Search PubMed⌕ Search

Biomedical subjects

S J Williams

Publications and source records attributed to S J Williams.

At least 91 records · Page 5Linked to original sources
PubMed1990

Randomised controlled trial of recombinant human interferon -alpha A for chronic active hepatitis B.

The efficacy of interferon treatment for Australian patients with chronic active hepatitis B (CAH-B) was assessed by a three-centre randomised controlled trial in Sydney and Brisbane. Thirty patients (29 with histologically-proven CAH-B with and without cirrhosis and one with chronic persistent hepatitis) were allocated to receive either thrice weekly intramuscular injections of recombinant human leucocyte interferon -alpha A (either 2.5, 5.0 or 10.0 million units/m2) for six months followed by 12 months of observation, or to be observed for 18 months without active treatment. Three of 23 treated patients but none of seven controls underwent clinical, biochemical and histological resolution of their disease with loss of HBsAg, HBeAg and HBV-DNA from serum. An additional six treated and two control patients underwent a sustained partial remission of their disease. This was characterised by resolution of symptoms and serum aminotransferase abnormalities in association with seroconversion from HBeAg positive to negative, loss of HBV-DNA from serum but persistent hepatitis B surface antigenaemia. In such patients, there was significant improvement in histological appearances but some necroinflammatory activity remained and fibrosis was unchanged. Although total response rates were similar in treated and control subjects, they appeared to occur earlier after interferon treatment. Treatment with interferon was associated with predictable but minor side effects that usually did not necessitate dose reduction and rarely compromised the patient's life style. Interferon is thus a feasible treatment for CAH-B. Complete responses occurred only in treated patients and partial responses appeared to occur earlier in treated than in untreated patients. However, differences in the partial response rate at 18 months were not significant and seroconversion from HBeAg positive to negative was not associated with complete histological resolution of disease activity. Hence, while interferon is a promising agent for treatment of CAH-B, efforts must continue to define more optimal treatment regimes and to identify those patients most likely to respond to this agent.

Adult↗
PubMed1989

Endoscopic management of inoperable cholangiocarcinoma using iridium-192.

We report a well tolerated endoscopic technique of administering intraluminal radiotherapy to 14 patients with inoperable cholangiocarcinoma, in which the iridium-192 wire source was inserted down a nasobiliary catheter placed within a previously inserted endoscopic biliary prosthesis, thus allowing bile flow to continue during treatment. Radiotherapy was commenced 2 weeks after biliary decompression, when the median serum bilirubin level had fallen from 213 to 34 mumol/l. A total radiation dose of 6000 cGy at 0.5 cm from the source was administered over a median of 85 h (range 77-116 h). In four patients there was a transient increase in serum bilirubin during iridium treatment and, in two cases (14 per cent), this was associated with mild cholangitis. Both cases resolved rapidly once the iridium wire and nasobiliary catheter were removed. The median hospital stay after treatment was 2.5 days (range 0-28 days). The late complications associated with stent blockage were minimized by routinely changing stents at 4-6 monthly intervals; ten of the patients have so far undergone from one to five (median three) stent changes. Five patients have died at 3.6-8.2 months (median 4.8 months) following iridium treatment; four had extensive type III hilar lesions at diagnosis. Nine patients are still alive at 5.4-31.0 months (median 16.4 months). The overall median survival after iridium therapy is 10.5 months. This technique of endoscopic biliary decompression before internal iridium administration minimizes complications by allowing biliary drainage during treatment. The role of this treatment in patients with inoperable cholangiocarcinoma awaits the results of randomized, controlled trials.

Adenoma, Bile Duct↗
PubMed1989

Serial antipyrine clearance studies detect altered hepatic metabolic function during spontaneous and interferon-induced changes in chronic hepatitis B disease activity.

The present study was performed to establish whether sequential determinations of antipyrine clearance, using a simplified two-point test, are sensitive and specific indicators of changes in chronic hepatitis B disease activity. Sixteen patients were studied on four or more occasions during 18 to 30 months. Eleven patients were treated with recombinant human alpha-interferon (2.5, 5.0 or 10 X 10(6) per m2, intramuscularly, three times per week, for 24 weeks), and five patients were untreated controls. Among seven patients, (six interferon-treated and one control) who lost hepatitis B e antigen from serum, antipyrine clearance improved by 46% (range: 20 to 160%) from 0.37 +/- 0.14 ml per kg per min (mean +/- S.D.) to 0.54 +/- 0.13 ml per kg per min, p less than 0.005. This change paralleled the loss of symptoms and reduction of serum ALT levels (from 206 +/- 189 IU per liter (mean +/- S.D.) to 38 +/- 12 IU per liter, p less than 0.005). Conversely, antipyrine clearance declined to previous levels when reactivation of chronic hepatitis B with reappearance of HBeAg in serum occurred. Regardless of changes in hepatitis B serology, when serum ALT values fluctuated by more than 20% (presumed to reflect fluctuations in necroinflammatory activity of the liver disease), antipyrine clearance also changed whereas serum albumin and bilirubin concentrations and prothrombin time did not. It is concluded that antipyrine clearance is a more sensitive and specific parameter than conventional indices for assessing hepatic metabolic function during changes in chronic hepatitis B disease activity. Remission in disease with loss of HBeAg from serum is associated with improved hepatic metabolic function as determined by the antipyrine clearance test.

Adult↗
PubMed1989

Kinetics of Tc-99m hexakis t-butyl isonitrile in normal and ischemic canine myocardium.

Hexakis 99mTc-tertiary butyl isonitrile (99mTc-TBI) was studied as a cardiac perfusion imaging agent in nine dogs with partial occlusion of the LAD. Thirty min after applying the stenosis, 99mTc-TBI was injected into the right atrium (RA) in five dogs and left atrium (LA) in four dogs. Normal and ischemic zone regional myocardial 99mTc-TBI activities were monitored continuously for 4 h. Dogs with LA injections had minimal and equivalent 4 h fractional clearance from the normal and ischemic zones. Dogs with RA injections had minimal, but significantly lower 4 h fractional 99mTc clearances in the ischemic zone (0.08 +/- 0.08) compared to the normal zone (0.16 +/- 0.07, P less than 0.05). The delayed ischemic zone clearance is probably due to the high initial lung uptake observed after RA injection. Despite the differences in clearance, this minimal amount of redistribution could not be detected on gamma camera images. The minimal myocardial washout and redistribution, and the 140 keV gamma make 99mTc-TBI a promising cardiac perfusion imaging agent.

Animals↗
PubMed1989

Rat but not human interferons suppress hepatic oxidative drug metabolism in rats.

An animal model suitable for in vivo studies of interferon-mediated suppression of hepatic oxidative drug metabolism has been developed. Rats were injected with either recombinant human interferon alpha A, recombinant human interferon gamma, recombinant rat interferon gamma, or vehicle and experiments were performed 24 h later. In some animals theophylline elimination was determined twice (10 days apart), once after interferon and once after vehicle. Theophylline clearance was also determined in the isolated perfused rat liver after pretreatment of animals with interferon or vehicle. Pretreatment of animals with rat interferon gamma significantly reduced theophylline clearance in the intact rat but neither human interferon alpha A nor human interferon gamma altered theophylline elimination in vivo. Similar results were observed in the isolated perfused rat liver. We then examined whether the effects of interferon on hepatic drug metabolism were generalized or confined to individual cytochrome P450 isozymes; androstenedione hydroxylation pathways were used as catalytic probes for individual cytochrome P450 isozymes. Rat interferon gamma (but not human interferon alpha A) decreased levels of total hepatic microsomal P450 and reduced androstenedione 16 beta-hydroxylation. The formation of three other hydroxylated androstenedione metabolites appeared reduced to a similar extent, although these changes were not significant. It is concluded that autologous but not heterologous interferons impair oxidative drug metabolism in the rat. The reduction of hepatic P450 produced by interferon may result from the suppression of multiple isozymes.

Androstenedione↗
PubMed1989

Chronic respiratory illness and disability: a critical review of the psychosocial literature.

The paper attempts to offer a critical review of the current psychosocial literature on chronic obstructive airways disease (COAD: emphysema, chronic obstructive bronchitis and chronic asthma) from a (medical) sociological perspective. Following a brief exposition of the clinical nature of COAD and its epidemiology the paper reviews some of the main psychosocial literature in the field. It then focuses on some of the problems concerning issues of methodology and measurement within the existing research, particularly the inadequacy of many of the 'quality of life' instruments and disability measures used; the lack of research which combines both quantitative and qualitative data; and the predominant concern with the psychological aspects of the condition to the detriment of the social dimensions involved. Using the International Classification of Impairments, Disabilities and Handicaps (ICIDH) as its conceptual scaffold, the paper then goes on to argue that a sociological perspective is both a necessary and essential complement to existing research in this area in order to achieve a fuller understanding of chronic respiratory illness/disability and its sequelae. Finally, the paper attempts to offer some possible reasons why chronic respiratory and disability has received relatively little attention from within the social sciences and concludes with some reflections and suggestions on possible future developments in research into chronic respiratory illness and disability from within the social sciences.

Depression↗
PubMed1989

Impairment, disability and handicap in chronic respiratory illness.

Chronic obstructive airways disease (COAD) is a major, though neglected, medical and social problem in the United Kingdom today. Dyspnoea is one of the most distressing and disabling symptoms of COAD, which is itself the largest single cause of absence from work in the United Kingdom. 92 patients suffering from COAD were interviewed in order to assess impairment, disability and handicap. Measures included spirometric tests of lung function; the Fletcher breathlessness grading scale, the oxygen cost diagram and a visual analogue scale of dyspnoea; the Functional Limitations Profile (FLP); and the shortened 12 item General Health Questionnaire (GHQ-12), supplemented by the 7-item GHQ sub-scales of anxiety and severe depression. Low correlations were found between lung function and disability (-0.38, P less than 0.001), accounting for only 14% of the variance, and high correlations were found to exist between measures of dyspnoea and disability (-0.90, P less than 0.001). Major areas of disability and handicap included; household management, ambulation, sleep and rest, recreation and pastimes and work. Financial problems and difficulties, housing problems and problems of social isolation were also frequently reported. The paper goes on to discuss both the need for a more integrated approach to the care and rehabilitation of COAD patients and their families and for a complementary social perspective and approach to COAD and its treatment.

Persons with Disabilities↗
PubMed1989

Resistance of metastatic pancreatic endocrine tumours after long-term treatment with the somatostatin analogue octreotide (SMS 201-995).

Ten patients with metastatic pancreatic endocrine tumours were treated with the long-acting somatostatin analogue octreotide (SMS 201-995). Three patients showed no response, clinically or biochemically, and treatment was therefore withdrawn. The seven remaining patients continued treatment for a median period of 28 months (range 13-54 months). Treatment was initially effective, symptoms improved and the concentrations of tumour-related hormones were reduced. Worsening of symptoms and rising levels of tumour-related hormone concentrations occurred a median of 5 months (range 1-6 months) after the start of therapy and were initially reversed by increasing the dose of octreotide over a median of 10 months (range 6-16 months). However, after a median of 13 months (range 5-34 months) at the maximum dosage, symptoms recurred and were no longer responsive to a further increase in dosage of octreotide or other therapeutic measures. All patients died within a period of 5 months once this resistant phase of their illness had been reached.

Adenoma, Islet Cell↗
PubMed1989

Assessing the economic impact of AIDS in local communities. Current and projected costs for San Diego County.

The economic cost of the acquired immunodeficiency syndrome (AIDS) in San Diego County, California, is forecast to increase from $103 million in 1986 to between $502 and $743 million in 1991, rising at a minimum average annual rate of 30% after adjusting for inflation. A greater emphasis on outpatient care and the use of new therapies that increase life expectancy by reducing the frequency and severity of morbidity will decrease the future annual cost of treatment but will have a small effect on total economic costs because of substantial foregone earnings by persons with AIDS. Estimating the economic impact of this disease provides valuable information for formulating effective strategies to treat AIDS patients, to provide education for limiting the spread of the human immunodeficiency virus, and to achieve other health objectives.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Characterization of technetium-99m-L,L-ECD for brain perfusion imaging, Part 1: Pharmacology of technetium-99m ECD in nonhuman primates.

Technetium-99m ethyl cysteinate dimer ([99mTc]ECD) is a neutral, lipophilic complex which rapidly crosses the blood-brain barrier. Brain retention and tissue metabolism of [99mTc]ECD is dependent upon the stereochemical configuration of the complex. While both L,L and D,D enantiomers are extracted by the brain, only the L,L but not the D,D form, is metabolized and retained in the monkey brain (4.7% injected dose initially, T 1/2 greater than 24 hr). Dynamic single photon emission computed tomography imaging studies in one monkey indicates 99mTc-L,L-ECD to be distributed in a pattern consistent with regional cerebral blood flow for up to 16 hr postinjection. Dual-labeled 99mTc-L,L-ECD and [14C]iodoantipyrine autoradiography studies performed 1 hr after administration show cortical gray to white matter ratios of both isotopes to be equivalent (approximately 4-5:1). These data suggest that 99mTc-L,L-ECD will be useful for the scintigraphic assessment of cerebral perfusion in humans.

Animals↗
PubMed1988

Symptomatic secondary hormone syndromes in patients with established malignant pancreatic endocrine tumors.

Over a five-year period, we measured concentrations of gut hormones in plasma samples from 353 patients in whom diagnoses of pancreatic endocrine tumors were subsequently confirmed. A median of 19 months (range, 7 to 120) after the initial diagnosis, 24 of these patients (6.8 percent) had elevated concentrations of other hormones in association with new clinical symptoms. In 13 of these patients (8 with glucagonomas, 3 with tumors secreting vasoactive intestinal polypeptide, and 2 with insulinomas), hypergastrinemia developed along with the clinical features of a gastrinoma; 5 patients died of gastrointestinal perforation or bleeding, apparently caused by this second tumor. We conclude that patients with pancreatic endocrine tumors, regardless of their initial clinical picture, require continued surveillance for new elevations of hormones.

Adenoma, Islet Cell↗
PubMed1988

Cardiac imaging and myocardial kinetics of technetium-tertiary butyl-isonitrile during dipyridamole-induced hyperemia.

UNLABELLED: To determine the myocardial kinetics of technetium-tertiary-butyl-isonitrile (Tc-TBI) during dipyridamole-induced hyperemia, the circumflex coronary arteries (LCX) of 15 dogs were partially occluded. Dipyridamole was then infused intravenously over 4 minutes, creating hyperemic flows in the anterior descending (LAD) coronary system. Tc-TBI was administered, then LAD and LCX regional myocardial Tc-TBI activities were continuously monitored with miniature detectors and gamma camera imaging over 3 hours. Microsphere-determined regional myocardial blood flows demonstrated an LCX/LAD flow ratio of 0.81 +/- 0.21 at rest and 0.45 +/- 0.24 (SD) during dipyridamole infusion. Three-hour fractional Tc-TBI clearance rates were minimal and were equal in the LAD (0.14 +/- 0.11) and LCX (0.13 +/- 0.12) zones (p = ns). Excellent gamma camera images, demonstrating the LCX defect, were obtained in all dogs. The correlation coefficient was 0.98 for regional myocardial blood flow vs initial Tc-TBI distribution. IN CONCLUSION: (1) Dipyridamole vasodilation unmasked coronary stenoses despite no flow disparities at rest. (2) The initial distribution of Tc-TBI is proportional to regional myocardial blood flow. (3) There is minimal washout and no redistribution into the initial defect over time, and thus image quality is stable over time. (4) Tc-TBI myocardial kinetics may be applicable to closely related agents currently being developed.

Animals↗
PubMed1988

The rib cage and abdominal components of respiratory system compliance in tetraplegic patients.

The specific compliance of the chest wall and lungs combined was measured in eight patients with stable tetraplegia. Expiration was impeded with a series of spring-loaded resistances, and end-expiratory pressures plotted against changes in chest wall volume at end-expiration. An optical contour mapping system was used to partition changes in chest wall volume into rib cage and abdominal components. These measurements suggest that the compliance of the whole system is reduced by one third in patients with stable tetraplegia, compared with normal subjects. This may be because of abnormal stiffening of the rib cage.

Abdominal Muscles↗
PubMed1987

Inhibition of theophylline metabolism by interferon.

1 day after a single intramuscular injection of recombinant human interferon alpha A in 5 patients with stable chronic active hepatitis B and 4 healthy controls theophylline clearance was significantly reduced and theophylline elimination half-life was significantly increased. There was a clear relation between pre-treatment and post-treatment theophylline clearance rates, indicating that the greatest effect of interferon was in subjects who were fast metabolisers of theophylline. These observations support the contention that the actions of endogenous interferon may account for the effects of immunisations and viral infections on hepatic drug metabolism. Moreover, treatment with interferon may cause clinically important drug interactions.

Adult↗
PubMed1987

Formation of acute pulmonary toxicants following thermal degradation of perfluorinated polymers: evidence for a critical atmospheric reaction.

In some small-scale tests of combustion-product toxicity, perfluorinated polymers (FP) have been shown to be much more toxic than other common materials. These studies were conducted to determine the conditions under which highly toxic decomposition products of FP are formed. A modification of the National Bureau of Standards exposure system (Levin et al. National Bureau of Standards 1982, NBS IR 82-2532) was used, in which materials could be heated either in a cup furnace or above a small methane flame. At 700 degrees C, the approximate lethal concentrations (ALCs) of the products formed from polytetrafluoroethylene (pTFE) and from hexafluoropropylene/tetrafluoroethylene copolymer (FEP) in the CH4 flame (applied for 1 min) are approximately 850 times higher than the ALCs of the products formed in the cup furnace. Analytically, the major products formed initially from pTFE at 700 degrees C under either condition (flame or cup furnace) are similar but they disappear rapidly in the presence of continuous heat. When the cup furnace is removed 1 min after pTFE is added (a procedure temporally similar to the use of the flame) the toxicity of the products is again low. However, when heat from either the cup furnace or from a small secondary flame is applied continuously (for up to 30 min) to the initial products formed from pTFE in the flame, high toxicity is observed. These observations are supported by pathological evaluation of the respiratory tracts of exposed rats. Thus, the inhalation toxicity of FP thermal decomposition products is related to a heat- and time-dependent atmospheric reaction. Such mechanisms should be considered in estimating the fire hazard of these materials in use.

Animals↗
PubMed1987

Lack of antibody induction following skin testing with histolyn-CYL: ELISA determinations with Histoplasma capsulatum yeast and mycelial phase antigens.

No significant increases in antibody levels (IgG, IgM) were detected when serum specimens obtained from individuals exhibiting a positive skin test to the Histoplasma capsulatum yeast phase reagent, Histolyn-CYL, were assayed by the indirect enzyme-linked immunosorbent assay (ELISA) using yeast and mycelial phase antigens.

Antibodies, Fungal↗
PubMed1987

Hepatitis B in Australia: determinants of intrafamily spread.

Strategies for the control of hepatitis B virus (HBV) infection rely on information about the modes of spread and the numbers of 'at risk' individuals in particular community subgroups. This study prospectively examined 377 family and household contacts of 145 patients with HBV infection to determine the incidence of and factors determining intrafamily spread. Two hundred and forty were contacts of 68 Asian patients and 137 were contacts of 77 Caucasian patients. Serological examination of all contacts demonstrated that 161 (43%) had HBV markers including 60 (16%) who were HBsAg positive. HBV transmission within families was greater if the index case was Asian rather than Caucasian (p less than 0.001), had an HBsAg positive mother rather than an HBsAg positive father (p less than 0.01), was HBeAg positive rather than HBeAg negative (p less than 0.002), and had chronic rather than acute HBV infection (p less than 0.001). However birthplace, family size, and the activity of the liver disease of the index case did not influence HBV transmission. Within Asian families, the risk of non-sexual and non-vertical transmission of hepatitis B appeared to be as high as 18% and continued after the first three years of life. It is concluded that hepatitis B prevention programmes should include vaccination of families of chronic HBV carriers, particularly those from endemic regions such as Asia.

Adolescent↗