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Biomedical subjects

R Lau

Publications and source records attributed to R Lau.

At least 19 recordsLinked to original sources
PubMed2005

Volume guarantee ventilation, interrupted expiration, and expiratory braking.

BACKGROUND: In volume guarantee ventilation with the Dräger Babylog 8000 ventilator, inspiratory and expiratory flows are monitored and the expiratory tidal volume calculated following each inflation. The pressure for the next inflation is modified to ensure the expired tidal volume is close to the set value. AIM: To investigate interrupted expiration observed during volume guarantee ventilation of spontaneously breathing, ventilated infants. METHODS: Spontaneously breathing infants, ventilated with volume guarantee, had recordings of gas flow, ventilator pressures, tidal volume waveforms, oximetry, heart rate, and transcutaneous oxygen and carbon dioxide during 10 minute recordings. RESULTS: A total of 6540 inflations were analysed from 10 infants; 62% were triggered. Two different patterns were found: (1) Normal volume guarantee pattern with 97% of triggered and 91% untriggered inflations. It had a normal expiratory curve and a mean expired tidal volume within 3% of the set volume, but a large variation due to the babies' breathing. (2) A pattern of interrupted expiratory flow after approximately 3% of inflations due to a small inspiration (approximately 1.3 ml/kg) during expiration. This led the ventilator to calculate an inappropriate total expired tidal volume for that inflation and an increase in the pressure for the next inflation. CONCLUSIONS: After about 3% of inflations, with volume guarantee ventilation, interruption of the expiration causes an increased pressure for the next inflation of approximately 4.9 cm H2O, compared with normal volume guarantee inflation. The interrupted expiration is most likely to be due to diaphragmatic braking.

Diaphragm↗
PubMed2005

Neonatal resuscitation 2: an evaluation of manual ventilation devices and face masks.

BACKGROUND: The key to successful neonatal resuscitation is effective ventilation. Little evidence exists to guide clinicians in their choice of manual ventilation device or face mask. The expiratory tidal volume measured at the mask (V(TE(mask))) is a good estimate of the tidal volume delivered during simulated neonatal resuscitation. AIM: To compare the efficacy of (a) the Laerdal infant resuscitator and the Neopuff infant resuscitator, used with (b) round and anatomically shaped masks in a model of neonatal resuscitation. METHODS: Thirty four participants gave positive pressure ventilation to a mannequin at specified pressures with each of the four device-mask combinations. Flow, inspiratory tidal volume at the face mask (V(TI(mask))), V(TE(mask)), and airway pressure were recorded. Leakage from the mask was calculated from V(TI(mask)) and V(TE(mask)). RESULTS: A total of 10,780 inflations were recorded and analysed. Peak inspiratory pressure targets were achieved equally with the Laerdal and Neopuff resuscitators. Positive end expiratory pressure was delivered with the Neopuff but not the Laerdal device. Despite similar peak pressures, V(TE(mask)) varied widely. Mask leakage was large for each combination of device and mask. There were no differences between the masks. CONCLUSION: During face mask ventilation of a neonatal resuscitation mannequin, there are large leaks around the face mask. Airway pressure is a poor proxy for volume delivered during positive pressure ventilation through a mask.

Air Pressure↗
PubMed2005

Neonatal resuscitation 3: manometer use in a model of face mask ventilation.

BACKGROUND: Adequate ventilation is the key to successful neonatal resuscitation. Positive pressure ventilation (PPV) is initiated with manual ventilation devices via face masks. These devices may be used with a manometer to measure airway pressures delivered. The expiratory tidal volume measured at the mask (V(TE(mask))) is a good estimate of the tidal volume delivered during simulated neonatal resuscitation. AIM: To assess the effect of viewing a manometer on the peak inspiratory pressures used, the volume delivered, and leakage from the face mask during PPV with two manual ventilation devices in a model of neonatal resuscitation. METHODS: Participants gave PPV to a modified resuscitation mannequin using a Laerdal infant resuscitator and a Neopuff infant resuscitator at specified pressures ensuring adequate chest wall excursion. Each participant gave PPV to the mannequin with each device twice, viewing the manometer on one occasion and unable to see the manometer on the other. Data from participants were averaged for each device used with the manometer and without the manometer separately. RESULTS: A total of 7767 inflations delivered by the 18 participants were recorded and analysed. Peak inspiratory pressures delivered were lower with the Laerdal device. There were no differences in leakage from the face mask or volumes delivered. Whether or not the manometer was visible made no difference to any measured variable. CONCLUSIONS: Viewing a manometer during PPV in this model of neonatal resuscitation does not affect the airway pressure or tidal volumes delivered or the degree of leakage from the face mask.

Air Pressure↗
PubMed2005

Pharyngeal pressure in preterm infants receiving nasal continuous positive airway pressure.

Pharyngeal pressures in 11 preterm infants, receiving binasal Hudson prong continuous positive airway pressure (CPAP) pressurised by bubbling bottles, were measured. The mean (95% confidence interval) pressure drop from the prongs to the pharynx was 3.2 (2.6 to 3.7) cm H(2)O with mouths open and 2.2 (1.6 to 2.8) cm H(2)O with mouths closed. Mouth closure augments CPAP transmission.

Air Pressure↗
PubMed2005

What do parents think about enrolling their premature babies in several research studies?

OBJECTIVE: To investigate parents' opinions about enrolling their premature baby into several research studies in the few days after birth. METHODOLOGY: A questionnaire was given to parents of premature babies in the neonatal intensive care unit who had been invited to join several studies (two to seven). RESULTS: All 50 mothers and 42 of 48 fathers completed the questionnaire independently; 28% had been asked to join two studies, 32% three, 24% four, 14% five, and 2% six studies. There were 61 babies with mean (SD) gestational age 26.9 (1.6) weeks and birth weight 877 (249) g. Nearly three quarters (71%) of the parents thought it was very good for their baby to be in a hospital that was carrying out a lot of research. Most (93%) thought that their baby would get the same or better care in a study. Only 15% thought their baby was too small for research studies. Almost all (98%) wanted to be involved in the decision about their baby joining a study. Only 22% were worried about the number of studies; 10% would not enroll their baby in any studies, but 74% were willing for their baby to join two or more studies, and 10% would enroll in all the studies. Most (94%) believed that their baby's participation would improve care of future babies. CONCLUSIONS: Most of these parents were willing to join several studies. The majority were not worried about their baby participating in the studies. The profession needs to be aware that parents are supportive of neonatal research and participation in multiple studies.

Adult↗
PubMed2005

Nasal continuous positive airway pressure: does bubbling improve gas exchange?

In a randomised crossover trial, 26 babies, treated with Hudson prong continuous positive airway pressure (CPAP) from a bubbling bottle, received vigorous, high amplitude, or slow bubbling for 30 minutes. Pulse oximetry, transcutaneous carbon dioxide, and respiratory rate were recorded. The bubbling rates had no effect on carbon dioxide, oxygenation, or respiratory rate.

Carbon Dioxide↗
PubMed2004

FlaC, a protein of Campylobacter jejuni TGH9011 (ATCC43431) secreted through the flagellar apparatus, binds epithelial cells and influences cell invasion.

Type III secretion systems identified in bacterial pathogens of animals and plants transpose effectors and toxins directly into the cytosol of host cells or into the extracellular milieu. Proteins of the type III secretion apparatus are conserved among diverse and distantly related bacteria. Many type III apparatus proteins have homologues in the flagellar export apparatus, supporting the notion that type III secretion systems evolved from the flagellar export apparatus. No type III secretion apparatus genes have been found in the complete genomic sequence of Campylobacter jejuni NCTC11168. In this study, we report the characterization of a protein designated FlaC of C. jejuni TGH9011. FlaC is homologous to the N- and C-terminus of the C. jejuni flagellin proteins, FlaA and FlaB, but lacks the central portion of these proteins. flaC null mutants form a morphologically normal flagellum and are highly motile. In wild-type C. jejuni cultures, FlaC is found predominantly in the extracellular milieu as a secreted protein. Null mutants of the flagellar basal rod gene (flgF) and hook gene (flgE) do not secrete FlaC, suggesting that a functional flagellar export apparatus is required for FlaC secretion. During C. jejuni infection in vitro, secreted FlaC and purified recombinant FlaC bind to HEp-2 cells. Invasion of HEp-2 cells by flaC null mutants was reduced to a level of 14% compared with wild type, suggesting that FlaC plays an important role in cell invasion.

Bacterial Adhesion↗
PubMed2003

Genomic context drives SCA7 CAG repeat instability, while expressed SCA7 cDNAs are intergenerationally and somatically stable in transgenic mice.

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant cerebellar ataxia caused by a CAG repeat expansion in the ataxin-7 gene. In humans, SCA7 is characterized by marked anticipation due to intergenerational repeat instability with a bias toward expansion, and is thus regarded as the most unstable of the polyglutamine diseases. To study the molecular basis of CAG/CTG repeat instability and its pathological significance, we generated lines of transgenic mice carrying either a SCA7 cDNA construct or a 13.5 kb SCA7 genomic fragment with 92 CAG repeats. While the cDNA transgenic mice showed little intergenerational repeat instability, the genomic fragment transgenic mice displayed marked intergenerational instability with an obvious expansion bias. We then went on to generate additional lines of genomic fragment transgenic mice, and observed that deletion of the 3' genomic region significantly stabilized intergenerational transmission of the SCA7 CAG92 repeat. These results suggest that cis-information present on the genomic fragment is driving the instability process. As the SCA7 genomic fragment contains a large number of replication-associated motifs, the presence of such sequence elements may make the SCA7 CAG repeat region more susceptible to instability. Small-pool and standard PCR analysis of tissues from genomic fragment mice revealed large repeat expansions in their brains and livers, but no such changes were found in any tissues from cDNA transgenic mice that have been shown to undergo neurodegeneration. As large somatic repeat expansions are absent from the brains of SCA7 cDNA mice, our results indicate that neurodegeneration can occur without marked somatic mosaicism, at least in these mice.

3' Untranslated Regions↗
PubMed2002

In vitro comparison of nasal continuous positive airway pressure devices for neonates.

OBJECTIVE: To compare the resistance in vitro of different devices used for the delivery of nasal continuous positive airway pressure (NCPAP) in neonates. DESIGN: Flows of 4-8 litres/min were passed through a selection of neonatal NCPAP devices (single prong, Duotube, Argyle prong, Hudson prong, Infant Flow Driver), and the resultant fall in pressure measured using a calibrated pressure transducer. RESULTS: The decrease in pressure (cm H(2)O) for each device (size in parentheses) at a constant flow of 6 litres/min was: Duotube: (2.5), 21; (3.0), 6.2; (3.5), 2.3; single prong: (2.5), 4.4; (3.0), 2.1; (3.5), 1.2; Argyle prong: (XS), 3.6; (S), 1.9; (L), 1.5; Hudson prong: (0), 3.1; (1), 1.8; (2), 0.6; (3), 0.4; (4), 0.3; Infant Flow Driver: (small), 0.3; (medium), -0.3; (large), -0.5. CONCLUSIONS: A large variation in the potential fall in pressure may occur in the clinical setting. Devices with short double prongs had the lowest resistance to flow. These results have implications in the selection of the optimal device/s for clinical application and for future comparisons in randomised trials of NCPAP in neonates.

Airway Resistance↗
PubMed2001

Effects of interleukin-12 on the immune response to a multipeptide vaccine for resected metastatic melanoma.

PURPOSE: Forty-eight patients with high-risk re-sected stage III or IV melanoma were immunized with two tumor antigen epitope peptides derived from gp100(209-217)(210M) (IMDQVPSFV) and tyrosinase(368-376)(370D) (YMDGTMSQV) emulsified with incomplete Freund's adjuvant (IFA). Patients received peptides/IFA with or without interleukin (IL)-12 30 ng/kg to evaluate the toxicities and immune responses in either arm with time to relapse and survival as secondary end points. PATIENTS AND METHODS: Immunizations were administered every 2 weeks for 8 weeks, then every 4 weeks for 12 weeks, and then once 8 weeks later. A leukapheresis to obtain peripheral-blood mononuclear cells for immune analyses was done before and after vaccination. Skin testing with peptides and recall reagents was performed before and after vaccinations. RESULTS: Local pain and granuloma formation, fever, and lethargy of grade 1 or 2 were observed. Transient vaccine-related grade 3-but no grade 4-toxicity was observed. Thirty-four of 40 patients developed a positive skin test response to the gp100 peptide but none to tyrosinase. Immune responses were measured by release of gamma-interferon in an enzyme-linked immunosorbent assay (ELISA) by effector cells in the presence of peptide-pulsed antigen-presenting cells or by an antigen-specific tetramer flow cytometry assay. Thirty-three of 38 patients demonstrated an immune response by ELISA after vaccination, as did 37 of 42 patients by tetramer assay. Twenty-four of 48 patients relapsed with a median follow-up of 20 months, and 10 patients in this high-risk group have died. CONCLUSION: These data suggest a significant proportion of patients with resected melanoma mount an antigen-specific immune response against a peptide vaccine and indicate that IL-12 may increase the immune response and supporting further development of IL-12 as a vaccine adjuvant.

Adolescent↗
PubMed2001

Delayed nausea and vomiting in children receiving antineoplastics.

BACKGROUND: The nature and prevalence of delayed antineoplastic-induced nausea and vomiting have not been well-described in children. This study describes the extent of delayed nausea and vomiting in children receiving antineoplastic agents as well as the drug therapies initiated in an attempt to prevent or manage it. PROCEDURE: All children receiving antineoplastics were eligible for study entry. The date and time of each emetic episode were recorded on each day antineoplastics were given and for 3 days thereafter. Nausea was self-assessed daily by children who were older than 3 years and were not developmentally delayed. Diet was also assessed daily. The emetic response, median nausea rating and median diet achieved were described. RESULTS: The emetic response of 124 children who received 174 antineoplastic cycles was evaluated. Most cycles (137/174;79%) were not associated with delayed vomiting. Cycles which included cisplatin, carboplatin, or cyclophosphamide; involved antineoplastic therapy given over 2 or more consecutive days; or were accompanied by vomiting during the acute phase were associated with a significantly higher incidence of delayed vomiting. Moderate to severe nausea was reported on 58% (267/459) of study days. No antiemetics were given on most study days (412/522;79%); nevertheless, most of the study days (381/412;93%) which were unaccompanied by antiemetic support during the delayed phase were completely free from vomiting. Antiemetics were most often given as single agents (ondansetron: 54 study days; dimenhydrinate: 17 study days; dexamethasone: 6 study days). Diet was largely unaffected during the study period. CONCLUSIONS: Antineoplastic-induced delayed nausea and vomiting may be less prevalent in children than in adults. Routine antiemetic administration during the delayed phase may not be warranted in all patients. Med Pediatr Oncol 2001;37:115-121.

Adolescent↗
PubMed2001

Stimulatory effects of leptin and muscle contraction on fatty acid metabolism are not additive.

Leptin has been shown to acutely stimulate fatty acid oxidation and triacylglycerol hydrolysis in skeletal muscle. These effects are similar to those induced by muscle contraction alone. Several studies have demonstrated that, during aerobic exercise, plasma leptin concentrations are well maintained; however, none has examined whether the stimulatory effects of leptin and contraction on muscle lipid metabolism are additive. This is the first study to examine the direct effect of leptin on lipid and carbohydrate (CHO) metabolism in isolated oxidative muscle over a range of contraction intensities. We examined the effect of leptin (10 microg/ml) on the synthesis and degradation of muscle lipid pools [phospholipid (PL), diacylglycerol (DG), triacylglycerol (TG)] and palmitate oxidation in isolated resting and contracting (2, 8, and 20 tetani/min) soleus muscles. At rest, leptin increased fatty acid oxidation (+ 40%, P < 0.05) and TG hydrolysis (+ 47%, P < 0.05), while blunting TG esterification (-20%, P < 0.05). Glucose oxidation was unaffected at rest in the presence of leptin. During tetanic contraction, fatty acid oxidation (+20-114%, P < 0.05) and TG esterification (+ 19-33%, P < 0.05) as well as net TG utilization (+ 23%, P < 0.05) were all significantly increased. However, leptin was without further effect on any of these parameters during contraction. Net utilization of intramuscular glycogen, as well as glucose oxidation, was unaffected during contraction by leptin. The findings of the present study indicate that leptin has an important influence on lipid metabolism in resting muscle, but not during contraction.

Animals↗
PubMed2001

Parents' coping in the neonatal intensive care unit: a theoretical framework.

The conceptual framework that has been widely used to study the coping strategies of parents of preterm infants in neonatal intensive care units (NICU) has been the transactional model of stress and coping proposed by Lazarus and colleagues. This model supports the cognitive system as the key factor in stress transactions. The cognitive system produces an interpretation of events that leads to making sense of numerous sensations and perceptions from both external and social sources as well as from the internal physiological environment. The individual cognitive system appraises stimuli in two ways: primary appraisal and secondary appraisal. Another factor that may influence the individual's coping effort is gender difference. Mothers and fathers of preterm infants have been found to use different coping strategies to deal with the preterm birth. Other factors such as personality traits and the perceived and actual availability of social support may also influence the parents' coping effort. Implications for clinical practice by the NICU interdisciplinary team are considered.

Adaptation, Psychological↗
PubMed2001

Low levels of cell cycle inhibitor p27kip1 combined with high levels of Ki-67 predict shortened disease-free survival in T1 and T2 invasive breast carcinomas.

Breast cancer is the second leading cause of cancer death in North American women. There is considerable need for better prognostic markers to identify those subsets of patients who would benefit from more aggressive therapy because their tumors show an increased risk of poor clinical behavior. p27kip1 is an important inhibitor of the cell cycle that acts by binding and inactivating cyclin-dependent kinases (CDKs). The aim of this study was to determine the prognostic value of loss of p27 protein in invasive breast cancer. We performed an immunohistochemical study of 147 patients with T1 and T2 invasive breast cancers and compared survival in the high p27 expressing group with that of the low p27 expressing group. On univariate analysis comparing tumor size, nodal status, Ki-67, c-erbB-2, p53 and estrogen receptor, low or absent p27kip1 is a strong predictor of reduced disease-free survival. Importantly, on multivariate analysis, the combined effect of low p27 with high Ki-67 is a stronger predictor of reduced disease-free survival than either marker alone. This simple, reliable and inexpensive assay, particularly when used in combination with Ki-67, improves the ability to predict disease recurrence and could become a useful adjunct of breast cancer evaluation to better identify high risk patients.

Adult↗
PubMed1999

DNA-PK, the DNA-activated protein kinase, is differentially expressed in normal and malignant human tissues.

DNA-PK is a nuclear, serine/threonine protein kinase required for repairing DNA double-strand breaks and for V(D)J recombination. To determine the distribution of DNA-PK in human tissues, we assayed paraffin-embedded sections of normal and cancerous tissues for DNA-PKcs and Ku80 by immunohistochemistry. We also assayed for Brca2, a human tumor suppressor gene that is implicated in the repair of DNA strand-breaks. Brca2 was strongly expressed in epithelial cells of the breast, endometrium, and thymus, in tingible body macrophages of follicular germinal centers of lymphoid tissue, and in reticuloendothelial cells in the spleen. DNA-PKcs and Ku80 expression was usually parallel, but both were expressed in a highly cell- and tissue-specific manner. The highest levels were observed in spermatogenic cells (but not in spermatozoa), and in neurons and glial cells of the central and autonomic nervous system. Neither protein was consistently expressed in liver nor in resting mammary epithelium, but lactating breast epithelium was strongly positive for DNA-PKcs and Ku80. In contrast to established human cell cultures, expression between cells in the same tissue was highly selective in the epidermis, exocrine pancreas, renal glomeruli, the red pulp of the spleen, and within cellular compartments of tonsils, lymph nodes, and thymus. Most cancerous tissues were consistently positive for DNA-PKcs and Ku80, except invasive carcinoma of the breast. DNA-PKcs, Ku80, and Ku70 mRNAs were expressed in all normal tissues with relatively little variation in levels. Our results suggest that the apparent absence of DNA-PKcs and Ku80 from some cells or tissues is a consequence of post-transcriptional mechanisms that regulate protein levels.

Base Sequence↗