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J R Williams

Publications and source records attributed to J R Williams.

At least 73 records · Page 4Linked to original sources
PubMed1998

Photodynamic tumor therapy: mitochondrial benzodiazepine receptors as a therapeutic target.

BACKGROUND: Photodynamic therapy employs photosensitive agents such as porphyrins to treat a variety of tumors accessible to light-emitting probes. This approach capitalizes on the selective retention of porphyrins by cancer cells. Cancer cells also have elevated levels of mitochondrial benzodiazepine receptors which bind porphyrins with high affinity. METHODS: Cultured cancer cell lines were exposed to porphyrin and porphyrin-like compounds and then irradiated with light. Cytotoxicity of this treatment was measured via clonogenic assays. Mitochondrial benzodiazepine receptor pharmacology was studied using [3H] PK11195 binding to cancer cell homogenates and isolated kidney mitochondrial membranes. RESULTS: We show that therapeutic potencies of porphyrins correlate closely with affinities for mitochondrial benzodiazepine receptors. Sensitivities of tumor cell lines to photodynamic therapy parallel their densities of these receptors. CONCLUSION: We propose that porphyrin photodynamic therapy is mediated by mitochondrial benzodiazepine receptors.

Mitochondria↗
PubMed1998

Clinical and pathologic findings in hemochromatosis hip arthropathy.

During a 9-year period, 15 patients with hemochromatosis hip arthropathy required 19 total hip arthroplasties for disabling hip pain. Preoperative presentation, hip function, pathologic evaluation of the femoral head, and radiographic findings were reviewed. Postoperative followup averaging 5.7 years (range, 2-11 years) was performed to assess hip pain and function after total hip arthroplasty. The average preoperative Hospital for Special Surgery hip score was 15 points (range, 4-24 points), and this improved to 30 points (range, 4-38 points) after total hip arthroplasty. Only one of 15 patients required revision surgery at 10 years for acetabular loosening. All other patients were pain free, with improved function at latest followup. Histologic evaluation of the resected femoral heads revealed evidence of primary or secondary osteonecrosis in seven of 19 (37%) specimens. Articular cartilage avulsion at the level of the tidemark was identified in eight of 19 (42%) specimens, and calcium pyrophosphate deposition was identified in five of 19 (26%) specimens. These pathologic findings suggest a predictable progression of the arthritic process in patients with hemochromatosis.

Aged↗
PubMed1997

The interdependence of staff and patient doses in interventional radiology.

Staff doses arising from the use of X-rays are principally due to scattered radiation. This is related to the dose received by the patient expressed as the dose-area product (DAP). Doses to patients in interventional radiology are generally higher than for other fluoroscopically guided procedures. Doses to interventional radiologists are, therefore, amongst the highest associated with the use of diagnostic X-rays. The results of staff dose monitoring normalized to DAP should provide an indicator of those procedures which are associated with particularly high radiation exposures to staff, and should help to identify those radiologists whose practice may result in unnecessarily high doses to themselves. A study has been made of patient doses in two X-ray rooms used for interventional procedures associated with vascular and liver diseases. Doses to radiologists in these rooms were normalized to DAP. It was found that the average doses to the body, neck and hands were 0.05, 0.89 and 2.45 microSv/(Gy cm2), respectively for those radiologists with no significant involvement in hepatobiliary procedures. Higher doses were found for one radiologist whose workload included biliary drainage. The whole body dose was 0.17 microSv/(Gy cm2) or 5.8 mSv per year. It was shown that the doses to the neck and hands for the biliary drainage work was 6.59 and 29.0 microSv/(Gy cm2), respectively. This study has demonstrated the value of DAP as a measure of radiologist workload in respect of its significance in terms of staff dose.

Catheterization↗
PubMed1996

After 4 years' work, revised Code of Ethics goes to General Council for decision.

The CMA's Committee on Ethics will present a revised Code of Ethics for consideration by General Council during the annual meeting in Sydney, NS, later this month. This article outlines the reasons for updating the current (1990) version of the code and explains some of the significant changes and omissions. If approved by General Council, the revised code will take effect immediately.

Canada↗
PubMed1996

Bioethics for clinicians: 1. Consent.

Patients are entitled to make decisions about their medical care and to be given relevant information on which to base such decisions. The physicians obligation to obtain the patient's consent to treatment is grounded in the ethical principles of patient autonomy and respect for persons and is affirmed by Canadian law and professional policy. A large body of research supports the view that the process of obtaining consent can improve patient satisfaction and compliance and, ultimately, health outcomes. An exception to the requirement to obtain consent is the emergency treatment of incapable persons, provided there is no reason to believe that the treatment would be contrary to the person's wishes if he or she were capable.

Aged↗
PubMed1996

Arachidonic acid activation of monocyte and neutrophil reactive oxygen in lung cancer patients undergoing pulmonary resection.

Reactive oxygen intermediate (roi) generation was investigated in phagocytes of 39 patients undergoing pulmonary resection for lung cancer and 39 paired healthy controls. Generation of roi in monocytes and neutrophils was monitored using 2',7'-dichlorofluorescin diacetate. Activation associated with hydrophobic interactions was probed by analysis of phagocyte roi activation by arachidonic acid and gamma-linolenic acid. Patient roi was measured pre-operatively and 2 and 7 days post-operatively. Elevated (P < 0.01) roi production was detected in neutrophils of lung cancer patients. Surgery was associated with an increase (P < 0.05-P < 0.01) in phagocyte roi at 2 and 7 days post-op. Phagocyte roi was stimulated by arachidonic acid and gamma-linolenic acid (1-40 microM) both pre- and post-operatively. Differences in arachidonic acid and gamma-linolenic acid stimulation between patient and control and pre- and post-op patient phagocytes suggest arachidonic acid involvement in phagocyte activation during reactive responses to lung carcinoma and surgery.

Arachidonic Acid↗
PubMed1996

The syntheses of 3-substituted perfluoroalkyl steroids.

The syntheses of three classes of C-3 perfluoroalkyl substituted steroids are described. They are the 3 beta-hydroxy-3 alpha-perfluoroalkylandrost-4-en-17-ones (5a-c), 3-perfluoroalkylandrosta-3,5-dien-3-ones (8a-c) and 3 beta-hydroxy-3 alpha-perfluoroalkylandrost-5-en-17-ones (12a-c). Addition of a series of perfluoroalkylorganometallic reagents (RFLi; RF = C2F5, C3F7, or C4F9) to the 3 position of silylated testosterone 2b afforded delta 4 perfluoroalkyl carbinols 3. In Scheme 1, deprotection with HF and oxidation at the C-17 carbon with PCC produced delta 4 ketones 5. In Scheme 2 dehydration of 3 with 1,2-phenylenephosphorochloridite and iodine afforded delta 3,5 dienes 6 which were deprotected and oxidized as above to the C-17 ketones 8. In Scheme 3 isomerization of the double bond of 3 from the C-4 to the C-5 position using the allylic halogenation followed by treatment with lithium aluminum hydride led to the synthesis of the double bond isomer series 12. A new method for dehydration was developed. On average and within experimental error, 3 beta-hydroxy-3 alpha-perfluoroalkylandrost-5-en-17 ones (12a-c) were better than the 3-perfluoroalkylandrosta-3,5-dien-17-ones (8a-c) and 3 beta-hydroxy-3 alpha-perfluoroalkylandrost-4-en-17-ones (5a-c) at inhibiting glucose-6-phosphate dehydrogenase.

Alkylation↗
PubMed1996

The genotype of the human cancer cell: implications for risk analysis.

An extremely large database describes genotypes associated with the human cancer phenotype and genotypes of human populations with genetic predisposition to cancer. Aspects of this database are examined from the perspective of risk analysis, and the following conclusions and hypotheses are proposed: (1) The genotypes of human cancer cells are characterized by multiple mutated genes. Each type of cancer is characterized by a set of mutated genes, a subset from a total of more than 80 genes, that varies between tissue types and between different tumors from the same tissue. No single cancer-associated gene nor carcinogenic pathway appears suitable as an overall indicator whose induction serves as a quantitative marker for risk analysis. (2) Genetic defects that predispose human populations to cancer are numerous and diverse, and provide a model for associating cancer rates with induced genetic changes. As these syndromes contribute significantly to the overall cancer rate, risk analysis should include an estimation of the effect of putative carcinogens on individuals with genetic predisposition. (3) Gene activation and inactivation events are observed in the cancer genotype at different frequencies, and the potency of carcinogens to induce these events varies significantly. There is a paradox between the observed frequency for induction of single mutational events in test systems and the frequency of multiple events in a single cancer cell, suggesting events are not independent. Quantitative prediction of cancer risk will depend on identifying rate-limiting events in carcinogenesis. Hyperproliferation and hypermutation may be such events. (4) Four sets of data suggest that hypermutation may be an important carcinogenic process. Current mechanisms of risk analysis do not properly evaluate the potency of putative carcinogens to induce the hypermutable state or to increase mutation in hypermutable cells. (5) High-dose exposure to carcinogens in model systems changes patterns of gene expression and may induce protective effects through delay in cell progression and other processes that affect mutagenesis and toxicity. Paradigms in risk analysis that require extrapolation over wide ranges of exposure levels may be flawed mechanistically and may underestimate carcinogenic effects of test agents at environmental levels. Characteristics of the human cancer genotype suggest that approaches to risk analysis must be broadened to consider the multiplicity of carcinogenic pathways and the relative roles of hyperproliferation and hypermutation. Further, estimation of risk to general human populations must consider effects on hypersusceptible individuals. The extrapolation of effects over wide exposure levels is an imprecise process.

Genetic Diseases, Inborn↗
PubMed1996

Density-dependent processes in the transmission of human onchocerciasis: relationship between microfilarial intake and mortality of the simuliid vector.

In order to construct an analytical model of onchocerciasis transmission, it is necessary to elucidate the functional relationships of the various population rate processes taking place within the human and vector hosts. Two previous papers have explored the evidence for density-dependent regulation in relation to microfilarial intake by, and larval development within, the Simulium host. This paper investigates the survivorship of wild-caught blackfly samples fed on subjects with different intensities of Onchocerca volvulus microfilarial infection. Analyses were based on data for Guatemalan S. ochraceum s.l. (possessing a well-developed cibarial armature), West African S. damnosum s.l. (forest species), and South Venezuelan S. guianense (the latter two lacking a toothed cibarium). The mean survival times of samples of the 3 species, kept under laboratory conditions, decreased as parasite intake increased, the rate of mortality being dependent on the fly's age (measured as time post-feeding) and on the worm load acquired. An empirical, time-dependent hazard function was fitted to observed death rates/fly/day which rose very shortly after engorgement, declined subsequently, and rose again throughout the extrinsic incubation period of the parasite. The parameters of this hazard model were all positively correlated with the density of microfilariae in the bloodmeal. Expressions of survivorship and life-expectancy as explicit functions of time post-feeding and mean parasite intake were derived. The average expectation of life at engorgement for uninfected flies in the laboratory was estimated to be around 1 week for both, armed and unarmed blackflies. Residual life-expectancy decreased with time post-feeding and microfilarial load in both categories of vectors. This decline (resulting from age- and parasite-dependent mortality rates) was much more pronounced in those species lacking a toothed fore-gut. Whilst a fraction of heavily infected S. ochraceum was able to survive the latent period of the parasite, being therefore potentially capable of transmitting the infection, equivalent worm loads in S. guianense resulted in a drastic reduction of the expectation of infective life. These results provide additional evidence to support the hypothesis that, in the case of intrinsically susceptible vectors, unarmed simuliids are more efficient at low microfilarial loads, when the transmission rate from human to vector host is higher, and parasite-induced fly mortality is negligible. The opposite takes place in armed flies, which perform poorly at low parasite burdens and better at heavier loads, with little parasite-induced vector death.

Animals↗
PubMed1996

The transmission dynamics of hepatitis B in the UK: a mathematical model for evaluating costs and effectiveness of immunization programmes.

Complex hepatitis B (HBV) epidemiology makes it difficult to evaluate and compare effectiveness of different immunization policies. A method for doing so is presented using a mathematical model of HBV transmission dynamics which can represent universal infant and adolescent vaccination strategies and those targeted at genito-urinary (GU) clinic attenders and infants born to infectious mothers. Model structure, epidemiological underpinning, and parameterization, are described. Data from the UK National Survey of Sexual Attitudes and Lifestyles is used to define patterns of sexual activity and GU clinic attendance; data deficiencies are discussed, in particular that of UK seroprevalence of HBV markers stratified by age, sex, and risk factors. General model predictions of endemic HBV marker prevalence in homosexual and heterosexual populations seem consistent with published UK data. The simulations exhibit non-linearities in the impact of different vaccination strategies. Estimated number of carriers prevented per vaccine dose for each strategy provides a measure of costs and benefits, varying temporally over the course of a programme, and with level of vaccine coverage. Screening before vaccination markedly increases payback per dose in homosexuals but not in heterosexuals; mass infant vaccination gives the poorest effectiveness ratio and vaccination of infants after antenatal screening the best; in general, increasing vaccine coverage yields lower pay-back per dose. The model provides a useful framework for evaluating costs and benefits of immunization programmes, but for precise quantitative comparison more UK epidemiological data is urgently needed.

Adolescent↗
PubMed1996

Optic neuritis in a child.

A previously healthy four-year-old girl developed bilateral loss of vision over one day. Her course of optic nerve abnormalities, a related neurologic episode, and the response to corticosteroid therapy is presented. The diagnosis of optic neuritis in a child is made infrequently in an emergency department, but it must be considered in any patient presenting with an acute nontraumatic loss of vision. The characteristic findings associated with optic neuritis, and a review of childhood cases, are discussed.

Acute Disease↗
PubMed1996

Delivery of albuterol in a pediatric emergency department.

STUDY OBJECTIVE: To determine if albuterol delivery by the combination of a metered-dose inhaler (MDI) with a spacer is equal in effectiveness to nebulization in a pediatric emergency department setting. DESIGN: Prospective series. SETTING: Urban children's hospital emergency department. PARTICIPANTS: Patients > or = six years of age with the diagnosis of acute asthma exacerbation. Exclusion criteria consisted of impending respiratory failure and corticosteroid administration within the preceding seven days. INTERVENTIONS: Patients were randomized into either the nebulizer treatment group or one of two MDI-spacer treatment groups (two spacers were evaluated). Each patient received three albuterol treatments administered evenly over one hour. The dose ratio for albuterol by nebulizer versus MDI-spacer was 6.9:1. Outcome was assessed by comparing the pre- and posttreatment percent predicted respiratory rate and percent predicted peak expiratory flow rate (PEFR) for each patient. RESULTS: Sixty patients were enrolled in the study. All three treatment groups showed significant improvement following albuterol therapy in both percent predicted respiratory rate and percent predicted PEFR. When comparing the three groups against each other in regard to outcome, no significant differences were found in improvement of percent predicted respiratory rate (P = 0.3258) or percent predicted PEFR (P = 0.9362). CONCLUSION: In a pediatric emergency department setting, aerosolized albuterol delivered by MDI-spacer was equal in effectiveness to nebulization in the acute asthma management of children > or = six years of age.

Adrenergic beta-Agonists↗
PubMed1996

Targeted hepatitis B vaccination--a cost effective immunisation strategy for the UK?

OBJECTIVE: To compare the potential cost effectiveness of vaccination against hepatitis B virus (HBV) targeted at genitourinary clinic (GU) attendees with that of universal infant vaccination. DESIGN: A mathematical model of sexual and perinatal transmission of HBV was used to compare the effectiveness among heterosexual and homosexual populations of programmes of mass infant vaccination and targeted immunisation of genitourinary medicine (GU) clinic attendees. Each was applied to 90% of the eligible population with differing assumptions about rates of compliance and seroconversion - problems of delivery (obtaining high compliance) was considered a significant drawback of targeted vaccination. Observed relationships between GU clinic attendance and sex partner change rates for heterosexuals and for homosexuals were used to define the rates of vaccination uptake within sexual activity risk groups. SETTING: England and Wales. RESULTS: Model results showed that for heterosexuals universal infant vaccination became more effective than clinic based vaccination only approximately 40 years after the start of the programme and that the predicted cost effectiveness of GU clinic vaccination was greater at all times. For homosexuals, clinic vaccination was always more effective over the time frame considered, but by 50 years if it were carried out without prior screening it had become appreciably less cost effective than a mass infant programme. With prior screening in GU clinics this cost effectiveness deficit was only marginal. CONCLUSIONS: Targeted vaccination might have a much greater potential than is realised at present, particularly if it were possible to improve compliance of clinic attendees. A fuller comparison between mass infant and targeted vaccination must await the specific inclusion in the model of other risk groups such as intravenous drug users. An important determinant of the relative merits of the two approaches is the relationship between rates of attendance and of changing sexual partners. Further research on this is required.

Adult↗
PubMed1996

Pulmonary nodules: effect on detection of spiral CT pitch.

PURPOSE: To compare spiral computed tomography (CT) performed at increased pitch with spiral CT performed at standard pitch in the detection of pulmonary nodules. MATERIALS AND METHODS: Spiral CT scanning of the thorax was performed with a pitch of 1.0 in 109 patients with pulmonary nodules due to metastases. The patients were also randomly assigned to undergo further scanning with a pitch of 1.2 (n = 34), 1.5 (n = 37), 2.0 (n = 38) at the same scanning session. The scan pairs were analysed for number, size, and distribution of nodules. RESULTS: A bias toward undercounting was noted on scans with a pitch of 1.5 and 2.0; however, this was not statistically significant. Correlation coefficients were r = .982, r = .977, and r = .989 for scans of pitch 1.2, 1.5, and 2.0, respectively. Disease in one patient would have been prospectively understaged from findings on a scan of pitch 2.0 because of poor conspicuity of a small solitary nodule. CONCLUSION: Findings from scans with increased pitch generally agree well with those from scans with standard pitch; however, there is a greater risk of understaging of disease in patients with solitary nodules as pitch increases. Pitch should be limited to no greater than 1.5 for initial staging of pulmonary metastatic disease.

Adult↗
PubMed1996

Scatter dose estimation based on dose-area product and the specification of radiation barriers.

Scatter dose as a function of dose-area product (DAP) has been studied over a range of tube potentials and scattering angles. Data are presented to permit the calculation of scatter dose from DAP at distances of 1 m or more from the patient. This method has been used to calculate absorbed dose to the walls of six existing X-ray rooms which are used for interventional radiology, angiography or barium contrast studies. These calculations have been compared with measurements using thermoluminescent dosemeters. The median ratio of measured to calculated dose was 0.50 and the maximum value was 1.26. It was concluded that the calculation of scatter dose from DAP using the factors derived in this report can be used as the basis for the specification of radiation protection barriers. The busiest room in this study in terms of DAP had a DAP rate of 224 Gy cm2 per day. From the scatter factors presented here, it was shown that the room walls did not need to have more than 1.2 mm of lead equivalence.

Angiography↗