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Biomedical subjects

G Leslie

Publications and source records attributed to G Leslie.

At least 19 recordsLinked to original sources

Adverse events experienced while transferring the critically ill patient from the emergency department to the intensive care unit.

OBJECTIVES: To determine the incidence and nature of adverse events and delay to patient transfer from emergency department to intensive care unit (ICU) in a metropolitan tertiary hospital. METHOD: A 6-month prospective observational study in conjunction with a retrospective chart audit on all emergency department patients admitted to ICU, including those admitted via theatre or after a computed tomography scan. RESULTS: Equipment problems was the most common adverse event occurring in 9% of patient transfers (n = 290). Hypothermia events occurred in 7% of transfers, cardiovascular events in 6% of patient transfers, delays to transfer >20 min occurred in 38% of the prospectively audited cases, with 14% waiting >1 h. One patient was found to have an incorrect patient identification band during a preoperative check. CONCLUSIONS: This study generally reported lower rates of adverse events than noted in previous studies involving critically ill transfers. The most significant finding was the application of an incorrect patient identification band and has prompted a review of practice. The establishment of benchmark indicators for adverse events and delays in transfer will be useful for future audits.

Adolescent↗

Progression of autoimmune diabetes: slowly progressive insulin-dependent diabetes mellitus or latent autoimmune diabetes of adult.

Autoimmune diabetes is due to destruction of insulin-secreting beta islet cells by an immune-mediated process, which is induced and promoted by the interaction of genetic and environmental factors. This form of diabetes is one of a group of autoimmune diseases that affect about 10% of the population in the developed world. The detection of diabetes-associated autoantibodies, including glutamic acid decarboxylase antibodies (GADA), islet cell antibodies (ICA), and insulinoma-associated (IA-2) autoantibodies is widely held to reflect an underlying autoimmune pathology but the clinical features associated with the presence of these diabetes-associated autoantibodies is highly variable ranging from lack of symptoms with normal glucose tolerance to catastrophic and potentially fatal diabetic ketoacidosis. It is the purpose of this article to establish the range of metabolic features associated with diabetes-associated autoimmune changes and discuss how this metabolic spectrum itself reflects a spectrum of immune and clinical changes that cast light on the nature of autoimmune diabetes.

Adult↗

ACCCN national nursing workforce survey of intensive care units.

A descriptive study was designed and implemented by the Australian College of Critical Care Nurses (ACCCN) Workforce Planning Advisory Committee to capture data pertaining to workforce issues of intensive care nurses. All intensive care units (ICUs) within Australia were mailed a self reporting survey. Despite a low response rate (52 per cent) and difficulty reported by respondents in gaining the appropriate data requested, the results revealed an interesting snapshot of the intensive care nursing workforce. Types of services offered by units varied considerably; paid overtime hours were low (< 2 per cent of total hours worked) and use of both part-time and agency staff was also low (10 per cent of total hours worked). Private hospitals utilised a greater proportion of part-time and agency nursing staff than public hospitals (20:10 per cent). The turnover rate for registered nursing staff was estimated at 18 per cent, with education, skill acquisition and improved communication reported as the major incentives used by managers to attract and retain staff. This study demonstrated that valuable data are currently uncaptured and recommends a more refined process of a national database to record and manage this important information for future workforce planning.

Australia↗

cis Expression of DC-SIGN allows for more efficient entry of human and simian immunodeficiency viruses via CD4 and a coreceptor.

DC-SIGN is a C-type lectin expressed on dendritic cells and restricted macrophage populations in vivo that binds gp120 and acts in trans to enable efficient infection of T cells by human immunodeficiency virus type 1 (HIV-1). We report here that DC-SIGN, when expressed in cis with CD4 and coreceptors, allowed more efficient infection by both HIV and simian immunodeficiency virus (SIV) strains, although the extent varied from 2- to 40-fold, depending on the virus strain. Expression of DC-SIGN on target cells did not alleviate the requirement for CD4 or coreceptor for viral entry. Stable expression of DC-SIGN on multiple lymphoid lines enabled more efficient entry and replication of R5X4 and X4 viruses. Thus, 10- and 100-fold less 89.6 (R5/X4) and NL4-3 (X4), respectively, were required to achieve productive replication in DC-SIGN-transduced Jurkat cells when compared to the parental cell line. In addition, DC-SIGN expression on T-cell lines that express very low levels of CCR5 enabled entry and replication of R5 viruses in a CCR5-dependent manner, a property not exhibited by the parental cell lines. Therefore, DC-SIGN expression can boost virus infection in cis and can expand viral tropism without affecting coreceptor preference. In addition, coexpression of DC-SIGN enabled some viruses to use alternate coreceptors like STRL33 to infect cells, whereas in its absence, infection was not observed. Immunohistochemical and confocal microscopy data indicated that DC-SIGN was coexpressed and colocalized with CD4 and CCR5 on alveolar macrophages, underscoring the physiological significance of these cis enhancement effects.

CD4 Antigens↗

Biocontrol of the sugarcane borer Eldana saccharina by expression of the Bacillus thuringiensis cry1Ac7 and Serratia marcescens chiA genes in sugarcane-associated bacteria.

The cry1Ac7 gene of Bacillus thuringiensis strain 234, showing activity against the sugarcane borer Eldana saccharina, was cloned under the control of the tac promoter. The fusion was introduced into the broad-host-range plasmid pKT240 and the integration vector pJFF350 and without the tac promoter into the broad-host-range plasmids pML122 and pKmM0. These plasmids were introduced into a Pseudomonas fluorescens strain isolated from the phylloplane of sugarcane and the endophytic bacterium Herbaspirillum seropedicae found in sugarcane. The ptac-cry1Ac7 construct was introduced into the chromosome of P. fluorescens using the integration vector pJFF350 carrying the artificial interposon Omegon-Km. Western blot analysis showed that the expression levels of the integrated cry1Ac7 gene were much higher under the control of the tac promoter than under the control of its endogenous promoter. It was also determined that multicopy expression in P. fluorescens and H. seropedicae of ptac-cry1Ac7 carried on pKT240 caused plasmid instability with no detectable protein expression. In H. seropedicae, more Cry1Ac7 toxin was produced when the gene was cloned under the control of the Nm(r) promoter on pML122 than in the opposite orientation and bioassays showed that the former resulted in higher mortality of E. saccharina larvae than the latter. P. fluorescens 14::ptac-tox resulted in higher mortality of larvae than did P. fluorescens 14::tox. An increased toxic effect was observed when P. fluorescens 14::ptac-tox was combined with P. fluorescens carrying the Serratia marcescens chitinase gene chiA, under the control of the tac promoter, integrated into the chromosome.

Animals↗

Simian immunodeficiency virus utilizes human and sooty mangabey but not rhesus macaque STRL33 for efficient entry.

It has been established that many simian immunodeficiency virus (SIV) isolates utilize the orphan receptors GPR15 and STRL33 about as efficiently as the chemokine receptor CCR5 for entry into target cells. Most studies were performed, however, with coreceptors of human origin. We found that SIV from captive rhesus macaques (SIVmac) can utilize both human and simian CCR5 and GPR15 with comparable efficiencies. Strikingly, however, only human STRL33 (huSTRL33), not rhesus macaque STRL33 (rhSTRL33), functioned efficiently as an entry cofactor for a variety of isolates of SIVmac and SIV from sooty mangabeys. A single amino acid substitution of S30R in huSTRL33 impaired coreceptor activity, and the reverse change in rhSTRL33 greatly increased coreceptor activity. In comparison, species-specific sequence variations in N-terminal tyrosines in STRL33 had only moderate effects on SIV entry. These results show that a serine residue located just outside of the cellular membrane in the N terminus of STRL33 is critical for SIV coreceptor function. Interestingly, STRL33 derived from sooty mangabeys, a natural host of SIV, also contained a serine at the corresponding position and was used efficiently as an entry cofactor. These results suggest that STRL33 is not a relevant coreceptor in the SIV/macaque model but may play a role in SIV replication and transmission in naturally infected sooty mangabeys.

Amino Acid Sequence↗

A prospective, randomized, controlled trial comparing transparent polyurethane and hydrocolloid dressings for central venous catheters.

BACKGROUND: This study was undertaken to determine the frequency of skin colonization, hub colonization, and central venous catheter colonization in transparent hydrocolloid versus standard polyurethane dressings. METHODS: Adult patients requiring the insertion of a multilumen central venous catheter in an intensive care unit were randomized to receive either a standard polyurethane dressing or a transparent hydrocolloid dressing. Cultures were obtained from 125 skin insertion sites, 141 catheter hubs, 128 catheter tips, and blood samples from 132 patients. Extensive data on patient and catheter characteristics were collected. RESULTS: Skin and hub cultures revealed no significant difference in degree of colonization. However, the hydrocolloid group had a significantly higher level of catheter colonization than the polyurethane group (P =.048). Conversely, there was a significantly higher frequency of positive blood cultures in the polyurethane group (P =.03), although the majority were considered to be potential contaminants. There were only 6 cases in which the same species was simultaneously isolated from a positive blood culture and a colonized catheter, 5 from the hydrocolloid group and 1 from the polyurethane group. CONCLUSIONS: The results of this study suggest that an increased risk of catheter colonization is associated with the use of hydrocolloid dressings, despite previous research suggesting that they significantly reduce microbial growth compared with standard polyurethane. The clinical significance of increased numbers of positive blood cultures in the polyurethane group requires further examination, although distinguishing between contamination and true infection in intensive care settings continues to be methodologically challenging. Further studies are required to determine whether these findings are generalizable across different study settings and whether similar outcomes are obtained when different brands of hydrocolloid dressing are used.

Adolescent↗

Prostacyclin concentrations and transitional circulation in preterm infants requiring mechanical ventilation.

AIM: To describe the association between early postnatal prostacyclin concentrations in preterm infants; echocardiographic measurements of ductal diameter and ventricular output and clinical outcomes of intraventricular haemorrhage (IVH) and patent ductus arteriosus (PDA). METHODS: Forty nine preterm infants born before 30 weeks of gestational age (median birthweight 980 g, median gestational age 27 weeks) underwent echocardiographic studies at 5, 12, 24 and 48 hours of postnatal age. Measurements included ventricular outputs and the ductal shunt diameter as a measure of the shunt size. Simultaneous measurements of blood pressures, mean airway pressure and inspired fraction of oxygen (FIO2) were recorded. A blood sample for the prostacyclin metabolite 6-ketoprostaglandin F1-alpha (6KPGF1 alpha) was taken at the 5 and 24 hour echocardiogram. RESULTS: The mean 6KPGF1 alpha concentrations were higher than adult concentrations at 5 (515 pg/ml) and 24 (255 pg/ml) hours. There was no association with gestational age. Raised 6KPGF1 alpha concentrations were related to increased need for mechanical ventilation and severity of respiratory disease. At 5 hours, increased 6KPGF1 alpha concentrations were associated with larger PDA and at 24 hours with larger PDA and higher left ventricular output. Infants with higher 6KPGF1 alpha concentrations were more likely to develop clinically significant PDA. There was no association between early measurements of 6KPGF1 alpha and IVH. CONCLUSIONS: Early postnatal prostacyclin concentrations are markedly raised in preterm infants, particularly in those with more severe lung disease. Raised 6KPGF1 alpha concentrations were associated with an increased ductal diameter and subsequent PDA, but not IVH.

6-Ketoprostaglandin F1 alpha↗

Higher SaO2 in chronic neonatal lung disease: does it improve sleep?

Sleep fragmentation, decreased rapid eye movement (REM) sleep time, and REM sleep hypoxemia have been reported in infants with chronic neonatal lung disease (CNLD) in early infancy despite an awake hemoglobin oxygen saturation (SaO2) >93%. Interestingly, higher inspired O2 concentrations have been demonstrated to reduce REM sleep fragmentation in CNLD patients in middle infancy. However, the effect of increased SaO2 on sleep architecture in infants with CNLD near the time of discharge from neonatal intensive care has not been reported. We performed paired overnight polysomnography in a sleep laboratory on 16 infants with CNLD (4 weeks median corrected age) in air or their usual inspired oxygen (SaO2 >93%) and again when receiving 0.25 L/min higher than baseline inspired oxygen via nasal catheters (SaO2 >97%). A control group of seven healthy preterm infants was similarly studied. For CNLD infants on supplemented O2, sleep duration decreased by 15% (422+/-66 min vs. 359+/-89 min; P< 0.005), and sleep efficiency decreased by 7% (73.2+/-10.6% vs. 66.4+/-14.0%; P < 0.005) but percentage of time in REM sleep (REM%) (31.5+/-8.9% vs. 29.8+/-8.6%; P=0.560), REM epoch duration (12.4+/-2.8 min vs. 13.4+/-4.3 min; P=0.420), and REM arousal index (18.6+/-6.5 vs. 18.8+/-7.2; P=0.990) were not significantly affected. Conversely, higher O2 did not alter sleep architecture in the control group. The mean non-REM (NREM) respiratory rate decreased (CNLD: P=0.003; controls: P=0.02), NREM SaO2 increased (P < 0.05), although the mean transcutaneous CO2 was unaltered in both CNLD and control groups. This study confirmed low REM% in CNLD infants in early infancy and demonstrated that a higher SaO2 adversely affected sleep time but did not influence REM sleep duration or arousal frequency. A target SaO2 >93% is, therefore, as efficacious as an SaO2 >97% in optimizing sleep architecture in CNLD infants.

Bronchopulmonary Dysplasia↗

Sleep, respiratory rate, and growth hormone in chronic neonatal lung disease.

This study assessed whether respiratory rates (RRs) correlate with urinary growth hormone (U-GH) excretion and sleep architecture in infants with chronic neonatal lung disease (CNLD) in early (1 month), middle (6 months), and late (10 months) infancy. Twenty-three preterm infants (CNLD=16, controls=7) were studied on 51 occasions. CNLD infants were stratified according to mean non-REM sleep respiratory rate (NREM RR) in early infancy into "High RR CNLD" infants (mean NREM RR >2 SD higher than controls) and "Normal RR CNLD" infants (mean NREM RR within 2 SD of controls' mean). "High RR CNLD" infants (RR >45) had a lower mean birthweight (P=0.015), current weight (P=0.042), current length (P=0.02), and growth velocity in early infancy (grams/week gained: P=0.042) than "Normal RR CNLD" and control infants. Mean (95% CI) U-GH excretion (ng U-GH/g urinary creatinine) was higher in "High RR CNLD" infants in air or their usual O2 (1,932 [459, 3,406]) than "Normal RR CNLD" (394 [147, 642]) and controls (320 [147, 492]) (P=0.024). With resolution of tachypnea by mid-infancy, hemoglobin oxygen saturation (SaO2) >93%, mean growth parameters and U-GH excretion for the "High RR CNLD" group were not significantly different from "Normal RR CNLD" and control groups. CNLD infants demonstrated increased sleep efficiency (P=0.016), whereas controls had similar sleep efficiency between early and middle infancy (P=0.452). Mean percent time in REM sleep (REM%) and slow wave sleep (SWS%) were not significantly different between early and middle infancy and did not vary in relation to respiratory rate. We conclude that tachypneic infants with CNLD have slower growth and elevated U-GH excretion in early infancy. With resolution of tachypnea, growth improved, U-GH excretion decreased, and sleep consolidation occurred. An elevated U-GH in tachypneic CNLD infants may reflect stress, compromised nutrition (GH resistance), or a feedback loop involving a direct effect of GH on lung growth and repair.

Bronchopulmonary Dysplasia↗

Longitudinal study of plasma cortisol and 17-hydroxyprogesterone in very-low-birth-weight infants during the first 16 weeks of life.

There are few published data on plasma cortisol and 17-hydroxyprogesterone (17-OHP) in very-low-birth-weight (VLBW) infants beyond the 1st week of life. We therefore measured plasma cortisol and 17-OHP longitudinally in 26 infants (median birth weight 930 g, median gestational age 28 weeks) from 1 to 16 postnatal weeks to document normative values. We also examined the effect of clinical state on plasma cortisol and 17-OHP levels. Median plasma cortisol decreased with postnatal age from 1 to 8 weeks (110 vs. 60 nmol/l; p = 0.0007) and with postconceptional age from 25 to 36 weeks (104 vs. 47 nmol/l; p = 0.002). Median plasma 17-OHP decreased with postnatal age from 1 to 16 weeks (17.0 vs. 7.1 nmol/l; p < 0.0005) and also with postconceptional age from 25 to 42 weeks (21.1 vs. 7.1 nmol/l; p < 0.0005). Plasma cortisol was not influenced by the clinical state. Median plasma 17-OHP was significantly higher for 'unwell' versus 'well' infants at 5-8 weeks postnatal age (23.0 vs. 12.5 nmol/l; p = 0.012) but not at other postnatal age intervals. These data provide information on adrenocortical function in VLBW infants during the first 4 months of life.

17-alpha-Hydroxyprogesterone↗

Isolation and characterization of porcine mannan-binding proteins of different size and ultrastructure.

The authors report on the purification and characterization of mannan- binding proteins (MBP) isolated from porcine serum. The MBPs were purified by use of PEG precipitation, affinity chromatography on mannan-Sepharose, protein A- and anti-porcine IgM-Sepharose followed by gel filtration. The MBP proteins were collagenase sensitive and showed gamma 1-gamma 2-electrophoretic mobility. The MBP designated pMBP-28 had a molecular mass of 28 kDa when analysed on SDS-PAGE under reducing conditions and eluted corresponding to a molecular mass of approximately 700 kDa on gel filtration chromatography. Electron micrographs of pMBP-28 revealed an oligomeric protein similar to rodent MBP-A and human MBP but with a predominance of penta- and hexameric molecules. Another protein designated pMBP-27 was composed of peptides of 27 kDa and had an Mr of 300-350 kDa on gel filtration chromatography. Electron microscopy of pMBP-27 showed dimer and trimer molecules; the trimers without distinct stalk regions. The N-terminal 26(pMBP-27) and 24(MBP-28) amino acid residues showed 54% and 58% identity with human MBP.pMBP-28 showed a higher degree of sequence similarity to rat and mouse MBP-A (60% identity) than to mouse and rat MBP-C (41-45% identity). Both pMBPs exhibited Ca2+-dependent binding to D-mannose immobilized on agarose but no significant binding to N-acetyl-D-glucosamine- or fucose-agarose. The results further suggested the presence of a third pMBP which copurified with pMBP-27 but this protein was not sequenced.

Amino Acid Sequence↗

Short-term outcome of mechanically ventilated infants weighing more than 2499 g at birth: a population based study.

Very little data exist describing the neonatal outcome of infants of birthweight 2500 g or more who require mechanical ventilation. Our aim was to collect population-based data on such infants in New South Wales (NSW), and to monitor their neonatal morbidity, mortality to 1 year of age and the associated risk factors. The study group (NICUS infants) comprised all 341 infants weighing > 2499 g who were admitted to the seven neonatal intensive care units in New South Wales and mechanically ventilated for 4 h or more between 1 January and 31 December, 1987. Two groups of infants emerged: those who were preterm and mostly had hyaline membrane disease, and term and post-term infants for whom the most common problem was 'perinatal asphyxia'. The most important factors associated with dying were a birthweight of over 3499 g (OR = 2.6; CI 1.03-6.6) and a 1 min Apgar score < 4 (OR = 4.8; CI 1.4-16.9). Study group mothers were significantly more likely than all NSW mothers to have had a spontaneous abortion in the previous pregnancy (P < 0.01), a pre-existing medical condition or an obstetric complication in this pregnancy, or a Caesarean section for this delivery (P < 0.001). This is the first population-based study of high-risk neonates without congenital anomalies to clearly document the worsening prognosis associated with a birthweight over 3499 g. Further research should be directed towards identifying prenatal and perinatal factors which might minimize the morbidity and mortality in this group of babies.

Apgar Score↗

Preparation of antigen-binding monomeric and half-monomeric fragments from human monoclonal IgM antibodies against colorectal cancer-associated antigens.

The large size of human IgM monoclonal antibodies (MAbs) may impede the tumor-localizing capacity. A procedure is described for the preparation of antigen-binding monomeric (IgMm) and half-monomeric (IgM1/2m) fragments from two human IgM MAbs, COU-1 and D4213. The fragments retained binding activity against colon carcinoma. Six different reducing reagents (dithiothreitol, 2-mercaptoethanol, 2-mercaptoethylamine, L-cysteine, metabisulphite, ascorbic acid) were investigated over a range of concentrations, pHs, and incubation periods. The reduced IgM preparations were alkylated with iodoacetamide and fractionated by high-performance gel permeation chromatography. The fractions were directly collected on ELISA plates coated with extracts of colon cancer cells. Antigen-binding IgMm and IgM1/2m fragments were obtained after treatment with mercaptoethanol, mercaptoethylamine, metabisulphite, and cysteine. IgMm and IgM1/2m fragments were also obtained after dithiothreitol treatment. These fragments were, however, nonreactive. The pH during the reduction was important for optimal yields of the fragments. The fragments obtained with 2-mercaptoethanol and mercaptoethylamine were most effective in binding to the cancer cell extract. The association constants per binding site for intact, monomeric, and half-monomeric COU-1 were by competitive inhibition assays estimated at 1.5 x 10(8) M-1, 3.1 x 10(8) M-1 and 4.0 x 10(6) M-1, respectively. The reduction of human IgM MAbs to IgMm and IgM1/2m fragments may facilitate the tumor localization when these are used in the diagnosis and therapy of cancer patients.

Alkylation↗

Influence of food intake and sexual segregation on longevity, organ weights and the incidence of non-neoplastic and neoplastic diseases in rats.

In a small-scale experiment the effects of four variables were investigated in male and female Wistar rats fed on a standard laboratory chow and not deliberately exposed to any carcinogen. The variables investigated were (i) diet restriction by limiting access to food to 6.5 hr/day instead of 24 hr/day; (ii) housing males in a single-sex room as distinct from a mixed-sex room; (iii) life-long segregation of males from females, as distinct from access to one virgin female for 5 days during each alternate week; and (iv) uniparity in females versus life-long virginity. The endpoints compared were body-weight gain, longevity, visible and palpable swellings, absolute and relative organ weights, microscopically confirmed malignant neoplasms that contributed to death before the end of the study at 2 yr, incidence of other neoplasms in decedents and rats killed at the end of the study, and the incidence of various non-neoplastic conditions including myocardial inflammation and fibrosis, chronic progressive nephropathy, liver glycogen storage and fatty degeneration, mammary gland hyperplasia and secretory activity, pancreatic polyarteritis, radiculoneuropathy and certain testicular changes. The results indicated major beneficial effects of dietary restriction on most of the endpoints. By comparison the other variables had only marginal effects. Leydig-cell hyperplasia and neoplasia occurred at significantly higher incidences in males housed intermittently with females than in permanently segregated males. No convincing differences were seen between females that littered once and those that remained virgins. The relevance of these findings to the prediction of cancer mortality risk in man and to the design of rodent carcinogenicity studies is discussed.

Animals↗

Topical iodine-containing antiseptics and neonatal hypothyroidism in very-low-birthweight infants.

The thyroid function of very-low-birthweight (VLBW; below 1500 g) infants admitted to neonatal intensive-care units was studied at two hospitals; one routinely used topical iodinated antiseptic agents and the other used chlorhexidine-containing antiseptics. Serial monitoring of urinary iodine excretion and serum thyrotropin and thyroxine levels was undertaken from birth for the first 4 weeks of life. Urinary iodine excretion rose dramatically in the 54 iodine-exposed infants and was up to fifty times greater than in the 29 non-exposed infants. Within 14 days, 25% (9 of 36) of the infants exposed to iodine had serum thyrotropin levels above 20 mIU/l, compared with none of the control group. The mean serum thyroxine level in these 9 infants (44.1 nmol/l) was significantly lower than that in exposed infants with normal thyrotropin levels (83.1 nmol/l) and in the non-exposed control group (83.0 nmol/l); thyroxine levels fell before serum thyrotropin rose. These disturbances in thyroid function correlated positively with urinary iodine excretion and hence iodine absorption. Thyroid function had returned to normal by the time of discharge from hospital. It is concluded that iodine absorption, from topical iodine-containing antiseptics, may cause hypothyroidism during a critical period of neurological development in the newborn infant. The routine use of iodine antisepsis in VLBW infants should be avoided because of this effect.

Administration, Topical↗