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1.  Whole-Genome Sequence of “Candidatus Liberibacter solanacearum” Strain R1 from California 
Genome Announcements  2014;2(6):e01353-14.
The draft whole-genome sequence of “Candidatus Liberibacter solanacearum” strain R1, isolated from and maintained in tomato plants in California, is reported. The R1 strain has the genome size of 1,204,257 bp, G+C content of 35.3%, 1,101 predicted open reading frames, and 57 RNA genes.
doi:10.1128/genomeA.01353-14
PMCID: PMC4276833  PMID: 25540355
2.  Grip strength at four years in relation to birth weight 
Journal of developmental origins of health and disease  2012;3(2):10.1017/S204017441100081X.
Consistent positive relationships have been found between birth weight and grip strength in adults but evidence in children is limited. In a prospective general population birth cohort (Southampton Women’s Survey) grip strength and anthropometry (height and weight) were measured in 968 children at age 4 years. Mean (standard deviation (S.D.)) birth weight was 3.48 (0.52) kg. Birth weight, adjusted for sex and gestational age, was positively associated with grip strength (β = 0.22 kg/S.D. increase in adjusted birth weight; 95% CI 0.11, 0.34). The relationship was attenuated after adjustment for current height and weight such that it became non-significant (β = 0.03 kg/S.D. increase in adjusted birth weight; 95% CI −0.08, 0.14), suggesting that body size may be on the causal pathway. Early influences on muscle development appear to impact on grip strength in children as well as adults.
doi:10.1017/S204017441100081X
PMCID: PMC3841813  PMID: 24294479
Birth weight; children; grip strength
3.  Meropenem Dosing in Critically Ill Patients with Sepsis Receiving High-Volume Continuous Venovenous Hemofiltration ▿  
Use of high ultrafiltrate flow rates with continuous venovenous hemofiltration (CVVHF) in critically ill patients is an emerging setting, for which there are few data to guide drug dosing. The objectives of this study were, firstly, to investigate the pharmacokinetics of meropenem in critically ill patients with severe sepsis who are receiving high-volume CVVHF with high-volume exchanges (≥4 liters/h); secondly, to determine whether standard dosing regimens (1,000 mg intravenously [i.v.] every 8 h) are sufficient for treatment of less susceptible organisms such as Burkholderia pseudomallei (MIC, 4 mg/liter); and, finally, to compare the clearances observed in this study with data from previous studies using lower-volume exchanges (1 to 2 liters/h). We recruited 10 eligible patients and collected serial pre- and postfilter blood samples and ultrafiltrate and urine samples. A noncompartmental method was used to determine meropenem pharmacokinetics. The cohort had a median age of 56.6 years, a median weight of 70 kg, and a median APACHE II (acute physiology and chronic health evaluation) score of 25. The median (interquartile range) values for meropenem were as follows: terminal elimination half-life, 4.3 h (2.9 to 6.0); terminal volume of distribution, 0.2 liters/kg (0.2 to 0.3); trough concentration, 7.7 mg/liter (6.2 to 12.9); total clearance, 6.0 liters/h (5.2 to 6.2); hemofiltration clearance, 3.5 liters/h (3.4 to 3.9). In comparing the meropenem clearance here with those in previous studies, ultrafiltration flow rate was found to be the parameter that accounted for the differences in clearance of meropenem (R2 = 0.89). In conclusion, high-volume CVVHF causes significant clearance of meropenem, necessitating steady-state doses of 1,000 mg every 8 h to maintain sufficient concentrations to treat less susceptible organisms such as B. pseudomallei.
doi:10.1128/AAC.01582-09
PMCID: PMC2897321  PMID: 20479205
4.  Parental smoking during pregnancy and offspring bone mass at age 10 years: findings from a prospective birth cohort 
Osteoporosis International  2010;22(6):1809-1819.
Summary
We investigated an intrauterine influence of maternal smoking during pregnancy on childhood bone mass. Daughters, but not sons, of mothers who smoked had higher bone mass at age 10 years. This appears to be due to familial factors related to parental smoking influencing increased offspring adiposity rather than a direct intrauterine effect.
Introduction
Neonatal studies have demonstrated an adverse relationship between maternal smoking in pregnancy and foetal bone mineral accrual. We aimed to investigate an intrauterine influence of maternal smoking during pregnancy on offspring bone mass at mean age 9.9 years.
Methods
We compared associations of maternal and paternal smoking in pregnancy with offspring total body less head (TBLH) and spine bone mineral content (BMC), bone area (BA), bone mineral density (BMD) and area-adjusted BMC (ABMC) in 7,121 children in the Avon Longitudinal Study of Parents and Children.
Results
Maternal smoking in any trimester was associated with increased TBLH BMC, BA and BMD in girls (mean difference [95% CI] (sex-specific SD scores), 0.13 [0.05–0.22], 0.13 [0.04–0.21], 0.13 [0.04–0.22], respectively) but not boys (0.01 [−0.07–0.09], 0.00 [−0.08–0.08], 0.04 [−0.05–0.12]), and also with spine BMC, BA and BMD in girls (0.13 [0.03–0.23], 0.12 [0.03–0.22], 0.10 [0.00–0.21]) but not boys (0.03 [−0.06–0.12], 0.00 [−0.09–0.09], 0.05 [−0.04–0.14]), but not with ABMC. Paternal smoking associations were similar, with no statistical evidence for a difference between maternal and paternal effects. Maternal associations increased on adjustment for offspring birth weight and gestational age, but attenuated to the null after adjustment for current height and weight.
Conclusions
We found little evidence that maternal smoking was related to bone mass in boys. In girls, maternal smoking associations were similar to those of paternal smoking, suggesting that these were attributable to shared familial characteristics, not intrauterine mechanisms.
Electronic supplementary material
The online version of this article (doi:10.1007/s00198-010-1415-y) contains supplementary material, which is available to authorized users.
doi:10.1007/s00198-010-1415-y
PMCID: PMC3092913  PMID: 20967424
ALSPAC; Bone mineral content (BMC); Bone mineral density (BMD); Childhood; Pregnancy; Smoking
5.  Respiratory management of the infant with type 1 spinal muscular atrophy 
Archives of Disease in Childhood  2005;90(7):709-711.
doi:10.1136/adc.2004.065961
PMCID: PMC1720500  PMID: 15970612
6.  Empyema: the use of broad range 16S rDNA PCR for pathogen detection 
Background: An increase in the incidence of thoracic empyema in children has been reported. The causative pathogen is often unknown as pleural fluid is frequently sterile at the time of culture. The role of unusual organisms is unclear.
Aims: (1) To compare the detection of organisms in pleural fluid from children with empyema using a molecular technique (16S rDNA polymerase chain reaction (PCR)) and bacterial culture. (2) To compare the concordance of organisms identified using the two techniques and the influence of prior antibiotic treatment on positive detection rate.
Methods: Pleural fluid from children admitted with empyema between January 2000 and February 2002 was cultured and additionally analysed using broad range 16S rDNA PCR.
Results: Pleural fluid was cultured from 32 patients, aged 1 month–16 years. Median duration of previous antibiotic therapy was 8 days (range 1–42 days). Six samples were culture positive and 22 were PCR positive. A causal organism was detected by PCR alone, after considering results from the local hospital, in 14 patients. There was complete concordance in organisms cultured and detected by PCR. Additional organisms detected by PCR were predominantly S pneumoniae, S pyogenes, and anaerobes.
Conclusions: Analysis of pleural fluid by broad range 16S rDNA PCR in addition to culture, increases organism identification in empyema.
doi:10.1136/adc.2003.042176
PMCID: PMC1720100  PMID: 15613518
7.  Multiple breath inert gas washout as a measure of ventilation distribution in children with cystic fibrosis 
Thorax  2004;59(12):1068-1073.
Background: Multiple breath inert gas washout (MBW) has been suggested as a tool for detecting early cystic fibrosis (CF) lung disease. A study was undertaken to compare the relative sensitivity of MBW and spirometry for detecting abnormal lung function in school age children with CF and to compare MBW results obtained from healthy children in the UK with those recently reported from Sweden.
Methods: Forced expiratory volume in 1 second (FEV1) and maximal expiratory flow when 25% of forced vital capacity remains to be expired (MEF25) were compared with the lung clearance index (LCI) derived from sulphur hexafluoride MBW in 22 children with CF aged 6–16 years and in 33 healthy controls.
Results: LCI was higher in children with CF than in healthy controls (mean difference 5.1 (95% CI of difference 4.1 to 6.1) and FEV1 and MEF25 z-scores were lower (mean difference –2.3 (95% CI –2.9 to –1.7) and –1.8 (95% CI –2.4 to –1.3), respectively; p<0.001 for all). There was a significant negative correlation between LCI and FEV1 (r2 = 0.62) and MEF25 (r2 = 0.46). However, while normal (⩾–1.96 z-scores) FEV1 and MEF25 results were seen in 11 (50%) and 12 (53%) children with CF, respectively, all but one of these children had an abnormally increased LCI. LCI was repeatable in both groups (within subject CV for three measurements 6% for CF and 5% for healthy children). In healthy subjects LCI was independent of age and virtually identical in the British and Swedish children (mean difference 0.1 (95% CI –0.1 to 0.4), p = 0.38)
Conclusions: MBW is reproducible between laboratories, generates normal ranges which are constant over childhood, and is more frequently abnormal than spirometry in children with CF.
doi:10.1136/thx.2004.022590
PMCID: PMC1746917  PMID: 15563707
8.  Sending children home on tracheostomy dependent ventilation: pitfalls and outcomes 
Archives of Disease in Childhood  2004;89(3):251-255.
doi:10.1136/adc.2003.028316
PMCID: PMC1719849  PMID: 14977704
9.  The use of nasal continuous positive airway pressure to treat obstructive sleep apnoea 
Archives of Disease in Childhood  2002;87(5):438-443.
Aim: To review 66 children with obstructive sleep apnoea (OSA) for whom a trial of nasal continuous positive airway pressure (nCPAP) was proposed.
Methods: Baseline sleep studies were performed to assess OSA severity; a trial of nCPAP was performed where moderate to severe OSA, not relieved by adenotonsillectomy, was found. The nCPAP trial was considered either technically successful (ST), if the child accepted the mask for sufficient time to determine nCPAP efficacy, or a technical failure (FT) if otherwise. Patients with an initial FT were offered a period of home acclimatisation to familiarise them with wearing the mask during sleep. ST patients in whom nCPAP was effective were established on long term therapy.
Results: Nasal CPAP trials were successful (ST) in 49/66 (74%) patients. Nasal CPAP efficacy could not be determined in the remaining 17 FT patients (26%), generally because of their poor nCPAP tolerance. These patients were subsequently considered for other treatment. A total of 42/49 (86%) ST patients were established on long term nCPAP therapy, 2/49 (4%) derived no benefit from nCPAP, while 5/49 (10%) refused long term nCPAP therapy. Of patients on long term nCPAP, the most frequently reported side effects were skin irritation and nasal dryness; however, these were not serious enough to require any patients to discontinue therapy. A period of home acclimatisation was found to be effective in increasing nCPAP acceptance, with 26% of FT children being subsequently successfully reassessed for nCPAP.
Conclusion: The use of nCPAP was feasible in a significant proportion of a paediatric OSA population. Failure was usually because of the child's intolerance of the nCPAP equipment. Nasal CPAP was an effective treatment in the majority of patients where it could be assessed, and was adopted as a long term therapy in most cases. We have successfully used nCPAP to treat OSA across a wide range of ages. Motivated parents and skilled support staff have proved essential for the success of nCPAP in a paediatric setting.
doi:10.1136/adc.87.5.438
PMCID: PMC1763069  PMID: 12390928
10.  Effects of hypertonic saline, alternate day and daily rhDNase on healthcare use, costs and outcomes in children with cystic fibrosis 
Thorax  2002;57(10):841-846.
Background: Daily recombinant human deoxyribonuclease (rhDNase) is an established but expensive treatment in cystic fibrosis (CF). An alternative lower cost therapy is hypertonic saline (HS), which has been shown to improve lung function in short term studies. This study compares the costs and consequences of daily rhDNase with alternate day rhDNase and HS in children with CF.
Methods: In an open, randomised, crossover trial, 48 children with CF were allocated consecutively to 12 weeks of once daily 2.5 mg rhDNase, alternate day 2.5 mg rhDNase, and twice daily 5 ml 7% HS. Outcomes assessed included forced expiratory volume in 1 second (FEV1) and quality of life. All healthcare resource use was prospectively recorded for each patient. Unit costs were collected and combined with resource use data to give the total health service costs per patient for each treatment strategy.
Results: Daily rhDNase resulted in a significantly greater increase in mean FEV1 than HS (8%, 95% CI 2 to 14) but there was no significant difference in FEV1 between daily and alternate day rhDNase (2%, 95% CI –4 to 9). Over a 12 week period the mean incremental costs of daily rhDNase compared with HS was £1409 (95% CI £440 to £2318), and the incremental cost of using daily rather than alternate day rhDNase was £513 (95% CI –£546 to £1510).
Conclusions: Daily rhDNase is more effective than 5 ml 7% HS twice daily delivered by jet nebuliser, but significantly increases healthcare costs. Administering rhDNase on an alternate day rather than a daily basis is as effective, with a potential for cost savings.
doi:10.1136/thorax.57.10.841
PMCID: PMC1746194  PMID: 12324668
11.  Randomised trial of intrapleural urokinase in the treatment of childhood empyema 
Thorax  2002;57(4):343-347.
Background: The role of intrapleural fibrinolytic agents in the treatment of childhood empyema has not been established. A randomised double blind placebo controlled trial of intrapleural urokinase was performed in children with parapneumonic empyema.
Methods: Sixty children (median age 3.3 years) were recruited from 10 centres and randomised to receive either intrapleural urokinase 40 000 units in 40 ml or saline 12 hourly for 3 days. The primary outcome measure was length of hospital stay after entry to the trial.
Results: Treatment with urokinase resulted in a significantly shorter hospital stay (7.4 v 9.5 days; ratio of geometric means 1.28, CI 1.16 to 1.41 p=0.027). A post hoc analysis showed that the use of small percutaneous drains was also associated with shorter hospital stay. Children treated with a combination of urokinase and a small drain had the shortest stay (6.0 days, CI 4.6 to 7.8).
Conclusion: Intrapleural urokinase is effective in treating empyema in children and significantly shortens hospital stay.
doi:10.1136/thorax.57.4.343
PMCID: PMC1746300  PMID: 11923554
12.  Bronchoconstriction following nebulised colistin in cystic fibrosis 
Archives of Disease in Childhood  2001;84(5):432-433.
Nebulised colistin is regularly used as antipseudomonal therapy in children with cystic fibrosis. We assessed bronchoconstriction in response to nebulised colistin in 58 children. Nebulised colistin significantly reduced FEV1, MEF25%, and SaO2 for 15 minutes. In 20 children the reduction was greater than 10% from baseline FEV1, and was still at that level in five at 30 minutes. Subjective assessment, baseline FEV1, and serum IgE were unable to identify susceptible children. It is recommended that children receiving colistin should be carefully assessed for bronchoconstriction.


doi:10.1136/adc.84.5.432
PMCID: PMC1718770  PMID: 11316693
14.  Core guidelines for the discharge home of the child on long term assisted ventilation in the United Kingdom 
Thorax  1998;53(9):762-767.
Paediatric home ventilation is a feasible option and can be successful in a wide range of conditions and ages. Advances in ventilator technology and an ethos of optimism for home care has increased the possibilities for discharging chronically ventilated children from intensive care units and acute medical beds. With careful planning the process can succeed, but difficulties often thwart the responsible team, especially when attempting discharge for the first time. These core guidelines aim to assist a smooth, swift and successful transfer. They were developed by a working party of interested professionals spanning a wide range of health care disciplines and represent a synthesis of views accumulated from the experiences of individual teams throughout the UK. Three case scenarios provide further illustrative detail and guidance.


PMCID: PMC1745309  PMID: 10319058
15.  Mucolytic therapy in cystic fibrosis. 
Journal of the Royal Society of Medicine  2001;94(Suppl 40):17-24.
PMCID: PMC1310581  PMID: 11601159
17.  Low Plasma Cefepime Levels in Critically Ill Septic Patients: Pharmacokinetic Modeling Indicates Improved Troughs with Revised Dosing 
Antimicrobial Agents and Chemotherapy  1999;43(10):2559-2561.
The pharmacokinetics of a 2-g bolus of cefepime were measured in critically ill patients with normal renal function. Variable and low trough plasma drug concentrations were found, and 8 of 10 patients had levels below the MIC at which 50% of the isolates are inhibited for Pseudomonas aeruginosa. Computer simulations predicted that continuous infusion and shorter dosing intervals would increase trough levels.
PMCID: PMC89521  PMID: 10508045
18.  Current status of long term ventilation of children in the United Kingdom: questionnaire survey 
BMJ : British Medical Journal  1999;318(7179):295-299.
Objectives
To identify the number and current location of children, aged 0 to 16 years, requiring long term ventilation in the United Kingdom, and to establish their underlying diagnoses and ventilatory needs.
Design
Postal questionnaires sent to consultant respiratory paediatricians and all lead clinicians of intensive care and special care baby units in the United Kingdom.
Subjects
All children in the United Kingdom who, when medically stable, continue to need a mechanical aid for breathing.
Results
141 children requiring long term ventilation were identified from the initial questionnaire. Detailed information was then obtained on 136 children from 30 units. Thirty three children (24%) required continuous positive pressure ventilation by tracheostomy over 24 hours, and 103 received ventilation when asleep by a non-invasive mask (n=62; 46%), tracheostomy (n=32; 24%), or negative pressure ventilation (n=9; 7%). Underlying conditions included neuromuscular disease (n=62; 46%), congenital central hypoventilation syndrome (n=18; 13%), spinal injury (n=16; 12%), craniofacial syndromes (n=9; 7%), bronchopulmonary dysplasia (n=6; 4%), and others (n=25; 18%). 93 children were cared for at home. 43 children remained in hospital because of home circumstances, inadequate funding, or lack of provision of home carers. 96 children were of school age and 43 were attending mainstream school.
Conclusions
A significant increase in the number of children requiring long term ventilation in the United Kingdom has occurred over the past decade. Contributing factors include improved technology, developments in paediatric non-invasive ventilatory support, and a change in attitude towards home care. Successful discharge home and return to school is occurring even for severely disabled patients. Funding and home carers are common obstacles to discharge.
Key messagesThe number of children requiring long term ventilatory support has increased substantially in the past 8 yearsVentilatory support at home is the best option for meeting the child’s psychological needs and enhancing quality of lifeThe majority of children dependent on long term ventilation live at home and attend mainstream schoolsA shift of care has occurred from intensive care units to less acute areas
PMCID: PMC27711  PMID: 9924054
20.  Detection of rifampin- and ciprofloxacin-resistant Mycobacterium tuberculosis by using species-specific assays for precursor rRNA. 
rRNA precursor (pre-rRNA) molecules carry terminal stems which are removed during rRNA synthesis to form the mature rRNA subunits. Their abundance in bacterial cells can be markedly affected by antibiotics which directly or indirectly inhibit RNA synthesis. We evaluated the feasibility of rapidly detecting antibiotic-resistant Mycobacterium tuberculosis strains by measuring the effects of brief in vitro antibiotic exposure on mycobacterial pre-rRNA. By hybridizing extracted M. tuberculosis nucleic acid with radiolabeled nucleic acid probes specific for pre-16S rRNA stem sequences, we detected clear responses to rifampin and ciprofloxacin within 24 and 48 h, respectively, of exposure of cultured cells to these drugs. Detectable pre-rRNA was depleted in susceptible cells but remained abundant in resistant cells. In contrast, no measurable responses to isoniazid or ethambutol were observed. Probes for pre-rRNA were specific for the M. tuberculosis complex when tested against a panel of eight Mycobacterium species and 48 other bacteria. After 24 h of incubation with rifampin, resistant M. tuberculosis strains were detectable in a reverse transcriptase PCR assay for pre-rRNA with a calculated lower limit of sensitivity of approximately 10(2) cells. Susceptible cells were negative in this assay at over 500 times the calculated lower limit of sensitivity. This general approach may prove useful for rapidly testing the susceptibility of slowly growing Mycobacterium species to the rifamycin and fluoroquinolone drugs and, with possible modifications, to other drugs as well.
PMCID: PMC163418  PMID: 8843282
21.  Why do patients default from follow-up at a genitourinary clinic?: a multivariate analysis. 
Genitourinary Medicine  1995;71(6):393-395.
OBJECTIVE--Firstly to compare the proportion of patients defaulting from follow up at a genitourinary medicine clinic with those attending other hospital based clinics. Secondly to determine which factors are associated with non attendance at a city centre genitourinary medicine clinic. METHODOLOGY--The proportion of patients who defaulted at a genitourinary medicine clinic, a general medical clinic, a general surgical clinic and a dermatology clinic during March 1995 were compared. A multivariate logistic regression analysis was performed comparing attenders and non attenders at the genitourinary medicine clinic with respect to time of appointment, diagnosis, previous contacts with clinic staff, potential domestic commitments and patient demographics in a prospective case control study. RESULTS--The default rate at the genitourinary medicine clinic was 15% compared with 13%, 15% and 14% for medical, surgical and dermatology clinics respectively. Patients who defaulted from the genitourinary medicine clinic (167) were compared with 172 attenders and significant differences found for timing of appointments, area of residence, frequency of counselling by the health advisor and age of the patient. Other factors such as the diagnosis, whether a woman had children, sexual orientation, whether negative results had been given over the phone, source of referral, sex of patient, employment status and the weather were not found to be significantly associated with defaulting from an appointment. CONCLUSIONS--The time of the appointment and being seen by a health advisor were the only variables identified over which the clinic has control and therefore could potentially reduce non attendance rates.
PMCID: PMC1196112  PMID: 8566981
22.  Phenolic acridine orange fluorescent stain for mycobacteria. 
Journal of Clinical Microbiology  1995;33(10):2763-2764.
A new fluorescence acid-fast staining method with acridine orange as the specific stain is presented. Only two reagents are required: the acridine orange-specific stain and a destaining-counterstaining reagent. Compared with auramine fluorescence acid-fast staining, there was less nonspecific staining of non-acid-fast debris which fluoresced a pale green contrasting color to provide a background in which to search for the red-to-orange fluorescing acid-fast bacilli. The results of the study indicate that the acridine orange method is superior to the auramine method in detecting acid-fast bacilli in specimen smears.
PMCID: PMC228571  PMID: 8567921
24.  Long term care for elderly people. 
Quality in Health Care  1993;2(3):198-203.
PMCID: PMC1055130  PMID: 10131468
25.  Laboratory aspects of "Mycobacterium genavense," a proposed species isolated from AIDS patients. 
Journal of Clinical Microbiology  1992;30(12):3206-3212.
"Mycobacterium genavense" is a proposed new species recently reported to cause disseminated infections in 18 patients with AIDS in Europe. We have recovered "M. genavense" as slowly growing fastidious mycobacteria in blood cultures of seven patients with AIDS. In the original studies of "M. genavense," the fastidious organism grew only in BACTEC 13A vials. The Seattle, Washington, isolates of "M. genavense" also failed to grow when subcultured from 13A vials to routine solid media, but dysgonic colonies were produced on Middlebrook 7H11 agar supplemented with mycobactin J. The mycolic acid pattern of patients' isolates closely resembled that of the type strain of Mycobacterium simiae when analyzed by one- and two-dimensional thin-layer chromatography and by high-performance liquid chromatography. Whole-cell fatty acid analyses by gas-liquid chromatography distinguished the isolates from M. simiae but misidentified them as Mycobacterium fortuitum. Sequence determinations of the hypervariable regions of the 16S rRNA gene indicate that these organisms belong to the recently proposed new species "M. genavense." Growth from Middlebrook 7H11 agar supplemented with mycobactin J consistently yielded positive tests for catalase (semiquantitative and at 68 degrees C), pyrazinamidase, and urease which enable mycobacteriology laboratories to presumptively identify "M. genavense" without nucleic acid analyses. The failure of "M. genavense" to grow on conventional mycobacterial solid media suggests that mycobacterial blood cultures should include a broth medium incubated for at least 8 weeks.
Images
PMCID: PMC270629  PMID: 1280652

Results 1-25 (54)