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An understanding of the pathophysiology of nausea and the mechanisms of antiemetics can help family physicians improve the cost-effectiveness and efficacy of therapy. Nausea and vomiting are mediated primarily by visceral stimulation through dopamine and serotonin, by vestibular and central nervous system causes through histamine and acetylcholine, and by chemoreceptor trigger zone stimulation through dopamine and serotonin. Treatment is directed at these pathways. Antihistamines and anticholinergic agents are most effective in patients with nausea resulting from vestibular and central nervous system causes. Dopamine antagonists block dopamine in the intestines and chemoreceptor trigger zone; indications for these agents are similar to those for serotonin antagonists. Serotonin antagonists block serotonin in the intestines and chemoreceptor trigger zone, and are most effective for treating gastrointestinal irritation and postoperative nausea and vomiting. Complementary and alternative therapies, such as ginger, acupressure, and vitamin B6, have variable effectiveness in the treatment of pregnancy-induced nausea. [ABSTRACT FROM AUTHOR]

Reduction of the heteroleptic Ln(III) precursors [Ln(Tp) 2 (OTf)] (Tp = hydrotris(1-pyrazolyl)borate; OTf = triflate) with either an aluminyl(I) anion or KC 8 yielded the adduct-free homoleptic Ln(II) complexes dimeric 1-Eu [{Eu(Tp)( μ-κ 1 : η 5 -Tp)} 2 ] and monomeric 1-Yb [Yb(Tp) 2 ]. Complexes 1-Ln have good solubility and stability in both non-coordinating and coordinating solvents. Reaction of 1-Ln with 2 Ph 3 PO yielded 1-Ln(OPPh3)2. All complexes are intensely coloured and 1-Eu is photoluminescent. The electronic absorption data show the 4f-5d electronic transitions in Ln(II). Single-crystal X-ray diffraction data reveal first μ-κ 1 : η 5 -coordination mode of the unsubstituted Tp ligand to lanthanides in 1-Eu.

The p53 transcription factor plays a key role both in cancer and in the cell-intrinsic response to infections. The ORFEOME project hypothesized that novel p53-virus interactions reside in hitherto uncharacterized, unknown, or hypothetical open reading frames (orfs) of human viruses. Hence, 172 orfs of unknown function from the emerging viruses SARS-Coronavirus, MERS-Coronavirus, influenza, Ebola, Zika (ZIKV), Chikungunya and Kaposi Sarcoma-associated herpesvirus (KSHV) were de novo synthesized, validated and tested in a functional screen of p53 signaling. This screen revealed novel mechanisms of p53 virus interactions and two viral proteins KSHV orf10 and ZIKV NS2A binding to p53. Originally identified as the target of small DNA tumor viruses, these experiments reinforce the notion that all viruses, including RNA viruses, interfere with p53 functions. These results validate this resource for analogous systems biology approaches to identify functional properties of uncharacterized viral proteins, long non-coding RNAs and micro RNAs., Competing Interests: The authors have declared that no competing interests exist. Author Kathleen Corcoran was unable to confirm their authorship contributions. On their behalf, the corresponding author has reported their contributions to the best of their knowledge.

Objective: Chemotherapy induced peripheral neuropathy (CIPN) is an adverse effect of certain chemotherapy agents that can result in dose reductions, permanent nerve damage, and chronic pain. Although pharmacological agents have been studied in this setting, there is no standard of care for the prevention of CIPN. Thus, the objective of this systematic review is to assess the efficacy and safety of cryotherapy for the prevention of CIPN., Data Sources: PubMed (1946 to February 2020) and Embase (1947 to February 2020) were utilized to conduct a literature search using the following search terms: antineoplastic agent(s), taxoid(s), or chemotherapy and neuralgia, peripheral nervous system diseases, peripheral neuropathy, or paclitaxel-induced peripheral neuropathy and cryotherapy, cryotherapy device, hypothermia, low temperature procedures, or ice., Data Summary: A total of 11 studies were included in the final assessment. Results of this systematic review indicate that the efficacy of cryotherapy in preventing CIPN is conflicting. This may be due to studies utilizing differing cryotherapy administration methods, study design, and including only a small number of patients. All included studies utilized cryotherapy with taxane-based chemotherapy treatments and cooling gloves and socks was the most common method of administration. Overall, cryotherapy was well-tolerated and no serious adverse effects were noted., Conclusions: Due to the absence of serious adverse effects, cryotherapy is a reasonable option to consider to prevent CIPN in patients receiving taxane-based chemotherapy. However, additional research is needed, including larger, better designed studies, to fully delineate the role of cryotherapy for CIPN.

The most prevalent microdeletion in humans occurs at 22q11.2, a region rich in chromosome-specific low copy repeats (LCR22s). The structure of this region has defied elucidation due to its size, regional complexity, and haplotype diversity, and is not well represented in the human genome reference. Most individuals with 22q11.2 deletion syndrome (22q11.2DS) carry a de novo hemizygous deletion of ~ 3 Mbp occurring by non-allelic homologous recombination (NAHR) mediated by LCR22s. In this study, optical mapping has been used to elucidate LCR22 structure and variation in 88 individuals in thirty 22q11.2DS families to uncover potential risk factors for germline rearrangements leading to 22q11.2DS offspring. Families were optically mapped to characterize LCR22 structures, NAHR locations, and genomic signatures associated with the deletion. Bioinformatics analyses revealed clear delineations between LCR22 structures in normal and deletion-containing haplotypes. Despite no explicit whole-haplotype predisposing configurations being identified, all NAHR events contain a segmental duplication encompassing FAM230 gene members suggesting preferred recombination sequences. Analysis of deletion breakpoints indicates that preferred recombinations occur between FAM230 and specific segmental duplication orientations within LCR22A and LCR22D, ultimately leading to NAHR. This work represents the most comprehensive analysis of 22q11.2DS NAHR events demonstrating completely contiguous LCR22 structures surrounding and within deletion breakpoints.

This study was conducted to determine the prevalence of respiratory viral infections (RVI) in persons living with HIV (PLH) admitted with a respiratory complaint using real-time reverse transcription polymerase chain reaction and primer-independent next-generation sequencing (NGS). Of 82 subjects, respiratory viruses were the most common pathogen identified in 27 (33%), followed by fungus and bacteria in 8 (10%) and 4 (5%) subjects, respectively. Among subjects with RVI, 11 (41%) required ICU admission and 16 (59%) required mechanical ventilation. The proportion of respiratory viruses identified, and the associated complicated hospital course highlights the significant role that RVIs play in the lung health of PLH., (© 2020 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Objective: Case reports and a case series have described relief of neuropathic pain (NP) after treatment with epidermal growth factor receptor inhibitors (EGFR-Is). These observations are supported by preclinical findings. The aim of this trial was to explore a potential clinical signal supporting the therapeutic efficacy of EGFR-Is in NP., Methods: In a proof-of-concept trial using a randomized, double-blind, placebo-controlled design, 14 patients with severe, chronic, therapy-resistant NP due to compressed peripheral nerves or complex regional pain syndrome were randomized to receive a single infusion of the EGFR-I cetuximab and placebo in crossover design, followed by a single open-label cetuximab infusion., Results: The mean reduction in daily average pain scores three to seven days after single-blinded cetuximab infusion was 1.73 points (90% confidence interval [CI] = 0.80 to 2.66), conferring a 1.22-point greater reduction than placebo (90% CI = -0.10 to 2.54). Exploratory analyses suggested that pain reduction might be greater in the 14 days after treatment with blinded cetuximab than after placebo. The proportion of patients who reported ≥50% reduction in average pain three to seven days after cetuximab was 36% (14% after placebo), and comparison of overall pain reduction suggests a trend in favor of cetuximab. Skin rash (grade 1-2) was the most frequent side effect (12/14, 86%)., Conclusions: This small proof-of-concept evaluation of an EGFR-I against NP did not provide statistical evidence of efficacy. However, substantial reductions in pain were reported, and confidence intervals do not rule out a clinically meaningful treatment effect. Evaluation of EGFR-I against NP therefore warrants further investigation., (© 2019 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Gut microbiota from individuals in rural, non-industrialized societies differ from those in individuals from industrialized societies. Here, we use 16S rRNA sequencing to survey the gut bacteria of seven non-industrialized populations from Tanzania and Botswana. These include populations practicing traditional hunter-gatherer, pastoralist, and agropastoralist subsistence lifestyles and a comparative urban cohort from the greater Philadelphia region., Results: We find that bacterial diversity per individual and within-population phylogenetic dissimilarity differs between Botswanan and Tanzanian populations, with Tanzania generally having higher diversity per individual and lower dissimilarity between individuals. Among subsistence groups, the gut bacteria of hunter-gatherers are phylogenetically distinct from both agropastoralists and pastoralists, but that of agropastoralists and pastoralists were not significantly different from each other. Nearly half of the Bantu-speaking agropastoralists from Botswana have gut bacteria that are very similar to the Philadelphian cohort. Based on imputed metagenomic content, US samples have a relative enrichment of genes found in pathways for degradation of several common industrial pollutants. Within two African populations, we find evidence that bacterial composition correlates with the genetic relatedness between individuals., Conclusions: Across the cohort, similarity in bacterial presence/absence compositions between people increases with both geographic proximity and genetic relatedness, while abundance weighted bacterial composition varies more significantly with geographic proximity than with genetic relatedness.

We use the "caterpillar" model for accurately calculating the inhomogeneous hydrodynamic friction along a microscopic slender cylindrical filaments using Oseen level hydrodynamics. The methodology is applied to study the motion of a flexible filament in a circularly polarized field. Our results predict that in dilute solution alignment occurs along the axis of the field. For electric fields, the strengths and frequencies required are deduced. These are experimentally accessible. We therefore propose that this is a practical method for aligning filaments such as microtubules and functionalized carbon nanotubes.

Objective: We sought to investigate the effects of HIV infection on the vaginal microbiota and associations with treatment and demographic factors. We thus compared vaginal microbiome samples from HIV-infected (HIV+) and HIV-uninfected (HIV-) women collected at two Chicago area hospitals., Design: We studied vaginal microbiome samples from 178 women analyzed longitudinally (n = 324 samples) and collected extensive data on clinical status and demographic factors., Methods: We used 16S rRNA gene sequencing to characterize the bacterial lineages present, then UniFrac, Shannon diversity, and other measures to compare community structure with sample metadata., Results: Differences in microbiota measures were modest in the comparison of HIV+ and HIV- samples, in contrast to several previous studies, consistent with effective antiretroviral therapy. Proportions of healthy Lactobacillus species were not higher in HIV- patients overall, but were significantly higher when analyzed within each hospital in isolation. Rates of bacterial vaginosis were higher among African-American women and HIV+ women. Bacterial vaginosis was associated with higher frequency of HIV+. Unexpectedly, African-American women were more likely to switch bacterial vaginosis status between sampling times; switching was not associated with HIV+ status., Conclusion: The influence of HIV infection on the vaginal microbiome was modest for this cohort of well suppressed urban American women, consistent with effective antiretroviral therapy. HIV+ was found to be associated with bacterial vaginosis. Although bacterial vaginosis has previously been associated with HIV transmission, most of the women studied here became HIV+ many years before our test for bacterial vaginosis, thus implicating additional mechanisms linking HIV infection and bacterial vaginosis.

Maintenance of myeloid cell homeostasis requires continuous turnover of phagocytes from the bloodstream, yet whether environmental signals influence phagocyte longevity in the absence of inflammation remains unknown. Here, we show that the gut microbiota regulates the steady-state cellular lifespan of neutrophils and inflammatory monocytes, the 2 most abundant circulating myeloid cells and key contributors to inflammatory responses. Treatment of mice with broad-spectrum antibiotics, or with the gut-restricted aminoglycoside neomycin alone, accelerated phagocyte turnover and increased the rates of their spontaneous apoptosis. Metagenomic analyses revealed that neomycin altered the abundance of intestinal bacteria bearing γ-d-glutamyl-meso-diaminopimelic acid, a ligand for the intracellular peptidoglycan sensor Nod1. Accordingly, signaling through Nod1 was both necessary and sufficient to mediate the stimulatory influence of the flora on myeloid cell longevity. Stimulation of Nod1 signaling increased the frequency of lymphocytes in the murine intestine producing the proinflammatory cytokine interleukin 17A (IL-17A), and liberation of IL-17A was required for transmission of Nod1-dependent signals to circulating phagocytes. Together, these results define a mechanism through which intestinal microbes govern a central component of myeloid homeostasis and suggest perturbations of commensal communities can influence steady-state regulation of cell fate., (© 2016 by The American Society of Hematology.)

Objective: To determine the effect of blood sampling through an intravenous catheter compared with a needle in Emergency Department blood sampling., Methods: We undertook a prospective, cross-sectional study in a UK university teaching hospital Emergency Department. A convenience sample of 985 patients who required blood sampling via venepuncture was collected. A total of 844 complete sets of data were analysed. The median age was 63 years, and 57% of patients were male. The primary outcome measure was the incidence of haemolysis in blood samples obtained via a needle compared with samples obtained via an intravenous catheter. Secondary outcome measures defined the effect on sample haemolysis of the side of the patient the sample was obtained from, the anatomical location of sampling, the perceived difficulty in obtaining the sample, the order of sample tubes collected, estimated tourniquet time and bench time. Data were analysed with logistic regression, and expressed as odds ratios (95% confidence intervals; P-values)., Results: Blood samples obtained through an intravenous catheter were more likely to be haemolysed than those obtained via a needle, odds ratio 5.63 (95% confidence interval 2.49-12.73; P<0.001)., Conclusion: Blood sampling via an intravenous catheter was significantly associated with an increase in the likelihood of sample haemolysis compared with sampling with a needle. Wherever practicable, blood samples should be obtained via a needle in preference to an intravenous catheter. Future research should include both an economic evaluation, and staff and patient satisfaction of separating blood sampling and intravenous catheter placement.

The mammalian intestine is colonized by beneficial commensal bacteria and is a site of infection by pathogens, including helminth parasites. Helminths induce potent immunomodulatory effects, but whether these effects are mediated by direct regulation of host immunity or indirectly through eliciting changes in the microbiota is unknown. We tested this in the context of virus-helminth coinfection. Helminth coinfection resulted in impaired antiviral immunity and was associated with changes in the microbiota and STAT6-dependent helminth-induced alternative activation of macrophages. Notably, helminth-induced impairment of antiviral immunity was evident in germ-free mice, but neutralization of Ym1, a chitinase-like molecule that is associated with alternatively activated macrophages, could partially restore antiviral immunity. These data indicate that helminth-induced immunomodulation occurs independently of changes in the microbiota but is dependent on Ym1., (Copyright © 2014, American Association for the Advancement of Science.)

Objective: To establish whether there is a consensus regarding the significance of testicular microlithiasis and a strategy for managing patients with this condition, amongst ultrasound practitioners in the UK., Methods: An electronic questionnaire was distributed to 1482 members of the British Medical Ultrasound Society (BMUS), requesting information from ultrasound practitioners involved in scrotal ultrasound about their interpretation of the risk associated with testicular microlithiasis and their departmental or personal recommendations for managing patients with this condition., Results: Responses were obtained from 221 BMUS members. Analysis demonstrated a wide variation in the significance attributed to the discovery of testicular microlithiasis and the risk of subsequent development of testicular germ cell tumours. There was also great variation in strategies for management of patients with testicular microlithiasis, including the need for surveillance ultrasound, amongst ultrasound practitioners regardless of their job description., Conclusion: Lack of consensus shown by this study highlights significant differences across the UK in managing patients with testicular microlithiasis and validates the importance of guidance currently being formulated by the European Society of Urogenital Radiology., Advances in Knowledge: We believe that this is the first survey to be conducted amongst imaging specialists in the UK regarding testicular microlithiasis and demonstrates that there is currently no uniform practice in managing patients with this condition.

Background: Gastro-oesophageal reflux symptoms (GERS) are common in the community. However, few studies have examined their long-term natural history, or impact on survival., Aim: To examine these issues in individuals recruited into a community-based screening programme for Helicobacter pylori in 1994., Methods: Data on mortality and cause of death at 10 years were obtained from the Office for National Statistics. Baseline demographic data, lifestyle factors, gastrointestinal symptoms and quality of life were recorded at study entry. The effect of all these factors on persistent and new-onset GERS, and 10-year mortality, were examined using univariate and multivariate analysis, with results expressed as odds ratios (ORs) or hazard ratios (HR) with 99% confidence intervals (CI)., Results: Of 3967 individuals providing complete GERS data at baseline and 10 years, 549 (13.8%) had GERS at baseline. Of these, 183 (33.3%) had persistent symptoms. Among 3418 individuals asymptomatic at baseline, approximately 0.8% per year developed new-onset GERS. No predictors of persistent GERS were identified. New-onset symptoms were associated with lower quality of life or presence of irritable bowel syndrome (IBS) at baseline, and higher body mass index (BMI) at 10 years. There were 8331 (99.1%) of 8407 subjects providing complete GERS data at baseline, 1289 (15.5%) of whom were symptomatic. Presence of GERS at baseline did not affect survival (HR: 0.84; 99% CI: 0.44-1.59)., Conclusions: Gastro-oesophageal reflux symptoms persisted in one-third of individuals, whilst new-onset gastro-oesophageal reflux symptoms were associated with poor quality of life, irritable bowel syndrome and higher body mass index. Gastro-oesophageal reflux symptoms did not impact adversely on survival., (© 2012 Blackwell Publishing Ltd.)

Objectives: Most chronic and recurrent gastrointestinal (GI) symptoms in the community are caused by functional GI disorders, such as functional dyspepsia and irritable bowel syndrome (IBS). It is not known, however, whether these conditions affect mortality. We present the results of a large community-based prospective study that examines this issue., Methods: This was a 10-year follow-up, conducted in 2004, of individuals recruited into a community-based screening program for Helicobacter pylori. Data on mortality and cause of death at 10 years were obtained from the Office for National Statistics. Baseline demographic data, lifestyle factors, GI symptoms, and quality of life were recorded at study entry. The effect of all these factors on 10-year mortality was examined using univariate analysis and multivariate Cox regression analysis. All results were expressed as hazard ratios (HRs) with 99% confidence intervals (CIs)., Results: Symptom data were available for 8,323 (99.0%) of 8,407 individuals originally enrolled, comprising over 84,000 years of follow-up: 3,169 (38.1%) subjects had dyspepsia, and 264 (3.2%) IBS. There were 137 (1.65%) individuals who had died at 10 years. After multivariate analysis, there was no significant difference in likelihood of death at 10 years in those with dyspepsia (HR: 0.94; 99% CI: 0.58-1.54) or IBS (HR: 1.35; 99% CI: 0.36-5.10), compared with those not meeting the criteria for either condition., Conclusions: Dyspepsia was not associated with an increased mortality in the community. Data for any effect of IBS on survival were less clear. Further studies are required to assess the impact of functional GI disorders on life expectancy.

In many cellular signaling pathways, key components form clusters at the cell membrane. Although much work has focused on the mechanisms behind such cluster formation, the implications for downstream signaling remain poorly understood. Here, motivated by recent experiments, we use particle-based simulation to study a covalent modification network in which the activating component is either clustered or randomly distributed on the membrane. We find that whereas clustering reduces the response of a single-modification network, it can enhance the response of a double-modification network. The reduction is a bulk effect: a cluster presents a smaller effective target to a substrate molecule in the bulk. The enhancement, on the other hand, is a local effect: a cluster promotes the rapid rebinding and second activation of singly activated substrate molecules. As such, the enhancement relies on frequent collisions on a short timescale, leading to an optimal ratio of diffusion to association that agrees with typical measured rates. We complement simulation with analytic results at both the mean-field and first-passage distribution levels. Our results emphasize the importance of spatially resolved models, showing that significant effects of spatial correlations persist even in spatially averaged quantities such as response curves., (Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

It has been more than 50 yr since the landmark article in which Holliday and Segar (Pediatrics 1957;19:823-32) proposed the rate and composition of parenteral maintenance fluids for hospitalized children. Much of our practice of fluid administration in the perioperative period is based on this article. The glucose, electrolyte, and intravascular volume requirements of the pediatric surgical patient may be quite different than the original population described, and consequently, use of traditional hypotonic fluids proposed by Holliday and Segar may cause complications, such as hyperglycemia and hyponatremia, in the postoperative surgical patient. There is significant controversy regarding the choice of isotonic versus hypotonic fluids in the postoperative period. We discuss the origins of perioperative fluid management in children, review the current options for crystalloid fluid management, and present information on colloid use in pediatric patients.

We describe a method to impose constraints in a molecular dynamics simulation. A technique developed to solve the special case of a linear topology (MILC SHAKE) is hybridized with the SHAKE algorithm. The methodology, which we term MILC-hybridized SHAKE (or MILCH SHAKE), applies to more complex topologies. Here we consider the important case of all atom models of alkanes. Exploiting the mass difference between carbon and hydrogen we show that for higher alkanes MILCH SHAKE can be an order of magnitude faster than SHAKE., (Copyright 2009 Wiley Periodicals, Inc.)

Microscopic semiflexible filaments suspended in a viscous fluid are widely encountered in biophysical problems. The classic example is the flagella used by microorganisms to generate propulsion. Simulating the dynamics of these filaments numerically is complicated because of the coupling between the motion of the filament and that of the surrounding fluid. An attractive idea is to simplify this coupling by modeling the fluid motion by using Stokeslets distributed at equal intervals along the model filament. We show that, with an appropriate choice of the hydrodynamic radii, one can recover accurate hydrodynamic behavior of a filament with a finite cross section without requiring an explicit surface. This is true, however, only if the hydrodynamic radii take specific values and that they differ in the parallel and perpendicular directions leading to a caterpillarlike hydrodynamic shape. Having demonstrated this, we use the model to compare with analytic theory of filament deformation and rotation in the small deformation limit. Generalization of the methodology, including application to simulations using the Rotne-Prager tensor, is discussed.

The case of a 6 week-old infant who presented with an anterior mediastinal mass that extended to the left neck is reported. During surgical dissection of the mass, the patient exhibited extreme hemodynamic instability consistent with a vasoactive tumor. The patient had a neuroblastoma with its origin in the posterior mediastinum, but with its mass effect in the anterior mediastinum and neck.

Background: There are few studies examining the stability of gastrointestinal symptoms during prolonged periods of follow-up., Aim: To examine this issue in individuals previously recruited into a community screening programme for Helicobacter pylori providing symptom data at study entry., Methods: All traceable participants were sent dyspepsia and IBS questionnaires by post at 10 years. Symptom subgroups were assigned at baseline and 10-year follow-up. Individuals symptomatic at both time points who changed subgroup were compared with those symptomatic and remaining in the same subgroup., Results: Three-thousand eight hundred and nineteen individuals provided data. At baseline, 2417 (63%) were asymptomatic or did not meet diagnostic criteria for a subgroup. Of these, 1648 (68%) remained asymptomatic at 10 years, whilst 769 (32%) reported symptoms. Of the 1402 individuals symptomatic at baseline, 404 (29%) remained in the same subgroup at 10 years, 603 (43%) changed subgroup and symptoms resolved or did not meet criteria for a subgroup in 395 (28%). Symptom stability was more likely in males [odds ratio (OR): 1.50; 99% confidence interval (CI): 0.97-2.31] and older subjects (OR per year: 1.09; 99% CI: 1.01-1.17)., Conclusion: Of those subjects symptomatic at baseline, almost three-quarters remained symptomatic at 10 years, but over 40% changed symptom subgroup.

Objective: Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder. The natural history of the condition has been studied extensively, but few studies have examined factors that predict its new onset or health care-seeking behavior., Methods: Individuals, now aged 50-59 yr, originally enrolled in a population-screening program for Helicobacter pylori (H. pylori) were contacted via postal questionnaire, utilizing the Manning criteria for IBS diagnosis. Baseline demographic data, quality of life, and IBS and dyspepsia symptom data were already on file. Consent to examine primary care records was sought, and data regarding IBS- and dyspepsia-related consultations were extracted., Results: Of 8,407 individuals originally involved, 3,873 (46%) provided symptom data at baseline and 10-yr follow-up. Of 3,659 individuals without IBS at baseline, 542 (15%) developed new-onset IBS at 10-yr follow-up. After multivariate logistic regression, lower quality of life at baseline (odds ratio [OR] 4.41, 99% confidence interval [CI] 2.92-6.65), dyspepsia at baseline (OR 1.77, 99% CI 1.28-2.46), and female gender (OR 2.14, 99% CI 1.56-2.94) were significant risk factors for new-onset IBS. Of 651 individuals with IBS at either baseline or 10-yr follow-up, 113 (17%) consulted a primary care physician with symptoms. H. pylori infection (OR 1.93, 99% CI 1.03-3.62) and any dyspepsia-related consultation (OR 2.14, 99% CI 1.15-4.00) significantly increased the likelihood of consultation., Conclusions: Poor quality of life at baseline was a strong predictor of new-onset IBS, but not of IBS-related consultation behavior, which was associated with consultation for dyspepsia during the study period.

Clonidine is experiencing increasing use in the pediatric population as a sedative and analgesic because of its central alpha2-adrenergic agonism. We report three cases of preoperative use of intranasal clonidine in pediatric patients, all for different indications. One patient was treated for preoperative agitation and hallucinations associated with oral midazolam. One patient was given clonidine as a premedicant. The third patient was treated for preoperative agitation and hypertension. All three patients had subjective resolution of indicated symptoms and none experienced adverse outcomes.

Background: Infection with Helicobacter pylori (H. pylori) is acquired mainly in childhood, with studies demonstrating this is related to living conditions. Effects of sibling number and birth order on prevalence of infection have not been extensively studied., Methods: The authors performed a cross-sectional survey of adults, aged between 50 and 59 years, previously involved in a community-screening programme for H. pylori in Leeds and Bradford, UK. Prevalence of H. pylori was assessed at baseline with urea breath test. All individuals who were alive, and could be traced, were contacted by postal questionnaire in 2003 obtaining information on number of siblings and birth order. Data concerning childhood socioeconomic conditions were stored on file from the original study., Results: 3928 (47%) of 8407 original participants provided data. Prevalence of infection increased according to sibling number (20% in those with none vs 63% with eight or more). Controlling for childhood socioeconomic conditions and birth order using multivariate logistic regression, infection odds were substantially increased with three siblings compared with none [odds ratio (OR) 1.51; 95% confidence interval (CI) 1.06-2.15], and a gradient of effect continued up to eight or more siblings (OR 5.70; 95% CI 2.92-11.14). Odds of infection also increased substantially with birth order, but the positive gradient disappeared on adjustment for sibling number and childhood socioeconomic conditions., Conclusions: : In this cross section of UK adults, aged 50-59 years, sibling number in the household, but not birth order, was independently associated with prevalence of H. pylori infection.

Objective: Dyspepsia is common, and the condition is often chronic, with a relapsing and remitting nature. Factors influencing the decision to consult a physician with symptoms remain unclear., Methods: The authors conducted a 10-yr follow-up longitudinal survey of individuals originally involved in a community-screening program for Helicobacter pylori (H. pylori). All surviving, traceable participants were contacted by validated postal dyspepsia questionnaire. Baseline demographic data, dyspepsia and irritable bowel syndrome (IBS) symptom data, and quality of life at study entry were already on file. Consent to examine primary care records was requested, and data regarding nonsteroidal anti-inflammatory drug and aspirin use, and dyspepsia and IBS-related consultations over the 10-yr study period were extracted from these., Results: Of 8,407 individuals originally involved, 3,266 (39%) gave consent to examination of primary care records. The mean age of included individuals was 55 yr, and 1,467 (45%) were male. 1,738 (53%) had dyspepsia, and 729 (42%) of these consulted a primary care physician as a result. Following multivariate logistic regression, H. pylori infection (odds ratio [OR] 1.76, 99% confidence interval [CI] 1.30-2.39), lower socioeconomic status (OR 1.68, 99% CI 1.02-2.76), frequent (OR 2.61, 99% CI 1.69-4.01) or severe (OR 1.87, 99% CI 0.99-3.52) symptoms, and increasing age (OR per year 1.06, 99% CI 1.0-1.11) were independent risk factors for consultation., Conclusions: Reasons for consulting a physician with dyspepsia are multifactorial, but H. pylori infection, lower socioeconomic status, frequent or severe symptoms, and increasing age are independent predictors of consultation.

Background: Numerous studies examining the prevalence and natural history of dyspepsia in the general population have been conducted. However, few have reported the effect of quality of life on the development of dyspepsia. A 10-year longitudinal follow-up study examining the effect of quality of life on subsequent dyspepsia was performed., Methods: Individuals originally enrolled in a population-screening programme for Helicobacter pylori were contacted through a validated postal dyspepsia questionnaire. Baseline demographic data, quality of life at original study entry, and dyspepsia and irritable bowel syndrome (IBS) symptom data were already on file. Consent to examine primary-care records was sought, and data regarding non-steroidal anti-inflammatory drugs (NSAID) and aspirin use were obtained from these., Results: Of 8407 individuals originally involved, 3912 (46.5%) provided symptom data at baseline and 10-year follow-up. Of 2550 (65%) individuals asymptomatic at study entry, 717 (28%) developed new-onset dyspepsia at 10 years, an incidence of 2.8% per year. After multivariate logistic regression, lower quality of life at study entry (OR 2.63; 99% CI 1.86 to 3.71), higher body mass index (OR per unit 1.05; 99% CI 1.02 to 1.08), presence of IBS at study entry (OR 3.1; 99% CI 1.51 to 6.37) and use of NSAIDs and/or aspirin (OR 1.32; 99% CI 0.99 to 1.75) were significant risk factors for new-onset dyspepsia., Conclusions: The incidence of new-onset dyspepsia was almost 3% per year. Low quality of life at baseline exerted a strong effect on the likelihood of developing dyspepsia at 10 years.

Background & Aims: Population screening and treatment of Helicobacter pylori has been advocated as a means of reducing mortality from gastric cancer, as well as dyspepsia and dyspepsia-related resource use. Previous programs have failed to demonstrate a significant effect on mortality or resource use, but follow-up was only for 1 or 2 years. We aimed to determine the effect of screening for H pylori on dyspepsia and dyspepsia-related resource use over 10 years., Methods: H pylori-positive individuals, aged 40-49 years, enrolled in a community screening program, randomized to eradication therapy or placebo in 1994, were sent a validated dyspepsia questionnaire by mail 10 years later, and primary care records were reexamined. Consultation, referral, prescribing, and investigation data related to dyspepsia were extracted. United Kingdom costs were applied to derive total cost per person (1 pound = 1.8 dollars)., Results: Of 2324 original participants, 1864 (80%) were traced and contacted. Of these, 1086 (47%) responded, and 919 (40%) agreed to a review of their primary care records. There was a 10-year mean saving in total dyspepsia-related costs of 117 dollars per person (95% confidence interval [CI] = 11 dollars-220 dollars, P = .03) with eradication therapy. Those symptomatic at baseline showed a nonsignificant trend toward resolution of symptoms at 10 years with eradication therapy (relative risk of remaining symptomatic, 0.89; 95% CI: 0.77-1.03)., Conclusions: There were significant reductions in total dyspepsia-related health care costs. The savings made were greater than the initial cost of H pylori screening and treatment.

In this study, we compared the effect of isoflurane and desflurane on the posterior tibial somatosensory evoked potential recorded by scalp electrodes during correction of idiopathic scoliosis in pediatric patients. Depth of sedation was controlled by maintaining bispectral index (BIS) at 60 throughout the study. Comparison of patients breathing desflurane and isoflurane showed an evoked cortical amplitude (N37-P45) of 0.53 +/- 0.3 microV versus 1.3 +/- 0.8 microV (P = 0.014), respectively. In addition to this comparison, a crossover design was included whereby the desflurane or isoflurane received in the first part of the study was changed to the other anesthetic. Substituting one anesthetic for another confirmed our initial finding that the cortical evoked amplitude is greater with isoflurane than with desflurane. No differential effect was found between desflurane and isoflurane on the evoked subcortical (N31-P34) amplitude or the P37 latency.

Unlabelled: In this study, we examined the emergence characteristics of children tracheally extubated while deeply anesthetized with desflurane (Group D) or sevoflurane (Group S). Forty-eight children were randomly assigned to one of the two groups. At the end of the operation, all subjects were tracheally extubated while breathing 1.5 times the minimal effective concentration of assigned inhaled anesthetic. Recovery characteristics and complications were noted. Group D patients had higher arousal scores on arrival to the postanesthesia care unit than Group S patients. Later arousal scores were not significantly different. No serious complications occurred in either group. Coughing episodes and the overall incidence of complications after extubation were more frequent in Group D. Readiness for discharge and actual time to discharge were not significantly different between groups. Emergence agitation was common in both groups (33% overall, 46% for Group D, and 21% for Group S). Narcotic administration in the postanesthesia care unit occurred more frequently in Group D (10 of 24 patients) versus Group S (3 of 24 patients). Premedication with oral midazolam resulted in significantly longer emergence times regardless of the potent inhaled anesthetic administered., Implications: Deep extubation of children can be performed safely with desflurane or sevoflurane. Airway problems occur more frequently with desflurane. Awakening occurs more quickly with desflurane. Midazolam premedication has a greater effect on emergence times than does the choice of inhaled anesthetic. Emergence agitation occurs frequently with either technique.

Clinical research on the deposition of inhaled substances (e.g. inhaled medications, airborne contaminants, fumes) in the lungs necessitates anatomical models of the airways. Current conducting airway models lack three-dimensional (3D) reality as little information is available in the literature on the distribution of the airways in space. This is a limitation to the assessment or predictions of the particle deposition in relation to the subject's anatomy. Detailed information on the full topology and morphology of the airways is thus required to model the airway tree realistically. This paper presents the length, diameter, gravity, coronal and sagittal angles that together describe completely the airways in 3D space. The angle at which the airways branch out from their parent (branching angle) and the rotation angle between successive bifurcation planes are also included. These data are from the study of two sets of airways computed tomography (CT) images. One CT scan was performed on a human tracheobronchial tree cast and the other on a healthy male volunteer. The airways in the first nine generations of the cast and in the first six conducting generations of the volunteer were measured using a computer-based algorithm. The data contribute to the knowledge of the lung anatomy. In particular, the spatial structure of the airways is shown to be strongly defined by the central airways with clear angular lobar patterns. Such patterns tend to disappear with a mean gravity, coronal and sagittal angles of 90 degrees in each generation higher than 13-15. The mean branching angle per generation appears independent of the lobe to which the airways belong. Non-planar geometry at bifurcation is observed with the mean (+/- SD) bifurcation plane rotation angle of 79 +/- 410 (n = 229). This angle appears constant over the generations studied. The data are useful for improving the 3D realism of the conducting airway structure modelling as well as for studying aerosol deposition, flow and biological significance of non-planar airway trees using analytical and computational flow dynamics modelling.

Studies of aerosol deposition in models of the human respiratory tract play a significant role in developing our understanding of drug delivery by inhalation and particle retention in the lungs during exposure to polluted environments. To use replica casts of human airways and compare the results with in vivo data, a device is required to simulate human breathing. The objective of this study was to simulate human breathing for nasal casts. Breathing through the nose is normally limited to about 50 L/min. Therefore, a system was built to simulate human breathing patterns as well as artificial ones up to this flow rate. The system consists of a reciprocating piston in a cylinder, which is displaced by a synchronous motor via a linear actuator. The desired signal to drive the motor is given in real time by purpose-written software. The rotation and position of the motor are controlled by an electronic position control unit. The validation of the system shows that it simulates breathing up to 50 L/min closely even for complex waveforms. At breathing rates above 50 L/min, a slight difference is apparent between the desired breathing pattern and the simulated one. The breathing simulator has been shown to be a reliable tool for reproducing a wide variety of breathing patterns.

Single-photon emission computed tomography (SPECT) imaging is being increasingly used to assess inhaled aerosol deposition. This study uses simulation to evaluate the errors involved in such measurements and to compare them with those from conventional planar imaging. SPECT images of known theoretical distributions of radioaerosol in the lung have been simulated using lung models derived from magnetic resonance studies in human subjects. Total lung activity was evaluated from the simulated images. A spherical transform of the lung distributions was performed, and the absolute penetration index (PI) and a relative value expressed as a fraction of that in a simulated ventilation image were calculated. All parameters were compared with the true value used in the simulation, and the errors were assessed. An iterative method was used to correct for the partial volume effect, and its effectiveness in improving errors was evaluated. The errors were compared with those of planar imaging. The precision of measurements was significantly better for SPECT than planar imaging (2.8 vs 6.3% for total lung activity, 6 vs 20% for PI, and 3 vs 6% for relative PI). The method of correcting for the influence of the partial volume effect significantly improved the accuracy of PI evaluation without affecting precision. SPECT is capable of accurate and precise measurements of aerosol distribution in the lung, which are improved compared with those measured by conventional planar imaging. A technique for correcting the SPECT data for the influence of the partial volume effect has been described. Simulation is demonstrated as a valuable method of technique evaluation and comparison.

Detailed information on biological branching networks (optical nerves, airways or blood vessels) is often required to improve the analysis of 3D medical imaging data. A semi-automated algorithm has been developed to obtain the full 3D topology and dimensions (direction cosine, length, diameter, branching and gravity angles) of branching networks using their CT images. It has been tested using CT images of a simple Perspex branching network and applied to the CT images of a human cast of the airway tree. The morphology and topology of the computer derived network were compared with the manually measured dimensions. Good agreement was found. The airways dimensions also compared well with previous values quoted in literature. This algorithm can provide complete data set analysis much more quickly than manual measurements. Its use is limited by the CT resolution which means that very small branches are not visible. New data are presented on the branching angles of the airway tree.

Unlabelled: We studied the emergence characteristics of unpremedicated children tracheally extubated while deeply anesthetized ("deep extubation") with isoflurane or sevoflurane. Forty children were assigned to one of two groups, Group I or Group S. At the end of the operation, Group I patients were extubated while breathing 1.5 times the minimum alveolar anesthetic concentration (MAC) of isoflurane. Group S patients were tracheally extubated while breathing 1.5 times the MAC of sevoflurane. Recovery characteristics and complications were noted. Group S patients were arousable sooner than Group I patients (10.1 + 6.5 vs 16.3 + 9.9 min). Later arousal scores and times to discharge were the same. There were no serious complications in either group. Breath-holding was more common in Group I. We conclude that the overall incidence of airway problems and desaturation episodes was similar between groups. Emergency delirium was common in both groups (32% overall: 40% for Group I, 25% for Group S)., Implications: Deep extubation of children can be safely performed with either isoflurane or sevoflurane. After deep tracheal extubation, airway problems occur but are easily managed. Return to an arousable state occurred more quickly with sevoflurane, although time to meeting discharge criteria was not different between the two groups. Emergence delirium occurs frequently with either technique.

Planar images of known, theoretical distributions of radioaerosol in the lung have been simulated using lung models derived from magnetic resonance studies on human subjects. Total lung activity was evaluated from the simulated images together with the absolute penetration index (PI) and a relative value expressed as a fraction of that in a simulated ventilation image. The accuracy and precision of these measurements were calculated by comparison with the true values used in the simulation. Total activity was assessed with systematic errors within 5% and precision within 6.5%. Measured PIs varied only slowly with true PI and inter-model variation masked changes between measurements on the different distributions. The relative PI reduced inter-model variation and provided significant differences between all the distributions. PI was significantly affected by misalignment of the lung region of interest. The conducting airways deposition fraction (CADF) used in the simulation correlated linearly with the fractional activity in a central lung region, allowing CADF to be estimated with a precision of 21%.

In a randomized controlled trial at Duke University and University of North Carolina Hospitals, 143 two to six year old children undergoing elective ambulatory surgery were randomized into a control group who received routine preoperative teaching or an intervention group who received an interactive teaching book. Changes in behaviour were measured by a Vernon behavioural questionnaire preoperatively and again two weeks postoperatively. A Global Mood Score was assessed in the preoperative holding area, at arrival into the operating room, and at the time of mask induction. The children in the control group were significantly more aggressive postoperatively than the intervention group (P < 0.05). Children who received the interactive teaching book exhibited higher levels of anxiety on the day of surgery, but fewer behavioural changes two weeks following surgery. Parents in the intervention group reported that preoperative teaching helped their child (87%) and themselves (83%).

Unlabelled: Three-dimensional assessment of pulmonary deposition of inhaled aerosol may be performed using SPECT. The use of aligned anatomical images enables improved accuracy of quantification and anatomical localization of deposition., Methods: Techniques of analyzing these data and their application to deposition studies of two nebulizer-generated aerosols (mass median diameter 1.5 and 6.5 microM respectively) in 12 normal subjects are described. The deposition data were transformed to a standard hemispherical shape and the mean distribution pattern for each aerosol evaluated. Deposition by airway generation was then calculated using a spatial model of airway morphology. The results were compared to those from planar image analysis., Results: The hemispherical transform yielded considerably more qualitative information on deposition pattern. The central-to-peripheral concentration ratio between conducting and alveolated airways was 5.27 for the coarser aerosol and 2.43 for the fine. The two-dimensional spatial estimates of the ratio were 2.61 and 2.03 respectively., Conclusion: Analysis of multimodality imaging data considerably enhanced information on deposition compared to planar imaging. It provides new data on aerosol deposition which will be of value to physicians involved in drug inhalation therapy.

Multimodality medical imaging enables measurement of the three-dimensional spatial distribution of a radiolabeled aerosol within the lung. Using a conceptual spatial morphological model these data may be transformed to provide information on deposition per airway generation. This methodology has been used to study the intrapulmonary deposition patterns of two formulations of a metered dose inhaler and two nebulizers in control subjects. The nebulizer study has also been stimulated using a computer model of deposition. The comparison between derived experimental results and those from computer modeling shows areas of agreement, although there are also areas of discrepancy. The new methodology has considerable potential value in the fields of inhalation therapy and deposition modeling, although more detailed validation is still required.

The technique of using a charged bolus of aerosol to deliver a drug or other agent is advantageous since sites of interest within the lung can be selectively targeted. Ideally, the volume of the bolus should match that of the targeted region allowing the aerosol bolus particles to be confined to the selected area during the pause period after inhalation. Our existing computer model for predicting the deposition of charged aerosol particles has been developed to encompass aerosol boli, some diseased lung morphologies and drug dose administered per breathing cycle. Aerosol deposition in the targeted region is found to be enhanced by increasing particle charge, pause period and particle size. For particles in the size range 1-2.5 microm, aerosol deposition in the region affected by bronchoconstriction does not alter significantly with flow rate variation (range 250-1000 ml s(-1)) for a targeted charged bolus of matched volume. The technique may enable the optimal delivery of therapeutic or other agents to diseased or normal lungs.

We performed a prospective, randomized, double-blinded study in 60 postoperative pediatric patients aged 6 wk to 7 yr to compare the efficacy of butorphanol given epidurally or intravenously in preventing the side effects of epidural morphine. Three groups of patients received 60 micrograms/kg epidural morphine; 20 patients also received epidural butorphanol 30 micrograms/kg, and 20 patients also received 30 micrograms/kg intravenous butorphanol. All patients were evaluated for analgesia, sedation, vomiting, urinary retention, pruritus, and respiratory depression for 24 h postoperatively. Although the overall incidence of side effects was not different in the three groups, the epidural butorphanol group had a significant decrease in severity of pruritus. Sedation was seen more frequently in the groups receiving butorphanol, but was most pronounced in the epidural butorphanol group. We conclude that butorphanol has little or no effect on the side effects of epidural morphine.

The use of epidural fentanyl infusion with patient-controlled epidural analgesia (PCEA) is becoming popular for postoperative analgesia in adults. Its use has not been reported in the pediatric population. We report our initial experience with this technique in pediatric patients. The charts of all children who received epidural fentanyl infusions for postoperative analgesia between June 1991 and February 1992, were reviewed. Thirty-one patients, ages 6 to 17 years (mean +/- SD, 13.2 +/- 2.7) received epidural fentanyl infusion with PCEA for 36 operative procedures. Epidural catheters were either inserted in the lumbar (n = 14) or thoracic (n = 22) epidural space at a level based on the surgery. A fentanyl bolus of 1.38 +/- 0.43 micrograms/kg was delivered via epidural catheter just prior to the conclusion of surgery. A continuous infusion of fentanyl (0.56 +/- 0.18 micrograms/kg/h) with a PCEA bolus (0.53 +/- 0.17 micrograms/kg) available every 15 minutes was initiated in the recovery room and was utilized for 8 to 110 hours (59 +/- 27 hours). Pain and sedation were assessed by verbal descriptive scales, and side effects were noted. Alterations in dosing regimen were made for inadequate analgesia or side effects. Analgesia was assessed as excellent or good in 78% of the patients, 91% in the thoracic catheter group and 57% in the lumbar catheter group (P < .02). Patients with thoracic catheters were more likely to need their infusion and PCEA doses decreased, whereas those with lumbar catheters more often needed their doses increased (P < .05). No patient had respiratory depression.(ABSTRACT TRUNCATED AT 250 WORDS)

Small infants with endobronchial lesions primarily due to traumatic suction catheter injuries are now undergoing argon laser surgery to remove obstructive tissue. Providing an anaesthetic for these infants can be challenging because of the small airways involved which must be shared by the anaesthetist and the surgeon. We have performed 30 argon laser endobronchial surgeries in nine infants. The lungs of the majority of patients were ventilated through a tracheostomy intraoperatively, while the surgeon passed the argon laser fibre through the suction port of a fibreoptic bronchoscope which was passed trans-nasally. Three infants were too small to allow passage of the fibreoptic bronchoscope past an artificial airway. In these patients surgery and ventilation were accomplished through a rigid bronchoscope. Three larger patients without tracheostomies were managed with a modified nasal airway for intraoperative ventilation in conjunction with the fibreoptic bronchoscope.

Pacemakers in children can present clinical challenges during surgery. We present a case report of an infant whose pacemaker reverted to a backup mode when electrocautery was used during surgery. The resulting bradycardia did not respond either to a magnet placed over the generator or to iv atropine. The circulation was supported by isoproterenol until the pacemaker was re-programmed by the manufacturer. Such devices require care and understanding if problems during surgery are to be avoided.