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Biomedical subjects

R Williams

Publications and source records attributed to R Williams.

At least 361 records · Page 20Linked to original sources
PubMed1997

MnDPDP-enhanced MR imaging of the liver. Correlation with surgical findings.

PURPOSE: To compare lesion detection and characterisation predicted by MnDPDP-enhanced MR imaging with surgical excision and pathological examination. MATERIAL AND METHODS: Ninety patients were intravenously infused at a rate of 2 to 3 ml/min with 5 mumol/kg mangafodipir trisodium (MnDPDP, Teslascan). The patients were examined with spin-echo and gradient-echo T1-weighted MR imaging at 1 h and 24 h after the end of infusion. The results were compared with identical pre-contrast sequences. In 20 of these patients, the pre-operative MR findings were compared with intra-operative ultrasonography and histology of the resected liver specimens. RESULTS: In those with liver metastases, there was a good correlation between MR and the hepatic disease in 11 out of 14 cases. In the group with primary liver tumours, MR findings correlated with hepatic disease in 5 out of 6 cases. CONCLUSION: Liver lesion characterisation is possible with MnDPDP, and MR contrast enhancement with this agent is considered to be an important adjunct to the radiological assessment of patients with neoplastic liver disease where accurate decisions for surgical planning are imperative.

Adolescent↗
PubMed1997

A focus of tick-borne relapsing fever in southern Zaire.

Relapsing fevers occur worldwide and are characterized by recurrent episodes of fever and spirochetemia. In central, eastern, and southern Africa, the disease is often caused by Borrelia duttonii, which is transmitted by the soft tick Ornithodors moubata. We conducted a field investigation in September 1994 at a hospital in Mitwaba, southern Zaire, which was the only medical facility within 150 km. The introduction of a rapid blood-smear staining technique allowed us to demonstrate that 4.3%-7.4% of the 25-50 new outpatients seen each day had relapsing fever. Because of the absence of malaria in this area, these patients account for most of the febrile patients. The incidence of relapsing fever among all pregnant women in the maternity ward was estimated to be 6.4%, and this condition often led to maternal death or to spontaneous abortion. The 16S rRNA gene of B. dutonii was sequenced after the spirochete was isolated from patients' blood samples and directly from Ornithodoros tick vectors. In this region of Africa, relapsing fever should now be considered an important public health priority.

Animals↗
PubMed1997

Experimental lobar pneumonia due to penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae in immunocompetent and neutropenic rats: efficacy of penicillin and teicoplanin treatment.

Lobar pneumonia models were established in rats by intratracheal inoculation of either penicillin-susceptible (immunocompetent model) or penicillin-resistant (immunocompetent and neutropenic models) Streptococcus pneumoniae. Untreated animals maintained a relatively high bacterial load in the lungs but only occasionally developed bacteraemia or pleurisy. The infection was rarely fatal in immunocompetent rats, but immunocompromised rats frequently died. Treatment i.m. with 10,000 IU/kg of procaine penicillin G (12 h after infection then bid for 3 days) or with a single i.v. dose of 5 or 10 mg/kg of teicoplanin significantly reduced lung bacterial loads of rats infected with the penicillin-susceptible strain. Against the penicillin-resistant strain, teicoplanin displayed a significant activity regardless of the immununological status of the animals. Penicillin G significantly reduced lung bacterial load of the penicillin-resistant strain only in immunocompetent rats and at a higher dose than needed in treatment of the penicillin-susceptible infection. The experimental models described here could be suitable for studying the efficacy of antibacterial agents against pulmonary infections caused by penicillin-susceptible and penicillin-resistant S. pneumoniae strains.

Animals↗
PubMed1997

The effect of ramoplanin coating on colonization by Staphylococcus aureus of catheter segments implanted subcutaneously in mice.

We investigated the effect of ramoplanin coating on Staphylococcus aureus colonization of catheter segments in mice. Segments (1 cm in length) were inserted subcutaneously, 10(7) cfu of S. aureus were inoculated nearby at different times and segments were removed 24 or 48 h later. Uncoated segments were colonized with 10(4) to >10(5) cfu, whereas ramoplanin-coated segments had mean counts of <10 to approximately 100 cfu. Ramoplanin coating may prevent colonization of catheters during the first few days after insertion.

Animals↗
PubMed1997

Bioartificial liver support: developments in hepatocyte culture and bioreactor design.

Bioartificial liver devices aim to support patients with acute liver failure (ALF) until orthotopic liver transplantation (OLT) or spontaneous recovery due to hepatic regeneration can occur. However, initial clinical experiences with two devices have indicated that functional efficacy in this setting may be less than in the experimental situation. Several fundamental issues remain unresolved, including the cell mass required to provide meaningful support and which of those hepatocyte components and bioreactor designs so far proposed is best able to do this. In particular, further studies of the efficacy of devices incorporating human hepatocyte lines transformed by either cultural conditions or genetic engineering and those based on multi-channel or flat bed bioreactor designs in which hepatocytes are co-cultured with non-parenchymal cells are awaited. Controlled trials on a multicentre basis in well-defined patient groups and with standardised outcome measures will be required to properly evaluate the clinical value of these devices. A better understanding of factors promoting recovery and regeneration of the native liver and to what extent these can be provided by extracorporeal devices will be essential to the further development of effective bioartificial liver support systems.

Animals↗
PubMed1997

N-acetylcysteine improves indocyanine green extraction and oxygen transport during hepatic dysfunction.

OBJECTIVES: To investigate whether the beneficial systemic hemodynamic effects of N-acetylcysteine, an agent that increases cyclic guanosine monophosphate (cGMP) concentration in fulminant hepatic failure, are present in a range of liver disorders and what concurrent effect this agent has on the hepatic-splanchnic circulation. SETTING: Liver Failure Unit, King's College Hospital, London, UK. PATIENTS: Fifteen patients with hepatic dysfunction who were mechanically ventilated, either after liver transplantation or during an acute or decompensated chronic liver disorder. INTERVENTIONS: Prostacyclin was administered at a continuous infusion rate of 5 ng/kg/min for 60 mins. After a washout period, the hemodynamic effects of this infusion were compared with the effects present during infusion of N-acetylcysteine at 150 mg/kg in 250 mL of 5% dextrose in water over 15 mins and then 50 mg/kg in 250 mL of 5% dextrose for 45 mins at an infusion rate of 62.5 mL/hr. MEASUREMENTS AND MAIN RESULTS: Following N-acetylcysteine infusion, the baseline oxygen delivery (DO2) increased from 667 +/- 154 to 751 +/- 166 (SD) mL/min/m2, and oxygen consumption (VO2) improved in 13 of 15 patients (150 +/- 30 to 169 +/- 25 mL/min/m2) (p< .01). Indocyanine green clearance, as determined by a fiberoptic physiologic monitoring system, also improved in 13 of 15 patients (7.3 +/- 4.2% to 11.8 +/- 4.0% [mean change 100%, 95% confidence interval 9 to 256]) (p = .002). Patients who were defined as responders in relation to systemic hemodynamics (VO2 of >10% from baseline [n = 6; 40%]) had a significantly lower baseline consumption compared with that of nonresponders (133 vs. 162 mL/min/m2, p = .04). No clear relationship between the increments in VO2 and indocyanine green clearance was observed (r2 = .21; p = .08). Prostacyclin resulted in moderate improvements in systemic DO2 (but not VO2) and a nonsignificant increase in indocyanine green clearance. CONCLUSION: N-acetylcysteine increases systemic VO2 in a proportion of patients with a wide variety of hepatic disorders. In addition, N-acetylcysteine elicits an improvement in indocyanine green clearance. These properties may be clinically useful in a range of critical illnesses where systemic or hepatic-splanchnic circulations are compromised.

Acetylcysteine↗
PubMed1997

Use of extracorporeal liver assist device and auxiliary liver transplantation in fulminant hepatic failure.

The case history of a 14-year-old boy with fulminant hepatic failure secondary to non-A, non-B hepatitis who fulfilled selection criteria for orthotopic liver transplantation is described. Two forms of liver support were used (extracorporeal liver assist device and an auxiliary partial orthotopic liver transplantation) to provide additional time to allow spontaneous recovery to occur. During the 66 h of extracorporeal haemoperfusion through the device, haemodynamic stability was maintained along with improvements in serum bilirubin (555 to 381 mumol/l), and international normalized ratio (INR) (3.7 to 2.9). Deterioration in these parameters was observed following cessation of treatment and 10 h later, after a donor liver had become available, an auxiliary transplant was performed. Clinical recovery, though initially slow, was eventually complete, with histopathological and scintigraphic evidence of full liver regeneration at 3 months. Withdrawal of his immunosuppressive drugs began at 6 months and was complete by 14 months after auxiliary transplantation. He has since remained well with normal liver function tests. Temporary liver support may provide additional time for spontaneous recovery of the native liver to occur in selected cases of fulminant hepatic failure, even when criteria are fulfilled for orthotopic liver grafting.

Adolescent↗
PubMed1997

Attitudes towards emotional expression and post-traumatic stress in survivors of the Herald of Free Enterprise disaster.

The relationship between self-reported attitudes towards emotional expression, assessed at three years after the accident, and post-traumatic symptoms, assessed at five years after the accident, was investigated in 37 survivors of the Herald of Free Enterprise disaster. It was found that lower scores on the attitudes towards emotional expression scale, indicating more negative attitudes (e.g. 'I think getting emotional is a sign of weakness') were associated with higher symptom scores. This association remained even when retrospectively assessed perceptions of helplessness during the disaster and symptoms assessed at three years were partialled out. Implications for therapeutic intervention are discussed.

Accidents, Traffic↗
PubMed1997

Ultrastructural analysis of primary human urethral epithelial cell cultures infected with Neisseria gonorrhoeae.

In men with gonococcal urethritis, the urethral epithelial cell is a site of infection. To study the pathogenesis of gonorrhea in this cell type, we have developed a method to culture primary human urethral epithelial cells obtained at the time of urologic surgery. Fluorescent analysis demonstrated that 100% of the cells stained for keratin. Microscopic analyses indicated that these epithelial cells arrayed in a pattern similar to that seen in urethral epithelium. Using immunoelectron and confocal microscopy, we compared the infection process seen in primary cells with events occurring during natural infection of the same cell type in men with gonococcal urethritis. Immunoelectron microscopy studies of cells infected with Neisseria gonorrhoeae 1291 Opa+ P+ showed adherence of organisms to the epithelial cell membrane, pedestal formation with evidence of intimate association between the gonococcal and the epithelial cell membranes, and intracellular gonococci present in vacuoles. Confocal studies of primary urethral epithelial cells showed actin polymerization upon infection. Polyclonal antibodies to the asialoglycoprotein receptor (ASGP-R) demonstrated the presence of this receptor on infected cells in the primary urethral cell culture. In situ hybridization using a fluorescent-labeled probe specific to the ASGP-R mRNA demonstrated this message in uninfected and infected cells. These features were identical to those seen in urethral epithelial cells in exudates from males with gonorrhea. Infection of primary urethral cells in culture mimics events seen in natural infection and will allow detailed molecular analysis of gonococcal pathogenesis in a human epithelial cell which is commonly infected.

Asialoglycoprotein Receptor↗
PubMed1997

New hepatitis C virus (HCV) genotyping system that allows for identification of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a.

Recent studies have focused on whether different hepatitis C virus (HCV) genotypes are associated with different profiles of pathogenicity, infectivity, and response to antiviral therapy. The establishment of a simple and precise genotyping system for HCV is essential to address these issues. A new genotyping system based on PCR of the core region with genotype-specific PCR primers for the determination of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a was developed. A total of 607 samples (379 from Japan, 63 from the United States, 53 from Korea, 35 from Taiwan, 32 from China, 20 from Hong Kong, 15 from Australia, 6 from Egypt, 3 from Bangladesh, and 1 from South Africa) were tested by both the assay of Okamoto et al. (H. Okamoto, Y. Sugiyama, S. Okada, K. Kurai, Y. Akahane, Y. Sugai, T. Tanaka, K. Sato, F. Tsuda, Y. Miyamura, and M. Mayumi, J. Gen. Virol. 73:673-679, 1992) and this new genotyping system. Comparison of the results showed concordant results for 539 samples (88.8%). Of the 68 samples with discordant results, the nucleotide sequences of the HCV isolates were determined in 23, and their genotypes were determined by molecular evolutionary analysis. In all 23 samples, the assignment of genotype by our new genotyping system was correct. This genotyping system may be useful for large-scale determination of HCV genotypes in clinical studies.

DNA Primers↗
PubMed1997

Hepatitis GB virus-C/hepatitis G virus infection in liver disease.

Hepatitis GB virus-C (HGBV-C)/hepatitis G virus (HGV) infection was investigated in 106 children with liver disease (54 boys and 52 girls, mean age 7.3 years); 12 with chronic hepatitis C virus infection, 29 with positive hepatitis B surface antigen, nine with idiopathic fulminant hepatic failure, seven with graft dysfunction after liver transplantation associated with autoimmune features, 20 with cryptogenic liver disease, and 29 with autoimmune liver disease. HGV RNA detected by reverse transcription polymerase chain reaction was found to be positive in 4/106 patients (3.8%). Risk factors were identified in three patients, including blood transfusion and/or medical treatment in Eastern Europe. The prevalence was higher than that of blood donors but lower than that of 2 adult patients with liver disease. HGV is not associated with any specific disease group and does not seem to be a major aetiological agent of liver disease in childhood in the UK.

Adolescent↗
PubMed1997

The role of signal averaged P wave duration and serum magnesium as a combined predictor of atrial fibrillation after elective coronary artery bypass surgery.

OBJECTIVE: To investigate the role of low serum magnesium as a trigger for atrial fibrillation in patients with a substrate for the arrhythmia (assessed by signal averaged P wave duration). DESIGN: A case-control study. SETTING: A regional referral cardiac centre. PATIENTS AND INTERVENTIONS: 105 consecutive patients undergoing elective coronary artery bypass surgery had signal averaged P wave recordings before operation. Serum electrolytes were analysed preoperatively and on days 1, 2, and 5 after surgery. MAIN OUTCOME MEASURES: Any episode of electrocardiographically recorded atrial fibrillation was taken as a study end point. RESULTS: Of 102 patients discharged, 27 (26%) had documented episodes of atrial fibrillation at a mean of 2.7 days after surgery. A combination of P wave duration > 155 ms and serum magnesium on the first postoperative day of < 0.7 mmol/l had a sensitivity of 75% and specificity of 80% for predicting atrial fibrillation. Duration of hospital stay (7.9 v 6.8 days) was longer in the atrial fibrillation group (P < 0.01). Stepwise regression showed age, serum magnesium < 0.7 mmol/l on the first postoperative day (both P < 0.001), angiotensin converting enzyme inhibitor withdrawal (P < 0.02), and signal averaged P wave duration (P = 0.04) to be independent predictors. CONCLUSIONS: The combination of signal averaged P wave duration and low serum magnesium on the first postoperative day identified the majority of patients with atrial fibrillation after coronary artery bypass surgery. Early identification and pharmacological treatment for selected patients may reduce the incidence of postoperative atrial fibrillation.

Aged↗
PubMed1997

Systemic and hepatic hemodynamic changes in acute liver injury.

Systemic and hepatic circulatory changes were studied in rats over the course of acute liver injury. Hepatic injury was induced by intraperitoneal injection of D-galactosamine (1.1 g/kg), and systemic and hepatic hemodynamics were measured over a 72-h period using a radioactive microsphere technique with direct measurement of arterial, portal venous, and hepatic venous blood oxygen content. Cardiac output increased to a maximum at 48 h, producing a marked increase (450%) in hepatic arterial blood flow so that it became the dominant supply of oxygen at the time of maximal hepatic injury. A subsequent increase in portal venous flow resulted in an overall increase in total hepatic blood flow of 500%. At this point the oxygen delivery by the hepatic arterial and portal venous systems was equal. These circulatory changes returned to control values by 72 h with recovery of liver function. These results demonstrate the development of a hyperdynamic circulation and a marked change in the normal relationship between portal venous and hepatic arterial blood flows that occur during hepatic injury.

Acute Disease↗
PubMed1997

Induction and role of NO synthase in hypotensive hepatic failure.

Nitric oxide (NO) plays an important role in the physiological and pathophysiological control of the vascular system. NO is synthesized by isoforms of the enzyme NO synthase (NOS). Hepatic failure is complicated by hypotension, low systemic vascular resistance, and resistance to vasoconstrictor drugs. The potential role of NO in these abnormalities was investigated by using in vitro pharmacological interventions on hepatic arteries obtained from both donor and recipient patients at the time of liver transplantation. The presence of NOS mRNA was investigated by reverse transcription polymerase chain reaction (RT-PCR) with primers designed from human endothelial NOS (eNOS) and inducible NOS (iNOS) cDNA sequences. Arteries from patients with hepatic failure had an impaired constrictor response to phenylephrine compared with those of donor arteries. The constrictor effect of phenylephrine was potentiated by NG-monomethyl-L-arginine, an inhibitor of NOS, which had no effect in donor control arteries. RT-PCR identified human eNOS mRNA in donor and recipient arteries and human iNOS mRNA in recipient arteries only. Induction of NOS in the vasculature with subsequent NO-induced vasodilatation may therefore contribute to the hemodynamic abnormalities observed in hepatic failure and potentially in other pathologies associated with endotoxemia. Whether selective inhibitors of iNOS will improve hemodynamic control or clinical outcome in these conditions requires further study.

Acetylcholine↗
PubMed1997

Placebos in clinical trials of psychotropic medication.

This paper represents the position of the Canadian Psychiatric Association on the ethical and scientific issues related to the use of placebos in the evaluation of new psychotropic drugs. The position taken by the Association is that new psychotropic medications must be shown to be effective and must be weighed against the best current interventions. Placebo controls may be appropriate under certain circumstances, even when an established intervention is effective. These include situations in which placebo response rates are high, variable, or close to response rates for effective therapies. Placebo controls are also appropriate when established interventions carry a high risk of side effects or are effective against only certain symptoms of the disorder.

Canada↗
PubMed1997

Clustering of childhood IDDM. Links with age and place of residence.

OBJECTIVE: To improve understanding of the etiology of IDDM by analyzing spatial and space-time distribution of the incidence in children. RESEARCH DESIGN AND METHODS: Statistical tests to detect clustering were applied to a population-based register of 1,490 children (aged 0-16 years) with IDDM in Yorkshire, northern England. The Knox test analyzed clustering in space and time, and the Potthoff-Whittinghill test quantified spatial differences in incidence between small-area census units (electoral wards). The Potthoff-Whittinghill test was conditioned for childhood population density and deprivation (Townsend index). RESULTS: Both tests demonstrated clustering of IDDM in Yorkshire children. Space-time and spatial clustering is strongest in the younger children (0-4 and 5-9 years of age), even after conditioning for known associations. Clustering was more common in the county of Humberside during the years 1982-1985 and in wards of low population density (< 0.26 0- to 16 year-old subjects per hectare). CONCLUSIONS: The study revealed a nonrandom space-time distribution of IDDM in children not accounted for by known covarying demographic factors. The Potthoff-Whittinghill test has not previously been applied to childhood IDDM. The new finding of strong clustering in young children is consistent with early exposure, possibly in utero, to infectious agents or localized environmental sources.

Adolescent↗