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Biomedical subjects

A J Wilson

Publications and source records attributed to A J Wilson.

At least 73 records · Page 4Linked to original sources

Severe exacerbation of chronic obstructive airways disease: health resource use in general practice and hospital.

The objective of this study is to examine the treatment of exacerbations of chronic obstructive airways disease (COAD) in the hospital and in the community setting using a retrospective study of patients admitted to a major teaching hospital combined with a general practice chart audit. The admission records for 248 admissions from 128 patients were reviewed. Most patients (70%) had visited their GP within 2 weeks of admission, antibiotics were prescribed for 30% of the exacerbations while 51% were treated with ingested corticosteroids. During hospitalization, features of infection were present in 64% (n = 159) of exacerbations and 79% (n = 196) received antibiotics. Patients were also treated with nebulized bronchodilators, oxygen and corticosteroids (82%). The median length of stay was 10 days (range 0-55). There was a high readmission rate (70%) at 1 year for exacerbation of COAD during the study period. Exacerbations of COAD frequently demonstrated the clinical features of infection. Treatment in general practice was less intensive than in hospital, and there is a need to reconcile these differences with studies of early therapy with antibiotics and corticosteroids. Although corticosteroids were used less often in general practice, the literature in this area is not conclusive and the evidence supporting guideline recommendations is not explicit. There are opportunities to examine the role of early therapy and early discharge programmes to minimize the cost burden from exacerbations of COAD.

Adrenal Cortex Hormones↗

Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV8)--a new human tumour virus.

Recently, a novel DNA virus has been molecularly cloned from Kaposi's sarcoma (KS) tissue, a tumour common in acquired immune deficiency syndrome (AIDS). Analysis of the viral genome confirms that it is a relative of human herpesviruses and the virus has been designated HHV-8. Epidemiological evidence suggests a strong aetiological link between the presence of HHV-8 DNA and/or antibodies against the virus, and KS. Additional sequence analysis suggests that the HHV-8 genome contains sequences which encode a D type cyclin and a number of other genes potentially implicated in growth deregulation which may be relevant to its proposed role as a transforming virus.

AIDS-Related Opportunistic Infections↗

Trypanosoma cruzi: use of herpes simplex virus-thymidine kinase as a negative selectable marker.

Trypanosoma cruzi, the protozoan that causes Chagas' disease, was transfected with a fusion gene of hygromycin phosphotransferase and herpes simplex virus-thymidine kinase, HyTK. Transfectants selected in hygromycin had thymidine kinase activity, whereas controls did not. In vitro growth of the mammalian life-stage forms, amastigotes and trypomastigotes, was inhibited 98% by the nucleoside analogue ganciclovir (5 micrograms/ml). Growth of the insect-stage form, epimastigotes, was not inhibited by ganciclovir (up to 250 micrograms/ml) or other nucleoside analogues. Intracellular uptake of ganciclovir by epimastigotes was found to be 10-fold less than that by amastigotes. Mice infected with the HyTK-expressing parasites and treated with ganciclovir had a statistically significant reduction of parasitemia by 57%; however, complete eradication of parasites was not achieved. The parasites recovered from the treated mice continued to be susceptible to ganciclovir in vitro. Parasite clones with higher expression of thymidine kinase were more sensitive to ganciclovir, suggesting that greater expression of the thymidine kinase gene may lead to parasites that can be fully eradicated from infected experimental animals.

3T3 Cells↗

Design of a summary screen for an ICU patient data management system.

The paper describes a used-centred design for the summary screen of a computerised ICU patient data management system (PDMS). The screen also forms the resting state display, or default screen, and provides the principal navigation tool to other functionality within the system. The design process identified the most frequent potential users of this screen to be the nurses. Their tasks and the information resources required to perform them were analysed. The analysis identified that the nurses' main task of planning and implementing patient care required an awareness of a set of physiological parameters which provided an overview of the patient's general condition. Novel formats are proposed for displaying the trends in physiological parameters and these have been incorporated into a proposed screen design. These display formats have been evaluated by ICU nurses; they were adjudged to be clear, relevant, easy to learn and simple to use. Nurses considered the content of the screen, and the display formats used, to be suitable for maintaining an awareness of a patient's state during routine patient management.

Evaluation Studies as Topic↗

A new method of accurately identifying costs of individual patients in intensive care: the initial results.

OBJECTIVES: To analyse the patient-related and non-patient-related costs of intensive care using an activity-based costing methodology. DESIGN: A retrospective cost analysis of 68 patients admitted sequentially over a 10-week period. SETTING: The Adult General Intensive Care Unit of the Royal Hallamshire Hospital, Sheffield. RESULTS: The results showed large variations in the costs obtained for individual patients. The calculation of the costs for the initial period of stay showed a wide variation depending on whether the costs were determined per calendar day or per first 24-h period. Significant correlations of costs between the first 24 h of stay and the admitting Acute Physiology and Chronic Health II score (p < 0.004) and daily costs with the Therapeutic Intervention Scoring System scores (p < 0.0001) were found. The average daily patient-related cost of care was Pounds 592. Overhead costs were calculated at Pounds 560 per patient day, which made the total cost of a day's treatment in intensive care Pounds 1152. CONCLUSIONS: The use of average costs or scoring systems to cost intensive care is limited, as these methods cannot determine actual resource usage in individual patients. The methodology described here allows all the resources used by an individual patient or group of patients to be identified and thus provides a valuable tool for economic evaluations of different treatment modalities.

APACHE↗

Insulin VNTR allele-specific effect in type 1 diabetes depends on identity of untransmitted paternal allele. The IMDIAB Group.

The IDDM2 type 1 diabetes susceptibility locus was mapped to and identified as allelic variation at the insulin gene (INS) VNTR regulatory polymorphism. In Caucasians, INS VNTR alleles divide into two discrete size classes. Class I alleles (26 to 63 repeats) predispose in a recessive way to type 1 diabetes, while class III alleles (140 to more than 200 repeats) are dominantly protective. The protective effect may be explained by higher levels of class III VNTR-associated INS mRNA in thymus such that elevated levels of preproinsulin protein enhance immune tolerance to preproinsulin, a key autoantigen in type 1 diabetes pathogenesis. The mode of action of IDDM2 is complicated, however, by parent-of-origin effects and possible allelic heterogeneity within the two defined allele classes. We have now analysed transmission of specific VNTR alleles in 1,316 families and demonstrate that a particular class I allele does not predispose to disease when paternally inherited, suggestive of polymorphic imprinting. But this paternal effect is observed only when the father's untransmitted allele is a class III. This allelic interaction is reminiscent of epigenetic phenomena observed in plants (for example, paramutation; ref. 17) and in yeast (for example, trans-inactivation; ref. 18). If untransmitted chromosomes can have functional effects on the biological properties of transmitted chromosomes, the implications for human genetics and disease are potentially considerable.

Alleles↗

Epithelial migration in the colon: filling in the gaps.

1. The efficient repair of gastrointestinal mucosal injuries is essential in the preservation of the epithelial barrier to luminal antigens. Accumulated evidence suggests that epithelial migration plays a major part in this repair by rapidly resealing defects induced by both physiological and pathological insults, a process termed restitution. 2. This migration has been modelled in various ways, most commonly in mechanically wounded monolayers of cell lines or cells in primary culture, and in wounded human or animal tissue. Evidence from these models indicates that migration is a highly complex process, which is likely to involve the tightly controlled spatial and temporal interaction of multiple factors: (i) extracellular molecules such as soluble factors (e.g. growth factors, trefoil peptides, cytokines) and matrix components (e.g. collagen, laminin, fibronectin); (ii) signalling molecules activated by the interaction of these factors with cell surface receptors (e.g. protein kinases, phospholipases, low-molecular-weight GTPases); (iii) factors which regulate adhesion to other cells (e.g. E-cadherin) and to matrix components (e.g. integrins, hyaluronic acid receptors); (iv) factors which regulate detachment from the extracellular matrix (e.g. urokinase-type plasminogen activator, matrix metalloproteinases); and (v) molecules which regulate cytoskeletal function (e.g. Rac), which allows the formation of specialized cellular processes termed lamellipodia. 3. The identification of physiologically relevant factors that stimulate epithelial cell migration, and a better understanding of their mechanism of action, may be beneficial in the development of novel therapeutic approaches in diseases such as inflammatory bowel disease through the pharmacological or dietary enhancement of this migration.

Animals↗

Short-chain fatty acids promote the migration of colonic epithelial cells in vitro.

BACKGROUND & AIMS: Repair of colonic epithelial erosions requires cell migration. This study aimed to examine the effects of physiologically relevant short-chain fatty acids on migration in colonic epithelial cell lines. METHODS: Butyrate, propionate, and acetate were added to confluent monolayers of LIM1215 colon cancer cells after wounding. Migration in circular wounds was assessed after 24 hours. RESULTS: The migration of LIM1215 cells was stimulated in a concentration-dependent manner by all short-chain fatty acids. In four experiments, 2 mmol/L butyrate, 8 mmol/L propionate, and 16 mmol/L acetate induced 112.6% +/- 6.7%, 98.5% +/- 5.4%, and 63.4% +/- 7.2% (mean +/- SEM) stimulation above control migration, respectively. Their effects were additive at submaximal concentrations and reversible. Butyrate also stimulated migration in two other colon cancer cell lines, Caco-2 and LIM2405. However, butyrate failed to stimulate the migration of nongastrointestinal and nonepithelial cell lines. The stimulatory effect of butyrate required protein and RNA synthesis but was independent of cell proliferation, presence of serum, beta-oxidation, transforming growth factor beta, intracellular acidification, and substratum composition. CONCLUSIONS: In wounded in vitro models of colonic epithelium, short-chain fatty acids promote cell migration. If such an effect occurs in vivo, it would have ramifications for the biology and pathobiology of the colonic mucosa.

Animals↗

Quantitative analysis of the plain radiographic appearance of Brodie's abscess.

RATIONALE AND OBJECTIVES: The authors quantitate the radiographic features that distinguish the plain radiographic appearance of Brodie's abscess (BA) from other solitary lesions of bone. METHODS: Plain radiographs of 709 solitary bone lesions were reviewed, including 21 BAs. These were analyzed according to demographic, gross anatomic, and structural features. Vector analysis of groups of features was performed to determine those that are most sensitive and specific for the radiographic appearance of BA relative to other lesions of bone. RESULTS: Brodie's abscesses, in our series, are most commonly medullary-based (86%) lytic lesions (100%), with a geographic pattern of destruction (100%), well-defined edges (90%), marginal sclerosis (86%), and no bone enlargement (95%). In general, they have no periosteal reaction (71%), cortical break (95%), or visible matrix (90%). They typically are localized to the diaphysis or metaphysis (86%) of tubular bones, particularly in the lower extremity (63%). By vector analysis, the radiographic and demographic description of BA that provided the greatest sensitivity (67%-76%) while maintaining high prevalence (20%-21%) included a well-defined lytic lesion with a geographic pattern of destruction, and no bone enlargement or matrix or cortical break arising in patients younger than 40 years old. Although BAs commonly are small lesions with maximum diameters < 50 mm, size criteria did not greatly affect the sensitivity or specificity for detection of BA in our database. The differential diagnosis generated by vector analysis includes osteoid osteoma, nonossifying fibroma, giant cell tumor, eosinophilic granuloma chondroblastoma, and fibrous dysplasia, as the major lesions. CONCLUSIONS: Although BA can present with a variety of radiographic features, a relatively specific set of radiographic characteristics can be defined to assist in plain-film diagnosis and to help refine the differential diagnosis of similar-appearing lesions.

Abscess↗

Quantitative analysis of the plain radiographic appearance of Ewing's sarcoma of bone.

RATIONALE AND OBJECTIVES: The authors quantitate the radiographic features that distinguish the plain radiographic appearance of Ewing's sarcoma (ES) from other solitary lesions of bone. METHODS: A total of 709 cases of focal bone lesions, including 44 ES, were analyzed according to demographic, anatomic, and plain radiographic features. Vector analysis of groups of features was performed to determine those that are most sensitive and specific for the appearance of ES in contrast with other lesions in the database. RESULTS: In our sample, Ewing's sarcoma is most consistently a medullary-based (91%) lytic (89%) lesion with at least a partially permeative appearance (82%), poorly defined edges (82%), no margination (91%), and a soft-tissue mass (61%). When these lesions occur in long bones, they most commonly are found in the diaphysis (75%) and are proximal more often than distal. Vector analysis suggests that any primary bone lesion without radiographically visible matrix and with either a soft-tissue mass, an appearance of permeative destruction alone or in combination with other patterns of bone destruction is suspect for the diagnosis. This small subset of common features appears to have a high sensitivity (89%) and prevalence (47%) of ES among the lesions meeting these criteria. Limiting the age of the patients to progressively younger age groups increases the specificity but lowers sensitivity. The vector analysis-generated differential diagnoses includes osteosarcoma, giant-cell tumor, lymphoma, and chondrosarcoma. CONCLUSIONS: A relatively specific set of radiographic features can be defined, which will assist in the radiographic diagnosis of ES and improve upon current textbook descriptions.

Adolescent↗

Diagnosis of injuries after stab wounds to the back and flank.

BACKGROUND: Historically, patients with deep posterior wounds underwent a formal celiotomy to rule out injury. Currently, we use a policy of selective management. The purpose of this review is to evaluate our experience with selective management to identify potential areas of further improvement. METHODS AND RESULTS: This study includes 203 patients over a 10-year period. By changing from a policy of mandatory exploration to selective management the total celiotomy rate decreased from 100 to 24% and the therapeutic celiotomy rate increased from 15 to 80%. CONCLUSIONS: In stable patients, a diagnostic peritoneal lavage should be performed as the initial diagnostic study. When diagnostic peritoneal lavage is negative, triple contrast computed tomography should be performed to evaluate the remaining retroperitoneal structures. Any suggestion of pericolonic extravasation of contrast or air, edema, or hemorrhage must be interpreted as a positive study and prompt consideration for operative exploration.

Abdominal Injuries↗

Acute cervical spine trauma: diagnostic performance of single-view versus three-view radiographic screening.

PURPOSE: To compare the diagnostic accuracy of single-view and three-view cervical spine radiographs in acute trauma. MATERIALS AND METHODS: Radiographs of 97 patients with acute cervical spine fractures were matched with those of 92 proved normal cases. Fourteen radiologists, including three senior attending radiologists each with more than 20 years of post-residency experience, four junior attending radiologists each with less than 5 years of practice experience, three senior radiology residents in their 3rd or 4th year of radiology residency, and four junior radiology residents at the end of their 1st year of radiology training, interpreted each case twice: once as a lateral-only study and again as a three-view study. Multireader-multicase receiver operating characteristic analysis was performed. Difficult cases were reviewed for trends in the errors. RESULTS: Eight of 14 readers detected fractures better with the three-view series. Among junior attending radiologists, the differences were statistically significant. Most improvements were in fractures of the dens and fractures and unilateral dislocations of the articular mass. Overall, sensitivity increased from 81.8% to 83.3%. The reliability of fracture classification improved. Less experienced readers performed better with the three-view series. CONCLUSION: A three-view screening radiographic series will allow most readers to detect a few more fractures than a single-view series. The improvements occur primarily in a subset of difficult-to-diagnose injuries.

Acute Disease↗

MR imaging of clinically suspected scaphoid fractures.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of MR imaging in revealing occult fractures in patients with clinically suspected acute scaphoid fractures who have normal or equivocal findings on radiographs. SUBJECTS AND METHODS: Thirty-six patients underwent MR imaging within 7 days of wrist injury. All had physical findings suggestive of scaphoid fracture. Coronal T1-weighted, short inversion time inversion recovery, and either T2-weighted or proton density-weighted fast spin-echo sequences with fat suppression were used. Follow-up radiographs were obtained at least 2 weeks after MR imaging whenever possible. All imaging studies were reviewed by two musculoskeletal radiologists. RESULTS: MR imaging revealed 22 occult fractures in 20 patients. Thirteen of these 22 fractures were in the scaphoid bone, and nine were in the distal radius. On MR images, 16 patients had no evidence of fracture. Follow-up radiographs were available in 14 of the 20 patients who had occult fracture revealed by MR imaging. Eleven of the 13 occult fractures of the scaphoid bone were followed up (two were lost to follow-up), and 10 of the 11 showed signs of healing. Five of the nine lesions of the distal radius were followed up, and three of these showed evidence of healing fracture. Three patients without MR evidence of a fracture had follow-up radiographs that showed no fracture. Three patients had findings consistent with bone contusion on MR images; in two patients, the contusion was associated with other fractures, and in one patient, the contusion was isolated. CONCLUSION: MR imaging can reveal occult wrist fractures when findings on radiographs are normal or equivocal.

Adult↗

Fatigue in selected primary care settings: sociodemographic and psychiatric correlates.

OBJECTIVES: To determine the prevalence and sociodemographic and psychiatric correlates of prolonged fatigue syndromes among patients in primary care. DESIGN: Prospective questionnaire survey. PATIENTS AND SETTING: Adults over 18 years attending three general practices in metropolitan Sydney and one on the Central Coast, north of Sydney. RESULTS: Of 1593 patients, 25% had prolonged fatigue, while 37% had psychological disorder. Of the patients with fatigue, 70% had both fatigue and psychological disorder, while 30% had fatigue only. The factors associated with prolonged fatigue were concurrent psychological disorder, female gender, lower socioeconomic status and fewer total years of education. Patients with fatigue were more likely to have a current depressive disorder. CONCLUSIONS: Prolonged fatigue/neurasthenia syndromes are common in Australian primary care settings, and are commonly associated with current depressive disorders. Such syndromes, however, do not fit readily into current international psychiatric classification systems.

Adolescent↗

IDDM2-VNTR-encoded susceptibility to type 1 diabetes: dominant protection and parental transmission of alleles of the insulin gene-linked minisatellite locus.

IDDM2-encoded predisposition to type 1 diabetes has recently been mapped to the minisatellite or variable number of tandem repeat (VNTR) locus upstream of the insulin and insulin-like growth factor II genes on human chromosome 11p15.5. In a UK case-control study (n = 228 sporadic diabetics; n = 441 healthy controls), we show here that the genotype homozygous for VNTR class I alleles is predisposing to disease (RR = 2.68), and VNTR class III alleles are dominantly protective (RR = 0.37). In 722 diabetic families from the UK (n = 356), USA (n = 173), Denmark (n = 55) and Sardinia (n = 138), we have analysed the transmission of class I alleles to diabetic offspring from class I/III heterozygous parents. We confirm that in families from the USA, class I alleles are transmitted preferentially from fathers. However, in family data sets from the UK, Denmark and Sardinia, the reverse is true and maternal transmission is stronger. Furthermore, in the UK family data set, the difference between maternal and paternal transmissions is significant (P < 0.05). It is therefore unlikely that 'maternal imprinting' alone explains the parent-of-origin effects in IDDM2-encoded predisposition to type 1 diabetes, at least not in the UK. There is a relationship between VNTR class (allele length) and insulin gene expression, though some results from different studies are conflicting. In the human adult cadaveric pancreas, we confirm our preliminary results that class III alleles are associated with lower levels of insulin mRNA in vivo. Similar results have been obtained independently in human foetal pancreas samples. It is difficult to explain how these marginally lower levels of insulin expression could account for the observed VNTR class III-encoded protective effect. Perhaps the site of action of IDDM2, mediated by VNTR allelic variation, is not the pancreas but some other organ such as the thymus.

Adolescent↗

Detection of occult wrist fractures by magnetic resonance imaging.

The early detection and management of wrist fractures may avert potential complications and patient morbidity. Five cases are described in which radiographically-occult fractures were clearly demonstrated by magnetic resonance imaging (MRI). These fractures were seen on MRI as a low signal linear band on T1- and T2-weighted images, with surrounding increased signal intensity from bone marrow oedema on T2-weighted images. In one case, intense oedema obscured the fracture line on the initial MR scan. MRI is useful in confirming the presence of a fracture, delineating its exact shape and location, and in the follow-up of these injuries during and after treatment.

Adult↗