Quantitative evaluation of dermatological antiseptics.

Topical antiseptics are frequently used in dermatological management, yet evidence for the efficacy of traditional generic formulations is often largely anecdotal. We tested the in vitro bactericidal activity of four commonly used topical antiseptics against Staphylococcus aureus, using a modified version of the European Standard EN 1276, a quantitative suspension test for evaluation of the bactericidal activity of chemical disinfectants and antiseptics. To meet the standard for antiseptic effectiveness of EN 1276, at least a 5 log10 reduction in bacterial count within 5 minutes of exposure is required. While 1% benzalkonium chloride and 6% hydrogen peroxide both achieved a 5 log10 reduction in S. aureus count, neither 2% aqueous eosin nor 1 : 10 000 potassium permanganate showed significant bactericidal activity compared with control at exposure periods of up to 1 h. Aqueous eosin and potassium permanganate may have desirable astringent properties, but these results suggest they lack effective antiseptic activity, at least against S. aureus.

Comparison of diagnostic clinical samples and environmental sampling for enterovirus and parechovirus surveillance in Scotland, 2010 to 2012.

Human enteroviruses (EV) and parechoviruses (HPeV) within the family Picornaviridae are the most common causes of viral central nervous system (CNS)-associated infections including meningitis and neonatal sepsis-like disease. The frequencies of EV and HPeV types identified in clinical specimens collected in Scotland over an eight-year period were compared to those identified in sewage surveillance established in Edinburgh. Of the 35 different EV types belonging to four EV species (A to D) and the four HPeV types detected in this study, HPeV3 was identified as the most prevalent picornavirus in cerebrospinal fluid samples, followed by species B EV. Interestingly, over half of EV and all HPeV CNS-associated infections were observed in young infants (younger than three months). Detection of species A EV including coxsackievirus A6 and EV71 in clinical samples and sewage indicates that these viruses are already widely circulating in Scotland. Furthermore, species C EV were frequently identified EV in sewage screening but they were not present in any of 606 EV-positive clinical samples studied, indicating their likely lower pathogenicity. Picornavirus surveillance is important not only for monitoring the changing epidemiology of these infections but also for the rapid identification of spread of emerging EV and/or HPeV types.

Identification of 28 novel mutations in the Bardet-Biedl syndrome genes: the burden of private mutations in an extensively heterogeneous disease.

Bardet-Biedl syndrome (BBS), an emblematic disease in the rapidly evolving field of ciliopathies, is characterized by pleiotropic clinical features and extensive genetic heterogeneity. To date, 14 BBS genes have been identified, 3 of which have been found mutated only in a single BBS family each (BBS11/TRIM32, BBS13/MKS1 and BBS14/MKS4/NPHP6). Previous reports of systematic mutation detection in large cohorts of BBS families (n > 90) have dealt only with a single gene, or at most small subsets of the known BBS genes. Here we report extensive analysis of a cohort of 174 BBS families for 12/14 genes, leading to the identification of 28 novel mutations. Two pathogenic mutations in a single gene have been found in 117 families, and a single heterozygous mutation in 17 families (of which 8 involve the BBS1 recurrent mutation, M390R). We confirm that BBS1 and BBS10 are the most frequently mutated genes, followed by BBS12. No mutations have been found in BBS11/TRIM32, the identification of which as a BBS gene only relies on a single missense mutation in a single consanguineous family. While a third variant allele has been observed in a few families, they are in most cases missenses of uncertain pathogenicity, contrasting with the type of mutations observed as two alleles in a single gene. We discuss the various strategies for diagnostic mutation detection, including homozygosity mapping and targeted arrays for the detection of previously reported mutations.

Amino acids do not suppress proteolysis in premature neonates.

To determine whether increased amino acid availability can reduce proteolysis in premature neonates and to assess the capacity of infants born prematurely to acutely increase the irreversible catabolism of the essential amino acids leucine (via oxidation) and phenylalanine (via hydroxylation to form tyrosine), leucine and phenylalanine kinetics were measured under basal conditions and in response to a graded infusion of intravenous amino acids (1.2 and 2.4 g. kg(-1). day(-1)) in clinically stable premature (approximately 32 wk gestation) infants in the 1st wk of life. In contrast to the dose-dependent suppression of proteolysis seen in healthy full-term neonates, the endogenous rates of appearance of leucine and phenylalanine (reflecting proteolysis) were unchanged in response to amino acids (297 +/- 21, 283 +/- 19, and 284 +/- 31 micromol. kg(-1). h(-1) for leucine and 92 +/- 6, 92 +/- 4, and 84 +/- 7 micromol. kg(-1). h(-1) for phenylalanine). Similar to full-term neonates, leucine oxidation (40 +/- 5, 65 +/- 6, and 99 +/- 7 micromol. kg(-1). h(-1)) and phenylalanine hydroxylation (12 +/- 1, 16 +/- 1, and 20 +/- 2 micromol. kg(-1). h(-1)) increased in a stepwise fashion in response to graded amino acids. This capacity to increase phenylalanine hydroxylation may be crucial to meet tyrosine needs when exogenous supply is limited. Finally, to determine whether amino acids stimulate glucose production in premature neonates, glucose rate of appearance was measured during each study period. In response to amino acid infusion, rates of endogenous glucose production were unchanged (and near zero).

Microbial colonization of soft contact lenses over time.

PURPOSE: To compare the bacterial colonization of soft contact lenses in subjects for successively increasing periods, up to 13 nights of wear. The aim of this study was to determine whether increasing the length of lens wear predisposed subjects to high levels of microbial colonization of lenses. METHODS: Subjects (N = 20) were divided into those with a prior history of adverse events (N = 6), gram-negative bacterial carriers (N = 6), and those with no previous history (N = 8). RESULTS: There were no temporal changes in microbial colonization of lenses. Lenses from all wearers were colonized at least once during the study by gram-positive bacteria at low numbers (<10 cfu/ml). Gram-negative bacteria colonized lenses at least once in 80% of all wearers. Lenses from gram-negative bacterial carriers were more frequently colonized by Staphylococcus aureus and Pseudomonas sp. compared with subjects with no previous history and subjects with a prior history of adverse events, respectively. Lenses from gram-negative bacterial carriers were less frequently colonized by a range of gram-positive bacteria compared with subjects with a prior history of adverse events. CONCLUSIONS: Increasing the length of lens wear up to 13 nights did not result in a predictable increase in bacterial colonization of contact lenses. Gram-positive bacteria were isolated frequently but in low numbers, whereas gram-negative bacteria were present sporadically.

Energy expenditure after surgical repair in children with cyanotic congenital heart disease.

OBJECTIVE: Infants with cyanotic congenital heart disease (CCHD) have previously been shown to have similar resting energy expenditures (REEs) and elevated total energy expenditures (TEEs) compared with age-matched healthy infants. The purpose of this investigation was to re-examine the REE and TEE of the same individuals at 5 years of age, after surgical repair of the heart defect was done, to determine whether metabolic differences persist. STUDY DESIGN: Seven children were studied approximately 2.6 years after they underwent surgical repair of CCHD along with 10 age-matched healthy children. Indirect calorimetry was used to determine REE, and the doubly labeled water method was used to determine TEE and body composition. RESULTS: Results were compared with single-factor repeated measures analysis of variance. No significant differences were found between groups in weight or body composition. No significant differences were found between groups in REE, TEE, or the energy expended in physical activity. CONCLUSION: We conclude that differences in TEE observed during infancy are no longer present in 5-year-old children after they undergo surgical repair of CCHD. Furthermore, the individual components of energy expenditure of children with CCHD after repair are indistinguishable from those of healthy age-matched children.

Energy expenditure in the extremely low-birth weight infant.

Information about energy requirements of extremely low-birth weight infants is sparse, despite the rapidly improving survival rates of this population. Metabolizable energy intake can be estimated from energy balance studies and the percentage of caloric intake that is actually absorbed by these infants is approximately 87%. Data on energy expenditure in extremely premature infants is limited; however, energy expenditure has been shown to increase with postnatal age. Because both intake and expenditure are affected by multiple factors, there is significant variability in estimates of the energy requirements in extremely low-birth weight infants. At present, no valid recommendations can be made regarding optimal energy requirements for the extremely low-birth weight infant, except that their requirements probably exceed those of stable, growing very low-birth weight infants, currently estimated at 105 to 135 kcal.kg-1d-1.

Incidence of contamination of preserved saline solutions during normal use.

PURPOSE: To ascertain the incidence of microbial contamination of preserved contact lens saline solutions with normal patient use. METHODS: Eight different brands of preserved saline were dispensed to 40 patients attending optometric practices in the Sydney area. After specific periods of time (7 to 28 days), the samples were collected and the solution bottle nozzles and contents underwent microbial analysis. RESULTS: The overall contamination rate was approximately 26% for contents only and 55% for nozzles of preserved saline solutions. This rate remained constant for all periods of use. Coagulase-negative Staphylococci were most frequently isolated. No Acanthamoebae were isolated. Saline preserved with ethylene-diamine-tetraacetic acid (EDTA) in conjunction with sorbic acid showed the highest percentage of sterility. CONCLUSIONS: The results of this study show that preserved saline became contaminated with gram-positive bacteria. This is in contrast to our previously published paper using unpreserved saline, where contamination was predominantly with gram-negative bacteria. The overall contamination rates with preserved saline were lower than for unpreserved saline.

Energy expenditure and energy intake during dexamethasone therapy for chronic lung disease.

Dexamethasone is commonly administered to ventilator-dependent preterm infants with chronic lung disease. Infants receiving dexamethasone therapy frequently exhibit decreased rates of weight gain. The purpose of this investigation was to determine whether decreased growth in infants receiving dexamethasone therapy is caused by increased energy expenditure. Twelve infants were studied: 6 received dexamethasone treatment at 2 wk of age and crossed over to receive placebo treatment at 4 wk; the treatment order was reversed in the other 6 infants. The doubly labeled water method was used to determine energy expenditure for a 1-wk period during each treatment phase. The rate of weight gain during dexamethasone treatment was 6.5+/-10.6 and 20.0+/-5.7 g/kg/d during placebo treatment. Energy expenditure was 93.1+/-34.6 kcal/kg/d during dexamethasone treatment and 88.3+/-37.1 kcal/kg/d during placebo treatment. Energy intake was 119.2+/-29.0 kcal/kg/d during dexamethasone treatment and 113.8+/-23.7 kcal/kg/d during placebo treatment. The difference between intake and expenditure, or the energy available for growth, was 26.2+/-36.8 kcal/kg/d during dexamethasone treatment and 25.5+/-37.4 kcal/kg/d during placebo treatment. No significant differences were found in energy expenditure or energy intake between the treatment phases. The reduced growth seen in infants receiving dexamethasone treatment cannot be explained by increased energy expenditure or decreased energy intake, but may be due to differences in the composition of newly accreted tissue.

Competing in the new health care paradigm: a novel personnel compensation model, Part I.

Operational issues in health care ultimately lead to discussions concerning personnel. Adequate staffing, "rightsizing," compensation, scheduling, morale, supervision, and organizational structure were subjects of the questions the Clinical Pathology Laboratories at the University of Virginia Medical Center asked in 1994. The answers were found in the design of a new skill-based personnel organizational model and compensation plan.

Increased energy expenditure in infants with cyanotic congenital heart disease.

Infants with cyanotic congenital heart disease (CCHD) often have reduced weight gain compared with infants in control groups. Our purpose was to conduct a longitudinal study of energy intake, resting energy expenditure (REE), and total energy expenditure (TEE) of a group of infants with CCHD. We hypothesized that increased REE and TEE and decreased energy intake in these infants would lead to reduced growth. Ten infants with uncorrected CCHD and 12 infants in a control group were studied at 2 weeks of age and again at 3 months. Indirect calorimetry was used to determine REE; the doubly labeled water method was used to determine TEE and intake. At 2 weeks and 3 months of age, infants with CCHD weighed significantly less than infants in the control group. No significant difference was seen in energy intake or REE between groups during either period. TEE was slightly but not statistically increased in the CCHD group at 2 weeks (72.6 +/- 17.4 vs 59.8 +/- 10.9 kcal/kg/d) and significantly increased at 3 months (93.6 +/- 23.3 vs 72.2 +/- 13.2 kcal/kg/d, P

Total but not resting energy expenditure is increased in infants with ventricular septal defects.

OBJECTIVE: The purpose of this study was to determine the effect of left-to-right shunting on the resting energy expenditure (REE), total energy expenditure (TEE), and energy intake in a group of 3- to 5-month-old infants with moderate to large unrepaired ventricular septal defects (VSDs) compared with age-matched, healthy infants. METHODS: Eight infants with VSDs and 10 healthy controls between 3 to 5 months of age participated in the study. Indirect calorimetry was used to measure REE and the doubly-labeled water method was used to measure TEE and energy intake. An echocardiogram and anthropometric measurements were performed on all study participants. Daily urine samples were collected at home for 7 days. Samples were analyzed by isotope ratio mass spectrometry. Data were compared using analysis of variance. RESULTS: No significant differences were found in REE (VSD, 42.2 +/- 8.7 kcal/kg/d; control, 43.9 +/- 14.1 kcal/kg/d) or energy intake (VSD, 90.8 +/- 19.9 kcal/kg/d; control, 87.1 +/- 11.7 kcal/kg/d) between the groups. The percent total body water was significantly higher in the VSD infants and the percent fat mass was significantly lower. TEE was 40% higher in the VSD group (VSD, 87.6 +/- 10.8 kcal/kg/d; control, 61.9 +/- 10.3 kcal/kg/d). The difference between TEE and REE, reflecting the energy of activity, was 2.5 times greater in the VSD group. CONCLUSIONS: REE and energy intake are virtually identical between the two groups. Despite this, infants with VSDs have substantially higher TEE than age-matched healthy infants. The large difference between TEE and REE in VSD infants suggests a substantially elevated energy cost of physical activity in these infants. These results demonstrate that, although infants with VSDs may match the energy intake of healthy infants, they are unable to meet their increased energy demands, resulting in growth retardation.

Determination of the specific activity of sheep plasma amino acids using high-performance liquid chromatography: comparison study between liquid scintillation counter and on-line flow-through detector.

A method was developed for the determination of the specific activities of leucine and phenylalanine in plasma using a flow-through scintillation counter coupled with high-performance liquid chromatography components. Results were compared with those obtained from liquid scintillation counting. Differences in the specific activities of leucine and phenylalanine between the two methods were not statistically significant. We concluded that flow-through radioactivity detection can be used for quantitative amino acid assays. However, the minimum activity that can be detected may be prohibitively low in certain applications.

The rise in caesarean section rate: the same indications but a lower threshold.

OBJECTIVE: To investigate the reasons for the rise in caesarean section rate and note any change in indications. DESIGN: A retrospective, descriptive study comparing the years 1962 and 1992. SETTING: A large city centre teaching hospital. RESULTS: There was an overall increase in the caesarean section rate from 6-8% in 1962 to 18.1% in 1992. No single cause contributed more than 30% towards this increase. The main indications in both years were similar: failure to progress (42.2% vs 36.7%) and fetal indications (18.1% vs 18.9%). The largest relative increases were in the malpresentation group (10.8% vs 16%) and previous caesarean section (4.5% vs 15.2%). CONCLUSIONS: These results suggest that there has been a lowering in the overall threshold concerning the decision to carry out a caesarean section rather than changes in obstetric management. Obstetricians and the women in their care have to decide whether the current balance between risk and benefit is acceptable or whether they wish to alter the underlying philosophy if any significant reduction is to be sustained.

Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk.

CONTEXT: Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections in children have occurred primarily in individuals with recognized predisposing risks. Community-acquired MRSA infections in the absence of identified risk factors have been reported infrequently. OBJECTIVES: To determine whether community-acquired MRSA infections in children with no identified predisposing risks are increasing and to define the spectrum of disease associated with MRSA isolation. DESIGN: Retrospective review of medical records. PATIENTS: Hospitalized children with S aureus isolated between August 1988 and July 1990 (1988-1990) and between August 1993 and July 1995 (1993-1995). SETTING: The University of Chicago Children's Hospital. MAIN OUTCOME MEASURES: Prevalence of community-acquired MRSA over time, infecting vs colonizing isolates, and risk factors for disease. RESULTS: The number of children hospitalized with community-acquired MRSA disease increased from 8 in 1988-1990 to 35 in 1993-1995. Moreover, the prevalence of community-acquired MRSA without identified risk increased from 10 per 100000 admissions in 1988-1990 to 259 per 100000 admissions in 1993-1995 (P<.001), and a greater proportion of isolates produced clinical infection. The clinical syndromes associated with MRSA in children without identified risk were similar to those associated with community-acquired methicillin-susceptible S aureus. Notably, 7 (70%) of 10 community-acquired MRSA isolates obtained from children with an identified risk were nonsusceptible to at least 2 drugs, compared with only 6 (24%) of 25 isolates obtained from children without an identified risk (P=.02). CONCLUSIONS: These findings demonstrate that the prevalence of community-acquired MRSA among children without identified risk factors is increasing.

The changing pattern of eclampsia over a 60-year period.

OBJECTIVE: To determine changes in the incidence and pattern of eclampsia within the same geographical area over a 60-year period. DESIGN: A retrospective, descriptive study of 1259 consecutive women classified, at the time, as having had an eclamptic convulsion between the years 1931 and 1990. SETTING: A large city centre teaching hospital and the surrounding catchment area. MAIN OUTCOME MEASURES: The changes in the incidence and timing of the convulsion and the outcomes for the mother and baby. RESULTS: Over the study period, the incidence of eclampsia fell by more than 90%, from 74.1/10,000 in the 1930s to 7.2/10,000 in the 1980s. Most of the reduction occurred over the first four decades, with little change in the last 20 years. Overall, 44% of the cases of eclampsia occurred in the antenatal period, 33% intrapartum and 23% postpartum. Since the biggest decreases were seen in the incidence of antenatal and particularly intrapartum eclampsia, there has been a relative increase in the proportion of eclampsia occurring postpartum. Maternal death from eclampsia occurred in 15.1% of cases between 1931 and 1940, 13.4% between 1941 and 1950, but fell dramatically to < or = 3.9% after 1950. There has been no maternal death since 1964. Apart from the first decade, postpartum eclampsia was associated with significantly less risk of death to the mother throughout the study period. Perinatal death rate has fallen steadily from 432.6/1000 cases of eclampsia between 1931 and 1940 over the first three decades, to 168.7/1000 between 1961 and 1970. There has been little change since, although a lower proportion of neonatal deaths occurred as stillbirths. CONCLUSIONS: We found a significant reduction in both the incidence of eclampsia and associated morbidity in this population over the last 60 years. This has occurred in association with the introduction of the National Health Service, widespread antenatal care for all and a general improvement in health and welfare. Any further reduction in the incidence in the UK may be difficult to achieve. Since the incidence of eclampsia is now low, efforts should perhaps be directed at minimising the morbidity associated with severe pre-eclampsia rather than prevention of convulsions.

Recombinant human relaxin as a cervical ripening agent.

OBJECTIVE: The aim of this study was to investigate the efficacy and safety of recombinant human relaxin (rhRIx) as a cervical ripening agent in women with an unfavourable cervix before induction of labour at term. DESIGN: A multi-centre, double-blind, placebo-controlled trial performed in Edinburgh, Glasgow and Oxford. Women were treated with 0, 1, 2 or 4 mg of rhRIx in a gel vehicle administered intravaginally. Analysis of variance tests were performed on all continuous variables, and Cochran Mantel-Haenszel tests employed for all discrete variables. PARTICIPANTS: Ninety-six women at 37 to 42 weeks of gestation with a singleton pregnancy and a modified Bishop score of < or = 4 were recruited. RESULTS: There was no significant difference in the change in modified Bishop score between the four treatment groups. The lengths of the first and second stages of labour were similar in all 4 groups. PGE2 and oxytocin requirements were similar in all groups, as was the mode of delivery. There was no evidence that relaxin was absorbed systemically when given in this way. CONCLUSION: Recombinant human relaxin 1 to 4 mg, administered as an intravaginal gel, has no effect as a cervical ripening agent before induction of labour at term.

Acute changes in leucine and phenylalanine kinetics produced by parenteral nutrition in premature infants.

To determine the effect of parenteral nutrition on the balance and catabolism of leucine (by oxidation) and phenylalanine (by hydroxylation) and to assess any acute changes in proteolysis and/or protein synthesis, leucine and phenylalanine kinetics were measured by stable isotope tracer infusions in nine 32-wk gestation premature infants under both basal conditions and in response to an i.v. infusion of glucose, lipid, and amino acids. Leucine and phenylalanine balance both changed from negative to positive during parenteral nutrition. However, leucine and phenylalanine catabolism were differently affected by parenteral nutrition; the rate of leucine oxidation increased 2-fold, whereas the rate of phenylalanine hydroxylation was unchanged from basal values. Phenylalanine utilization for protein synthesis and leucine utilization for protein synthesis (based on both plasma leucine and alpha-ketoisocaproic acid enrichments) increased significantly during parenteral nutrition. The endogenous rates of release of leucine (based on plasma leucine enrichment) and phenylalanine (both reflecting proteolysis) were significantly reduced during parenteral nutrition. The endogenous rate of release of leucine (based on alpha-ketoisocaproic acid enrichment) was slightly but not significantly lower during parenteral nutrition. The substantial increase in leucine oxidation without changes in phenylalanine hydroxylation suggests a possible limitation in the phenylalanine/tyrosine supply during parenteral nutrition. In addition, these results suggest that premature infants respond to parenteral nutrition with acute increases in whole body protein synthesis as well as a probable reduction in proteolysis.