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Biomedical subjects

R Williams

Publications and source records attributed to R Williams.

At least 181 records · Page 10Linked to original sources
PubMed2000

Paracetamol hepatotoxicity and alcohol consumption in deliberate and accidental overdose.

We studied the relationship between alcohol consumption and hepatotoxicity related to paracetamol ingestion both in cases of overdose with suicidal intent and in cases where paracetamol was apparently taken for therapeutic reasons. In a retrospective study of 553 patients admitted to a specialist liver unit between January 1987 and December 1993 with paracetamol-induced hepatotoxicity, there was no difference in the severity of the hepatotoxicity following either a deliberate or an inadvertent overdose. Heavy alcohol consumption was more common in males than females and more commonly associated with deliberate overdoses of >15 g. There was no correlation between alcohol consumption and severity of hepatotoxicity (mean INR and the serum creatinine levels over the first 7 days after the overdose). The significantly lower platelet count in heavy drinkers was probably the consequence of direct alcohol toxicity to the marrow. Overall there was a greater incidence of heavy alcohol consumption amongst therapeutic misadventure compared to deliberate overdose cases, but there was no difference between the two groups when amounts of <10 g/day were involved. Eleven (29%) patients in the therapeutic misadventure group were depressed, 10 of whom had previously attempted suicide. In conclusion, we were unable to demonstrate that heavy drinkers develop more severe hepatotoxicity following paracetamol overdose than non-drinkers, and from the material reported in this study, accidental overdose is a better defining term than therapeutic misadventure.

Acetaminophen↗
PubMed2000

Evaluation of the efficacy and safety of rifaximin in the treatment of hepatic encephalopathy: a double-blind, randomized, dose-finding multi-centre study.

OBJECTIVE: To determine the efficacy, tolerability and safety of oral rifaximin given at three dose levels in patients with cirrhosis and mild to moderate hepatic encephalopathy (HE). DESIGN: Prospective, double-blind, randomized, parallel-group study. SETTING: Multi-centre trial in four university teaching hospitals. PARTICIPANTS: Fifty-four patients with cirrhosis and mild to moderate HE. INTERVENTION: Seven days treatment with rifaximin, 600, 1200 or 2400 mg/day in three divided doses. MAIN OUTCOME MEASURE: Change in the portal-systemic encephalopathy (PSE) index between baseline and day 7, calculated on the basis of mental state, asterixis, number connection test time, EEG mean cycle frequency and blood ammonia concentrations. RESULTS: Treatment with rifaximin was associated with an improvement in the PSE index. There was a trend towards a greater treatment effect of rifaximin with the highest dose of 2400 mg/day. Rifaximin was well tolerated; the few treatment-related adverse events showed no consistent pattern or dose relationship. CONCLUSION: Rifaximin may be useful as alternative or adjuvant therapy for grade I-III hepatic encephalopathy in patients with cirrhosis at a dose of 1200 mg/day.

Administration, Oral↗
PubMed2000

Granulocyte colony-stimulating factor improves function of neutrophils from patients with acute liver failure.

OBJECTIVE: To evaluate the in vitro effects of granulocyte colony-stimulating factor (G-CSF) on function of neutrophils in acute liver failure (ALF). METHODS: Neutrophil functions (superoxide and hydrogen peroxide production; phagocytosis and killing; complement receptor expression) were determined simultaneously in 23 patients with ALF due to paracetamol overdose and compared with 23 healthy control subjects. RESULTS: Phagocytosis was reduced in neutrophils from ALF patients compared to controls (P< 0.005) and was significantly increased by incubation with 1,000 or 5,000 IU/ ml G-CSF (P< 0.05). This correlated with increased expression of CD11b (r= 0.93) and CD18 (r= 0.98) after incubation with 5,000 IU/ml G-CSF (P< 0.05). Killing was reduced in ALF neutrophils compared to controls (P< 0.005) and was similarly restored by G-CSF (P< 0.005). An increase in killing correlated with increases in production of superoxide (r = 0.96) and hydrogen peroxide (r= 0.97) by ALF neutrophils after incubation with 1,000 and 5,000 IU/ml of G-CSF when formylmethionylleucylphenylalanine (fMLP) was the stimulant. G-CSF at 5,000 IU/ml increased the production of hydrogen peroxide (P< 0.01) when zymosan was the stimulant. CONCLUSIONS: G-CSF improves the neutrophil dysfunction of ALF.

Adolescent↗
PubMed2000

Future prospects for anti-cytokine treatment.

The era of anti-cytokine treatment in rheumatology has just begun. The first generation therapeutic agents, biological agents that block tumour necrosis factor alpha such as monoclonal antibodies or receptor Ig fusion proteins are safe and effective, and so this has generated much interest in how to increase the benefit or deliver it more cost effectively. This article provides a personal view of the coming trends in anti-cytokine treatment. Which of these will be realised in the future will be of interest.

Antirheumatic Agents↗
PubMed2000

Swelling and cyanosis of the tongue associated with use of a laryngeal mask airway.

We present a case report of a patient who developed acute swelling of the tongue during anaesthesia using the laryngeal mask airway. The swelling was thought to be due to obstruction of the venous drainage of the tongue. This was associated with isolated cyanosis of the tongue and paraesthesia. The swelling and cyanosis of the tongue resolved rapidly after removal of the laryngeal mask airway. The patient suffered paraesthesia of the tip of the tongue that lasted for two weeks.

Adult↗
PubMed2000

Differential expression of nuclear retinoid receptors in normal and malignant prostates.

PURPOSE: To determine (1) whether nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs) are differentially expressed in normal and in cancerous human prostate tissues and (2) whether oral fenretinide therapy impacts the expression of these receptors in prostate cancer. PATIENTS AND METHODS: In situ hybridization with antisense riboprobes was used to probe for RAR and RXR transcripts in prostate tissues in a two-phased study: (1) expression of retinoid receptors in eight normal prostates was compared with their expression in 10 randomly picked radical prostatectomy specimens (group A); (2) expression of retinoid receptors was determined in 22 radical prostatectomy specimens from participants in a clinical study (group B). Twelve patients received oral fenretinide 200 mg/d, and 10 received placebo pills for 28 days before surgery. RESULTS: RARalpha, RARgamma, RXRalpha, and RXRgamma mRNAs were detected in most normal and cancerous prostates. In group A, RARbeta mRNA was expressed in only four of 10 malignant prostates but was present in seven of eight benign prostates (P =.05). RXRbeta mRNA was expressed in four of eight benign prostates and in zero of 10 malignant prostates (P =.023). In group B prostates, RARbeta and RXRbeta mRNAs were markedly reduced in all cancers and in the adjacent, nonmalignant tissue. There were no differences between receptor expression in the fenretinide-treated group and the placebo group. CONCLUSION: RARbeta and RXRbeta mRNAs are selectively lost in both prostate cancer and adjacent morphologically normal prostatic tissue, supporting the concept of a field of carcinogenesis. One month of oral fenretinide (200 mg/d) did not influence the expression of retinoid receptors in prostate cancer.

Aged↗
PubMed2000

The physics of sub-bandage pressure measurement.

Compression therapy is the principal treatment for leg ulcers associated with venous disease. The extent of compression generally can be estimated from the general Laplace equation relating pressure, bandage tension and leg radius. This study aimed to investigate the physical forces under long stretch bandages applied under constant tensions to cylinders of three defined radii ('model limbs'). Force expressed as pressure was measured under one, two and three layers of eight long stretch bandages and a plastic film (control) using temperature-compensated, strain-gauge pressure transducers. The bandages were applied at the manufactures' recommended extensions/tensions and at constant tensions (2-10N) to three rigid plastic tubes of increasing size, covered with a layer of soft foam. Foams of different hardnesses ranging from 20 to 230N were assessed. The median applied pressure and observed bandage characteristics changed with bandage type. The median applied pressure also changed with tension, number of layers, tube radius and foam hardness. The inter-layer shear component also tended to increase with the number of layers. An increase in sub-bandage pressure was observed relative to the radius, tension, foam hardness and number of layers but the relationship was not directly proportional. The shear force tended to be associated with increased bandage layers.

Bandages↗
PubMed2000

A bench-top method for evaluating modular total hip component combinations.

A modular total hip prosthesis allows the surgeon to vary head size, neck length, and acetabular coverage. Different combinations, however, may increase the risk of impingement of the prosthesis neck on the acetabular liner, leading to dislocation. We developed a bench-top model to test different modular component combinations to determine how far the femoral component could travel within the acetabular liner before impingement led to dislocation. We tested two hip systems, each from a different manufacturer. Certain components increased the risk of impingement and dislocation: skirted necks, smaller heads, and lipped liners. While the contribution of each component was small, the risk was additive, so that the combination of a small head with a skirted neck in a lipped liner actually reduced the available range of motion by 18 degrees, from 146 degrees to 128 degrees, in the first system, and by 13 degrees, from 156 degrees to 143 degrees in the other. This method could be adapted to test a wide range of component configurations, from a number of manufacturers. These findings may be useful in avoiding potentially unstable configurations when given a choice of modular components.

Hip Prosthesis↗
PubMed2000

The validity of information on "race" and "Hispanic ethnicity" in California birth certificate data.

OBJECTIVE: To evaluate the validity of racial/ethnic information in California birth certificate data. DATA SOURCES: Computerized birth certificate data and postpartum interviews with California mothers. STUDY DESIGN AND DATA COLLECTION: Birth certificates were matched with face-to-face structured postpartum interviews with 7,428 mothers to compare racial/ethnic information between the two data sources. Interviews were conducted in Spanish or English during delivery stays at 16 California hospitals, 1994-1995. PRINCIPAL FINDINGS: The sensitivity of racial/ethnic classification in birth certificate data was very high (94 percent to 99 percent) for African Americans, Asians/Pacific Islanders, Europeans/Middle Easterners, and Latinas (Hispanics). For Native Americans, however, the sensitivity was only 54 percent. The positive predictive value of birth certificate classification of race/ethnicity was high for all racial/ethnic groups (96 percent to 97 percent). CONCLUSIONS: Despite limited training of birth clerks, the maternal racial/ethnic information in California birth certificate data appears to be a valid measure of self-identified race and Hispanic ethnicity for groups other than Native Americans.

Adolescent↗
PubMed2000

Biomechanical performance of silicone and latex external condom catheters.

Standard in vivo biomechanical performance tests and a pilot clinical study of latex external condom catheters (ECCs) and silicone ECCs demonstrated the superior performance of the silicone ECC over that of the latex ECC. The silicone ECC has a self-adhesive that binds more securely to human skin than the self-adhesive of latex ECC. In addition, the moisture vapor transmission through silicone is significantly greater than through latex. The aggressive self-adhesive of the silicone ECC significantly reduced ECC catheter pop-off compared to that of latex ECC. Silicone ECC removal can be facilitated by the application of a warm, wet cloth to the exterior surface of the silicone ECC, which significantly reduces its self-adhesive force. Constant, gentle traction is then applied to the silicone catheter outlet end to achieve atraumatic silicone ECC removal. On the basis of the results of these standardized tests and pilot study, the silicone ECC is recommended for incontinent men without obstructive uropathy.

Adhesives↗
PubMed2000

Water-soluble organotellurium compounds inhibit thioredoxin reductase and the growth of human cancer cells.

The thioredoxin system (NADPH, thioredoxin reductase/ thioredoxin) is important for cancer cell growth and inhibition of apoptosis and presents an attractive target for anticancer drug development. Thioredoxin reductase is a selenocysteine-containing flavoenzyme that catalyzes the reduction of oxidized thioredoxin. This enzyme could therefore be used for regulating the activity of the thioredoxin system. Water-soluble organotellurium compounds of the diaryl telluride, alkyl aryl telluride and dialkyl telluride type, carrying sulfopropyl groups, were found to be the most efficient tellurium-based inhibitors of thioredoxin reductase ever tested. Some of the compounds inhibited the enzyme at submicromolar levels. The compounds also inhibited the growth of MCF-7 and HT-29 human cancer cells in culture at the 5-10 microM level but their hydrophilicity seemed to restrict cellular uptake.

Antineoplastic Agents↗
PubMed2000

Serum and cerebrospinal fluid biochemical markers of ALS.

To date there is no satisfactory serum or cerebrospinal fluid (CSF) metabolic marker with which to identify patients with ALS. The goal of finding a suitable marker will be more feasible following the identification of defined subgroups of patients with ALS. Some aspects of neurotransmitter chemistry in CSF seem worthy of further investigation, in particular, clarification of whether there is a significant elevation of CSF glutamate in a subgroup of patients and whether there are robust alterations in the noradrenaline transmitter system. It seems unlikely, in the face of present evidence, that the presence of aberrant exitatory amino acid transporter 2 transcripts in CSF will prove to be a useful marker of ALS. Increased levels of 3-nitrotyrosine and neurofilament light in CSF, while not entirely disease-specific for ALS, may nevertheless prove useful confirmatory markers of the disease and its progression.

Amyotrophic Lateral Sclerosis↗