Biomedical subjects

K Byth

Publications and source records attributed to K Byth.

At least 37 records · Page 2Linked to original sources

PubMed1998

Cytomegalovirus and human herpesvirus 6 both cause viral disease after renal transplantation.

BACKGROUND: Systemic viral disease after renal transplantation, especially after treatment with OKT3 or antithymocyte globulin, has usually been attributed to cytomegalovirus (CMV) infection. Identification of human herpesvirus 6 (HHV6) has raised the possibility that infection or reactivation of this virus may also occur in the same setting. METHODS: We thus examined the incidence of CMV and HHV6 infection in a prospective blinded consecutive series of 30 renal and renal/pancreas transplant patients, 22 of whom received OKT3, antithymocyte globulin, or both. RESULTS: Clinical diagnosis of a viral syndrome was made in 15 patients. Three patients with only HHV6 DNA in urine or serum had fever and abnormal liver function but not neutropenia. All five CMV-seronegative patients who received positive kidneys developed moderate to severe disease with fever and neutropenia but also had HHV6 DNA in urine or serum. Seven CMV-seropositive patients developed disease, mostly after OKT3/antithymocyte globulin, but six shed both CMV and HHV6 in urine or serum. The simultaneous detection of both HHV6 and CMV DNA in either urine or serum was the strongest predictor of disease (and also the severity of disease), with an odds ratio of 99.0 (95% confidence intervals 5.4-1814, P<0.002). CONCLUSION: Most systemic viral disease after renal transplantation may be due to either coinfection or reactivation of CMV and HHV6 together. A wider understanding of risk factors for severe viral disease in this setting may come from testing for both viruses in all donors and patients in both clinical practice and clinical trials.

Acyclovir↗

PubMed1998

Hepatocellular proliferation and development of hepatocellular carcinoma: a case-control study in chronic hepatitis C.

Patients with hepatitis C have an increased risk of developing hepatocellular carcinoma (HCC). This is related to the stage of chronic liver disease, as characterized histologically by hepatic fibrosis and architectural distortion, but it is unclear whether histological markers can define the risk of developing HCC. We conducted a case-control immunohistochemical study of Ki-67, a marker for hepatocellular proliferation, in livers of 18 patients who had developed HCC more than 2 years after the biopsy specimen had been taken. Using conditional logistic regression analysis, the results were compared with 18 selected controls, who were age-matched patients with hepatitis C of similar histological stage who had not developed HCC. We also examined livers for cellular dysplasia, p53 mutations, and bcl-2 overexpression, and assessed whether the results could be correlated with demographic and disease-related variables, such as gender, region of birth, alcohol consumption, severity of liver disease, HCV genotype, and markers of hepatitis B virus (HBV) infection. Livers from patients who developed HCC were more often positive for Ki-67 (13 of 18 [72%] v 9 of 18 [50%]; P = .06) and tended to have higher mean Ki-67 scores (6 +/- 7.5 v 3 +/- 4.4; P = .10) compared with control cases. In the HCC-predisposed group, three livers showed large cell dysplasia, two were positive for p53 mutations, and two for bcl-2 overexpression. In contrast, in the non-HCC group, only one case had dysplasia, and none were positive for immunostaining for p53 or bcl-2 mutations. With the exception of one case, all livers with large cell dysplasia or p53 mutations and bcl-2 overexpression were also positive for Ki-67. Twelve (55%) of the 22 Ki-67-positive cases were anti-HBc-positive in the serum, in contrast to 2 of 14 (14%) patients in the Ki-67-negative group (P = .01). Patients with evidence of past infection with HBV were more often Ki-67 positive than those who had no evidence of past infection (85% [11 of 13] v 45% [10 of 22]; P = .02). There were no other associations between demographic or disease-related variables and Ki-67 expression. Increased hepatocellular proliferative activity, as assessed by Ki-67 expression, may be one factor indicative of an increased risk of developing HCC among patients with chronic hepatitis C. Furthermore, past infection with HBV appears to be an important correlate of increased hepatocellular proliferation in hepatitis C.

Adult↗

PubMed1998

How much does alcohol contribute to the variability of hepatic fibrosis in chronic hepatitis C?

In order to determine the contribution of alcohol intake to the severity of hepatic fibrosis in patients with chronic hepatitis C, we studied associations between various levels of alcohol intake, other demographic variables and semiquantitative liver histology in 434 cases of chronic hepatitis C. Clinical, demographic and disease-related data were entered into a relational database. Liver histology was scored according to Scheuer. The average daily alcohol intake for the year preceding liver biopsy (recent exposure) and for earlier periods (past exposure) was categorized into five levels of intake. One-third of patients gave a history of alcohol intake that had exceeded 40 g/day for at least 5 years. By univariate analysis, age, but not recent or past alcohol intake or other baseline variables, was associated with portal score (r = 0.14, P = 0.004), fibrosis score (r = 0.46, P < 0.001), total Scheuer score (r = 0.35, P < 0.001). However, by multivariate analysis, age (P < 0.001), past (but not present) alcohol intake (P < 0.001) and birth in Egypt (P = 0.006) were independently associated with fibrosis score. Age, past alcohol and birth place in Egypt contributed 27% to total variance of the hepatic fibrosis score, while age alone accounted for 23%. Age also independently predicted portal activity (P = 0.02) and total Scheuer score (P < 0.001), whereas past alcohol intake correlated with total Scheuer score (P = 0.002) but not with other histological indices. A separate multivariate analysis was performed on a more homogeneous subgroup of 196 patients who acquired hepatitis C by injection drug use. In this subgroup, age (P < 0.05) and past alcohol (P < 0.05) were independently associated with fibrosis score. In both the overall and subgroup analyses, there was a threshold level of past alcohol intake (>80 g/day) beyond which the risk of fibrosis increased significantly. It is concluded that toxic levels of alcohol exposure for at least 5 years accentuate hepatic fibrosis in hepatitis C but the influence of alcohol appears to be minor compared with age and other variables and is exerted only at toxic levels of intake.

Adult↗

PubMed1998

Effects of hepatitis G virus coinfection on severity of hepatitis C: relationship to risk factors and response to interferon treatment.

The aims of the present study were to identify characteristics that are more often associated with hepatitis G virus (HGV) coinfection in Australian patients infected with the hepatitis C virus (HCV) and to investigate the effects of HGV on the histological and functional severity of chronic hepatitis C. Serum samples from 209 patients with chronic hepatitis C were tested for HGV-RNA using single-round reverse transcriptase-polymerase chain reaction to primers directed at the NS5 region of the HGV genome. Hepatitis G virus RNA was detected in 40 cases (19%). Hepatitis G virus-coinfected patients tended to be younger and parenteral risks could be identified in all but six. Although country of birth did not differ significantly between the coinfected and HCV-alone groups, HGV-positive patients appeared to be less likely to have originated from Asia. On logistic regression analysis, HCV genotype 3a was found in a significantly higher proportion of patients with HGV coinfection than other genotypes (P < 0.01). Liver histology and response to interferon were similar in the HGV-coinfected and HCV-alone groups and liver-related complications appeared to occur less frequently in patients with both HGV and HCV. On univariate analysis, antipyrine clearance was found to be higher in the coinfected group (P < 0.05), implying better preservation of hepatic metabolic function, but this difference was lost when adjusted for HCV genotype. In conclusion, coinfection with HGV was more commonly associated with HCV genotype 3a, a genotype associated with injection drug use in younger patients. However, the presence of HGV coinfection did not adversely affect liver disease or the response to interferon treatment in patients with chronic hepatitis C.

Adult↗

PubMed1998

Molecular epidemiology of hepatitis C in Australia.

The aim of this study was to determine the distribution of hepatitis C virus (HCV) genotypes in Australian patients with hepatitis C and to identify factors associated with particular genotypes. Serum isolates of HCV-RNA were genotyped using a commercial oligonucleotide hybridization (line probe) assay. Relationships between demographic factors, mode of HCV transmission and HCV genotype were assessed by logistic regression analysis. Among 463 patients with hepatitis C, 425 tested positive for HCV-RNA and a single HCV genotype was identified in 420 cases. The patients' places of birth were Australia or New Zealand (62%), Asia (13%), Europe (12%), Mediterranean (6%), Middle East (6%) and other countries (< 1%). The most common genotypes were type 1 (52%) or type 3 (32%); type 2 (9.3%), type 4 (5.5%) and type 6 (1.7%) were less common. Patients with genotype 1b were older (48 +/- 13 years, P< 0.001) and patients with genotype 3 were younger than the remaining patients (37 +/- 11 years vs 42 +/- 12 years, P< 0.001). Among type 1 isolates, 1b was more common for patients born outside Australia compared with those born in Australia (50% vs 13%, P< 0.001) whereas non-1b subtypes were more common among Australian-born patients. Likewise, 21 of 23 (91%) patients with type 4 were from Egypt and six of seven (86%) with type 6 were from Vietnam. The relative importance of parenteral risk factors for HCV also varied according to geographic origin. Thus, a definite risk factor for HCV acquisition was identified in > 95% of Australian-born patients, but in only 33% of Asian or Mediterranean-born patients. Logistic regression analysis indicated that region of birth and risk factor (intravenous drug use or not) would allow 98% of type 4 cases and 76% of type 1b cases to be identified correctly. In summary, region of birth, patterns of migration over time and risk factors for transmission of HCV interact to determine the distribution of HCV genotypes in a multi-racial community like Australia.

Adult↗

PubMed1998

Comparison of the Quintest to the lancet in allergic skin testing.

Many skin testing devices have been commercially available over recent years, but use has been limited because of significantly greater costs of such devices. Therefore, the lancet continues to be the most widely used skin testing device in Australia. This study compared performance of another multitest device, the Bayer Quintest to the Becton Dickinson Microlance. Nineteen atopic volunteers were skin tested using histamine dihydrochloride 10 mg/ml, glycerosaline and eight allergens. In 190 tests, 6 discrepancies between the Quintest and Microlance occurred. The Microlance produced slightly larger wheals than the Quintest, reaching statistical significance in 3 allergens. We found the Quintest comparable to the Microlance in concordance of positive and negative allergen responses and in wheal size. The Quintest had higher acceptability to both participants and staff for comfort, ease of use and safety. The Quintest's major advantage is the ability to rapidly screen large numbers of subjects, especially during clinical trials. The major limitation is it's cost.

Adult↗

PubMed1996

Does sotalol have reverse-use dependence during tachyarrhythmias?

This study assessed the effect of intravenous sotalol on right ventricular effective refractory period at right ventricular pacing rates of 600 and 300 ms cycle length at 3, 6, 9, and approximately 30 minutes after the dose of sotalol. Similar percent increases occurred in the ventricular effective period at the 2 heart rates at all tested times (p >0.2 in each case), and it was concluded that there is no evidence for reverse-use dependence of intravenous sotalol in its effects on right ventricular refractoriness over this range of heart rates.

Aged↗

PubMed1996

Virus and host factors are both important determinants of response to interferon treatment among patients with chronic hepatitis C.

Virus and host factors have both been linked to the response to interferon treatment among patients with chronic hepatitis C but their relative importance and potential interactions are unclear. Hepatitis C virus genotype and level of viraemia were determined in pretreatment sera from 65 Australian patients treated with interferon-alpha 2b (IFN-alpha 2b), 3 MU tiw for 6 months. Hepatitis C viraemia was quantitated by a competitive reverse transcription-polymerase chain reaction (RT-PCR) method and genotype was determined by a line probe assay. By univariate analysis, there were positive associations between initial (short-term) responses to IFN treatment and younger age (P = 0.004), absence of cirrhosis (P = 0.01), and injecting drug use as risk factor for infection (P = 0.05) but not gender, duration of infection, or level of viraemia. Genotype appeared to be important (P = 0.06) but failed to reach statistical significance. By multivariate analysis, absence of cirrhosis was the only significant independent predictor of treatment response (P = 0.01). Among initial responders, the factors associated with long-term response were the pretreatment HCV RNA titre and the duration of infection. There was a close association between viral genotype, but not viral load, and the severity of liver disease. An interplay of factors determines the outcome of a 6-month course of interferon treatment for hepatitis C. Severity of liver disease, but not the viral load, is the most crucial determinant of initial response to interferon, and histological severity appeared to be influenced by the viral genotype. The level of hepatitis C virus (HCV) viraemia and the duration of infection are independent determinants of long-term response by affecting the relapse rate after interferon treatment.

Chronic Disease↗

PubMed1996

Influence of clinicopathological variables on CYP protein expression in human liver.

Drug metabolism is usually impaired in malnourished patients with decompensated cirrhosis, but the separate influence of clinicopathological variables, including nutritional status, on the expression of hepatic cytochrome P450 proteins has not been well characterized. We determined the hepatic content of CYP1A2, CYP2C8/10, CYP2E1 and CYP3A proteins in 71 subjects, 21 with histologically normal livers and 50 with chronic liver disease, and then tested for potential relationships between patient variables and individual CYP proteins by multivariate linear regression analysis. Variables analysed included nutritional status (determined by experienced clinicians), serum albumin and bilirubin concentrations, prothrombin time, the grade of ascites and hepatic encephalopathy, and the Child-Pugh score. Impaired nutrition and cachexia were associated with reductions of CYP2C8/10 levels of approximately 19 and 39%, respectively, relative to cases in which nutrition was replete. Similarly, CYP2E1 protein was reduced by approximately 13 and 26%, according to the apparent severity of nutritional impairment. In contrast, nutritional status did not contribute to variability in expression of CYP1A2 or CYP3A proteins. Of the clinicopathological variables analysed, only serum bilirubin was shown to have an independent influence on CYP protein content. Thus, elevated serum bilirubin concentrations were associated with significant declines in the contents of CYP1A2 and CYP2C8/10 but not CYP3A or CYP2E1. The mechanisms for the effects of nutritional status and serum bilirubin concentration on the levels of CYP proteins are unclear, but could be mediated by factors such as cytokines, dietary composition and alterations in the level of serum bile acids. Knowledge of the influence of clinicopathological factors and nutritional status on CYP expression should lead to more rational drug prescribing in patients with hepatic disease.

Bilirubin↗

PubMed1996

Some factors associated with mortality in perforated peptic ulcer: a case-control study.

This study examined the associations of individual coexisting illnesses, septicaemia, intra-abdominal abscess, marital status, smoking and alcohol use, with mortality following perforation of peptic ulcer without pre-operative evidence of haemorrhage. Patients who died in hospital following ulcer perforation (cases; n = 300) were compared with patients who survived following ulcer perforation (controls; n = 276). The controls were frequency-matched to the cases on age, sex and perforation site. Data were analysed by logistic regression. Cardiac, respiratory, cerebrovascular, renal, liver and malignant diseases, and septicaemia and intra-abdominal abscess were associated with mortality and the coexisting illnesses were significantly increased in cases compared to controls both on admission and at the end of hospital stay. During hospitalization, the odds of pneumonia decreased in cases, otherwise there was little change in strengths of associations over this period. Being widowed or never married was positively associated with mortality, and moderate alcohol use was negatively associated. In conclusion, this study identifies several coexisting illnesses, septicaemia and intra-abdominal abscess as risk factors for mortality following ulcer perforation. The results suggest that, with little exception, the same level of mortality risk is associated with coexisting illnesses whether the beginning or end of hospital stay is used as the index time point.

Abdominal Abscess↗

PubMed1996

Sequential changes in serum levels of individual bile acids in patients with chronic cholestatic liver disease.

In order to determine the value of serum bile acids in predicting the course of chronic cholestatic liver diseases, we measured individual serum bile acids serially, using high-performance liquid chromatography, over a 4 year observation period in 12 patients with primary biliary cirrhosis and six patients with primary sclerosing cholangitis. The changes in individual serum bile acids and the ratios thereof, conventional liver tests and Child-Turcotte and Mayo scores were compared between survivors (n = 10) and patients who underwent liver transplantation for (n = 3) or died of the liver disease (n = 5). Patients with a serum total chenodeoxycholic acid concentration at study entry that exceded 15 mumol/L were 10 times more likely to die or need a liver transplant in the following 4 years than those with chenodeoxycholic acid levels < 15 mumol/L (P < 0.05). None of the other biochemical parameters or clinicopathological scores could similarly discriminate between the two groups at entry. Time-dependent analyses for the cholic acid/chenodeoxycholic acid ratio, serum total bilirubin and albumin concentrations and Child-Turcotte and Mayo scores were able to differentiate between primary sclerosing cholangitis patients who died or were transplanted and those who were not, whereas age of the patients and other parameters did not. The taurocholic acid/taurochenodeoxycholic acid ratio fell during progression of primary biliary cirrhosis but rose in temporal relationship with primary sclerosing cholangitis. This differential pattern of change was unique compared with other clinical and laboratory indices. In conclusion, serum chenodeoxycholic acid levels and the cholic acid/chenodeoxycholic acid ratio in both diseases were independent indices that allowed for the prediction of survival or the need for liver transplantation. These indices are worthy of further examination in a larger group of patients as prognostic criteria for chronic cholestatic liver disease and in the assessment of the efficacy of therapeutic interventions, including liver transplantations.

Adult↗

PubMed1996

Twin- versus single-bag disconnect systems: infection rates and cost of continuous ambulatory peritoneal dialysis.

Although twin-bag disconnect fluid-transfer systems for continuous ambulatory peritoneal dialysis (CAPD) have a lower rate of catheter-related infection than single-bag systems, their greater monetary purchase cost has prevented universal adoption. Therefore, a single-center randomized study was performed in 63 adult patients to compare the efficiency and total cost of Freeline Solo (FS, twin-bag) and Basic Y (BY, single-bag) systems. Patients were new to CAPD (N = 39), or had a new CAPD catheter, or had had no episodes of peritonitis or exit-site infection in the previous 12 months (N = 24). Total follow-up was 631 patient months (pt.mon), and 53 patients were still on the trial at its termination. Patients rated FS as easier to use than BY (P < 0.001). Peritonitis occurred on 23 occasions in 12 out of 30 patients using BY, and on seven occasions in five of 33 patients using FS. Time to first infection was less with BY than FS (hazard ratio, 2.4; 95% confidence interval (CI), 1.0 to 5.3; P < 0.04). Cumulative incidence of peritonitis was 1 per 14.0 pt.mon with BY and 1 per 46.5 pt.mon with FS (odds ratio, 3.6; 95% CI 1.5 to 8.5; P = 0.004). Length of hospitalization for peritonitis or exit-site infection was 98 days in six patients with BY, versus 17 days in two patients with FS. With BY, four catheters were removed because of infection, but none with FS (P < 0.05). With BY, the total cost of infection was $AUD127,079 ($5033 per pt.yr) versus $19,250 ($704 per pt.yr) with FS, which offset the higher purchase cost of FS. The total cost of CAPD was $AUD956 per pt.yr less with FS than BY. In conclusion, the higher purchase cost of the FS twin-bag system is more than offset by savings from its lower incidence of peritonitis.

Adolescent↗

PubMed1995

Age but not gender selectively affects expression of individual cytochrome P450 proteins in human liver.

Multivariate linear regression analysis was used to examine the influence of age, gender and environmental variables on the hepatic content of cytochromes P450 (CYP, P450) 1A2, 2C, 2E1 and 3A in 71 subjects; 21 with histologically normal livers and 50 with chronic liver disease. There was a clear negative association between age and total P450 content, NADPH-cytochrome c reductase activity and levels of 2E1 and 3A proteins. 1A2 and 2C proteins were unaltered with advancing age. Gender did not influence the expression of any of the CYP proteins. Cigarette smoking was associated with enhanced levels of 1A2, but effects of drug ingestion and alcohol consumption were not apparent in this study, probably because of case selection. It is concluded that age but not gender is a constitutional factor that influences the hepatic content of cytochrome P450 and selected CYP proteins.

Aging↗

PubMed1995

Localisation of ventricular tachycardia substrates by analysis of the surface QRS recorded during ventricular tachycardia.

BACKGROUND: Analysis of the surface ECG can predict the locations of pacing foci but is of limited value for locating arrhythmogenic substrates causing ventricular tachycardia because of the effects of myocardial infarction, ischaemia, and bundle branch block on ventricular activation. AIM: To determine whether analysis of the initial 60 ms segment of the surface QRS improves the accuracy of the ECG for predicting ventricular tachycardia origin we correlated the locations of 37 arrhythmogenic areas present in 20 patients with the 3D vectors of the ventricular tachycardias generated by each respective area. METHODS: The 3D vector of each ventricular tachycardia morphology was calculated from the integrals of the initial 60 ms of the surface vectorcardiogram and from the entire QRS recorded in each lead of the Frank orthogonal lead vectorcardiogram. Sixty eight-morphologies of ventricular tachycardia were mapped using simultaneous recordings from 60 catheter electrodes. RESULTS: Ventricular tachycardias with 3D vectors directed inferiorly and posteriorly or superiorly and anteriorly were more likely to originate from the septum, P = 0.04, whereas tachycardias directed superiorly and to the right were more likely to originate from the inferior wall and the cardiac apex, P = 0.001. However, the same arrhythmogenic area could generate multiple ventricular tachycardias with different 3D vectors. In addition, ventricular tachycardias with similar 3D vectors were generated by arrhythmogenic areas in the septal, apical and inferior walls. The variances of the mean 3D vectors of ventricular tachycardias originating from each of 12 different cardiac regions were no different when based on the initial 60 ms of the surface QRS than on the entire surface QRS. CONCLUSION: Analysis of the surface ECG provides only an approximate guide to the locations of arrhythmogenic areas generating ventricular tachycardia even when analysis is restricted to the initial forces in the surface QRS. Therefore, detailed mapping is needed to accurately determine the number and location of arrhythmogenic areas.

Bundle-Branch Block↗

PubMed1995

Pre-translational regulation of cytochrome P450 genes is responsible for disease-specific changes of individual P450 enzymes among patients with cirrhosis.

We have recently reported that disease-specific differential alterations in the hepatic expression of xenobiotic-metabolizing cytochrome P450 (CYP P450) enzymes occur in patients with advanced liver disease. In order to determine whether the observed changes in CYP proteins are modulated at pre- or post-translational levels, we have now examined the hepatic levels of mRNA for CYPs 1A2, 2C9, 2E1 and 3A4 by solution hybridization in the same livers of 20 controls (surgical waste from histologically normal livers), 32 cases of hepatocellular and 18 of cholestatic severe chronic liver disease. CYP1A2 mRNA and CYP1A immunoreactive protein were both reduced in livers with hepatocellular and cholestatic types of cirrhosis. In contrast, CYP3A4 mRNA and protein were reduced only in livers from patients with hepatocellular diseases. For 1A2 and 3A4 there were significant correlations between mRNA species and the respective protein contents (rS1A2 = 0.74, rS3A4 = 0.64, P < 0.0001). CYP2C9 mRNA was reduced in patients with both cholestatic and hepatocellular types of liver disease, but 2C protein was reduced only in patients with cholestatic dysfunction. The correlation between CYP2C9 mRNA and protein, was also significant (rs = 0.36, P < 0.005) but mRNA levels accounted for only 13% of the variability in protein rankings. This is probably a consequence of other CYP2C proteins apart from 2C9 being detected by the anti-2C antibody. CYP2E1 mRNA and protein were reduced in patients with cholestatic liver disease, but in hepatocellular disease the expression of only CYP2E1 mRNA was decreased. CYP2E1 mRNA was significantly correlated with CYP2E1 protein but accounted for only 18% of the variability in protein rankings (rs = 0.43, P < 0.0005). Taken collectively these data indicate that the disease-specific alterations of xenobiotic-metabolizing CYP enzymes among patients with cirrhosis is due, at least in part, to pre-translational mechanisms. The lack of a strong correlation between CYP2E1 mRNA and protein suggests that this gene, like its rat orthologue, may be subject to pre-translational as well as translational and/or post-translational regulation.

Cytochrome P-450 Enzyme System↗

PubMed1995

Antipyrine clearance and response to interferon treatment in patients with chronic active hepatitis C.

To determine whether hepatic metabolic function affects the response to interferon treatment, we measured antipyrine clearance (APC) in 85 patients with chronic active hepatitis C and compared the results with treatment outcome. Among 55 patients who responded to interferon by normalization of alanine transaminase (ALT), median APC before treatment was 0.47 (range, 0.12 to 0.98; normal range, 0.34 to 1.02 mL/min/kg body wt), a value that was significantly greater than in 30 nonresponders (0.23; 0.08 to 0.67 mL/min/kg body wt, P < .001). APC was closely associated with response to interferon. The response rate among cases with values > 0.25 mL/min/kg body weight was 79%, the same as in cases without cirrhosis. Cases without cirrhosis and with APC of > 0.25 mL/min/kg body weight had an 85% chance of responding to interferon; this was unlikely a simple reflection of histological activity, because the correlation with Scheuer score was poor in this subgroup (r = -.31, P < .05). A second, independent group of 43 patients was used to test the predictive value of APC (using 0.25 mL/min/kg body wt as a cut-off) for response to interferon treatment. In this group, APC correctly predicted positive response to interferon in 75% of cases. APC was also used to measure the effects of treatment on hepatic metabolic function. Regardless of outcome, there was no change in APC at the end of a 6-month course of interferon treatment. Six months later, however, improvement in APC (14%; P < .05) was evident among responders but not in those who had failed to respond to interferon.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

The myelodysplastic syndromes: an analysis of prognostic factors in 226 cases from a single institution.

Two hundred and twenty-six patients were diagnosed with myelodysplastic syndrome (MDS), according to the French-American-British (FAB) criteria, over a 13-year period, and studied retrospectively in a single institution in order to study indicators which were prognostically significant. Analysis of clinical and laboratory data indicated that the FAB classification, the Bournemouth, Dusseldorf, Goasguen, Sanz and FAB Scoring Systems were all good predictors of survival. We found advancing age, haemoglobin (Hb) < or = 9 g/dl, platelet count < or = 50 x 10(9)/l, increased peripheral total white cell count (WCC) and monocytosis, increased bone marrow blasts, dysgranulopoiesis, and bone marrow fibrosis were significant adverse prognostic variables. The commonest complication and cause of death was infection; however, infective episodes were not significantly associated with low neutrophil counts (either < or = 1.5 x 10(9)/l or < or = 0.8 x 10(9)/l) and there was also no significant association between neutropenia and survival. These findings indicate that neutrophil dysfunction plays an important role in the clinical progression of patients with MDS. The effect of new therapeutic modalities, such as the haemopoietic growth factors, on reducing infective episodes may be as significant as their effect on increasing neutrophil counts.

Adult↗

PubMed1995

'Atypical' tremor.

The tremor present in a small number of patients who present with features of both Parkinson's disease (PD) and essential tremor (ET) is ill-defined. We therefore studied 8 such patients with 'atypical' tremor and compared them clinically to 11 PD and 10 ET patients in a double-blind, cross-over, placebo-controlled trial. Tremor was assessed via accelerometry and surface EMG. Tremor frequency and the acute tremorlytic response to propranolol were not useful in discriminating between groups. Over 80% of atypical and PD patients showed alternating EMG, whereas 90% of ET patients had synchronous EMG activity. Tremor amplitude improved by > 90% in 38% of atypical, 27% of PD and none of the ET patients after single-dose L-dopa/benserazide (300/75 mg), a response which was significantly different between the ET and PD groups. Failure to differentiate electrophysiologically and pharmacologically between the atypical and other groups probably relates to clinical heterogeneity in the atypical group.

Benserazide↗