Search PubMed⌕ Search

Biomedical subjects

C Keller

Publications and source records attributed to C Keller.

At least 109 records · Page 6Linked to original sources
PubMed2000

Block of wild-type and inactivation-deficient cardiac sodium channels IFM/QQQ stably expressed in mammalian cells.

The role of inactivation as a central mechanism in blockade of the cardiac Na(+) channel by antiarrhythmic drugs remains uncertain. We have used whole-cell and single channel recordings to examine the block of wild-type and inactivation-deficient mutant cardiac Na(+) channels, IFM/QQQ, stably expressed in HEK-293 cells. We studied the open-channel blockers disopyramide and flecainide, and the lidocaine derivative RAD-243. All three drugs blocked the wild-type Na(+) channel in a use-dependent manner. There was no use-dependent block of IFM/QQQ mutant channels with trains of 20 40-ms pulses at 150-ms interpulse intervals during disopyramide exposure. Flecainide and RAD-243 retained their use-dependent blocking action and accelerated macroscopic current relaxation. All three drugs reduced the mean open time of single channels and increased the probability of their failure to open. From the abbreviation of the mean open times, we estimated association rates of approximately 10(6)/M/s for the three drugs. Reducing the burst duration contributed to the acceleration of macroscopic current relaxation during exposure to flecainide and RAD-243. The qualitative differences in use-dependent block appear to be the result of differences in drug dissociation rate. The inactivation gate may play a trapping role during exposure to some sodium channel blocking drugs.

Amino Acid Substitution↗
PubMed2000

Mutations in the low-density-lipoprotein receptor gene in German patients with familial hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is an autosomal dominant disorder of lipid metabolism characterized by elevated low-density lipoproteins (LDL), the formation of tendon and skin xanthomata and the development of premature coronary atherosclerosis. It is caused by a defect in the receptor-mediated hepatic uptake of LDL due to mutations in the LDL receptor. In 25 FH families with a total of 160 members and in two individuals without available relatives, all of German origin, we identified LDL receptor mutations by a multiplex-PCR-based single-strand conformation polymorphism method followed by direct sequencing. Of the 24 mutations found, 15 are missense mutations, 2 are nonsense mutations, 4 are small deletions or insertions leading to frameshifts, 2 are an in-frame insertion and deletion, respectively, and one is a splice site mutation. Propositi carrying mutations that are known to completely abolish receptor function (nonsense and frameshift mutations, missense mutation V480M) had significantly higher untreated total and LDL-cholesterol levels compared to those patients carrying missense and in-frame insertion mutations of unknown functional consequence, which may lead to either reduced or completely abolished receptor function (11.30+/-1.64 vs 9.76+/-1.50 mmol/L, and 9.39+/-1.23 vs 7.99+/-1.45 mmol/L, respectively). These results confirm the clinical and molecular heterogeneity of FH and the influence of different functional classes of mutations on lipid values.

Adolescent↗
PubMed2000

Does efficacy of seal and fibreoptic view change during anaesthesia with the laryngeal mask airway: a comparison of oxygen and oxygen-nitrous oxide gas mixtures.

BACKGROUND: We test the hypothesis that oropharyngeal leak pressure (OLP) and fibreoptic position (FP) are stable for the laryngeal mask airway (LMA) during anaesthesia with and without nitrous oxide. METHODS: Forty paralysed anaesthetised patients (ASA 1-2, aged 18-80) were randomly allocated to receive 100% oxygen (O2 group) or 33% oxygen in nitrous oxide (O2-N2O group) for maintenance. In vivo intracuff pressure (CP) using a size 5 LMA was adjusted to 60 cm H2O. OLP, FP and CP were measured every 5 min for 30 min. RESULTS: CP was higher in the O2-N2O group than the O2 group, other than at time zero (all: P<0.0001). CP increased every 5 min in the O2-N2O group (all: P<0.0001), but not in the O2 group. There were no differences in OLP and FP between groups at any time. There were no significant changes in OLP or FP with time within each group. There were no changes in OLP greater than 1.5 cm H2O and no change in FP for any patient. CONCLUSION: We conclude that OLP and FP are stable for the LMA during anaesthesia lasting 30 min with or without nitrous oxide.

Adolescent↗
PubMed2000

Emergence characteristics and postoperative laryngopharyngeal morbidity with the laryngeal mask airway: a comparison of high versus low initial cuff volume.

In this study we tested the hypothesis that the initial cuff volume of the laryngeal mask airway influences emergence characteristics and postoperative laryngopharyngeal morbidity. One hundred and sixty adult patients undergoing minor surgery were randomly assigned for airway management with the laryngeal mask airway with either a fully inflated cuff (LMA-High) or a semi-inflated cuff (LMA-Low). Anaesthesia was with propofol, nitrous oxide, oxygen and isoflurane. Following insertion, the cuff was inflated with either 15 or 30 ml for the size 4 (females) and 20 or 40 ml for the size 5 (males). At the end of surgery, a blinded observer documented the presence or absence of adverse airway events (hypoxia, hypercapnea, coughing, retching, regurgitation/vomiting, airway obstruction, hypoventilation, hiccupping, biting, body movement or shivering) during every 1 min epoch and cardiorespiratory variables (heart rate, mean blood pressure, arterial oxygen saturation, end-tidal carbon dioxide and respiratory rate) every 5 min until the patient was awake and the laryngeal mask airway removed. Patients were interviewed about pharyngolaryngeal morbidity (sore throat, dysphonia and dysphagia) immediately before leaving the postanaesthesia care unit and 18-24 h following surgery. Analysis by epoch showed more partial airway obstruction in the LMA-High group, but analysis by patient numbers revealed no difference. Heart rate was slightly higher in the LMA-High group upon arrival in the postanaesthesia care unit, but otherwise there were no differences in cardiorespiratory responses. Sore throat and dysphagia were more common in the LMA-High group. We conclude that, in general, emergence characteristics with the laryngeal mask airway are not influenced by the volume of air used to inflate the cuff, but that postoperative sore throat and dysphagia are more likely at high initial cuff volumes.

Adolescent↗
PubMed2000

DALI apheresis in hyperlipidemic patients: biocompatibility, efficacy, and selectivity of direct adsorption of lipoproteins from whole blood.

Recently, the first apheresis technique for direct adsorption of low-density lipoprotein (LDL) and lipoprotein(a) [Lp(a)] from whole blood (DALI) was developed that does not require a prior plasma separation. That markedly simplifies the extracorporeal circuit. The aim of the present study was to test the acute biocompatibility, efficacy, and selectivity of DALI apheresis. In a prospective clinical study, 6 hypercholesterolemic patients suffering from angiographically proven atherosclerosis were treated 4 times each by DALI. 1.3 patient blood volumes were treated per session at blood flow rates of 60-80 ml/min using 750 or 1,000 ml of polyacrylate/polyacrylamide adsorber gel. The anticoagulation consisted of an initial heparin bolus followed by a citrate infusion. The sessions were clinically essentially uneventful. Mean corrected reductions of lipoproteins amounted to 65% for LDL-cholesterol, 54% for Lp(a), 28% for triglycerides, 1% for HDL-cholesterol, and 8% for fibrinogen. The selectivity of lipoprotein removal was high. Cell counts remained virtually unchanged and no signs of hemolysis or clotting were detected. Cell activation parameters elastase, beta-thromboglobulin, interleukin-1beta, and IL-6 showed no significant increase. Complement activation was negligible. There was significant, but clinically asymptomatic, bradykinin activation in the adsorber with mean maxima of 12,000 pg/ml in the efferent line at 1,000 ml of treated blood volume. In conclusion, DALI proved to be safe, selective, and efficient for the adsorption of LDL-C and Lp(a), which simplifies substantially the extracorporeal therapy in hypercholesterolemic patients.

Acrylic Resins↗
PubMed2000

Effect of low-dose citrate anticoagulation on the clinical safety and efficacy of direct adsorption of lipoproteins (DALI apheresis) in hypercholesterolemic patients: a prospective controlled clinical trial.

Direct adsorption of lipoproteins (DALI) is the first lipid apheresis system compatible with whole blood with the advantage of a very simple procedure. A mixture of heparin plus citrate (ACD-A) is used for the anticoagulation regimen (AR). A clinical, prospective, controlled crossover study was performed to test the safety and efficacy of low-dose citrate (LDC) anticoagulation in DALI. Five chronic DALI patients suffering from coronary heart disease and hypercholesterolemia underwent 3 DALI sessions each using the LDC anticoagulation regimen (60 IU heparin/kg body weight as initial bolus; 1:40 ACD-A: blood as perfusion). This was compared to 3 sessions per patient with the standard AR (bolus of 20 IU heparin/kg, 1:20 ACD-A as perfusion). Patient blood volumes (1.6; average of 7,040 ml) were treated with 750 ml adsorber gel per session at a blood flow rate of 60 ml/min. Mean LDL and Lp(a) reductions exceeded 60% with both AR. No clinical side effects were observed. Both AR controlled the coagulation well as evidenced by a sufficient prolongation of the partial prothrombin time (PTT) and activated clotting time as well as low thrombin-antithrombin (TAT) formation. Biocompatibility parameters exhibited favorable results (low activation of complement and cells, and only slight formation of C3a, C5a, beta-thromboglobulin, elastase, and TNF-alpha). The asymptomatic bradykinin generation was comparable in both study arms. LDC optimized the ionized calcium levels and pH in the efferent blood postadsorber. LDC anticoagulation was safe and effective, and may further improve the tolerance of DALI apheresis in hypercholesterolemic patients.

Adsorption↗
PubMed2000

Performance of the size 5 laryngeal mask airway in males and females.

We compare the functional performance (ease of insertion, oropharyngeal leak pressure and anatomic position) of the size 5 LMA in males and females over a range of cuff volumes. We also determine 1) if age, height, weight and body mass index predict functional performance and 2) the relationship between oropharyngeal leak pressure (OLP) and anatomic position (judged by fibreoptic scoring). One hundred male and one hundred female paralysed, anaesthetised patients were studied. The number of insertion attempts and time to placement were recorded. OLP and fibreoptic score (FOS) were measured during inflation of the cuff from 0-40 ml in 10 ml increments. There were no failed insertions. Insertion times were similar for males and females. There were no differences in OLP or FOS between males and females at any cuff volume. For males, OLP increased from 0 to 10 ml and 10 to 20 ml (p < 0.001), but was unchanged from 20 to 30 and 30 to 40 ml. For females, OLP increased from 0 to 10 ml, 10 to 20 ml (p < 0.001) and decreased from 20 to 30 ml (p = 0.02), but was unchanged from 30 to 40 ml. For males, FOS increased from 0 to 10 ml (p = 0.02) and 10 to 20 ml (p < 0.001), but was unchanged from 20 to 30 and 30 to 40 ml. For females, FOS increased from 0 to 10 ml (p = 0.02), 10 to 20 ml (p < 0.001), decreased from 20 to 30 ml (p = 0.001), but was unchanged from 30 to 40 ml. There was a significant positive correlation with height and OLP in males and females at higher cuff volumes, but no correlation with any other variable. There was no correlation between OLP and FOS at any cuff volume for males, but there was a correlation at 0 (p = 0.03) and 10 ml (p = 0.01) for females. We conclude that ease of insertion, efficacy of seal and anatomic position for the size 5 LMA is similar in males and females. Age, weight and body mass index do not predict performance, but efficacy of seal improves with increasing patient height. Fiberoptically determined anatomic position is a poor predictor of efficacy of seal. The shape of the pharynx may be different between tall and short adults.

Adult↗
PubMed2000

A fibreoptic scoring system to assess the position of laryngeal mask airway devices. Interobserver variability and a comparison between the standard, flexible and intubating laryngeal mask airways.

We determined the interobserver reliability of a fibreoptic scoring system for assessing the position of the laryngeal mask airway (LMA), the flexible laryngeal mask airway (FLMA) and the intubating laryngeal mask airway (ILM). We also compare fibreoptic position between the devices. Thirty anaesthetised adult patients were studied in random order in a triple crossover manner. Two observers blinded to each others findings scored the fibreoptic position as follows: 4, only vocal cords visible; 3, vocal cords plus posterior epiglottis visible; 2, vocal cords plus anterior epiglottis visible; 1, vocal cords not seen. Interobserver reliability was examined using intraclass correlation coefficient (ICC). Interobserver reliability was graded as excellent for the LMA (ICC = 0.89), FLMA (ICC = 0.87) and ILM (ICC = 0.79). Fibreoptic scores were higher for the LMA and FLMA compared with the ILM (both p < 0.001). We conclude that interobserver reliability for the fibreoptic scoring system is excellent for the LMA, FLMA and ILM. Fibreoptic position is better for the LMA and FLMA compared with the ILM. Fibreoptic scoring has potential utility for research and clinical practice with laryngeal mask devices.

Adult↗
PubMed2000

Social and contextual etiology of coronary heart disease in women.

We explored the social and contextual etiology of coronary heart disease (CHD) prevention and management in women. Social and contextual influences on CHD risk include such factors as socioeconomic status, access to healthcare, cultural mores, working conditions including work overload, multiple role responsibilities, and social isolation. Women, particularly economically disadvantaged women, occupy lower levels on the social status hierarchy and, therefore, experience more stressful life experiences, less favorable living conditions, and less opportunity to affect positive health behavior and outcomes. Women are often discriminated against economically, politically, and socially, and this discrimination may adversely affect their efforts at CHD health promotion and treatment. Multiple role responsibilities within the family and psychosocial factors, including chronic life stress, are critical to an understanding of the health status of women, particularly poor and minority women. Although community-based interventions appear to be ideal for addressing the contextual risks related to CHD in women, a number of issues need to be considered, for example, the limited acknowledgment of secular trends in economic development that influence lifestyle decisions and health promotion efforts. Directions for research and interventions include recognition of the full spectrum of CHD risk in women, recognition of culturally competent interventions, and recognition of the need for empowerment of women.

Aged↗
PubMed2000

Mucosal pressure and oropharyngeal leak pressure with the ProSeal versus laryngeal mask airway in anaesthetized paralysed patients.

The ProSeal laryngeal mask airway (PLMA) is a new laryngeal mask device with a larger, wedge-shaped cuff and a drainage tube. We tested the hypothesis that directly measured mucosal pressure and oropharyngeal leak pressure (OLP) are higher for the PLMA compared with the laryngeal mask airway (LMA). We also assess the mechanism of seal, and the reliability of cuff volume, in vivo intracuff pressure and calculated mucosal pressure (in vivo minus in vitro intracuff pressure) to predict directly measured mucosal pressure. Thirty-two anaesthetized, paralysed adult patients were randomly allocated to receive either a size 4 LMA or PLMA. Microchip sensors were attached at locations corresponding to: (a) base of tongue; (b) distal oropharynx; (c) hypopharynx; (d) lateral pharynx; (e) posterior pharynx; and (f) pyriform fossa. In vitro and in vivo intracuff pressures, OLP and directly measured mucosal pressure were documented at zero volume and after each 10 ml up to 40 ml. Directly measured mucosal pressure was similar between devices for a given cuff volume, but was lower for the PLMA for a given OLP. Directly measured mucosal pressure was highest in the distal oropharynx for both devices, but rarely (< 5%) exceeded 35 cm H2O. OLP was higher for the PLMA at all cuff volumes. Directly measured mucosal pressure was usually lower than OLP for both devices, and there was a positive correlation between directly measured mucosal pressure and OLP. Cuff volume, in vivo intracuff pressure and calculated mucosal pressure were poor to moderate predictors of directly measured mucosal pressure for the LMA and PLMA. We conclude that the PLMA forms a better seal than the LMA without an increase in directly measured mucosal pressure.

Adult↗
PubMed2000

Sevoflurane, but not propofol, significantly prolongs the Q-T interval.

UNLABELLED: Prolongation of the Q-T interval may be associated with polymorphic ventricular tachycardia known as torsade de pointes, syncope and sudden death. Existing data show that isoflurane prolongs the Q-T interval, whereas halothane shortens it. The aim of this study was to determine whether sevoflurane or propofol affects the Q-T interval. Thirty female patients undergoing gynecologic surgery were randomly assigned to two groups, one receiving inhaled induction with sevoflurane and the other receiving total IV anesthesia with propofol. Before and 20 min after the induction, a six-lead electrocardiogram was recorded, and blood pressure was measured. The Q-T interval and heart rate adjusted Q-T interval (Q-Tc interval) were significantly prolonged during the administration of anesthesia with sevoflurane, while the Q-T interval was significantly shortened, and the Q-Tc interval was statistically unaffected during propofol anesthesia administration. We conclude that, in otherwise healthy female patients, sevoflurane prolongs the Q-Tc. IMPLICATIONS: In this study, we evaluated the effect of sevoflurane induction and anesthesia versus propofol induction and anesthesia on the Q-T interval. Sevoflurane significantly prolonged the Q-T interval and the heart rate adjusted Q-T interval, whereas propofol shortened the Q-T interval but not the heart rate adjusted Q-T interval.

Adult↗
PubMed2000

A pilot study of pharyngeal pulse oximetry with the laryngeal mask airway: a comparison with finger oximetry and arterial saturation measurements in healthy anesthetized patients.

UNLABELLED: We compared pharyngeal SpO(2) by using the laryngeal mask airway (LMA) to finger SpO(2) and oxygen saturation from arterial blood samples (SaO(2)). We studied 20 hemodynamically stable, well oxygenated, anesthetized patients (ASA physical status I-III, aged 18-80 yr). A single-use pediatric pulse oximeter was attached to the back plate of a size 5 LMA. Pharyngeal and finger SpO(2) (dominant index finger) and SaO(2) (nondominant radial artery) were measured with the cuff volume at 0-40 mL in the neutral position. The intracuff pressure was then set at 60 cm H(2)O in the neutral position, and readings were taken with the head-neck flexed, extended, and rotated. SaO(2) was the same as pharyngeal SpO(2) at 20 and 30 mL cuff volume, but higher than pharyngeal SpO(2) at all other cuff volumes and head-neck positions (P < 0.04). SaO(2) was always higher than finger SpO(2) (P < 0.01). Pharyngeal SpO(2) was higher than finger SpO(2) at cuff volumes 10-40 mL and in the flexed and rotated head-neck positions (all: P < 0.007), but was lower at 0 cuff volume (P < 0.0001) and similar in the extended head-neck position. There was an increase in pharyngeal SpO(2) between 0 and 10 mL cuff volume (P < 0.0001), but no changes thereafter. Pharyngeal SpO(2) was similar in the flexed, rotated and extended head-neck positions. Pharyngeal SpO(2) agrees more closely with SaO(2) (mean difference < 0.7%) than finger SpO(2) (mean difference > 1.1%) at 10-40 mL cuff volume and in head-neck flexion. The standard error of limits was identical (0.09) for both finger SpO(2) and pharyngeal SpO(2) if data at 0 cuff volume are excluded. We conclude that pharyngeal SpO(2) with the LMA is feasible and generally provides more accurate readings than finger SpO(2) in hemodynamically stable, well oxygenated, anesthetized patients. IMPLICATIONS: Pharyngeal oximetry with the laryngeal mask airway is feasible and generally provides more accurate readings than finger oximetry in hemodynamically stable, well oxygenated, anesthetized patients.

Adult↗
PubMed2000

Inert gas exchange during pneumoperitoneum at incremental values of positive end-expiratory pressure.

UNLABELLED: Laparoscopy is a surgical technique for a growing variety of abdominal operations. In patients undergoing this procedure, arterial blood oxygenation and hemodynamics are frequently depressed. This study evaluated the effect of different levels of positive end-expiratory pressure (PEEP) during intraperitoneal CO(2) insufflation on the lung's ventilation-perfusion distribution in a porcine model. We studied 13 anesthetized pigs with an intraperitoneal pressure of 15 cm H(2)O applied at either incremental values of PEEP (5-20 cm H(2)O, increments of 5 cm H(2)O) or a constant PEEP of 5 cm H(2)O. The effects of CO(2) pneumoperitoneum on inert gas exchange and hemodynamics were examined with the multiple inert gas elimination technique. During pneumoperitoneum, gas exchange was most augmented by 15 and 20 cm H(2)O of PEEP. Although the differences in hemodynamics between the individual settings were insignificant, 10 cm H(2)O of PEEP provided the smallest impairment of hemodynamics. We conclude that PEEP of 15 H(2)O during pneumoperitoneum resulted in a modest hemodynamic depression but significant gas exchange augmentation in our experiment. IMPLICATIONS: Anesthetized pigs, with a pneumoperitoneum of 15 cm H(2)O, were treated either with incremental values of positive end-expiratory pressure (5-20 cm H(2)O, increments of 5 cm H(2)O) or with a constant positive end-expiratory pressure of 5 cm H(2)O. Fifteen and 20 cm H(2)O resulted in significantly improved pulmonary gas exchange compared with 5 cm H(2)O.

Animals↗
PubMed2000

Continuous positive airway pressure at 10 cm H(2)O during cardiopulmonary bypass improves postoperative gas exchange.

UNLABELLED: Postbypass pulmonary dysfunction including atelectasis and increased shunting is a common problem in the intensive care unit. Negative net fluid balance and continuous positive airway pressure (CPAP) have been used to reduce the adverse effects of cardiopulmonary bypass (CPB) on the lung. To determine whether CPAP at 10 cm H(2)O during CPB results in improved postoperative gas exchange in comparison with deflated lungs during CPB, we examined 14 patients scheduled for elective cardiac surgery. Seven patients received CPAP at 10 cm H(2)O during CPB, and in the other seven patients, the lungs were open to the atmosphere (control). Measurements were taken before and after CPB, after thoracic closure, and 4 h after CPB in the intensive care unit. CPAP at 10 cm H(2)O resulted in significantly more perfusion of lung areas with a normal ventilation/perfusion distribution (V(A)/Q) and significantly less shunt and low V(A)/Q perfusion 4 h after CPB in comparison with the control group. Consequently, arterial oxygen partial pressure was significantly higher and alveolar-arterial oxygen partial pressure difference was significantly smaller. We conclude that CPAP at 10 cm H(2)O during CPB is a simple maneuver that improves postoperative gas exchange. IMPLICATIONS: Inflation of the lungs at a pressure of 10 cm H(2)O as compared with leaving the lungs deflated during cardiopulmonary bypass was examined. Lung inflation during bypass resulted in significantly improved postoperative gas exchange.

Aged↗
PubMed2000

A pilot study of left tracheal pulse oximetry.

We tested the hypothesis that left tracheal pulse oximetry (SpO(2)) is more accurate than finger SpO(2) when compared with oxygen saturation from arterial blood samples (SaO(2)) in anesthetized patients with normal thoracic anatomy. We also tested the hypothesis that tracheal oximetry readings are primarily derived from the tracheal mucosa. We studied 20 hemodynamically stable, well oxygenated, anesthetized patients with normal anatomy (ASA physical status I-III, 18-80 yr old). A single-use pediatric pulse oximeter was attached to the left lateral surface of a tracheal tube cuff. Tracheal and finger SpO(2) (dominant index finger), and SaO(2) (nondominant radial artery) were taken with the intracuff pressure at 0-60 cm H(2)O. Tracheal SpO(2) was the same as SaO(2) at an intracuff pressure of 10-60 cm H(2)O, but was less when the intracuff pressure was zero (P<0.0001). Tracheal SpO(2) was higher than finger SpO(2) at an intracuff pressure of 10-60 cm H(2)O (all: P <0.001), but was lower when the intracuff pressure was zero (P< 0.0001). SaO(2) was always higher than finger SaO(2) (P<0.0001). Tracheal SpO(2) was lower at an intracuff pressure of zero (P< 0.0001), but was otherwise similar over the range of intracuff pressures. SaO(2) and finger SpO(2) did not vary with intracuff pressure. Tracheal SpO(2) agrees more closely with SaO(2) than finger SpO(2) at an intracuff pressure of 10-60 cm H(2)O (mean difference < 0.2%). We conclude that left tracheal SpO(2) is feasible and provides similar readings to arterial blood samples and more accurate readings than finger oximetry in hemodynamically stable, well oxygenated, anesthetized patients with normal thoracic anatomy. Tracheal oximetry readings are not primarily derived from the tracheal mucosa. The technique merits further evaluation.

Adolescent↗