Can flow cytometry reduce the workload for cervical screening? The results of a series of 622 specimens.

A simple method permitting the flow cytometric examination of cervical specimens has been developed and an assessment made of the feasibility of relying on this method to screen women for cervical neoplasia. Examination of four flow cytometric parameters showed differences between morphologically normal and abnormal specimens and allowed identification of a proportion of the normal specimens. The system had a false negative rate of 8%. Our experience with cervical specimens has revealed a number of problems associated with their examination by flow cytometry and these are discussed.

A toxicity study of recombinant interferon-gamma given by intravenous infusion to patients with advanced cancer.

Eighteen patients with solid tumours were treated with human recombinant interferon-gamma at escalating dose levels starting at 1 X 10(6) units/m2 per infusion and rising through 3 X 10(6), 6 X 10(6), 9 X 10(6) and 22 X 10(6) to a maximum of 110 X 10(6) units/m2 per infusion. The IV infusions were given three times a week over a 4-week period. Side effects were seen in all patients, but were mild except at the highest dose. Acute dose-related effects included pyrexia, tiredness, thirst, chills and rigors. Chronic dose-related effects included anorexia, lethargy, weakness, disorientation, a trace of proteinuria and minimal rises in liver enzymes. In addition, effects were observed which were not related to dose. These included headache, nausea and vomiting, backache, myalgia, flatulence and a mild, transient reduction in neutrophils and erythrocytes. At the highest dose level dose-limiting toxicity was observed, consisting in severe tiredness and anorexia, hypotension, disorientation and changes on the electrocardiograph. Overall, toxicity was similar to that seen with preparations of interferon-alpha, except that no tolerance to the effects of interferon-gamma was noted. We observed less hepatic and haematological toxicity, but also recorded flatulence, handcramps and electrocardiograph changes, which have not been reported with interferon-alpha. When given according to this regimen, doses of 22 X 10(6) units/m2 per infusion of recombinant interferon-gamma were generally well tolerated by the patients.

Demonstration of an epitope of the transferrin receptor in human cervical epithelium--a potentially useful cell marker.

The distribution of an epitope of the transferrin receptor in the human uterine cervical epithelium has been investigated. Immunohistochemical staining, both immunofluorescent and immunoperoxidase, was performed on biopsy specimens and cytological samples from normal, dysplastic, and neoplastic cervical epithelia using the monoclonal OKT9 antibody. The results of staining 145 cervical biopsy specimens with OKT9 showed widespread staining in all malignant epithelia and most severely dysplastic epithelia. No such staining was seen in either normal epithelia or in mildly dysplastic epithelia apart from the staining of the basal cell layer in some normal epithelia. The incidence of staining in the 50 cervical cytocentrifuge preparations was not as high as that in the 145 tissue sections. The potential role of the OKT9 antibody in both the screening of cervical cytocentrifuge preparations and the prediction of malignancy is discussed. The antibody is considered to be of more value in the examination of biopsy material than of cytocentrifuge preparations.

Immunohistochemical detection of Ca antigen in normal, dysplastic and neoplastic squamous epithelia of the human uterine cervix.

Immunohistochemical staining was performed on biopsies and cytological samples from normal, dysplastic and neoplastic squamous epithelia using the monoclonal Ca 1 antibody. The results of staining 92 biopsies and 20 cytological samples are described and it is reported that positive staining with Ca 1 antibody was detected in normal, dysplastic and neoplastic epithelia. The role of the Ca 1 antibody in the study of cervical cancer is discussed.

A phase 1 study of recombinant interferon-gamma given intravenously by portable mini-pump: a preliminary report.

Recombinant interferon-gamma was given to patients with tumours by a six-hour intravenous infusion using a portable mini-pump, to assess the side-effects of the drug. At present, 11 patients have been treated; 2 adenocarcinoma of the ovary, 3 squamous carcinoma of the bronchus, 1 adenocarcinoma of the breast, 1 adenocarcinoma of the stomach, 1 Hodgkin's lymphoma, 1 case of two primaries, adenocarcinoma of the breast and ovary, and 1 adenocarcinoma of unknown origin. Two patients received 1 X 10(6) units/m2/infusion, four received 3 X 10(6) U/m2/inf., three received 6 X 10(6) U/m2/inf. and two received 9 X 10(6) U/m2/inf. Two further dose levels will be used in the future; 27 and 51 X 10(6) U/m2/inf. Three 6-hour infusions a week were given for a four week period. The major side-effects of gamma-interferon were dose-related pyrexia with rigors to which there was no tachyphylaxis, acute and chronic tiredness, nausea with or without vomiting, headache, backache and myalgia. There was also a dose-dependent immediate but mild and transient decrease in the total white cell count. All effects have been transient, and none have been severe. We have also noticed that intravenous infusions by mini-pumps are tolerated far better by the patients than conventional drip systems, and we feel mini-pumps are the ideal way to give intravenous infusions.

Histological evidence of hepatitis-B-virus infection with negative serology in children with acute leukaemia who develop chronic liver disease.

A high percentage of patients with acute leukaemia in established remission develop chronic liver disease: how important hepatitis-B-virus (HBV) infection is as an aetiological factor is not clear. The presence of HBV markers in liver and serum of 23 leukaemic children with liver disease was investigated at the time of a diagnostic biopsy just before treatment withdrawal. Although, at this time, none had HBV antigens or antibodies in the serum by radioimmunoassay, HBsAg was detected by direct immunofluorescence in the cytoplasm of hepatocytes in 13 children, 7 of whom also had hepatitis-B core or e antigens in hepatocyte nuclei. This pattern of both cytoplasmic and nuclear fluorescence was present in 4 of 6 patients with the histological features of chronic active hepatitis on liver biopsy. The failure of release of viral antigens into serum and the absence of an adequate immune response were probably due to the intense chemotherapy used to induce and maintain remission, since HBV markers appeared in the serum within 15 months of stopping treatment in 8 of the children in whom viral antigens had been detected in liver tissue but in none of those whose biopsy specimens were negative by immunofluorescence. These results suggest that HBV infection may be an important cause of chronic liver disease in children with leukaemia and show that during treatment serological tests may fail to detect the presence of the virus.

Clinical evaluation of the modified Makari skin test in minimal residual malignant disease.

The results of a double-blind controlled study of the modified Makari skin test in urological malignancy are described. The study suggests that the test will be useful in the monitoring of primary treatment and in the detection of recurrent malignancy and thus indicates a role for the Makari skin test in minimal residual malignant disease.

Clinical evaluation of the Makari test in urological malignancies.

The results of a double-blind controlled study of the modified Makari skin test for the detection of cancer are described. The test identified malignant disease in 95% of 37 patients with primary cancer and in 74% of 81 with recurrent cancer after the exclusion of "anergic" patients. The study suggests that the test will be useful in the monitoring of primary treatment and in the detection of recurrent malignancy.

Serum protein changes in breast cancer: a prospective study.

Sixty women admitted to the King's College Hospital group for biopsy of a lump in the breast have been followed sequentially for one year. Thirty women had early operable breast cancer and 30 had benign breast disease. Each patient had 10 serum proteins measured preoperatively and postoperatively at three months and at one year. The patients with breast cancer had significantly higher levels of beta2 glycoprotein preoperatively and caeruloplasmin at one year postoperatively than those with benign breast disease. There were a number of significant correlations between serum protein levels and the progression of breast cancer as measured by the clinical score. There were significant correlations with caeruloplasmin preoperatively and at three months postoperatively. Prealbumin and haemopexin showed correlations preoperatively; alpha1 antitrypsin and beta2 glycoprotein only correlated at three months postoperatively. A longer follow-up will be required to establish the value of serum protein changes which could predict the development of metastases in patients with breast cancer.

Prognostic value of serum levels of immunoglobulins (IgG, IgA, IgM and IgE) in breast cancer: a preliminary study.

One hundred and sixty women admitted for breast tumour biopsy to the King's College Hospital group have been followed sequentially for 2 years. Sixty-nine women had early operable breast cancer and 91 had benign breast disease. All these women had serum immunoglobulin IgG, IgA, IgM and IgE levels measured preoperatively and postoperatively at 3 months, 1 year and 2 years. No differences were found in any of the serum immunoglobulin levels between the two groups at any time. There was, however, a positive correlation between the extent of metastatic breast cancer and the serum level of various immunoglobulins, particularly IgA. There was no evidence that routine postoperative radiotherapy influenced the levels of serum immunoglobulins. The findings suggest a secondary defence reaction against increasing tumour load, and do not support the theory of an early immune defect in immunoglobulin metabolism which could play a part in the pathogenesis of breast cancer. Although there is no diagnostic value in measuring the levels of serum immunoglobulins in patients with breast tumours, there may be some value in following the levels in cancer patients, as a guide to subclinical spread of the disease.

Modified Makari skin test in follow-up of bladder-cancer patients.

123 patients who had been treated for carcinoma of the bladder and who were clinically recurrence-free at the time of their initial Makari skin test are being followed-up; 77 were negative and 46 positive. 48 of these patients have been followed-up so far, for 3-9 months, with cystoscopic review and repeat Makari testing; 75 have still to be followed-up. The high initial positive rate of 37% has been largely explained by the discovery of a recurrent tumour at the first cystoscopy after the test. The concordance between tumour status and repeat Makari testing indicates its ability to detect early recurrence.

The modified Makari skin test in urology--is it significant?

The Makari test is able to detect the presence of cancer in 95% of patients with primary tumours having excluded anergic patients. The test is useful in monitoring primary treatment. A long-term follow-up is necessary to determine the reason for patients' unexplained positive reactions in a control group of patients.