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Biomedical subjects

R Williams

Publications and source records attributed to R Williams.

At least 523 records · Page 29Linked to original sources
PubMed1995

Detection of hepatitis E virus genome and gene products in two patients with fulminant hepatitis E.

Non-isotopic in situ hybridization (digoxigenin-labeled probe directed towards hepatitis E virus ORF1) and immunohistochemistry (against hepatitis E virus ORF2 and ORF3) were applied to detect hepatitis E virus genome and gene product in the liver tissue of two patients with fulminant hepatitis E seropositive for hepatitis E virus RNA. Both hepatitis E virus RNA and hepatitis E virus antigens were detected exclusively in the cytoplasm of hepatocytes and not detected in other cell types. In both patients, more than 50% of the hepatocytes were positive for both hepatitis E virus RNA and hepatitis E virus antigens, most of which showed degenerative changes. This is consistent with the histological appearance of marked loss of hepatocytes with acinar collapse. Interestingly, denaturation of the RNA before in situ hybridization was found to enhance hepatitis E virus RNA detection. We conclude that: (1) hepatitis E virus RNA and hepatitis E virus antigens can be demonstrated in the liver in hepatitis E virus-related fulminant hepatitic failure, (2) hepatitis E virus is hepatocyte-tropic within the liver, (3) cytoplasmic localization of hepatitis E virus RNA and hepatitis E virus antigens is consistent with cytoplasmic replication, and (4) the presence of degenerative changes in hepatitis E virus positive cells, together with the histological appearance of hepatocyte loss in the absence of significant inflammatory infiltrate, suggests that hepatitis E virus-related fulminant hepatitic failure is mediated by a cytopathic mechanism.

Acute Disease↗
PubMed1995

Evaluation of efficacy and safety of thymus humoral factor-gamma 2 in the management of chronic hepatitis B.

BACKGROUND/AIMS: We investigated the antiviral and immunomodulatory effects of a combination treatment using thymus humoral factor-gamma 2 and alpha-interferon in patients with chronic hepatitis B in whom previous monotherapy with interferon had failed. METHODS: Nine HBeAg and HBV-DNA seropositive patients received thymus humoral factor-gamma 2 alone for 2 months, thymus humoral factor-gamma 2 plus alpha-interferon for 2 months and finally alpha-interferon alone for 2 months. RESULTS: Treatment with thymus humoral factor-gamma 2 alone was not associated with any side effects. The interferon-induced lymphopenia was significantly less marked during the combined therapy in comparison to the previous course with interferon alone (mean reduction of lymphocyte counts 33.5 +/- 11.6% versus 56.3 +/- 16.7%, respectively, p < 0.05). The combination of thymus humoral factor-gamma 2 plus interferon showed a significantly more profound inhibition of serum HBV-DNA (mean reduction from the pretreatment level 90.6 +/- 13.3%) compared to the earlier monotherapy with interferon in the same patients (mean reduction 55.5 +/- 34.7%, p < 0.01). As a result of the combined thymus humoral factor-gamma 2 plus alpha-interferon regimen three out of nine patients became HBV-DNA negative and seroconverted to anti-HBe. Thymus humoral factor-gamma 2 appears to exert mainly a functional effect on T lymphocytes, as interleukin-2 production was increased in the majority of treated patients, whilst the expression of lymphocyte activation markers remained unchanged. CONCLUSIONS: These data suggest that thymus humoral factor-gamma 2 may be useful in a combined therapeutic approach in chronic HBV carriers.

Adult↗
PubMed1995

Induction of T-helper cell response to hepatitis B core antigen in chronic hepatitis B: a major factor in activation of the host immune response to the hepatitis B virus.

The T helper (Th) cell response to hepatitis B core antigen (HBcAg) was analyzed in 76 chronic hepatitis B virus (HBV) carriers with varying degrees of hepatic inflammation and HBV replication. Fifty-five patients had active viral replication, 28 with minimal histological changes and normal alanine transaminase (ALT) and 27 with active hepatic inflammation and elevated ALT. The remaining 21 chronic hepatitis B surface antigen (HBsAg) carriers had undetectable HBV replication, minimal histological activity, and normal ALT. In addition, 34 chronic HBV carriers were studied prospectively during treatment with alpha-interferon. The HBcAg-specific Th cell response was evaluated by a proliferative assay using 3H-thymidine uptake and gamma-interferon production by peripheral blood mononuclear cells. The proliferative response and gamma-interferon production of patients with active hepatic inflammation were significantly higher than in patients with minimal histological changes and in controls. In the longitudinal analysis during alpha-interferon treatment, 22 of 34 patients sustained an ALT flare accompanied by a parallel, significant Th cell response, which preceded or coincided with the ALT flare. The elevation in the Th cell response and the ALT flare were followed by a significant rise in the serum immunoglobulin (Ig) M anti-HBc index. Ten of twenty-two patients with an enhanced Th cell response and an ALT flare seroconverted after alpha-interferon treatment. The Th cell activity in the 10 responders rapidly subsided after hepatitis B e antigen (HBeAg) to anti-HBe seroconversion, whereas in the 12 nonresponders it remained elevated.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1995

Adaptive estimation of single response evoked potentials.

A new adaptive filtering algorithm and structure is developed to estimate response-to-response variations in evoked responses. The evoked responses are modeled as the sum of three uncorrelated signal components: ensemble average, noise, and stochastic signal variation. A two stage time sequenced filter structure exhibiting improved convergence characteristics is developed along with a modified P-vector algorithm (mPa) which eliminates the need for a separate desired signal electrode. The mPa adaptive filter is tested with simulated and human EP data. The mPa filter is able to estimate signal variations from one response to the next.

Algorithms↗
PubMed1995

Metabolic derangements in nonmodulating hypertension.

A positive association exists between insulin resistance, dyslipidemia, and hypertension, specifically salt-sensitive hypertension. A subgroup of salt-sensitive normal and high renin hypertensives called nonmodulators (NM) manifest an inability to modulate the adrenal and renal blood flow responses to a change in dietary sodium. Therefore, we tested the hypothesis that the NM subgroup would be insulin resistant and dyslipidemic when compared with normal and high renin hypertensives, in whom modulation is intact (M). Forty-six nondiabetic hypertensive individuals were evaluated and their modulation status defined by either renal or adrenal criteria. Fasting blood was drawn for measurement of several metabolic factors. Since the NM group had a greater body mass index (BMI) it was subdivided into a "lean" subgroup that matched the BMI of the M group. The fasting insulin levels in both the total NM and lean NM groups was significantly higher than in the M group (P = .013 and .04, respectively). There were no differences in age, blood pressure, or plasma/serum levels of glucose, triglycerides, total cholesterol, or potassium. NM had elevated fasting insulin levels compared to M, compatible with an insulin resistant state, but this insulin resistance are dissociable in the hypertensive population.

Blood Glucose↗
PubMed1995

Complementary and combinatorial patterns of Notch gene family expression during early mouse development.

The Drosophila Notch gene encodes a transmembrane receptor involved in the regulation of cell fate. It exerts its effect by lateral specification, inductive signaling and is also important for cell adhesion and axonal pathfinding. In this report we analyse the expression of the three mammalian Notch homologues during early mouse development by in situ hybridization. The Notch 1, 2 and 3 genes show dynamic and complex expression patterns, in particular during gastrulation and somitogenesis and in early nervous system formation. During gastrulation, the Notch genes are expressed in non-overlapping, successive patterns. Notch 3 is widely expressed in both ectoderm and mesoderm. Notch 2 is then expressed in the node, notochord and neural groove while Notch 1 becomes highly expressed in presomitic mesoderm. As somitogenesis begins, Notch 2 expression is activated in newly forming somites while Notch 3 is activated in mature somites. Various neural crest cell populations and ectodermal placode cells can be defined by expression of specific combinations of Notch genes. All three Notch genes are expressed within cells of the dorsal neural tube at E9.5, although neural crest cells that have begun migrating all show distinct patterns of Notch expression. Finally, Notch 1 expression is observed not only in placodes, but also in cells migrating from placodes to the site of the ganglia anlagen. This expression pattern may be analogous to Notch expression in the peripheral nervous system of Drosophila, suggesting that mammalian Notch genes may also be involved in axonal pathfinding.

Animals↗
PubMed1995

31P nuclear magnetic resonance spectroscopy of acutely ischaemic limbs: the extent of changes and progress after reconstructive surgery.

31P Nuclear magnetic resonance (NMR) spectroscopy of the tibialis anterior muscle was carried out on nine acutely ischaemic limbs in eight patients before and after revascularization, in 15 limbs of 13 claudicants at rest, in 17 patients with normal lower limb circulation suffering chronic renal failure, and in six healthy subjects. Claudicants, renal failure and healthy limbs showed similar inorganic phosphate/phosphocreatine ratios (Pi/PCr). Healthy volunteers after 30-min tourniquet ischaemia and patients with acutely ischaemic limbs showed significantly raised Pi/PCr ratios (P < 0.05). There was an association between Pi/PCr ratios and the systolic ankle:brachial pressure index in acutely ischaemic limbs. In the acute patients, the Pi/PCr ratios returned to normal after successful revascularization, the time course varying between 3 days and 3 months. Intracellular acidosis was observed in one patient who was also the only individual to develop reperfusion injury following reconstructive surgery. Acidosis may be a sign of muscle changes which lead to reperfusion injury.

Adult↗
PubMed1995

Apraclonidine and anterior segment laser surgery. Comparison of 0.5% versus 1.0% apraclonidine for prevention of postoperative intraocular pressure rise.

PURPOSE: To compare the efficacy of 0.5% and 1.0% apraclonidine in preventing laser-induced intraocular pressure (IOP) elevation after trabeculoplasty, neodymium: YAG (Nd: YAG) iridotomy, and capsulotomy. METHODS: This is a prospective, masked, and randomized study of 83 patients undergoing trabeculoplasty, 62 patients undergoing iridotomy, and 57 patients undergoing capsulotomy. Surgical eyes received one drop of 0.5% or 1.0% apraclonidine immediately after surgery. RESULTS: Intraocular pressure reduced 2 hours after trabeculoplasty in the 0.5% (P = 0.028) and 1.0% (P = 0.004) groups. Intraocular pressure was higher than baseline in a greater number of eyes treated with 0.5% (12 of 39 eyes, 31%) compared with 1.0% apraclonidine (5 of 44 eyes, 11%) (P = 0.032). Intraocular pressure in eyes with a narrow chamber angle was reduced in 16 (85%) of 19 eyes treated with 0.5% and in 10 (84%) of 12 eyes treated with 1.0% apraclonidine after iridotomy. Of patients with chronic angle-closure glaucoma, IOP was similar to prelaser values in 11 (69%) of 16 eyes treated with 0.5% (P > 0.7) and 12 (80%) of 15 eyes treated with 1.0% apraclonidine (P > 0.3). In patients undergoing capsulotomy, pressure was significantly lowered in the 0.5% group (P = 0.04) but not in the 1.0% apraclonidine group. After capsulotomy, both treatment groups had similar (P > 0.3) numbers of eyes with an IOP less than baseline (83% for 0.5% apraclonidine and 81% for 1.0% apraclonidine). CONCLUSION: The single postoperative administration of 0.5% apraclonidine is as effective as the 1.0% concentration in preventing IOP elevation immediately after trabeculoplasty, iridotomy, or capsulotomy.

Adrenergic alpha-Agonists↗
PubMed1995

Factor VIII gene inversions in severe hemophilia A patients.

The mutations causing hemophilia A are very heterogeneous with the exception of a large inversion involving intron 22 in the factor VIII (FVIII) gene which appears to be the underlying defect in approximately 45% of all severely affected patients (FVIII < or = 1%). In these patients it is thought that the factor VIII gene is disrupted within intron 22 due to inappropriate recombination of FVIIIA with one of 2 homologous regions upstream of the factor VIII gene resulting in a large (approximately 500 kb) inversion. The inversion can be detected by Southern blot analysis and greatly enhances the accuracy of genetic counselling services available to families with severe hemophilia A. We report here the presence of this mutation in a study of 27 unrelated families with severe hemophilia. The factor VIII inversion was identified in 12 of 27 (44%) severe hemophilia A patients and has been successfully used for direct carrier analysis and prenatal diagnosis.

Blotting, Southern↗
PubMed1995

Serious infections caused by multiply-resistant Enterococcus faecium.

Three liver transplant patients developed serious intraabdominal infections and recurrent bacteremias due to strains of Enterococcus faecium with high-level resistance to vancomycin. The enterococci were also resistant to all other antibacterials except pristinamycin, which, given orally, proved ineffective. One strain was sensitive to tetracycline. Increasingly, clinicians are likely to encounter infections caused by multiply-resistant enterococci, and these cases illustrate the seriousness of such infections in compromised patients.

Abdomen↗
PubMed1995

Self-directed learning in problem-based health sciences education.

PURPOSE: To determine the amounts of time that physiotherapy (PT) and occupational therapy (OT) students in problem-based curricula spent in non-scheduled and scheduled educational activities, and to determine whether the students increased or decreased the time spent in educational activities as they progressed through the curricula. METHOD: The participants were the 29 PT and 29 OT students in the classes of 1992 in the two-year problem-based educational programs at McMaster University. Each student was randomly assigned to different days of the week to record his or her time utilization for a 24-hour period in each of weeks three, seven, and 11 of the second, fourth, and sixth units of the seven-unit curricula. Weeks 11 of the second and fourth units emphasized clinical education; the other weeks involved academic study only. RESULTS: During the academic weeks, the grand ratios of non-scheduled to scheduled time were 2.8:1 for the PT students and 2.9:1 for the OT students. During the two weeks focusing on clinical education, the ratios were lower: 0.4:1 and 0.2:1 for the PT students, and 1:1 and 0.8:1 for the OT students (the discrepancy between the groups may be due to the fact that the OT students had academic assignments during their clinical placements, while the PT students did not). As the students proceeded through the programs, a general decrease in time spent in educational activities was noted. CONCLUSION: The general decrease in time spent in educational activities as the students progressed through the programs was probably due to their becoming familiar with expectations and their gaining efficiency in using learning resources.

Adult↗
PubMed1995

Quantitative assessment of serum beta-2-microglobulin in liver transplant recipients and relationship to liver graft rejection.

OBJECTIVE: To investigate the usefulness of serum beta 2-microglobulin determination in the diagnosis of acute liver allograft rejection. DESIGN: Prospective study. SETTING: Liver transplant unit. PATIENTS: Twenty consecutive patients who underwent liver transplantation because of a non-virus-related end-stage liver disease. METHODS: Serum samples were collected before the transplant, at days 7, 30 and 90 and whenever a clinical complication developed after liver transplantation. beta 2-Microglobulin was quantified using a new quantitative automated microparticle enzyme immunoassay. RESULTS: Serum beta 2-microglobulin levels increased significantly (P < 0.05) during rejection episodes and correlated with the degree of hepatocyte injury as assessed using serum aspartate aminotransferase levels. Increased beta 2-microglobulin levels were also found in surgical or infectious post-transplant complications. A significant difference in beta 2-microglobulin values was recorded between patients with rejection and only those with bacterial sepsis. CONCLUSION: Although highly sensitive in recognizing damage to the graft, determination of beta 2-microglobulin was not sufficiently specific to differentiate between rejection and other post-transplantation complications.

Adult↗
PubMed1995

Antibody-directed complement-mediated cytotoxicity to hepatocytes from patients with chronic hepatitis B.

The susceptibility of hepatocytes from patients with chronic hepatitis B to complement-dependent cytotoxicity mediated by heterologous antibodies to hepatitis B virus core (anti-HBc) and surface (anti-HBs) antigens and to hepatic asialoglycoprotein receptor was examined using a microcytotoxicity assay. The anti-HBc-induced cytotoxicity was found to be markedly enhanced against hepatocytes isolated from patients with chronic active hepatitis (72.6 +/- 9.5% (mean +/- s.e.m.); n = 6) over that against hepatocytes from individuals with chronic persistent hepatitis or inactive liver cirrhosis (40.6 +/- 18.6%; n = 4) (P = 0.019). Overall, values of the anti-HBc-directed cytotoxicity were higher in patients positive for HBcAg in hepatocytes and seropositive for hepatitis B virus e antigen (HBeAg). Hepatocytotoxicity was also exerted by anti-HBs and anti-asialoglycoprotein receptor antibodies in the presence of complement, but it was not seemingly related to disease activity. These results indicate that hepatitis B virus core and surface antigens and asialoglycoprotein receptor at the hepatocyte surface can be recognized by antibodies, and raise the possibility that complement-dependent cytolysis may contribute to the injury of hepatitis B virus-infected hepatocytes. The data also suggest that liver cells of patients with severe chronic hepatitis might be more susceptible to anti-HBc antibody-directed complement-mediated cytotoxicity than those with inactive liver histology.

Adult↗
PubMed1995

Liver transplantation for acute and chronic viral hepatitis.

Hepatotrophic viruses are responsible for a substantial proportion of cases of both end-stage chronic liver disease and of acute liver failure which are treated by liver transplantation. We review here current practice in transplantation for viral-induced liver disease addressing, in particular, the selection of patients for transplantation and the increasingly recognized problem of recurrent disease in liver grafts.

Acute Disease↗