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Biomedical subjects

D White

Publications and source records attributed to D White.

At least 37 records · Page 2Linked to original sources

Complications following endovascular abdominal aortic aneurysm repair.

There is a growing population of patients who have undergone endovascular abdominal aortic aneurysm repair (EVAR) and thus there is an increasing likelihood that radiologists who are unfamiliar with this technique and its complications will have to report radiological investigations on one of these patients. The purpose of this review is to describe and illustrate the normal and abnormal radiological appearances after EVAR on plain radiography, ultrasound and CT.

Aorta, Abdominal↗

The LIM domain gene LMO4 inhibits differentiation of mammary epithelial cells in vitro and is overexpressed in breast cancer.

LMO4 belongs to a family of LIM-only transcriptional regulators, the first two members of which are oncoproteins in acute T cell leukemia. We have explored a role for LMO4, initially described as a human breast tumor autoantigen, in developing mammary epithelium and breast oncogenesis. Lmo4 was expressed predominantly in the lobuloalveoli of the mammary gland during pregnancy. Consistent with a role in proliferation, forced expression of this gene inhibited differentiation of mammary epithelial cells. Overexpression of LMO4 mRNA was observed in 5 of 10 human breast cancer cell lines. Moreover, in situ hybridization analysis of 177 primary invasive breast carcinomas revealed overexpression of LMO4 in 56% of specimens. Immunohistochemistry confirmed overexpression in a high percentage (62%) of tumors. These studies imply a role for LMO4 in maintaining proliferation of mammary epithelium and suggest that deregulation of this gene may contribute to breast tumorigenesis.

Adaptor Proteins, Signal Transducing↗

Identification of a new fibroblast growth factor receptor, FGFR5.

A novel fibroblast growth factor receptor (FGFR), designated FGFR5, was identified from an EST database of a murine lymph node stromal cell cDNA library. The EST has approximately 32% identity to the extracellular domain of FGFR1-4. Library screening with this EST identified two full-length alternative transcripts which we designated as FGFR5 beta and FGFR5 gamma. The main difference between these transcripts is that FGFR5 beta contains three extracellular Ig domains whereas FGFR5 gamma contains only two. A unique feature of FGFR5 is that it does not contain an intracellular tyrosine kinase domain. Predictive structural modelling of the extracellular domain of FGFR5 gamma suggested that it was a member of the I-set subgroup of the Ig-superfamily, consistent with the known FGFRs. Northern analysis of mouse and human FGFR5 showed detectable mRNA in a broad range of tissues, including kidney, brain and lung. Genomic sequencing identified four introns but identified no alternative transcripts containing a tyrosine kinase domain. Extracellular regions of FGFR5 beta and 5 gamma were cloned in-frame with the Fc fragment of human IgG(1) to generate recombinant non-membrane bound protein. Recombinant FGFR5 beta Fc and R5 gamma Fc demonstrated specific binding to the ligand FGF-2, but not FGF-7 or EGF. However, biological data suggest that FGF-2 binding to these proteins is with lower affinity than its cognate receptor FGFR2C. The above data indicate that this receptor should be considered as the fifth member of the FGFR family.

3T3 Cells↗

Development of inhalational agents for oncologic use.

Because regional chemotherapy has been useful in treatment and palliation of many cancer types, the concept of delivering drugs by inhalation for the treatment of cancers in the lung is attractive. Much higher local drug exposure can be achieved with total doses considerably lower than those required for systemic administration, resulting in lower exposure of nonrespiratory tract tissues to potentially toxic drugs. Regional delivery of chemotherapy to the respiratory tract has been shown to have activity in preclinical and clinical studies. Technical improvements in delivery methods have now made it possible to conduct trials of inhalational agents, both to treat cancers affecting the respiratory tract and to deliver other drugs used in cancer patients. This review discusses the rationale of drug delivery by the inhalational route, its technical challenges, preclinical and clinical experiences, limitations, and promise.

Administration, Inhalation↗

Dental attendance in 1998 and implications for the future.

The 1998 survey of Adult Dental Health in the UK was carried out under the auspices of the Office of National Statistics together with the Universities of Birmingham, Dundee, Newcastle-upon-Tyne and Wales. A key behavioural indicator in these decennial surveys is whether people say they go to a dentist for a regular dental check-up, an occasional dental check-up or only when they have trouble with their teeth. The proportion of dentate adults in the UK who report attending for regular dental check-ups has risen from 43% in 1978 to 59% in 1998. Older adults (over 55 years old) in 1998 were the most likely to say they attend for regular dental check-ups. Many younger adults (16-24) in 1998 said they went to a dentist less often than 5 years previously, they were also the least likely to say they attend for regular dental check-ups. Dental anxiety remains a problem for many dental patients but another factor of importance to many is their want to be involved in the treatment process and especially to be given an estimate of treatment costs.

Adolescent↗

The impact of oral health on people in the UK in 1998.

Knowledge of the extent of dental disease gives a clinical indication of the experience of dental problems but it does not necessarily reflect the problems that people experience as a result of their dentition. It is becoming increasingly appreciated that the way a disease affects people's lives is just as important as epidemiological measures of its prevalence or incidence. The 1998 Adult Dental Health survey is the first of the decennial series of UK adult dental health surveys to use and report a measure of the self-perceived impact on people of the dental and periodontal diseases and other oral conditions. Over half (51%) of dentate adults said they had been affected in some way by their oral health, and in 8% of cases the impact was sufficient to have reduced their quality of life.

Adult↗

Etretinate augments interferon beta-1b effects on suppressor cells in multiple sclerosis.

BACKGROUND: Interferon beta treatment is only partially effective in multiple sclerosis (MS) suggesting a potential role for adjunctive therapies. Retinoids can augment the clinical efficacy of type 1 interferons in patients with cancer. We reasoned that the same might hold in MS. Interferon beta-1b added to peripheral blood mononuclear cells in vitro partially reverses the CD8 suppressor cell defect of patients with MS. All-trans retinoic acid added to peripheral blood mononuclear cells from untreated patients with MS or from controls potentiates this ability of interferon beta-1b to augment CD8 suppressor cell function in vitro. OBJECTIVE: To determine whether retinoid administration to patients with MS who are being treated with interferon beta-1b augments their CD8 suppressor cell function. SETTING: A university hospital MS clinic. PARTICIPANTS: Patients with MS who were being treated with interferon beta-1b, 14 patients with secondary progressive MS and 3 patients with relapsing remitting MS. RESULTS: Seventeen patients with MS received etretinate treatment for up to 6 months. Planned dosing was 10 mg 3 times daily for the first month, 25 mg twice daily for the second and third months, and 10 mg twice daily thereafter. The 25-mg twice daily dose was not well tolerated and of the 14 patients who remained in the phase 1 clinical trial through month 3 dose reduction to 10 mg thrice daily was required in 1 patient and to 10 mg twice daily in 4 patients. Eleven patients completed the trial. Etretinate treatment significantly augmented suppressor function over baseline values at 1, 3, and 6 months. No meaningful change was noted in disability or quality of life over the course of the phase 1 clinical trial. Neuropsychological testing of completers suggested improvement on selected aspects of verbal memory at 6 months compared with baseline values. CONCLUSIONS: Etretinate treatment at a dose of 10 mg twice or three times daily augments suppressor cell function in patients with MS receiving interferon beta-1b. Higher dose etretinate treatment (25 mg twice daily) is poorly tolerated by patients with MS. Even at 10 mg twice daily adverse experiences involving the mucous membranes and the skin become troublesome for some, but not all, patients. Whether pulse therapy or administration of retinoid restricted to the day of interferon beta dosing will also augment suppressor function, while being better tolerated, remains to be determined.

Adjuvants, Immunologic↗

The role of perfectionism and excessive commitment to exercise in explaining dietary restraint: replication and extension.

UNLABELLED: The etiological complexity of the eating disorders has incited researchers to examine how personality characteristics and other variables operate jointly in the development of deviant eating patterns. OBJECTIVE: This study investigated the independent, interactive, and indirect prediction of dietary restraint by perfectionism and excessive commitment to exercise. METHOD: Multiple regression analyses designed to test moderating and mediating models were conducted on a sample of female university students (n = 269). RESULTS: Several dimensions of perfectionism, as well as excessive commitment to exercise, significantly and independently predicted dietary restraint in these women. There was no evidence for an interaction effect. Mediation analyses suggested that for selected dimensions of perfectionism, the direct relationship between perfectionism and dietary restraint is partially explained by excessive commitment to exercise. DISCUSSION: Interventions aimed at challenging perfectionistic standards in the context of dieting need to address not only one's self-standards, but one's perceptions of standards held by others. The mediating role of excessive exercise commitment pinpoints this variable as an alternative intervention target in the prevention of excessive dieting.

Adult↗

Detection of arboviral RNA directly from mosquito homogenates by reverse-transcription-polymerase chain reaction.

Many arthropod-borne viruses (arboviruses) are important human pathogens medically. The development of an effective technique to detect the viruses by using nucleic acid amplification, such as polymerase chain reaction (PCR), improves not only clinical diagnosis but also virologic surveillance of mosquito vectors in the field. In this study, the development of an improved and simplified assay is described for detection of mosquitoes infected with eastern equine encephalitis (EEE) virus, Cache Valley (CV), and California (CAL) serogroup viruses from field-collected mosquito pools. As little as 5 microl of homogenate from mosquito pools was used in the reverse transcription (RT) reaction followed by the use of three sets of specific primers for the PCR. Positive pools were determined by finding PCR bands of the expected size for each arbovirus. The confirmation and identification of Bunyaviruses was done by sequencing the PCR product. In 1999, West Nile virus (WNV) was identified as the etiologic agent of an outbreak of human encephalitis in New York City. It is shown that this protocol is also able to detect West Nile viral RNA in a pool of 100 mosquitoes containing one infected mosquito.

Aedes↗

'RETCIF': a rapid, sensitive method for detection of viruses, applicable for large numbers of clinical samples.

Rapid detection of viruses in clinical samples is important for continuing appropriate antiviral treatment and discontinuing unnecessary antibacterial treatment, as well as for excluding viral pathogens. Yet detection of viral agents may require numerous susceptible cell lines. Even with the shell vial culture method, it is cumbersome for handling large volumes of specimens. A procedure has been developed, which is time and cost-saving and uses specific cell lines in a 96-well microtitre plate and monoclonal antibodies (RETCIF-rapid enhanced tissue culture immunofluorescence). Each clinical sample was inoculated into 12 different wells with five different cell lines. Enhancement was achieved by sonication, centrifugation and hormonal supplementation to the medium used. Cytomegalovirus (CMV), herpes simplex virus (HSV) and respiratory viruses were detected by monoclonal antibodies on day 2, whilst varicella zoster virus (VZV) and enteroviruses were detected on days 5 and 7, respectively. During July-December 1998, 3298 patient specimens were compared by RETCIF and a modified shell vial method. Either or both methods isolated 779 viruses (24% positivity rate), whilst both methods detected 621. Of the 779 viruses, 87% (679) were isolated by the shell vial method in an average time of 4.9 days. For RETCIF the respective rate was 92.5% (721), in an average time of 3.0 days. The RETCIF method is a time-saving procedure, with higher isolation rates than the shell vial method.

Antibodies, Monoclonal↗

Aortic side branch embolization before endovascular aneurysm repair: incidence of type II endoleak.

PURPOSE: To assess the feasibility of embolization of aortic side branches and its impact on the incidence of type II endoleak after endovascular aneurysm repair. MATERIALS AND METHODS: Endovascular aneurysm repair was performed in 74 patients. Aortic side branch vessels were evaluated on the preoperative angiogram and computed tomography (CT) and, where embolization of lumbar and inferior mesenteric vessels was considered technically possible, this was attempted prior to endovascular repair. Follow-up CT was used to assess the presence of type II endoleak. RESULTS: Seventy-two patients were followed up for longer than 1 month. Embolization was attempted in 25 cases, successfully in 10, with partial success in 11, and failure in four. Twenty patients with successful or partly successful preoperative embolization were discharged and followed-up. Four (20%) had demonstrable type II endoleak during follow-up, with two of these persisting at latest follow-up. Of 43 patients without previous embolization, there were 10 (23.3%) type II endoleaks during the follow-up period, four of these persisting. In cases with type II endoleak, mean sac diameter change was -0.5 mm in the cases with previous embolization and +3.1 mm without. The mean period to onset of type II endoleak was 6.9 months without, and 15.3 months with, previous embolization. CONCLUSION: Although the cohort size is below a level that would confer significance, the trend of these findings is such as to suggest a lack of influence of aortic side branch embolization on the incidence of type II endoleak during the follow-up period.

Angiography↗

Inhibition of return in children with perinatal brain injury.

Inhibition of return is a bias in attention that reduces the likelihood of returning attention to previously viewed locations. This attention bias develops during the first 6 months of life and is putatively mediated by midbrain structures. The present study evaluated the effects of perinatal lesions on the development of inhibition of return. Thirty-three children with perinatal injury resulting in spastic diplegic cerebral palsy were grouped based on magnetic resonance exams. Children with anterior (n = 5), posterior (n = 12), diffuse (n = 8), or no apparent (n = 8) lesions were compared with a group of age-matched children without neurologic injury (n = 39) on an orienting task designed to elicit inhibition of return. Short-delay trials demonstrated grossly intact facilitation of attention for all groups. Long-delay trials that produced inhibition of return in the control and posterior injury groups indicated a disruption of inhibition of return in the groups with anterior and diffuse lesions. The findings are consistent with previous reports that anterior regions are important for the developing attention system, and that bilateral injury can result in unilateral disruption of visual attention.

Attention↗

An inter-university community child health clinical placement programme for medical students.

BACKGROUND: Inpatient teaching no longer reflects the full spectrum of paediatric practice and community-based programmes with clearly defined aims and evaluation of learning are becoming increasingly important. Competition for community resources poses threats to the delivery of effective community child health learning programmes by individual medical schools. OBJECTIVES: To develop and evaluate a combined inter-university, child-focused, active learning programme in community child health. METHODS: A total of 55 postgraduate-entry medical students from the Flinders University of South Australia and 97 undergraduate-entry University of Adelaide students were placed with 25 community child health agencies and instructed to assess services from a client perspective by tracking one child and family through multiple agency contacts. Following each placement, achievement of specific programme aims was evaluated by students and agency staff using a 7-point Likert scale. RESULTS: Students and agency staff indicated substantial achievement of programme aims. Mean agency ratings were significantly higher than student ratings for three aims: students' experiencing a wider spectrum of health care problems than in teaching hospitals (5.7 +/- 1.5 versus 4.9 +/- 1.6, P < 0.001); the importance of social and environmental factors (5.9 +/- 1.0 versus 5.2 +/- 1.4, P < 0.001), and the importance of coordinating care (6.0 +/- 1.0 versus 5.2 +/- 1.2, P < 0.001). Ratings from undergraduate-entry students differed from those of postgraduate-entry students only with respect to the importance of social and environmental factors (4.8 +/- 1.4 versus 5.7 +/- 1.1, P < 0.001). CONCLUSIONS: The new collaborative Community Child Health Programme substantially achieved learning aims and demonstrated effective integration of postgraduate- and undergraduate-entry medical students from two universities.

Adult↗

Molecular microbial diversity of a spacecraft assembly facility.

In ongoing investigations to map and archive the microbial footprints in various components of the spacecraft and its accessories, we have examined the microbial populations of the Jet Propulsion Laboratory's Spacecraft Assembly Facility (JPL-SAF). Witness plates made up of spacecraft materials, some painted with spacecraft qualified paints, were exposed for approximately 7 to 9 months at JPL-SAF and examined the particulate materials collected for the incidence of total cultivable aerobic heterotrophs and heat-tolerant (80 degrees C for 15-min.) spore-formers. The results showed that the witness plates coated with spacecraft qualified paints attracted more dust particles than the non-coated stainless steel witness plates. Among the four paints tested, witness plates coated with NS43G accumulated the highest number of particles, and hence attracted more cultivable microbes. The conventional microbiological examination revealed that the JPL-SAF harbors mainly Gram-positive microbes and mostly spore-forming Bacillus species. Most of the isolated microbes were heat resistant to 80 degrees C and proliferate at 60 degrees C. The phylogenetic relationships among 23 cultivable heat-tolerant microbes were examined using a battery of morphological, physiological, molecular and chemotaxonomic characterizations. By 16S rDNA sequence analysis, the isolates fell into seven clades: Bacillus licheniformis, B. pumilus, B. cereus, B. circulans, Staphylococcus capitis, Planococcus sp. and Micrococcus lylae. In contrast to the cultivable approach, direct DNA isolation, cloning and 16S rDNA sequencing analysis revealed equal representation of both Gram-positive and Gram-negative microorganisms.

Bacillus↗

AlphaB-crystallin expression in celiac disease - a preliminary study.

AIM: To investigate immunohistochemically alphaB-crystallin expression and distribution in biopsy sections of the small intestine of patients with celiac disease, and the relationship, if there is any, between the expression of this heat shock protein and the degree of mucosal atrophy. METHODS: Biopsy specimens of 22 subjects (12 celiac patients and 10 "normal" individuals) were investigated by immunoperoxidase screening procedures using monoclonal antibodies to detect the presence of alphaB-crystallin. Sections from each case were stained with hematoxylin and eosin to assess mucosal morphology. RESULTS: The epithelial cells of the small intestine stained more intensively for alphaB-crystallin in patients with celiac disease than in "normal" patients. The quantity and degree of intensity of immunohistochemically demonstrable alphaB-crystallin and its intracellular distribution in the duodenal mucosa of the patients with celiac disease were closely related to the degree of villus atrophy. There was a strong correlation between the number of patients with celiac disease and percentage staining score of alphaB-crystallin per total score (Pearson's r = 0.754, p = 0.123). The mean percentage score per total score was 20% among the patients with celiac disease. On the other hand, there was a weak negative correlation between the number of normal controls and percentage score per total score (Pearson's r= -0.126, p = 0.437). The mean percentage score per total score was 4.6% among the normal controls. AlphaB-crystallin stained the supra-nuclear region of the enterocytes with a 75% sensitivity and 71% specificity. CONCLUSION: AlphaB-crystallin, a stress response protein, is expressed in the small intestinal mucosa of patients with celiac disease, and the degree of mucosal atrophy compares significantly with the intensity of expression of alphaB-crystallin. We therefore conclude that an inappropriate stress response involving this heat-shock protein within the mucosa itself may be crucial as an initiating event in the architectural derangement of the mucosal damage associated with celiac disease.

Adult↗

Breast density as a predictor of mammographic detection: comparison of interval- and screen-detected cancers.

BACKGROUND: Screening mammography is the best method to reduce mortality from breast cancer, yet some breast cancers cannot be detected by mammography. Cancers diagnosed after a negative mammogram are known as interval cancers. This study investigated whether mammographic breast density is related to the risk of interval cancer. METHODS: Subjects were selected from women participating in mammographic screening from 1988 through 1993 in a large health maintenance organization based in Seattle, WA. Women were eligible for the study if they had been diagnosed with a first primary invasive breast cancer within 24 months of a screening mammogram and before a subsequent one. Interval cancer case subjects (n = 149) were women whose breast cancer occurred after a negative or benign mammographic assessment. Screen-detected control subjects (n = 388) were diagnosed after a positive screening mammogram. One radiologist, who was blinded to cancer status, assessed breast density by use of the American College of Radiology Breast Imaging Reporting and Data System. RESULTS: Mammographic sensitivity (i.e., the ability of mammography to detect a cancer) was 80% among women with predominantly fatty breasts but just 30% in women with extremely dense breasts. The odds ratio (OR) for interval cancer among women with extremely dense breasts was 6.14 (95% confidence interval [CI] = 1.95-19.4), compared with women with extremely fatty breasts, after adjustment for age at index mammogram, menopausal status, use of hormone replacement therapy, and body mass index. When only those interval cancer cases confirmed by retrospective review of index mammograms were considered, the OR increased to 9.47 (95% CI = 2.78-32.3). CONCLUSION: Mammographic breast density appears to be a major risk factor for interval cancer.

Adult↗