Oncogenes and cell proliferation.
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Apoptosis↗
Biomedical subjects
C Marshall
Publications and source records attributed to C Marshall.
Causes of hypercarbia with oxygen therapy in patients with chronic obstructive pulmonary disease.
OBJECTIVES: To compare data derived from a computer model of the pulmonary circulation with data from a case series of patients with chronic obstructive pulmonary disease (COPD). To evaluate the specific factors contributing to CO2 retention due to oxygen therapy in patients with acute exacerbations of COPD. DESIGN: Data from a computer model of the pulmonary circulation were compared with a previous case series. PATIENTS: Patient data were derived from previous case series. INTERVENTIONS: Simulated application of oxygen therapy. MEASUREMENTS AND MAIN RESULTS: The computer model of the pulmonary circulation generates data comparable with those data from a series of patients with COPD treated with supplemental oxygen and permits identification of the causes for hypercarbia. Therapy with supplemental oxygen alters hypoxic pulmonary vasoconstriction and modulates the Haldane effect, resulting in changes in physiologic deadspace. CONCLUSION: Changes in physiologic deadspace are sufficient to account for the hypercarbia developed by patients with acute exacerbations of COPD when treated with supplemental oxygen.
Blood Pressure↗
Pulmonary artery NADPH-oxidase is activated in hypoxic pulmonary vasoconstriction.
An NADPH-oxidase complex containing at least two protein components (gp91-phox and p22-phox) and a unique low redox potential (-245 mV) cytochrome b-245 is the source of superoxide generated for bacterial killing in neutrophils and has been suggested as the oxygen sensor in the carotid body. In pure cultures of smooth muscle cells from calf small pulmonary arteries (300 microns diameter) the presence of the 91 kD protein specific to this cytochrome was demonstrated by Western blot analysis with monoclonal antibody 48. Low-temperature-difference spectrophotometry of homogenates of these cells demonstrated the characteristic cytochrome b-245 spectrum when titrated between redox potentials of -152 and -345 mV, consistent with the low redox potential form. When these same cells were exposed to hypoxia (approximately 40 mmHg), superoxide production increased significantly from 1.4 +/- 0.2 to 73 +/- 12 nmoles.min-1 mg-1 protein. Hypoxic generation of superoxide was inhibited by the NADPH-oxidase inhibitor diphenyleneiodonium (DPI: 10 microM) but not by the mitochondrial inhibitor myxathiazole (10 microM). The hypoxic superoxide increase was significantly greater than that observed from smooth muscle cells from large pulmonary arteries or from large or small systemic arteries. Fluorescence immunocytochemistry revealed the presence of the NADPH-oxidase protein in the walls of pulmonary arteries in rat lung slices, and confocal microscopy showed the complex to be widely distributed in the vicinity of the arterial smooth muscle walls. In hypoxia or norepinephrine (NP)-induced vasoconstriction of pulmonary artery rings from cats, the sensitivity to inhibition by DPI was observed to be significantly greater for hypoxia (ED50 = 0.8 microM) than for NP-induced (ED50 = 13.4 microM) constriction. Together these observations demonstrate that the unique cytochrome b-245 containing NADPH-oxidase is present in pulmonary artery smooth muscle and that an NADPH-oxidase or NADH-oxidoreductase complex is activated to release superoxide by hypoxic conditions. It is concluded that a trans-membrane NADPH-oxidase is the most likely and that activation of this system may be involved in the initiation of hypoxic pulmonary vasoconstriction.
Animals↗
Mucinous adenocarcinoma in the abomasum of a cow.
A cow with mucinous adenocarcinoma of the abomasum presented to the teaching hospital with a markedly distended abdomen from which 80 liters of fluid was drained during trocharization. An exploratory laparotomy allowed removal of an additional 80 liters of fluid from the peritoneal cavity and revealed a diffusely thickened parietal peritoneum and a palpable cranial abdominal mass. The cow was euthanatized. At necropsy, the abomasum was diffusely thickened and firm. The peritoneal and pleural surfaces were covered with numerous coalescing, firm white nodules. Microscopically, the thickened abomasum was multifocally effaced by aggregates, cords, and acini of neoplastic cells separated by amphophilic, foamy to wispy periodic acid-Schiff- and alcian blue-positive material. Cell boundaries were indistinct and large, clear, colorless intracytoplasmic vacuoles were common.
Abomasum↗
14-3-3 proteins: structure resolved, functions less clear.
The crystal structures of 14-3-3 proteins reveal that they form dimers with a deep groove running along the length of the dimer. The location of conserved residues in this groove suggests that it plays an essential role in the adaptor functions of these proteins.
14-3-3 Proteins↗
Prevention of emesis after strabismus repair in children: a prospective, double-blinded, randomized comparison of droperidol versus ondansetron.
STUDY OBJECTIVE: To compare the effectiveness of ondansetron with droperidol in preventing postoperative emesis in children after strabismus repair. DESIGN: Randomized, double-blind study. PATIENTS AND SETTING: 57 ASA physical status I and II children aged 3 to 14 years, undergoing outpatient strabismus repair in two separate study centers. INTERVENTIONS: Patients were randomized to receive either 0.15 mg/kg intravenous (i.v.) ondansetron or 0.075 mg/kg i.v. droperidol shortly after induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Number of episodes of emesis and times to discharge from the recovery room and ambulatory center were assessed. Twenty-nine (94%) of 31 children who received ondansetron and 21 (81%) of 26 children who received droperidol were emesis-free (p = NS). There were no significant differences in the number of episodes of emesis on the day after surgery or times to discharge. CONCLUSIONS: Ondansetron is at least as effective as droperidol in reducing the frequency of emesis in children after strabismus repair, and it did not shorten times to discharge home. The low number of patients in our study may have masked a difference in effect between the two groups. The clinician should decide whether the increased cost of ondansetron justifies its use over other antiemetics.
Adolescent↗
Effect of multilevel sequential stenosis on lower extremity arterial duplex scanning.
BACKGROUND: The sensitivity of lower extremity arterial duplex scanning in detecting a > 50% stenosis may be decreased in extremities with multilevel sequential stenosis. PATIENTS AND METHODS: The results of lower extremity arterial duplex scanning of the common femoral, upper and lower superficial femoral, above- and below-knee popliteal arteries, and tibioperoneal trunk in 80 extremities of 44 patients were compared to those of arteriography. Thirty-one arterial segments in 27 extremities had a > 50% stenosis. The stenoses were categorized as first order (first or only stenotic segment in the extremity, n = 23) and second order (stenosis occurring distal to a > 50% stenosis, n = 4, or occlusion, n = 4). RESULTS: The sensitivity, specificity, and positive predictive values of duplex scan detection of a > 50% arterial stenosis or occlusion were 86%, 96%, and 67% for the common femoral artery; 95%, 98%, and 95% for the upper superficial femoral artery; 97%, 90%, and 88%, for the lower superficial femoral artery; 84%, 90%, and 87% for the above-knee popliteal artery; 47%, 98%, and 90% for the below-knee popliteal artery; and 25%, 100%, and 100% for the tibioperoneal trunk. Duplex scanning detected 18 (78%) of the 23 first-order stenoses compared to only 1 (13%) of the 8 second-order stenoses in limbs with multilevel sequential disease (P < 0.01). The peak systolic velocity at the stenotic site was significantly higher for first-order (mean +/- SD 168 +/- 54 cm/s) compared to second-order (38 +/- 13 cm/s) stenoses (P < 0.00002). CONCLUSIONS: Duplex scanning was highly sensitive in detecting lower extremity first-order stenoses. Low peak systolic velocities at second-order stenoses of limbs with multilevel sequential disease significantly decreased the sensitivity of duplex scanning.
Arterial Occlusive Diseases↗
Two novel antithrombin variants, Asn187Asp and Asn187Lys, indicate a functional role for asparagine 187.
Three unrelated families have been identified with mutations involving asparagine 187. Two of these families are asymptomatic and were identified during the screening of random blood donors, whilst the third has a history of recurrent thromboembolic disease. In two families the mutation (6460 AAC-->GAC) results in an asparagine to aspartate substitution and is associated with normal immunological levels of antithrombin but a reduction in functional activity. In the third family the mutation (6462 AAC-->AAA) results in an asparagine to lysine substitution at residue 187 and is associated with a parallel reduction in both immunological and functional antithrombin levels. Asparagine 187 is located in the middle of the F helix of antithrombin and forms the major link between the F helix and strand 3 of the A sheet. The F helix is seen to overlie the A sheet of the molecule and moves with strands 2 and 3 of this sheet as they open to allow entry of the reactive site loop to form strand 4. Substitutions of asparagine 187 are, therefore, likely to disrupt this sliding movement leading to a loss of inhibitory activity.
Adult↗
Clinical outcome and quality of life following enterocystoplasty for idiopathic detrusor instability and neurogenic bladder dysfunction.
OBJECTIVE: To study the long-term outcome of patients undergoing enterocystoplasty. PATIENTS AND METHODS: The study comprised 48 patients (17 men and 31 women; mean age 46 years) who underwent enterocystoplasty for idiopathic detrusor instability (DI, 35 patients) or neurogenic bladder dysfunction (13 patients). Symptoms were scored from 0 to 14 and the overall outcome and generic quality of life were assessed using a Visick grading system (groups A to E) and the Nottingham Health Profile (NHP). These assessments were carried out before, 3 months after operation and at the final follow-up (38 +/- 18 months, range 13-78). Urodynamic studies were performed before and after operation. RESULTS: No patient died after operation and there was minimal early morbidity. Late complications (> 30 days) included incisional hernia (3), anastomotic perforation (1), calculus formation (1) and urethral stricture (1). Clean intermittent self-catheterization (CISC) was performed by 36 (75%) patients. Early symptomatic outcome was good in 40 (83%) patients, moderate in seven (15%) and unsatisfactory in one (2%) patient. The mean symptom scores before and 3 months after surgery were 10 (range 2-14) and 3 (range 2-14), respectively (P < 0.001). There was a significant increase in total bladder capacity (307 +/- 140 to 588 +/- 217 mL; P < 0.001) and bladder compliance (37 +/- 50 to 169 +/- 162 mL/cm H2O; P < 0.001). DI persisted in 15 (31%) patients. NHP scores revealed significant improvements in all domains. Final assessment showed a less satisfactory situation, with recurrent urinary tract infection (UTI) in 17 (37%) patients, a need for long-term antibiotic therapy in seven (15%) and a change in bowel habit in 15 (33%) (13 DI, two with neurogenic bladder dysfunction). CISC was performed by 39 (85%) patients. The long-term outcome was good or moderate in 12 patients (92%) with neurogenic bladder dysfunction and good or moderate in only 19 patients (58%) with DI. CONCLUSION: Clam enterocystoplasty remains an effective management option in some patients with DI, but most patients with neurogenic bladder dysfunction do well. The procedure is, however, associated with long-term complications such as disturbance of bowel habit and recurrent UTIs, which impair the outcome in the long-term in patients with DI despite general improvements in irritative bladder symptoms.
Adult↗
Identifying the relationship between work and nonwork stress among bank managers.
The purpose of this study was to (1) test the effects of various demographic and socioeconomic variables on perceived stress among bank managers in both work and nonwork environments and (2) to ascertain whether the correlation is significant between perceived stress in the work and nonwork environments among the same bank managers. Significant differences were found between genders, among management levels, and among age groups. A multiple linear regression test showed a positive relationship between perceived stress at work and away from work.
Adult↗
Role of hypoxic pulmonary vasoconstriction in pulmonary gas exchange and blood flow distribution. 1. Physiologic concepts.
The regulation of the distribution of ventilation/perfusion ratios by hypoxic pulmonary vasoconstriction contributes to both the efficiency of gas exchange and to pulmonary hemodynamics. In this review, the first of two part series, are summarized the physiologic principles on which the analysis of ventilation/perfusion ratios and of pressure-flow relationships are based. A new combined analysis is introduced that permits the important contributions of hypoxic pulmonary vasoconstriction to overall gas exchange to be demonstrated in the circumstances of clinical complexity.
Humans↗
Role of hypoxic pulmonary vasoconstriction in pulmonary gas exchange and blood flow distribution. 2. Pathophysiology.
In this review, the second of a two part series, the analytic techniques introduced in the first part are applied to a broad range of pulmonary pathophysiologic conditions. The contributions of hypoxic pulmonary vasoconstriction to both homeostasis and pathophysiology are quantitated for atelectasis, pneumonia, sepsis, pulmonary embolism, chronic obstructive pulmonary disease and adult respiratory distress syndrome. For each disease state the influence of principle variables, including inspired oxygen concentration, cardiac output and severity of pathology are explored and the actions of selected drugs including inhaled nitric oxide and infused vasodilators are illustrated. It is concluded that hypoxic pulmonary vasoconstriction is often a critical determinant of hypoxemia and/or pulmonary hypertension. Furthermore this analysis demonstrates the value of computer simulation to reveal which of the many variables are most responsible for pathophysiologic results.
Humans↗
The dose-response relationship for hypoxic pulmonary vasoconstriction.
In 12 pentobarbital anesthetized dogs the lungs were independently ventilated with a double piston ventilator. The right lung was ventilated throughout with 100% oxygen. Blood was drawn from the right atrium and pumped through a bubble oxygenator to a cannula in the ligated left main pulmonary artery. The pressures in the left main pulmonary artery and the left atrium were recorded during constant flow while the oxygen tension in the left lung alveolar gas and the perfusate were varied either to match each other (Protocol 1) or differ (Protocol 2) over the range from "zero" to "100%" oxygen. From the combined data a three dimensional response surface for hypoxic pulmonary vasoconstriction was derived. The maximum increase of pulmonary vascular resistance (r%PVRmax) was defined at a stimulus oxygen tension (PSO2) of 10 mmHg amounting to a 3.15 +/- (0.18)-fold increase of the vascular resistance on "100%" oxygen. The stimulus oxygen tension was shown to be PSO2 = PVO2(0.41) x PAO2(0.59) and the dose-response sigmoid for hypoxic pulmonary vasoconstriction in canine lungs was derived as r%PVRmax = 100 (PSO2(-2.616))/(6.683 x 10(-5) + PSO2(-2.616)) These results appear to reconcile observations from a number of laboratories and to be of quite general application.
Animals↗
Comparison of different bolus doses of morphine for patient-controlled analgesia in children.
Forty children undergoing appendicectomy were allocated randomly to receive one of two PCA regimens with morphine. Group B10 received bolus doses of 10 micrograms kg-1 and group B20 received bolus doses of 20 micrograms kg-1. In both groups there was a lockout interval of 5 min and a background infusion of 4 micrograms kg-1 h-1. Group B20 self-administered considerably more morphine (P < 0.01) than group B10. There was no difference between the pain scores of the groups at rest. Group B20 had significantly (P < 0.05) smaller pain scores during movement than group B10 and the latter group suffered significantly (P < 0.01) more hypoxaemic episodes than group B20. There were no differences between the groups in the incidence of vomiting, excess sedation or the amount of time spent asleep at night.
Adolescent↗
Continent urinary diversion using the Mitrofanoff principle.
OBJECTIVE: To review the clinical and symptomatic outcome of patients undergoing cystectomy and continent urinary diversion using the Mitrofanoff principle. PATIENTS AND METHODS: There were seven men and five women (median age 62 +/- 21 years: range 21-79). The underlying diagnoses were: bladder carcinoma (8), neuropathic bladder disease (1), bladder exstrophy (1), tuberculosis (1) and interstitial cystitis (1). An ileo-caecal segment was used for construction of the reservoir. The appendix was used as a catheterizable conduit in 11 patients and a narrowed ileal tube in one patient. Symptomatic outcome was assessed by using a modified Visick grading. The median follow-up period was 15 +/- 10 months (range 6-39). RESULTS: The median hospital stay was 22 days. There were no post-operative deaths, but major post-operative complications developed in three patients and included intra-abdominal lymphocele (1), intra-abdominal abscess formation (1) and prolonged ileus (1). In the late post-operative period (> 30 days), four patients developed stenosis of the mucocutaneous junction and required dilatation. The overall symptomatic outcome was satisfactory in 11 patients. There were no deaths in the peri-operative period and none of the patients has since required revision. Urinary continence was achieved in all 12 patients during the day. One patient reported minimal, occasional leakage at nights. The median catheterization interval was 4 +/- 1 hours during the day (range 3-5) and 7 +/- 1 hours at night (range 6-9). CONCLUSION: Our experience with the Mitrofanoff procedure has been limited to a small number of patients. Despite this, the clinical outcome of the procedure was satisfactory. The procedure potentially offers an effective continence mechanism with acceptable post-operative morbidity.
Adult↗
The concept of advocacy.
In safeguarding the patient, the nurse supports and thereby advocates the patient's interests in teh restoration of the patient's health and well-being. This article explores the concept of advocacy, discusses some of its complex issues and highlights its implications for nursing practice with some reference to the theatre setting. An advocate is one who pleads the cause of another. According to Tschudin, advocacy is a fundamental aspect of an ethic of caring in that with courage born of compassion one is able to respond in a caring way to the needs and rights of another. An advocate must take positive steps to restore another person's autonomy when it is threatened or diminished, otherwise all talk of advocacy is simply lip-service. In theatre nursing the scope for acting as the patient's advocate is a reality because most surgery necessitates the use of general anaesthesia resulting in the patients' loss of consciousness and they are therefore unable to maintain their own interests. The anaesthetised patient who has entrusted his life into the hands of the theatre team relies on this duty of care to maintain his dignity and safety. As Bandman and Bandman purport, the nurse recognises that his or her first duty is to protect and care for the patient's health and safety.
Humans↗
Crystallization of inhibited aspartic proteinase from Candida albicans.
A major secreted aspartic proteinase from Candida albicans has been crystallized in the presence of inhibitors to prevent autodegradation. With pepstatin a cleaved form of the enzyme was nevertheless found in the crystals whereas with the inhibitor A70450 the enzyme remained intact. The crystals containing pepstatin were not suitable for X-ray data collection while the crystals containing A70450 grew by vapour diffusion as tetragonal bipyramids, space group P4(3)2(1)2 (or P4(1)2(1)2), a = b = 76.2 A, c = 126.1 A, with one molecule in the asymmetric unit and they diffract to beyond 2.2 A.
Aspartic Acid Endopeptidases↗
Nurse management. Loud, louder, loudest.
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England↗