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Biomedical subjects

R Fisher

Publications and source records attributed to R Fisher.

At least 127 records · Page 7Linked to original sources

A comparison of methods for alcohol and marijuana anticipatory guidance with adolescents.

The purpose of this study was to compare adolescents' knowledge of alcohol after receiving either a computer-assisted instruction program or physician-delivered anticipatory guidance or no intervention. In addition, adolescents' satisfaction was compared between intervention groups. A total of 89 adolescents attending a general medical clinic were randomly assigned to one of three conditions. The participants were from low-to-middle income families, and the mean age was 15.5 years. A two-way analysis of variance found significant main effects for both group and sex. Those adolescents in both intervention groups were significantly more knowledgeable, and males demonstrated the highest knowledge scores. There was a significant interaction between group and sex, with females more satisfied with the computer-assisted instruction as compared to males who preferred anticipatory guidance. These data suggest that the use of computer technology during a well-adolescent health visit is effective and efficient in transmitting drug-related information.

Adolescent↗

HIV infection among injecting drug users in Asia: an evolving public health crisis.

Injecting drug use is being reported from an increasing number of Asian and other Third World countries. HIV continues to spread globally among and from populations of injecting drug users (IDUs), although the rate of spread appears to have slowed down recently in some industrialized countries. Asia produces two-thirds of the world's supply of opium. In recent years the rapid development of new illicit drug trade routes in efforts to evade detection by law enforcement authorities has exposed new populations in Asia to drug injecting and, thus, the risk of HIV infection. Epidemic spread of HIV has recently commenced in some Asian countries among injecting drug users, and others are at substantial risk of an HIV epidemic among their IDU populations. The speed of spread and the consequences of HIV infection among IDUs in Asian and other Third World countries are even more profound than in western countries. Asian countries attempting to control this component of the epidemic often have greater difficulty than industrialized countries because of their proximity to drug producing areas, scarcity of resources and a greater likelihood of pragmatic policies conflicting with traditional values. Vigorous efforts are urgently required at both a national and international level to raise awareness of the consequences of an uncontrolled epidemic of HIV among IDUs in Asian and other countries, and to support the implementation of policies which are likely to reduce the spread of HIV.

Asia↗

Chorionic villus sampling in Auckland 1989-90.

AIMS: to perform an audit of all 197 chorionic villus sampling procedures performed in Auckland in 1989-90. METHOD: an attempt to trace the outcome in all 197 cases and this was possible in 188 cases. RESULTS: 89% of chorionic villus samples were performed transvaginally and 11% transabdominally. The total fetal loss rate was 9.6% (18) with six spontaneous miscarriages before 20 weeks gestation (3.2%), one intermediate fetal death and one neonatal death. There were 10 elective terminations of pregnancy following abnormal results so the spontaneous loss rate was 4.3%. CONCLUSIONS: the loss rate was lower than that reported in the European and Canadian multicentre trials. The sampling success rate, however, was poor with 13.7% failed procedures. This improved in the second year of the service to 10%. There were no failure cultures or examples of mosaicism.

Abortion, Spontaneous↗

Resistance of primary isolates of human immunodeficiency virus type 1 to neutralization by soluble CD4 is not due to lower affinity with the viral envelope glycoprotein gp120.

Recombinant soluble CD4 (rsCD4) has potent antiviral activity against cell line-adapted isolates of the human immunodeficiency virus type 1 (HIV-1) but low activity toward HIV-1 primary isolates from patients. A simple hypothesis proposed to explain this discrepancy, which questions the therapeutic utility of soluble CD4-based approaches, is that the major envelope glycoprotein, gp120, of patient virus has lower affinity for CD4 than does gp120 from laboratory viruses. To test this hypothesis, we have produced pairs of low- and high-passage HIV-1 isolates which, depending on culture passage history, display dramatically different sensitivities to neutralization by rsCD4. Here, we present evidence that the HIV-1 major envelope glycoprotein cDNAs cloned from one such isolate pair show only minor differences in their deduced gp120 primary structures, and these occur outside regions previously shown to be involved in CD4 interactions. In addition, recombinant gp120 from a low-passage rsCD4-resistant patient virus binds rsCD4 with high affinity, equal to that previously measured for recombinant gp120 from high-passage cell line-adapted virus isolates. These data indicate that differences in CD4-gp120 affinity do not account for rsCD4 resistance in HIV-1 recently isolated from patients.

Amino Acid Sequence↗

Mortality in DSM-IIIR schizophrenia.

Mortality was investigated in 356 DSM-IIIR schizophrenics admitted to a university psychiatric hospital over a 12-year period. Determination of death was made through a record-linkage process and observed death was compared with the mortality experience of the general population of the State of Iowa. Schizophrenics had nearly a three-fold increase in overall mortality. Mortality was primarily attributable to unnatural causes of death, particularly suicide, which was more than twenty-three times greater than expected. Mortality was greater in schizophrenic patients younger than 40 years and during the early portion of follow-up. Studies of mortality in psychiatric patients continue to be important, particularly as diagnostic criteria become better refined.

Adult↗

Iodine-125 irradiation of choroidal melanoma: clinical experience from the Prince of Wales and Sydney Eye Hospitals.

We examined the records of 53 patients treated for choroidal melanoma between 1985 and 1989. The aim of this study was to assess the safety and short-term results of iodine-125 episcleral plaque therapy. There were 28 males and 25 females, aged 20 to 77 years (median 61 years), treated for single tumours with a median diameter of 9 mm (range 5 to 15 mm) and with a median thickness of 4 mm (range 2 to 10 mm). The plaques containing iodine-125 seeds were chosen according to tumour size: 10 mm (16 patients); 15 mm (36 patients); 20 mm (one patient). All patients are alive at last follow-up (median 1.3 years, range 4 months to 3.3 years). Four patients underwent enucleation for melanoma progression. Thirty patients have developed some type of complication (more than one complication occurred in the same eye in 12 patients): retinitis (19), optic neuropathy (7); cataract (4), rubeosis iridis (2). Overall, visual acuity deteriorated in 32 patients, remained stable in 12 patients and improved in 9 patients. Iodine-125 plaque therapy appears to offer patients good prospects of tumour control and preservation of useful vision.

Adult↗

A multisite physician's office laboratory evaluation of an immunological method for the measurement of HbA1c.

OBJECTIVE: To evaluate the clinical performance of a new immunological HbA1c method in physicians' office laboratories. RESEARCH DESIGN AND METHODS: Three physicians' offices participated in the evaluations. The clinicians routinely use HbA1c test results to monitor their patients' long-term blood glucose control. Precision and interlaboratory variability were assessed using three levels of lyophilized controls. Correlation of the method's results to currently available laboratory methods was made. Comparison of finger-stick (capillary) results to venous EDTA whole blood results was made on 134 patients. Physician and laboratory personnel input was evaluated with regard to the clinical utility of the system. RESULTS: The CVW and CVB were a maximum of 4.5 and 4.4% for the immunoassay system on three levels of control materials at the three sites. Interlaboratory variability among the control means was found to be 4.9-5.4, 8.0-8.3, and 11.7-12.0% HbA1c. Correlation coefficients (r) ranged from 0.95 to 0.99. There was a positive bias by the DCA 2000 compared with the in-house method at site 1. Minimal negative biases were seen by the DCA 2000 with comparative methods used at sites 2 and 3. Median percentage differences with the comparative methods were 12, -1.4, and -5.6%. Comparison of capillary to venous sample results, from the DCA 2000, showed no clinically significant differences. Operator and physician feedback were positive with respect to technical ease in performance of the test and accuracy of results. CONCLUSIONS: Precision was acceptable and interlaboratory variability was low. The immunological method correlated well with manual ion-exchange and automated HPLC methods. The small sample size and good comparison between capillary and venous sample results make fingerstick sampling acceptable. The method provided immediate test results (within 9 min) to the clinicians.

Blood Specimen Collection↗

Epitope recognition of conserved HIV envelope sequences by human cytotoxic T lymphocytes.

CTL constitute an essential part of the immune response against the HIV. CTL recognize peptides derived from viral proteins together with the MHC class I molecules on the surface of infected cells. The CTL response could be important in prevention or control of infection with HIV by destroying virus-producing cells. In this study we have attempted to identify peptide epitopes recognized by HIV-specific CTL. Using synthetic peptides, we have identified six conserved peptidic epitopes on the gp120 envelope glycoprotein recognized by polyclonal human CTL in association with HLA-A2 class I transplantation Ag. These results were confirmed by two approaches: i) blocking of CTL activities with antibodies specific for three of these conserved peptides; and ii) construction of doubly transfected P815-A2 target cells, using deletions of the HIV env gene. Vaccination or immunotherapy in HLA-A2 individuals can thus be considered using highly conserved HIV env peptidic sequences.

Amino Acid Sequence↗

Expression of the Blast-1 activation/adhesion molecule and its identification as CD48.

We have analyzed the induction and expression of Blast-1 at the mRNA and protein levels and demonstrated its identity with CD48. Blast-1/CD48 is expressed on a wider range of cell types, notably T cells and monocytes, than previously thought, but appears to be restricted to lymphoid and myeloid cells. Resting B and T cells express Blast-1/CD48 molecules at the cell surface; however, they lack the epitope recognized by the 17D6 mAb. Resting B cells express no detectable Blast-1/CD48 mRNA. Induction by EBV infection or stimulation with PMA, IL-4, or PHA results in increased levels of Blast-1/CD48 protein (both 6.28 and 17D6 epitopes) at the cell surface. Detailed analysis of EBV-induced expression revealed that it is due to increased steady-state levels of Blast-1/CD48 mRNA induced by transforming but not nontransforming strains of the virus. Induction by IL-1 beta, ionomycin, or suboptimal levels of PMA plus ionomycin results in increased expression of the 17D6 epitope only. In transfected Cos-7 cells Blast-1/CD48 at the cell surface expresses only the 6.28 epitope, whereas cytoplasmic molecules express both 17D6 and 6.28 epitopes. We suggest that these results are most consistent with the idea that Blast-1/CD48 molecules are complexed at the surface of resting cells and Cos-7 cells, resulting in masking of the 17D6 epitope. Activation causes dissociation of the complex, revealing the 17D6 epitope. The existence of 17D6+6.28- Blast-1/CD48 molecules was demonstrated by immunoprecipitation analysis, which also revealed that, unlike the rest of the molecules, this subset was resistant to digestion with glyosylphosphatidylinositol-specific phospholipase C.

Antibodies, Monoclonal↗

Results of radiotherapy for localised prostatic carcinoma treated at the Prince of Wales Hospital, Sydney.

Between 1980 and 1986 a total of 218 patients with localised prostatic carcinoma received radical pelvic radiotherapy at The Prince of Wales Hospital, Sydney. The mean follow-up time was 4.6 years. The five-year actuarial overall survival rate was 63% (death from all causes) and the five-year cancer-specific survival rate was 73% (death from or with prostate cancer). The overall survival was significantly worse with more advanced clinical stage of the disease (P = 0.003) and with poor histological differentiation of the tumour (P = 0.001). The five-year actuarial rate for local control of tumour in the pelvis was 84%. Late treatment-related complications (occurring or persisting beyond six months) were mild or moderate and the majority settled with conservative management. Only five patients experienced severe complications (necessitating surgical treatment). Of 42 patients with normal potency documented before radiotherapy who were not subsequently hormonally manipulated 23 (55%) retained potency at two years. These results for definitive radiotherapy for localised prostatic carcinoma indicate good local control with minimal morbidity and compare favourably with other published results.

Aged↗

Metabolism of dichlorobenzenes in organ cultured liver slices.

A novel in vitro system was used to evaluate tissue specific toxicity. This system utilizes precision cut organ slices in dynamic organ culture and is viable for up to 24 hrs. The three isomers of dichlorobenzene were added to liver slices prepared from Sprague Dawley rats or human donors. The precursor dichlorobenzenes were radiolabelled and metabolites were separated by classes (i.e. glucuronides, sulfates and glutathione and cysteine conjugates). Covalent Binding of the dichlorobenzenes was also determined after extensive extraction of the tissue. The total amount of metabolism of the dichlorobenzenes varied depending on the isomer and the type of tissue. For example, the Sprague-Dawley rat liver slices metabolized 1,2-DCB and 1,3-DCB at approximately the same rate while 1,4-DCB was metabolized at a slower rate. This metabolism profile was also seen in the majority of the adult human liver slices. However, the fetal human slices showed that 1,4-DCB was metabolized to a greater extent than 1,3-DCB or 1,2-DCB while 1,3-DCB was metabolized at a faster rate than 1,2-DCB. Our results show that liver slices in organ culture are a suitable system for species comparisons and of structure/activity relationships in xenobiotic metabolism with an emphasis on the fate of reactive intermediates. In addition, this system is suitable for evaluation of hepatotoxic potency.

Animals↗

Cryopreservation of pig and human liver slices.

The ability to cryopreserve human liver slices would greatly enhance the opportunities to test potentially hepatotoxic drugs and environmental contaminants as well as the metabolism of these compounds. This study focused on trying to cryopreserve pig and human liver slices. Since the acquisition of human liver tissue is unpredictable and scarce, an animal model was sought to predict problems associated with cryopreservation of human tissue. The pig liver was chosen because of its anatomical and physiological resemblance to human liver. The human liver tissues that did become available were obtained through the Arizona Organ Bank and the National Disease Research Interchange and from surgical liver resections. An in vitro culture system that employed precision-cut liver slices was used in this study. Different types and concentrations of cryoprotectants, cooling rates, and culture media were all tried in an attempt to cryopreserve pig and human liver slices. The viabilities of fresh and cryopreserved liver slices were evaluated using slice K+ retention and protein synthesis. Pig liver slices following cryopreservation retained between 80 and 85% of intracellular K+ content and protein synthesis as compared to controls using 1.4 M Me2SO, a 12 degrees C/min cooling rate, and a rapid rewarming rate of direct submersion of the slice into 37 degrees C fetal calf serum. Human liver slices following cryopreservation retained between 54 and 89% of intracellular K+ content and protein synthesis as compared to controls using the same protocol as for pigs, except that lower cooling rates were giving better results. The large variation seen in cryopreserved human liver slices was due to the length of warm and cold ischemia to which the tissue was exposed before arriving at the laboratory. This study indicated that pig and human liver slices can be cryopreserved and used for future toxicological and metabolic studies.

Animals↗

Total serum IgD is increased in atopic subjects.

We have developed a sandwich-type ELISA system for measuring total IgD levels in the serum of atopics and non-atopic controls. In this ELISA system, affinity purified goat anti-human IgD was used for capture. Results were superior to those obtained with monoclonal anti-human IgD antibody. No cross-reactivity could be demonstrated to IgG, IgM, IgA or IgE. The assay showed minimal non-specific binding even with initial serum dilutions of 1:2. The results obtained were reproducible among replicates (Mean CV +/- SEM = 0.03 +/- 0.002; n = 251), between dilutions (CV = 0.08 +/- 0.006; n = 108), and between assays (CV = 0.05 +/- 0.12; n = 5). We used routine radioimmunoassay for measuring total serum IgE. Using these assays total serum IgD and IgE levels were measured in 75 atopic patients and 33 normal subjects. None of the atopics had recent immunotherapy. As expected, the geometric mean serum IgE in atopics (373 ng/ml) was significantly higher than that in normal subjects (49 ng/ml) (P less than 0.01). However, geometric mean serum IgD was also significantly higher in atopics (20.3 micrograms/ml) than that in normal subjects (8.4 micrograms/ml) (P less than 0.02). In both atopic and normal groups, mean serum IgD level did not differ significantly on the bases of age, sex or asthmatic status. Furthermore, total serum IgD was not significantly correlated with total serum IgE (r = 0.14; P = 0.14; n = 108), indicating that immunoregulatory control of the basal levels of the two isotypes is not linked.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Pilonidal sinus in an amputee.

A pilonidal sinus developed in the superio-medial aspect of the thigh of an above-knee amputee. This is an unusual site for the condition to develop. We suggest that the same aetiological factors that were responsible for the "Jeep Bottom" of World War II were also responsible for this problem in the amputation stump of a Falklands campaign casualty.

Adult↗

In-vitro hepatotoxicity of three dichlorobenzene isomers in human liver slices.

1 The cytotoxicity of dichlorobenzenes in cultured rat liver slices has previously been shown to be strain specific and biotransformation related. 2 In order to extrapolate animal models to humans, the dichlorobenzenes were incubated with human liver slices to try to clarify their hepatotoxic potential in man. 3 The degree of hepatotoxicity observed with the dichlorobenzenes depended on whether Waymouth's or Krebs-Henseleit was used as the incubation medium. 4 All three dichlorobenzenes (1 mM) produced no significant differences from control when incubated in Waymouth's medium. However, in the Krebs-Henseleit buffer there was a substantial increase in cytotoxicity. 5 In both incubation mediums the dichlorobenzene isomers exhibited the following rank order 1,3-DCB greater than 1,2-DCB greater than 1,4-DCB. 6 1,2-dichlorobenzene hepatotoxicity was blocked by metyrapone, 1,3-dichlorobenzene toxicity was blocked by SKF 525-A and neither one of these inhibitors could block the 1,4-dichlorobenzene cytotoxicity. 7 The use of human liver tissues to evaluate potential toxicants merits consideration since the hepatotoxicity of xenobiotics and drugs in man is the ultimate question.

Adolescent↗

Valproic acid hepatotoxicity in human liver slices.

Precision cut human liver slices were incubated in organ culture with valproic acid (VPA) to identify patterns of sensitivity to VPA-induced hepatotoxicity. The slices were incubated in Krebs-HEPES buffer supplemented with 25mM glucose and 84 micrograms/ml gentamycin. At 2, 4, 6, 12, 18 and 24 hr slices were taken and analyzed for K+ retention, synthesis of protein and LDH leakage. All three of these viability indicators showed that certain human livers were more susceptible to VPA-induced hepatotoxicity than others. In the limited group of human livers investigated (n = 9) we found one to be particularly sensitive and two relatively insensitive to VPA toxicity. The remaining tissues were of intermediate sensitivity towards VPA. At this time there is no correlation between the human livers that were susceptible to VPA induced hepatotoxicity and age or sex. This study was designed to show that VPA does induce hepatotoxicity in vitro at therapeutically relevant concentrations. Future studies will show whether VPA hepatotoxicity correlates with VPA metabolism, nutritional status or concomitant therapy.

Adolescent↗