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Biomedical subjects

R Fisher

Publications and source records attributed to R Fisher.

At least 19 recordsLinked to original sources

Analysis of failure following definitive radiotherapy for invasive transitional cell carcinoma of the bladder.

PURPOSE: To assess prognostic factors for bladder relapse and distant failure following definitive radiotherapy for invasive transitional cell carcinoma (TCC) of the bladder. METHODS AND MATERIALS: Retrospective review of patients treated in the period 1977 to 1990 by definitive radiotherapy. The factors studied included age, sex, T stage, histological grade, tumor multiplicity, ureteric obstruction, total radiation dose, and use of neoadjuvant chemotherapy. The endpoints studied were bladder relapse and distant failure. RESULTS: There were 342 patients with a mean follow-up time of 7.9 years. Bladder relapse was observed in 159 patients. The overall actuarial bladder relapse rate at 5 years was 55% (SE = 3%). Prognostic factors for a higher bladder relapse rate were: tumor multiplicity (p < 0.001), presence of ureteric obstruction (p = 0.001), and higher T stage (p = 0.044). Distant failure occurred in 39 patients. The overall actuarial distant failure rate at 5 years was 28% (SE = 3%). Prognostic factors for a higher distant failure rate were: ureteric obstruction (p = 0.003) and higher T stage (p = 0.030). CONCLUSION: In our study, patients with invasive bladder TCC fell into distinct prognostic groups determined by the three independent factors, ureteric obstruction, tumor multiplicity, and T stage. These factors provided estimated risks of bladder relapse by 5 years which ranged from 34% to 91%. Knowledge of these prognostic factors can help in the selection of patients more suited for bladder preservation by definitive radiotherapy.

Actuarial Analysis

Risk-based prenatal screening for trisomy 18 using alpha-fetoprotein, unconjugated oestriol and human chorionic gonadotropin.

Nine centres collaborated to examine the feasibility of a screening method for trisomy 18 that was based on assigning individual risk, using a combination of maternal age and measurements of alpha-fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotropin (hCG). Second-trimester measurements of these analytes were obtained from 94 trisomy 18 pregnancies. In the 89 pregnancies without an associated open defect, the median levels for AFP, uE3, and hCG were 0.65, 0.43 and 0.36 multiples of the unaffected population median, respectively. The strongest individual predictor of risk for trisomy 18 was uE3, followed by hCG, AFP, and maternal age, in that order. Using a method of individual risk estimation that is based on the three markers and maternal age, 60 per cent of pregnancies associated with trisomy 18 would be detected at a risk cut-off level of 1:100, with a false-positive rate of about 0.2 per cent. One in nine pregnancies identified as being at increased risk for trisomy 18 would be expected to have an affected pregnancy. This risk-based screening method is more efficient than an existing method that is based on fixed analyte cut-off levels. Even though the birth prevalence of trisomy 18 is low, prenatal screening can be justified when performed in conjunction with Down syndrome screening and when a high proportion of women offered amniocentesis have an affected fetus.

Adult

The use of implants for orthodontic correction of an open bite.

This case illustrates the integration of maxillofacial surgery, orthodontics, prosthodontics and periodontics in the treatment of an adult male. A traumatic injury to the lower jaw was the stimulus for the patient to seek orthodontic correction of a severe malocclusion including crossbites and an anterior open bite. The loss of a large portion of the anterior alveolar process of the lower jaw including six teeth was corrected with an implant bearing prosthesis which was subsequently used as anchorage to correct the malocclusion. Through the combined efforts of the above disciplines, properly orchestrated, this patient was treated in an effective and successful manner.

Adult

Mammary cancer in transgenic mice expressing insulin-like growth factor II (IGF-II)

The effect of insulin-like growth factor II (IGF-II) on tumour development in the mouse mammary gland was studied. To promote extra IGF-II expression in the mammary gland, sheep beta-lactoglobulin regulatory elements were attached to the coding regions of the mouse Igf-2 gene and injected into the pronuclei of mouse zygotes. Mammary tumours developed in each of the four independent lines of mice which expressed transgene IGF-II in the gland. Tumours from two of the lines grew after transplantation to both male and female hosts. Primary tumours contained stromal and epithelial regions, but the tumours were dominated by mammary adenocarcinoma after transplantation. The tumours expressed high levels of Igf-2 mRNA transcribed from the integrated transgenes.

Adenocarcinoma

Ewing's sarcoma as a second malignant neoplasm in a child previously treated for Wilms' tumor.

PURPOSE: Second malignant neoplasms (SMNs) are a rare occurrence after the successful treatment of childhood cancer. For survivors of Wilms' tumor, the 10-year cumulative risk of developing an SMN has been estimated to be 1%. Bone sarcomas arising within the radiation field are a common occurrence, yet Ewing's sarcoma has been rarely reported as an SMN. PATIENTS AND METHODS: A 10-year-old girl presented with dyspnea 5 years after the diagnosis of stage III favorable histology Wilms' tumor and was found to have a right intrathoracic mass arising from the eighth and ninth ribs. The mass was located at the edge of the previous radiation field. RESULTS: Tumor cytogenetics and immunocytochemistry were helpful in establishing the diagnosis of Ewing's sarcoma. Treatment included combination chemotherapy, with hematopoietic growth factor support, and excluded anthracyclines and radiotherapy. More than 1 year after the diagnosis of Ewing's sarcoma, the patient has completed therapy with no evidence of disease. CONCLUSIONS: This is the first report to our knowledge of Ewing's sarcoma arising in the irradiation field of a patient treated previously for Wilms' tumor.

Child

Breast cancer following treatment for Hodgkin's disease: the need for screening in a young population. Australasian Radiation Oncology Lymphoma Group (AROLG)

Several recent publications have highlighted the issue of an increased risk of breast cancer in women treated with radiotherapy, chemotherapy, or combined modality therapy for Hodgkin's disease. The risk is greatest in women 30 years or younger at the time of treatment. In the Australasian Radiation Oncology Lymphoma Group database, 60% of women fell into this age category. This article reviews the available data pertaining to induction of breast cancer by radiotherapy for Hodgkin's disease. Breast examination should now be an integral part of the long term follow up for these women. There is also a case for the use of screening mammography. Any breast mass developing subsequent to treatment for Hodgkin's disease should be regarded with a high index of clinical suspicion and, accordingly, biopsies should be performed in the majority of cases, even when mammography is negative.

Adult

Periodontal treatment needs and oral hygiene among Ethiopian immigrants.

Periodontal disease studies in developing countries over the past four decades indicate periodontitis to be a major problem, even in populations with relatively low caries rates. The aim of this study was to document levels of periodontal treatment needs, as well as oral hygiene levels for a large sample covering all ages of an Ethiopian Jewish population recently immigrated into Israel. Over 800 subjects from the total of 15,000 Ethiopians who immigrated were examined utilising the PTNS Index and the OHI-S Index. Results indicate that all the examined population was in need of oral hygiene instruction. Almost 80 per cent are in need of scaling and approximately 20 per cent are in need of more complex treatment such as surgery. Significant differences were found according to age. This could be attributed to the high OHI-S scores, ranging from 2.53 at age 0-12 to 4.82 at the 51+ age group, with a mean Debris Index of 2.12 for the total population. It is suggested that this population should be exposed immediately to preventive and treatment programmes to improve oral hygiene and decrease needs for future, costly periodontal treatment.

Adolescent

Disproportionate growth in mice with Igf-2 transgenes.

Injection transgenesis was used to study the long-term effects of excess insulin-like growth factor II on mouse growth and differentiation. By using a construct in which the coding region of the mouse insulin like growth factor II gene (Igf-2) was placed under the control of a keratin gene promoter, four transgenic lines were established, all of which displayed overgrowth of the skin as judged by wrinkling. In addition to high levels of expression in the skin, transgene transcripts were also present in the alimentary canal and uterus. At most of the sites of transgene expression the cell number (DNA content) was greatly increased, indicating a local action of the excess insulin-like growth factor II on cell multiplication. Adult total live weight was slightly increased and there was no macroscopic evidence of tumor formation. The characteristics of these transgenic mice indicate distinct local and systemic actions for insulin-like growth factor II.

Aging

Cresol isomers: comparison of toxic potency in rat liver slices.

A comparison of the toxicity of cresol isomers (o-, m-, and p-methylphenol) was carried out using precision-cut rat liver slices as a test system. At equimolar concentrations p-cresol was the most toxic isomer. A 5- to 10-fold higher concentration of either the o- or m-isomers was required to observe the same degree of cell killing as p-cresol. The toxicity of p-cresol was inhibited by the thiol precursor N-acetylcysteine and was enhanced by pretreatment of liver slices with diethyl maleate to deplete glutathione. These treatments, however, had little effect on either o- or m-cresol toxicity. p-Cresol rapidly depleted intracellular glutathione levels, while the o- and m-isomers depleted glutathione to a lesser extent. [14C]p-cresol was metabolized to a reactive intermediate which covalently bound to slice protein and was inhibited by N-acetylcysteine. In microsomal incubations covalent binding of [14C]p-cresol metabolites was also observed. This binding was inhibited by glutathione and resulted in the formation of a glutathione conjugate. In the absence of glutathione, p-hydroxybenzyl alcohol was the major microsomal metabolite formed from p-cresol, but this compound was not toxic to liver slices at a concentration of 2 mM. These results demonstrate that p-cresol is the most toxic cresol isomer in rat liver tissue and that its toxicity is dependent on the formation of a reactive intermediate. The results also suggest that the mechanism(s) of toxicity of the o- and m-isomers may differ from that of p-cresol.

Acetylcysteine

Absorption of liposome-encapsulated tetracaine versus nonliposome-encapsulated tetracaine from open wounds in rabbits.

The plasma tetracaine concentration versus time profiles for liposome-encapsulated tetracaine (LET) versus nonliposome-encapsulated tetracaine (NLET) were determined after topical application to open wounds in six rabbits (three in LET and three in NLET). H3-tetracaine preparations of LET or NLET were applied randomly to uniform dermal lacerations in anesthetized rabbits. Plasma tetracaine concentrations (ng/mL) of arterial blood samples obtained were measured at predetermined intervals (0.25, 0.5, 1.0, 2.0, and 24 hours) by isotope tracer assay. Results (mean +/- standard deviation) showed the peak plasma tetracaine concentration (Cmax) and the time to Cmax were 40.8 +/- 5.1 ng/mL and 40.1 +/- 7.3 minutes for LET, and 117.8 +/- 9.7 ng/mL and 49.1 +/- 50.2 minutes for NLET. Plasma tetracaine concentrations at all samples times were significantly lower for LET versus NLET. Liposome encapsulation of topically applied tetracaine significantly decreases both the peak and overall plasma tetracaine concentrations compared with the nonencapsulated form. The data suggest that liposome encapsulation of topically applied local anesthetics such as a solution of tetracaine, adrenaline, and cocaine, might reduce the potential systemic toxicity caused by rapid absorption of these compounds.

Absorption

Attitudes of parents of young children to sperm donation--implications for donor recruitment.

An anonymous questionnaire was circulated to parents of young children to survey exposure to publicity about and attitudes to sperm donation (n = 192 couples; 50% response rate). Of those surveyed, 55% of men and women had seen or heard of the need for sperm donors; for 26% of couples, one or both partners had considered donation, and among half of those (13% of total) no objections to donating were raised. However, only two men had approached the clinic as donors. Objections to donation centred mainly on discomfort at having children outside their family, worry about future contact with donor insemination children, and worry about incest. Women were three times as likely to raise these objections as men. Of all respondents, 20% thought a donor should be used for only one recipient couple, while 50% suggested three or fewer families. Overall, 41% rated having non-identifying information about the recipient couple(s) as an important aspect of sperm donation, although only 9% of men and 17% of women considered personal contact important. While many people are aware of and receptive to the idea of being donors, very few act. Many would prefer that their spermatozoa were used for only one or a few couples about whom they had some information.

Adult

The incidence and severity of postoperative nausea and vomiting in patients exposed to positive intra-operative suggestions.

In a double-blind study, the effects of positive intra-operative suggestions on the incidence and severity of postoperative nausea and vomiting were studied in 60 patients randomly selected to undergo routine major gynaecological surgery. Patients who received positive suggestions suffered significantly less nausea and vomiting in the 24 h after surgery.

Anesthesia, General

Results of external beam radiotherapy in 448 patients with clinically localized adenocarcinoma of the prostate.

The results of external beam radiotherapy for clinically localized adenocarcinoma of the prostate in 448 patients treated in the period 1980-90 were reviewed. The average follow up was 4.9 years. The patients were aged 44-87 years (median 69 years) and all had histopathological evidence of adenocarcinoma by needle biopsy or transurethral resection of prostate. The histopathological grading was: 127 G1; 154 G2; 127 G4; 28 Gx. Clinical staging according to TNM (American Urological Association) was: 29 T0 (A2); 4 T1 (B1); 173 T2 (B2); 176 T3 (C1); 63 T4 (C2); 3 Tx. Routine surgical pelvic lymph node staging was not performed but patients had radiological (computerized tomography scan or lymphogram) nodal staging: 350 N0; 22 N1; 12 N2; 64 Nx. High energy linear accelerator external beam radiotherapy was given by multiple fields to total doses of 50-70 Gy (median 60 Gy). The majority of patients (307, 69%) was treated by a uniform policy under the care of one radiation oncologist (HM). The rates of local and distant failure at 5 years were 10% (s.e. = 2%) and 42% (s.e. = 3%), respectively. The late complication rate at 5 years was 25% (s.e. = 2%), comprising mild 16%, moderate 7% and severe 1.3%. The 5 year overall survival rate was 64% (s.e. = 2%) and the cancer-specific survival rate was 74% (s.e. = 3%). Both histological grade and clinical stage were strongly predictive of overall survival and distant failure. Only histological grade was predictive of local failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma

Pulmonary embolism: prediction of the usefulness of initial ventilation-perfusion scanning with chest radiographic findings.

PURPOSE: To evaluate the usefulness of ventilation-perfusion scanning when chest radiographic findings are abnormal to decide which patients should initially undergo angiography because of suspected pulmonary embolism. MATERIALS AND METHODS: The records of 951 patients who underwent examination between April 1, 1992, and August 24, 1993, were reviewed, and the results of ventilation-perfusion scanning and chest radiography were correlated. RESULTS: Approximately 8% of patients with radiographic findings of no acute disease, pleural effusion, and linear atelectasis had high-probability ventilation-perfusion scans. Pulmonary edema and parenchymal consolidation categories had fewer high-probability studies (3% and 1%, respectively; P < .01). The chance of obtaining a nondiagnostic result was similar for the first three categories (12%) but was more likely for pleural effusion and parenchymal consolidation (36% and 82%, respectively; P < .01). CONCLUSION: The results of ventilation-perfusion scanning are not useful with focal radiographic consolidation. It may be appropriate to proceed directly to pulmonary angiography in many of these patients.

Humans

High plasma insulin-like growth factor-II and low lipid content in transgenic mice: measurements of lipid metabolism.

Transgenic mice were made by introducing extra copies of the mouse insulin-like growth factor-II (IGF-II) gene driven by the bovine keratin 10 promoter (BKVI). The adult plasma IGF-II levels were elevated at least three times in one line. In this line, there was a lower lipid content of both brown and white adipose depots at 2-4 months of age, and 40% less fat in the carcass at 7-9 months. The low lipid phenotype was not detected in the carcass at 2 weeks after birth. The lean characteristic was attributed to circulating IGF-II because the transgene was not expressed in fat. At 2-4 months of age, the transgenes oxidized more oral lipid, and less of this lipid was incorporated into the whole body and the epididymal fat. In contrast, the interscapular brown adipose tissue maintained lipid incorporation and lipoprotein lipase activity despite its reduced size. The altered activity of the brown adipose tissue may account for the gradual onset and persistence of the lean feature of the transgenic mice. There were no substantial changes in lipogenesis which could account for the low fat content. The plasma levels of IGF-I, insulin, glycerol, non-esterified fatty acids, triacylglycerols and glucose were not greatly changed and the pituitary GH content was within the normal range.

Adipose Tissue

Prevalence of dental caries among Ethiopian emmigrants.

Studies have documented the prevalence of caries in developing countries. The current study adds to this body of knowledge. Of the total Ethiopian Jewish population who emmigrated to Israel in 1991, a sample of over 800 individuals was randomly selected representing all age groups. DMF-T and DMF-S scores were recorded, as well as percentages of caries free individuals. Results indicated that almost no fillings or crowns had been provided to the study population. The Missing 'M' component was low as was the Decay 'D' component, although this increased with increasing age, ranging from 0.33 D-T at the 0-12 age group to 2.46 at the 51+ age group. In the permanent dentition 88.4 per cent of those 0-12 years of age were caries free and 74.5 per cent were caries free in both the primary and permanent dentition. Almost 59 per cent of the 13-20 years olds were caries free and 32.8 per cent of those 21-50 years old. Only 16.7 per cent were caries free at age 51+ years old. The data indicate a relatively low prevalence of both coronal and root caries, and an effort has to be made to keep these figures low for years to come mainly by diet and dental health education.

Adolescent

Characteristics of a two-site immunoradiometric assay for human skeletal alkaline phosphatase in serum.

This two-site IRMA includes specific monoclonal antibodies for measuring skeletal alkaline phosphatase (B-ALP) in human serum. Assay calibration is based on mass units (micrograms per liter) and was established with purified B-ALP from a human osteosarcoma cell line, SAOS-2. Precision studies demonstrated intra- and interassay CVs of 3-5% and 5-7%, respectively. Relative reactivity studies showed that the assay has a sevenfold preference for detecting B-ALP compared with the liver isoenzyme in serum. The normal reference interval for 478 healthy adults was 5-22 micrograms/L. Method comparison studies showed good correlation between this B-ALP assay (y) and commercially available electrophoretic methods (x) (y = 0.3540x + 20.5, R2 = 0.929) in a pagetic population. Temporal profiles for total ALP, this IRMA B-ALP assay, and B-ALP by electrophoresis in three pagetic patients were parallel. We conclude that this assay demonstrates good analytical performance and would be useful for the clinical assessment of metabolic bone disorders.

Adult