Human serum deoxythymidine-5'-triphosphatase activity as a parameter in the diagnosis and follow-up of large bowel carcinoma.

Serum deoxythymidine-5'-triphosphatase (dTTPase) levels were determined in 71 patients with large bowel cancers at different clinical stages: 10 patients in Duke's Stage A; 37, in Duke's Stage B; and 24, in Duke's Stage C. The dTTPase values of patients in Duke's Stage B and C are significantly elevated over normal healthy controls, and a correlation was observed between tumor stage and dTTPase activity. While dTTPase levels rise in patients with increasing tumor burdens, they decline in patients with undetectable tumor tissue after radical surgery. Six of 15 courses are documented, illustrating that, after successful operation, enzyme levels revert to normal. In all patients, carcinoembryonic antigen levels were determined along with dTTPase values, and both sets of data were correlated with each other indicating a correlation coefficient of zero. So, if both dTTPase and carcinoembryonic antigen are taken into account, the sensitivity of detection of colorectal carcinomas rises to 66% for all patients and to 92% for patients with a colorectal carcinoma of Duke's Stage C.

Demonstration of elevated anti-Lewis antibodies in sera of cancer patients using a carcinoembryonic antigen-polyethylene glycol immunoassay.

The serum levels of carcinoembryonic antigen (CEA) and CEA-binding proteins of 68 controls and 170 cancer patients were determined. The CEA levels were determined by a double-antibody radioimmunoassay using radiolabeled CEA, and the CEA-binding proteins were determined by an immunoassay utilizing radiolabeled CEA and polyethylene glycol. The major CEA-binding proteins in serum were anti-blood group antibodies as demonstrated by differential binding of serum proteins from A, B, or O positive individuals to radiolabeled CEA's which were previously shown to carry specific blood group determinants. No statistically significant differences were observed for the binding of control versus cancer patient sera to CEA-A (carrying blood group A1), except, as expected, A negative (O or B positive) individuals gave high binding to CEA-A, while A positive individuals gave low binding to CEA-A. Statistically significant differences were observed for controls versus cancer patients for binding to CEA-Lewisab (CEA-Leab). CEA-Leab-binding activity was higher in females and smokers in the control group, but this distinction was not found in the cancer patients. The high levels of anti-Leab antibodies may be explained in females by exposure to fetal antigens during pregnancies and in smokers or cancer patients by exposure to precursors to blood group substances. The sera of 7% of the patients with colonic carcinoma, 18% of the patients with breast carcinoma, and 23% of the patients with bronchogenic carcinoma bound more CEA-Leab than did the serum of the highest male control. A correlation between CEA-Leab-binding activity and the levels of serum CEA was found for patients with colonic carcinoma but was not significant for the groups with other cancers or the control group. Serial determinations of CEA-Leab-binding activity for 21 patients with bronchogenic carcinoma changed congruently with the serum levels of CEA in 12 cases. The significance of these results in terms of expression of immature blood group antigens, the subsequent production of antibodies against them, and the prognostic value of this response is discussed.

Sensitive detection of carbohydrate determinants on carcinoembryonic antigen preparations by lectin and antibody binding using polyethylene glycol.

Blood group determinants have been found in five carcinoembryonic antigen (CEA) preparations with a lectin and antibody-binding assay using polyethylene glycol 6000 to separate free from bound radiolabeled antigen. The assay described gives excellent sensitivity for the binding or inhibition of binding of various lectins or antibodies to CEA. One of the CEA preparations investigated has an A1 determinant, another has a B determinant, and all have H, Lea, Leb, and MN blood group determinants. In addition, all of the preparations tested bound concanavalin A. These findings are consistent with the idea that incomplete or unexpected glycosylation patterns occur in glycoproteins produced by tumor cells. Since antibodies directed against blood group substances cross react with carbohydrate determinants on CEA, clinical determinations of CEA or anti-CEA levels in serum may be adversely affected.

Histological and ultrastructural findings in chloroquine-induced cardiomyopathy.

Light microscopic and ultrastructural findings in patients suffering from chloroquine-induced cardiomyopathy are reviewed. Based on our own observations in an autopsy case, functional and morphological similarities between chloroquine effects and hereditary lysosomal storage diseases are discussed.

[Sonographic differential diagnosis of extrahepatic cholestasis]. / Sonographische Differentialdiagnose der extrahepatischen Cholostase.

The value of sonography for aetiological diagnosis was examined in 196 patients with extrahepatic cholestasis. For each patient a diagnosis was prospectively worked out by sonography and compared with the true diagnosis established by endoscopic retrograde pancreaticocholangiography (ERCP), and/or computed tomography (CT), surgical intervention, autopsy and unequivocal clinical course. In 72 patients cholangiolithiasis was the cause of the obstruction. It was diagnosed by sonography with a sensitivity of 86% and a specificity of 93%. With 25 patients with another benign cause of cholestasis the diagnosis was made by sonography in 23 cases. In 93 patients the underlying malignant disease was recognised sonographically with a sensitivity of 95% and a specificity of 100%.

[Demonstration of circulating CEA or CEA-like antigens and immunoglobulin G containing immune complexes in colorectal carcinoma]. / Nachweis zirkulierender, CEA oder CEA-ähnliche Antigene und Immunoglbulin G enthaltender Immunkomplexe beim kolorektalen Karzinom.

A sandwich method was developed for the detection of carcinoembryonic antigen (CEA) and CEA-like molecules and immunoglobulin G (IgG) containing immune complexes (CEA-IgG-IC) in human sera. Rabbit anti-CEA ( Dako , FRG) was adsorbed to polypropylene tubes. CEA-like molecules and IgG containing immune complexes bound to the solid phase. They were detected by binding peroxidase-labelled anti-IgG antibodies and quantified by measuring the optical density (OD) at 492 nm after oxidation of orthophenylene diamine. Sera of 68 controls had a mean OD 492 of 1.19 +/- 0.26 (means +/- SD). An extinction of more than 1.97 (means + 3 SD) was judged as elevated. Fourteen of 69 patients after surgical treatment of colorectal carcinoma showed elevated OD 492 up to a value of 3.92. In five patients with benign diseases of colon or rectum normal values were found. In 7 of 41 patients without recurrence or metastases CEA-IgG-IC were elevated although the CEA was normal, and in one case both parameters were elevated. In four of 22 patients with tumor progression CEA-IgG-IC and CEA were elevated, whereas in two cases only CEA-IgG-IC were found.

[Fasciitis with eosinophilia and hypergammaglobulinaemia (author's transl)]. / Fasziitis mit Eosinophilie und Hypergammaglobulinämie.

A case of fasciitis with eosinophilia and hypergammaglobulinaemia (Shulman's syndrome) in a 33-year-old patient is described. Both the lower arms and the lower legs were affected. The diagnosis was established by biopsy which revealed cellular infiltration of the deep fascia with thickening. In addition to typical symptoms there was hepatosplenomegaly. Gastrointestinal or haematological disease was excluded. Under systemic corticosteroid administration all symptoms of fasciitis quickly disappeared.

[Diagnostic native roentgenology of operated pituitary adenomas (author's transl)]. / Röntgennativdiagnostik operierter Hypophysenadenome

Cases showing the value and limitations of diagnostic native roentgenology in recurrent pituitary adenomas were selected from a total of 217 patients. Recurrence is recognized by progressive intrasellar space occupation. Bone apposition at the contours of the sella turcica resulting in reduction of volume and calcifications of the sellar region permit exclusion of intrasellar recurrence. Marking the area of operation improves native roentgenology. Bone apposition of acromegaly may obscure recurrences. According to the literature, about 50% of recurrences can be diagnosed roentgenologically. On the contrary recurrences can be excluded in 10-20% of roentgenologically successfully operated patients.

[Fatal vacuolar cardiomyopathy in chronic chloroquine drug treatment]. / Letale vakuoläre Kardiomyopathie bei chronischer Chloroquin-Medikation.

Clinical and morphological findings recorded in an 81-year-old woman patient with a 45-year history of rheumatoid arthritis treated with long-term chloroquine therapy are reported. The cause of death was low cardiac output syndrome, which upon autopsy and postmortem toxicological analyses was classified as vacuolar chloroquine-induced cardiomyopathy. The pathogenesis and the morphological and clinical characteristics of cardiotoxic effects of chloroquine are reviewed.

[The value of anamnesis, clinical findings and laboratory parameters in the diagnosis of giant cell arteritis]. / Der Wert von Anamnese, Befund und Labor für die Diagnose der Riesenzellarteriitis.

In 67 patients with giant cell arteritis (GCA) and 133 control patients, the value of eight clinical parameters and five laboratory findings for the diagnosis of GCA was analyzed. Out of the clinical parameters characteristic for GCA, headaches, visual disturbance, pains of the shoulder or hip regions and fever were of diagnostic value. Of the laboratory findings, only the BSR was of diagnostic value. Inappetence, exhaustion and fatigue, although characteristic of GCA, as well as blood count, alpha-globulins, CRP and alkaline serum phosphatase were of no value in differentiating between GCA and other diseases. Each of the valuable parameters increased the probability of diagnosing GCA from 33% (incidence of GCA in our patients) up to between 48% and 52%. The simultaneous evaluation of several parameters elevated the probability of diagnosing GCA to up to 88%. These results provide a basis for a rational decision in favor of or against biopsy of the temporal artery. In the case of a negative histology, they help to decide in favor of or against long term corticoid therapy.

[Carcinoembryonic antigens (CEA) in patients with metastatic breast cancer under endocrine and therapeutic treatment (author's transl)]. / Carcinoembryonales Antigen (CEA) im Plasma bei Patienten mit metastasierenderm Mammakarzinom unter endokriner und zytostatischer Therapie.

Carcinoembryonic antigen (CEA) was determined in 72 patients with metastatic breast cancer under various kinds of treatment. In 53 cases, CEA levels were elevated. They correlated with free interval, metastatic spreading, alkaline phosphatase (AP) and gamma-glutamyltranspeptidase (gamma-GT). Serial CEA determinations in 50 of the 72 patients revealed increased CEA levels in connexion with progressive tumour growth and decreased CEA levels in connexion with response to treatment. CEA may therefore be useful in helping to assess the extension of the tumour and the effect of treatment in patients with matastatic breast cancer.

[Anabolic therapy in metastatic breast cancer]. / Anabole Therapie bei metastasierendem Mamma-Karzinom.

The medical records of 66 women treated with metenolone for metastasized breast carcinomas were analysed. In 26 patients a remission developed with a mean duration of 8.2 (3-29) months. Patients whose treatment started in the first year after the menopause as well as patients with a beneficial effect of a therapeutic ovariectomy in the past were more often improved by metenolone than average. Metenolone had a better effect against osseous metastases than against visceral metastases. In most cases the treatment was well tolerated. In four patients, however, the treatment had to be interrupted because of cholestasis, pulmonary embolism and hypercalcaemia.

[Early judgement on the results in radiation therapy of colorectal cancer: determination of carcinoembryonic antigen (CEA) in blood serum at daily intervals from the beginning of irradiation (author's transl)]. / Frühzeitige Erfolgsbeurteilung der Strahlentherapie von rektosigmoidalen Karzinomen. Die Bestimmung des Karzinoembryonalen Antigens (CEA) im Serum in Tagesabständen zu Beginn der Bestrahlung.

Carcinoembryonic antigen (CEA) and lactatedehydrogenase (LDH) as tumor cell markers have been determined in the blood serum of 10 patients with colorectal cancer, who underwent preoperative irradiation with 200 to 250 rad daily (total focal dose 2000 to 2500 rad). Daily analysis was made during the irradiation, and, moreover, a determination 2 weeks after the resection of the tumor. Simultaneously CEA and LDH were determined in 10 controls. Serum CEA and LDH levels were found significantly increased in tumor patients as compared to controls. The course was characterized by a peak of LDH on days 4 and 7 from the onset of radiation treatment, while serum CEA did not show a peak in the total of the tumor patients; but in 3 individual patients a peak was detected. In 5 patients, with low CEA values from the beginning, no significant modifications of CEA did appear. Thus, some of the patients undergoing irradiation revealed CEA kinetics conform to theoretical considerations, suggesting a response to irradiation of the colorectal carcinoma. The prognostic value of the early CEA kinetics during radiation treatment should be examined in patients being irradiated for inoperable local recurrence.

[Prognostic value of serum CEA and therapy-induced nonspecific CEA levels in metastasizing breast carcinoma]. / Prognostische Aussage des Serum-CEA und therapiebedingte unspezifische CEA-Verläufe beim metastasierenden Mammakarzinom.

In 57 patients with metastasized breast carcinoma, serum CEA levels (CEA-Ria-Kit, Abbot) were correlated with the clinical course under endocrine or cytostatic therapy. In 20 patients, CEA was determined at intervals of 1 to 3 days over the first 4 weeks of treatment and in 21 patients at intervals of 1-3 weeks. In 16 patients, CEA was determined prior to treatment. The clinical development was judged according to the program of UICC. We found pretreatment CEA values higher than 25 ng/ml serum mostly in patients with liver involvement and in patients with progression under the following therapy. In 22 patients, progress or remission of the disease were correlated with CEA increase or decrease of more than 20% during the first 8 weeks. In 11 patients, we found no correlation between CEA and clinical course. From the remaining 8 cases, CEA levels were out of the measuring range in 6 patients, in 2 patients we were unable to interpret the clinical course doubtlessly. There were no short-termed CEA alternations after the start of the treatment rendering a possible early estimation of the therapy effect. In 5 of 23 patients treated with methylprogesteronacetate and aminoglutethimide a continuous CEA increase developed despite clinical remission. This was not found in 10 patients treated with cytostatic chemotherapy. The pretreatment CEA is a useful prognostic parameter in patients with metastasizing breast cancer. CEA should be determined weekly in patients with increasing CEA levels under therapy and monthly in patients with decreasing CEA levels. The possibility of a tumor-independent CEA rise as a side-effect of treatment must be taken into consideration.