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.
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.
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.
A novel protein kinase, which was only active when phosphorylated by the mitogen-activated protein kinase (MAP kinase), has been purified 85,000-fold to homogeneity from rabbit skeletal muscle. This MAP kinase activated protein kinase, termed MAPKAP kinase-2, was distinguished from S6 kinase-II (MAPKAP kinase-1) by its response to inhibitors, lack of phosphorylation of S6 peptides and amino acid sequence. MAPKAP kinase-2 phosphorylated glycogen synthase at Ser7 and the equivalent serine (*) in the peptide KKPLNRTLS*VASLPGLamide whose sequence is similar to the N terminus of glycogen synthase. MAPKAP kinase-2 was resolved into two monomeric species of apparent molecular mass 60 and 53 kDa that had similar specific activities and substrate specificities. Peptide sequences of the 60 and 53 kDa species were identical, indicating that they are either closely related isoforms or derived from the same gene. MAP kinase activated the 60 and 53 kDa forms of MAPKAP kinase-2 by phosphorylating the first threonine residue in the sequence VPQTPLHTSR. Furthermore, Mono Q chromatography of extracts from rat phaeochromocytoma and skeletal muscle demonstrated that two MAP kinase isoforms (p42mapk and p44mapk) were the only enzymes in these cells that were capable of reactivating MAPKAP kinase-2. These results indicate that MAP kinase activates at least two distinct protein kinases, suggesting that it represents a point at which the growth factor-stimulated protein kinase cascade bifurcates.
Meyer and Wilson's (1990) 12S rRNA phylogeny unites lungfish and tetrapods to the exclusion of the coelacanth. These workers also provide a list of morphological features shared in common between modern lungfish and tetrapods, and they conclude that these traits were probably present in their last common ancestor. However, the exquisite fossil records of the abundant extinct lungfishes and rhipidistians show that at least 13 out of Meyer and Wilson's 14 supposed ancestral traits were not present in the last common ancestor of lungfishes and tetrapods. Using extant taxa to infer ancestral morphologies is fraught with difficulties; just like molecular sequences, ancestral character states of morphological traits may be severely overprinted by subsequent modifications. Modern lungfish are air-breathing nonmarine forms, yet their Devonian forebears were marine fish that did not breathe air. Fossils dating from the time of origin of tetrapods in the Devonian offer the only hope of understanding the morphological innovations that led to tetrapods; morphological analysis of the "living fossils," the coelacanth and lungfish, only lends confusion.
Feline intrapulmonary arteries (mean diameter, 0.9 mm) were equilibrated in Earle's solution at constant tension in a chamber bubbled with an hyperoxic gas mixture (30% oxygen, 5% carbon dioxide, balance nitrogen). The endothelium was removed from half the vessels by gentle rubbing. The isometric response to the addition of acetylcholine (1*10(-6) M) was dilator in the vessels with endothelium and constrictor in those without endothelium. Intermittent exposure to a hypoxic gas mixture (0% oxygen, 5% carbon dioxide, balance nitrogen) for 20 min with five repetitions demonstrated sustained constrictor responses in the presence or absence of endothelium. Endothelial cells are, therefore, not required for the mediation of hypoxic pulmonary vasoconstriction.
The amino acid sequence of the dual specificity mitogen-activated protein kinase kinase (MAPKK) has been determined by cDNA cloning and amino acid sequencing. MAPKK (393 residues, Mr 43,330) is a new member of the protein kinase subclass that comprises byr1 and STE7 that are involved in pheromone dependent signal transduction in yeast, wis1 a mitotic regulator in S. pombe and PBS2, which confers antibiotic resistance in S. cerevisiae.
Thirteen renal allograft recipients (6 patients on cyclosporine/7 patients on azathioprine) participated in a short-term oral protein-loading study to determine the effect of cyclosporine on an allograft's functional reserve. The baseline glomerular filtration rate of the two groups were similar (52 +/- 18 ml/min/1.73 m2 for the azathioprine/conventional therapy (CT) group and 47 +/- 12 ml/min/1.73 m2 for the cyclosporine (CsA) group), as were the baseline effective renal plasma flows (218 +/- 78 ml/min/1.73 m2 and 222 +/- 75 ml/min/1.73 m2, respectively). At 3 hr following the protein load there was an increase in GFR to 66 +/- 28 ml/min/1.73 m2 in the CT group. The GFR (39 +/- 8 ml/min/1.73 m2) of the CsA group at this time was unchanged. The responses in ERPF were similar. No significant difference was found between the two groups baseline RAA profiles (4.7 +/- 3.3 ng/ml/hr (CT) and 4.7 +/- 1.7 ng/ml/hr [CsA]), or those at the third hour (8.1 +/- 8.3 ng/ml/hr (CT) and 3.5 +/- 1.9 ng/ml/hr [CsA]). The data in this study indicate that CsA alters the renal allograft's response to a protein meal. This difference may be related to an altered vasodilatory response. This altered vascular reactivity may be mediated through renin activation and/or other hemodynamic regulators such as prostaglandins.
In six anesthetized and mechanically ventilated adult sheep, the bronchial artery was perfused with blood from an oxygenator-pump circuit. When the lungs were ventilated with 100% O2 and the bronchial O2 tension (PbrO2) was approximately 600 Torr, the mean of the pulmonary vascular resistances (PVR) measured at the beginning (3.32 +/- 0.29 units) and end (3.17 +/- 0.13 units) of the experiment was 3.24 +/- 0.20 units. When the PbrO2 was changed to 58 +/- 1 Torr, the PVR (2.99 +/- 0.14 units) did not change significantly. However, when the lungs were ventilated with air as PbrO2 was decreased to 91 +/- 4, 77 +/- 3, 56 +/- 2, and 42 +/- 1 Torr, the PVR increased to 3.67 +/- 0.18, 4.03 +/- 0.16, 4.79 +/- 0.19, and 4.71 +/- 0.35 units, respectively. However, when the PbrO2 was decreased further to 26 +/- 1 and 13 +/- 1 Torr, the PVR decreased to 3.77 +/- 0.28 and 3.91 +/- 0.30 units, respectively. In contrast, the bronchial vascular resistance decreased monotonically as PbrO2 decreased. The bronchial circulation supplies vasa vasorum to the walls of all but the smallest pulmonary arteries, and it is therefore suggested that the PO2 of the bronchial circulation is responsible for the bimodal response of the pulmonary vasculature, with stimulation of hypoxic pulmonary vasoconstriction at moderate hypoxemia and of hypoxic pulmonary vasodilation at profound hypoxemia. The physiological and pathophysiological significance of the influence of systemic PO2 on pulmonary vascular tone is discussed.
Elder abuse encompasses physical, psychological, and financial abuse and also includes the violation of an individual's rights, or social abuse. Detection of elder abuse is often obstructed by the denial or shame of the abused older adult and the denial or improper assessment by health care professionals. The ethical struggle professionals face when they suspect abuse may also impede assessment or intervention. Preliminary data on etiologic factors related to elder abuse suggest that misinformation, the caregiver's lack of understanding of the needs of older adults, social isolation, a history of dysfunctional family relationships, and the psychopathologic factors of the caregiver are salient factors for understanding elder abuse. In addition, caregiver burden related to the care of the impaired elder and other external life events is a risk factor for elder abuse. Self-neglect is the type of elder abuse most often reported and the most difficult to handle, because older adults have a right to refuse services. Home care providers often face practical and ethical dilemmas in cases of self-neglect. When making an assessment for elder abuse, it is best to use a multidisciplinary approach. In addition to physical indicators (bruises, malnutrition, fractures), attention must be paid to the social, family, and sexual history of the patient. The psychological history of the patient and caregiver is also important. Reporting laws exist in all states, and health care practitioners must become familiar with the laws in their states. Awareness of elder abuse by professionals working in home care is essential, because the failure to detect abuse can interfere with interventions and in some cases lead to death.
Erythema multiforme is reported for the first time in 2 South African horses. Both horses displayed a sudden, fulminant outbreak of raised, non-alopecic and non-pruritic plaques over the dorsolateral aspects of the neck and trunk. In both cases the distribution of the lesions was bilaterally symmetrical. Histopathological findings included hydropic degeneration of basal epidermal cells, eosinophilic necrosis of individual or groups of keratinocytes, intra-epidermal and sub-epidermal cleft formation and mixed, dermal, perivascular infiltrates. An initiating cause could not be identified in either case. Both horses underwent gradual spontaneous remission within 3 months.
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Inhalational anesthetics inhibit hypoxic pulmonary vasoconstriction (HPV). One mechanism suggested for this action is stimulation of release of endothelium-derived relaxing factor. The present study has tested this hypothesis. These studies were performed in 66 ventilated and perfused isolated rat lungs. There were three study protocols. Study 1 examined the effect of HPV of the inhibition of soluble guanylate cyclase by methylene blue (MB). In the presence or absence of MB, the lungs constricted to hypoxia with pulmonary artery pressure increases of 8.6 +/- 0.2 cmH2O and 11.5 +/- 0.4 cmH2O, respectively, and halothane, enflurane, and isoflurane caused a reversible 50% decrease in the pulmonary pressor response, but acetylcholine (ACh) was vasodilatory in the saline group and vasoconstrictor in the MB group. In Study II a dose-response curve was established for the potent stimulator (Sin 1) of the enzyme guanylate cyclase. In the presence of MB the dose-response curve for Sin 1 was shifted to the right with an increase in the ED50 for Sin 1 from 44 microM for the control to 85 microM for the MB group. In Study III, baseline pulmonary artery pressure was increased with U46619, and the hypoxic pressor response was increased (28.9 +/- 2.5 cmH2O), but halothane again caused a 50% decrease (11.0 +/- 1.8 cmH2O) in the response to hypoxia. In summary, when soluble guanylate cyclase activity is inhibited by MB, the inhibition of hypoxic pulmonary vasoconstriction by halothane, isoflurane, or enflurane was unaltered, and release of endothelium-derived relaxing factor (EDRF) is therefore not an essential mechanism underlying this action.