Situations vacant the shortage of midwives in New Zealand.
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Cultural Characteristics↗
Biomedical subjects
S Stewart
Publications and source records attributed to S Stewart.
Characterization of the acidic domain of the IE1 regulatory protein from Orgyia pseudotsugata multicapsid nucleopolyhedrovirus.
This study presents a detailed analysis of the acidic N-terminal region of the Orgyia pseudotsugata multicapsid nucleopolyhedrovirus (OpMNPV) transactivator IE1. The N-terminal region of IE1 is rich in acidic amino acids and has been hypothesized to be an acidic activation domain. Removal of the N-terminal 126 amino acids containing the acidic domain of IE1 resulted in complete loss of transactivation activity, indicating that this region is essential for transactivation. The OpMNPV acidic domain was replaced with the archetype acidic activation domain from VP16 and the acid-rich region of Autographa californica multicapsid NPV (AcMNPV) IE1. These chimeric constructs were fully capable of transactivation in transient assays. The chimeric OpMNPV IE1s containing the herpes simplex virus VP16 and AcMNPV IE1 acidic activation domains consistently transactivated a reporter gene to higher levels than the OpMNPV IE1 acidic activation domain. Transactivation by the chimeric constructs is enhanced synergistically when cotransfected with IE2 into Lymantria dispar and Spodoptera frugiperda cells. Both N- to C-terminal and C- to N-terminal deletions of the OpMNPV acidic activation domain were constructed to define functional domains within the OpMNPV IE1 acidic activation domain. At least two potential activation domains were identified. Within each of these domains, two core regions at amino acids 28-43 and amino acids 113-124 were identified that were similar to core regions of VP16 and GAL4, which contain predominately acidic and bulky hydrophobic amino acids.
Amino Acid Sequence↗
Cloning and characterization of GETS-1, a goldfish Ets family member that functions as a transcriptional repressor in muscle.
An Ets transcription factor family member, GETS-1, was cloned from a goldfish retina cDNA library. GETS-1 contains a conserved Ets DNA-binding domain at its N-terminus and is most similar to ternary complex factor (TCF) serum-response-factor protein-1a (SAP-1a). GETS-1 is expressed in many tissues, but is enriched in retina and brain. As with the TCFs SAP-1a and ets-related protein (ERP), overexpression of the GETS-1 promoter suppresses nicotinic acetylcholine receptor epsilon-subunit gene expression in cultured muscle cells. A consensus Ets binding site sequence in the promoter of the epsilon-subunit gene is required for GETS-1-mediated repression. GETS-1 repressor activity is abrogated by overexpression of an activated Ras/mitogen-activated protein kinase (MAP kinase) or by mutation of Ser-405, a MAP kinase phosphorylation site in GETS-1. Fusion proteins created between GETS-1 and the Gal4 DNA-binding domain show that, like other TCFs, GETS-1 contains a C-terminal activation domain that is activated by a Ras/MAP kinase signalling cascade. Interestingly, mutation of Ser-405 located within this activation domain abrogated transcriptional activation of the fusion protein.
Amino Acid Sequence↗
Cost-effectiveness analysis comparing liposomal anthracyclines in the treatment of AIDS-related Kaposi's sarcoma.
Liposomal formulations have been shown to alter the efficacy and toxicity profiles of anthracylines for patients with HIV-related advanced Kaposi's sarcoma (KS). Using decision-analysis models, the costs and cost-effectiveness of the two U.S. Food and Drug Administration (FDA)-approved liposomal formulations of these agents were estimated. Estimates of costs, effectiveness, and cost-effectiveness were derived from clinical trial data of separate, randomized phase III trials of pegylated liposomal doxorubicin (20 mg/m2 every 3 weeks) and liposomal daunorubicin (40 mg/m2 every 2 weeks). Clinical response rates were 59% for pegylated liposomal doxorubicin and 25% for liposomal daunorubicin. Despite higher acquisition costs for pegylated liposomal doxorubicin, total estimated costs of treatment for KS and chemotherapy-related hematologic toxicities were similar ($7,066 U.S. compared with $6,621 U.S. for liposomal daunorubicin). Cost-effectiveness profiles, defined as average costs per responder, favored pegylated liposomal doxorubicin ($11,976 U.S./responder versus $26,483 U.S./responder for liposomal daunorubicin), reflecting the higher reported response rate in the phase III trial. Sensitivity analyses suggested that the costs and cost-effectiveness results would not differ markedly when evaluated over a range of assumptions, including response rate, neutropenia rate, and dosage variations.
Acquired Immunodeficiency Syndrome↗
Effects of a home-based intervention among patients with congestive heart failure discharged from acute hospital care.
BACKGROUND: We examined the effect of a home-based intervention (HBI) on readmission and death among "high-risk" patients with congestive heart failure discharged home from acute hospital care. METHODS: Hospitalized patients with congestive heart failure and impaired systolic function, intolerance to exercise, and a history of 1 or more hospital admissions for acute heart failure were randomized to either usual care (n=48) or HBI at 1 week after discharge (n=49). Home-based intervention comprised a single home visit (by a nurse and pharmacist) to optimize medication management, identify early clinical deterioration, and intensify medical follow-up and caregiver vigilance as appropriate. The primary end point of the study was frequency of unplanned readmissions plus out-of-hospital deaths within 6 months of discharge. Secondary end points included duration of hospital stay and overall mortality. RESULTS: During follow-up, patients in the HBI group had fewer unplanned readmissions (36 vs 63; P=.03) and fewer out-of-hospital deaths (1 vs 5; P=.11): 0.8+/-0.9 vs 1.4+/-1.8 (mean +/- SD) events per patient assigned to HBI and usual care, respectively (P=.03). Patients in the HBI group also had fewer days of hospitalization (261 vs 452; P=.05) and fewer total deaths (6 vs 12; P=.11). Patients assigned to usual care were more likely to experience 3 or more readmissions for acute heart failure (P=.02). Predictors of unplanned readmission were (1) 14 days or more of unplanned readmission during the 6 months before study entry (odds ratio [OR], 5.2; 95% confidence interval [CI], 1.8-16.2), (2) previous admission for acute myocardial ischemia (OR, 3.3; 95% CI, 1.2-9.1), and (3) an albumin plasma concentration of 38 g/L or less (OR, 2.4; 95% CI, 1.2-6.0). Home-based intervention was also associated with a trend toward reduced risk of unplanned readmission (OR, 0.4; 95% CI, 0.2-1.1). CONCLUSION: Among a cohort of high-risk patients with congestive heart failure, HBI was associated with reduced frequency of unplanned readmissions plus out-of-hospital deaths within 6 months of discharge from the hospital.
Acute Disease↗
The kinase suppressor of Ras (KSR) modulates growth factor and Ras signaling by uncoupling Elk-1 phosphorylation from MAP kinase activation.
The Ras GTPase plays an essential role in many cellular signal transduction events. Activation of the mitogen activated protein (MAP) kinase is a primary consequence of Ras activation and plays a key role in mediating Ras signal transduction. A novel kinase, KSR, has recently been functionally isolated as a positive regulator of Ras signaling in Caenorhabditis elegans vulval induction and Drosophila photoreceptor differentiation. We have examined the effect of KSR on growth factor and Ras-induced MAP kinase signaling in mammalian cells. Surprisingly, we observed that KSR specifically blocks EGF and Ras-induced phosphorylation and activation of ternary complex factors (TCF), physiological substrates of MAP kinases, without affecting the activation of MAP kinase itself. A kinase-deficient mutant of KSR, KSR-RM, appears to function as a dominant interfering mutant which elevates phosphorylation of Elk-1, a member of the TCF family, and Elk-1-dependent transcription. The effect of KSR on Elk-1 was significantly decreased by inhibition of calcineurin, a putative Elk-1 phosphatase. These observations demonstrate that KSR is capable of uncoupling the MAP kinase activation from its target phosphorylation, and thus provide a novel mechanism for modulating the Ras-MAP kinase signaling pathway. This study provides the first evidence that signal output of MAP kinase cascades is subject to regulation at a level independent of MAP kinase activity.
3T3 Cells↗
Aspergillus infection of the respiratory tract after lung transplantation: chest radiographic and CT findings.
The objective of our study was to assess radiographic and CT findings in lung transplant patients with evidence of Aspergillus colonization or infection of the airways and correlate the findings with clinical, laboratory, bronchoalveolar lavage, biopsy and autopsy findings. The records of 189 patients who had undergone lung transplantation were retrospectively reviewed for evidence of Aspergillus colonization or infection of the airways. Aspergillus was demonstrated by culture or microscopy of sputum or bronchoalveolar lavage fluid or histologically from lung biopsies or postmortem studies in 44 patients (23 %). Notes and radiographs were available for analysis in 30 patients. In 12 of the 30 patients (40 %) chest radiographs remained normal. In 11 of 18 patients with abnormal radiographs pulmonary abnormalities were attributed to invasive pulmonary aspergillosis (IPA) in the absence of other causes for pulmonary abnormalities (8 patients) or because of histological demonstration of IPA (3 patients). In these 11 patients initial radiographic abnormalities were focal areas of patchy consolidation (8 patients), ill-defined pulmonary nodules (2 patients) or a combination of both (1 patient). In some of the lesions cavitation was demonstrated subsequently. At CT a "halo" of decreased density was demonstrated in some of the nodules and lesion morphology and location were shown more precisely. Demonstration of Aspergillus from the respiratory tract after lung transplantation does not necessarily reflect IPA but may represent colonization of the airways or semi-invasive aspergillosis. The findings in patients with IPA did not differ from those described in the literature in other immunocompromised patients, suggesting that surgical disruption of lymphatic drainage and nervous supply or effects of preservation and transport of the transplant lung do not affect the radiographic appearances.
Adult↗
High-resolution computed tomographic appearance of MALToma of the lung.
MALToma of the lung is rare and advances in molecular techniques have only recently allowed accurate diagnostic classification of the previously termed "pseudolymphomas" by demonstrating that many are monoclonal B-cell proliferations of MALT tissue and therefore true low-grade lymphomas. No significant previous contribution was found in the literature regarding the high-resolution CT appearance (HRCT) of these tumours. We describe the high-resolution CT appearances in five cases presenting to our institution from 1994 to 1997. The HRCT scans (1-mm sections at 10- to 15-mm intervals) were performed as the opacities seen radiographically were thought to be part of a diffuse lung process. In one patient a spiral sequence was performed through the main airway. Multifocal, ill-defined nodules containing air bronchograms were seen in four cases and focal lobar consolidation in one case. Interlobular septal thickening, centrilobular micronodules and bronchial wall thickening were seen in two cases. Mediastinal lymphadenopathy and pleural reaction do not appear to be characteristic features. The appearance of multifocal consolidation is similar to that seen in bronchoalveolar cell carcinoma and cryptogenic organising pneumonia.
Adenocarcinoma, Bronchiolo-Alveolar↗
Knotted ureteral stent: a minimally invasive technique for removal.
PURPOSE: We describe a useful technique for untying a knotted ureteral catheter. MATERIALS AND METHODS: An Amplatz super stiff guide wire was advanced through the lumen of the stent and with uniform force the knot was untied. RESULTS: The knot was untied and the stent was removed. A nephrostomy tube or other more invasive techniques for removal were avoided. CONCLUSIONS: An Amplatz super stiff guide wire passed retrograde via the ureteral stent lumen should be considered as a valid alternative to percutaneous removal of a knotted ureteral stent.
Aged↗
Complications employing the holmium:YAG laser.
We report the operative and early postoperative complications and limitations in 133 patients treated with the holmium laser. Complications included urinary tract infection (N = 3), postoperative bradycardia (1), inverted T-waves (1), intractable flank pain (1), urinary retention (1), inability to access a lower-pole calix with a 365-microm fiber (9), stone migration (5), and termination of procedure because of poor visibility (2). No ureteral perforations or strictures occurred, and no complications were directly attributable to the laser. The holmium laser was capable of fragmenting all urinary calculi in this study. In our initial experience, the holmium laser is safe and effective in the treatment of urinary pathology. Use of laser fibers larger than 200 microm occasionally limits deflection of the endoscope into a lower-pole or dependent calix.
Adolescent↗
Effects of home-based intervention on unplanned readmissions and out-of-hospital deaths.
OBJECTIVE: To determine the effect of a home-based intervention (HBI) on the frequency of unplanned readmission and out-of-hospital death among patients discharged home from acute hospital care. DESIGN: A randomized controlled trial comparing HBI with usual care (UC). SETTING: A tertiary referral hospital servicing the northwestern region of Adelaide, South Australia. PARTICIPANTS: Medical and surgical patients (n = 762) discharged home after hospitalization. INTERVENTION: Home-based intervention (n = 381) consisted of counseling of all patients before discharge followed by a single home visit (by a nurse and pharmacist) to those patients considered to be at high risk of readmission (n = 314) in order to optimize compliance with and knowledge of the treatment regimen, identify early clinical deterioration, and intensify follow-up of such patients where appropriate. MEASUREMENTS: The primary endpoint was the number of unplanned readmissions plus out-of-hospital deaths over a 6-month follow-up period. RESULTS: During the study follow-up, the major endpoint occurred most commonly in the UC group (217 vs 155 episodes: P < .001). Overall, the HBI group demonstrated fewer unplanned readmissions (154 vs 197: P = .022), out-of-hospital deaths (1 vs. 20: P < .001), total deaths (12 vs. 29: P = .006), emergency department attendances (236 vs 314: P < .001), and total days of hospitalization (1452 vs 1766: P < .001). There was a disproportionate reduction in multiple events among HBI patients (P = .035). Hospital-based costs of health care during study follow-up tended to be lower in the HBI group ($A2190 vs $A2680 per patient: P = .102). Mean cost of HBI was $A190 per patient visited, whereas other community-based health care costs were similar for both groups. CONCLUSIONS: Among high-risk patients discharged from acute hospital care, HBI is beneficial in limiting unplanned readmissions and reducing risk of out-of-hospital death. It may be particularly cost-effective if applied selectively to patients with a history of frequent unplanned hospital admission.
Aged↗
Nurse led, multidisciplinary intervention in chronic heart failure.
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Heart Failure↗
Public health: where should we be in 10 years?
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Health Services↗
Alpha-1 antitrypsin deficiency alleles and severe cystic fibrosis lung disease.
BACKGROUND: Alpha-1 antitrypsin (alpha 1-AT) is the most abundant proteinase inhibitor within the lung. We have recently reported the surprising observation that cystic fibrosis patients with mild to moderate deficiency of alpha 1-antitrypsin have significantly better pulmonary function than non-deficient patients. This study may have been biased as it did not include the most severely affected patients who have died in childhood or those who have undergone orthotopic lung transplantation. The prevalence of alpha 1-antitrypsin deficiency alleles in this most severely affected group of patients with cystic fibrosis was therefore assessed. METHODS: DNA was obtained from neonatal blood spots from children with cystic fibrosis who had died from pulmonary disease and from formalin fixed lung tissue from transplanted cystic fibrosis patients. The common S and Z deficiency alleles of alpha 1-AT were sought by amplification mutagenesis of the appropriate region of the alpha 1-AT gene followed by restriction enzyme digestion with Xmn I and Taq I, respectively. RESULTS: Seventy-nine patients were identified (seven dead, 72 transplanted). Two patients (2.5%) were heterozygous for the Z allele of alpha 1-AT and four (5.1%) were heterozygous for the S allele. This is not significantly different from the incidence in the normal population of 4% and 8% for the S and Z alleles, respectively. CONCLUSIONS: These data support previous findings that deficiency of alpha 1-AT is not associated with more severe pulmonary disease in cystic fibrosis and may be associated with milder lung disease. Further work is needed to clarify the mechanisms underlying the progressive lung damage in cystic fibrosis.
Adult↗
Improving surgical resection rate in lung cancer.
BACKGROUND: Surgical resection is the recognised treatment of choice for patients with stage I or II non-small cell lung cancer (NSCLC). In the UK surgical resection rates have remained far lower (< 10%) than those achieved in Europe and the USA (> 20%), despite the recent introduction of fast access investigation units. It remains unclear therefore why UK surgical resection rates lag so far behind those of other countries. METHODS: A new quick access two stop investigation service was established at Papworth in November 1995 to investigate all patients presenting to any of three surrounding health districts with suspected lung cancer. Once staging was complete, all patients with confirmed lung cancer were reviewed by a multidisciplinary team which included an oncologist and a thoracic surgeon. Time from presentation to definitive treatment and surgical resection rates were reviewed. RESULTS: Two hundred and nine (76%) of a total of 275 consecutive patients investigated had confirmed lung cancer (28 small cell, 181 non-small cell). Of the remainder, eight patients (2%) had metastatic disease, four (1%) had other thoracic malignancy (thymoma, mesothelioma), four patients (1%) had benign thoracic tumours, and 50 (18%) had other non-malignant diseases. Of the 181 patients with non-small cell primary lung cancer, 47 (25%) underwent successful surgical resection, of whom 59% had stage I and 21% stage II disease. The failed thoracotomy rate was 11%. Median time from presentation at the peripheral clinic to surgical resection was 5 weeks (range 1-13). CONCLUSION: Quick access investigation, high histological confirmation rates, routine CT scanning, and review of every patient with confirmed lung cancer by a thoracic surgeon led to a substantial increase in the successful surgical resection rate. These results support the growing concern that many patients with operable tumours are being denied the chance of curative surgery in our present system.
Aged↗
Randomized comparative trial of pegylated liposomal doxorubicin versus bleomycin and vincristine in the treatment of AIDS-related Kaposi's sarcoma. International Pegylated Liposomal Doxorubicin Study Group.
PURPOSE: Cytotoxic chemotherapy is frequently required for the more severe manifestations of human immunodeficiency virus (HIV)-related Kaposi's sarcoma. Combinations of bleomycin and vincristine (BV) or BV with the addition of doxorubicin (ABV) are the most commonly used regimens against which new treatments may be compared. We report a multicenter phase III study that compared pegylated liposomal doxorubicin (PLD) to the BV combination. PATIENTS AND METHODS: We conducted a randomized study that compared PLD 20 mg/m2 with a combination of bleomycin 15 IU/m2 and vincristine 2 mg in 241 patients with HIV-related Kaposi's sarcoma. Both regimens were administered by intravenous infusion every 3 weeks for six cycles. RESULTS: A total of 121 patients received PLD and 120 patients the BV combination. The response to PLD was superior to BV: 58.7% versus 23.3% (P < .001). Patients who were randomized to receive BV, however, were more likely to terminate treatment early because of an adverse event (26.7% v 10.7%), and fewer completed the full six cycles of treatment (30.8% v 55.4%). Treatment with BV was associated with a significantly higher incidence of peripheral neuropathy (P < .001), whereas PLD treatment was more commonly associated with neutropenia and delays in receiving treatment (P < or = .001). CONCLUSION: Pegylated liposomal doxorubicin is an effective treatment for HIV-related Kaposi's sarcoma with a higher response rate than the BV combination. It is well tolerated but more myelosuppressive.
Acquired Immunodeficiency Syndrome↗
Nontraumatic rupture of the thoracic aorta: chest radiographic features of an often unrecognized condition.
OBJECTIVE: The purpose of our study was to evaluate chest radiographic features of nontraumatic mediastinal hemorrhage occurring after extrapericardial thoracic aorta rupture. MATERIALS AND METHODS: Twenty-seven consecutive chest radiographs obtained at admission of patients with hemorrhage from ruptured thoracic aorta aneurysms, aortic dissections, or penetrating aortic ulcers were randomized with radiographs of 23 subjects with nonruptured thoracic aorta aneurysms, 20 subjects with nonruptured dissections, and 20 control subjects. Diagnoses were established by interpreting CT scans, MR images, and findings at surgery or autopsy or both. A retrospective review was performed by three independent radiologists who were unaware of patients' diagnoses. Observers assessed 20 parameters on each of these 90 radiographs and summarized their findings with final diagnoses. The 20 parameters were analyzed with logistic regression and rank correlation to determine the best predictors of hemorrhage. RESULTS: Logistic regression analysis showed a combination of obscuration or convexity of the aorticopulmonary window and a displaced left paraspinal interface to be the most useful predictor of hemorrhage (p < .05). Rank correlation analysis indicated obscuration or convexity of the aorticopulmonary window; a displaced left paraspinal interface; enlarged aortic knob width; enlarged thoracic aorta size; an enlarged, obscured, or irregular aortic margin; and left pleural or extrapleural space fluid were potential individual predictors of hemorrhage (p < .05). Observer sensitivities for recognizing hemorrhage were 30-59% and specificities were 83-91%. Sensitivities for distinguishing an abnormal (n = 70) from a normal (n = 20) mediastinum were 79-90% and specificities were 65-90%. CONCLUSION: Obscuration or convexity of the aorticopulmonary window and a displaced left paraspinal interface on radiographs may indicate mediastinal hemorrhage. Further imaging is required to establish a definitive diagnosis.
Adult↗