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Biomedical subjects

A Forbes

Publications and source records attributed to A Forbes.

At least 109 records · Page 6Linked to original sources

Cell migration in Drosophila.

Recent genetic studies in Drosophila have identified signals that direct cell movement, mechanisms that transduce such signals within migrating cells and some of the molecular machinery underlying cell motility. Activation of the fibroblast growth factor receptor signaling pathway is required for migration of the cells of the developing respiratory system and mesoderm. A signal dependent on 3-hydroxy-3-methylglutanyl Coenzyme A reductase attracts migrating primordial germ cells to the somatic gonad, whereas the phosphohydrolase, phosphatidic acid phosphatase type 2, repels germ cells. In the female germline, the migratory path of border cells is directed by the homophilic adhesion molecule E cadherin.

Animals↗

Determinants of antibodies to Cryptosporidium infection among gay and bisexual men with HIV infection.

A cross-sectional serosurvey for markers of prior Cryptosporidium infection was conducted among homosexual or bisexual males infected with human immunodeficiency virus (HIV); of 262 individuals approached, 236 (90%) agreed to participate. Serological response to two Cryptosporidium antigens was measured using a Western blot assay. The intensity or detection of serological responses to two Cryptosporidium antigens was not associated with CD4 cell counts or tap water consumption. A number of sexual practices were related to increased serological response for only the 27-kDa marker, including having had sex within the past 2 years, having anal sex and having had a larger number of sex partners during the past 2 years. Attending a spa or sauna was related to serological response to both the 27-kDa and 17-kDa markers. Based on these results, activities related to sexual activity appear to be a significant risk factors for prior Cryptosporidium infection.

AIDS-Related Opportunistic Infections↗

Expression of syndecan-1 in inflammatory bowel disease and a possible mechanism of heparin therapy.

Heparin apparently aids healing in ulcerative colitis although its mechanism of action is unknown. The purpose of this study was to investigate the hypothesis that heparin functions as a coreceptor molecule for basic fibroblast growth factor, a role usually performed by heparan sulfate chains on syndecan-1. A marked reduction of syndecan-1 immunostaining was found in reparative epithelium from inflammatory bowel disease patients. Removal of heparan sulfate on gastrointestinal epithelial cells in vitro reduced the proliferative response to basic fibroblast growth factor. The response to basic fibroblast growth factor was completely restored by the addition of heparin. Loss of syndecan-1 expression occurs in the regenerative mucosa in inflammatory bowel disease. Although this may facilitate tissue motility, its loss probably adversely affects the ability of cells to bind basic fibroblast growth factor. The present data show that heparin may substitute the loss of functional activity of syndecan-1 in the binding of basic fibroblast growth factor.

Cells, Cultured↗

Residential characteristics influence Der p 1 levels in homes in Melbourne, Australia.

BACKGROUND: Exposure to house dust mite (HDM) allergens is an important risk factor for childhood asthma. Knowledge of environmental determinants of HDM allergen levels is essential before designing rational avoidance measures. AIM: To investigate the effect of domestic characteristics on HDM allergen (Der p 1) levels in Melbourne homes. METHODS: Dust was collected from bed and floor of the bedrooms in 485 houses over a period of one year. Dust was analysed for Der p 1 levels using an enzyme-linked immunosorbent assay. Temperature and relative humidity were measured at the visit. Details of residential characteristics were collected using a questionnaire. Statistically significant predictors of Der p 1 levels (P < 0.05) were identified using multiple linear regression. RESULTS: High levels of Der p 1 were observed in the floors (geometric mean 17.2 microg/g fine dust) as well as in the beds (geometric mean 20.3 microg/g fine dust). Der p 1 levels in the floor dust were significantly lower in winter and spring. They were higher in houses built before 1980 and those with central heating, weather board walls, damp bedrooms or fitted old wool carpets. Der p 1 levels in bed dust were significantly higher in houses built before 1980, with wooden floors built on stumps, with high relative humidity, with visible mould in the room, in beds with an old mattress or in beds without a quilt. CONCLUSIONS: We would encourage construction of homes without carpets, wooden floors on stumps or weather board walls.

Allergens↗

Prevalence and residential determinants of fungi within homes in Melbourne, Australia.

BACKGROUND: Recent epidemiological studies suggest that the adverse respiratory health effects caused by the inhalation of fungal propagules are substantial. Knowledge of the prevalence and environmental determinants of indoor fungal levels is essential in designing effective avoidance measures. AIM: To investigate the prevalence of fungi and the influence of residential characteristics on levels of fungi within homes in Melbourne, Australia. METHODS: Floor dust and air samples were collected from bedrooms in 485 houses over 1 year. The dust was analysed for ergosterol, a marker of cumulative fungal biomass exposure. Total and genera-specific fungal propagules were identified in air samples. Details of the relevant residential characteristics were documented using a questionnaire. Independent predictors (P < 0.05) of ergosterol and total fungal propagules were identified by multiple linear regression. RESULTS: Fifty-five percent of the houses had viable fungal propagules exceeding 500 CFU/m3. Cladosporium and Penicillium were identified as the most prevalent and abundant fungal genera in indoor air. The median ergosterol level in bedroom floor was 3.8 microg/g of dust. Multivariate analysis showed that total fungal propagules in indoor air were lower in bedrooms with a ceiling fan, without visible mould, and those that were more frequently vacuumed, had a solid fuel fire, had windows closed at the time of the sampling or lacked pets. The presence of more than one cat had the greatest effect on total fungal propagules. Ergosterol levels were significantly lower in homes without old fitted carpets, visible mould or pets and those with frequent airing and regular use of an extractor fan in the kitchen. Old wall-to-wall carpets had the greatest effect on ergosterol. CONCLUSIONS: High indoor fungal exposures were associated with infrequent ventilation or vacuuming, presence of pets, visible mould and old carpets.

Adult↗

Gender differences in knee cartilage volume as measured by magnetic resonance imaging.

OBJECTIVE: The aim of this study was to analyze sex differences in knee cartilage volume. METHODS: Articulate cartilage volumes were determined by processing images acquired in the sagittal plane using T1-weighted fat saturation magnetic resonance on an independent work station. The knees of 28 subjects (17 male, 11 female) who underwent MRI for clinical indications (pain <3 months) but who had a normal X-ray and structurally normal MRI were examined. RESULTS: Males had significantly larger cartilage volumes than females, with difference in cartilage volume remaining statistically significant after adjusting for age, height, weight and bone volume. The differences for males relative to females were: femoral cartilage volume [4.1 ml 95% CI (2.0, 6.1)]; and patella cartilage volume [1.4 ml (0.2, 2.7)]. Although not statistically significant, the tibial cartilage volume also showed these sex differences. Exploratory analysis indicated an increasing gender difference with increasing age for patellar cartilage volume. CONCLUSION: Men have significantly larger knee cartilage volume than women, independent of body and bone size. The mechanisms for this will need to be determined.

Adult↗

Linkage of inflammatory bowel disease to human chromosome 6p.

Inflammatory bowel disease (IBD) is characterized by a chronic relapsing intestinal inflammation. IBD is subdivided into Crohn disease and ulcerative colitis phenotypes. Given the immunologic dysregulation in IBD, the human-leukocyte-antigen region on chromosome 6p is of significant interest. Previous association and linkage analysis has provided conflicting evidence as to the existence of an IBD-susceptibility locus in this region. Here we report on a two-stage linkage and association analysis of both a basic population of 353 affected sibling pairs (ASPs) and an extension of this population to 428 white ASPs of northern European extraction. Twenty-eight microsatellite markers on chromosome 6 were genotyped. A peak multipoint LOD score of 4.2 was observed, at D6S461, for the IBD phenotype. A transmission/disequilibrium test (TDT) result of P=.006 was detected for D6S426 in the basic population and was confirmed in the extended cohort (P=.004; 97 vs. 56 transmissions). The subphenotypes of Crohn disease, ulcerative colitis, and mixed IBD contributed equally to this linkage, suggesting a general role for the chromosome 6 locus in IBD. Analysis of five single-nucleotide polymorphisms in the TNFA and LTA genes did not reveal evidence for association of these important candidate genes with IBD. In summary, we provide firm linkage evidence for an IBD-susceptibility locus on chromosome 6p and demonstrate that TNFA and LTA are unlikely to be susceptibility loci for IBD.

Alleles↗

Parenteral nutrition.

The indications for parenteral nutrition have been examined over the past year. These studies have mostly supported the enteral compared to the intravenous route. Because a formal diagnosis of intestinal failure has not always been the key to initiating intravenous nutrition, however, the clinical applications of their conclusions are uncertain. Studies have also focused on supplementing intravenous nutrition with glutamine; the lack of ideal control groups makes interpretation difficult. Finally, based on present evidence, a pragmatic approach to the provision of intravenous nutrition can be supported.

Journal Article↗

Extraintestinal manifestations of ulcerative colitis following restorative proctocolectomy.

BACKGROUND: Rheumatological and other extraintestinal manifestations (EIM) are common in inflammatory bowel disease (IBD) but also seem to occur in patients after restorative proctocolectomy and formation of an ileo-anal pouch. The prevalence and significance of these symptoms have not been established in this clinical context. OBJECTIVE: To evaluate prospectively the prevalence and associations of EIM of IBD in ulcerative colitis (UC) patients following restorative proctocolectomy (RP) and to compare the findings to those in a control group of familial adenomatous polyposis (FAP) patients who had undergone similar surgery. METHODS: One hundred and twenty-three (97 UC and 26 FAP) consecutive patients with ileal pouches undergoing long-term follow-up underwent an assessment of rheumatological symptoms and signs, similarly of other EIM; each underwent pouch endoscopy and biopsy. RESULTS: Symptoms in the joints were reported in 30 (31%) of UC patients compared to two (8%) FAP patients (P = 0.02). Twenty-four (80%) of the affected patients had a polyarticular arthralgia affecting primarily the knees, and small joints of the hands. Clinical findings and radiological investigations were almost exclusively normal. Most patients had mild symptoms, with only 12 of the 30 reporting interference with daily life. The presence of symptoms in the joints was not associated with a positive family history for IBD or other EIM, the presence of non-rheumatological EIM or the presence of pouchitis. Histological scores of pouch inflammation did not differ between those with and without symptoms of the joints. CONCLUSIONS: A mild polyarticular arthralgia, similar to that associated with active IBD, is common following RP and may commence after surgery. It is not associated with the presence of pouch inflammation.

Adult↗

Evaluation of a randomised controlled trial of adult asthma education in a hospital setting.

BACKGROUND: Although patient education is a key step in the Australian Asthma Management Plan, its impact has not been assessed in a hospital outpatient asthma clinic. METHODS: A controlled trial was undertaken in 125 adults with asthma recruited from the Alfred Hospital Asthma and Allergy Clinic and randomly allocated to an intervention (n = 64) or control (n = 61) group. Subjects in the intervention group attended three education sessions, each of 90 minutes duration, spread over three successive weeks. Asthma knowledge, quality of life, self-management skills, and attitudes and beliefs about asthma were assessed by questionnaires at baseline and after six months. The intervention group was also assessed immediately after the three education sessions. The control group was evaluated after six months of usual care. RESULTS: Asthma knowledge improved significantly in the intervention group after three education sessions (p = 0.0001) and this was retained six months later (p = 0.03). The impact of asthma on quality of life decreased significantly immediately after intervention (p = 0.03) but this was not maintained six months later (p = 0.35). On the other hand, the intervention had little impact on self-management skills or attitudes and beliefs about asthma. However, the control group had also improved their knowledge, quality of life and self-management skills after six months of usual care. The difference in mean change in knowledge score at six months between the intervention and control groups was not significant (p = 0.51). CONCLUSIONS: In contrast to some other studies, a limited asthma education programme in a hospital outpatient setting had a positive impact on patients' knowledge of asthma, but not on their quality of life, self-management skills, or attitudes and beliefs about asthma.

Adult↗

Predictors and timing of adverse experiences during trandsdermal nicotine therapy.

OBJECTIVES: Difficulty sleeping is a recognised tobacco withdrawal symptom, but sleep problems, like application site reactions, are commonly reported as adverse reactions to transdermal nicotine therapy. However, no studies have examined potential predictive factors associated with the occurrence of expected adverse experiences during transdermal nicotine therapy. The subject of skin tolerability among patients with a history of eczema, psoriasis or other skin disorders is of particular interest, as are the relationships between plasma concentrations of nicotine, concurrent smoking, sleep problems and nausea. METHODS: The cohort study involving 1392 participants was designed to assess the timing, severity and predictive factors of adverse experiences reported during 24-hour transdermal nicotine therapy. Data were collected on patients aged 18 to 70 years old who were smokers and who had expressed a strong desire to stop smoking. The intervention consisted of brief behavioural counselling, a booklet containing smoking cessation advice and instructions for use of the patches, and a 12-week course of decreasing transdermal nicotine doses. RESULTS: Follow-up was available on 1392 out of 1481 study participants. The majority of adverse experiences were mild. Sleep problems occurred in 669 out of 1392 (48%) participants and most often commenced on the day of smoking cessation. Application site reactions occurred in 478 out of 1392 (34%) participants and most often occurred after 6 days of therapy. No predictor had an adjusted hazard ratio above 2. Statistically significant (p < 0.05) predictors of sleep problems were successfully quitting smoking and female gender. Predictors of application site reactions were psoriasis or eczema, other skin conditions, age <40 years, female gender, place of birth outside Australasia, and trade or university education level. Substantially increased nicotine intake during therapy compared with baseline smoking occurred in 8% of participants who smoked concurrently, and 4% of participants who did not (p = 0.1). Increased nicotine intake was associated with a modest increase in the overall rate of adverse experiences (89% vs 63%, p = 0.04) and dizziness/lightheadedness (17% vs 3%, p = 0.03), but not with sleep problems or cardiovascular events. CONCLUSIONS: Transdermal nicotine therapy appears to be well tolerated, even if the user smokes concurrently. Sleep disturbance during therapy appeared to be primarily associated with tobacco withdrawal rather than with nicotine excess from treatment with transdermal nicotine. Study participants with pre-existing skin disorders were somewhat more likely to report mild application site reactions than other participants.

Administration, Cutaneous↗

Systematic review of randomised controlled trials of interventions for painful shoulder: selection criteria, outcome assessment, and efficacy.

OBJECTIVE: To review the efficacy of common interventions for shoulder pain. DESIGN: All randomised controlled trials of non-steroidal anti-inflammatory drugs, intra-articular and subacromial glucocorticosteroid injection, oral glucocorticosteroid treatment, physiotherapy, manipulation under anaesthesia, hydrodilatation, and surgery for shoulder pain that were identified by computerised and hand searches of the literature and had a blinded assessment of outcome were included. MAIN OUTCOME MEASURES: Methodological quality (score out of 40), selection criteria, and outcome measures. Effect sizes were calculated and combined in a pooled analysis if study population, end point, and intervention were comparable. RESULTS: Thirty one trials met inclusion criteria. Mean methodological quality score was 16.8 (9.5-22). Selection criteria varied widely, even for the same diagnostic label. There was no uniformity in the outcome measures used, and their measurement properties were rarely reported. Effect sizes for individual trials were small (range -1.4 to 3.0). The results of only three studies investigating "rotator cuff tendinitis" could be pooled. The only positive finding was that subacromial steroid injection is better than placebo in improving the range of abduction (weighted difference between means 35 degrees (95% confidence interval 14 to 55)). CONCLUSIONS: There is little evidence to support or refute the efficacy of common interventions for shoulder pain. As well as the need for further well designed clinical trials, more research is needed to establish a uniform method of defining shoulder disorders and developing outcome measures which are valid, reliable, and responsive in affected people.

Anti-Inflammatory Agents, Non-Steroidal↗

A standardized protocol for measurement of range of movement of the shoulder using the Plurimeter-V inclinometer and assessment of its intrarater and interrater reliability.

OBJECTIVE: To develop a standardized protocol for measurement of shoulder movements using a gravity inclinometer designed for use in clinical trials, and to assess its intra- and interrater reliability in a group of manipulative physiotherapists. METHODS: After instruction, 6 manipulative physiotherapists independently assessed 8 movements of the shoulder, including total and glenohumeral flexion (TF, GHF), total and glenohumeral abduction (TA, GHA), external rotation in neutral (ERN) and abduction (ERA), internal rotation in abduction (IRA), and hand behind back (HBB), in random order in 6 patients with shoulder pain and stiffness according to a 6 x 6 Latin square design using the standardized protocol. The assessments were then repeated. Analysis of variance was used to partition total variability into components of variance in order to calculate intraclass correlation coefficients (ICCs). RESULTS: The intra- and interrater reliability of the different movements varied widely. Reliability was higher for TF and TA than for the corresponding glenohumeral movements (e.g., intrarater ICCs: TF = 0.80, GHF = 0.65, TA = 0.75, GHA = 0.62). Interrater reliability was higher in the second round suggesting a practice effect (e.g., round 1, 2 interrater ICCs TF = 0.62, 0.82; TA = 0.62, 0.88; ERN = 0.85, 0.95). CONCLUSION: The measurement of the active range of TF, TA, ERN, and HBB, measured by manipulative physiotherapists following the standardized protocol, has intra- and interrater reliability acceptable for use as an outcome measure in clinical trials assessing interventions for shoulder pain.

Humans↗

Intra-abdominal and pelvic abscess in Crohn's disease: results of noninvasive and surgical management.

BACKGROUND: Intra-abdominal and pelvic abscesses occur in 10-30 per cent of patients with Crohn's disease. The aim of this study was to establish the clinical characteristics and outcome of patients admitted over a 4-year period with an abdominal or pelvic abscess secondary to Crohn's disease. METHODS: Patients with Crohn's disease-related intra-abdominal or pelvic abscess were identified from a prospectively collected database, comprising all admissions between 1991 and 1994. Medical records were reviewed retrospectively and data gathered regarding management and outcome. RESULTS: Thirty-six patients were identified with Crohn's disease-related abscess, of whom 15 were considered for initial percutaneous drainage. Drainage was technically possible in eight of these patients: it failed in four, gave good long-term results in two, and was followed by recurrence after 3 years in one and by later surgery unrelated to the abscess in one. Twenty-eight patients underwent surgery, with only four requiring a stoma. Complications occurred in 12 patients. At 3 months, 22 of the 36 patients were in remission. CONCLUSION: Crohn's intra-abdominal abscesses are associated with a high morbidity rate. Selected cases can be drained percutaneously, without adding to the morbidity, and sometimes resulting in abscess resolution.

Abdominal Abscess↗

Single- versus multiple-dose antimicrobial prophylaxis for major surgery: a systematic review.

BACKGROUND: Single-dose antimicrobial prophylaxis for major surgery is a widely accepted principle; recommendations have been based on laboratory studies and numerous clinical trials published in the last 25 years. In practice, single-dose prophylaxis has not been universally accepted and multiple-dose regimens are still used in some centres. Moreover, the principle has recently been challenged by the results of an Australian study of vascular surgery. The aim of this current systematic review is to determine the overall efficacy of single versus multiple-dose antimicrobial prophylaxis for major surgery and across surgical disciplines. METHODS: Relevant studies were identified in the medical literature using the MEDLINE database and other search strategies. Trials included in the review were prospective and randomized, had the same antimicrobial in each treatment arm and were published in English. Rates of postoperative surgical site infections (SSI) were extracted, 2 x 2 tables prepared and odds ratios (OR) [with 95% confidence intervals (95% CI)] calculated. Data were then combined using fixed and random effects models to provide an overall figure. In this context, a high value for the combined OR, with 95% CI > 1.0, indicates superiority of multiple-dose regimens and a low OR, with 95% CI < 1.0, suggests the opposite. A combined OR close to 1.0, with narrow 95% CI straddling 1.0, indicates no clear advantage of one regimen over another. Further subgroup analyses were also performed. RESULTS: Combined OR by both fixed (1.06, 95% CI, 0.89-1.25) and random effects (1.04, 95% CI, 0.86-1.25) models indicated no clear advantage of either single or multiple-dose regimens in preventing SSI. Likewise, subgroup analysis showed no statistically significant differences associated with type of antimicrobial used (beta-lactam vs other), blinded wound assessment, length of the multiple-dose arm (> 24 h vs 24 h or less) or type of surgery (obstetric and gynaecological vs other). CONCLUSIONS: Continued use of single-dose antimicrobial prophylaxis for major surgery is recommended. Further studies are required, especially in previously neglected surgical disciplines.

Anti-Bacterial Agents↗

Loss of Bcl-2 expression correlates with tumour recurrence in colorectal cancer.

AIMS: To investigate the association between immunohistochemical expression of Bcl-2 and p53 in colorectal cancer and tumour recurrence following surgery. METHODS: Sixty six cases of Dukes' B colorectal carcinoma were studied. All tumours were moderately differentiated and were shown to be histologically clear of the resection margins. Immunohistochemistry was performed on formalin fixed paraffin wax embedded tissue using monoclonal antibodies for p53 and Bcl-2. The Bcl-2 staining was assessed separately for relative intensity of staining and percentage of positive tumour cells and given a final score which combined the two factors. The p53 staining was assessed on number of positive tumour cells only. The patterns of immunostaining of those cases in which there had been tumour recurrence were compared with those cases in which there was no tumour recurrence (controls). RESULTS: A statistically significant inverse association was found between Bcl-2 score and tumour recurrence (median Bcl-2 score of 6 (interquartile range (IQR) 2-9) in patients with recurrent disease; median Bcl-2 score of 8 (IQR 6-10) in those without recurrence; p = 0.03). When examined separately, both the intensity of expression and percentage of positive tumour cells were significantly associated with tumour recurrence (p = 0.04 in each case). There was no association between p53 staining and tumour recurrence. CONCLUSION: Results suggest that, when controlled for differentiation, Bcl-2 expression is a prognostic marker and may be useful as an adjunctive test in clinical decision making.

Biomarkers, Tumor↗

Three important subgroups of hypertensive persons at greater risk of intracerebral hemorrhage. Melbourne Risk Factor Study Group.

Hypertension as a risk factor for intracerebral hemorrhage (ICH) is poorly quantified, particularly in the setting of the use of modern antihypertensive agents. To investigate this, we studied 331 consecutive hospital cases of primary ICH verified by computed tomography or autopsy, occurring during the period 1990 through 1992, and 331 age- and sex-matched community-based control subjects in a city-wide study involving 13 hospitals. Hypertension approximately doubled the risk of ICH (adjusted odds ratio [OR], 2.45; 95% confidence interval [CI], 1.61 to 3.73). The OR associated with hypertension was significantly greater among those who had ceased taking medications, supervised and unsupervised (OR, 4.98; 95% CI, 2.25 to 11.02), compared with those who had not (OR, 1.95; 95% CI, 1.20 to 3.16), were under the age of 55 years (OR, 7.68; 95% CI, 2.65 to 22.5), or were current smokers (OR, 6.12; 95% CI, 2.29 to 16.35). The presence of hypertension did not influence size or location of the hemorrhage. However, those dying from ICH displayed a greater risk of ICH due to hypertension than survivors, with the ratio of the two ORs being 5.47 (95% CI, 1.23 to 24.44). These findings provide evidence for a greater increase in risk of ICH due to hypertension among younger persons, current smokers, and those discontinuing antihypertensive therapy. This is the first direct evidence for a link between stopping antihypertensive medication use and stroke risk; targeting these individuals for more intensive monitoring and education on the importance of risk factor modification may help to reduce the impact of this form of stroke.

Adolescent↗