How to take (and keep) the weight off.
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Body Mass Index↗
Biomedical subjects
C Keller
Publications and source records attributed to C Keller.
Pressures exerted against the cervical vertebrae by the standard and intubating laryngeal mask airways: a randomized, controlled, cross-over study in fresh cadavers.
UNLABELLED: In this randomized, controlled, cross-over study, we measured the pressures exerted by the standard laryngeal mask airway (LMA) and the intubating laryngeal mask airway (ILM) against the cervical vertebrae during insertion, intubation, and maneuvers commonly used to facilitate intubation. We also assessed the effect of these pressures on cervical spine (C-spine) movement. Twenty cadavers (6-24 h postmortem) without cervical abnormality were initially studied. Three microchip pressure sensors were implanted into the pharyngeal surface of C2-3. The size 5 ILM and LMA were inserted in random order into each cadaver with the head-neck in the neutral position. Maximal cervical pressures (CPmax) were recorded for both devices during cuff inflation from 0-40 mL and with the intracuff pressure (ICP) at 60 cm H2O, insertion, fiberscope-guided intubation, partial withdrawal/reinsertion (ILM only), elevation/depression of the handle with 20 N of force applied (ILM only). In five additional matched cadavers, the effect of pressure on posterior displacement of C3 was assessed, and CPmax was measured during laryngoscope- and fiberscope-guided oro/nasotracheal intubation (controls). CPmax was higher for the ILM than the LMA over the inflation range (96 vs 15 cm H2O; P < 0.0001) and with the ICP at 60 cm H2O (95 vs 10 cm H2O; P < 0.0001). During cuff inflation, CPmax was generally unchanged for the ILM but was always increased for the LMA. CPmax for the LMA and ILM was similar during insertion (224 vs 273 cm H2O) but higher for the ILM during fiberscope-guided intubation (96 vs 43 cm H2O; P < 0.0001). At 60 cm H2O ICP, CPmax increased during LMA (224 cm H2O; P < 0.0001) and ILM insertion (273 cm H2O; P < 0.0001) and increased for the LMA (43 cm H2O; P < 0.0001) but was unchanged for the ILM (96 cm H2O) during fiberscope-guided intubation. For the ILM, CP-max increased during handle depression (394 cm H2O; P < 0.0001) and partial withdrawal/reinsertion (265 cm H2O; P < 0.0001) but decreased during handle elevation (6 cm H2O; P < 0.00001). CPmax for the controls was usually zero and was always less than the LMA/ ILM (P < 0.0001). The mean (range) for posterior displacement of C3 was 0.8 (0-2) mm at 100 cm H2O and 2.8 (1-5) mm at 400 cm H2O. Laryngeal mask devices exert greater pressures against the cervical vertebrae than established intubation techniques and can produce posterior displacement of the C-spine. IMPLICATIONS: Laryngeal mask devices exert greater pressures against the cervical vertebrae than established intubation techniques and can produce posterior displacement of the cervical spine. We recommend that laryngeal mask devices only be used in the unstable cervical spine if difficulties are anticipated or encountered with established techniques, pending the results of studies demonstrating its relative safety.
Aged↗
Translational inhibition of messenger RNA of the human pi class glutathione S-transferase by antisense oligodeoxyribonucleotides.
In this study, a T7 plasmid expression vector containing the cDNA of a variant human GST-pi gene, hGSTP1*C, was used to examine the translational inhibition of the GST-pi mRNA with antisense deoxyribonucleotides (AS-ONs), and to investigate the dependency of the inhibition on ribonuclease (RNAse) H, AS-ON and target mRNA sequence specificity and AS-ON back bone modification. Translational inhibition of hGSTP1*C mRNA showed significant AS-ON concentration-dependency and was both target mRNA and AS-ON sequence specific. Fully modified phosphoromonthioate AS-ONs were less inhibitory than their partial phosphoromonthioate analogs; unmodified AS-ONs were inactive. RNAse H enhanced the translational inhibition by AS-ON specific to the translation initiation region mRNA, and was associated with cleavage of the target mRNA at the site of AS-ON:mRNA hybridization. AS-ONs directed to the A-->G and C-->T transitions, unique to hGSTP1*C, were more RNAse H-dependent than AS-ONs directed against the translation initiation site, indicating a greater involvement of RNAse H-dependent mRNA cleavage in the mechanism of translational inhibition by AS-ON at the polymorphic site. These data suggest that AS-ONs provide a potentially effective means of specific down-regulation of the human GST-pi gene, and demonstrate that the sites of GST-pi gene allelo-polymorphism can be targeted to translationally down-regulate the different GST-pi gene variants, specifically and differentially targeted.
Base Sequence↗
Calcium and insulin-like growth factor I stimulation of sodium-dependent phosphate transport and proliferation of cultured rat osteoblasts.
Calcium (Ca) stimulates proliferation of osteoblasts in vitro, an effect proposed to be mediated by IGF I. Addition of 1 mM Ca or of 1 nM IGF I to the medium (0.3 mM Ca) of a rat bone-derived cell line, PyMS, stimulated not only DNA synthesis but also sodium-dependent (Nad) phosphate (Pi) uptake, the latter, within 2 h. These cells barely express and produce IGF I. IGF binding protein-3 which inhibits IGF action decreased neither basal nor Ca-stimulated but IGF I-stimulated NadPi transport and DNA synthesis, indicating that Ca stimulated NadPi transport and DNA synthesis independently of IGF I. The effects of Ca and IGF I on DNA synthesis were additive. 1 microM nifedipine blocked IGF I- and Ca-stimulated DNA synthesis but not NadPi transport, suggesting that Ca influx is not mediating the NadPi transport-enhancing IGF I signal but is required for IGF I-induced osteoblast proliferation.
Alanine↗
Heterozygosity for the missense mutation Ala370-->Thr in exon 8 of the low density lipoprotein receptor gene does not cause hypercholesterolemia.
Familial hypercholesterolemia (FH) is caused by mutations in the low-density lipoprotein (LDL) receptor gene. We used a multiplex-PCR based single-strand conformation polymorphism analysis to screen the promotor region and all 18 exons of the LDL receptor gene for mutations in patients clinically diagnosed as having FH to identify their particular gene defect. An affected proband was found to be heterozygous for a missense mutation, replacing guanine to adenine at nucleotide 1171 of exon 8 of the gene. This mutation is predicted to cause a substitution of alanine to threonine at codon 370 (A370T). The base exchange abolishes a HaeIII restriction site. PCR of exon 8 followed by restriction enzyme digestion with HaeIII conveniently allowed to screen the whole family and 101 unrelated normocholesterolemic subjects from the same ethnic background for the presence of this mutation. The A307T mutation did not cosegregate with the clinical phenotype of hypercholesterolemia in the affected family. Furthermore the mutation was identified in a heterozygous state in 12 out of 101 and in a homozygous state in 1 out of 101 normocholesterolemic subjects, indicating that this mutation is a frequent genetic variation of the LDL receptor gene in the population examined. Lipid values of probands carrying the wild type LDL receptor allele and the mutation in a heterozygous state did not differ significantly. The proband carrying the mutation on both LDL receptor alleles had high normal cholesterol and LDL cholesterol levels. The A370T mutation represents the third single-amino acid change of the LDL receptor protein reported so far, which, in a heterozygous state, is not associated with the clinical phenotype of familial hypercholesterolemia. The pathophysiologic significance of homozygosity for this mutation remains to be clarified.
Adult↗
Association of genetic polymorphisms in the ACE, ApoE, and TGF beta genes with early onset ischemic heart disease.
BACKGROUND: The genetic factors that contribute to ischemic heart disease (IHD) are poorly understood, and it is likely that multiple genes acting independently or synergistically contribute to the risk of IHD and outcome. The genes for angiotensin-converting enzyme (ACE) and apolipoprotein E (ApoE) have been implicated independently in the risk of IHD. HYPOTHESIS: This study examined whether genetic polymorphisms in the ACE and ApoE genes are associated with early onset IHD. Polymorphisms in a third gene, transforming growth factor beta 2 (TGF beta 2), with a known role in wound repair and cardiac development, are also examined with respect to early onset IHD. METHODS: In all, 101 patients with IHD and onset of disease before 55 years for men and 60 years for women, and 100 controls with angiographically confirmed normal coronary arteries were recruited for this study. The ACE, ApoE, and TGF beta 2 genotypes were determined by polymerase chain reaction amplification or Southern blotting and were compared with the patient's clinical and family histories. RESULTS AND CONCLUSION: The frequency of the ACE D allele was significantly lower in the patient group (0.475) than in the control group (0.59, p = 0.03), which was attributed to a reduction in the number of patients with the DD genotype (patients: 24% DD, controls: 33% DD). Sudden cardiac death was also associated with the DD genotype. These data are consistent with the ACE D allele contributing to a fatal outcome. No association between the DD genotype and risk of myocardial infarction, presenting age, extent of vessel disease, family history, hypertension, or hypercholesterolemia was seen. Analysis of the ApoE genotype showed no association with early onset IHD. There was no evidence for a synergistic effect between the ACE and ApoE genotypes on the risk of early onset IHD. A polymorphism in the TGF beta 2 gene was rare and not associated with early onset IHD.
Adult↗
Patient outcomes with positive pressure versus spontaneous ventilation in non-paralysed adults with the laryngeal mask.
PURPOSE: To compare patient outcomes for positive pressure ventilation (PPV) and spontaneous ventilation (SV) in non-paralysed patients with the LMA using either isoflurane or sevoflurane anaesthesia. METHODS: One hundred and sixty four adult patients were studied. Anaesthesia was with fentanyl/propofol and N2O 66% in O2 with 0.75 MAC isoflurane or sevoflurane and either PPV or SV. Positive pressure ventilation was with tidal volumes of 6-8 ml.kg-1. Peak airway pressures were < 15 cm H2O. Patients were evaluated for airway problems, cardiorespiratory effects, and anaesthesia emergence times. RESULTS: There were no failed episodes of PPV or SV. Gastric insufflation was not detected by epigastric auscultation. Airway problems and cardiovascular effects were similar among groups. During maintenance: SpO2 was greater in the PPV group than in the SV group (98.4 vs 97%, P < 0.001); also, (PETCO2) (34 vs 43 mmHg) and the respiratory rate (RR) (15 vs 19 min-1) were higher and the minute ventilation (MV) (5.7 vs 7.2 L) were lower in the SV groups (P < 0.0001). Shorter times to LMA removal and orientation were observed in the sevoflurane groups (P < 0.0001). CONCLUSIONS: Patient outcome is similar for SV and PPV in non-paralysed adult patients with the LMA. Isoflurane and sevoflurane at 0.75 MAC provide suitable conditions for maintenance and emergence, but emergence is more rapid with sevoflurane.
Adult↗
Inhibition of adenylate cyclase of rat hepatic membranes by glycosaminoglycans.
Glycosaminoglycans are long non-branched polysaccharides composed of repeating disaccharide units. In a previous in vitro study we have shown that such molecules are able to modulate substrate phosphorylation catalyzed by cAMP-dependent protein kinase. Here, we investigate the impact of glycosaminoglycans, such as heparan sulfate, dermatan sulfate, chondroitin 4- and 6-sulfate, keratan sulfate and hyaluronic acid upon adenylate cyclase, which directly regulates cAMP-dependent protein kinase activity via cAMP synthesis. In rat liver plasma membrane preparation we have determined forskolin- and guanosine-5'-beta, gamma-imidotriphosphate-induced cAMP formation catalyzed by adenylate cyclase in the presence of increasing concentrations of glycosaminoglycans. The results indicate that glycosaminoglycans strongly influence enzymic conversion of ATP into cAMP. The highest reduction of adenylate cyclase activity is observed in the presence of dermatan sulfate and heparan sulfate. Moreover, the inhibitory effect of these two glycosaminoglycans is higher when guanosine-5'-beta, gamma-imidotriphosphate, instead of forskolin, is used as stimulator of adenylate cyclase. Further characterization of enzyme inhibition mediated by dermatan sulfate shows that this molecule exerts an inhibitory effect of mixed type.
Adenosine Triphosphate↗
Pharyngolaryngeal morbidity with the intubating laryngeal mask airway.
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Deglutition Disorders↗
Positive pressure ventilation with the laryngeal mask airway in non-paralysed patients: comparison of sevoflurane and propofol maintenance techniques.
We have compared anaesthetic maintenance and emergence characteristics of propofol and sevoflurane with the laryngeal mask airway (LMA) at commonly used doses in 185 ASA I-II patients, in a randomized, prospective study. Anaesthesia was induced with propofol 2.5-3.5 mg kg-1 and fentanyl 1-3 micrograms kg-1. Neuromuscular blocking agents were not used. All patients underwent positive pressure ventilation (PPV) with tidal volumes of 6-8 ml kg-1 to maintain normal end-tidal carbon dioxide concentration. Anaesthesia was maintained with 66% nitrous oxide in oxygen and infusion of propofol 6 or 8 mg kg-1 h-1, or 1% or 1.5% end-tidal sevoflurane. There were no failed insertion attempts and adequate ventilation was achieved in all patients. During emergence, there was a greater incidence of excitatory phenomena with 1% and 1.5% sevoflurane (95% confidence intervals (CI) 4-19%) compared with propofol (95% CI 0-4%). Sevoflurane 1.0% (95% CI 37-71%) was associated with the greatest overall incidence of respiratory and haemodynamic problems. This was significantly higher compared with propofol 6 mg kg-1 h-1 (95% CI 19-36%). Shorter times to LMA removal were observed with 1% and 1.5% sevoflurane compared with propofol (P < 0.0002). Postoperative problems did not differ between groups. We conclude that propofol 6-8 mg kg-1 h-1 and 1.5% sevoflurane were suitable for maintenance of anaesthesia for musculoskeletal surgery in non-paralysed ASA I-II patients undergoing PPV with the LMA. Emergence was more rapid with sevoflurane, but was associated with more excitatory phenomena.
Adult↗
Influence of cuff volume on oropharyngeal leak pressure and fibreoptic position with the laryngeal mask airway.
We studied the size 4 laryngeal mask airway (LMA) to test the hypothesis that oropharyngeal leak pressure and fibreoptic position improves with increasing cuff volume. After LMA insertion, 50 anaesthetized adult patients had the cuff inflated in 5-ml increments to 40 ml. Oropharyngeal leak pressure was optimal at 15 ml and decreased at higher volumes. The fibreoptic position was optimal at 0-20 ml and deteriorated at higher volumes. Gastric insufflation was detected more frequently when the cuff volume exceeded 20 ml. We conclude that inflation of the size 4 LMA to the maximum recommended volume provides suboptimal conditions and that this value should be reduced from 30 to 20 ml.
Adult↗
Saline as an alternative to air for filling the laryngeal mask airway cuff.
We have assessed a new method to evacuate saline completely from the laryngeal mask airway (LMA) cuff and tested the hypothesis that intracuff pressures, fibreoptic position and oropharyngeal leak pressures are similar for saline compared with air during nitrous oxide-oxygen anaesthesia. Eight size 4 LMA were inflated with saline 30 ml. After syringe evacuation, median residual weight was 0.56 (range 0.24-0.98) g; after additional manual cuff squeezing it was 0.26 (0.21-0.35) g; and after drying for 12 h at 60 degrees C with the valve open it was -0.02 (-0.05-0.04) g. Pressure-volume curves of four size 3-5 LMA showed that compliance was lower for the saline-filled cuff. A clinical study of 20 patients allocated randomly to have saline or air in the cuff showed a significant increase in intracuff pressure with air, but not saline, during nitrous oxide-oxygen anaesthesia. The fibreoptic position of the LMA changed more frequently in the air, compared with the saline-filled group (four of 10 vs none of 10; P = 0.04). Oropharyngeal leak pressures were similar between groups. We conclude that the saline-inflated LMA cuff was reliably emptied and more stable in terms of intracuff pressures and possibly fibreoptic position. Filling the LMA cuff with saline is a viable option during laser surgery to the airway.
Adolescent↗
The laryngeal mask and high-frequency jet ventilation for resection of high tracheal stenosis.
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Anastomosis, Surgical↗
Bronchial mucus transport velocity in paralyzed anesthetized patients: a comparison of the laryngeal mask airway and cuffed tracheal tube.
UNLABELLED: We compared bronchial mucus transport velocity (BTV), an index of mucociliary clearance, between the laryngeal mask airway (LMA) and the tracheal tube (TT). Forty patients were studied during propofol anesthesia and muscle relaxation with rocuronium. BTV was measured 10 and 60 min after insertion of the airway device by fiberoptic observation of the movement of methylene blue dye injected onto the dorsal surface of the left main bronchus. BTV for the LMA was similar at 10 and 60 min (13.9 +/- 2.0 and 13.6 +/- 2.1 mm/min, respectively). BTV for the TT was significantly faster at 10 min that at 60 min (13.0 +/- 1.4 vs 6.9 +/- 1.2 mm/min, respectively; P < 0.00001). BTV was similar for both devices at 10 min (TT 13.0 +/- 1.4 mm/min versus LMA 13.9 +/- 2.0 mm/min), but was significantly faster for the LMA than for the TT at 60 min (LMA 13.6 +/- 2.1 mm/min versus TT 6.9 +/- 1.2 mm/min; P < 0.00001). We conclude that the LMA impedes mucociliary clearance less than the TT in anesthetized patients. This may have implications for reducing the risk of retention of secretions, atelectasis, and pulmonary infection. IMPLICATIONS: This study compares bronchial mucus transport velocity, an index of mucociliary clearance, in anesthetized patients between two airway devices, the cuffed tracheal tube and the laryngeal mask airway. We have shown that the laryngeal mask airway impairs mucociliary clearance less than the tracheal tube. This may have implications for reducing the risk of retention of secretions, atelectasis, and pulmonary infection.
Adult↗
A comparison of the disposable versus the reusable laryngeal mask airway in paralyzed adult patients.
UNLABELLED: A disposable (polyvinyl chloride) laryngeal mask airway (LMA) with dimensions identical to, but physical properties different from (stiffer tube/thicker cuff), the reusable (silicone) LMA has recently become available. We performed a randomized, cross-over study of 60 paralyzed, anesthetized patients to test the hypothesis that the use of these devices was different in terms of ease of insertion, airway sealing pressure, fiberoptic position, and changes in intracuff pressure during N2O anesthesia. We also tested the hypothesis that the airway sealing pressure of the LMA is suboptimal if the cuff is inflated to a high intracuff pressure. Both the devices were inserted into each patient in random order, and their performance was assessed at two intracuff pressures (60 and 180 cm H2O) by a blind observer. Subsequently, intracuff pressures were measured during N2O anesthesia for the second device. Ease of insertion was similar: there was no difference in first attempt success rates (97% vs 98%) and insertion times (15 vs 13 s) for the disposable and reusable LMA, respectively. There were no differences in airway sealing pressure or fiberoptic position. Airway sealing pressure was significantly higher at 60 cm H2O intracuff pressure compared with the airway sealing pressure at 180 cm H2O for both devices (P < 0.02). During N2O anesthesia, the intracuff pressure remained stable for the disposable LMA but increased significantly for the reusable LMA. We conclude that the disposable and reusable LMAs perform similarly in paralyzed adult patients, but that the disposable LMA has more stable intracuff pressures during N2O anesthesia. Inflation of the LMA to high intracuff pressures produces a suboptimal seal. IMPLICATIONS: This randomized, single-blind, within-patient study of 60 adult patients shows that the disposable (polyvinyl chloride) and reusable (silicone) laryngeal mask airways perform similarly, but that the disposable laryngeal mask airway has more stable intracuff pressures during N2O anesthesia. Inflation of either device to high intracuff pressures produces a suboptimal seal.
Adult↗
A comparison of pharyngeal mucosal pressure and airway sealing pressure with the laryngeal mask airway in anesthetized adult patients.
UNLABELLED: We measured pharyngeal mucosal pressures at six different locations on the laryngeal mask airway (LMA) and tested the hypothesis that the efficacy of the seal is not related to pharyngeal mucosal pressure. Twenty anesthetized, paralyzed adult patients were studied. Microchip sensors were attached to the size 5 LMA at locations corresponding to the lateral and posterior pharynx, the hypopharynx, the pyriform fossa, the base of tongue, and the oropharynx. Mucosal pressures and airway sealing pressures were recorded during inflation of the cuff from 0 to 40 mL in 10-mL increments. The highest mean mucosal pressure was in the oropharynx (26 cm H2O), and the lowest was in the posterior pharynx (2 cm H2O). Mucosal pressures increased with increasing intracuff pressure and cuff volume, but the rate of increase varied among locations. Airway sealing pressure increased with increasing intracuff volume from 0 to 10 mL (P < 0.0001) and 10 to 20 mL (P = 0.0001), was unchanged from 20 to 30 mL, and decreased from 30 to 40 mL (P = 0.005). The airway sealing pressure was higher than pharyngeal mucosal pressure until the intracuff volume was > or =30 mL. There was no correlation between mucosal pressures and airway sealing pressure at any location. We conclude that the efficacy of the seal is not related to pharyngeal mucosal pressure. Pharyngeal mucosal pressures are generally lower than those considered safe for the tracheal mucosa during prolonged intubation. IMPLICATIONS: We measured pharyngeal mucosal pressures at six different locations on the laryngeal mask airway and showed that the efficacy of the seal is not related to pharyngeal mucosal pressure. Pharyngeal mucosal pressures are generally lower than those considered safe for the tracheal mucosa during prolonged intubation.
Adult↗
Carolyn Murdaugh as a transformational leader.
This article presents the lessons learned from Dr Carolyn Murdaugh, a transformational leader in the field of cardiovascular nursing as well as the larger community of scientists and scholars. Dr Murdaugh has inspired us and empowered us with the love of learning, science, and caring for others and ourselves. We present aspects of Dr Murdaugh's leadership, including her abilities to create a vision, model professional commitment, the value of hard work, and the creation of balance.
Cardiovascular Diseases↗
A urea cycle defect presenting as acute cerebellar ataxia in a 3-year-old girl.
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Amino Acid Metabolism, Inborn Errors↗