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Biomedical subjects

R Fisher

Publications and source records attributed to R Fisher.

At least 37 records · Page 2Linked to original sources
PubMed2001

Non-toxic ubiquitous over-expression of utrophin in the mdx mouse.

Duchenne muscular dystrophy (DMD) is an inherited, severe muscle wasting disease caused by the loss of the cytoskeletal protein, dystrophin. Patients usually die in their late teens or early twenties of cardiac or respiratory failure. We have previously demonstrated that the dystrophin related protein, utrophin is able to compensate for the loss of dystrophin in the mdx mouse, the mouse model of the disease. Expression of a utrophin transgene under the control of an HSA promoter results in localization of utrophin to the sarcolemma and prevents the muscle pathology. Here we show that the over-expression of full-length utrophin in a broad range of tissues is not detrimental in the mdx mouse. These findings have important implications for the feasibility of the up-regulation of utrophin in therapy for DMD since they suggest that tissue specific up-regulation may not be necessary.

Aging↗
PubMed2001

Pregnancy outcomes and community health: the POUCH study of preterm delivery.

In light of the social/ethnic disparity in preterm delivery (PTD) rates, the Pregnancy Outcomes and Community Health (POUCH) Study takes a broad view of the determinants of PTD by attempting to link underlying biological and psychosocial factors. The relationships between placental pathology, maternal biomarkers, and antecedent psychosocial factors are evaluated in three hypothesised pathways of PTD - one characterised primarily by infection, one by maternal vascular disease, and one by premature elevations in corticotropin releasing hormone in the absence of histological evidence of placental pathology. Within each pathway, an emphasis is placed on understanding the roles of stress and of maternal serum alpha-fetoprotein, an early biomarker associated with PTD. The POUCH Study enrolls pregnant women from five Michigan communities. Information about these women and their environments is gathered through detailed interviews and collection of biological samples including hair, urine, saliva, blood, vaginal fluid, and vaginal smear at 15-26 weeks of gestation. We have chosen to focus on the second trimester--a time when pathological processes may have evolved to a detectable stage, but generally before the onset of biological changes that accompany labour. This focus is consistent with the long-range goal of early detection/intervention and prevention of PTD.

Adult↗
PubMed2001

Pediatric Asthma Study of the State Medical Society of Wisconsin.

PROBLEM: Asthma management should follow evidence-based national guidelines. We compared patient self-reports of usual care to clinical practice guidelines. METHODS: Cross-sectional survey of parents of 245 children age 2-14 years with asthma seen by physicians at 13 practices in Wisconsin. RESULTS: Most children with asthma were atopic and a substantial number experienced psychosocial problems. Families infrequently used written care plans. Knowledge about asthma triggers, especially tobacco smoke, was deficient. Increasing asthma severity was associated with poorer health. Although most parents rated their physician's expertise as excellent or very good, one-third of children with persistent symptoms used no daily control medication. Significant differences were observed between primary care and specialty care with the best asthma self-management done by patients of specialists. CONCLUSION: Care of Wisconsin children with asthma inconsistently follows national guidelines. They and their families require improved education, written care plans, appropriate medications, and psychosocial support.

Adolescent↗
PubMed2000

A randomized prospective trial of low-dose OKT3 induction therapy to prevent rejection and minimize side effects in recipients of kidney transplants.

BACKGROUND: We attempted to minimize the undesired side effects and maximize the benefit of OKT3 induction therapy in renal transplantation. METHODS: One hundred and one recipients of kidney-only transplants were randomized to three groups. Each received low-dose 2.5-mg OKT3 induction for 7-14 days, but different premedication on days 0, 1, and 2. Group I was given 250 mg i.v. methylprednisolone at 1 and 6 hr, and group II received another 500 mg at 1 hr before initial OKT3. Group III received Atgam 15 mg/kg on day 0 and began OKT3 on day 1. A CD3+ T-cell cut-off of 50/mm3 was used to guide therapy. Maintenance therapy included cyclosporine and steroids for each patient. However, groups I and II were also given mycophenolate mofetil, and group III received azathioprine as a third agent. All rejections were biopsy confirmed and Banff scored. RESULTS: No differences in demographic or transplant characteristics were noted between groups I, II, and III, and mean follow-up was 25.7 (1-38) months. There was no significant difference in actuarial patient (90%, 91%, 94%) or graft survival (83%, 88%, 84%) at 3 years between the respective groups. Mean creatinine values and infectious complications were similar for each group. No patient experienced acute rejection during induction, and eight patients required dose escalation to sustain suppression of CD3 counts. The incidence of acute rejection at 6 and 12 months was significantly (P=0.004) greater in group III (38.2, 44.1%) than in either group I (15.1, 18.1%) or group II (14.7, 17.6%); relative risk 1.988 (95% CI 1.012-3.906). Formation of anti-OKT3 antibody was significantly (P=0.006) greater in group III (26.5%) than in group I (6%) or group II (2.9%). Group I recipients enjoyed significantly (P=0.001) fewer (2.17) OKT3 side effects on days 0, 1, and 2 than group II (3.03) or group III (2.49), and contained the largest number (61%) of recipients who experienced no side effects. Group I also exhibited the most suppressed profile of OKT3-induced release of tumor necrosis factor-alpha (P=0.006), interferon-gamma (P=NS), and interleukin-6 (P=0.01) on days 0 and 1. CONCLUSIONS: Low-dose 2.5-mg OKT3 with pretreatment of split-dose steroids on days 0, 1, and 2 provides the most effective method for OKT3 induction, which minimizes side effects for most patients. Subsequent maintenance therapy with cyclosporine, mycophenolate mofetil, and steroids provides effective rejection prophylaxis without increased complications for up to 3 years. Predepletion of T cells before exposure to OKT3 does not prevent cytokine release.

Acute Disease↗
PubMed2000

The impact of coronary stenting on immediate procedural complication and long-term clinical restenosis at Waikato Hospital.

AIM: Clinical data on coronary stenting from within New Zealand is scarce and, in particular, the impact of current stent technologies is unknown. We reviewed all angioplasties undertaken at Waikato Hospital over a two year period to determine the clinical effect of coronary stenting on the local population. METHODS: Data from all patients who underwent coronary angioplasty at Waikato Hospital between July 1, 1995 and July 1, 1997 were included. Stents were deployed either to remedy sub-optimal results, or were electively used for saphenous vein grafts or restenotic lesions. Patient follow-up was obtained through a combination of database review, chart search and GP or patient contact. RESULTS: 662 lesions were dilated in 441 patients. 91 lesions were stented, 52.7% for sub-optimal results following balloon angioplasty. 98% of patients were followed up at six months. Whilst procedural success rate was higher in stented patients compared to unstented patients (96.7% vs 87.5% respectively, p=0.009) the in-hospital sub-acute occlusion rate was also increased (6.8% vs 1.9% respectively, p=0.007). At six months, coronary restenosis requiring repeat angioplasty was infrequent (10.9% overall) with no significant difference between the two groups (8.1% vs. 11.2% for stented vs unstented patients respectively, p=NS). CONCLUSIONS: The use of stents appears effective in improving immediate procedural success rates. Despite stented patients being at higher risk initially, their complication and six month clinical restenosis rates were similar.

Angioplasty, Balloon, Coronary↗
PubMed2000

Relationship between expression of the KAI1 metastasis suppressor and other markers of advanced bladder cancer.

Expression of a newly described inhibitor of tumour metastasis, KAI1, was examined in bladder cancer progression and compared with the expression of p53 and pRb, which are markers of advanced disease. KAI1 mRNA (by in situ hybridization) and protein levels (by immunohistochemistry) were examined in 135 paraffin-embedded bladder tissue sections. Significant decreases in KAI1 mRNA and protein levels were detected between normal and tumour tissue (p<0.001 and p=0.026, respectively), and between non-invasive and invasive tumours (p=0.046 and p<0.001, respectively). Loss of KAI1 protein expression was accompanied by a shift in staining pattern from a uniform distribution to a weaker, membranous or heterogeneous pattern. Normal tissue and low-grade tumours showed little p53 protein staining. High level staining (indicative of mutant p53) was associated with increased grade in non-invasive tumours (p=0.031) but was not significantly higher in invasive tumours. Whilst p53 protein staining increased with malignant progression and KAI1 mRNA expression decreased, there was no significant correlation between the two patterns (p=0.33, adjusted for group, p=0.18) or when only cancer samples were analysed (p=0.065, adjusted for group, p=0.26), even when taking into account overexpression of MDM-2 protein as a pathway for inactivation of p53. There was no correlation between loss of KAI1 mRNA expression and gain of abnormal pRb staining (p=0. 30, or adjusted for tumour samples only, p=0.59). These results suggest that loss of KAI1 expression is associated with invasive bladder cancer, but is not related to mutation of p53 or to loss of normal pRb expression.

Antigens, CD↗
PubMed2000

Emotional suppression: can it predict cancer outcome in women with suspicious screening mammograms?

BACKGROUND: Previous studies have implicated emotional suppression, in particular suppression of anger, in the onset and progression of breast cancer. Many of these studies used non-standardized measures and failed to control for the effects of age and/or possible knowledge of diagnosis. The present study aimed to avoid these methodological errors in investigating the relationship of emotional suppression to a diagnosis of breast cancer in a large mammography screened population. METHOD: Data were collected from 1151 women with suspicious mammograms recalled to a breast screening programme. Prior to multidisciplinary assessment women were asked to complete the Courtauld Emotional Control Scale. Imaging assessment outcome data and biopsy results were collected. RESULTS: Fifteen per cent of this population subsequently were diagnosed with breast cancer. There were no significant associations between a cancer outcome and emotional suppression before or after the highly significant effect of age was taken into account. CONCLUSIONS: These results suggest that suppression of emotion may not be relevant to the development of breast cancer. Its role in the progression of existing disease requires clarification.

Adult↗
PubMed2000

Early glottic carcinoma: results of treatment by radiotherapy.

The purpose of the present paper was to review the results of treating early (stages T1-2N0) glottic, squamous cell carcinoma by radiotherapy in the Department of Radiation Oncology, Prince of Wales Hospital, Sydney. A retrospective review was carried out of all patients seen in the department from 1967 to 1994, inclusive. To be eligible, patients had to have newly diagnosed cancer and to have been treated with curative intent by radiotherapy alone. Three hundred and sixty-nine patients satisfied the eligibility requirements. The mean follow-up time was 12.2 years (maximum: 28 years). At 5 years the actuarial local control rate was 80% (84% for stage T1 and 72% for T2). The ultimate local control rate was 96%. The overall survival rates at 5 and 10 years were 73% and 52%, respectively. The risk of nodal recurrence was much higher after persisting disease or local recurrence. Our results confirm the high cure rates achieved with this modality of treatment and are comparable with those reported in the literature.

Carcinoma, Squamous Cell↗
PubMed1999

Association of maternal IgM concentrations above the median at 15-19 weeks of gestation and early preterm delivery.

IgM concentrations greater than the median in maternal serum collected at 15-19 weeks of pregnancy were strongly associated (odds ratio 15.6) with delivery before 29 weeks. Our results suggest that the postulated inflammatory component in the aetiology of very preterm delivery may elicit a measurable maternal humoral response as early as mid-trimester.

Case-Control Studies↗
PubMed1999

A mouse fibroblast line cycles between monolayer and spheroid forms, regulates Met and HGF expression, and releases an attachment and growth-promoting substance.

A subline of mesoderm-derived mouse NIH3T3 fibroblasts was selected for its ability to proliferate in serum-free media. This cell line (SFDH) grows as a monolayer at low density and spontaneously forms dense, multicellular spheroids at high density. Spheroid formation can also be induced by the addition of dexamethasone, polybrene, or heparin. Spheroids eventually detach from the substrate, but will reattach and re-form monolayers when transferred to fresh culture vessels and media, repeating the cycle again upon reaching high density. Thin section analysis of spheroids shows morphologically-distinct regions of cells, including an attenuated outer surface and a cuboidal interior with occasional lumen-like areas. Over time in culture, spheroids express increasing levels of met, the Met ligand-SF/HGF and cytokeratin, an epithelial marker, in comparison to monolayers. Both monolayer and spheroid-derived cells are rapidly tumorigenic in nude mice. Media conditioned by SFDH cells contain factors that stimulate growth and attachment of a variety of tumorigenic and non-tumorigenic cell lines, inducing cells to divide in serum-free media for up to 14 days when plated on tissue culture-treated and nontreated plastic surfaces pre-coated with SFDH conditional media. The growth-stimulating activity fractionates as a single peak over a sepharose column in the presence of 6 m urea, and sediments as a high molecular weight complex. Growth-stimulating activity can be neutralized by several antisera specific for hepatocyte growth factor, and the same sera recognize a novel approximately 37 kD protein in active supernatants. The cyclic, continuous nature of alternating monolayer and spheroid forms makes this cell line appropriate for studying changing gene expression patterns in progressive cell-cell/cell-matrix interactions.

3T3 Cells↗
PubMed1999

Random monoallelic expression of the imprinted IGF2 and H19 genes in the absence of discriminative parental marks.

The IGF2 and H19 genes are genomically imprinted and expressed preferentially from the paternal and maternal alleles, respectively, during human prenatal development. The exact role of the parental imprint(s), however, is not known. To explore this issue in some detail, we have examined human androgenetic cells which by definition should be incapable of allelic discrimination given the paternal origin of both genomes. Allele-specific in situ hybridisation analysis of dispermic complete hydatidiform moles shows that IGF2 and H19 can be found to be transcriptionally active in a variegated manner, which results in the generation of random monoallelic expression patterns. This data shows that imprinted genes can be expressed monoallelically in the absence of discriminating parental marks and raises the question whether or not mechanisms underlying monoallelic expression preceded the acquisition of parental imprints during evolution.

Alleles↗
PubMed1999

Lansoprazole in the treatment of heartburn in patients without erosive oesophagitis.

BACKGROUND: This randomized, double-blind, multicentre study compared lansoprazole with placebo for symptomatic relief of patients with non-erosive gastro-oesophageal reflux disease (GERD). METHODS: 214 patients with symptomatic, non-erosive GERD (moderate to severe daytime and/or night-time heartburn greater than half the days over the past 6 months and during the 7- to 10-day pre-treatment period) were randomized to either lansoprazole 15 mg or lansoprazole 30 mg, or placebo o.d. for 8 weeks. RESULTS: Daily diary data indicated that on the first treatment day a statistically significantly smaller percentage of lansoprazole patients reported daytime and night-time heartburn and antacid usage, compared with placebo patients. Lansoprazole patients also reported statistically significant less severe daytime and night-time heartburn on the first treatment day. During 0-4, 4-8, and 0-8 weeks of therapy, a statistically significant smaller percentage of days and nights with heartburn, less severe daytime and night-time heartburn, and less antacid usage were observed in the lansoprazole group compared to the placebo group. The percentages of patients with adverse reactions were similar in the lansoprazole and placebo groups. CONCLUSIONS: The results of this study demonstrate that lansoprazole is an appropriate therapy for patients with symptomatic non-erosive GERD.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Insurance and the risk of ruptured appendix in the adult.

BACKGROUND: Disparities in medical care related to the insurance status of patients have been reported. A retrospective analysis was performed to examine the insurance-related differences in the risk of appendiceal perforation in the Prince of Wales Hospital (POWH), New South Wales. METHODS: Computerized data of 1179 patient years who had a diagnosis of appendicitis and were admitted to the POWH over the preceding 10 years were examined. The outcome measure was appendiceal perforation. Patient variables examined were insurance status, sex, age, and socio-economic status (SES). Three hundred patients over the same period were identified who had an appendicectomy but not appendicitis. Multiple logistic regression and Fisher's exact test were used for statistical analysis. RESULTS: The overall perforation rate in 1179 patients was 17%. The only factor that was related to an increased risk of perforation was age over 50 years (odds ratio (OR) 1.57; 95% confidence interval (CI) 1.04-2.53). Sex, insurance status or SES were not associated with a higher risk of perforation. The overall rate of negative appendicectomy was 20% (300 of 1479 patients), and the rate was higher in the uninsured patients (22 vs 17%, P = 0.014, Fisher's exact test). CONCLUSIONS: Lack of health insurance was not associated with an increased incidence of appendiceal perforation at the POWH. Age over 50 years was identified as the only risk factor for appendiceal perforation. The lower negative appendicectomy rate in the insured group may be because of better diagnostic ability of consultants compared to registrars.

Acute Disease↗
PubMed1999

Extremity soft tissue sarcoma: factors predictive of local recurrence and survival.

BACKGROUND: To identify risk factors for local recurrence and overall survival in patients with extremity soft tissue sarcoma. METHODS: A retrospective study was performed of all patients with extremity soft tissue sarcoma treated at the Combined Surgical Oncology Clinic in the Institute of Oncology at Prince of Wales Hospital between 1972 and 1992. Variables analysed included clinical presentation, patient characteristics, tumour characteristics, treatment factors and outcome. RESULTS: One hundred and nineteen patients were eligible for the study. The most common type of presentation was with a painless mass, usually in the thigh. Local control rates at 5 and 10 years were 75% and 73%. Local control was higher in patients who had more radical surgery and in those who received adjuvant radiotherapy. Tumour size and high grade were independent risk factors for poorer survival. Patients over 50 had poorer survival than younger patients and those who presented with recurrent tumours also tended to have poor survival compared to patients presenting de novo. The respective 5- and 10-year survival rates were 65% and 62%. CONCLUSION: This study suggests that local control of extremity soft tissue sarcoma is improved by radical surgery and by the addition of radiotherapy when more conservative procedures are used. Overall survival appeared to be largely determined by patient (age, recurrent presentation) and tumour characteristics (grade, size).

Amputation, Surgical↗