Biomedical subjects
M C Kew
Publications and source records attributed to M C Kew.
Hepatitis B virus status of black women with hepatocellular carcinoma.
The reason why hepatocellular carcinoma occurs less frequently in women than in men is unknown. The possibility that differences in the hepatitis B virus status between men and women with this tumor might be important in this regard was investigated in 75 black women and 75 age- and ethnically-matched men with hepatocellular carcinoma. Prevalences of hepatitis B surface antigen, core antibody alone, and total hepatitis B virus markers were not significantly different in the two sexes. It is concluded that women with hepatocellular carcinoma are just as likely as men to be, or to have been, infected with hepatitis B virus. Because the hepatitis B virus and contraceptive steroids might conceivably act as cocarcinogens, the age distribution of women with hepatocellular carcinoma was determined. Thirty-nine percent were of child-bearing age. Of these, 44% were positive for surface antigen and 17% for core antibody alone. Ninety percent of these women had one or more hepatitis B virus markers.
Uptake of Tc-99m di-isopropyliminodiacetic acid by hepatocellular carcinoma: concise communication.
Uptake of Tc-99m di-isopropyliminodiacetic acid (DISIDA) by hepatocellular carcinoma was assessed in 30 patients showing obvious liver defects on a Tc-99m tin colloid image. In none of these patients was there complete "filling in" of the defects, and even partial "filling in" occurred in only 11 (36.7%). There was no uptake of Tc-99m DISIDA by the primary tumor in the remaining 19 patients (63.3%). In 19 of the 30 patients an attempt was made to correlate the degree of histologic differentiation of the tumor with the uptake of DISIDA by the tumor. No difference in uptake could be demonstrated between well, moderately, and poorly differentiated tumors. Tc-99m DISIDA was not taken up by pulmonary metastases in the only two patients tested. We conclude that imaging with Tc-99m DISIDA in conjunction with Tc-99m colloid is of no value in the specific diagnosis of hepatocellular carcinoma.
Fatal heat-stroke in a child taking appetite-suppressant drugs.
An 11-year-old girl who was taking two appetite-suppressant agents as part of a weight-reducing regimen developed heat-stroke while taking part in a 'nature hike' at an ambient temperature of 34 degrees C. The other 107 participating children suffered no significant ill-effects. Sympathomimetic amines used as appetite suppressants can produce heat intolerance by two mechanisms: they increase endogenous heat production as a result of their stimulatory effects on the central nervous system, and they impede the dissipation of heat from the body by producing peripheral vasoconstriction.
Carcino-embryonic antigen in hepatocellular carcinoma. Report of a patient with very high serum concentrations.
Serum carcino-embryonic antigen (CEA) concentrations are frequently raised in patients with hepatocellular carcinoma, but the degree of elevation is slight or moderate. In contrast, patients with hepatic metastases from colonic carcinomas and various other entodermal and non-entodermal tumours have very high serum values. This difference may be useful in the differential diagnosis between primary and metastatic liver carcinomas. However, exceptions do occur, as shown by the present report of a patient with hepatocellular carcinoma who had a serum CEA concentration of 1,600 ng/ml.
Serum immunoreactive calcitonin concentrations in hepatocellular carcinoma.
Having found raised serum calcitonin concentrations in 94% of patients with hepatocellular carcinoma when using a dextran-coated-charcoal radio-immunoassay, we have now repeated the study, using a double-antibody radio-immunoassay, in 102 further patients with hepatocellular carcinoma and 35 matched controls. Serum immunoreactive calcitonin concentrations (iCT) in the controls ranged from 10 to 310 pg/ml (mean 154.6 pg/ml). Values in the tumour patients ranged from 10 to 1,650 pg/ml (mean 302.6 pg/ml). The mean figures were significantly higher in the tumour patients (P less than 0.001), 35.5% of them having values above 310 pg/ml. In 65 of the patients serum iCT concentrations were also determined by dextran-coated-charcoal radio-immunoassay. Values ranged from 10 to 10,780 pg/ml (mean 2,179 pg/ml). If 1,000 pg/ml is taken as the upper limit of normal, 69% of the patients had raised iCT concentrations. There was a good correlation (r = 0.67; P less than 0.001) between serum iCT values measured with both methods in 50 patients. If measured by the double-antibody radio-immunoassay method, the serum calcitonin value is not useful as a marker for hepatocellular carcinoma.
Oral contraceptives and hepatocellular carcinoma.
A 23-year-old woman was seen with an acute hemoperitoneum caused by rupture of a hepatocellular carcinoma. She died two years after hepatic artery ligation. The patient had been taking oral contraceptives for periods of one year and ten months, separated by a pregnancy. The association between oral contraceptive steroids and hepatocellular carcinoma is briefly reviewed.
Hepatitis-B virus infection in black children with hepatocellular carcinoma.
The hepatitis B virus (HBV) status of six unselected South African Black children, aged 10 to 16 years, with hepatocellular carcinoma (HCC) was investigated. The characteristics of the tumor were similar to those seen in Black adults. Hepatitis B surface antigen and antibody to the core antigen were present in the serum of all the children, and hepatitis Be antigen was detected in four of the children. The serum of the two patients without e antigen was positive for e antibody, and all sera were negative for hepatitis B surface antibody. Taken in conjunction with the HBV status of southern African Black adults with HCC, these findings raise the possibility that nearly all, if not all, Black patients with this tumor are or have been infected with HBV. Moreover, if HBV is oncogenic, tumor formation may occur within 10 years of the initial infection, which occurs in early childhood in southern African Blacks.
Hepatocellular carcinoma in rural southern African blacks.
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Nonspecific blinding of insulin to gamma globulin in the serum of black patients with hepatocellular carcinoma and other forms of liver disease.
The study was prompted by the apparent detection of insulin antibodies in a black patient with HCC and recurrent hypoglycemia who had never received insulin. It consisted of two parts. Initially the sera of 30 individuals (six normoglycemic HCC patients, three with HCC and recurrent hypoglycemia, 11 patients with noncancerous liver diseases, and 10 healthy black controls) were analyzed for the presence of insulin (and glucagon) antibodies by precipitating the bound, labeled hormone with ethanol and also by the technique of radioimmunoelectrophoresis. In the nine HCC patients, binding of 125I-insulin averaged 13% by ethanol separation and 0.018 mU/ml with radioimmunoelectrophoresis, levels that were similar to those of patients with noncancerous liver disease and significantly higher than those of the healthy controls. Mean binding of 125I-glucagon was 11% in HCC sera. Serum binding of labeled hormones correlated significantly with IgG concentrations in the patients. The second part of the study attempted to define the nature of insulin binding in HCC and other forms of liver disease. After confirmation of the increased serum binding of labeled insulin by another method of precipitation, PEG, an attempt was made to compete with the labeled insulin for its serum binding sites by adding a large amount of unlabeled insulin. This binding was not displaceable, however, and was therefore considered nonspecific. When the same procedures were repeated using normal serum to which increasing amounts of gamma globulin were added, the nonspecific binding of insulin increased in a linear fashion. Furthermore, a similar degree of high nonspecific insulin binding occurred in six patients with multiple myeloma and raised serum IgG concentrations. We therefore conclude that in the many clinical situations where hypergammaglobulinemia exists, false positive tests for the detection of antibodies against insulin (and probably other peptide hormones) will emerge unless appropriate methods are used to check for nonspecific peptide binding.
Systemic manifestations of malignant disease.
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Absorption of biliary cobalamin in baboons following total gastrectomy.
Absorption of radiolabeled cobalamin in baboons was assessed by whole body counting. Retention of biliary cobalamin and an aqueous solution of cyanocobalamin was measured in normal baboons and in baboons after total gastrectomy by using 57Co-labeled biliary cobalamin and 58C0-cyanocobalamin, with and without baboon gastric juice containing intrinsic factor. Radiolabeled biliary cobalamin was obtained by intravenous injection of 57Co-cyanocobalamin in baboons and collection of bile through a cannula placed in the common bile duct. Cobalamin absorption was not completely abolished by gastrectomy and biliary cobalamin was better retained than cyanocobalamin; intrinsic factor enhanced absorption of both forms. After gastrectomy there was steady depletion of liver and serum cobalamin levels, which ceased after a new equilibrium was reached between a progressively diminishing cobalamin loss and the impaired but significant residual level of absorption. These studies in the nonhuman primate provide further information concerning the enterohepatic circulation of cobalamin and suggest that the form of cobalamin in bile may be more readily absorbed than is cyanocobalamin or that bile itself may have an enhancing effect on cobalamin absorption. The data also suggest that physiologically significant amounts of cobalamin may be absorbed in the absence of a gastric source of intrinsic factor.
Integration of hepatitis B virus DNA into the genome of liver cells in chronic liver disease and hepatocellular carcinoma. Studies in percutaneous liver biopsies and post-mortem tissue specimens.
We used recombinant-DNA technology and gel electrophoresis to find hepatitis B virus DNA (HBV-DNA) in liver and tumor tissue from patients with hepatocellular carcinoma and chronic liver disease, and to study the integration of HBV-DNA into the genome of these tissues' cells. In 12 patients with hepatocellular carcinoma who had hepatitis B surface antigen (HBsAg) in their serum, integrated HBV-DNA was identified in the tumors; it was also found in tumors from three of eight patients who were seronegative for HBsAg but positive for antibody to HBsAg. In some cases, integrated HBV-DNA was also present in nontumorous liver tissue that had the same hybridization pattern or one different from that of the tumor. In five carriers of HBsAg who had evidence of the carrier state and chronic liver disease for less than two years, HBV-DNA was present but not integrated in liver tissue. In the two patients who had carried HBsAg for more than eight years, HBV-DNA was integrated into the host genome. These data suggest that integration of HBV-DNA into hepatocytes occurs during the course of persistent HBV infection and precedes development of gross neoplasm.
Monoclonal gammopathy associated with idiopathic stenosing papillitis. A case report.
Stenosing papillitis is a recently recognized cause of obstructive jaundice. Although many liver disorders are associated with a polyclonal increase in serum immunoglobulin levels, a monoclonal increase is relatively rare. A patient with monoclonal gammopathy associated with idiopathic stenosing papillitis is reported. The gammopathy has persisted for 3 years after surgical relief of the obstructive jaundice.
Hepatitis B virus-associated liver disease after renal transplantation.
A retrospective analysis of the first 200 recipients of renal transplants at the Johannesburg Hospital showed that 23 (11,5%) were chronic carriers of the hepatitis B virus (HBV) and a further 10 (5%) had previously been exposed to the virus as evidenced by detectable concentrations of antibody to the hepatitis B surface antigen in their serum. In no patient did graft function appear to suffer as a result of chronic HBV infection. However, 7 of the patients with hepatitis B surface antigenaemia had biochemical evidence of liver dysfunction. In 3 of these patients liver tissue was examined histologically; 2 had a macronodular cirrhosis and 1 chronic persistent hepatitis. One further patient developed acute fulminant B virus hepatitis and was the only one who died of liver failure in either group. Chronic infection with HBV may cause liver disease in renal transplant recipients, and strict techniques to limit the spread of the virus in renal transplant and dialysis units should continue to be enforced.
Cyclic nucleotides in biological fluids in hepatocellular carcinoma.
To investigate the prediction that urinary cGMP (UcGMP) and cAMP (UcAMP) excretion is altered in a manner consistent with unregulated cell growth in hepatocellular carcinoma (HCC), we studied 31 patients with this disease, 25 without apparent disease, 16 with various hepatic diseases, and 16 with nonhepatic neoplasms. Results were expressed as UcGMP excretion per 100 ml glomerular filtration because reduced creatinine excretion in patients with muscle wasting or renal dysfunction may spuriously elevate UcGMP. UcGMP excretion was elevated in 80% of patients with HCC, 75% of patients with hepatic disease and 68% of patients with other neoplasms. Mean values for UcAMP excretion did not differ significantly from normal values. Plasma and ascitic fluid cGMP concentrations in HCC and hepatic diseases were raised. These results support the hypothesis of a shift in cyclic nucleotide metabolism toward cGMP in malignant diseases. However, UcGMP measurement does not detect progression of cirrhosis to HCC.
The hepatitis-B virus and hepatocellular carcinoma.
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Hepatocellular cancer in Southern African blacks: HBeAg, anti-HBe, IgM-anti-HBc and other markers of hepatitis B.
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