A new respiratory scoring system for evaluation of respiratory outcomes in children with spinal muscular atrophy type1 (SMA1) on SMN enhancing drugs.

Nusinersen (NUS), the first treatment approved for Spinal Muscular Atrophy type 1 (SMA1), was made available in the UK for SMA1 through the Expanded Access Program (EAP) in 2017. The Great Ormond Street Respiratory (GSR) score was developed as an objective respiratory assessment for children with SMA1 during their treatment. Aims: Track respiratory status of SMA1 children over the course of Nusinersen treatment and compare GSR scores amongst SMA1 sub-types. Single centre study on SMA1 patients using the GSR score at set time points: prior to first NUS dose; 2 weeks post end of loading doses; 2 weeks post-subsequent doses. GSR score ranges 1-28, being 1-9 = Stable minimal support, thorough to 23-28 = Poor reserve with maximum support. 20 SMA1 children underwent NUS treatment between January 2017 - November 2018. Median age of diagnosis was 5.0 months. NUS started at median of 9.57 months. From 5th dose onwards, GSR scores were significantly lower for Type 1C patients compared to Type 1B By month 18, irrespective of subtypes, the whole cohort appears to stabilise GSR Scores. As treatment duration increases, an overall stabilisation of respiratory status across the cohort was observed. Further longitudinal studies are needed to validate the GSR.

Respiratory and upper limb function as outcome measures in ambulant and non-ambulant subjects with Duchenne muscular dystrophy: A prospective multicentre study.

The field of translational research in Duchenne muscular dystrophy (DMD) has been transformed in the last decade by a number of therapeutic targets, mostly studied in ambulant patients. A paucity of studies focus on measures that capture the non-ambulant stage of the disease, and the transition between the ambulant and non-ambulant phase. In this prospective natural history study, we report the results of a comprehensive assessment of respiratory, upper limb function and upper limb muscle strength in a group of 89 DMD boys followed in 3 European countries, 81 receiving corticosteroids, spanning a wide age range (5-18 years) and functional abilities, from ambulant (n = 60) to non-ambulant (n = 29). Respiratory decline could be detected in the early ambulatory phase using Peak Expiratory Flow percentage predicted (PEF%), despite glucocorticoid use (mean annual decline: 4.08, 95% CI [-7.44,-0.72], p = 0.02 in ambulant; 4.81, 95% CI [-6.79,-2.82], p < 0.001 in non-ambulant). FVC% captured disease progression in non-ambulant DMD subjects, with an annual loss of 5.47% (95% CI [-6.48,-4.45], p < 0.001). Upper limb function measured with the Performance of Upper Limb (PUL 1.2) showed an annual loss of 4.13 points (95% CI [-4.79,3.47], p < 0.001) in the non-ambulant cohort. Measures of upper limb strength (MyoGrip and MyoPinch) showed a continuous decline independent of the ambulatory status, when reported as percentage predicted (grip force -5.51%, 95% CI [-6.54,-4.48], p < 0.001 in ambulant and a slower decline -2.86%; 95% CI -3.29,-2.43, p < 0.001, in non-ambulant; pinch force: -2.66%, 95% CI [-3.82,-1.51], p < 0.001 in ambulant and -2.23%, 95% CI [-2.92,-1.53], p < 0.001 in non-ambulant). Furthermore, we also explored the novel concept of a composite endpoint by combining respiratory, upper limb function and force domains: we were able to identify clear clinical progression in patients in whom an isolated measurement of only one of these domains failed to appreciate the yearly change. Our study contributes to the field of natural history of DMD, linking the ambulant and non-ambulant phases of the disease, and suggests that composite scores should be explored further.

Neonatal extracorporeal membrane oxygenation: practice patterns and predictors of outcome in the UK.

OBJECTIVE: To review the UK neonatal extracorporeal membrane oxygenation (ECMO) service and identify predictors of outcome. DESIGN: Retrospective review of the national cohort. PATIENTS AND INTERVENTIONS: 718 neonates received ECMO for respiratory failure between 1993 and 2005. MEASUREMENTS AND RESULTS: Diagnoses were: 48.0% meconium aspiration syndrome (97.1% survivors), 15.9% congenital diaphragmatic hernia (CDH; 57.9% survivors), 15.9% sepsis (62.3% survivors), 9.5% persistent pulmonary hypertension (79.4% survivors), 5.6% respiratory distress syndrome (92.5% survivors) and 5.1% congenital lung abnormalities (24.3% survivors). The overall survival rate of 79.7% compared favourably with the worldwide Extracorporeal Life Support Organization (ELSO) Registry. Over the period of review, pre-ECMO use of advanced respiratory therapies increased (p<0.001), but ECMO initiation was not delayed (p = 0.61). The use of veno-venous (VV) ECMO increased (p<0.001) and average run time fell (p = 0.004). Patients treated with VV ECMO had a survival rate of 87.7% compared with 73.4% in the veno-arterial (VA) ECMO group; only 42.4% of those needing conversion from VV to VA ECMO survived. In non-CDH neonates, lower birth weight, lower gestational age, older age at ECMO and higher oxygenation index (OI) were associated with increased risk of death. In CDH neonates, lower birth weight and younger age at ECMO were identified as risk factors for death. CONCLUSION: The UK neonatal ECMO service achieves good outcomes and with overall survival rate reaching 80% compares favourably with international results. Advanced respiratory therapies are used widely in UK ECMO patients. Identification of higher OI and older age at ECMO as risk factors in non-CDH neonates reinforces the importance of timely referral for ECMO.

Maternal alcohol consumption.

Background Despite decades of research, the aetiology of attention deficit disorder with hyperactivity (ADHD) remains largely unknown. Next to a strong genetic component, increasing evidence suggests additional adverse impact of environmental factors, two of which have, although controversially, withstood meta-analysis: gestational exposure to smoking (OR 2.39) and low birth weight (OR 2.64). Several studies have investigated a possible association between prenatal exposure to alcohol and ADHD, although the matter is complicated due to foetal alcohol syndrome disorders (FASD) with ADHD-like symptoms. Questions Can an estimate of the effect of gestational exposure to alcohol for ADHD be determined? What is the relevance of primary care services in screening and intervention in mild to moderate drinking in pregnant women? Method MEDLINE, Cinahl, PsychInfo, EMBASE (1995-2008) were searched for articles in English, supplemented by a manual search. Out of 23 reviewed studies, three were included in the metaanalysis; one further study was added to undertake a sub-analysis comparing severe versus mild alcohol consumption. Summary odds ratios (OR) were extracted and fixed/random-effects meta-analysis were used for combining the OR's. Heterogeneity across the studies was formally assessed using Cochran's Q. Results An OR of 2.33 (95% CI, 1.18-4.61), (z = 2.43, p = 0.02) suggests that exposed children are 2.33 times more likely to have ADHD than non exposed children. Discussion Our meta-analysis suggests that children exposed to alcohol during pregnancy are at risk for ADHD. However, evidence is sparse and it remains uncertain whether a causal association exists. Further research is needed into dose-response relationship, timing of exposure, influence of genetic factors involved in maternal alcohol abuse and the role of FASD in ADHD-like symptoms. If a detrimental effect of mild to moderate drinking on the offspring is supported by stronger evidence, primary care services could have a major role in prevention and early intervention. This would be in addition to their already established role in helping heavy drinking mothers.

Delayed diagnosis of congenital heart disease worsens preoperative condition and outcome of surgery in neonates.

OBJECTIVES: To assess whether the route by which neonatal congenital heart disease (CHD) is first recognised influences outcome after surgery. METHODS: Surgical neonates admitted to a tertiary cardiac unit between March 1999 and February 2002 were retrospectively reviewed with analysis of risk factors for outcome. Three routes to initial recognition of CHD were compared: antenatal diagnosis, detection on the postnatal ward, and presentation after discharge to home. Outcome measures were mortality and duration of perioperative ventilation. RESULTS: 286 neonates had cardiac surgery with a median duration of ventilation of 101 h and in-hospital mortality of 12%. Recognition of CHD was antenatal in 20%, on the postnatal ward in 55% and after discharge to home in 25%. Multiple regression analyses, including the cardiac diagnosis, associated problems and other risk factors, indicated that severe cardiovascular compromise on admission to the cardiac unit was significantly related to mortality and prolonged ventilation. Considered in isolation, the route to recognition of heart disease did not influence mortality or ventilation time. Route to initial recognition did, however, influence the patient's condition on admission to the cardiac unit. Cardiovascular compromise and end organ dysfunction were least likely when recognition was antenatal and most common when presentation followed discharge to home. CONCLUSION: The setting in which neonatal CHD is first recognised has an impact on preoperative condition, which in turn influences postoperative progress and survival after surgery. Optimal screening procedures and access to specialist care will improve outcome for neonates undergoing cardiac surgery.

Randomised, double blind trial of oxytocin nasal spray in mothers expressing breast milk for preterm infants.

BACKGROUND: Human milk has considerable short and long term benefits for preterm infants, but mothers may experience difficulties in expressing breast milk for infants too immature or sick to breast feed. Oxytocin has been used to assist breast feeding and milk expression, but few data are available to support this intervention in the neonatal unit setting. AIM: To test the hypothesis that oxytocin nasal spray increases early milk output in mothers expressing milk for preterm infants. METHODS: A randomised, double blind trial of oxytocin nasal spray (100 microl per dose) versus placebo was conducted in mothers delivering infants <35 weeks gestation. Sprays were used before expression of milk using an electric pump up to day 5. MAIN OUTCOME: Total weight of milk expressed while using spray (study powered to detect >1SD difference between groups). SECONDARY OUTCOMES: Pattern of milk production; number of pumping sessions; weight/fat content of milk expressed during a fixed 20 minute period on day 5 ("physiological study"); mother's opinion of expressing and spray assessed by questionnaire. RESULTS: Fifty one mothers were randomised (27 oxytocin, 24 placebo). Total milk production did not differ between groups. Repeated measures analysis of variance suggested significantly (p = 0.001) different patterns of milk production, with initial faster production in the oxytocin group then convergence between groups. Parity did not influence the response to the intervention. No significant differences were seen in milk weight or fat content in the physiological study nor in mothers' opinions of milk expression and treatment. CONCLUSIONS: Despite marginal differences in the pattern of early milk production, the use of oxytocin nasal spray did not significantly improve outcome. Most mothers believed they were receiving the active spray, suggesting a significant placebo effect (supported by limited data from historical controls) and benefits from the extra breast feeding support available during the study.

The Chrispin-Norman score in cystic fibrosis: doing away with the lateral view.

The Chrispin-Norman chest radiograph scoring (CNS) system is widely used to assess respiratory disease progression in cystic fibrosis (CF). Frontal and lateral chest radiographs were performed. The present authors developed a modified CNS, which obviates the need for the lateral film. This study compares the original and the current authors' modified scoring system. A total of 50 chest radiographs from CF children, taken between August and December 2003, were scored according to the original and modified CNS. Two observers scored all 50 chest radiographs, scoring in random order the frontal radiographs, and separately the frontal and lateral radiographs together. There was no evidence of a difference between the methods for either observer, using the Bland and Altman 95% limits of agreement as follows: observer 1 (-2.0-1.9), and observer 2 (-1.77-2.2). No evidence of a difference between the observers for either method was found, comparing the 95% limits of agreement (-5.5-5.7) with the modified CNS (-5.6-6.4). In conclusion, in terms of the final score, good agreement was found between the use of the original and modified Chrispin-Norman score. In addition, low inter-observer variability was shown for both methods. The use of the modified Chrispin-Norman chest radiograph scoring system to stage disease severity in cystic fibrosis removes the need for a lateral chest radiograph.

The presence of vesicoureteric reflux does not identify a population at risk for renal scarring following a first urinary tract infection.

BACKGROUND: Childhood urinary tract infection (UTI) with or without vesicoureteric reflux (VUR) may predispose to renal scarring. There is no clear consensus in the literature regarding imaging following UTI in infancy. AIMS: To define the role of cystography following a first UTI in children aged under 1 year, when urinary tract ultrasonography (US) is normal. METHODS: Retrospective data collection of 108 children (216 renal units) aged under 1 year at the time of a bacteriologically proven UTI. All had a normal US and underwent both catheter cystogram and DMSA test. Sensitivity, specificity, likelihood ratios positive and negative, and diagnostic odds ratio were calculated for VUR on cystography versus scarring on DMSA. RESULTS: VUR was shown in 25 (11.6%) renal units. Scarring on DMSA was seen in 8 (3.7 %) kidneys. Only 16% of kidneys with VUR had associated scarring; 50% of scarred kidneys were not associated with VUR. The likelihood ratio positive was 4.95 (95% CI 2.22 to 11.05) and the likelihood ratio negative was 0.56 (95% CI 0.28 to 1.11). The diagnostic odds ratio was 8.9, suggesting that cystography provided little additional information. CONCLUSION: Since only 16% of children with VUR had an abnormal kidney, the presence of VUR does not identify a susceptible population with an abnormal kidney on DMSA. In the context of a normal ultrasound examination, cystography contributes little to the management of children under the age of 1 year with a UTI. In this context, a normal DMSA study reinforces the redundancy of cystography.

Maternal phenylketonuria: report from the United Kingdom Registry 1978-97.

BACKGROUND: The effects of maternal phenylalanine on the fetus include facial dysmorphism, microcephaly, intrauterine growth retardation, developmental delay, and congenital heart disease. AIMS: To evaluate the impact of phenylalanine restricted diet in pregnant women with phenylketonuria (PKU) on their offspring. METHODS: Data on virtually all pregnancies of women with PKU in the United Kingdom between 1978 and 1997 were reported to the United Kingdom PKU Registry. The effect of the use and timing in relation to pregnancy of a phenylalanine restricted diet on birth weight, birth head circumference, the presence or absence of congenital heart disease (CHD), 4 year developmental quotient, and 8 year intelligence quotient were examined. RESULTS: A total of 228 pregnancies resulted in live births (seven twin pregnancies were excluded). In 110 (50%), diet started before conception. For this group mean (SD) birth weight was 3160 (612) g, birth head circumference 33.6 (1.9) cm, 4 year DQ 108.9 (13.2), 8 year IQ 103.4 (15.6), and incidence of CHD was 2.4%. In comparison, for those born where treatment was started during pregnancy (n = 91), birth weight was 2818 (711) g, birth head circumference 32.7 (2.0) cm, 4 year DQ 96.8 (15.0), 8 year IQ 86.5 (13.0), and incidence of CHD was 17%. Month-by-month regression analyses suggested that metabolic control by 12-16 weeks gestation had most influence on outcome. CONCLUSIONS: Many features of the maternal PKU syndrome are preventable by starting a phenylalanine restricted diet. Women with PKU and their carers must be aware of the risks and should start the diet before conception, or as soon after as possible.

Predicting outcome in ex-premature infants supported with extracorporeal membrane oxygenation for acute hypoxic respiratory failure.

OBJECTIVE: To identify predictors of outcome in ex-premature infants supported with extracorporeal membrane oxygenation (ECMO) for acute hypoxic respiratory failure. METHODS: Retrospective review of ex-premature infants with acquired acute hypoxic respiratory failure requiring ECMO support in the United Kingdom from 1992 to 2001. Review of follow up questionnaires completed by general practitioners and local paediatricians. RESULTS: Sixty four ex-premature infants (5-10 each year) received ECMO support, despite increased use of advanced conventional treatments over the decade. The most common infective agent was respiratory syncytial virus (85% of cases). Median birth gestation was 29 weeks and median corrected age at the time of ECMO support was 42 weeks. Median ECMO support duration was relatively long, at 229 hours. Survival to hospital discharge and to 6 months was 80%, remaining similar throughout the period of review. At follow up, 60% had long term neurodisability and 79% had chronic pulmonary problems. Of pre-ECMO factors, baseline oxygen dependence, younger age, and inpatient status were associated with non-survival (p < or = 0.05). Of ECMO related factors, patient complications were independently associated with adverse neurodevelopmental outcome and death (p < 0.01). CONCLUSIONS: Survival rates for ex-premature infants after ECMO support are favourable, but patients suffer a high burden of morbidity during intensive care and over the long term. At the time of ECMO referral, baseline oxygen dependence is the most important predictor of death, but no combination of the factors considered was associated with a mortality that would preclude ECMO support.

The GP perspective: problems experienced in providing diabetes care in UK general practice.

AIMS: To describe the problems and barriers perceived by general practitioners (GPs) whilst providing diabetes care in primary care in England and Wales and to identify those health authorities (HAs) in which primary care reported the most and least difficulty. DESIGN: Descriptive postal survey using a self-administered questionnaire. SUBJECTS: One thousand eight hundred and seventy-three randomly sampled GP practices (one in five practices). RESULTS: One thousand three hundred and twenty (70%) responded. Getting patients to alter their lifestyles was perceived as causing the most difficulty in managing individual patients, followed by lack of time, patients' nonattendance, noncompliance with medical regimens and poor communication with secondary care. The greatest barriers to practices providing desirable care were lack of time/under-funding and keeping up to date in the area of diabetes, followed by lack of space, inadequate chiropody, dietetics, ophthalmology and access to secondary care. There are important differences between HAs in the difficulties experienced by primary care teams and we have ranked the HAs accordingly. CONCLUSION: The study has identified what problems need tackling in order to assist primary care to deliver good quality diabetes care, and has highlighted HAs where primary care needs further help, and HAs where examples of good practice may be found and useful lessons learnt. This should form the basis of a needs-based research and development programme for diabetes in primary care.

Risk and prevention of type II diabetes: offspring's views.

BACKGROUND: People with a parent with type II diabetes have an increased risk of the disease. There is increasing evidence for the possibility of prevention, particularly by attaining and maintaining normal weight and adequate levels of physical exercise. No prior studies have reported awareness of risk and prevention in this high-risk group. AIM: To explore beliefs about personal risk of diabetes and prevention in people with a parent with type II diabetes. DESIGN OF STUDY: A total of 254 adults with type II diabetes were identified from five randomly selected practices in south London. Self-report questionnaires were sent to 152 eligible offspring of these patients. A total of 105 of the offspring returned the self-report questionnaires and participated in the study. SETTING: Five randomly selected practices in south London. METHODS: Patients with type II diabetes in five randomly selected practices in south London were asked if we might contact their offspring. One randomly selected offspring (over 18 years of age) from each family completed a self-report questionnaire. RESULTS: Of 254 adults with type II diabetes 152 had eligible offspring. A total of 105 (69%) of the offspring participated in the study. A total of 69 (66%) of these offspring believed their personal risk of developing diabetes was 'low'. At least 28 (28%) and maybe as many as 73 (70%) underestimated the risk of diabetes in offspring. Compared with the number thinking their current risk was low significantly more (95 versus 69) thought that their risk would be low if neither of their parents had diabetes. Fifty-seven (54%) thought prevention was possible. Sixteen thought taking more exercise was important for prevention and only seven thought that weight control was important. Many had good general knowledge about diabetes and its complications but awareness of the relationship between diabetes and cardiovascular disease was poor. CONCLUSIONS: People with a parent with type II diabetes are usually aware that they have an increased risk of diabetes. However, they often underestimate that risk and know little about potentially useful preventive strategies. They need accurate information about these matters if they are to reduce their risk of diabetes and its complications.

A survey of diabetes care in general practice in England and Wales.

BACKGROUND: The focus of care for people with diabetes has shifted from hospital to general practice. Many practices now offer diabetes care via dedicated mini-clinics, shared care schemes or opportunistically. There has never been a national survey of the organisation of diabetes care in general practice. AIM: To describe some key features of diabetes care in primary care in England and Wales. METHOD: Descriptive postal questionnaire survey to one in five (1873) randomly sampled general practices. RESULTS: Seventy per cent (1320) of practices responded. Of these, 96% had diabetes registers identifying 1.9% of their population as having diabetes; 71% held clinics run by a general practitioner (GP) and a nurse (64%) or a nurse alone (34%); 80% felt adequately supported; and 54% shared patient management protocols with the local secondary care team. Overall, practices provided most of the routine diabetes care for 75% of their diabetic patients. The majority of GPs and practice nurses had received some recent, albeit brief, diabetes education. CONCLUSION: A large proportion of diabetes care now takes place in the community, much of it delivered by practice nurses. The organisational infrastructure necessary for delivering good care is in place. Many practices have a special interest in diabetes with the majority feeling adequately supported by secondary care. However, there are concerns about the educational needs of those providing care. More work needs to be done to ensure seamless care across the primary-secondary care interface.

How silent is perioperative myocardial ischemia? A hemodynamic, electrocardiographic, and biochemical study in patients undergoing coronary artery bypass graft surgery.

OBJECTIVE: To analyze the relationship among Holter electrocardiogram (ECG) recordings, hemodynamic measurements indicative of global myocardial oxygen balance, and serum cardiac troponin I concentrations (cTnI) in the early postoperative period after coronary artery bypass graft (CABG) surgery. DESIGN: Prospective observational study. SETTING: University teaching hospital. PARTICIPANTS: Thirty patients undergoing CABG surgery. INTERVENTIONS: ECG measurements consisted of Holter and standard ECG recordings. Hemodynamic measurements included heart rate, systolic and diastolic blood pressure (SBP, DBP), pulmonary capillary wedge pressure, and cardiac index (CI). Derived indices included tension time index (TTI), rate-pressure product, pressure work index (PWI), and endocardial viability ratio (EVR). Serial measurements of cTnI concentrations were measured postoperatively; the area under the cTnI concentration time curve was calculated for each patient (AUC cTnI). MEASUREMENTS AND MAIN RESULTS: Episodes of myocardial ischemia were associated with small but significant rises in SBP (p = 0.01), DBP (p = 0.001), and TTI (p = 0.005) compared with periods without ischemia in the same patients. Serum cTnI concentrations 24 hours after cardiopulmonary bypass (p = 0.03) and AUCcTnI (p = 0.01) values were greater in patients who developed ECG myocardial ischemia compared with patients who did not. CONCLUSIONS: The small changes in hemodynamics seen, although statistically significant, are unlikely to be the primary cause of the ischemia. They more likely reflect an independent process that causes or occurs as a result of ischemic episodes. Ischemic episodes detected by the Holter monitor are associated with significant release of cardiac troponin from the myocardium.

More good than harm: a randomised controlled trial of the effect of education about familial risk of diabetes on psychological outcomes.

BACKGROUND: Offspring of people with type 2 diabetes underestimate their risk of developing the disease and know little about primary prevention. However, education about risk might cause psychological harm. AIM: To examine cognitive and psychological effects of education about personal risk. METHOD: Patients with type 2 diabetes were recruited from randomly selected general practices. One of their adult offspring was randomly selected and randomly allocated into one of three groups: 1. Group 1: given an initial interview, education, and a final interview; 2. Group 2: given an initial and final interview; and 3. Group 3: given one interview only. Psychological outcomes were assessed using Hospital Anxiety and Depression Scale (HAD) and Positive Well-Being Scale (PWB) scores. RESULTS: Sixty-nine per cent (105/152) of eligible offspring participated. Ninety-one per cent (96/152) completed the study. Comparing first and final interviews, in Group 1, significantly fewer responders at final interview (after education) thought that their risk of developing diabetes was 'low' (65% versus 41%, P = 0.027), while in Group 2, there was no significant change in risk perception (P = 0.13). Significantly fewer people in the educated group (Group 1, final interview) than in the control group (Group 3) thought their risk of developing diabetes was 'low' (41% versus 77%, P = 0.002). Risk education did not affect total HAD scores or PWB scores significantly. CONCLUSION: Educating offspring of people with type 2 diabetes in this way about their risk of diabetes and possible preventive strategies increases their perception of personal risk but does not cause psychological harm.

The effects of acutely administered low dose sarin on cognitive behaviour and the electroencephalogram in the common marmoset.

Previous studies have suggested that administration of a clinically sign-free dose of sarin to non-human primates gives rise to subtle changes in brain electrical activity as measured by electroencephalography (EEG) several months following exposure. The functional significances of such changes are unclear. The present study monitored EEG by using implantable radiotelemetry, and also assessed the performance of complex behavioural tasks, in non-human primates for up to 15 months following exposure to a low dose of sarin. Baselines of EEG and behaviour were shown to be stable over several months in control animals. The doses of sarin administered caused erythrocyte cholinesterase inhibitions of 36.4% to 67.1%. Overall, no significant changes in EEG patterns were observed although there were increases in beta 2 amplitude which approached significance (p=0.07). No deleterious effects on performance were seen on the touchscreen mediated discrimination tasks presented from the Cambridge Neuropsychological Test Automated Battery (CANTAB). This study illustrates the validity of the approach employed and makes an important contribution to the investigation of the long-term effects of organophosphorous compounds.

Synergism between sevoflurane and intravenous fentanyl on A delta and C somatosympathetic reflexes in dogs.

UNLABELLED: In this study, we defined the nature of the interactions between sevoflurane and fentanyl on spontaneous and reflex-evoked sympathetic activity, resting heart rate (HR), and mean arterial pressure (MAP). Spontaneous renal sympathetic nerve activity (RSNA) and A delta- and C-fiber-mediated somatosympathetic reflexes, evoked by electrical stimulation of radial nerves, and HR and MAP were recorded in anesthetized dogs. In one group, the effects of incremental doses of 2-64 micrograms/kg fentanyl i.v. were observed. It had a greater inhibitory effect on C than on A delta reflexes, which were abolished by mean cumulative doses of 64 micrograms/kg and approximately 128 micrograms/kg, respectively. Although 1.5% sevoflurane reduced C reflexes by 28% and A delta reflexes by only 12%, it reduced the total doses of fentanyl required for their abolition to 32 micrograms/kg and 64 micrograms/kg, respectively. Mean RSNA, HR, and MAP values were reduced by 46%, 54%, and 30%, respectively, by fentanyl alone and by 23%, 11%, and 17%, respectively, in response to 1.5% sevoflurane. The combination of fentanyl and sevoflurane caused reductions of 44%, 54%, and 41%, respectively, which indicates a less than additive effect. These results indicate that sevoflurane interacts synergistically with fentanyl to depress A delta and C somatosympathetic reflexes, whereas for RSNA, HR, and MAP, their effects were less than the additive. IMPLICATIONS: Although fentanyl caused a greater depression of C than of A delta reflexes to the point of abolition, the maximal depression of spontaneous sympathetic activity, heart rate, and arterial pressure occurred at smaller doses. The combined depressant effects of sevoflurane and fentanyl were synergistic on somatosympathetic reflexes but were less than additive on spontaneous sympathetic activity, heart rate, and arterial pressure.

Relationship between change in amniotic fluid index and volume of fluid removed at amnioreduction.

OBJECTIVE: To determine the relationship between the change in amniotic fluid index (AFI) and the volume of fluid removed at amnioreduction. METHODS: In a prospective study of 20 twin and 19 singleton pregnancies undergoing amnioreduction for severe polyhydramnios, AFI was measured immediately before and after the procedure and was correlated with the volume of fluid withdrawn. RESULTS: A significant linear relationship was found between AFI change and the volume drained in all pregnancies (Y = -4.2X; R2 = 0.49; P = .002). This relationship was similar in singleton and twin pregnancies. However, there was a significant absolute difference in AFI change between singleton and twin pregnancies of 7.9 cm (95% confidence interval 0.41, 15.2; P = .04). CONCLUSION: These findings support the use of the four-quadrant AFI as a semiquantitative index of amniotic fluid volume. This relationship can be used to predict the drainage volume required to achieve a target AFI with amnioreduction and thus avoid repeated AFI measurements during the procedure itself.

Influence of respiratory distress syndrome on body composition after preterm birth.

AIM: To observe changes in body composition during the first week after birth, in preterm neonates with and without respiratory distress syndrome (RDS), so as to be able to provide optimal fluid and energy intake. METHODS: Twenty four babies with RDS and 19 healthy preterm babies, with gestational ages ranging from 26-36 weeks, were studied daily for the first week after birth. Total body water (TBW) was measured using bioelectrical impedance analysis. The babies were weighed daily and a record made of fluid and energy intake. Body solids were calculated as the difference between body weight and TBW. RESULTS: There was a highly significant reduction in body weight by the end of the week, with the RDS babies losing more than the healthy babies (RDS 7.6%; non-RDS 3.7%). There was no significant difference in the amount of TBW at birth in the babies with and without RDS (RDS 85.1%; non-RDS 85.5%) and both groups lost the same amount of body water (RDS 10.9%; non-RDS 9.9%) by the end of the first week. The amount of total body water lost was unrelated to the volume of fluid administered. There was a loss of body solids during the first day in the RDS group, but, overall, there was a highly significant increase in both groups between birth and day 7, which was greater in the healthy babies (RDS 13.0%; non-RDS 42.7%). CONCLUSIONS: Loss of body water after birth occurs to the same extent in healthy preterm neonates and in babies with RDS and is unrelated to the volume of fluid administered. Given adequate nutritional support, an increase in body solids can accompany early postnatal weight loss and begins almost immediately after birth, in both healthy preterm babies and babies with RDS.