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Biomedical subjects

M C Kew

Publications and source records attributed to M C Kew.

At least 109 records · Page 6Linked to original sources
PubMed1986

Hepatocellular carcinoma in urban born blacks: frequency and relation to hepatitis B virus infection.

Chronic hepatitis B virus infection is far less common in urban born than in rural born southern African blacks, who also have a high incidence of hepatocellular carcinoma. A case-control study was carried out to determine the relative frequency of hepatocellular carcinoma and its relation to hepatitis B virus infection in urban born blacks. Three hundred and ninety two black patients with hepatocellular carcinoma and matched controls seen at two city hospitals were classified by questioning as urban born or rural born. The ratio of rural born to urban born blacks among the controls was 1.1:1.0 (207/185), whereas in the patients with cancer the ratio was 4.8:1.0 (324/68) (p less than 0.0001). Analysis of the prevalence of hepatitis B markers in 62 urban born and matched rural born blacks with hepatocellular carcinoma showed no differences in the frequency of current or past hepatitis B virus infection. It is concluded that urban born blacks are less likely than rural born blacks to develop hepatocellular carcinoma, but when they do the tumour is equally likely to be related to infection with hepatitis B virus. The findings lend further support to an important role for chronic hepatitis B virus infection in the aetiology of hepatocellular carcinoma.

Adolescent↗
PubMed1986

The value of serum concentrations of tissue polypeptide antigen in the diagnosis of hepatocellular carcinoma.

Tissue polypeptide antigen (TPA) is a polypeptide isolated from malignant cells and found in high concentration in the serum of patients with various tumors. No information is available with respect to hepatocellular carcinoma (HCC). Serum TPA concentrations were measured in 290 patients with HCC, 85 healthy controls, 33 patients with amebic hepatic abscesses, 43 with chronic hepatitis or cirrhosis, and 39 with acute hepatitis. Raised values were found in 96% of the HCC patients, but also in 61% of patients with amebic abscesses, 86% with chronic hepatic parenchymal disease, and 90% with acute hepatitis. If a cut-off level of 500 IU/L was used, this reduced the sensitivity of TPA in HCC to 46%, but still left 46% of patients with acute hepatitis with raised values. TPA is comparable in sensitivity with alpha-fetoprotein as a marker for HCC, but its lack of specificity severely limits its clinical usefulness.

Adolescent↗
PubMed1986

Prevalence of hepatitis B virus infection among black children in Soweto.

Roughly 15% of black children in rural areas of southern Africa are carriers of the hepatitis B virus. The purpose of the present study was to determine the prevalence of chronic hepatitis B virus infection among urban black children born and growing up in Soweto. A total of 2364 children were studied, ranging in age from 3 to 19 years, and of these, 1319 (56%) were girls. The children were drawn from the highest and the lowest socioeconomic classes. Serum samples were tested for all hepatitis B virus markers as well as IgG antibody against hepatitis A virus. HBsAg was detected in 23 (0.97%) of the children, anti-HBc and anti-HBs together in 155 (6.6%), anti-HBc alone in 17 (0.7%), and anti-HBs alone in 72 (3%). Of the 2364 children, 2097 (88.5%) were negative for all hepatitis B virus markers. IgG antibody to hepatitis A virus was present in 175 (97%) of a sample of 179 children. There was no difference in prevalence of hepatitis B virus markers between children from the upper and lower socioeconomic classes. HBsAg was more common in boys (16 out of 1043 (1.5%) than girls (seven out of 1321 (0.57%), and the prevalence of all hepatitis B virus markers increased with age. The youngest carrier of hepatitis B virus was 7 years old. The remarkable difference in the hepatitis B virus carrier rate between urban and rural black children offers a unique opportunity to investigate the favourable influences operating in an urban environment to limit the prevalence of hepatitis B virus infection.

Adolescent↗
PubMed1986

Small and asymptomatic hepatocellular carcinoma detected by alpha-fetoprotein screening in black hepatitis B carriers. A report of 2 cases.

Two patients in whom asymptomatic and small hepatocellular carcinomas (HCC) were detected by alpha-fetoprotein (AFP) screening are reported. Both patients were hepatitis B surface antigen-positive. In the first patient, the tumour grew slowly and was resected more than 2 years after a significant elevation in serum AFP levels had been first detected and 13 months after hepatic angiography confirmed the presence of a vascular tumour. In the second patient, a small encapsulated HCC was diagnosed by AFP screening and hepatic imaging. The clinical course in these 2 patients illustrates that small, asymptomatic and encapsulated HCCs do occur in southern African black hepatitis B carriers. Regular screening of patients at risk may be justified.

Adult↗
PubMed1986

Pityriasis rotunda. A cutaneous marker of hepatocellular carcinoma in South African blacks.

Although paraneoplastic phenomena occur frequently in patients with hepatocellular carcinoma, cutaneous changes have rarely been reported. During the past two years, ten South African blacks with hepatocellular carcinoma and pityriasis rotunda have been seen in a single hospital. The rash affected the trunk, especially the lower back and buttocks. The lesions ranged in size from 1.5 to 25 cm and were always multiple. They had a characteristic circular or arcuate configuration with scaling and varying degrees of hyperpigmentation. Pityriasis rotunda may prove to be a useful cutaneous marker of hepatocellular carcinoma in South African blacks.

Aged↗
PubMed1986

The effect of RU 41.740 (Biostim) on the production of interleukin-1 by monocytes and enriched large granular lymphocytes in normals and patients with hepatocellular carcinoma.

The effect of RU 41.740 on natural killer (NK) cell cytotoxicity from normals and patients with advanced hepatocellular carcinoma (HCC) was studied. RU 41.740-treated normal enriched large granular lymphocytes (LGLs) showed increased cytotoxic activity against 51Cr-labelled K562 cells. Although the drug increased the cytotoxic activity of LGLs from HCC patients, these results were not statistically significant. As LGLs have been shown to release interleukin-1 (IL-1) after suitable stimulation the effects of RU 41.740 on production of this cytokine from both monocytes and LGLs was studied. The drug stimulated IL-1 release from normal cells but monocyte and LGL IL-1 production from HCC patients was not influenced by RU 41.740 by RU 41.740. It is concluded, therefore, that although RU 41.740 can stimulate natural cytotoxicity and IL-1 production by normal LGLs, it is unable to correct the defect which exists in these functions in patients with large mass tumours.

Adjuvants, Immunologic↗
PubMed1986

Recombinant leucocyte interferon treatment of chronic hepatitis B. An analysis of two therapeutic trials.

We have investigated the efficacy of recombinant alpha-interferon treatment of chronic hepatitis B virus (HBV) infection in two therapeutic trials. Forty-four patients positive for HBsAg, HBeAg, DNA polymerase and HBV-DNA were studied. Fourteen carriers were treated in the first trial with doses ranging from 18 to 50 million units (mu)/m2 3 times per week. Six of 14 treated carriers (43%) have a sustained loss of HBeAg, HBV-DNA and DNA polymerase. Four lost HBsAg (29%). Two of 11 (18%) untreated carriers lost HBeAg, but none lost HBsAg (P = 0.05). Nineteen patients were entered in a second trial to assess dose response. Fourteen were treated with doses ranging from 2.5 to 10 mu/m2. Five patients were untreated. Two treated patients seroconverted to anti-HBe, and a third cleared HBsAg and seroconverted to anti-HBs. None of the controls was anti-HBe-positive. Thus 9/28 (32%) carriers have lost replicating HBV versus 2/16 (13%) of untreated patients. Elevated pretreatment serum ALT concentrations and severe chronic active hepatitis were associated with inhibition of viral replication in treated patients suggesting that seroconversion may require an appropriate host response. The efficacy of recombinant interferon is restricted, but it may be of benefit in a proportion of carriers.

Adult↗
PubMed1986

Detection of alpha-foetoprotein messenger RNA in human hepatocellular carcinoma and hepatoblastoma tissue.

Alpha-foetoprotein (AFP) synthesis, although repressed in normal adults, is increased in the majority of patients with hepatocellular carcinoma (HCC). We have investigated whether active transcription of the AFP gene may explain raised serum AFP concentrations in patients with HCC and hepatoblastoma by assaying human tumour and non-neoplastic tissue by molecular hybridization for the presence of mRNA encoding AFP. Ten operative HCC and six autopsy HCC specimens, two HCC cell lines, and one hepatoblastoma specimen were examined. Total cellular RNA and poly-(A)+ RNA were extracted and AFP mRNA sequences sought by dot-blot and Northern blot hybridisation to a human cDNA AFP probe. Cellular AFP was localised by avidin-biotin staining. AFP mRNA was detected in 8/10 operative specimens, as well as PLC/PRF/5 nude mouse tumours. Weaker hybridization was detected in 4/6 autopsy specimens. Signals of comparable intensity to that in operative tumours were detected in non-neoplastic tissue of 6 patients. AFP mRNA from nude mouse tumours migrated as a 20S discrete band on agarose gel electrophoresis, whereas a more complex hybridization pattern was evident in human tumours. Positive cytoplasmic immuno-staining for AFP was observed in 4 tumours and 2 corresponding non-neoplastic specimens and in a HCC cell line. In non-neoplastic liver, AFP was localised in cells that appeared dysplastic. Thus steady-state levels of AFP mRNA are detectable in human HCC tissue and surrounding non-neoplastic liver. These findings may prove pertinent to an understanding of the genetic expression of AFP in malignant hepatocytes, and the sequence of events leading to uncontrolled cellular proliferation.

Carcinoma, Hepatocellular↗
PubMed1986

The use of interferon functional assays in the laboratory monitoring of patients with hepatocellular carcinoma receiving interferon.

Patients with hepatocellular carcinoma receiving recombinant leukocyte alpha interferon therapy were monitored using a series of assays to evaluate various components of the interferon system. Pretherapy serum interferon concentrations were not elevated significantly in these patients, although elevated levels were recorded after initiation of therapy. Both before and after interferon treatment, the peripheral blood leukocytes of the patients were shown to be capable of producing both gamma and alpha interferon when appropriately stimulated in vitro. The patients' peripheral blood leukocytes also responded to interferon therapy, with 85% resisting viral replication after treatment was initiated. However, interferon did not appear to be of therapeutic value in these patients.

Adult↗
PubMed1986

Demonstration of post-traumatic bile leak using technetium-99m DISIDA.

A 25-year-old miner was admitted with an acute abdomen and marked pallor following a crush injury to the abdomen. CT showed an irregular, patchy appearance of the posterosuperior portion of the liver with a coefficient of density appreciably less than the rest of the liver, consistent with the presence of a hepatic hematoma. The patient was treated conservatively. During the two weeks that followed, fluid accumulated in the peritoneal cavity. At laparotomy, a large volume of bile- and blood-stained fluid was found in the peritoneal cavity. Tc-99m DISIDA imaging was done after laparotomy.

Adult↗
PubMed1986

The development of hepatocellular cancer in humans.

The biological characteristics of hepatocellular cancer vary appreciably in different parts of the world, but especially between regions with very high and low incidences of the tumour. Hepatocellular cancer is multifactorial in origin, and the pattern of its aetiological associations differs between populations at high and low risk. In Africans and Chinese, who have the highest incidences of hepatocellular cancer, the hepatitis B virus is the most important causal association. The viral carrier state is acquired during early childhood, and carries a relative risk for the development of the tumour of over 200. Integration of hepatitis B virus DNA probably acts as a genotoxic initiator in the multistep process of hepatocarcinogenesis, although the precise mechanisms involved have not been determined. Aflatoxin ingestion may also have an aetiological role in high incidence regions, probably as a genotoxic or epigenetic promoter to hepatitis B virus-initiated carcinogenesis. In low risk populations cirrhosis is the most important causal association of hepatocellular cancer. The cirrhosis is often the result of alcohol abuse, but the tumour may complicate all aetiological forms of this disease. Whether neoplasia is an inevitable consequence of the hyperplasia of cirrhosis, or the increased hepatocyte turnover rate acts as a promoter is not known. Hepatitis B virus infection plays a lesser part, and aflatoxin no part at all.

Adult↗
PubMed1985

Smoking as a risk factor in hepatocellular carcinoma. A case-control study in southern African blacks.

Two hundred forty southern African black patients with hepatocellular carcinoma and control subjects matched for race, sex, age, and urban or rural background were questioned about their smoking habits. Patients with hepatocellular carcinoma were not more likely to smoke or to smoke heavily than the control subjects. This was also true of the subgroups: men and women, and urban and rural background. There was a slightly increased relative risk associated with smoking in all patients who showed no serum markers of current or past hepatitis-B virus infection and in patients older than 50 years who did not have markers of current or past hepatitis-B virus infection. However, this was not statistically significant, and was not supported by a linear trend, the risk in heavy smokers being less than 1. Rural black patients, who have a higher incidence of hepatocellular carcinoma than urban black patients, smoked less than their urban counterparts. We conclude that smoking is not an unqualified risk factor for hepatocellular carcinoma in southern African black patients. There may, however, be a trend toward smoking playing an etiologic role in patients without hepatitis-B virus infection, especially in older patients.

Adult↗
PubMed1985

Serum vitamin B12 binders in South African blacks with hepatocellular carcinoma.

Sera from 242 South African blacks with hepatocellular carcinoma were assayed for unsaturated vitamin B12 binding capacity (UBBC) and vitamin B12 activity. Six patients were younger than 20 years of age, and 24% were younger than 30 years of age. Eighty-four percent of the patients had a slightly raised UBBC and 86% had a slightly elevated vitamin B12 value, but in no patient was an exceptionally high UBBC present. Serum UBBC and vitamin B12 were not higher in younger patients, and raised UBBC values were not related to serum alpha-fetoprotein values. Serum UBBC and vitamin B12 concentrations were not significantly different in patients with and without coexisting cirrhosis. In none of the patients with a UBBC above 3000 pg/ml was the fibrolamellar variant of hepatocellular carcinoma present. The authors conclude that South African blacks with hepatocellular carcinoma do not secrete an abnormal vitamin B12 binding protein.

Adolescent↗
PubMed1985

Detection of markers of hepatitis B virus infection in urine of chronic carriers.

Urine from 19 chronic hepatitis B virus (HBV) carriers was tested for markers of HBV infection. Hepatitis B surface and e antigens were excreted in the urine of about one-half of the patients, but not in any consistent pattern. HBV DNA, a much more sensitive indicator of infectivity, was found in only one specimen and then in very low concentration. We conclude that urine of chronic HBV carriers is not a major vehicle for the transmission of hepatitis B.

Autoradiography↗
PubMed1985

Defective interleukin-1 production by natural killer cells of patients with cancer.

Large granular lymphocytes (LGLs) from patients with malignant disease and from controls were activated by endotoxin or K562 cells, and the supernatants assayed for interleukin-1 (IL-1) activity. Normal LGLs produced significant amounts of IL-1, the activity of which could be neutralized by anti-human IL-1 antiserum. In patients with advanced cancer depressed IL-1 production was observed, which generally correlated with the degree of cytotoxicity produced by the LGLs. Prior treatment of the LGLs with interferon increased production of IL-1 by both control and patient cells. It is suggested that LGLs coming into contact with K562 cells produce IL-1, which is important in the effector-target cell interaction. The decreased cytotoxic activity of LGLs from cancer patients could be related to a defect in IL-1 production, an effect which can be partially corrected by in vitro interferon treatment.

Adult↗
PubMed1985

Replication of hepatitis B virus in adult carriers in an endemic area.

We have examined serological markers of replicative and nonreplicative infection in 124 adult, black South African carriers of hepatitis B virus (HBV), in whom this infection is predominantly acquired in early childhood. The mean age of the group was 36 years. Antibody to hepatitis B e antigen (anti-HBe) was present in the serum of 93.5% of these carriers. Only 25.8% of the carriers were positive for HBV DNA in serum, and in the majority of these only trace amounts were detectable. IgM antibody to hepatitis B core antigen (IgM anti-HBc) was negative in 54% of the carriers, and only 26% had IgM anti-HBc in high titer. A significantly greater proportion of carriers who were positive for anti-HBe were positive for IgM anti-HBc (43.1%) than were positive for HBV DNA (24.5%). Serum aminotransferases were less than twofold elevated in 90.3% of the carriers. Only one carrier has thus far developed hepatocellular carcinoma. These results suggest that there is an inexorable progression to predominantly nonreplicative infection in the majority of southern African adult, black carriers, an occurrence that may take several decades. In areas endemic for HBV infection, antiviral agents effective against replicative HBV will have to be administered in childhood.

Adult↗
PubMed1985

Technetium-99m glucoheptonate as a scanning agent in hepatocellular carcinoma.

Technetium-99m glucoheptonate (Tc-99m GH) is concentrated in pulmonary and cerebral tumors. The purpose of this study was to assess the uptake of this radionuclide by hepatocellular carcinoma. Its concentration by the primary tumor was compared with that in the non-neoplastic hepatic tissue in 31 patients who showed obvious defects on a colloid scan, and its uptake by pulmonary metastases was examined in six patients with x-ray evidence of this complication. In two patients, the uptake by the tumor was greater than, in six it was equal to, and in ten it was less than that in the non-neoplastic hepatic tissue. In the remaining 13 patients, there was no concentration at all in the tumor. In none of the six patients with multiple pulmonary metastases could uptake of Tc-99m GH by the metastases be demonstrated. It is concluded that Tc-99m GH is of limited value in the diagnosis of primary or metastatic hepatocellular carcinoma.

Adult↗