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Biomedical subjects

G Farrell

Publications and source records attributed to G Farrell.

At least 19 recordsLinked to original sources
PubMed1997

Efficacy and tolerance of a 6-month treatment course of daily interferon-alpha 2a for chronic hepatitis C with cirrhosis. The Australian Hepatitis C Study Group.

Response to interferon-alpha (IFN-alpha) treatment in hepatitis C is poorer when cirrhosis is present. In the third Australian multicentre hepatitis C trial, Aushep-3, we examined the efficacy and tolerability of an intensive 24-week course of interferon-alpha 2a in Child-Pugh grade A patients with chronic hepatitis C and cirrhosis. This was an open uncontrolled trial of 4.5 million units (MU) of IFN-alpha 2a daily for 24 weeks; follow-up was 48 weeks. Chronic hepatitis C and cirrhosis were confirmed histologically. HCV RNA was determined in serum by reverse transcriptase polymerase chain reaction (PCR), and viral genotyping was by line-probe assay. Treatment response was defined as a reduction of alanine aminotransferase (ALT) to less than 1.5 times the upper limit of normal (and by at least 50% of pretreatment values) at weeks 20 and 24. Sustained response was defined as normal serum ALT after treatment from trial week 28 until week 48. Among the 56 patients, a treatment response occurred in 18 (32% by intention-to-treat; 42% of those who completed treatment) and eight (14%) had a sustained response. At 24 weeks, HCV RNA was not detectable in 12 of 17 treatment responders, and remained negative at 48 weeks in six of eight sustained responders. Treatment response by genotype occurred in 75% of patients with HCV type 2, in 38% with HCV type 3a and in 12% with HCV genotype 1. Sustained response occurred in only one (4%) patient with HCV genotype 1 but in five (20%) with genotypes 2 or 3a. Among 13 patients withdrawn, nine were for adverse effects, most often haematological; 10 others underwent dose reduction for adverse effects. It is concluded that a sustained biochemical and viral response to treatment with IFN-alpha 2a can be obtained in some patients with hepatitis C and cirrhosis, particularly those with genotypes 2 or 3a. Therefore, patients with cirrhosis should be considered for interferon treatment on an individual basis. Genotyping may improve case selection, but vigilance is required for haematological complications.

Adult↗
PubMed1997

Diterpenoids from germander, an herbal medicine, induce apoptosis in isolated rat hepatocytes.

BACKGROUND & AIMS: Germander was withdrawn from the market after its use for weight control caused an epidemic of hepatitis. Its toxicity was shown to be caused by diterpenoids and their cytochrome P4503A-mediated metabolic activation into electrophilic metabolites that deplete cellular thiols. The aim of the present study was to determine the mechanisms of cell death. METHODS: Isolated rat hepatocytes were incubated for 2 hours with germander diterpenoids (100 micrograms/mL). RESULTS: Diterpenoids decreased cell glutathione, increased cytosolic [Ca2+], activated Ca(2+)-dependent tissue transglutaminase forming a cross-linked protein scaffold, and caused internucleosomal DNA fragmentation and the ultrastructural features of apoptosis. Cell death was prevented by decreasing metabolic activation (with troleandomycin), preventing depletion of glutathione (with cystine), blocking activation of Ca(2+)-modulated enzymes (with calmidazolium), or inhibiting internucleosomal DNA fragmentation (with aurintricarboxylic acid). Apoptosis was increased and diterpenoids caused overexpression of p53 and interleukin 1 beta-converting enzyme in rats treated with dexamethasone (cytochrome P4503A inducer). Apoptosis was also increased by a diet deficient in sulfur amino acids. CONCLUSIONS: The germander furano diterpenoids cause apoptosis within 2 hours in isolated rat hepatocytes. Electrophilic metabolites may stimulate apoptosis by decreasing thiols, increasing [Ca2+], and activating Ca(2+)-dependent transglutaminase and endonucleases.

Amino Acids, Sulfur↗
PubMed1996

Telephoning a nursing department: callers' experiences.

This preliminary, exploratory study examined the level of satisfaction of patients and relatives with the telephone communication skills of nurses. Results indicate that callers experienced several difficulties, particularly with regards to knowing who they were speaking to, being treated as an individual rather than just another caller, having their calls dealt with efficiently, or redirected correctly. It is suggested that nurse educators include training in telephone use in courses on communication skills.

Communication↗
PubMed1994

Comparative study of three doses of interferon-alpha 2a in chronic active hepatitis B. The International Hepatitis Trial Group.

To determine the efficacy of interferon-alpha 2a in chronic active hepatitis B, 238 patients were randomly divided, into four groups: three groups received either 2.5 MIU m-2, 5.0 MIU m-2 or 10.0 MIU m-2, three times weekly by intramuscular injection for 12-24 weeks; and a control group received no treatment. Patients were followed for up to 12 months after treatment was discontinued. There was a statistically significant difference in response [clearance of hepatitis B e antigen (HBeAg) and hepatitis B viral DNA (HBV-DNA)] between treated and untreated patients (37 vs 13%) but no statistically significant difference was seen between treatment groups (33%, 34% and 43% for the 2.5, 5.0 and 10.0 MIU m-2 groups, respectively). A transient rise in transaminases (seroconversion hepatitis) was seen in responders, but levels returned to within the normal range after response to treatment. In patients responding to interferon therapy there was a significant reduction in the severity of the hepatitis. Interferon-alpha 2a was generally well tolerated with respect to vital signs and laboratory parameters.

Adolescent↗
PubMed1992

Liver function tests in persons receiving anticonvulsant medications.

Liver function tests were carried out in 206 adults and children taking anticonvulsants to ascertain the prevalence of biochemical abnormalities in asymptomatic patients. It was observed that serum gamma-glutamyl transpeptidase was elevated in 74.6% of patients, alkaline phosphatase in 29.7% and alanine aminotransferase in 25.2% of cases. These figures are similar to those previously reported in the literature and probably reflect hepatic enzyme induction by the anticonvulsants. It is suggested that there is no value in the routine performance of liver function tests in patients with epilepsy. However, such patients should be informed of the symptoms of hepatic dysfunction and asked to report for liver function tests should they have such symptoms.

Adolescent↗
PubMed1992

The effect of posture on three objective audiological measures.

This study examines the effect of posture on click evoked otoacoustic emissions, tympanic membrane displacement, and travelling wave velocity obtained using the auditory brainstem response. Statistically significant changes with posture were observed for each technique. The changes in evoked emission and tympanic membrane displacement measurements were comparable with those reported by previous experiments. Travelling wave velocity measurements were shown to be sensitive to inferred posturally-induced changes in labyrinthine fluid pressure of around 150 mm saline. There was no statistically significant correlation between posturally-induced changes measured by the three techniques. It is suggested that different mechanisms are responsible for the posturally-induced changes observed for the three techniques.

Adult↗
PubMed1991

A non-invasive, objective test of endolymphatic hydrops.

Our previous work has shown that auditory brainstem responses (ABRs) can be used to measure the basilar membrane travelling wave velocity (TWV). Based upon the hypothesis that increased pressure in the scala media will increase the stiffness of the basilar membrane and, hence, increase the speed of the travelling wave. ABRs have been used to provide a means of objectively testing for endolymphatic hydrops. Ten normally hearing subjects and 20 Meniere's patients were tested. The data for the Meniere's group show that the TWV was within normal limits at all frequencies tested, except 5.7 kHz. At this frequency, the TWV greatly exceeded that of the normal group. A short duration (15-30 min) clinical test has been developed which involves the recording of two masked brainstem responses and the measurement of the difference in wave V latencies. Clinical verification that the technique is valid was obtained by monitoring patients undergoing glycerol dehydration. The additional hardware to enable this test to be carried out with a standard evoked response system has been constructed and three, parallel, clinical trials are in hand. Currently, this technique is being applied to longitudinal studies of Meniere's patients and to evaluating the action and efficacy of various drugs. A double-blind trial using a placebo and two different drugs is underway and preliminary results are presented here.

Adolescent↗
PubMed1991

Apparent travelling wave velocity changes in cases of endolymphatic hydrops.

This study attempted to develop a test which would be specific for endolymphatic hydrops. It is based upon the hypothesis that increased pressure in the scala media will alter the stiffness of the basilar membrane and hence increase the speed of the travelling wave. Auditory brainstem-derived responses were used to measure the basilar membrane travelling wave velocity in normals and to take the equivalent measures in Meniere's patients. Ten normally hearing subjects and 20 Meniere's patients were tested. The data for the Meniere's group showed that the travelling wave velocities were within normal limits at all frequencies tested, except 5.7 kHz where the travelling wave velocity greatly exceeded that of the normal group. A theoretical possibility that these findings may be the result of damaged and broadened VIIIth nerve tuning curves is discussed but travelling wave measures and psychophysical tuning curve measurements on the Meniere's group, normals and noise-induced hearing loss (NIHL) cases showed that this was not a significant factor. The data indicate that this technique can detect endolymphatic hydrops and a short duration clinical procedure has been devised.

Adolescent↗
PubMed1991

Isochronic mapping: a preliminary report of a new technique.

A new technique which we have named 'isochronic mapping' is described. The conventional technique of plotting isopotential maps shows little or no contrast for far-field potentials such as the auditory brainstem response (ABR). However, by modifications to the mapping software, the latency values of a peak can be plotted and lines of equal time or isochronic maps can be produced. Data from a normal subject has been obtained for both the compound and derived ABRs and are described in detail. The data are clear but the time delays between earliest and latest projections of a peak are hard to interpret. For monaural click stimulation, wave JV of the ABR projects first to the contralateral side of the head then moves towards the stimulated ear arriving some 0.3 ms later. Possible interpretations of this finding are discussed but further experimentation is needed to develop our understanding of these data.

Acoustic Stimulation↗
PubMed1989

Verification of a new test of endolymphatic hydrops.

A new objective test of endolymphatic hydrops has been described previously. The test uses auditory brain-stem response (ABR) techniques to estimate the basilar membrane travelling wave velocity (TWV). The underlying hypothesis is that raised pressure in the scala media will lead to an increase in the stiffness of the basilar membrane and that this will give rise to a travelling wave velocity that is greater than normal. It was considered that verification of the technique could be obtained by carrying out the new test before and during a glycerol dehydration procedure. Patients who required this procedure for verification of the diagnosis or as a prognostic indicator for sacculotomy, underwent the following tests. Prior to dehydration an audiogram, the ABR TWV test and a blood sample (for plasma osmolality) were taken. The patient was then given the appropriate amount of glycerol mixed with lemon juice and laid on a bed in a test room. The audiogram and a blood sample were repeated every hour and the ABR TWV test was repeatedly carried out every twenty minutes between the other tests. Six of these procedures have been carried out. In five of them the 0.5 and 1 kHz average threshold improved by at least 10dB and in all those cases the ABR TWV test showed an abnormal pre-dehydration result which moved towards the normal value following dehydration. One patient gave ABR TWV results that were within normal limits before and during the procedure and gave an audiometric change of only 5dB.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Clinical methods for the objective estimation of loudness discomfort level (LDL) using auditory brainstem responses in patients.

Our previous work showed that the slope of the JV latency/intensity function can be used to estimate the loudness discomfort level (LDL). In this study, the previous work was repeated using normal subjects and patients whose LDL was unknown at the time of test. The results showed that the original model still applied. Further measures were taken to evaluate clinical methods of applying this technique. Four basic approaches were used, a 'correction factor' model and a 'curve-fitting' model and these were applied to data obtained from measurements taken in both 5 dB and 10 dB increments. The results showed that the 'correction factor' models were better than the 'curve-fit' approach. The prediction of LDL based upon the 5 dB increment data gave the greater accuracy but the 10 dB increment data gave predictions that were sufficiently accurate for clinical use (95% confidence limits of +/- 8 dB). Thus this ABR estimator has wide application and good accuracy in estimating subjective LDL. A clinical protocol for applying this technique is described.

Adolescent↗
PubMed1988

Hepatic testosterone metabolism in male rats with portal bypass.

This study was performed to ascertain whether testosterone metabolism is altered in male rats with portal bypass, and whether such changes could contribute to the reduction in serum testosterone concentration and raised serum estrogen levels that are observed in this situation. The metabolic clearance rate of testosterone was determined by a prime-dose constant-infusion technique in male rats subjected to complete portal vein ligation and in sham-operated controls. Testosterone clearance was similar in rats with portal vein ligation and control rats (9.01 +/- 2.29 and 8.26 +/- 2.83 ml/min, respectively) but the clearance per gram of liver was greater in rats with portal vein ligation than in controls (1.18 +/- 0.18 versus 0.68 +/- 0.24 ml/min.g liver, p less than 0.0001). After 180 min of [3H]testosterone infusion, [3H]estradiol comprised 1.2% of plasma total radioactivity in male controls but was increased to 11% in rats with portal vein ligation (p less than 0.005). Similarly, biliary excretion of [3H]estradiol was eightfold greater in male rats with portal vein ligation compared with controls (p less than 0.001). In control male rats, the major metabolites of testosterone present in bile were 2 alpha-hydroxytestosterone, 16 alpha-hydroxytestosterone, and 7 alpha-hydroxytestosterone. Portal bypass was associated with reduced biliary excretion of 2 alpha-hydroxytestosterone and 16 alpha-hydroxytestosterone to approximately 50% of control, but there was no change in the excretion of 7 alpha-hydroxytestosterone. Conversely, portal bypass was associated with increased formation of dihydrotestosterone, indicating stimulated activity of testosterone 5 alpha-reductase. It is concluded that portal bypass in male rats is associated with altered pathways of testosterone metabolism and, in particular, with increased aromatization of testosterone to estradiol. The site of such estradiol formation has not been determined by this in vivo study. However, selective changes occurred in the regiospecific and stereospecific hydroxylation pathways of testosterone and in 5 alpha-reductase activity after portal bypass in male rats. It is concluded that portal bypass, in the absence of parenchymal liver damage, results in demasculinization and feminization of C19 steroid metabolism in the male rat liver. These metabolic changes could be revelant to the pathogenesis of changes in sexual characteristics in cirrhosis.

Animals↗
PubMed1987

The objective estimation of loudness discomfort level using auditory brainstem evoked responses.

The loudness discomfort level (LDL) is of importance in the fitting of hearing aids, but very young children are unable to provide a subjective judgement of LDL. Therefore the relationship between Jewett wave V latency and subjective loudness was investigated to ascertain if objective estimation of LDL is possible. ABR recordings were taken from 8 normally hearing subjects at the stimulus intensity corresponding to their LDL and at stimulus levels from 10 to 30 dB below this. The wave V latency/intensity function did not correlate well with the LDL. However, the slope of this function did correlate to a high degree and a predictive model of LDL was derived. Identical measurements were then taken from a sample of 12 cochlear-impaired subjects with a range of audiometric profiles. Their subjective LDLs could be predicted from the wave V latency function to an accuracy of +/- 5 dB, using the model derived from the normally-hearing subjects. This model appeared to be equally valid for all the degrees and profiles of hearing loss included in the sample and showed a closer relationship to LDL than did absolute wave V latency or estimates derived from the acoustic reflex.

Adult↗
PubMed1986

Myocutaneous fenestration in sleep apnea patients.

We present a patient with severe obstructive sleep apnea syndrome (OSAS), including O2 desaturations to 11%, who was successfully managed with myocutaneous fenestration tracheostomy. The myocutaneous fenestration technique employs bilateral horizontal skin-platysma advancement flaps sutured directly to a tracheal fenestra created between rings two to four. It conforms ideally to the unique physical and psychological demands of the sleep apnea patient. Rapid healing time and minimal granulation tissue, combined with a permanently functional, yet reversible and minimally disfigurative stoma, highlight the advantages of the technique over standard tracheostomy. The myocutaneous fenestration tracheostomy is uniquely applicable to the surgical treatment of patients with moderate to severe obstructive sleep apnea.

Humans↗
PubMed1985

Halothane hepatitis. Detection of a constitutional susceptibility factor.

We studied susceptibility to halothane hepatitis with an in vitro test that detects cell damage from electrophilic drug intermediates. Metabolites of phenytoin were generated by incubation of phenytoin with rat hepatic microsomes in the presence of the epoxide hydrolase inhibitor 1,1,1-trichloropropene oxide (TCPO), which prevents the further metabolism of phenytoin to an inert metabolite. In lymphocytes exposed to this system, cytotoxicity was measured by trypan blue dye exclusion and was expressed as the percentage increase in trypan blue-positive cells after the addition of TCPO. In the presence of TCPO, lymphocytes from 11 patients with halothane hepatitis exhibited an increase in cytotoxicity at 0.06 mM phenytoin that was eight times greater than the increase in healthy controls (54 +/- 10 per cent [mean +/- S.E.M.] vs. 7.1 +/- 2.2 per cent, P less than 0.0001). Patients with other liver diseases and persons recently exposed to halothane without adverse effects did not differ from healthy controls. In three patients with halothane hepatitis who were studied serially, the lymphocyte abnormality was still present after 13 months. Family studies revealed abnormal results on 10 cytotoxicity tests among 19 members of four families. We propose that there is a familial, constitutional susceptibility factor that predisposes persons to halothane hepatitis.

Adult↗