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Biomedical subjects

D Bolton

Publications and source records attributed to D Bolton.

At least 19 recordsLinked to original sources

Management of transfusion-related acute lung injury with extracorporeal cardiopulmonary support in a four-year-old child.

We report a case of successful management of transfusion-related acute lung injury (TRALI) with prolonged cardiopulmonary bypass support in a 4-yr-old patient undergoing elective cardiac surgery. TRALI was diagnosed clinically and immunologically by detection of reactive antibodies in a unit of fresh frozen plasma that had been administered to the patient. The aetiology and management of TRALI are briefly discussed and possible implications of this case for the management of TRALI are highlighted.

Cardiopulmonary Bypass↗

Structure and properties of a dimeric N-terminal fragment of human ubiquitin.

Previous peptide dissection and kinetic experiments have indicated that in vitro folding of ubiquitin may proceed via transient species in which native-like structure has been acquired in the first 45 residues. A peptide fragment, UQ(1-51), encompassing residues 1 to 51 of ubiquitin was produced in order to test whether this portion has propensity for independent self-assembly. Surprisingly, the construct formed a folded symmetrical dimer that was stabilised by 0.8 M sodium sulphate at 298 K (the S state). The solution structure of the UQ(1-51) dimer was determined by multinuclear NMR spectroscopy. Each subunit of UQ(1-51) consists of an N-terminal beta-hairpin followed by an alpha-helix and a final beta-strand, with orientations similar to intact ubiquitin. The dimer is formed by the third beta-strand of one subunit interleaving between the hairpin and third strand of the other to give a six-stranded beta-sheet, with the two alpha-helices sitting on top. The helix-helix and strand portions of the dimer interface also mimic related features in the structure of ubiquitin. The structural specificity of the UQ(1-51) peptide is tuneable: as the concentration of sodium sulphate is decreased, near-native alternative conformations are populated in slow chemical exchange. Magnetization transfer experiments were performed to characterize the various species present in 0.35 M sodium sulphate, namely the S state and two minor forms. Chemical shift differences suggest that one minor form is very similar to the S state, while the other experiences a significant conformational change in the third strand. A segmental rearrangement of the third strand in one subunit of the S state would render the dimer asymmetric, accounting for most of our results. Similar small-scale transitions in proteins are often invoked to explain solvent exchange at backbone amide proton sites that have an intermediate level of protection.

Amino Acid Sequence↗

Coagulation factor activity during neonatal extra-corporeal membrane oxygenation.

OBJECTIVE: To ascertain the activity of major coagulation factors during the first 24 h of extra-corporeal membrane oxygenation (ECMO) used to support hypoxaemic neonates. DESIGN AND SETTING: A prospective observational study in a regional centre for ECMO and paediatric cardiac surgery, placing 15-20 neonates on ECMO per year. PATIENTS: Ten neonates receiving ECMO for severe hypoxaemia. MEASUREMENT AND RESULTS: The activity of major clotting factors, of the inhibitor anti-thrombin III and of markers of blood activation were measured during the first 24 h of neonatal extra-corporeal membrane oxygenation (ECMO) and prior to initiation of ECMO. There was laboratory evidence of factor deficiency and of activation of coagulation at all stages. The initiation of ECMO leads to an initial worsening of coagulopathy, but factor deficiency and abnormal activation of coagulation is also seen prior to ECMO in these very sick neonates. CONCLUSION: If factor deficiency is to be avoided a pro-active approach is required to rapidly correct factor activity. This would include the use of fresh frozen plasma. The effect of such an approach on outcome is at yet uncertain.

Biomarkers↗

Neurological and neuropsychological signs in obsessive compulsive disorder: interaction with behavioural treatment.

The main aim of this study was to test the hypothesis that neurological soft signs and neuropsychological abnormalities associated with obsessive-compulsive disorder (OCD) predict poor response to behavioural treatment. The design permitted investigation of secondary hypotheses, regarding correlations among these neurological markers and levels of symptomatology, and their stability in relation to changes in levels of symptomatology. Thirty-five participants satisfying DSM-IV diagnostic criteria for OCD were assessed pre- and postbehavioural treatment using a scaled measure of symptom severity, and a battery of tests sensitive to neuropsychological deficits associated with OCD. Eighteen of the participants were also assessed on an inventory of neurological soft signs. Neither neuropsychological test deficits nor neurological soft signs pretreatment predicted response to behavioural treatment. Lower performance on neuropsychological tasks and symptom severity were both significantly correlated with levels of soft signs. Some neurological markers were less severe posttreatment, but these changes were not related to treatment response.

Adolescent↗

The long-term psychological effects of a disaster experienced in adolescence: I: The incidence and course of PTSD.

Previous studies have shown that children and adolescents exposed to traumatic experience in a disaster can suffer from high levels of post-traumatic stress. The present paper is the first a series reporting on the long-term follow-up of a group of young adults who as teenagers had survived a shipping disaster-the sinking of the "Jupiter" in Greek waters-between 5 and 8 years previously. The general methodology of the follow-up study as a whole is described, and the incidence and long-term course of Post-Traumatic Stress Disorder (PTSD). It is the first study of its kind on a relatively large, representative sample of survivors, using a standardised diagnostic interview, and comparing survivors with a community control group. Survivors of the Jupiter disaster (N = 217), and 87 young people as controls, were interviewed using the Clinician Administered PTSD Scale (CAPS). Of the 217 survivors, 111 (51.7%) had developed PTSD at some time during the follow-up period, compared with an incidence in the control group of 3.4 % (N = 87). In the large majority of cases of PTSD in the survivors for whom time of onset was recorded, 90 % (N = 110), onset was not delayed, being within 6 months of the disaster. About a third of those survivors who developed PTSD (30%, N = 111) recovered within a year of onset, through another third (34 %, N = 111) were still suffering from the disorder at the time of follow-up, between 5 and 8 years after the disaster. Issues relating to the generalisability of these findings are discussed.

Adolescent↗

The long-term psychological effects of a disaster experienced in adolescence: II: General psychopathology.

Children and adolescents exposed to trauma can suffer major adverse psychological effects including not only post-traumatic stress but also other psychological disorders. This study investigates the long-term course of general psychopathology following trauma in adolescence using a standardised diagnostic interview and comparisons with a matched control group. Young people (N= 216) who as teenagers had survived a shipping disaster-the sinking of the "Jupiter" in Greek waters-between 5 and 8 years previously and 87 young people as matched controls were interviewed. The survivors showed raised rates of diagnosis in a range of anxiety and affective disorders during the follow-up period. The highest rates were among the survivors who had developed Post-Traumatic Stress Disorder (PTSD), and those survivors who had not were generally similar to the controls. Onset of anxiety and affective disorders varied between being indefinitely close to the disaster to years later. Differences in rates of disorder between the survivor and control groups had lessened by the time of follow-up but were still apparent, due to continuing distress among the survivors still suffering from PTSD, and to a lesser extent among those who had recovered from PTSD. Generalisability of the findings are discussed.

Adolescent↗

Risk factors for long-term psychological effects of a disaster experienced in adolescence: predictors of post traumatic stress disorder.

This paper examines risk factors for the development of Post Traumatic Stress Disorder (PTSD), and its severity and chronicity, in a group of 217 young adults who survived a shipping disaster in adolescence. The survivors were followed up 5 to 8 years after the disaster. Risk factors examined fell into three main categories: pre-disaster child and family vulnerability factors, including childhood psychopathology; objective and subjective disaster-related experiences; and post-disaster factors, including results from screening questionnaires administered 5 months post-disaster, coping mechanisms adopted subsequently, life events, and availability of social supports. Developing PTSD following the disaster was significantly associated with being female, with pre-disaster factors of learning and psychological difficulties in the child and violence in the home, with severity of exposure to the disaster, survivors' subjective appraisal of the experience, adjustment in the early post-disaster period, and life events and social supports subsequently. When all these factors were considered together, measures of the degree of exposure to the disaster and of subjective appraisal of life threat, and ratings of anxiety obtained 5 months post-disaster, best predicted whether survivors developed PTSD. For those survivors who developed PTSD, its duration and severity were best predicted not by objective and subjective disaster-related factors, but by pre-disaster vulnerability factors of social, physical, and psychological difficulties in childhood together with ratings of depression obtained 5 months post-disaster, and whether survivors received post-disaster support at school. The implications of these findings are considered for targeting assessment and intervention efforts at survivors most at risk of developing difficulties in adjustment following similar traumatic experiences.

Adolescent↗

Solution structure of the N-terminal F1 module pair from human fibronectin.

Multiple sites within the N-terminal domain (1-5F1) of fibronectin have been implicated previously in fibronectin matrix assembly, heparin binding, and binding to cell surface proteins of pathogenic bacteria. The solution structure of 1F1(2)F1, the N-terminal F1 module pair from human fibronectin, has been determined using NMR spectroscopy. Both modules in the pair conform to the F1 consensus fold. In 4F1(5)F1, the only other F1 module pair structure available, there is a well-defined intermodule interface; in 1F1(2)F1, however, there is no detectable interface between the modules. Comparison of the backbone 15N-{1H} NOE values for both module pairs confirms that the longer intermodule sequence in 1F1(2)F1 is flexible and that the stabilization of the 4F1 C-D loop observed in 4F1(5)F1, as a result of the intermodule interface, is not observed in 1F1(2)F1.

Amino Acid Sequence↗

Postempiricism and psychological theory.

Discusses postempiricism as a view of scientific knowledge and of knowledge in general. It gives a prominent role to theory in relation to experience, experiment, and action and emphasizes the contextual nature of knowledge. The articles by Dishion and Patterson (this issue), Evans (this issue), and Liddle (this issue) are all positioned clearly in this contemporary epistemology. Fonagy's (this issue) analysis of the apparent restriction of psychoanalytic methods of change is discussed.

Adolescent↗

Effect of dehairing operations on microbiological quality of swine carcasses.

To develop a hazard analysis and critical control point plan for food processing operations, critical control points must be determined. Swine slaughtering and dressing operations were investigated to establish their critical control points. We monitored the microbiology of swine carcasses by surface swabbing carcass bellies at various steps during the process and by quantitating total aerobic plate count (APC) and coliforms. Starting with a dehaired carcass, the sequential steps monitored included presingeing, postsingeing, polishing, and chilling. Initial results indicate that singeing and chilling substantially reduced the levels of APC and coliforms, whereas polishing increased their levels. The hygienic characteristics of individual operations involved in dressing swine carcasses were then evaluated in the second experiment. A set of 40 randomly selected carcasses leaving singeer, polisher, shaver, and washer were sampled. Carcasses were heavily contaminated during the final polishing procedure, and the APC increased threefold compared with prepolishing levels. Washing reduced the bacterial numbers by 69%. To reduce the microbial load on swine carcasses, final polishing and manual shaving steps were not used during the dressing operation on a set of 90 carcasses. APCs on singed carcasses were reduced from 1.34 to -0.15 log10 CFU/cm2 when the final polisher and manual shavers were not used. However, carcasses were subsequently recontaminated with bacteria after evisceration, and the APCs were similar (P > 0.05) regardless of whether the final polishing and manual shaving steps were used, averaging 1.30 and 1.46 log10 CFU/cm2. These results indicated that individual operations can be identified as critical control points, appropriate limits can be set and monitored in a hazard analysis and critical control point system, and steps where further changes to reduce bacterial levels may be needed for swine slaughtering plants.

Abattoirs↗

Co-ordinating care for Canadian travellers.

Case management is a popular term these days. It refers to caring for the whole patient and his or her family by incorporating all necessary resources available within the community.

Canada↗

Transurethral Nd:YAG laser prostatectomy with a laterally firing fiber: local effects on tissue associated with erectile dysfunction.

BACKGROUND AND OBJECTIVES: Transurethral laser prostatectomy is anticipated to become a recognized alternative to conventional transurethral resection of the prostate. However, the effects of this procedure on the nerves of the pelvic plexus and erectile dysfunction remain unaddressed. The objective of this study was to evaluate the effects of laser energy on extent of prostatic damage as well as injury to periprostatic cavernosal nerves and erectile dysfunction in a canine model. STUDY DESIGN/MATERIALS AND METHODS: Six adult male mongrel dogs underwent transurethral laser prostatectomy at 30 (n = 3) and 40 (n = 3) watt power settings. Total laser energy delivered varied between 6,000 and 13,800 joules. Erectile function was evaluated by pelvic nerve stimulation at 2, 4, and 8 weeks. Animals were then sacrificed to assess histopathology of the prostate at each time point. RESULTS: Histopathologic changes were noted in the prostate in a dose-dependent manner and did not vary with different laser power settings. In dogs that received approximately 10,000 J, substantial prostate ablation confined within the capsule was achieved in every prostate gland. Adequate erectile responses were noted in five of six animals; all received < 10,000 J. In one animal that received a total dose of 13,800 J, an erectile response was not obtained, and histology revealed both prostatic capsule perforation in close proximity to the cavernous nerves and thermal neural damage. CONCLUSIONS: We conclude that cavernous nerve damage may result from excessive doses of laser energy during transurethral laser treatment of the prostate gland. In canines, the upper limit for periprostatic injury is between 10 and 14,000 joules.

Aluminum Silicates↗

Characterization and development of UCI 107, a primary human ovarian carcinoma cell line.

We introduce a new epithelial ovarian carcinoma cell line (UCI 107) from a patient with papillary adenocarcinoma of the ovary who had not been previously treated. The growth characteristics, chemosensitivity, tumorgenicity, cytogenetics, antigen expression, and receptor status were examined. A standardized photometric assay was implemented to determine the response to single drug agents including doxorubicin (ADR), cisplatin (CDDP), and Taxol. Tumorgenicity was determined utilizing female athymic mice implanted either subcutaneously (sc) or intraperitoneally (ip) with 1 x 10(7) UCI 107 cells. UCI 107 cells grow rapidly in culture with lag phase of approximately 48 hr, population doubling time of 24-36 hr, and saturation density of 4.8 x 10(5) cells/cm2. The 50% inhibitory concentration values for the chemotherapeutic agents were 0.170, 0.029, and 0.330 microM for ADR, Taxol, and CDDP, respectively. Nude mice produced ip tumors within 15 days, resulting in death from carcinomatosis 40-45 days postimplantation. Subcutaneous tumor nodules (100 mm3) were observed in nude mice 12-13 days post-tumor implantation reaching a maximum tumor volume of approximately 10,000 mm3 by Day 30. The cytogenetic composite karyotype is as follows: 46, X, der (X) t (X;7) (p11;q22), inv dup (1) (q12;q32), t (6;6;11;22) (p21.3;q16;q23.3;q13.3), del (13) (q14.1). The cell line expresses progesterone receptor, increased levels of p53 protein, and cytokeratins. It does not appear to express Her-2/neu protein, estrogen receptor, nor the CA 125 tumor marker. In conclusion, UCI 107 displays unique cellular properties which make it an attractive model for the study of ovarian cancer.

Animals↗

Long-term course of obsessive-compulsive disorder treated in adolescence.

OBJECTIVE: To investigate the long-term course of obsessive-compulsive disorder treated in adolescence. METHOD: Fifteen young adults treated for the disorder in adolescence, mainly through not only by behavior therapy and family therapy, were followed up between 9 and 14 years later. RESULTS: Data were collected on 14 of the cases (93%, N = 15) from various sources including interview in person in 6 cases. Of the 14 cases, 6 were found to satisfy DSM-III-R criteria for obsessive-compulsive disorder at long-term follow-up, while 8 were not. These recovered participants were not currently taking medication, and long-lasting recovery was associated with good social adjustment. Chronic course was not attributable to lack of subsequent treatment. CONCLUSIONS: The recovery rate of 57% (N = 14) is similar to those found in other recent studies of outcome following vigorous treatment in adolescence. The findings are over the longest follow-up period so far reported for obsessive-compulsive disorder treated in adolescence. Positive response to treatment in adolescence can be followed by relapse after longer periods than have usually been studied.

Adjustment Disorders↗

Fibroepithelial ureteral polyps and urolithiasis.

Fibroepithelial polyps are the most common benign tumor of the ureter. Most of the literature regarding their cause ascribes it to chronic infection. These publications, however, show that the majority of such cases never were associated with a documented urinary tract infection. Fibroepithelial polyps appear with equal frequency in male and female subjects and are found in all age groups including children, in contrast to what would have been expected with an infectious cause. Four histologically confirmed cases of fibroepithelial polyps were associated with chronic inflammation of the upper urinary tract related to the presence of calculi and/or Double J ureteral stents. All patients were managed successfully by endoscopic means, preserving renal function. Fibroepithelial ureteral polyps may be associated with urolithiasis, which serves as a source of chronic inflammation. A review of the literature is presented and supports these observations.

Adult↗