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Biomedical subjects

M J Bishop

Publications and source records attributed to M J Bishop.

At least 19 recordsLinked to original sources

2-(Anilinomethyl)imidazolines as alpha(1)-adrenoceptor agonists: the identification of alpha(1A) subtype selective 2'-carboxylic acid esters and amides.

2-(Anilinomethyl)imidazolines with 2'-esters or 2'-amides are potent agonists of the cloned human alpha(1)-adrenoceptors in vitro. The size and shape of the ortho substituent can have significant effects on the potency, efficacy, and subtype selectivity of these 2-(anilinomethyl)imidazolines. alpha(1A)-subtype selective agonists have been identified.

Adrenergic alpha-1 Receptor Agonists↗

Epidural naloxone reduces intestinal hypomotility but not analgesia of epidural morphine.

PURPOSE: Epidural morphine is associated with decreased bowel motility and increased transit time. Low doses of intravenous naloxone reduce morphine-induced pruritus without reversing analgesia, but the effect of epidural naloxone on bowel motility has not been studied. Therefore we evaluated bowel motility and analgesia when naloxone was co-administered with morphine into the epidural space. METHODS: Forty-three patients having combined thoracic epidural and general anesthesia for subtotal gastrectomy were randomly assigned to one of two study groups. All received a bolus dose of 3 mg epidural morphine at the beginning of surgery, followed by a continuous epidural infusion containing 3 mg morphine in 100 ml bupivacaine 0.125% with either no naloxone (control group, n = 18) or a calculated dose of 0.208 microg x kg(-1) x hr(-1) of naloxone (experimental group, n = 25) for 48 hr. We measured the time to the first postoperative passage of flatus and feces to evaluate the restoration of bowel function, and visual analog scales (VAS) for pain during rest and movement. Scores were assessed at 2, 4, 8, 16, 24, 36 and 48 hr postoperatively. RESULTS: The experimental group had a shorter time to the first postoperative passage of flatus (5 1.9 +/- 1 6.6 hr vs 87.0 +/- 19.5 hr, P < 0.001 ) and feces (95.3 +/- 25.0 hr vs 132.9 +/- 29.4 hr, P < 0.001). No differences were found in either resting or active VAS between the two groups. CONCLUSION: Epidural naloxone reduces epidural morphine-induced intestinal hypomotility without reversing its analgesic effects.

Analgesia, Epidural↗

Comparison of surgical outcomes between teaching and nonteaching hospitals in the Department of Veterans Affairs.

OBJECTIVE: To determine whether the investment in postgraduate education and training places patients at risk for worse outcomes and higher costs than if medical and surgical care was delivered in nonteaching settings. SUMMARY BACKGROUND DATA: The Veterans Health Administration (VA) plays a major role in the training of medical students, residents, and fellows. METHODS: The database of the VA National Surgical Quality Improvement Program was analyzed for all major noncardiac operations performed during fiscal years 1997, 1998, and 1999. Teaching status of a hospital was determined on the basis of a background and structure questionnaire that was independently verified by a research fellow. Stepwise logistic regression was used to construct separate models predictive of 30-day mortality and morbidity for each of seven surgical specialties and eight operations. Based on these models, a severity index for each patient was calculated. Hierarchical logistic regression models were then created to examine the relationship between teaching versus nonteaching hospitals and 30-day postoperative mortality and morbidity, after adjusting for patient severity. RESULTS: Teaching hospitals performed 81% of the total surgical workload and 90% of the major surgery workload. In most specialties in teaching hospitals, the residents were the primary surgeons in more than 90% of the operations. Compared with nonteaching hospitals, the patient populations in teaching hospitals had a higher prevalence of risk factors, underwent more complex operations, and had longer operation times. Risk-adjusted mortality rates were not different between the teaching and nonteaching hospitals in the specialties and operations studied. The unadjusted complication rate was higher in teaching hospitals in six of seven specialties and four of eight operations. Risk adjustment did not eliminate completely these differences, probably reflecting the relatively poor predictive validity of some of the risk adjustment models for morbidity. Length of stay after major operations was not consistently different between teaching and nonteaching hospitals. CONCLUSION: Compared with nonteaching hospitals, teaching hospitals in the VA perform the majority of complex and high-risk major procedures, with comparable risk-adjusted 30-day mortality rates. Risk-adjusted 30-day morbidity rates in teaching hospitals are higher in some specialties and operations than in nonteaching hospitals. Although this may reflect the weak predictive validity of some of the risk adjustment models for morbidity, it may also represent suboptimal processes and structures of care that are unique to teaching hospitals. Despite good quality of care in teaching hospitals, as evidenced by the 30-day mortality data, efforts should be made to examine further the structures and processes of surgical care prevailing in these hospitals.

Education, Medical, Graduate↗

Recertification of respiratory therapists' intubation skills one year after initial training: an analysis of skill retention and retraining.

Allied health personnel and nonanesthesiologist physicians often undergo training in tracheal intubation but then may actually use the skill relatively infrequently. This study assessed retention of skills one year after initial training and identified specific areas of knowledge critical to successful performance of intubation. Eleven respiratory therapists on the staff of a 253-bed hospital, each of whom had been trained one year previously in airway management, were evaluated. Prior to returning to the operating room for skills assessment and recertification, each respiratory therapist took a 21-question written exam. Therapists then went to the operating room and a trained observer (anesthesiologist) monitored the intubations performed to see whether critical steps were followed, while a second observer monitored a checklist of skills performed. The attending anesthesiologist recertified the therapist only when all steps were correctly performed and the intubation was successful. There was a poor correlation (r = -0.25, p > 0.1) between the number of intubations performed by the therapists for emergencies in the previous year and the number of intubations needed to be recertified. There was a negative correlation (r = -0.8, p < 0.05) between the score on the written test and the number of intubations required for recertification-a higher score meant fewer intubations were needed to achieve recertification. First-pass success occurred significantly more frequently if all skills tested were performed correctly (50/75 first-pass successes had all skills performed correctly vs 10/28 for failed first-pass, p < 0.01). The most common errors were levering the blade on the upper teeth (12/91) and tube not inserted from the right side of the mouth (28/104). When the blade was levered, 8 of 10 intubations failed. When the tube was not inserted from the right side of the face, 6 of 12 failed. The useful findings of this study are: (1) occasional performance of intubation did not ensure skill maintenance; (2) cognitive and procedural abilities correlated, suggesting benefits to study as well as to practical training; and (3) two specific mistakes were associated with a high incidence of failure.

Allied Health Personnel↗

Epidural naloxone reduces pruritus and nausea without affecting analgesia by epidural morphine in bupivacaine.

PURPOSE: To determine whether epidural naloxone preserved analgesia while minimizing side effects caused by epidural morphine. METHODS: Eighty patients undergoing combined epidural and general anesthesia for hysterectomy were randomly assigned to one of four groups. All received 2 mg epidural morphine bolus one hour before the end of surgery and a continuous epidural infusion was started containing 4 mg morphine in 100 ml bupivacaine 0.125% with either no naloxone (Group 1, n = 20), 0.083 microg x kg(-1) x hr(-1) of naloxone (Group 2, n = 20), 0.125 microg x kg(-1) x hr(-1) of naloxone (Group 3, n = 20) or 0.167 microg x kg(-1) x hr(-1) of naloxone (Group 4, n = 20). Analgesia and side effects were evaluated by blinded observers. RESULTS: The combination of epidural morphine and bupivacaine provided good analgesia. Eight hours after the end of surgery, the pain score in the group receiving the highest dose of naloxone was lower than in the control group (VAS 1.2 vs. 2.0, P<0.05) but there was less pruritus in the high-dose naloxone group (itching score 1.3 vs. 1.9, P<0.05). Pain scores were no different in any of the naloxone groups from the control group. Itching was less in both of the higher dose naloxone groups (P<0.05 at 8, 16, and 32 hours). The incidence of vomiting in the control group was 40% vs. 5% for high dose naloxone group (P<0.05). CONCLUSIONS: Epidural naloxone reduced morphine-induced side effects in dose-dependent fashion without reversal of the analgesic effect.

Adult↗

Effects of fenoterol and ipratropium on respiratory resistance of asthmatics after tracheal intubation.

We have studied the effects of a beta-agonist, fenoterol, and a cholinergic antagonist, ipratropium, on post-intubation total respiratory system resistance (Rrs) in asthmatics who developed increased Rrs after tracheal intubation. Sixteen stable asthmatics in whom Rrs increased after intubation were allocated randomly to receive either 10 puffs of fenoterol (group F) or 10 puffs of ipratropium (group IB) via a metered dose inhaler 5 min after intubation. Anaesthesia was induced and maintained with propofol i.v. Rrs was recorded before treatment and again 5, 15 and 30 min after treatment. Rrs decreased significantly from pretreatment values by mean 53 (SD 8)%, 53 (7)% and 58 (6)% at 5, 15 and 30 min, respectively, in group F, but declined by only 12 (6)%, 15 (4)% and 17 (5)% in group IB. At all times after treatment, patients in the fenoterol group had significantly lower Rrs values than those in the ipratropium group. We conclude that increased Rrs after tracheal intubation in asthmatics can be reduced effectively by treatment with fenoterol. A secondary finding of our study was that even after induction of anaesthesia with propofol, patients with a history of asthma may develop high Rrs.

Adrenergic beta-Agonists↗

Endotracheal intubation, but not laryngeal mask airway insertion, produces reversible bronchoconstriction.

BACKGROUND: Tracheal intubation frequently results in an increase in respiratory system resistance that can be reversed by inhaled bronchodilators. The authors hypothesized that insertion of a laryngeal mask airway would be less likely to result in reversible bronchoconstriction than would insertion of an endotracheal tube. METHODS: Fifty-two (45 men, 7 women) patients were randomized to receive a 7.5-mm (women) or 8-mm (men) endotracheal tube or a No. 4 (women) or No. 5 (men) laryngeal mask airway. Anesthesia was induced with 2 microg/kg fentanyl and 5 mg/kg thiopental, and airway placement was facilitated with 1 mg/kg succinylcholine. When a seal to more than 20 cm water was verified, respiratory system resistance was measured immediately after airway placement. Inhalation anesthesia was begun with isoflurane to achieve an end-tidal concentration of 1% for 10 min. Respiratory system resistance was measured again during identical conditions. RESULTS: Among patients receiving laryngeal mask airways, the initial respiratory system resistance was significantly less than among patients with endotracheal tubes (9.2+/-3.3 cm water x 1(-1) x s(-1) [mean +/- SD] compared with 13.4+/-9.6 cm water x 1(-1) x s(-1); P < 0.05). After 10 min of isoflurane, the resistance decreased to 8.6+/-3.6 cm water x 1(-1) x s(-1) in the endotracheal tube group but remained unchanged at 9.1+/-3.3 cm water x 1(-1) x s(-1) in the laryngeal mask airway group. The decrease in respiratory system resistance in the endotracheal tube group of 4.7+/-7 cm water x 1(-1) x s(-1) was highly significant compared with the lack of change in the laryngeal mask airway group (P < 0.01). CONCLUSIONS: Resistance decreased rapidly only in patients with endotracheal tubes after they received isoflurane, a potent bronchodilator, suggesting that reversible bronchoconstriction was present in patients with endotracheal tubes but not in those with laryngeal mask airways. A laryngeal mask airway is a better choice of airway to minimize airway reaction.

Anesthesia↗

The identification and characterization of microsatellites in the compact genome of the Japanese pufferfish, Fugu rubripes: perspectives in functional and comparative genomic analyses.

Fugu rubripes (Fugu) has one of the smallest recorded vertebrate genomes and is an economic tool for comparative DNA sequence analysis. Initial characterization of 128 kb of Fugu DNA attributed the compactness of this genome, in part, to a sparseness of repetitive DNA sequence compared with mammalian genomic sequences. This paper describes a new and comprehensive analysis in which 501 theoretically possible microsatellites with a repeat unit of one to six bases were used to query two orders of magnitude more Fugu DNA (i.e. 11.338 Mb). A total of 6042 microsatellites were identified and categorized. In decreasing order, the 20 most frequently occurring microsatellites are AC, A, C, AGG, AG, AGC, AAT, AAAT, ACAG, ACGC, ATCC, AAC, ATC, AGGG, AAAG, AAG, AAAC, AT, CCG and TTAGGG. The 20 most frequently occurring microsatellites represent 81.79% of all microsatellites identified. Our results indicate that one microsatellite occurs every 1.876 kb of DNA in Fugu, 11.55% of the microsatellites are detected in open reading frames that are predicted protein coding regions. With respect to the proportion of microsatellites present in open reading frames and the total abundance (bp) of all microsatellites, the genome of Fugu is similar to the genome of many other vertebrate species. Previous estimates performed indicate that approximately 1% of many vertebrate genomes are comprized of microsatellite sequences. However, many differences prevail in the abundance and frequency of the individual microsatellite classes. Many of the frequently occurring microsatellites in Fugu are known to code in other species for regions in proteins such as transcription factors, whilst others are associated with known functions, such as transcription factor binding sites and form part of promoter regions in DNA sequences of genes. Therefore, it is likely that such repeats in genomes have a role in the evolution of genes, regulation of gene expression and consequently the evolution of species.

Animals↗

Reference cDNA library facilities available from European sources.

cDNA libraries are the cornerstone of efforts to identify the relatively small regions of genomes that are responsible for biological effects. Gene hunter seeking candidate genes, via a variety of approaches, ultimately focus on the cloning, sequencing, and expression of cDNAs. Assistance is now available to researchers in the form of genome programs, whose initial goals include assembly of a complete collection of expressed sequences derived from the genome of interest. The concept of reference sets of cDNA libraries is that the aims of genome programs are served most effectively by different laboratories working on a common set of high-quality arrayed cDNA libraries, using different experimental approaches, thereby reducing unnecessary duplication of effort, and maximizing the amount of information that one set of resources can provide.

DNA, Complementary↗

Cough during emergence from isoflurane anesthesia.

UNLABELLED: We evaluated the effects of smoking history and albuterol treatment on the amplitude and frequency of cough during emergence from anesthesia. Before induction of anesthesia, 68 patients were randomized to receive two puffs of a placebo or two puffs of albuterol via a metered dose inhaler. Anesthesia was then induced with thiopental, fentanyl, and succinylcholine. The patients' tracheas were intubated with an 8.0 mm-endotracheal tube, and isoflurane administration was initiated. At the end of surgery, isoflurane was discontinued, and the pressure in the endotracheal tube cuff was monitored via the pilot balloon while the end-tidal isoflurane concentration was recorded. Of the 68 patients, 52 coughed before responding to command, but the incidence did not differ between smokers and nonsmokers (33 of 43 vs 19 of 25), nor did it differ between albuterol-treated and untreated patients. There was no difference in the frequency or amplitude of coughs between smokers and nonsmokers, nor did albuterol affect either variable. The mean end-tidal concentration at which cough first occurred was 0.30%+/-0.02%, and only 5% of patients coughed at values >0.6%. We conclude that 1) cough is frequent during emergence; 2) smoking does not affect emergence cough; 3) albuterol treatment does not affect emergence cough; and 4) patients are unlikely to cough at end-tidal values of isoflurane >0.6%. IMPLICATIONS: Most patients cough as they awaken from general anesthesia given via an endotracheal tube. In our study population, cough was frequent but generally did not occur until the end-tidal concentration of isoflurane was <0.6%. Smokers were no more likely to cough than nonsmokers, and the beta-adrenergic agonist albuterol did not prevent cough.

Albuterol↗

Red-blood-cell augmentation of hypoxic pulmonary vasoconstriction: hematocrit dependence and the importance of nitric oxide.

Red blood cells (RBCs) are known to augment hypoxic pulmonary vasoconstriction (HPV). To determine whether this phenomenon is hematocrit (Hct) dependent and related to alterations of either nitric oxide (NO) or adenosine metabolism, we studied mechanically ventilated, pump-perfused lungs from euthanized New Zealand White rabbits. Lungs were perfused in situ in a recirculating manner at constant flow; perfusates consisted of Krebs-Henseleit buffer or buffer plus washed RBCs at a Hct of 10% or 30%. HPV was quantitated as the increase in pulmonary artery pressure (Ppa) from baseline after 5 min of hypoxia. In three experimental sets, we studied the effects of Hct on HPV and expired NO, the effects of nitric oxide synthase (NOS) inhibition, and the effects of adenosine receptor blockade. HPV was greater at a higher Hct, and expired NO varied inversely with Hct and decreased with hypoxia. NOS inhibition eliminated RBC-dependence of HPV. Adenosine-receptor blockade did not affect the RBC-dependence of HPV. We conclude that HPV is dependent on Hct, and that this phenomenon may be related to scavenging of NO but not adenosine by RBCs.

Adenosine↗

Reduction in post-intubation respiratory resistance by isoflurane and albuterol.

PURPOSE: This study examined the bronchodilating effects of 0.6 MAC and 1.1 MAC isoflurane (ISF) on respiratory system resistance (Rrs) following tracheal intubation and determined whether albuterol supplements that effect. METHODS: Sixty-seven adult patients were anaesthetized with 2 micrograms.kg-1 fentanyl and 5 mg.kg-1 thiopentone and their tracheas intubated following administration of 1 mg.kg-1 succinylcholine. Respiratory system resistance was measured following intubation and the patients then randomized to receive either 1.1 MAC ISF in oxygen or 0.6 MAC ISF in 50% nitrous oxide and oxygen. Ten minutes later, Rrs was again measured. Patients were then further randomized to receive albuterol or a placebo using incremental doses of 2, 5, and 10 puffs (albuterol puff = 90 micrograms) delivered via a metered dose inhaler at ten minute intervals. RESULTS: Isoflurane at 1.1 MAC decreased post-intubation Rrs by 23 +/- 5% (mean +/- sem) whereas the decrease was only 7 +/- 5% for 0.6 MAC ISF (P < 0.01). Two puffs of albuterol resulted in a further decrease of 12 +/- 3% (mean +/- sem) in Rrs compared with a 2 +/- 4% decrease in the placebo groups (P < 0.05). Additional puffs of albuterol resulted in no further changes in Rrs. CONCLUSION: We conclude that following tracheal intubation the reduction in Rrs produced by ISF is highly concentration dependent. Albuterol results in a small further reduction in Rrs.

Adrenergic beta-Agonists↗

Effects of intrathecal opioid on extubation time, analgesia, and intensive care unit stay following coronary artery bypass grafting.

STUDY OBJECTIVE: To determine if intrathecal opioid decreases time to extubation after coronary artery bypass surgery without compromising postoperative analgesia. DESIGN: Prospective randomized trial. SETTING: Veterans Affairs Hospital. PATIENTS: 21 ASA physical status III and IV men scheduled for elective coronary bypass surgery, who had not received medications that would impair anticoagulation at the time of surgery. INTERVENTIONS: Patients were randomized to receive 10 micrograms/kg morphine and 25 micrograms fentanyl intrathecally preoperatively (n = 12) or no intrathecal opioid (n = 9). The latter group received 25 to 50 micrograms/kg fentanyl and 0.05 to 0.1 mg/kg midaxolam intraoperatively, whereas the intrathecal opioid group received intravenous (i.v.) fentanyl and midazolam only as needed. Both groups were administered i.v. morphine and midazolam postoperatively as needed by intensive care unit (ICU) personnel who were blinded to the treatment group. MEASUREMENTS AND MAIN RESULTS: For the first 24 hours postoperatively, pain levels (0 = none, to 10 = most severe) and sedation levels (1 = none, to 5 = unconscious) were measured hourly. The time to extubation and discharge from the ICU was recorded. ECG evidence of myocardial ischemia was noted. Pain scores were low for both groups (1.5), but the intrathecal opioid subjects exhibited less sedation than the high-dose fentanyl subjects [means +/- standard deviation (SD) of 2.3 +/- 0.4 vs. 2.8 +/- 0.5, p = 0.03]. Extubation time was 12 hours shorter in the intrathecal opioid group (2.9 +/- 5.3 vs. 14.7 +/- 6.8, p = 0.001). The five subjects with a one day ICU stay were all in the intrathecal opioid group (p = 0.04). The incidence of myocardial ischemia did not differ between the two groups. CONCLUSIONS: Intrathecal opioid can facilitate early extubation and discharge from the ICU without compromising analgesia or increasing myocardial ischemia.

Aged↗

The effect of isoflurane, halothane, sevoflurane, and thiopental/nitrous oxide on respiratory system resistance after tracheal intubation.

BACKGROUND: After tracheal intubation, lung resistance and therefore respiratory system resistance (R[rs]) routinely increase, sometimes to the point of clinical bronchospasm. Volatile anesthetics generally have been considered to be effective bronchodilators, although there are few human data comparing the efficacy of available agents. This study compared the bronchodilating efficacy of four anesthetic maintenance regimens: 1.1 minimum alveolar concentration (MAC) end-tidal sevoflurane, isoflurane or halothane, and thiopental/nitrous oxide. METHODS: Sixty-six patients underwent tracheal intubation after administration of 2 microg/kg fentanyl, 5 mg/kg thiopental, and 1 mg/kg succinylcholine. Vecuronium or pancuronium (0.1 mg/kg) was then given to ensure paralysis during the rest of the study. Postintubation R(rs) was measured using the isovolume technique. Maintenance anesthesia was then randomized to thiopental 0.25 mg x kg(-1) x min(-1) plus 50% nitrous oxide, or 1.1 MAC end-tidal isoflurane, halothane, or sevoflurane. The R(rs) was measured after 5 and 10 min of maintenance anesthesia. Data were expressed as means +/- SD. RESULTS: Maintenance with thiopental/nitrous oxide failed to decrease R(rs), whereas all three volatile anesthetics significantly decreased R(rs) at 5 min with little further improvement at 10 min. Sevoflurane decreased R(rs) more than either halothane or isoflurane (P < 0.05; 58 +/- 14% of the postintubation R(rs) vs. 69 +/- 20% and 75 +/- 13%, respectively). CONCLUSIONS: After tracheal intubation in persons without asthma, sevoflurane decreased R(rs) as much or more than isoflurane or halothane did during a 10-min exposure at 1.1 MAC.

Adult↗

CO2 transport in normovolemic anemia: complete compensation and stability of blood CO2 tensions.

Isovolemic hemodilution does not appear to impair CO2 elimination nor cause CO2 retention despite the important role of red blood cells in blood CO2 transport. We studied this phenomenon and its physiological basis in eight New Zealand White rabbits that were anesthetized, paralyzed, and mechanically ventilated at a fixed minute ventilation. Isovolemic anemia was induced by simultaneous blood withdrawal and infusion of 6% hetastarch in sequential stages; exchange transfusions ranged from 15-30 ml in volume. Variables measured after each hemodilution included hematocrit (Hct), arterial and venous blood gases, mixed expired PCO2 and PO2, and blood pressure; also, O2 consumption, CO2 production, cardiac output (Q), and physiological dead space were calculated. Data were analyzed by comparison of changes in variables with changes in Hct and by using the model of capillary gas exchange described by Bidani (J. Appl. Physiol. 70: 1686-1699, 1991). There was complete compensation for anemia with stability of venous and arterial PCO2 between Hct values of 36 +/- 3 and 12 +/- 1%, which was predicted by the mathematical model. Over this range of hemodilution, Q rose 50%, and the O2 extraction ratio increased 61% without a decline in CO2 production or a rise in alveolar ventilation. The dominant compensations maintaining CO2 transport in normovolemic anemia include an increased Q and an augmented Haldane effect arising from the accompanying greater O2 extraction.

Anemia↗