Biomedical subjects

S K Roberts

Publications and source records attributed to S K Roberts.

At least 19 recordsLinked to original sources

PubMed2006

Review article: management of patients with chronic hepatitis C virus infection and "normal" alanine aminotransferase activity.

BACKGROUND: Hepatitis C virus infection, a major cause of chronic liver disease, occurs with normal serum alanine aminotransferase activity in approximately 25% of patients. These patients have historically remained untreated but substantial evidence indicates liver damage, progression of disease and impaired quality of life in some individuals. AIM: To review the current management of patients with chronic hepatitis C and normal alanine aminotransferase activity. METHODS: This review represents the summary of discussions at a Clinical Workshop with a comprehensive literature searching of available databases (PubMed and Embase). RESULTS: Current limits defining normal serum alanine aminotransferase activity are not representative of a "healthy" status. Most patients with hepatitis C and normal alanine aminotransferase levels have histologically proven liver damage that, although generally mild, may be significant (> or =F2) in up to 20% of patients and progresses at approximately 50% of the rate in patients with elevated alanine aminotransferase levels. Some patients have persistently normal alanine aminotransferase activity and may have a more benign outcome, but a significant proportion (> or =20%) experience periods of increased serum alanine aminotransferase activity which may be associated with enhanced disease progression. CONCLUSIONS: A treatment approach that considers host and virus-related variables and optimizes patient and cost benefits may therefore provide more effective management of patients with chronic hepatitis C and normal alanine aminotransferase activity.

Alanine Transaminase↗

PubMed2006

Multidimensional single-molecule imaging in live cells using total-internal-reflection fluorescence microscopy.

We have developed a wide-field total-internal-reflection fluorescence microscope capable of imaging single molecules in live cells, resolved in both wavelength and polarization. We show fluorescence resonance energy transfer between single pairs of fluorescent molecules bound to signaling receptors in the plasma membrane of live cells and demonstrate the importance of polarization discrimination in addition to wavelength separation.

Animals↗

PubMed2006

Sustained virological response rates and durability of the response to interferon-based therapies in hepatitis C patients treated in the clinical setting.

International controlled trials have demonstrated increasing sustained virological response (SVR) rates to interferon-based therapies in hepatitis-C-treated patients. Response rates of 6-20% in the era of interferon monotherapy are compared with 42-82% with pegylated interferon plus ribavirin. The virological durability of the SVR is unknown and the optimal follow-up for these patients is unclear. The aim of our study was to determine SVR rates and the durability of the response to interferon-based therapies in the clinical setting. From our database of 1540 hepatitis C patients, 344 treatment courses of at least 12 weeks duration were identified, including interferon monotherapy (175 patients), interferon plus ribavirin (96 patients) and peginterferon plus ribavirin (73 patients). Interferon monotherapy was associated with an SVR rate of 5% in 103 genotype 1 patients and 25% in 72 genotype 2/3 patients. Response rates were higher (P < 0.001) with interferon plus ribavirin-41% in 34 genotype 1 patients and 73% in 62 genotype 2/3 patients-and with peginterferon plus ribavirin-47% in 47 genotype 1 patients and 79% in 26 genotype 2/3 patients. Of 147 patients with an SVR, 146 (>99%) remained hepatitis C virus PCR negative during a mean 2.3 years (range 0.3-10.3) of follow-up. In conclusion, with advances in therapies, we are achieving higher response rates in hepatitis C patients treated in the clinical setting. We can now expect an SVR in over half of the treated patients. Importantly, the response is durable and medium and long-term follow-up of these patients are of low yield and largely unnecessary.

Adolescent↗

PubMed2005

Interactions of plasma osmolality with arterial and central venous pressures in control of sympathetic activity and heart rate in humans.

Plasma osmolality alters control of sympathetic activity and heart rate in animal models; however, it is unknown whether physiological increases in plasma osmolality have such influences in humans and what effect concurrent changes in central venous and/or arterial pressures may have. We tested whether physiological increases in plasma osmolality (similar to those during exercise dehydration) alter control of muscle sympathetic nerve activity (MSNA) and heart rate (HR) in humans. We studied 17 healthy young adults (7 women, 10 men) at baseline and during arterial pressure (AP) transients induced by sequential injections of nitroprusside and phenylephrine, under three conditions: control (C), after 1 ml/kg intravenous hypertonic saline (HT1), and after 2 ml/kg hypertonic saline (HT2). We continuously measured HR, AP, central venous pressure (CVP; peripherally inserted central catheter) and MSNA (peroneal microneurography) in all conditions. Plasma osmolality increased from 287 +/- 1 mosmol/kg in C to 290 +/- 1 mosmol/kg in HT1 (P < 0.05) but did not increase further in HT2 (291 +/- 1 mosmol/kg; P > 0.05 vs. C). Mean AP and CVP were similar between C and HT1, but both increased slightly in HT2. HR increased slightly but significantly during both HT1 and HT2 vs. C (P < 0.05). Sensitivity of baroreflex control of MSNA was significantly increased vs. C in HT1 [-7.59 +/- 0.97 (HT1) vs. -5.85 +/- 0.63 (C) arbitrary units (au).beat(-1).mmHg(-1); P < 0.01] but was not different in HT2 (-6.55 +/- 0.94 au.beat(-1).mmHg(-1)). We conclude that physiological changes in plasma osmolality significantly alter control of MSNA and HR in humans, and that this influence can be modified by CVP and AP.

Adult↗

PubMed2004

Exercise-related abdominal pain as a manifestation of the median arcuate ligament syndrome.

Abdominal pain related to exercise, often loosely referred to as 'stitch', is not uncommon, particularly among participants in sports that involve running. The cause of this typically transient pain is poorly understood with several aetiologies proposed including diaphragmatic ischaemia (1, 2). Other gastrointestinal symptoms that are common during prolonged or high-intensity exercise include nausea, diarrhoea and gastrointestinal bleeding (3, 4). These symptoms are also usually transient and are thought to protect against critical organ damage by promoting cessation of exercise. Decreased gastrointestinal blood flow, increased motility and altered neuroendocrine modulation are postulated disease mechanisms (3). We report here a case of an elite runner with exercise-related severe abdominal pain and diarrhoea related to compression of the coeliac axis by the median arcuate ligament. Complete symptom relief was achieved with surgical division of the constricting ligament. The clinical characteristics and pathogenesis of coeliac axis compression syndrome are discussed.

Abdominal Pain↗

PubMed2003

Eicosanoid involvement in the regulation of behavioral fever in the desert locust, Schistocerca gregaria.

The desert locust Schistocerca gregaria behaviorally thermoregulates in order to try and maintain a favoured "set point" body temperature. Locusts infected with the deuteromycete fungal pathogen Metarhizium anisopliae var acridumchoose a significantly elevated temperature. This "behavioral fever" greatly delays the progress of mycosis. We have confirmed this phenomenon and shown that desert locusts also fever when infected with the bacterial pathogen Serratia marcescens. Elevation in the prefered environmental temperature occurs also upon injection with laminarin and lipopolysaccharide (microbial cell wall components). Since such treatments also stimulate the immune system it would appear that "behavioral fever" is probably a feature of the immune response. The eicosanoid biosynthesis inhibitor dexamethasone prevented laminarin invoked fever. This effect was reversable by arachidonic acid. Therefore in common with the febrile response in mammals behavioral fever in insects may be mediated locally by circulating eicosanoids.

Animals↗

PubMed2002

Evaluating biofilm growth of two oral pathogens.

AIMS: To determine the expediency of a microtitre assay system for establishing, quantifying and antimicrobial testing of two representative oral pathogens. METHODS AND RESULTS: Streptococcus mutans and Porphyromonas gingivalis were used. Morphological characteristics of the attached population were evaluated. Biofilm growth was evaluated spectrophotometrically (undisturbed and 1 N NaOH dissipated biofilm). The minimum concentration of chlorhexidine gluconate that inhibited biofilm growth was determined. Growth of the biofilms was successfully monitored by direct optical density measurements or those re-suspended in 1 N NaOH. The latter was necessary when glucans were present in Strep. mutans biofilms. The minimum concentration of chlorhexidine gluconate that inhibited biofilm growth was 1.25 microg ml(-1) for both species. The attached bacteria exhibited common biofilm characteristics. SIGNIFICANCE AND IMPACT OF THE STUDY: The assay system developed was especially useful for monitoring the growth of adherent Strep. mutans in the presence of glucans, which is particularly significant for the study of anti-plaque chemicals.

Anti-Infective Agents, Local↗

PubMed2001

Recurrent autoimmune hepatitis after orthotopic liver transplantation.

To determine the frequency, risk factors, and consequences of recurrent autoimmune hepatitis after liver transplantation, 41 patients with type 1 disease were monitored after surgery in accordance with a surveillance protocol. Tacrolimus or cyclosporine plus prednisone were administered to each patient, and liver biopsy examinations were performed at least annually according to protocol. Corticosteroid therapy was ultimately discontinued in only 2 patients. Recurrent disease was defined as the presence of lymphoplasmacytic infiltrates in liver tissue in the absence of other causes of allograft dysfunction. Autoimmune hepatitis recurred in 7 patients (17%), and the mean time to recurrence was 4.6 +/- 1 years. Recurrence was asymptomatic in 4 of 7 patients and detected only by surveillance liver biopsy assessment in 2 patients. Histological changes were mild, and there was no progression to cirrhosis during 4.9 +/- 0.9 years of observation. Five-year patient (86% v. 82%; P =.9) and graft (86% v. 67%; P =.5) survival rates were not statistically different between patients with and without recurrent disease. HLA-DR3 or HLA-DR4 occurred more commonly in patients with than without recurrence (100% v. 40%; P =.008) and healthy subjects (100% v. 49%; P =.01). Recurrent disease was unrelated to donor HLA status. In conclusion, recurrence after transplantation for type 1 autoimmune hepatitis is common. Its mild manifestations and favorable prognosis may reflect early detection by a surveillance protocol and/or continuous corticosteroid treatment. HLA-DR3- or HLA-DR4-positive recipients are at risk for recurrence regardless of donor HLA status.

Adult↗

PubMed2000

Primary hepatocellular carcinoma in Australia, 1978-1997: increasing incidence and mortality.

OBJECTIVES: To describe trends in primary hepatocellular carcinoma (HCC) incidence and mortality in Australia between 1978 and 1997, and to delineate the effects of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection by examining cases of HCC in Australian-born and overseas-born people separately. DESIGN AND SETTING: Retrospective analysis of national incidence and mortality data in which the underlying cause was coded as HCC (International classification of diseases, ninth revision [ICD-9] code 155.0). MAIN OUTCOME MEASURES: Changes in age-standardised HCC incidence rates in men and women between 1983 and 1996; age-standardised HCC death rates in Australian-born and overseas-born men and women between 1978 and 1997. RESULTS: Age-standardised incidence rates increased in men and women (from 2.06 and 0.57 per 100,000 respectively in 1983-1985 to 3.97 and 0.99 respectively in 1995-1996). Age-standardised death rates increased in Australian-born and overseas-born men and overseas-born women (from 1.43, 2.35 and 0.62 respectively per 100,000 in 1978-1982 to 2.50, 4.41 and 1.36 respectively in 1993-1997). However, death rates in Australian-born women did not increase (0.58 per 100,000 in 1978-1982 and 0.63 in 1993-1997). CONCLUSIONS: HCC incidence and death rates in Australia have increased over the past two decades, except in Australian-born women. A likely explanation for at least a portion of this increase is increased prevalences of HBV and HCV infection in Australia.

Age Factors↗

PubMed2000

The effects of ABA on channel-mediated K(+) transport across higher plant roots.

The transport and accumulation of K(+) in higher plant roots is regulated by ABA. Molecular and electrophysiological techniques have identified a number of discrete transporters which are involved in the translocation of K(+) from the soil solution to the shoots of higher plants. Furthermore, recent reports have shown that ABA regulates K(+) channel activity in maize and Arabidopsis roots which suggests that ABA regulation of K(+) transport in roots is, at least in part, ion channel-mediated. The signalling processes which underlie the ABA regulation of K(+) channels have been investigated. The effects of ABA on the membrane potential of intact maize root cells were also studied. It was found that ABA regulated the membrane potential of root cells and that this regulation is consistent with the hypothesis that ABA-induced K(+) accumulation in roots is mediated by K(+) channels.

Abscisic Acid↗

PubMed1999

Divalent cation block of inward currents and low-affinity K+ uptake in Saccharomyces cerevisiae.

We have used the patch clamp technique to characterize whole-cell currents in spheroplasts isolated from a trk1Delta trk2Delta strain of Saccharomyces cerevisiae which lacks high- and moderate-affinity K+ uptake capacity. In solutions in which extracellular divalent cation concentrations were 0.1 mM, cells exhibited a large inward current. This current was not the result of increasing leak between the glass pipette and membrane, as there was no effect on the outward current. The inward current comprised both instantaneous and time-dependent components. The magnitude of the inward current increased with increasing extracellular K+ and negative membrane potential but was insensitive to extracellular anions. Replacing extracellular K+ with Rb+, Cs+, or Na+ only slightly modulated the magnitude of the inward current, whereas replacement with Li+ reduced the inward current by approximately 50%, and tetraethylammonium (TEA+) and choline were relatively impermeant. The inward current was blocked by extracellular Ca2+ and Mg2+ with apparent Kis (at -140 mV) of 363 +/- 78 and 96 +/- 14 microM, respectively. Furthermore, decreasing cytosolic K+ increased the magnitude of the inward current independently of the electrochemical driving force for K+ influx, consistent with regulation of the inward current by cytosolic K+. Uptake of 86Rb+ by intact trk1Delta trk2Delta cells was inhibited by extracellular Ca2+ with a Ki within the range observed for the inward current. Furthermore, increasing extracellular Ca2+ from 0.1 to 20 mM significantly inhibited the growth of these cells. These results are consistent with those of the patch clamp experiments in suggesting that low-affinity uptake of alkali cations in yeast is mediated by a transport system sensitive to divalent cations.

Calcium↗

PubMed1997

Management of haematemesis and melaena.

Upper gastrointestinal bleeding remains a common medical emergency with high morbidity and mortality. High risk patients are best managed in specialised units. Endoscopy is the procedure of choice for diagnosis and haemostatic therapy of peptic ulcers, reducing deaths and the probability of rebleeding, as well as the need for surgery; for acute variceal bleeding, pharmacotherapy followed by endoscopic ligation is recommended.

Esophageal and Gastric Varices↗

PubMed1997

Liver transplantation for cryptogenic cirrhosis.

End-stage liver disease secondary to cryptogenic cirrhosis is the indication for orthotopic liver transplantation (OLT) in 7% to 14% of recipients. However, there are no reports documenting the outcome of OLT for this indication. The aim of this study was to determine (1) survival and (2) the incidence of histological recurrence of cryptogenic cirrhosis after OLT. Between March 1985 and December 1994, 560 OLTs were performed at our institution. Of these, 39 transplants for cryptogenic cirrhosis were in patients who met the following criteria: antinuclear antibody < 1:40; negative anti-smooth muscle antibody, antimitochondrial antibody, polymerase chain reaction for hepatitis C virus, and hepatitis B surface antigen results; normal ceruloplasmin and alpha-1 antitrypsin phenotype; transferrin saturation < 65%; and liver biopsy specimen not suggestive of hemochromatosis or other known disorders. Histological recurrence was assessed with protocol liver biopsies in all patients who survived longer than 6 months. The mean age of cryptogenic recipients at the time of transplantation was significantly lower (40.6 years; range, 3 to 63 years) than that of noncryptogenic recipients (48.5 years; range, 1-70; P < .03). Median modified Child's-Pugh score was slightly higher for cryptogenic recipients at the time of transplantation (10.0 + 0.08 standard error of mean [SEM]), than for the noncryptogenic recipients (9.0 + 0.03 SEM; P < .02). Actuarial survival was 72% (+ 0.07 SEM) at 1 and 58% (+ 0.08 SEM) at 5 years for cryptogenic recipients compared with 89% at 1 and 80% at 5 years for noncryptogenic recipients. The difference in survival was significant (P < .001) at both 1 and 5 years. Among the 27 cryptogenic recipients surviving more than 6 months (mean follow-up, 5.5 years), 6 have persistent hepatitis histologically without apparent infectious, vascular, biliary, or drug origins. Four patients (15%) had chronic active hepatitis, and 2 (7%) had steatohepatitis. No cases of recurrent cryptogenic cirrhosis were seen. OLT for cryptogenic cirrhosis is associated with a poor outcome compared with other indications, hepatitis of uncertain origin occurred in 22% of cryptogenic recipients surviving longer than 6 months, and no evidence of recurrence of cryptogenic cirrhosis was seen thus far in follow-up.

Adolescent↗

PubMed1997

The pathobiology of biliary epithelia.

Our understanding of the pathobiology of biliary epithelia is rapidly growing because of a surge of investigative activity. This became possible after suitable experimental models and techniques were developed with which to study cholangiocyte biology. Although the molecular mechanisms of bile formation by cholangiocytes and the role of these cells as a major cellular target in a variety of severe hepatobiliary diseases are currently being investigated, many questions remain unanswered, particularly regarding cholangiocellular functions, both in normal and abnormal conditions. As current experimental models become more refined, scientists with interests as diverse as cell biology and physiology, morphology, pharmacology, immunology, genetics, and oncology can be expected to further clarify the pathobiology of biliary epithelia.

Autoimmune Diseases↗

PubMed1996

Rat hepatocytes transport water mainly via a non-channel-mediated pathway.

During bile formation by the liver, large volumes of water are transported across two epithelial barriers consisting of hepatocytes and cholangiocytes (i.e. intrahepatic bile duct epithelial cells). We recently reported that a water channel, aquaporin-channel-forming integral protein of 28 kDa, is present in cholangiocytes and suggested that it plays a major role in water transport by these cells. Since the mechanisms of water transport across hepatocytes remain obscure, we performed physiological, molecular, and biochemical studies on hepatocytes to determine if they also contain water channels. Water permeability was studied by exposing isolated rat hepatocytes to buffers of different osmolarity and measuring cell volume by quantitative phase contrast, fluorescence and laser scanning confocal microscopy. Using this method, hepatocytes exposed to hypotonic buffers at 23 degrees C increased their cell volume in a time and osmolarity-dependent manner with an osmotic water permeability coefficient of 66.4 x 10(-4) cm/s. In studies done at 10 degrees C, the osmotic water permeability coefficient decreased by 55% (p < 0.001, at 23 degrees C; t test). The derived activation energy from these studies was 12.8 kcal/mol. After incubation of hepatocytes with amphotericin B at 10 degrees C, the osmotic water permeability coefficient increased by 198% (p < 0.001) and the activation energy value decreased to 3.6 kcal/mol, consistent with the insertion of artificial water channels into the hepatocyte plasma membrane. Reverse transcriptase polymerase chain reaction with hepatocyte RNA as template did not produce cDNAs for three of the known water channels. Both the cholesterol content and the cholesterol/phospholipid ratio of hepatocyte plasma membranes were significantly (p < 0.005) less than those of cholangiocytes; membrane fluidity of hepatocytes estimated by measuring steady-state anisotropy was higher than that of cholangiocytes. Our data suggests that the osmotic flow of water across hepatocyte membranes occurs mainly by diffusion via the lipid bilayer (not by permeation through water channels as in cholangiocytes).

Animals↗

PubMed1996

Prognosis of histological cirrhosis in type 1 autoimmune hepatitis.

BACKGROUND & AIMS: Cirrhosis connotes irreversible damage to the liver and shortened life expectancy. The aim of this study was to evaluate the impact of cirrhosis on treatment response and survival in type 1 autoimmune hepatitis. METHODS: One hundred twenty-eight patients were evaluated for histological cirrhosis. Response to treatment, predictors for cirrhosis, and outcomes were determined. RESULTS: Thirty-seven patients (29%) had histological cirrhosis at entry, whereas 36 of the 91 patients without cirrhosis (40%) developed it during 39 +/- 32 months. Development of cirrhosis was predicted by lower serum albumin levels (P=0.04) and higher prothrombin times (P<0.001) at presentation. The frequencies of remission, relapse after drug withdrawal, and treatment failure were comparable in patients with and without cirrhosis at entry. The overall 10-year survival (93%) was similar to that of an age-and sex-matched cohort from the population at large (94%). Ten-year survival was not different between those with and those without cirrhosis at entry (89% and 90%, respectively), even with transplantation as an end point. CONCLUSIONS: Patients with histological cirrhosis at presentation respond to corticosteroid therapy as well as patients without cirrhosis. Low serum albumin levels and hypoprothrombinemia at presentation predict the development of cirrhosis. Histological cirrhosis does not diminish survival expectations.

Adult↗

PubMed1995

Risk factor assessment for the acquisition of fluoroquinolone-resistant isolates of Pseudomonas aeruginosa in a community-based hospital.

A case-control study was performed in a community-based nonteaching hospital to assess patient risk factors for the acquisition of fluoroquinolone-resistant isolates of Pseudomonas aeruginosa. Fifty-five patients who were hospitalized between July 1, 1993 and December 31, 1993 and who had P. aeruginosa recovered from a clinical specimen were included in the analysis. Two patient populations were designated based on the fluoroquinolone susceptibility of their P. aeruginosa isolates. Statistical evaluation using univariate analysis of demographic and clinical data from the 42 patients with quinolone-susceptible P. aeruginosa and the 13 patients with quinolone-resistant P. aeruginosa demonstrated that prior receipt of a fluoroquinolone was the only significant risk factor for the subsequent emergence of fluoroquinolone resistance among P. aeruginosa isolated from patients hospitalized in this small community-based institution (p = 0.0196). Multivariate analysis supported the finding that prior receipt of a fluoroquinolone was the major risk factor for the isolation of fluoroquinolone-resistant P. aeruginosa (p = 0.0004); isolation of this Gram-negative bacillus from sputum (p = 0.0306) and a history of recent surgery (p = 0.0058) were also significantly associated as risk factors for resistance.

Adolescent↗

PubMed1994

Cholangiocytes express the aquaporin CHIP and transport water via a channel-mediated mechanism.

Cholangiocytes line the intrahepatic bile ducts and regulate salt and water secretion during bile formation, but the mechanism(s) regulating ductal water movement remains obscure. A water-selective channel, the aquaporin CHIP, was recently described in several epithelia, so we tested the hypothesis that osmotic water movement by cholangiocytes is mediated by CHIP. Isolated rodent cholangiocytes showed a rapid increase in volume in the presence of hypotonic extracellular buffers; the ratio of osmotic to diffusional permeability coefficients was > 10. The osmotically induced increase in cholangiocyte volume was inversely proportional to buffer osmolality, independent of temperature, and reversibly blocked by HgCl2. Also, the luminal area of isolated, enclosed bile duct units increased after exposure to hypotonic buffer and was reversibly inhibited by HgCl2. RNase protection assays, anti-CHIP immunoblots, and immunocytochemistry confirmed that CHIP transcript and protein were present in isolated cholangiocytes but not in hepatocytes. These results demonstrate that (i) isolated cholangiocytes and intact, polarized bile duct units manifest rapid, mercury-sensitive increases in cell size and luminal area, respectively, in response to osmotic gradients and (ii) isolated cholangiocytes express aquaporin CHIP at both the mRNA and the protein level. The data implicate aquaporin water channels in the transcellular movement of water across cholangiocytes lining intrahepatic bile ducts and provide a plausible molecular explanation for ductal water secretion.

Animals↗