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Biomedical subjects

A Forbes

Publications and source records attributed to A Forbes.

At least 199 records · Page 11Linked to original sources
PubMed1989

Thiopental infusion in the treatment of intracranial hypertension complicating fulminant hepatic failure.

Intracranial hypertension complicating fulminant hepatic failure has a mortality in excess of 90% in the presence of renal failure if not rapidly responsive to mannitol and ultrafiltration. Based on data which suggest that barbiturates can be of value in controlling the intracranial hypertension of head injury, intravenous thiopental was assessed in 13 patients with fulminant hepatic failure. All had developed acute renal failure complicated by intracranial hypertension unresponsive to other modes of therapy and were likely by all published criteria to have little chance of survival. The dosage of thiopental was adjusted incrementally until intracranial pressure, measured by extradural transducers, fell to within normal limits or adverse hemodynamic changes occurred. The intracranial pressure was reduced, in each case, by 185 to 500 mg (median: 250 mg) thiopental given over 15 min, and in eight cases continuing infusion achieved stable normal intracranial pressure and cerebral perfusion pressure. Five of the patients made a complete recovery and there were only three deaths from intracranial hypertension. Side effects were few and included minor hypotension controlled by dose reduction. The response of otherwise intractable intracranial hypertension and the 38% survival rate was remarkable for a group of patients with such a poor prognosis.

Adult↗
PubMed1989

Investigation of upper gastrointestinal symptoms in patients with AIDS.

Double contrast barium radiology and upper gastrointestinal endoscopy were compared prospectively on 45 occasions in patients infected with HIV who presented with upper gastrointestinal symptoms. In 40 cases, a definite pathological diagnosis was reached and in four cases no organic basis for symptoms could be found. A correct and complete diagnosis was made on visual endoscopic criteria in 43 cases (95.5%) but in only 14 cases (31.1%) from barium studies alone. Radiology showed no abnormality in 22 cases where pathological changes were documented (oesophageal candidiasis in 21 cases). Where pathological confirmation of diagnosis existed (40 cases), endoscopy (without pathological support) had a sensitivity of 97.5% and a specificity of 100% compared with the sensitivity and specificity of 25 and 100% for barium studies. The difference between the sensitivities of the two methods was highly significant (P less than 0.005). The combination of oral candidiasis and upper gastrointestinal symptoms without dysphagia or weight loss was so strongly associated with uncomplicated oesophageal candidiasis (negative predictive value 93%; P less than 0.025), that this is supported as a basis for therapy without the need for further investigation, although if upper gastrointestinal investigation is required, endoscopy should be the method of choice.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Safety and efficacy of acetarsol suppositories in unresponsive proctitis.

In a prospective open study, 10 patients with intractable proctitis were treated with acetarsol suppositories (250 mg b.d. for 4 weeks) and were monitored clinically, biochemically and toxicologically. Proctitis resolved symptomatically and sigmoidoscopically within 2 weeks in nine patients; one patient was unaffected. The only side-effect was of transient thrombocytosis in a single patient. Maximal blood and urinary arsenic concentrations occurred after 1 week's treatment with a total inorganic arsenic in the hazardous range in six patients; subsequent concentrations fell despite continuing therapy and at 4 weeks potentially hazardous values persisted in only two patients. Continued renal excretion and diminished absorption across an improved rectal mucosa is thought to be responsible for this paradox. Arsenic levels fell rapidly when acetarsol was withdrawn and were indistinguishable from pretreatment values within 4 weeks. Short-term acetarsol therapy offers a useful additional measure when local steroids have failed to control ulcerative proctitis; it appears to be safe and formal controlled comparisons with other therapeutic options are therefore legitimate.

Adult↗
PubMed1988

Elevation of serum sex hormone-binding globulin in females with fulminant hepatitis B virus infection.

Amongst adults exposed to the hepatitis B virus (HBV), the infection pursues a fulminant course more frequently in females, while conversely a chronic carrier state is more frequent in males. Because of these differences in sex ratio, we investigated the relationship between the outcome of HBV infection and serum concentrations of sex hormone-binding globulin (SHBG), a circulating glycoprotein that exerts an important influence on the balance of free sex hormones. SHBG levels were significantly elevated in females with fulminant HBV infection compared to females with either uncomplicated acute or chronic HBV infection (P less than .05 and P less than .001, respectively). That this was not a nonspecific effect of fulminant hepatitis was confirmed by the significantly higher levels in this group than in age-matched females with fulminant hepatitis unrelated to HBV (P less than .05). In contrast, four of 15 female HBsAg carriers had SHBG values in the male range, and these included three of four patients who had acquired HBV as adults. SHBG levels were normal in all male groups. These results suggested that for adults the hormonal environment may be important in determining the course of HBV infection.

Acute Disease↗
PubMed1988

The role of ultrasound scanning in management after liver transplantation.

A total of 368 ultrasound scans in 72 patients following liver transplantation have been reviewed. Thirty-seven intra-abdominal fluid collections were identified. Twenty-four resolved spontaneously and 13 required aspiration under ultrasound control. Dilated bile ducts were seen in 22 patients, 11 of whom required further intervention. The main indications for intervention post-transplantation were increasing or late onset (after 3 months) duct dilatation. Recurrent or persistent fluid collections particularly in the right subhepatic space also indicate further investigation. Twelve ultrasound-guided liver biopsies were performed to detect rejection or tumour recurrence. Eight cases of portal vein anastomotic narrowing and three abnormalities of the inferior vena cava were also detected.

Adolescent↗
PubMed1988

An analysis of cyclosporine efficacy and toxicity after liver transplantation.

The use of cyclosporine long term after orthotopic liver transplantation has been analyzed in 73 adults with particular reference to the dose of drug used, either alone or in combination with other immunosuppressive agents, and the side effects observed. The first 22 patients were given cyclosporine 10 mg/kg/day for up to 2 years, but thereafter in these, and in all the other patients, the drug dose was regulated by whole blood trough levels. The proportion of patients maintained on cyclosporine alone increased from 11% at 3 months to 54.9% and 55.6% at 3 and 4 years, respectively. The dose of prednisolone used in combination with cyclosporine was lower than that used with azathioprine (P less than 0.05) up to 12 months after transplantation, but thereafter no significant difference was found. Acute cellular rejection was seen in 5 patients and in all instances was related to cessation of cyclosporine, while 10 patients developed chronic graft rejection manifested by the vanishing bile duct syndrome. At 12 months and onward, 54.5-73.3% of patients had normal serum bilirubin levels, and 47.6-80.0% had aspartate aminotransferase levels in the normal range. Cyclosporine was discontinued in 12 patients, in 8 cases because of impairment of renal function or hypertension. A trend toward rising serum creatinine levels was seen, and after 4 years on cyclosporine none of 12 patients had normal levels, and these exceeded 200 mumol/L in 5. The rise in creatinine levels was probably in part related to the higher doses used early in the study period. The incidence of hypertension progressively increased from 15.3% at 3 months to 63.6% at 4 years in patients maintained on cyclosporine.

Adolescent↗
PubMed1988

Metastatic islet cell tumour with clinical manifestations of insulin and glucagon excess: successful treatment by hepatic artery embolization and chemotherapy.

A patient with a metastatic islet cell tumour with clinical features of both insulin and glucagon excess is reported. This appears to be only the third such case in the literature and the first in whom the initial symptoms were of the glucagonoma syndrome. Radiologically and biochemically defined complete remission was induced within 9 months of hepatic arterial embolization and cyclical chemotherapy with 5-fluorouracil and streptozocin; complete remission has been maintained for a further 23 months without therapy.

Adenoma, Islet Cell↗
PubMed1988

Hepatic haemangioma: a critical review of diagnosis and management.

Twenty-four adults (10 male; age 27-65 years, median 43.5) with hepatic haemangioma are reviewed. Fifteen had right hypochondrial pain (lesions 8 cm or more in diameter in nine). Six lesions were found incidentally, at ultrasound examination or elective cholecystectomy. Diagnosis, from ultrasonic and angiographic appearances, was confirmed in 12 by percutaneous biopsy without complication. Eleven patients were followed untreated for up to 60 months (median 24 months): lesion size (median 2.5 cm) did not change and all remained well. Surgical resection succeeded in two of three patients; the third and eight other patients (seven with symptoms) with lesions 3 to 30 cm in diameter were selected for Gelfoam embolization. Transient minor side effects preceded improvement in most, but two patients (with lesions of 20 cm or greater in diameter) developed multiple liver abscesses: recovery was protracted. Embolization failed in three; two remain well, untreated, to 24 and 51 months. Two patients had hepatic artery ligation, one with radiotherapy. Further imaging at from eight to 60 months (median 24) showed little change in lesion size or vascularity with any non-resectional technique. Expectant management of small asymptomatic haemangiomas appears appropriate. Embolization may reduce pain but the risk of abscess formation is high for large tumours, and reduction in size or vascularity of lesions is unlikely whatever their initial diameter.

Adult↗
PubMed1987

Interactions of foetal steroid binding protein with other binding proteins in human serum.

Foetal steroid binding protein (FSBP) which is present in normal human serum sometimes exhibits unusual sex-steroid binding; its effects on steroid action are uncertain but potentially important in view of the different levels seen in populations at different risk of breast cancer. Studies of the binding of 5 alpha-dihydrotestosterone to FSBP were conducted at varying concentrations of human serum albumin (HSA) and sex hormone binding globulin (SHBG). The saturable, specific binding of purified FSBP (Ka approximately equal to 5 X 10(8) l/mol), was transformed to a rising, plateau pattern by the addition of HSA. In equilibrium dialysis, FSBP competed with HSA or SHBG in a strictly proportional way when the third protein was absent. In the presence of HSA an initial sharp shift of ligand from SHBG to FSBP was observed with increasing FSBP concentration, but this was reversed as higher levels were reached. Steroid binding by FSBP in vivo may be determined predominantly by its interactions with other binding proteins.

Blood Proteins↗
PubMed1987

Response to cyproterone acetate treatment in primary hepatocellular carcinoma is related to fall in free 5 alpha-dihydrotestosterone.

The male preponderance in cirrhotic patients with primary hepatocellular carcinoma (HCC) and the presence of androgen receptors in tumour tissue suggest possible benefit from anti-androgenic therapy. Twenty-five cirrhotic patients with irresectable HCC (23 male) were treated with cyproterone acetate (CPA) 300 mg daily. Hepatic ultrasound, alpha-fetoprotein and total and free sex steroid levels were monitored. Five patients had an objective response to therapy with a median duration of 8 weeks and survival in excess of 29 weeks. Median survival for all patients was 14 weeks. Apart from transient paranoia in two cases, side-effects were minimal. Total androgen levels (measured in 13 patients) had fallen significantly at 10 weeks, but free 5 alpha-dihydrotestosterone (DHT) which had fallen by 4.8 pM (median) in five responders, had risen by 5.05 pM in eight non-responders: P less than 0.025. The apparent correlation of response with reduction in free DHT suggests that hormonal manipulation may be effective in HCC if free DHT is reliably reduced. This has been achieved in other conditions by the combination of CPA with low dose oestrogen or with LHRH agonists.

Adult↗
PubMed1987

Chemotherapy and radiotherapy of malignant hepatic tumours.

Cure of primary liver tumours remains possible only by surgery and early diagnosis will therefore continue to be important; the value of regular screening of cirrhotic patients for development of HCC by ultrasound scanning and estimation of AFP is now established. Prognosis of irresectable HCC depends largely on the general condition of the patient at the time of diagnosis and is better in the absence of cirrhosis. Radiotherapy has little role in the management of patients with HCC, but benefit with acceptable morbidity may be obtained from parenteral chemotherapy, with doxorubicin or its derivatives used as single agents, or with a combination of 5-FU and methyl-CCNU. There may be advantage from regional therapy given via the hepatic artery and early results from the combination of embolization with arterial doxorubicin are encouraging. The use of radiolabelled antibodies to tumour-related determinants of hormonal manipulation show promise. Worthwhile results from the non-surgical management of peripheral (intrahepatic) cholangiocarcinoma and primary hepatic sarcoma remain scarce. Isolated hepatic metastases from colorectal primaries may be resectable; for those that are not, results from regional chemotherapy with 5-FU or FUDR are encouraging, but cost and high morbidity currently limit more general application.

Adenoma, Bile Duct↗
PubMed1987

HLA antigens in chronic pancreatitis.

Since immunological and hereditary factors may be important in chronic pancreatitis, histocompatibility antigens of classes I and II were studied in 50 British Caucasian patients, after exclusion of insulin-dependent diabetics for whom HLA associations are recognised. Chronic pancreatitis was defined by at least two independent criteria, and only subjects with alcohol-related and idiopathic disease were included. In 22 patients (21 male), weekly ethanol intake had chronically exceeded 100 g (usually substantially so); the remaining 28 had idiopathic chronic pancreatitis (ICP). Twenty patients (40%) had autoantibodies, in 11 (22%) to gastric parietal cells. Nine of those with ICP (three male) had parietal cell antibody, more than expected for the age/sex distribution. There were overall increased frequencies of HLA Cw5 and B44. In ICP there were increased frequencies of HLA A25 and Cw1, and a decreased frequency of B7. In patients with alcohol-related disease there were increased frequencies of Cw5 (50.0% vs control 15.9%), B44 (54.5% vs 29.4%), and DR4 (61.1% vs 33.6%). The increased frequency of Cw5 in alcohol-related disease alone remained significant after correction (p less than 0.05). A hypothesis that hereditary and possibly immunological factors may contribute to the aetiology of chronic pancreatitis is supported.

Alcoholism↗
PubMed1987

Hepatic sarcomas in adults: a review of 25 cases.

Twenty-five patients with an apparently primary sarcoma of the liver are reviewed. Presenting complaints were non-specific, but hepatomegaly and abnormal liver function tests were usual. Use of the contraceptive pill (four of 11 women) was identified as a possible risk factor; one patient had previously been exposed to vinyl chloride monomer. Detailed investigation showed that the primary tumour was extrahepatic in nine of the 25 patients. Distinguishing features of the 15 patients with confirmed primary hepatic sarcoma included a lower incidence of multiple hepatic lesions and a shorter time from first symptoms to diagnosis, but the most valuable discriminator was histology. Angiosarcomas and undifferentiated tumours were all of hepatic origin, epithelioid haemangioendotheliomas (EHAE) occurred as primary and secondary lesions and all other differentiated tumours arose outside the liver. The retroperitoneum was the most common site of an occult primary tumour and its careful examination therefore crucial: computed tomography scanning was found least fallible in this respect in the present series. Where resection (or transplantation), the best treatment, was not possible, results of therapy were disappointing, prognosis being considerably worse for patients with primary hepatic tumours. Patients with EHAE had a better overall prognosis regardless of primary site.

Adolescent↗
PubMed1987

Effect of cirrhosis on accuracy of 99Tcm-tin colloid scintigraphy and ultrasound scanning in diagnosis of hepatocellular carcinoma.

The effect of cirrhosis on the accuracy of ultrasonography and scintigraphy in the diagnosis of hepatocellular carcinoma (HCC) has not been established. We have therefore studied the findings on ultrasound and scintigraphy in four groups of patients. Fourteen had HCC and cirrhosis, 13 had HCC but no cirrhosis, 53 had cirrhosis but no HCC and 31 had evidence neither of cirrhotic nor malignant liver disease. The accuracies of a positive interpretation of HCC on ultrasound and scintigraphy in the absence of cirrhosis were 85% and 66% respectively (NS), but fell (significantly in the case of scintigraphy: p less than 0.05) to 80% and 31% respectively in the presence of cirrhosis (p less than 0.01). The poorer performance of scintigraphy in the presence of cirrhosis was a result both of its lower sensitivity (50% compared with 85%) and the greater frequency of false positives (28% vs 5%: p less than 0.001). The accuracy of a negative interpretation of HCC on scintigraphy in the absence of cirrhosis was 96% but fell to 84% in the presence of cirrhosis, whereas on ultrasound it remained the same (96%). In conclusion, we recommend ultrasound in preference to scintigraphy as a more accurate technique for the diagnosis of HCC in the presence of cirrhosis.

Carcinoma, Hepatocellular↗
PubMed1987

Foetal steroid binding protein in British and Japanese women.

In order to examine the newly-discovered sex-steroid binding protein, foetal steroid binding protein (FSBP) in different populations, its binding characteristics and its level were studied by two-tier column ligand binding assay and enzyme-linked immunosorbent assay (ELISA) respectively. In 10 Japanese premenopausal women, analysis of 5 alpha-dihydrotestosterone (DHT) binding in the Cibacron Blue 3GA-Sepharose 6B portion of the column showed a rising plateau pattern with a mean maximum binding of 31.1 +/- 7.41%, whereas of 9 similar British women, 8 displayed unsaturable, non-cooperative binding of 11.6 +/- 8.22% (P less than 0.01). After partial purification of FSBP in these samples, the protein exhibited saturable binding kinetics, median binding 25 (interquartiles 23-34) and 19 (13-25) nmol DHT/l in Japanese and British women, respectively (P less than 0.05). By analyzing FSBP by ELISA in 56 Japanese (45 premenopausal) and 59 British (25 premenopausal) women, higher levels were obtained in the whole Japanese group (P = 0.0016) and in the premenopausal Japanese women (P = 0.018) than in their British counterparts. In both nationalities, FSBP levels were higher in premenopausal women, and there was a significant negative correlation of FSBP with age in both populations, particularly in postmenopausal women. FSBP levels did not correlate with weight, parity, sex hormone binding globulin or albumin levels. The influence of FSBP on free steroid levels remains unclear, but some relationship with ovarian function seems a possibility.

Adult↗