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Biomedical subjects

R Fisher

Publications and source records attributed to R Fisher.

At least 109 records · Page 6Linked to original sources

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↗

Myelination in cerebellar slice cultures: development of a system amenable to biochemical analysis.

Myelin deposition and maintenance are critical to proper function of the mammalian nervous system. Previous investigations of myelination in the central nervous system (CNS) were hampered by the lack of an in vitro system that can faithfully reproduce in vivo events yet is amenable to biochemical investigation. We have developed a procedure, based on organotypic cultures, which permits efficient preparation of large numbers of cerebellar slice cultures that can be easily manipulated. Cultures have been examined to document myelination biochemically (by incorporation of [35S]sulfate into sulfolipids), immunohistochemically (by labeling the myelin components myelin basic protein and galactocerebroside), and morphologically (by both light and electron microscopy). We tested the effects of biologically active peptides and antibodies on myelination in the thin slices. The results indicate that the cultures provide an in vitro system that can be used to examine specific cellular events that occur during CNS myelination.

Animals↗

General practice.

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Family Practice↗

Local failure in childhood rhabdomyosarcoma and undifferentiated sarcoma: prognostic factors and implications for curative therapy.

In this retrospective review, the risk factors for local failure in childhood rhabdomyosarcoma and undifferentiated sarcoma were assessed in 49 patients managed by a multi-disciplinary team at the Prince of Wales Children's Hospital, Sydney, between 1970 and 1988. Average follow-up time was 6.1 years. Sixteen of 49 patients experienced local failure defined as local recurrence after complete excision (5/20) or progressive local disease following incomplete resection (11/29). Fourteen of 16 patients who experienced local failure have died. Using logrank analysis of time to local failure, we found significantly increased risk with "non-embryonal" histology (P = 0.032), residual tumour (P = 0.052, higher IRS group (P = 0.088), "inadequate radiotherapy" for residual tumour (P = 0.001), delay in definitive local treatment (P = 0.038) and Adriamycin-containing chemotherapy (P = 0.017). When these factors were examined by multivariate analysis (Cox regression), only the presence of residual tumour after resection, "inadequate radiotherapy" for residual tumour (P < 0.001), and delay in definitive local therapy (P < 0.037) were shown to have independent significant association with local failure. We conclude that local failure may be avoided by prompt local treatment by either complete surgical resection or adequate radiotherapy.

Adolescent↗

Correlation of metabolism, covalent binding and toxicity for a series of bromobenzene derivatives using rat liver slices in vitro.

For many acute-acting chemicals, toxic responses observed in vivo correlate strongly with metabolic activation and macromolecular covalent binding (CVB) observed in vitro and often in vivo; bromobenzene (BB) is a classic example of this behavior. Substituent groups modulate the toxicity of bromobenzene in vivo and in liver slices cultured in vitro in parallel fashion [Fisher, R., Hanzlik, R.P., Gandolfi, J.A., and Brendel, K. (1992), In Vitro Toxicology, 4, 173-186]. In the present study we used the liver slice system to examine the relationship between toxicity, metabolism and covalent binding amongst a series of [3H/14C] dual labelled BB derivatives including (in order of increasing hepatotoxicity) o-bromoanisole (BA), o-bromotoluene (BT), o-bromobenzonitrile (BBN), BB and o-dibromobenzene (DBB). Among these congeners apparent relative rates of metabolism varied only 4-fold, but the most extensively metabolized compounds were the least toxic. CVB varied 7-fold across the series, and those compounds which bound the most frequently were the most toxic. For each compound the relative binding index (RBI = pmol bound/nmol metabolized) and the average retention of tritium relative to carbon-14 in the CVB fraction were constant throughout the 24 h incubations, suggesting that the metabolic profile of each compound remained constant with time. The RBI values, however, did not reflect relative toxicity as well as total CVB values. The T/C ratios of the CVB residues varied from 0.36 (for BA) to 0.81 (for BBN), indicating that ortho-substitution on BB exerts important qualitative as well as quantitative effects on overall metabolism and reactive metabolite formation. The finding that relative toxicity among a series of bromobenzene congeners is paralleled by their relative covalent binding measured in the same system in which toxicity is assessed adds support to the hypothesis that covalent binding contributes to the observed toxicity, rather than merely being a correlated epiphenomenon.

Animals↗

Improved survival in biliary atresia patients in the present era of liver transplantation.

Therapy for patients with biliary atresia (BA) has become controversial, with orthotopic liver transplantation (OLTx) suggested in place of portoenterostomy. This is based on the unpredictable success of portoenterostomy, and the increased difficulty of the OLTx procedure following prior extensive liver surgery. The survival rate reported here for infants transplanted after unsuccessful portoenterostomy does not support this approach. OLTx was undertaken in 37 patients when end-stage liver failure followed primary portoenterostomy. Recipient age ranged from 6 months to 14 years (median, 13 months), and weight ranged from 5 to 45 kg (median, 8 kg) at the time of OLTx. Reduced-size allografts were used as the primary allograft in 25 patients (23 left lobe), and 12 received whole-organ allografts. Retransplantation was required in 5 patients, each received a reduced-size allograft. There was no increased incidence of vascular complications, primary nonfunction, irreversible rejection, intestinal perforation, biliary complications, sepsis, or lymphoma comparing the BA patients with all other non-BA patients who had undergone OLTx (all P = .16). There was no statistically significant difference in mean operative blood loss between BA patients (EBL = 1.99 BV) and non-BA patients (1.50 BV) (P = .14). Actuarial survival for the series of BA patients was 89% at 1 year, and 80% at 2 years. Following the introduction of reduced-size allografts, donor organs were selected for use with a priority on donor stability. The actuarial survival for BA patients during this time has improved to 96% at 1 year, and 91% at 2 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗