential of immunomodulatory drugs in asthma therapy. This study examines the effects of the anti-inflammatory compound colchicine on early and late allergen-induced, IgE-mediated airway reactions. METHODS: Nine mildly allergic asthmatic subjects were evaluated in a single-blind, two-way crossover study designed to examine the effects of colchicine and placebo on early and late airway reactions to ragweed allergen and related changes in nonspecific responsiveness to methacholine. RESULTS: Compared with placebo, colchicine provided 19% (p = 0.036) and 40% (p = 0.004) inhibition of early and late airway reactions to allergen, respectively. Allergen-induced increases in methacholine responsiveness were observed with both types of treatment, although there was a trend toward a smaller increase after administration of colchicine (p = 0.13). We also found that methacholine responsiveness per se was not directly altered by colchicine (n = 7). In 6 subjects, we found suppression of neutrophil leukotriene B4 generation after colchicine treatment, suggesting that the colchicine dose (0.6 mg twice daily) was sufficient to produce an anti-inflammatory effect. Further in vitro studies using purified human lung tissue mast cells failed to demonstrate inhibition of mediator release at concentrations corresponding to achievable tissue or blood levels during the in vivo trial. CONCLUSION: Colchicine partially inhibits IgE-mediated early and late airway reactions at conventional clinical doses. This inhibitory effect may be mediated via suppression of some cell species other than the lung tissue mast cell. Controlled studies to examine the benefits of colchicine in clinically evidenced asthma are warranted.

Critical periods for the effects of alcohol exposure on learning in rats.

Critical periods for alcohol-induced deficits in spatial navigation and passive avoidance learning were investigated with a rat model of fetal alcohol syndrome. Rats were exposed to alcohol prenatally (Gestational Days 1-10 or 11-22) or postnatally (Postnatal Days 2-10) or throughout all 3 periods. Offspring were tested in either a spatial navigation or an avoidance task as juveniles or adults. As juveniles, the combined exposure group took longer to learn the spatial navigation task compared with all other groups. This effect was not seen in adults. Passive avoidance performance was not affected. These results suggest that long-term exposure to alcohol during development has adverse effects on spatial learning. The lack of differences in the short-term exposure groups implies that there may not be 1 critical period of alcohol exposure, but that the adverse effects of alcohol during development may be cumulative on some behaviors.

Acute myelomonocytic leukaemia following atypical congenital rubella.

The child of a woman immunised against rubella presented at 5 months with developmental delay and recurrent infection; she was shown to have congenital rubella. At 15 months she developed acute myelomonocytic leukaemia (AMML). Rubella is difficult to diagnose after immunisation. AMML has not been previously described in association with congenital rubella, as far as is known.

Impaired spatial navigation in adult female but not adult male rats exposed to alcohol during the brain growth spurt.

Two groups of male and female rats were given the same dose of alcohol using an artificial rearing procedure on postnatal days 4-10. One group received the alcohol in a condensed manner each day which caused cyclic blood alcohol concentrations (BACs) with high peaks. A second group received the alcohol in a uniform manner over each day which resulted in moderate, stable BACs. Two control groups consisted of male and female rats artificially reared but not exposed to alcohol and rats reared normally by dams. All rats were raised to 90 days of age and then tested for spatial navigation ability in the Morris water maze, which involved locating a hidden underwater platform using distal extramaze cues. Neither the alcohol treatments nor the artificial rearing had any effects on performance of adult male rats relative to suckle controls in this task. In contrast, the condensed alcohol exposure but not the uniform alcohol exposure resulted in detrimental performance in the Morris water maze by adult female rats. When the ability to locate and escape onto a visible platform was examined, there were no differences between the female groups given condensed alcohol exposure or artificially reared on milk solution alone. Thus, exposure to high BACs during the brain growth spurt has a lasting and selective detrimental effect on spatial navigation learning in adult female but not adult male rats.

Critical periods for the effects of alcohol exposure on brain weight, body weight, activity and investigation.

Using an animal model of fetal alcohol syndrome - which equates peak blood alcohol concentrations across different developmental periods - critical periods for the effect of alcohol on brain weight, activity and investigative behavior were examined. The periods of alcohol exposure were from gestational day (GD) 1 through 10, GD 11 through 22, postnatal day (PD) 2 through 10, or all three periods combined. The critical period of alcohol exposure for an increase in activity in juveniles was GD 11 through 22. This pattern was not seen in the same animals in adulthood; instead, increases in both activity and investigation were seen in animals exposed from PD 2 through 10 and not seen in animals exposed during all three periods combined. Brain weight was reduced by alcohol exposure from GD 11 through 22, PD 2 through 10 and all three periods combined. The period from PD 2 through 10 was the only period when the brain weight to body weight ratio was reduced. In conclusion, exposure to alcohol during the periods in the latter half of gestation or early postnatal period seem to have the most deleterious effects on the brain, activity and investigation in the rat. In addition, the effects of alcohol exposure over both the prenatal and postnatal period cannot be easily predicted from the effects of shorter periods of exposure.

Sympathetic control of tryptophan uptake and morphine analgesia in stressed rats.

Guanethidine treatment decreased morphine analgesia exhibited by restrained rats but had no effect on morphine analgesia exhibited by unrestrained rats or on baseline pain sensitivity. Guanethidine also prevented the rise in tryptophan uptake into the brain induced by the restraint stress. It is argued that the prevention of the stress-induced increase in brain tryptophan uptake is causal to guanethidine's attenuation of morphine analgesia exhibited by restrained rats, since the increase in brain tryptophan uptake has already been shown to be critical to this phenomenon. The blockade of the stress-induced increase in brain tryptophan uptake and morphine analgesia by guanethidine support the hypothesis that these effects depend upon sympathetic activity.

Electrolytic raphe magnus lesions block analgesia induced by a stress-morphine interaction but not analgesia induced by morphine alone.

Morphine analgesia in the tail withdrawal test was examined in rats which had had lesions of the nucleus raphe magnus (NRM) or sham operations. Half of the rats were tested while restrained, whereas the other half were not restrained. In the sham-operated rats, restraint potentiated the analgesic response to morphine. Lesions of the NRM had no effect on unrestrained rats but reduced the morphine analgesia exhibited by restrained rats so that it was indistinguishable from that of unrestrained rats. The NRM seems to be involved in analgesia induced by an interaction of morphine and restraint but not in analgesia induced by morphine alone.

Evidence that stress augments morphine analgesia by increasing brain tryptophan.

Morphine analgesia measured by the tail withdrawal test was examined in rats that were either restrained or left free during testing. It was found that restraint potentiated morphine analgesia and decreased the latency of the peak analgesic effect. Methysergide, a serotonin antagonist, and valine, which prevents the increase in brain tryptophan induced by restraint, blocked the effect of restraint on morphine analgesia. Valine did not alter analgesia in unrestrained rats. An increase in brain tryptophan uptake induced by stress is suggested as a possible mechanism by which stress can interact with pain modulation systems.

Genotyping of Pseudomonas aeruginosa in cystic fibrosis suggests need for segregation.

BACKGROUND: Emerging resistance of Pseudomonas aeruginosa within cystic fibrosis (CF) populations is attributed to antibiotic pressure and spread of transmissible strains. We describe increasing resistance of P. aeruginosa isolates, resulting in the identification of two multiresistant strains and their impact on morbidity. METHODS: Susceptibility reports of all P. aeruginosa isolates since 1998 in our unit were reviewed. Isolates were submitted for genomic finger-printing by pulsed-field gel electrophoresis. Clinical measures and the consumption of treatment resources were compared between those harbouring resistant organisms and those with sensitive strains. RESULTS: Analysis of 407 reports from 43 patients revealed isolation of multiresistant (MR) organisms increased during 1999. Those harbouring MR strains consumed more resources than non-MR. Strain typing showed a new 'Sheffield' strain in seven patients (100% MR), and the 'Liverpool' strain in 10 patients (40% MR). Individuals in these groups consumed significantly more resources than 23 patients with unique, susceptible strains (4% MR). DISCUSSION: Increasing resistance in isolates of P. aeruginosa may herald the arrival of a transmissible strain in CF Units which though sometimes sensitive, may become multiply resistant and require more intensive treatment. We now segregate those with transmissible strains from each other and from those with unique strains.