An unusual cause of pyrexia.
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Carcinogens↗
Biomedical subjects
A A Dunk
Publications and source records attributed to A A Dunk.
Interaction between warfarin and topical miconazole cream.
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Aged↗
Restenting malignant oesophageal strictures.
BACKGROUND: Self-expanding metal stents are used to palliate malignant strictures of the oesophagus. This study was designed to identify the characteristics of patients requiring restenting of malignant oesophageal strictures. METHODS: Fifty-three stents were inserted in 42 patients. Thirty-two patients did not require further stenting (once-stented group). Ten patients received second stents for recurrent oesophageal obstruction (restented group), with one patient requiring restenting a second time. Comparisons were drawn between the once-stented and restented groups with regard to survival, patient, tumour and procedural characteristics. RESULTS: There were no significant differences with regard to tumour grade, tumour type, involvement of the cardia, procedural difficulties or the need for postprocedural oesophageal dilatation between the two groups. Survival from initial stenting was significantly greater in the restented group (median 24 (range 4-43) weeks) than in the once-stented group (median 9.5 (range 1-84) weeks) (P < 0.05). The mean length of stents used in the once-stented group was significantly greater than that of the initial stents used in the restented group (12 versus 10 cm, P = 0.032). CONCLUSION: Inserting a covered stent through a previously inserted uncovered stent is an uncomplicated and well tolerated technique which maintains palliation from obstructing oesophageal carcinoma. The need for restenting cannot be predicted on the basis of tumour characteristics alone.
Adenocarcinoma↗
Duodeno-jejunal adenocarcinoma and coeliac disease.
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Adenocarcinoma↗
The value of flumazenil in the reversal of midazolam-induced sedation for upper gastrointestinal endoscopy.
Fifty patients who underwent diagnostic upper gastrointestinal endoscopy after midazolam sedation were randomized to receive (after completion of the examination) either the benzodiazepine receptor antagonist flumazenil or an identical-looking placebo. The speed of recovery from sedation was assessed by reaction time testing, measurement of critical flicker fusion frequency, and the semi-quantitative SOCA scoring system. Measurements were made up to 6 h post examination in all subjects, and at 12 and 24 h in all in-patients (n = 20). Flumazenil-treated patients were significantly more alert than those who received placebo at 10 min, 30 min, 1 h and 2 h (P less than 0.001 in all instances). Thereafter the two groups were similar. There was no evidence of recurrence of sedation in flumazenil-treated patients, nor did this drug adversely affect the period of anterograde amnesia between the administration of midazolam and flumazenil.
Adolescent↗
The safety and efficacy of tripotassium dicitrato bismuthate (De-Nol) maintenance therapy in patients with duodenal ulceration.
Seventy-one patients whose duodenal ulcers had healed after a 4-week treatment period with tripotassium dicitrato bismuthate (TDB) were randomly allocated to receive maintenance treatment with either one TDB swallow tablet nocte (equivalent to 120 mg Bi2O3) or an identical placebo. During 12 months of follow-up, no side-effects were reported by TDB-treated patients, blood bismuth levels did not rise above discontinuation threshold concentrations (greater than 50 micrograms/L in the first 6 months, or greater than 100 micrograms/L in the second 6 months), and there were no adverse effects on haematological or biochemical indices. Ulcer relapse was significantly less in TDB-treated patients (P less than 0.025). Cumulative relapse rates at 6 and 12 months were 51% and 66%, respectively, for placebo-treated patients and 26% and 31%, respectively, for those who received TDB. It is likely that TDB is a safe and effective maintenance treatment for patients with duodenal ulcer disease.
Adult↗
Neuropsychological deficits and morphological MRI brain scan abnormalities in apparently healthy non-encephalopathic patients with cirrhosis. A controlled study.
By means of psychometric testing, we have determined the frequency of latent hepatic encephalopathy in a group of 19 cirrhotics with no clinical evidence of encephalopathy. Magnetic resonance imaging (MRI) of the brain was performed in order to determine whether morphological cerebral abnormalities were associated with latent encephalopathy. Nineteen age and educationally matched patients with normal liver function acted as controls. Significant differences (P less than 0.05) between cirrhotics and controls were found in tests of short-term visual memory and speed of reaction to light (cirrhotics 316 +/- 132 ms vs. controls 225 +/- 36 ms), sound (cirrhotics 361 +/- 152 ms vs. controls 236 +/- 52 ms) and choice (cirrhotics 651 +/- 190 ms vs. controls 406 +/- 101 ms) stimuli (all values mean +/- S.D.). Reitan trail test performance, however, was similar in both groups. (Trail A: cirrhotics 43 +/- 19 s vs. controls 35 +/- 13 s; Trail B: cirrhotics 105 +/- 66 s vs. controls 93 +/- 36 s.) In patients with cirrhosis, MRI revealed statistically significant increases in the maximum fissure width of right frontal sulci, right and left parietal sulci, inter-hemispheric fissure width and in bicaudate index. These changes, indicating cerebral atrophy, were largely confined to alcoholics. There was poor correlation between measurements of cerebral morphology and neuropsychological performance, only 10% of associations achieving statistical significance.
Adult↗
Hepatocellular carcinoma: clinical, aetiological and pathological features in British patients.
We have examined the clinical, prognostic, aetiological and pathological features of 41 consecutive British patients with hepatocellular carcinoma (HCC). Presenting symptoms were often vague, and patients were generally in poor condition at diagnosis, 56% being of WHO grade 2 performance score or higher. Ascites (46%) and jaundice (35%) were often present at diagnosis, and the median duration of survival from diagnosis was only 6 weeks. Only initial performance grade (p less than 0.0001) and serum bilirubin concentration (p = 0.02) significantly affected prognosis. Serum alphafoetoprotein (AFP) was positive by counter-immune electrophoresis in only 34%, but increased to 68% when radioimmunoassay was used. Cirrhosis was present in 33 patients (80%) and was most often cryptogenic (12) or alcoholic (7) in origin. Serum HBsAg was detected in 5 patients (12%) and, of the remainder tested, 21% had serological evidence of past HBV exposure. None of 8 serum HBsAg-negative tumour specimens had detectable HBV-DNA integration into the tumour cell genome. Liver-cell dysplasia was noted in 56% of patients with liver biopsies predating the diagnosis of HCC, and in 78% of biopsies taken at the time of HCC diagnosis. The commonest histological pattern was trabecular (71%). Other forms were rare; the fibrolamellar pattern was only seen in 2 patients.
Adolescent↗
Human hepatocellular carcinoma tumor xenografts. Their androgen-receptor status and growth responses to castration.
Castrated or sham-operated male athymic mice were inoculated with cells from the human hepatocellular carcinoma cell line PLC/PRF/5. There were no significant differences between the two groups with respect to the number of animals developing tumors, the time to tumor development, or the subsequent rate of increase in either tumor base area or mouse serum alpha-fetoprotein concentration. Androgen receptors were assayed in nuclei obtained from three separate liver cancer cell lines and from normal adult human liver. Similar concentrations, ranging from 235 to 550 fmol/mg DNA, of nuclear androgen receptors were detected in all tissues. Low percentages of androgen receptors were retained on DNA-cellulose. Although the presence of receptors implies the potential for metabolic effects of androgens in normal and malignant liver, our in vivo studies suggest that castration does not alter significantly the growth of liver cancer xenografts in athymic mice.
Animals↗
The effects of propranolol on hepatic encephalopathy in patients with cirrhosis and portal hypertension.
Beta adrenoreceptor blocking drugs have been used for the prevention of haemorrhage from oesophageal varices. However, it is possible that these agents, by virtue of their effects on hepatic blood flow, may impair liver function and precipitate hepatic encephalopathy. We have therefore studied the effect of the beta blocking drug propranolol on hepatic encephalopathy in patients with cirrhosis and portal hypertension. Twenty patients were randomly assigned to receive 4 weeks treatment with propranolol or an identical-looking placebo, the former given in a dose sufficient to reduce resting pulse rate by greater than or equal to 25%. Before and after treatment patients were assessed for the severity of liver disease and the presence of encephalopathy. EEG mean cycle frequency and fasting arterial ammonia concentrations were also measured, and in order to detect latent hepatic encephalopathy, each patient underwent a battery of psychometric tests. Patients were blinded as to their treatment, as were those assessing their responses. Neither propranolol nor placebo had any significant effect on the parameters measured. On propranolol median EEG mean cycle frequency fell from 9.08 ct s-1 (range 8.63-11.0 ct s-1) to 8.73 ct s-1 (range 8.27-11.44 ct s-1), and median fasting arterial ammonia concentration fell from 66 mumol litre-1 (range 40-329 mumol litre-1) to 49 mumol litre-1 (range 37-188 mumol litre-1). Psychometric test values, while initially abnormal and suggestive of latent hepatic encephalopathy in the majority of patients, did not change significantly during the study.
Adult↗
Review: the treatment of hepatocellular carcinoma.
Surgical resection offers the only realistic hope of cure in hepatocellular carcinoma (HCC) but is usually not possible, either because the tumour is widespread throughout the liver at diagnosis, or because liver function is adversely affected by concomitant cirrhosis. The results of operation in early asymptomatic disease are, however, encouraging and efforts should be made to screen regularly the cirrhotic population at risk of HCC development. The prognosis for inoperable patients remains gloomy, though exciting new treatment methods exist which require extensive evaluation. An anthracycline given as single agent intravenous therapy is probably the current treatment of choice for inoperable patients, though only 20-30% will show a response. Intra-arterial therapy has not yet been convincingly shown to have any advantages over intravenous therapy. The evaluation of clinical trials in HCC would be made easier if response criteria were standardized and universally adopted, and if trials were properly controlled and of sufficient sample size to test adequately the hypothesis in question. This review deals only with the specific treatment of HCC. HCC prevention, the early diagnosis of HCC, and the relief of symptoms in HCC, though areas of obvious importance, are outside the scope of this review.
Carcinoma, Hepatocellular↗
Conductive education for motor disorders.
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Child↗
In vitro and in vivo tumour localisation with a monoclonal antibody directed against a membrane antigen on the human hepatocellular carcinoma cell line PLC/PRF/5.
A monoclonal antibody, designated K-PLC1, has been produced to a tumour-associated antigen on the cell membrane of the PLC/PRF/5 cell line. Using an indirect immunofluorescence technique this antibody produced membrane staining of three hepatocellular carcinoma (HCC) cell lines and it has positively stained 10 of 11 human HCC biopsy specimens. In vitro, 125I-labelled K-PLC1 binds specifically to PLC/PRF/5 cells, as shown by competitive inhibition experiments. Tumours derived from the PLC/PRF/5 cell line were grown in nude mice and groups of tumour-bearing animals were injected with either [125I]K-PLC1 or [125I]mouse IgG, and then killed at 1, 4 or 7 days post injection. Bound radioactivity was counted in a variety of solid organs. Tumour:liver ratios for K-PLC1 were greater than those for mouse IgG at each time point, the differences being greatest on day 4 (ratio K-PLC1 4.4 +/- 0.93, ratio mouse IgG 1.53 +/- 0.60, mean +/- SD, P less than 0.05). The amount of [125I]K-PLC1 bound was greater in the tumour than in any other solid organ, the differences again being maximal on day four. Blood pool radioactivity however remained high throughout the study period. We conclude that anti-HCC monoclonal antibodies may be of value as immunodiagnostic and immunotherapeutic agents in human HCC.
Animals↗
Human lymphoblastoid interferon does not increase survival when added to mitozantrone in the treatment of hepatocellular carcinomas.
Human lymphoblastoid interferon, in an initial dose of 2.5 MU m-2 weekly i.m., was given with mitozantrone 12 mg m-2 i.v. every 3 weeks to 15 patients with hepatocellular carcinoma. The survival curve for these patients was worse than that of 15 patients previously treated with mitozantrone alone; there were more long-term survivors in those not given interferon; more side-effects were seen in the group given interferon. The addition of interferon to mitozantrone in the management of hepatocellular carcinoma is not recommended.
Adolescent↗
Natural killer cell activity in hepatocellular carcinoma. In vitro and in vivo responses to interferon.
We have measured natural killer (NK) cell activity in patients with hepatocellular carcinoma (HCC) and have examined the effects of in vitro and in vivo administration of alpha-interferon (IFN) on NK cell activity. The NK cell cytotoxicity of HCC patients was significantly lower than that of patients with cirrhosis or healthy controls. Reduced NK cell cytotoxicity in HCC did not correlate significantly with either the serum alpha-foetoprotein concentration or the patient WHO performance grade. NK cell cytotoxicity in all groups could be increased by prior incubation of effector cells with IFN, but this was significant only in HCC patients, in whom 10 IU/ml of IFN increased NK cell cytotoxicity from 37 +/- 10% to 53 +/- 8% (effector to target ratio, 50:1, mean +/- SEM; p less than 0.05). Further increases in IFN concentration failed to increase NK cell activity further. NK cell cytotoxicity was measured immediately before and 24 h after 2.5 x 10(6) IU/m2 of IFN was given subcutaneously to four HCC patients. NK cell cytotoxicity rose from 27 +/- 9% to 61 +/- 5% (effector to target ratio, 50:1, mean +/- SEM; p = 0.05).
Carcinoma, Hepatocellular↗
Hepatocellular carcinoma and the hepatitis B virus: a study of British patients.
We have examined the relationship between hepatitis B virus infection and hepatocellular carcinoma in a series of 50 British patients with histologically-proven hepatocellular carcinoma. Serum HBsAg was detected in 10 patients (20 per cent), and of the remainder, 21 per cent of those tested had serological evidence of past hepatitis B virus exposure. None of nine tumour specimens from serum HBsAg negative patients had detectable HBV-DNA integration into the tumour cell genome. The presence or absence of serum HBsAg was of no prognostic significance in British patients with hepatocellular carcinoma. Liver cell dysplasia, a possible pre-malignant lesion, was noted in 53 per cent of patients who had had liver biopsies before the diagnosis of hepatocellular carcinoma, and in 79 per cent of biopsies taken at the time of diagnosis of hepatocellular carcinoma. The presence of liver cell dysplasia was not more common in serum HBsAg positive patients.
Adolescent↗
Human lymphoblastoid interferon. In vitro and in vivo studies in hepatocellular carcinoma.
We have examined the growth inhibitory effects of human lymphoblastoid interferon (IFN) on the human hepatocellular carcinoma (HCC) cell line PLC/PRF/5. In vitro, PLC/PRF/5 cells were sensitive to the antiproliferative effects of IFN, growth inhibition being noted at concentrations as low as 1.25 i.u. ml-1. Athymic mice with xenografted tumours derived from the PLC/PRF/5 cell line were treated daily with IFN or a saline control. An IFN dose of 2 X 10(5) i.u./day was found capable of significantly slowing tumour growth rate and prolonging mouse survival. Further studies to examine the mechanisms involved in growth inhibition in vivo demonstrated that IFN was capable of inducing the activity of the enzyme 2,5-oligoadenylic acid (2,5 A) synthetase, a potent inhibitor of protein synthesis, in tumour xenografts but not in mouse tissue, and that IFN significantly enhanced the membrane display of HLA class I glycoproteins on tumour cells, though histology did not reveal any increase in tumour infiltration by host lymphocytes. We conclude that IFN exerts potent growth inhibitory effects on the HCC cell line PLC/PRF/5 both in vitro and in vivo and its mode of action in this animal model system appears to be predominantly mediated by a direct antiproliferative effect on tumour cells.
2',5'-Oligoadenylate Synthetase↗
Mitozantrone as single agent therapy in hepatocellular carcinoma. A phase II study.
Thirty-five patients with hepatocellular carcinoma (HCC) have been treated with the Anthracenedione derivative, Mitozantrone. One complete and 5 partial responses were seen in 22 evaluable patients and in a further 4 patients tumour size remained static for lengths of time ranging from 13 to 42 weeks. Therapy was well tolerated. Bone marrow suppression was dose-limiting but easily managed by dose reduction. Other acute toxicity was rare, vomiting and hair loss being reported only once each. Cardiac 'events' occurred in 5 patients, 3 of whom had received high total cumulative doses of Mitozantrone. We conclude that Mitozantrone is of clinical benefit in HCC and that its usage is compatible with a good quality of survival. Its cardiotoxic potential requires further evaluation.
Adult↗