Turning a "blind eye" to vertical blinds in hospital wards.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to C Barker.
Explore the source record for details and available documents.
BACKGROUND/PURPOSE: Neutropenic enterocolitis (typhlitis) is a common consideration after bone marrow transplantation. This study reviews the authors' experience with abdominal pain and typhlitis in an active pediatric bone marrow transplant program. METHODS: The Pediatric Bone Marrow Transplant Program Database was reviewed for patients presenting with abdominal pain or typhlitis. RESULTS: From 1993 to 2000 a total of 142 transplants have been performed. Of these, 97 patients had abdominal pain, and 5 had radiologically proven typhlitis. Nonspecific abdominal pain developed on the 12 +/- 11th day posttransplant, whereas patients in whom typhlitis developed were diagnosed on day 15.5 +/- 7. All patients were treated with prophylactic antibiotics consisting of acyclovir, fluconazole, and septra. With the onset of abdominal pain, 73 of 97 patients were placed on therapeutic antibiotics; patients identified with typhlitis had amphotericin plus GCSF added. No clinical features differentiated abdominal pain patients from typhlitis. Oral feeding and time of discharge was similar in both groups. Surgical intervention was not required, and no patients died with typhlitis. CONCLUSIONS: Abdominal pain is a common symptom after bone marrow transplant; however, typhlitis is relatively rare, and surgical intervention was not required in this series. Broad-spectrum (including fungal) antibiotic therapy appears to be an effective treatment for typhlitis in this patient population.
Bone morphogenetic protein (BMP)-1, which belongs to the tolloid subgroup of astacin-like zinc metalloproteinases, cleaves the C-propeptides of procollagen at the physiologic site and is, therefore, a procollagen C-proteinase (PCP). Cleavage occurs between a specific alanine or glycine residue (depending on the procollagen chain) and an invariant aspartic acid residue in each of the three chains of procollagen. To learn more about how BMP-1 exhibits PCP activity we mapped the primary structure of BMP-1 onto the x-ray crystal structure of astacin and identified residues in the metalloproteinase domain of BMP-1 for subsequent site-directed mutagenesis studies. Recombinant wild-type and mutant BMP-1 were expressed in COS-7 cells and assayed for PCP activity using type I procollagen as the substrate. We showed that substitution of alanine for Glu(94), which occurs in the HEXXH zinc-binding motif of BMP-1, abolishes PCP activity. Furthermore, mutation of residues Lys(87) and Lys(176), which are located in the S1' pocket of the enzyme and are therefore adjacent to the P1' residue in the substrate, reduced the proteolytic activity of BMP-1 by approximately 50%. A surprising observation was that mutation of Cys(66) reduced the activity to 20%, suggesting that this residue is crucial for activity. Further experiments showed that Cys(66) and Cys(63), which are located in the tolloid-specific sequence Cys(63)-Gly(64)-Cys(65)-Cys(66) in the active site, most likely form a disulfide bridge.
The inability of the cattle pathogen Trypanosoma brucei brucei to infect humans is due to an innate factor in human serum termed Trypanosome Lytic Factor (TLF). Human haptoglobin-related protein is the proposed toxin in TLF and can exist either as a component of a minor subclass of high-density lipoprotein (TLF-1) or as a lipid free, high molecular weight protein complex (TLF-2). The trypanolytic activity of both TLF-1 and TLF-2 has been studied in vitro but their relative contributions to protection against T. b. brucei infection in vivo has not been established. In the present studies we show that treatment of T. b. brucei infected mice with TLF-1 resulted in a dose dependent decrease in parasite numbers but did not affect parasite numbers in mice infected with Trypanosoma brucei rhodesiense, the causative agent of the human sleeping sickness. Similarly, pretreatment of mice with TLF-1 resulted in protection against a challenge by T. b. brucei but had no effect on T. b. rhodesiense challenge. Induction of the acute phase protein haptoglobin, a natural antagonist of TLF-1, diminished but did not abolish the protection against trypanosome challenge. In addition, haptoglobin knockout mice showed higher levels of TLF-1 mediated protection against a T. b. brucei challenge. These results suggest that while TLF-1 is active in vivo, even in the presence of elevated levels of haptoglobin, its activity is modulated in a dose dependent fashion by haptoglobin in the circulation.
Standard therapy for advanced or metastatic colorectal cancer consists of 5-fluorouracil plus leucovorin (5-FU/LV) administered intravenously (i.v.). Capecitabine (Xeloda), an oral fluoropyrimidine carbamate which is preferentially activated by thymidine phosphorylase in tumour cells, mimics continuous 5-FU and is a recently developed alternative to i.v. 5-FU/LV. The choice of oral rather than intravenous treatment may affect medical resource use because the two regimens do not require the same intensity of medical intervention for drug administration, and have different toxicity profiles. Here we examine medical resource use in the first-line treatment of colorectal cancer patients with capecitabine compared with those receiving the Mayo Clinic regimen of 5-FU/LV. In a prospective, randomised phase III clinical trial, 602 patients with advanced or metastatic colorectal cancer recruited from 59 centres worldwide were randomised to treatment with either capecitabine or the Mayo regimen of 5-FU/LV. In addition to clinical efficacy and safety endpoints, data were collected on hospital visits required for drug administration, hospital admissions, and drugs and unscheduled consultations with physicians required for the treatment of adverse events. Capecitabine treatment in comparison to 5-FU/LV in advanced colorectal carcinoma resulted in superior response rates (26.6% versus 17.9%, P=0.013) and improved safety including less stomatitis and myelosuppression. Capecitabine patients required substantially fewer hospital visits for drug administration than 5-FU/LV patients. Medical resource use analysis showed that patients treated with capecitabine spent fewer days in hospital for the management of treatment related adverse events than did patients treated with 5-FU/LV. In addition, capecitabine reduced the requirement for expensive drugs, in particular antimicrobials fluconazole and 5-HT3-antagonists to manage adverse events. As anticipated with an oral home-based therapy patients receiving capecitabine needed more frequent unscheduled home, day care, office and telephone consultations with physicians. In the light of clinical results from the phase III trial demonstrating increased efficacy in terms of response rate, equivalent time to progression (TTP) and survival (OS), and a superior safety profile, the results from this medical resource assessment indicate that capecitabine treatment of colorectal cancer patients results in a substantial resource use saving relative to the Mayo Clinic regimen of 5-FU/LV. This benefit is derived principally from the avoidance of hospital visits for i.v. drug administration, less expensive drug therapy for the treatment of toxic side-effects, and fewer treatment-related hospitalisations required during the course of therapy for adverse drug reactions in comparison to patients treated with 5-FU/LV.
This study examined what parents of children with disabilities and special needs found helpful about belonging to mutual support groups. Quantitative data (based on 56 parents from 6 groups) indicated that members found the groups very helpful and were very satisfied with the support they received from their groups; they also described the groups as high in cohesion, expressiveness, task orientation, and self-discovery. A grounded theory analysis of focus group data (based on 43 parents from 5 of the groups) indicated that such support was helpful in three broad domains: (1) the sociopolitical, which involved developing a sense of control and agency in the outside world; (2) the interpersonal, which involved a sense of belonging to a community; and (3) the intraindividual, which involved self change. A central theme of identity change emerged as superordinate to these three categories.
OBJECTIVE: We sought to define the learning curve relative to the incidence and range of intraoperative problems and to establish guidelines for troubleshooting during the endovascular repair of infrarenal aortic aneurysms. METHODS: We prospectively evaluated our first 75 consecutive cases over a 12-month period and focused on perioperative critical events and adjunctive procedures as categorical outcome measures collected during the operation. Patients were separated into three groups on the basis of the date of their operation, such that group 1 consisted of our first 25 cases, group 2 our next 25 cases, and group 3 our last 25 cases. RESULTS: At least one critical event and adjunctive procedure marked 67 (89%) of 75 cases. In 51%, there were at least two critical events and adjunctive procedures. There were no immediate open conversions or intraoperative deaths. Access problems occurred in 28% of the 75 cases and were addressed by use of brachial-femoral artery access (30%), iliac artery/aortic bifurcation balloon angioplasty (8%), and iliofemoral conduits (4%). Graft foreshortening was the most common deployment event (44%), necessitating distal covered extensions. Iliac graft limb twists and kinks occurred in 12% of cases and were managed with balloon angioplasty and uncovered stents. General incidents included balloon ruptures (10%), arterial dissections (6%), iliac artery rupture (2.6%), and lower extremity ischemia (4%). The two cases of iliac artery rupture were managed with distal covered extensions, and there were no cases of atheroemboli. Intraoperative endoleaks were encountered in 44% of the cases and included proximal attachment sites (15%), distal attachment sites (9%), type 2 sources, and "blushes." Management of intraoperative endoleaks included proximal/distal covered extensions and re-ballooning. Our 30-day endoleak rate was 20%. The incidence of critical events did not decrease in the latter one third compared with the first two thirds of cases. CONCLUSIONS: Critical events occur frequently during endovascular repair of aortic aneurysms. The intraoperative problems range from the common endoleaks, access and deployment issues, and balloon ruptures, to rare but life-threatening complications such as iliac artery rupture. A toolbox of accessories that includes wires, catheters, large balloons, covered proximal and distal extensions, and uncovered stents is essential given the frequency of adjunctive procedures. Successful aortic endografting requires more than mere familiarity with basic endovascular techniques.
OBJECTIVE: In this study, we aimed to determine the extent to which wide dynamic range compression and compression limiting could benefit severely and profoundly hearing-impaired adults. DESIGN: Subjects were fitted with multi-memory hearing aids incorporating frequency independent input-controlled compression with a 2:1 compression ratio and output-controlled compression limiting. The input compression threshold (CT) was varied to establish the lowest level that maintained audibility for conversational intensity speech without acoustic feedback oscillation. Where a low (40 to 57 dB SPL) CT was possible, this was compared with a moderate (65 to 74 dB SPL) level. The preferred input compression setting was subsequently compared with linear, compression-limited amplification in the same aids. In the three cases where 2:1 input compression could not be used, because of feedback or loudness insufficiency problems, compression limiting was compared with peak clipping. Field trials were conducted over a 2- or 3-mo period to establish preferences. RESULTS: Nine of the 16 subjects preferred the inclusion of the higher level input compression, and one preferred lower level input compression. Four subjects preferred linear, compression-limited amplification, one favored peak clipping, and one could not be satisfied with any of the options provided. CONCLUSIONS: 2:1 input compression was useful, and preferred by 10 of the subjects, but for nine subjects the preferred CT was relatively high. With a group 4-frequency average loss of 87 dB HTL, the results demonstrate that fast-acting, low compression ratio systems can be useful for losses traditionally regarded as the domain of linear amplification.
The killing of Listeria monocytogenes following exposure to low pH, organic acids, and osmotic stress was enhanced by the addition of 5% (vol/vol) ethanol. At pH 3, for example, the presence of this agent stimulated killing by more than 3 log units in 40 min of exposure. The rate of cell death at pH 3.0 was dependent on the concentration of ethanol. Thus, while the presence 10% (vol/vol) ethanol at pH 3.0 stimulated killing by more than 3 log units in just 5 min, addition of 1.25% (vol/vol) ethanol resulted in less than 1 log unit of killing in 10 min. The ability of 5% (vol/vol) ethanol to stimulate killing at low pH and at elevated osmolarity was also dependent on the amplitude of the imposed stress, and an increase in the pH from 3.0 to 4.0 or a decrease in the sodium chloride concentration from 25 to 2.5% led to a marked reduction in the effectiveness of 5% (vol/vol) ethanol as an augmentative agent. Combinations of organic acids, low pH, and ethanol proved to be particularly effective bactericidal treatments; the most potent combination was pH 3.0, 50 mM formate, and 5 % (vol/vol) ethanol, which resulted in 5 log units of killing in just 4 min. Ethanol-enhanced killing correlated with damage to the bacterial cytoplasmic membrane.
Explore the source record for details and available documents.
Can virtual reality exposure therapy be used to treat people with social phobia? To answer this question it is vital to known if people will respond to virtual humans (avatars) in a virtual social setting in the same way they would to real humans. If someone is extremely anxious with real people, will they also be anxious when faced with simulated people, despite knowing that the avatars are computer generated? In [17] we described a small pilot study that placed 10 people before a virtual audience. The purpose was to assess the extent to which social anxiety, specifically fear of public speaking, was induced by the virtual audience and the extent of influence of degree of immersion (head mounted display or desktop monitor. The current paper describes a follow up study conducted with 40 subjects and the results clearly show that not only is social anxiety induced by the audience, but the degree of anxiety experienced is directly related to the type of virtual audience feedback the speaker receives. In particular, a hostile negative audience scenario was found to generate strong affect in speakers, regardless of whether or not they normally suffered from fear of public speaking.
The possibility of an effect of ethnicity on the pharmacokinetics of mycophenolic acid, the immunosuppressive metabolite of the prodrug mycophenolate mofetil, was studied over 90 days following renal transplantation in African American (n = 13) and Caucasian patients (n = 20). Since renal dysfunction and time after transplant surgery are two factors known to alter mycophenolic acid pharmacokinetics, two-way analysis of variance of the data at each time point with ethnicity and renal function status as covariates was used to evaluate the possibility of an ethnicity effect on the pharmacokinetic parameters. No statistically significant difference based on ethnicity was detected for the primary pharmacokinetic parameters, abbreviated mycophenolic acid area under the concentration-time curve (MPA AUC), or the predose trough concentration on study days 4, 7, 14, 28, or 90. A statistically significant decrease in MPA AUC and increase in oral apparent clearance were observed in renally impaired patients regardless of ethnicity on days 4, and 4 and 7, respectively. The suggested mechanism for these differences is uremia-induced increased MPA free fraction, leading to a temporary increased clearance for this restrictively cleared drug.
Evidence exists demonstrating that infection with hepatitis C virus impairs health-related quality of life, but less is known about the effect of fatigue, a common symptom, on everyday life. The psychometric properties of the fatigue severity scale (FSS) were explored to determine suitability as an outcome measure in clinical trials. The FSS includes nine items developed to measure disabling fatigue and a visual analog scale (VAS) to measure overall fatigue. Using baseline data from three clinical trials (n = 1225) involving chronic hepatitis C patients, scaling and psychometric characteristics of the FSS were assessed. The SF-36 was also used in the trials. Item response theory analysis demonstrated that the FSS items can be placed along a single homogenous domain, fatigue. Internal consistency reliability was 0.94. Test-retest reliability was 0.82 for the total score and 0.80 for the VAS. The total score and the VAS were significantly correlated with the SF-36 vitality subscale (r = -0.76 and r = -0.76 respectively). Correlations with other SF-36 subscales were moderate (r = -0.46 to r = -0.67, all p < 0.0001). In summary, the FSS possesses good psychometric properties.
PURPOSE: Endovascular treatment of abdominal aortic aneurysms (AAAs) is a technically demanding procedure that is based on the complexity and multiplicity of steps and the guidewire and catheter manipulations required. Brachial artery catheterization is an adjunctive technique that can facilitate the placement of an endoluminal prosthesis. METHODS: Brachial access was used during endoluminal AAA repair in 79 of 103 consecutive patients with a modular-design stent-graft prosthesis at two institutions. RESULTS: Left brachial access facilitated (1) angiography to guide juxtarenal device deployment, (2) antegrade contralateral limb access, (3) device delivery through disadvantaged iliac arteries by means of a brachial femoral wire, (4) access to renal arteries when necessary, and (5) catheter exchanges and a reduction in fluoroscopic positional changes. Complications included one puncture-site pseudoaneurysm, seven hematomas, and 29 patients with extensive ecchymosis. The length of stay was not prolonged in any case. There were no embolic, oculocerebral, or ischemic upper extremity events. CONCLUSIONS: Brachial artery catheterization, as an adjunctive technique to endoluminal AAA repair, offers noteworthy technical advantages with few, but self-limiting complications.
PURPOSE: During endovascular grafting of an abdominal aortic aneurysm (AAA), iliac limb extension to the external iliac artery may be indicated when the common iliac artery is ectatic or aneurysmal. Preliminary or concomitant coil embolization of the internal iliac artery (IIA) is thus necessary to prevent potential reflux and endoleak. We sought to determine the safety of hypogastric flow interruption in this setting. METHODS: We retrospectively reviewed 156 patients who underwent stent-graft AAA repair at two institutions between February 1, 1998, and January 31, 1999. Coil embolization of one or both IIAs was undertaken when the diameter of the common iliac artery was more than 20 mm to enable limb endograft extension to the external iliac artery. Bilateral procedures were staged. RESULTS: Thirty-nine (25%) of 156 patients were selected for coil embolization of one (n = 28) or both (n = 11) IIAs. The interventions were performed before (n = 31) or during (n = 8) the stent-graft procedure. Complications included groin hematomas in 3 patients, iliac artery dissection in 1, failure to catheterize the IIA in 2, and transient rise in the serum creatinine level in 3. One patient had erectile dysfunction, and five patients (13%) had buttock claudication after unilateral occlusion. Serious ischemic complications were not observed. CONCLUSION: Coil embolization of one or both IIAs appears to be safe in the setting of endovascular grafting of AAA. Buttock claudication is a relatively significant problem and may limit applicability of this strategy to patients who are unfit for standard open repair.
General practitioners' (GPs') treatment of patients with common emotional problems often includes some form of psychological management within the consultation. Such psychological management may be limited to listening and discussion or may also include more specific psychological approaches, such as use of counselling, problem-solving, or cognitive-behavioural techniques. This paper defines GP psychological management and reviews what is known about its frequency and effectiveness. MEDLINE and PsychLIT searches were undertaken of empirical studies of the psychological management of emotional problems by GPs in routine consultations published up to 1998. Thirty-six studies were identified. Most lacked details of the nature of the psychological management reported, making it difficult to compare studies. The frequency of use of psychological management by GPs was found to be generally less when rated by external observers than when assessed by GP self-report. There is preliminary evidence from a few studies of the clinical effectiveness of GP psychological management in routine consultations.
The majority of patients with common emotional or psychological problems are treated solely by general practitioners (GPs). Such treatment frequently includes some form of psychological management within the consultation, whether limited to listening and discussion or involving more specific techniques. This paper sets out a research agenda for the development of effective approaches to GP psychological management. Evidence is reviewed on three core components of all psychological treatments: establishing a positive therapeutic relationship, developing a shared understanding of the problem, and promoting change in behaviour, thoughts or emotions. The application of these components in GP psychological management is outlined and methodological issues in the development and evaluation of GP management approaches are discussed. Since the number of patients with emotional problems seen by each GP is so large, the population effects of even small improvements in psychological management would be sizeable.