Biomedical subjects
Publications and source records attributed to C Marshall.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
A large-scale malaria intervention programme using insecticide-treated bed nets and chemoprophylaxis administered to children was introduced into a rural area of The Gambia. The operation was carried out using the existing primary health care (PHC) service in the region. Training of the village health workers, sensitization of the communities, and implementation of net impregnation and the drug delivery programme are described. This delivery system resulted in over 90% of nets being treated with insecticide and 80% of children receiving over 90% of their tablets during the rainy season. There was considerable variation in the distribution of permethrin on a bed net and between individual nets, which is likely to facilitate the spread of insecticide resistance in the local mosquito populations. Bed nets made from heavier fabrics tended to absorb more insecticide than those made from lighter materials. Four months after dipping, 89% of the insecticide had been lost from treated nets. This was probably due mainly to women washing their nets, an activity carried out on average once every 2 months during the rainy season. The high number of insecticide-treated bed nets in the study area demonstrated that a malaria control programme operated through a PHC system can be implemented successfully.
A man with allergic bronchopulmonary aspergillosis had pneumothorax and bronchopleural fistula while impacted mucus was being successfully dislodged from bronchiectatic airways. We believe this is the first report of pneumothorax with bronchopleural fistula in a patient with active ABPA, and we have proposed a mechanism to explain the development of this complication.
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This study examined the effect of sensory affect stimulation (SAS) delivered through the volar surface of the wrist on pregnancy-induced nausea and vomiting. Twenty-three women with significant nausea and vomiting in the first 14 weeks of pregnancy were enrolled in a randomized, crossover study comparing an active SAS unit and an inactive placebo unit. Twenty-one women experienced improvement in symptoms, 20 (87%) with the SAS unit and 10 (43%) with the placebo device. Nine women had an improvement with both devices. Eleven women reported an improvement with SAS only, while one woman had placebo improvement only. SAS applied to the wrist can effectively improve pregnancy-induced nausea and vomiting as compared to a placebo device.
Plasma membrane-enriched fractions were prepared from human embryonic retinal cells transformed with either adenovirus E1A and oncogenic ras DNA, or E1A and E1B DNA. Ras comprised 5-10% of the membrane protein from the E1A/ras transformed cells, whereas the membranes from E1A/E1B transformed cells did not overexpress Ras. The membranes from E1A/ras cells contained MAP kinase kinase kinase (MAPKKK) activity, even after washing in 0.5 M NaCl, whereas the membranes from E1A/E1B cells did not. Neither membrane fraction contained MAP kinase kinase or MAP kinase activity after washing with 0.5M NaCl. Immunoblotting experiments revealed about 10-fold more c-Raf in the membranes from E1A/ras cells than from E1A/E1B cells, and 50-60% of the MAPKKK activity in Triton X100-solubilised membranes from E1A/ras cells was immunoprecipitated with anti-Raf antibodies. A striking enrichment of c-Raf in the plasma membranes of E1A/ras cells was also demonstrated by immunocytochemistry, where it was co-localized with Ras. The MAPKKK activity in E1A/ras membranes was unaffected by incubation with protein phosphatases or by inclusion of protein phosphatase inhibitors during isolation, nor was it activated by GTP-Ras or inhibited by GDP-Ras. The results support the view that Ras and c-Raf interact with one another, but that neither c-Raf phosphorylation nor its interaction with GTP-Ras are alone sufficient for activation. The identification of MAPKKK activity in the membranes of ras-transformed cells may prove useful in elucidating the mechanism by which Raf is activated by Ras.
Stimulation of PC12 cells with nerve growth factor (NGF) increased mitogen-activated protein kinase kinase (MAPKK) activity > 20-fold after 5 min to a level that was largely sustained for at least 90 min. MAPKK activity was stimulated to a similar level by epidermal growth factor (EGF), but peaked at 2 min, declining thereafter and returning to basal levels after 60-90 min. Activation of MAPKK by either growth factor occurred prior to the activation of MAP kinase, consistent with MAPKK being the physiological activator of MAP kinase. The results demonstrate that the transient activation of MAPKK by EGF and its sustained activation by NGF underlies the transient and sustained activation of MAP kinase induced by EGF and NGF respectively. NGF or EGF induced the same two forms of MAPKK that were resolved on a Mono Q column. The Peak-1 MAPKK was activated initially and partially converted into the more acidic peak-2 MAPKK after prolonged growth-factor stimulation. The Peak-2 MAPKK was 20-fold more sensitive to inactivation by the catalytic subunit of protein phosphatase 2A. Stimulation with NGF caused a striking translocation of MAP kinase from the cytosol to the nucleus after 30 min, but not nuclear translocation of MAP kinase occurred after stimulation with EGF. The results suggest that sustained activation of the MAP kinase cascade may be required for MAP kinase to enter the nucleus, where it may initiate the gene transcription events required for neuronal differentiation of PC12 cells.
The genomes of the four primate lentiviral groups are complex and contain several regulatory or accessory genes. Two of these genes, vpr and vpx, are found in various combinations within the four groups and encode proteins whose functions have yet to be elucidated. Comparison of the encoded protein sequences suggests that the vpx gene within the HIV-2 group arose by the duplication of an ancestral vpr gene within this group. Evolutionary distance analysis showed that both genes were well conserved when compared with viral regulatory genes, and indicated that the duplication occurred at approximately the same time as the HIV-2 group and the other primate lentivirus groups diverged from a common ancestor. Furthermore, although the SIVagm vpx proteins are homologous to the HIV-2 group vpx proteins, there are insufficient grounds from sequence analysis for classifying them as vpx proteins. Because of their similarity to the vpr proteins of other groups, we suggest reclassifying the SIVagm vpx gene as a vpr gene. This creates a simpler and more uniform picture of the genomic organization of the primate lentiviruses and allows the genomic organization of their common precursor to be defined; it probably contained five accessory genes: tat, rev, vif, nef and vpr.