Acetaminophen toxicity in an urban county hospital.
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Acetaminophen↗
Biomedical subjects
R Williams
Publications and source records attributed to R Williams.
Breaking the barriers for improved glycaemic control: primary care and secondary care interface.
The prevalence of diabetes is predicted to increase dramatically over the next 30 years, mostly as a result of Type 2 diabetes. To manage this increased burden, the following measures must be implemented: diabetes care must be delivered in the most suitable locations; people with diabetes must remain in contact with the appropriate healthcare professionals; and health professionals must use the most effective methods to treat their patients. The structure for diabetes care suggested by the World Health Organization uses terminology that is familiar universally. The reality, in terms of what can be delivered at primary- and secondary-care level will, however, differ greatly according to the extent of service development and the resources available. The optimum forum for diabetes care should have the advantages of the primary-care setting and, when required, the main advantages of the secondary-care setting, i.e. specialized knowledge and more sophisticated facilities. In most healthcare systems, particularly those without financial disincentives to the patient to be followed up in hospital, the tendency remains for secondary care to 'capture' and retain patients for longer than is required clinically. The end results are the overloading of hospital services, inappropriate use of resources and the tendency for patients to default from care because of the relative inaccessibility and remoteness of the hospital service. Issues with special reference to different models of diabetes care, use of patient registers and clinical guidelines, and the perceptions of patients regarding the successful use of services are presented.
Blood Glucose↗
Adverse events associated with vitamin K1: results of a worldwide postmarketing surveillance programme.
We compared adverse events associated with a conventional vitamin K(1) preparation, Konakion, with a new mixed micellar formulation, Konakion MM. Data were obtained worldwide from spontaneous reports, clinical trials and postmarketing surveillance. During the period 1974 to July 1995, an estimated 635 million adults and 728 million children were prescribed Konakion or Konakion MM. Of the 404 adverse events in 286 subjects reported, 387 (96%) were associated with Konakion. Konakion MM accounted for 4% (n=17) of the reported adverse events, and 5% of total sales figures. Thirteen of the 17 adverse events (76%) reported for Konakion MM were minor injection site reactions. Overall, 120 of the adverse events were serious, of which 117 (98%) were associated with Konakion. Eighty-five probable anaphylactoid reactions (of which six were fatal) were reported for conventional Konakion, compared with one non-fatal anaphylactoid reaction for Konakion MM. During the last 12 months of postmarketing surveillance, there were 14 serious adverse events reported in an estimated 21 million individuals treated with Konakion, but none in the 13 million who received Konakion MM. These results suggest that the Cremophor EL-solubilized preparations of vitamin K(1) have a higher profile of adverse events, including anaphylactoid reactions, than the newer mixed micellar preparation, Konakion MM.
Journal Article↗
Defining the outcome of immunosuppression withdrawal after liver transplantation.
Successful immunosuppression withdrawal should benefit the natural history of organ transplantation patients. To identify the clinical hazards of removing drug treatment and possible characteristics that predict a favorable outcome in long-term liver recipients, immunosuppression was withdrawn completely and the clinicopathological outcome documented in 18 liver recipients. Indication for transplantation, HLA matching, early rejection history, and presence of microchimerism were examined as predictors of outcome. Chimerism was determined by polymerase chain reaction-based examination for donor-specific HLA-DRB1 alleles and Y-gene-specific nucleotide sequences. At 3 years, 5 patients (28%) remained completely off immunosuppression; 12 patients (67%) experienced histological graft changes: acute rejection in 4, portal tract inflammation/hepatitis in 7, and necrosis in 1. Hepatitis B or C viral infections did not account for the nonrejection patterns. Unmasking of systemic disorders occurred. Chimerism, demonstrated in 7 patients (39%), with skin the optimal tissue, was not associated with tolerance. Parameters associated with successful drug withdrawal were transplantation for non-immune-mediated liver disorders, fewer donor-recipient HLA A, B, and DR mismatches, and a low incidence of early rejection. Immunosuppression withdrawal is a feasible option in a proportion of selected liver recipients, but identification of tolerant patients remains imprecise.
Adult↗
Use and outcome of liver transplantation in acetaminophen-induced acute liver failure.
Once defined clinical criteria are fulfilled in acetaminophen-induced hepatotoxicity, prognosis without orthotopic liver transplantation (OLT) may be very poor. In the present study, we examined the application and outcome of OLT in 548 patients admitted to a single center between 1990 and 1996. Four hundred twenty-four (77%) of the patients studied did not fulfill transplantation criteria, and 396 of these (93%) survived. The majority of the 28 nonsurvivors (7%) in this group fulfilled two of three combined criteria, and the finding of a high APACHE III score could be used as an indicator for the need for OLT. Of the 56 patients (45%) not listed, in only a small proportion was this caused by psychiatric reasons, and in the majority, it was a consequence of the rapid development of multiple organ failure and cerebral edema. This also applied to 24 (35%) of the 68 listed patients in whom the rapidity of clinical deterioration, reflected in increasing APACHE III scores, was such that even with the prompt availability of donor organs, OLT was not possible. In the final event, only 44 (35%) of those who fulfilled criteria underwent OLT, of whom 33 (75%) survived to leave the hospital. Survival was greatest in those receiving unreduced grafts, and markers of early graft function differed significantly between survivors and nonsurvivors. Liver transplantation is an effective treatment in a relatively small number of patients with acetaminophen-induced hepatotoxicity, and for a substantial proportion, transplantation was never an option because of the rapidity of clinical deterioration. APACHE III scoring may be of value in decision making and in better defining patients in clinical trials.
Acetaminophen↗
A randomized study comparing ribavirin and interferon alfa monotherapy for hepatitis C recurrence after liver transplantation.
Hepatitis C virus (HCV) infection usually recurs after orthotopic liver transplantation (OLT), and most patients develop graft damage. This study compared the efficacy of interferon alfa (IFN-alpha) and ribavirin monotherapies in liver transplant recipients with chronic hepatitis C in the graft. Thirty OLT recipients with chronic hepatitis C were randomized to receive either IFN-alpha (3 MU three times a week) or ribavirin (up to 1.2 g daily) for 24 weeks. Virological, biochemical, and histological responses to treatment were assessed. Twenty-eight patients completed the treatment regimen, two ribavirin-treated patients being withdrawn because of severe hemolysis. Normalization of serum aspartate aminotransferase was achieved in 13 of 14 patients receiving ribavirin (93%) and 6 of 14 patients receiving IFN-alpha (43%; P=.01). Lobular inflammation was reduced in 9/14 ribavirin-treated (64%) and 3 of 14 IFN-alpha-treated patients (21%; P=.05), each of whom had a biochemical response. However, the total histological activity index did not improve in either the interferon (P=.43) or the ribavirin (P=.96) group. Posttreatment viremia levels were significantly reduced in IFN-alpha-treated (P=.05) but not in ribavirin-treated (P=.88) patients. Hemolysis occurred in all ribavirin-treated patients, with serum hemoglobin decreasing to < 10 g/dL in 50%. Total leukocyte and lymphocyte counts decreased significantly during ribavirin treatment (P=.02 and P=.004, respectively). We concluded that in patients with chronic hepatitis C after OLT, IFN-alpha retains an antiviral effect whereas ribavirin is superior in achieving normalization of serum aspartate aminotransferase levels and reducing lobular inflammation, but not the total histological activity index. These findings provide a rationale for combination therapy in the post-OLT setting, although patients must be carefully monitored for hemolysis.
Adult↗
Tolerance and latent cellular rejection in long-term liver transplant recipients.
Tolerance develops in a proportion of long-term liver transplant recipients but currently cannot be identified before an attempt at withdrawal from immunosuppression therapy. In the present study, we have examined the immunophenotypic characteristics of the cellular infiltrate in portal tracts and lobules as observed in liver biopsy specimens in relation to the outcome of subsequent withdrawal from immunosuppression therapy. Cryostat biopsy specimens from 27 long-term recipients before drug withdrawal, and from 10 patients with recent transplants who were having acute rejection, were analyzed. Immunohistochemical staining was performed for CD3+ (pan T cell), CD8+ (cytotoxic), CD4+ (helper), CD45RO+ (memory), CD45RA+ (naive), CD56+ (natural killer), CD68+ (macrophage), and CD8+ perforin+ cells. Fewer CD8+ and CD3+ cells were present in the lobular areas of biopsy specimens from patients who were successfully withdrawn from immunosuppression therapy (n = 6) compared with biopsy specimens from patients with nontolerant grafts (n = 9; 15 vs. 23 cells/high-power field [hpf] [P < .01] and 16 vs. 26 cells/hpf [P < .03], respectively) or biopsy specimens obtained during acute rejection (15 vs. 31 cells/hpf [P < .01] and 16 vs. 32 cells/hpf [P < .01]). Cell frequencies in the biopsy specimens of nontolerant long-term patients were similar to those found with acute rejection. Immunophenotyping the lobular inflammation within long-term liver allografts assists in identifying those patients in whom drug withdrawal is likely to be unsuccessful and in whom it is postulated a form of inactive, latent cellular rejection exists.
Adolescent↗
Human leukocyte antigen-C genes and susceptibility to primary sclerosing cholangitis.
Genetic susceptibility to primary sclerosing cholangitis (PSC) is associated with the extended HLA A1-B8-DR3 haplotype and also with the DRB3*0101-DRB1*0301-DQA1*0103-DQB1*0603 haplotype. However, very few studies have considered the role of HLA C which lies between HLA A and B, is highly polymorphic, and encodes proteins which play an important role in immunoregulation and in disease susceptibility. Traditional assignment of HLA Cw antigens by serology is both inaccurate and unreliable, with a high error rate. The aim of this study was to characterize the distribution of HLA C alleles in a large group of patients with primary sclerosing cholangitis by using a recently developed polymerase chain reaction-based genotyping technique. Ninety-three white adult patients of northern European origin with well characterized PSC and 100 geographically and racially matched controls were studied. HLA C and HLA DRB1 alleles were assigned by polymerase chain reaction-based genotyping, HLA A and B antigens by standard microlymphocytotoxicity test and extended haplotypes were constructed according to known patterns of linkage disequilibrium. The Cw*07 gene was found in 67.7% of patients versus 54% of controls (P = .051, OR = 1.79). This increase was a result of inheritance of the Cw*0701 allele which was found in 51.6% of patients compared with 34% of controls (P = .013, OR = 2.07). There were no significant differences in the frequencies of any of the other Cw alleles including the Cw*07 group: Cw*0702, Cw*0703, and Cw*0704. HLA-encoded genetic susceptibility to PSC is associated with the HLA Cw*0701 allele, but the association is weak and may simply reflect linkage disequilibrium with the HLA B8-DR3 haplotype. These findings indicate that the telomeric limit of HLA-encoded susceptibility to primary sclerosing cholangitis lies close to the HLA C locus.
Alleles↗
The significance of aerobic gram-negative bacilli in clinical specimens following orthotopic liver transplantation.
In a prospective study of 284 liver transplant patients, we sought associations between aerobic gram-negative bacillus acquisition or infection and 35 preoperative, perioperative, and postoperative variables. Although the 128 (45%) who acquired aerobic gram-negative bacilli had longer admissions (P = 0.0001), no associations were found with pretransplant variables. Fifty-three (41%) of the 128 acquired coliforms (e.g., Escherichia coli, Klebsiella spp., or Enterobacter spp.), 50 (39%) acquired nonfermentative bacilli (e.g., Acinetobacter spp., Pseudomonas spp., or Stenotrophomonas maltophilia), and a further 25 (20%) acquired both. Acquisition progressed to infection in 58% of patients who acquired coliforms but in only 18% of patients who acquired nonfermentative bacilli (P = 0.005). Acinetobacter spp. were isolated from more patients than other bacilli but rarely caused infection. The positive predictive values for infection of acquiring coliforms or nonfermentative bacilli in clinical material were 42% and 17%, respectively. This study allowed us to determine for each clinical site the positive predictive values for infection of acquisition of different aerobic gram-negative bacilli. Our results should contribute to the rationalization of antimicrobial prescribing for this patient group.
Adolescent↗
Left-ventricle boundary detection from nuclear medicine images.
We present here a new algorithm for segmentation of nuclear medicine images to detect the left-ventricle (LV) boundary. In this article, other image segmentation techniques, such as edge detection and region growing, are also compared and evaluated. In the edge detection approach, we explored the relationship between the LV boundary characteristics in nuclear medicine images and their radial orientations: we observed that no single brightness function (eg, maximum of first or second derivative) is sufficient to identify the boundary in every direction. In the region growing approach, several criteria, including intensity change, gradient magnitude change, gradient direction change, and running mean differences, were tested. We found that none of these criteria alone was sufficient to successfully detect the LV boundary. Then we proposed a simple but successful region growing method--Contour-Modified Region Growing (CMRG). CMRG is an easy-to-use, robust, and rapid image segmentation procedure. Based on our experiments, this method seems to perform quite well in comparison to other automated methods that we have tested because of its ability to handle the problems of both low signal-to-noise ratios (SNR) as well as low image contrast without any assumptions about the shape of the left ventricle.
Heart Ventricles↗
Preoperative investigation and indication for operation in hepatocellular carcinoma.
Hepatocellular carcinoma remains a highly prevalent tumor in the Orient and Africa, and detection rates are now increasing in Western countries. Surgical modalities such as hepatic resection and orthotopic liver transplantation are considered the only curative treatments for patients with hepatocellular carcinoma. However, the majority of patients present with advanced disease and are unsuitable for surgical treatment. This fact emphasises the importance of screening programs, usually based on hepatic ultrasonography and measurement of alpha-fetoprotein levels, to facilitate early detection of this tumor in those patients at risk. Subsequent investigations in patients with suspicious lesions on ultrasonography and/or elevated alpha-fetoprotein levels are aimed at confirming the diagnosis of hepatocellular carcinoma, tumor staging, and assessing underlying hepatic functional reserve, thereby establishing the suitability of the patient for potentially curative surgical treatment. This paper reviews preoperative investigations and current indications for surgical treatment in patients with hepatocellular carcinoma.
Carcinoma, Hepatocellular↗
Deprivation state but not nicotine content of the cigarette affects responding by smokers on a progressive ratio task.
In two experiments, we used a progressive ratio schedule to explore factors associated with smoking motivation. In study 1, smokers who had abstained for more than 8 h bar-pressed for longer to obtain puffs on a cigarette than did non-deprived smokers. Neither group, however, showed nicotine-induced improvements in performance on an attention-demanding task. In the second study, two groups of minimally deprived smokers worked on the progressive ratio task for puffs of either a standard or an ultralow nicotine cigarette. The amount of work expended for puffs was the same for both cigarettes. The groups were also indistinguishable in terms of their subjective experience of the impact of smoking. These results suggest that the addition of nicotine to the cigarette may not have an immediate impact on the effort expended for a puff on that cigarette, and that short term changes in craving may be observed independent of satiety effects associated with nicotine ingestion. We conclude that the progressive ratio task is a useful and sensitive measure of desire to smoke, although the two experiments highlight the complexity of the relationship between subjective, objective and behavioural measures of smoking and nicotine ingestion in humans.
Adolescent↗
MRI of optic nerve and postchiasmal visual pathways and visual evoked potentials in secondary progressive multiple sclerosis.
We studied the relationship between abnormalities shown by MRI and functional disturbances in the visual pathway as assessed by the visual evoked potential (VEP) in 25 patients with established multiple sclerosis (MS); only 4 of whom had a history of acute optic neuritis. Optic nerve MRI was abnormal in 19 (76%) and is thus useful in detecting subclinical disease. Optic nerve total lesion length and area on the STIR sequence was found to correlate significantly with prolongation of the VEP latency. This may reflect a predominantly demyelinating rather than inflammatory origin for the signal change in the optic nerve.
Adult↗
A model for making outcomes research standard practice in clinical dietetics.
In today's rapidly changing health care environment, it is imperative that dietitians demonstrate the importance of their role as health care providers by initiating and participating in outcomes research. Patient care should be based on empirical studies, and clinical dietitians should participate in or be at the helm of such investigations. Nutrition research is usually accomplished and reported by persons with MD or PhD degrees who do not have clinical training in nutrition and does not often address situations encountered by dietitians in clinical settings. This article examines the extent to which clinical dietitians are conducting and reporting outcomes research, their attitudes about such research, and how they think they could best acquire the skills needed to incorporate outcomes research into their practice. Results indicate that clinical dietitians are not writing a substantial percentage of articles and that reports of outcomes research are not commonly included in clinical nutrition journals. Clinical dietitians appear to value the inclusion of research in clinical practice, but they are not spending a great amount of time doing research. Dietitians report being comfortable about participating in research but not about designing, conducting, and reporting research. Results from several surveys were used to develop a model for integrating research in clinical practice. This model includes the research process as a basis for clinical practice. A model for collaborative efforts between clinical and academic dietitians is also proposed and emphasizes the responsibility of academic dietetics training programs in the integration of research and clinical practice.
Attitude of Health Personnel↗
The effect of tacrolimus (FK506) on intestinal barrier function and cellular energy production in humans.
BACKGROUND & AIMS: The maintenance of the intestinal mucosal barrier may be energy dependent. Tacrolimus is a potent immunosuppressive drug that decreases mitochondrial adenosine triphosphate production and increases intestinal permeability in animals. METHODS: Twelve liver graft recipients receiving tacrolimus, 9 healthy volunteers, and 5 liver graft recipients not receiving immunosuppression underwent a combined absorption-permeability-mitochondrial function test using 5 g lactulose, 1 g L-rhamnose, 0.5 g D-xylose, 0.2 g 3-O-methyl-D-glucose, 1 mg/kg 2-keto[1-13C]isocaproic acid ([13C]KICA), and 20 mg/kg L-leucine. The respiratory quotient and resting energy expenditure were measured by indirect calorimetry. Tacrolimus pharmacokinetic profiles and levels of endotoxin and IgM and IgG endotoxin core antibodies were determined. RESULTS: Tacrolimus inhibited the decarboxylation of [13C]KICA, the resting energy expenditure, and the respiratory quotient in an exposure-dependent manner, suggesting an inhibition of mitochondrial respiration. Tacrolimus inhibited intestinal absorptive capacity in an exposure-dependent manner. Tacrolimus-treated patients had an increased intestinal permeability and significantly higher endotoxin levels compared with healthy volunteers. CONCLUSIONS: Tacrolimus inhibits cellular energy production in humans at clinically relevant doses. This is associated with an increased intestinal permeability, endotoxemia, and an impaired intestinal absorptive capacity.
Adolescent↗
Mortality in men of Irish heritage in West Scotland.
Britons of Irish parentage have been found to exhibit poorer health and to die at a younger age than the general population. This paper expands the investigation of Irish mortality patterns in Britain, to include men with patrilineal Irish descent from the immigration of the 19th and 20th centuries. Five thousand, seven hundred and sixty-six male employees aged between 35 and 64 y were examined in 27 workplace settings in Glasgow, Grangemouth and Clydebank between 1970 and 1973. Twenty-one years' mortality follow-up was analysed from a survey involving a health questionnaire and medical examination, using name analysis to identify those of patrilineal Irish descent. Fitting Cox's proportional hazards model to date of death, using date of birth and Irish names as covariates, resulted in the patrilineal Irish showing elevated mortality from all cases (relative risk 1.22; 95% CI [1.08, 1.38]) and coronary heart disease (relative risk 1.53; 95% CI [1.27, 1.83]). Mortality risk for men with an Irish surname was also elevated for cerebrovascular disease (relative risk 1.30; 95% CI [0.86, 1.95]), respiratory disease (relative risk 1.17; 95% CI [0.73, 1.86]) and injury or poisoning (relative risk 1.42; 95% CI [0.78, 2.61]), although the low numbers of men dying from these causes, meant that differences did not reach statistical significance at the 5% level. No differences were observed for cancer or other causes. Previous work has shown high mortality for second generation Irish, whereas this study indicates high all-cause mortality and an excess of deaths for coronary heart disease in the much larger group of men with patrilineal Irish descent from the immigration of the 19th and 20th centuries.
Adult↗
Impact of HBV, HCV and GBV-C/HGV on hepatocellular carcinomas in Europe: results of a European concerted action.
BACKGROUND/AIMS: To investigate the impact of hepatitis B (HBV) and C (HCV) infections on hepatocellular carcinoma (HCC) in Europe. METHODS: Five hundred and three patients with HCC, from six liver centers, were included. All 503 sera and 80 liver samples were tested for HBV DNA and HCV RNA by polymerase chain reaction. GBV-C/HGV RNA was also tested in 57 sera. RESULTS: HBsAg and anti-HCV were detected in 19% and 40.1% of the patients, respectively. Serum and liver HBV DNA were detected in 82% and 91% of the HBsAg positive subjects. HBV DNA was also detected in the serum and liver of 33% and 47% of HBsAg negative patients. In this group, serum HBV DNA was more prevalent in anti-HBs and/or anti-HBc patients (47.9%), compared to those without any HBV marker (25.1%). HCV RNA was detected in 89% and 7% of anti-HCV positive and negative cases, respectively, HCV 1b being the most prevalent genotype (80%). Coinfection with HBV and HCV was shown in 20.4% of patients, while only 29% had neither HBV nor HCV GBV-C/HGV RNA was detected in only 4/57 sera. CONCLUSIONS: This study offers the first large analysis of HCC in Europe, based on both serology and molecular tests. It demonstrates the major impact of HBV and HCV, but not of GBV-C/HGV, in liver carcinogenesis in Northern as well as Southern Europe. It also stresses the need to use viral genome detection in epidemiological studies when serological tests are negative.
Aged↗
Association between HLA class II genotype and spontaneous clearance of hepatitis C viraemia.
BACKGROUND/AIMS: Hepatitis C virus (HCV) infection becomes chronic in most cases, with only 10-20% of those infected not developing persistent viraemia. The immune response to HCV may be an important determinant of disease resolution and can be influenced by a number of host factors. The aim of this study was to assess the role of host HLA class II type in influencing viral clearance or susceptibility to chronic HCV infection. METHODS: We have compared the distribution of HLA DRB1, DQA1 and DQB1 alleles in 49 patients with spontaneous clearance of HCV infection (HCV antibody positive but persistently HCV RNA negative), with 55 chronically infected patients and 134 racially matched controls. RESULTS: Three alleles were found significantly more frequently in patients with spontaneous viral clearance compared to those with chronic infection-DRB1*04 (pc=0.0022, odds ratio OR=4.52), DQA1*03 (pc=0.0012, OR=4.69) and DQB1*0301 (pc=0.0078, OR=5.09). DQB1*0302 was found at reduced frequency in all HCV-antibody-positive patients compared to controls (pc=0.0063). CONCLUSIONS: DRB1*04, DQA1*03 and DQB1*0301 are associated with spontaneous clearance of HCV viraemia, with the primary association likely to be with DQB1*0301 and the associations with DRB1*04 and DQA1*03 being due to linkage. In addition, DQB1*0302 is associated with protection from HCV infection. These findings suggest that host HLA class II genotype is an important factor in determining the outcome of infection with hepatitis C virus.
Adolescent↗