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S Webster

Publications and source records attributed to S Webster.

At least 19 recordsLinked to original sources
PubMed2004

The multidisciplinary approach to mental health crisis management: an Australian example.

Changes within the Australian health care system have led many people with mental health disorders to use emergency departments as the point of access to mental health services. Staff in emergency departments are not necessarily equipped to assess the needs of such clients. This paper briefly describes the development of a multidisciplinary mental health liaison team, within the emergency department of one hospital in Sydney, which was designed to assist both staff and clients. Available evidence suggests the implementation of the team has been a success, however, more research is required to confirm the effectiveness of this approach. Questions are raised about appropriate referral and follow-up for some clients. The study also found deficiencies in the method of routine data collection (Emergency Department Identification System), which makes formal auditing of the team and the services it provides a difficult task.

Adolescent↗
PubMed2004

Optical properties of vanadium oxide nanotubes.

The optical properties of vanadium oxide nanotube dispersions have been characterized using visible and near infrared absorption spectroscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, and nonlinear transmission of optical intensities in the visible and near infrared. Using transmission electron microscopy, optical properties have been correlated to the occurrence of two distinct nanoparticle morphologies: nanotubes and unrolled tubes or platelets. Raman spectroscopy indicates that color changes associated with tub unrolling can be attributed to V2O5 formation. The nanotube and platelet morphologies both show strong optical intensity limiting at 532 and 1064 nm. However, dependencies on repetition rate suggest that slightly different mechanisms dominate at the two wavelengths.

Crystallization↗
PubMed2001

Systemic delivery of an adenoviral vector encoding canine factor VIII results in short-term phenotypic correction, inhibitor development, and biphasic liver toxicity in hemophilia A dogs.

Canine hemophilia A closely mimics the human disease and has been used previously in the development of factor VIII (FVIII) protein replacement products. FVIII-deficient dogs were studied to evaluate an in vivo gene therapy approach using an E1/E2a/E3-deficient adenoviral vector encoding canine FVIII. Results demonstrated a high level of expression of the canine protein and complete phenotypic correction of the coagulation defect in all 4 treated animals. However, FVIII expression was short-term, lasting 5 to 10 days following vector infusion. All 4 dogs displayed a biphasic liver toxicity, a transient drop in platelets, and development of anticanine FVIII antibody. Canine FVIII inhibitor development was transient in 2 of the 4 treated animals. These data demonstrate that systemic delivery of attenuated adenoviral vectors resulted in liver toxicity and hematologic changes. Therefore, the development of further attenuated adenoviral vectors encoding canine FVIII will be required to improve vector safety and reduce the risk of immunologic sequelae, and may allow achievement of sustained phenotypic correction of canine hemophilia A.

Adenoviridae↗
PubMed2001

Comorbidities and quality of life in patients with interferon-refractory chronic hepatitis C.

OBJECTIVES: Patients with chronic hepatitis C (HCV) consistently report a reduction in multiple domains of health-related quality of life (HRQOL) that does not correlate with liver disease severity. This may in part be due to the use of insensitive HRQOL instruments or extrahepatic factors that independently influence HRQOL. We hypothesized that a past history of substance abuse or active medical and psychiatric comorbidities would correlate with HRQOL scores. METHODS: In 107 patients who had failed previous interferon therapy, HRQOL was measured by using the modified SF-36, a disease-specific instrument, and the Health Utilities Index (HUI) Mark III, a generic instrument. RESULTS: Multiple SF-36 subscale and summary scores as well as the HUI Mark III attributes of emotion and pain were significantly reduced in the study population compared with healthy controls (p < 0.001). Serum alanine aminotransferase and HCV RNA levels, HCV genotype, liver histology, and HCV risk factors as well as demographic variables did not correlate with modified SF-36 and HUI scores. In addition, a history of alcohol abuse or dependency and intravenous drug use or dependency, identified in 52 and 51% of participants, respectively, did not correlate with HRQOL scores. However, the presence of one or more active medical comorbidities, defined as a chronic medical condition requiring treatment and monitoring, was significantly associated with both the modified SF-36 scores and HUI attribute deficits (p < 0.001). In particular, painful medical comorbidities or depressed mood requiring treatment were significantly associated with modified SF-36 scores and with HUI attribute deficits and utility scores (p < 0.001). CONCLUSIONS: Active medical and psychiatric comorbidities may account for some of the reduction and variability in HRQOL scores in patients with chronic HCV who have failed previous interferon therapy. Future studies that control for the presence of active comorbidities in large groups of treatment naive patients with varying severity of chronic HCV are needed to confirm these findings.

Adult↗
PubMed2000

Predictive value of plasma human chorionic gonadotrophin following assisted conception treatment.

A total of 429 pregnancies after assisted conception treatment was analysed, using receiver operator characteristic curves. The best balance between sensitivity and specificity for predicting viable (single and multiple births) and non-viable (fetal heart positive abortions, ectopic and biochemical pregnancies) outcomes was human chorionic gonadotrophin (HCG) 50 IU/l on day 14 and 200 IU/l on day 21 after treatment. Utilizing these indices all pregnancies could be classified into one of four groups. In group A (day 14 HCG <50 IU/l and day 21 <200 IU/l), the probability of a birth was 0%, pregnancy loss 72% and ectopic pregnancy 28%. Conversely for group D (day 14 HCG >50 IU/l and day 21 >1000 IU/l), the likelihood of a birth was 90%, pregnancy loss 8% and ectopic pregnancy only 1%. Between groups A and D there was, as expected, a gradually shifting balance in favour of a reduction in ectopic (28, 13, 3, 1%) and biochemical pregnancies (70, 36, 33, 2%) and an increase in fetal heart positive pregnancy losses (2, 6, 13, 7%) and births (0, 44, 50, 90%). The majority of multiple pregnancies (98%) occurred in group D. Two accurately linked HCG measurements allowed a greater predictive accuracy of pregnancy outcome than could be obtained using either alone.

Adult↗
PubMed1999

Donor variation in the growth properties and osteogenic potential of human marrow stromal cells.

Human marrow stromal cells (MSCs) were isolated from posterior illiac crest marrow aspirates obtained from 17 healthy donors, ages 19-45 years, with no apparent physical disability. First passage hMSCs exhibited growth rates in vitro that varied up to 12-fold between donors. No correlation between growth rate and the age or gender of the donor was evident (P </= 0.05). When hMSCs were cultured without passage for eight days (subconfluent cultures) or 22 days (confluent cultures) in the absence of any osteogenic agonists, levels of alkaline phosphatase enzyme activity varied 40-fold and 10-fold, respectively, between donors. When exposed to osteo-inductive media, donor populations also showed dramatic differences in levels of bone-specific gene induction. Collectively, these data demonstrate that hMSC cultures are composed of a heterogeneous mixture of cells at various stages of differentiation and with distinct osteogenic potentials. Differences in both growth rate and ALP activity were evident in hMSC cultures established from multiple aspirates obtained over a six month period from the same donors. Therefore, it appears that cellular heterogeneity produced by the method of harvest is propagated within and among different donor populations during culture expansion in vitro.

Adult↗
PubMed1999

Alternative pathway of complement is activated during in vitro ventricular assist.

BACKGROUND: Although ventricular assist devices (VAD) have improved survival in selected patients, their use continues to be complicated by thromboembolism and end-organ failure. Complement activation may play a role in the pathogenesis of these complications. Previous studies have found that the complement common terminal pathway is activated during VAD circulation. C3a levels rise dramatically during VAD use. Because the C3a fragment is generated by either the alternative or classical pathway, the purpose of this study is to determine the relative importance of the respective pathways in complement activation during in vitro VAD circulation. METHODS: Six in vitro VAD circuits were simulated for 3 days using 450 mL of human blood. Temperature, activated clotting time, pH, pCO2, pO2, Ca2+, and glucose were maintained at physiologic levels. Enzyme immunoassays were used to measure concentrations of fragment Bb to indicate alternative pathway activation and fragment C4d to indicate classical pathway activation. RESULTS: Fragment Bb concentrations rise from 1.92 to 10.77 micrograms/mL during the first 6 hours of circulation. Thereafter, Bb levels plateau. C4d concentrations slowly rise from a baseline of 1.49 to 6.84 micrograms/mL in 72 hours. CONCLUSIONS: These findings suggest that both the alternative and classical pathways of complement are activated during VAD circulation. Alternative pathway activation precedes classical pathway activation during in vitro VAD circulation and may be of greater clinical importance during clinical VAD circulation.

Assisted Circulation↗
PubMed1998

Irreversible dimerization/tetramerization and post-translational modifications inhibit proteolytic degradation of A beta peptides of Alzheimer's disease.

Experimental evidence increasingly implicates the beta-amyloid peptide in the pathogenesis of Alzheimer's disease. Beta-amyloid filaments dramatically accumulate in the neuritic plaques and vascular deposits as the result of the brain's inability to clear these structures. In this paper, we demonstrate that in addition to the intrinsic stability of A beta N-42, the time dependent generation of irreversibly associated A beta dimers and tetramers incorporated into A beta filaments are themselves resistant to proteolytic degradation. The presence of post-translational modifications such as isomerization of aspartyls 1 and 7, cyclization of glutamyl 3 to pyroglutamyl and oxidation of methionyl 35, further contribute to the insolubility and stability of A beta. All these factors promote the accumulation of neurotoxic amyloid in the brains of patients with Alzheimer's disease, and should be considered in therapeutic strategies directed towards the dissociation of the brain's A beta filaments.

Alzheimer Disease↗
PubMed1998

Complications of obstetric epidural analgesia and anaesthesia: a prospective analysis of 10,995 cases.

Although epidural anaesthesia and analgesia are widely used in obstetrics, there are no large contemporary prospective series detailing associated complications. Prospective data was collected on all obstetric epidural blocks performed for labour and delivery in a single institution between July 1989 and August 1994. A data entry sheet was compiled and entered onto a computer database. Confidence intervals for proportions were calculated using standard methods. Information from 10 995 epidural blocks was analysed. Epidural analgesia in labour was the primary indication in 7648, and anaesthesia for caesarean section in 3311. Minor complications included failed or abandoned insertion (incidence 0.5%), reinsertion of the epidural catheter (5%), and inadequate anaesthesia (1.7%) or analgesia (0.9%). Three percent were associated with venous puncture and 0.6% with accidental dural puncture. Maternal mortality was zero. Unexpectedly high blocks occurred on eight occasions (0.07%), two requiring intubation and ventilation. Three women (0.06%) experienced mild respiratory depression after postoperative epidural opioid. There was no major local anaesthetic toxicity or neurological deficit. The incidence of potentially life-threatening morbidity was thus 0.02% although in both cases outcome was good. The only persisting complication was neurological, an apparent epidural catheter-induced traumatic mononeuropathy.

Journal Article↗
PubMed1998

High-protein diets augment albuminuria in rats with Heymann nephritis by angiotensin II-dependent and -independent mechanisms.

Urinary albumin excretion (U(alb)V) increases following dietary protein augmentation (DPA) in nephrotic humans and rats. Angiotensin-converting enzyme inhibitors (ACEI) blunt, but do not entirely prevent, increased U(alb)V at doses that reduce blood pressure and entirely block the pressor effect of exogenously administered angiotensin I (Ang-I), suggesting that angiotensin II (Ang-II) might not mediate the effect of DPA on U(alb)V. We determined the effect of losartan (Los), a specific Ang-II receptor antagonist, and compared its effect to that of enalapril (En), an ACEI, on DPA-induced increase in U(alb)V in rats with passive Heymann nephritis (HN). When Los was administered to HN rats for 48 h prior to DPA from 8.5 to 40% casein. U(alb)V increased in an identical fashion in treated and untreated rats, even though Los caused hypotension and prevented the pressor effect of infused Ang-II. Only on day 6 after DPA did U(alb)V decrease. We then measured the effect of duration of pretreatment with Los on Ang-II binding to isolated glomeruli. Maximal inhibition of Ang-II binding required treatment with Los for 6 days. We then pretreated HN rats with either En or Los for 6 days prior to DPA. In contrast to administration of Los for 2 days prior to DPA, pretreatment with either Los or En for 6 days entirely prevented any increase in U(alb)V. We then increased dietary NaCl from 0.2% to 2% (HS) to determine whether En or Los would modulate U(alb)V after DPA when Ang-II activity was suppressed. En reduced the DPA-mediated increase in U(alb)V regardless of dietary NaCl, while Los was effective only in when dietary NaCl was reduced (0.2%), suggesting that under these conditions ACEI reduces U(alb)V by a mechanism that is independent of inhibition of Ang-II and that high protein diets augment U(alb)V by both Ang-II-independent and Ang-II-dependent mechanisms.

Albuminuria↗
PubMed1998

Phase II study of dexverapamil plus anthracycline in patients with metastatic breast cancer who have progressed on the same anthracycline regimen.

The purpose of this study is to evaluate whether metastatic breast cancer that has progressed on an anthracycline-containing drug regimen will subsequently respond to that identical regimen if dexverapamil, a modulator of P-glycoprotein-mediated drug resistance, is given concomitantly. Eligible patients received 180 mg/m2 dexverapamil every 6 h for 15 doses with the anthracycline administered 30 min after the seventh dose. Blood for dexverapamil levels was drawn before and 30 min after this dose. When possible, biopsies were obtained to measure mdr-1 expression by reverse transcription-PCR and by image cytometry. Of the 21 patients entered onto the trial, 20 were evaluable for response. There were two partial responses (10%) that both lasted for 6 months, and two additional patients had stable disease. Seven patients had asymptomatic cardiotoxicity consisting of hypotension (24%), bradycardia (5%), or prolongation of the P-R interval (14%). Two patients developed acute congestive heart failure, one on dexverapamil and one 10 days after stopping it. Dexverapamil did not seem to increase anthracycline toxicity. The median trough dexverapamil plus norverapamil level on day 3 was 1110 ng/ml (range, 186-3385 ng/ml), and the median peak level was 2164 ng/ml (range, 964-8382 ng/ml). There was poor correlation between reverse transcription-PCR and image cytometry for the level of mdr-1 expression. Because dexverapamil has been shown to affect doxorubicin pharmacokinetics subsequent to the initiation of this trial, it cannot be concluded that the responses seen were necessarily due to P-glycoprotein inhibition. Additional studies are necessary to determine whether mdr-1 modulators can reverse clinical drug resistance in breast cancer patients. The intrinsic cardiotoxicity of dexverapamil makes it less suitable for such studies than several other available agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Abnormalities of heart rate and rhythm in bovine spongiform encephalopathy.

Heart rates of healthy cows and cows suspected of having bovine spongiform encephalopathy were measured by auscultation and by a portable cardiac monitor. Bradycardia was demonstrated in suspect cases which were confirmed histopathologically. Disturbances in cardiac rhythm were also evident in some cases. Healthy cows deprived of food exhibited bradycardia. The administration of pharmacological doses of atropine indicated that bradycardia in BSE was mediated by increased vagal influence, suggesting that the cardioinhibitory reflexes in the caudal brainstem were functionally altered by the disease.

Animals↗
PubMed1997

Aggregation state-dependent activation of the classical complement pathway by the amyloid beta peptide.

Activation of the classical complement pathway has been widely investigated in recent years as a potential mechanism for the neuronal loss and neuritic dystrophy characteristic of Alzheimer's disease (AD) pathogenesis. We have previously shown that amyloid beta peptide (A beta) is a potent activator of complement, and recent evidence suggesting that the assembly state of A beta is crucial to the progress of the disease prompted efforts to determine whether the ability of A beta to activate the classical complement pathway is a function of the aggregation state of the peptide. In this report, we show that the fibrillar aggregation state of A beta, as determined by thioflavin T fluorometry, electron microscopy, and staining with Congo red and thioflavine S, is precisely correlated with the ability of the peptide to induce the formation of activated fragments of the complement proteins C4 and C3. These results suggest that the classical complement pathway provides a mechanism whereby complement-dependent processes may contribute to neuronal injury in the proximity of fibrillar but not diffuse A beta deposits in the AD brain.

Amyloid beta-Peptides↗
PubMed1997

Charge-based binding of complement component C1q to the Alzheimer amyloid beta-peptide.

Activation of the classical pathway in Alzheimer's disease derives from the binding of the first protein, subcomponent C1q, to the amyloid beta-peptide (A beta). Analysis of the binding of C1q to A beta by competitive enzyme-linked immunosorbent assay shows that A beta fragments 1-16 and 1-28 but not 12-28 and 17-42 are capable of inhibiting the A beta/C1q interaction, implicating the A beta 1-11 region as the C1q binding site. Binding is also shown to be inhibited by conditions of high ionic strength, suggesting that charged side chains in the A beta 1-11 region are critical to the A beta/c1q interaction. Ultrastructural evidence of binding is provided by platinum replica electron microscopy. Along with a previous demonstration of the 14-26 region of the C1q A chain as the A beta binding site, these findings suggest that attractions between a negative charge cluster in A beta 1-11 and a positive charge cluster in C1qA14-26 mediate the binding of A beta and C1q.

Alzheimer Disease↗
PubMed1996

Relative efficacies of amyloid beta peptide (A beta) binding proteins in A beta aggregation.

The aggregation of amyloid beta peptide (A beta) into its fibrillar, cross beta-pleated configuration is generally viewed as a critical event in the pathophysiology of Alzheimer's disease (AD). A diverse group of molecules, the A beta binding proteins, has been evaluated for their effects on this process. However, most of these studies have used micromolar or greater reagent concentrations, and their different methods have not permitted quantitative comparisons of the efficacy of different A beta binding proteins in augmenting or inhibiting aggregation. In the present work we have undertaken a coherent analysis using fluorimetry of thioflavin T-stained experimental solutions. The complement protein C1q, serum amyloid P, and transthyretin significantly enhanced the formation of precipitable, cross beta-pleated aggregates in solutions of 800 nM A beta 1-42. Under these same experimental conditions, alpha 1-antichymotrypsin had no significant effect on the aggregation process, and both the E3 and E4 isoforms of apolipoprotein E were significant inhibitors. There was a non-significant trend toward the E3 isoform exhibiting greater inhibition than the E4 isoform. Of the aggregation-facilitating molecules, C1q was substantially and significantly the most potent.

Alzheimer Disease↗
PubMed1996

Four outbreaks of Salmonella enteritidis phage type 4 food poisoning linked to a single baker.

An outbreak of gastrointestinal illness occurred among a party of diners at a hotel in South Yorkshire. A case control study identified a gateau, from an outside supplier, as the likeliest vehicle of infection. Further gateaux from the same baker's premises and other outlets were examined microbiologically. Three other outbreaks of food poisoning in neighbouring districts were recognised and found to be associated with gateaux supplied by the same baker. A total of 32 cases were identified. Stool specimens from 24 cases grew Salmonella enteritidis phage type (PT) 4. The same organism was also grown from gateau in the domestic refrigerator of the chef of one hotel, cheesecake made by the same baker, and a gateau and ingredients from the baker's premises. The isolates of S. enteritidis PT4 were all fully sensitive to antibiotics, and had the same plasmid and pulsed field gel electrophoresis profiles. It is most likely that cross contamination occurred from infected raw eggs on the baker's premises. The control measures instituted probably prevented two further outbreaks, and the baker now uses only pasteurised eggs. The benefits of close cooperation between different local and health authority districts in the investigation of the outbreaks are discussed.

Disease Outbreaks↗