Biomedical subjects
Publications and source records attributed to F Bach.
Totally implantable ports have gained popularity as venous access in the treatment of cancer. A case is reported with an uncommon but very serious complication, i.e., cytostatic extravasation secondary to a broken implanted catheter. Guidelines for implantation and remedies are recommended.
Tissue polypeptide antigen (TPpA) in the cerebrospinal fluid (CSF) was measured in 59 consecutive breast cancer patients with suspected central nervous system (CNS) metastases. Subsequently, we determined that 13 patients had parenchymal brain metastases, 10 had leptomeningeal carcinomatosis, and 36 had no CNS involvement. The concentration of TPpA, which is a nonspecific marker for cell proliferation, was significantly higher in patients with CNS metastases than in those without it (P less than .0001; Mann-Whitney test). A tentative cutoff value for CNS metastases was set at 95 U/L TPpA; the upper limit of values indicating absence of CNS metastases was 89 U/L. Given these cutoff points, the sensitivity of TPpA as a marker for CNS metastases was 74% and the specificity was 100%; the predictive values of positive and negative tests were 100% and 86%, respectively. In 16 patients with CNS metastases, no correlation was found between TPpA activity in corresponding CSF and blood samples (correlation coefficient, Spearman's rho = .4; P greater than .1). In three patients treated for leptomeningeal carcinomatosis, the measurements of CSF TPpA showed correlation between the presence of tumor cells in the CSF and neurological clinical function. TPpA concentrations decreased in parallel with the clinical response and increased prior to CNS disease progression. As a marker for CNS metastases, the level of TPpA in the CSF in breast cancer patients appears to be superior to the level of protein, lactate dehydrogenase, or glucose, which showed very low sensitivity (41%, 47%, and 8%, respectively). For quantitative evaluation of treatment for leptomeningeal carcinomatosis, the TPpA level appears to be valuable and superior to CSF cytology, because tumor cells are not always present in CSF samples from patients with this condition.
A total of 26 evaluable patients with previously untreated, non-resectable adenocarcinoma of the lung were given 80 mg/m2 i.v. teniposide daily for 5 days every 3 weeks. Three partial responses (11%) were obtained that lasted for 12, 11 and 32 weeks, respectively. Leucopenia was the dose-limiting side effect, with WBC counts of less than 2 x 10(9)/l being observed in 42% of patients, resulting in one septic death. At the dose and schedule used in the present study, teniposide showed only limited activity in adenocarcinoma of the lung.
Cellular and mitochondrial swelling are regarded as typical intra-ischemic alterations ("IIA"), contraction band lesions (CBL), in contrast, as products of post-ischemic reperfusion. The occurrence of both types of structural deterioration was investigated in Purkinje fibres and subendocardial and intramural working myocardium: initially after St. Thomas- or HTK cardioplegia, then during ensuing global ischemia up to the "practical limit of resuscitability", and following post-ischemic reperfusion. Generally, Purkinje fibres are not better preserved than neighbouring working myocardium. Comparing St. Thomas- and HTK cardioplegia, considerable quantitative, but not qualitative differences in the reaction patterns of different cell types or layers arise. Immediately after cardioplegia, CBL are completely lacking in both cell types. During ischemia, CBL occur occasionally in Purkinje fibres and seldom in subendocardial working myocardium, "IIA" predominate. During post-ischemic reperfusion "IIA" tend to reverse in all layers, whereas CBL are found to remain in the subendocardial cell types. In intramural layers, CBL occur only during reperfusion. Thus, we deduce that cardioplegia only modulates the severity of "IIA" and the frequency of CBL, but cannot abolish the particular sensitivity of subendocardial Purkinje fibres to global ischemia. Prerequisites for the development of irreversible CBL are on the one hand ischemic metabolic alterations and corresponding energy deficits, and, on the other hand, a supply of oxygen. The oxygen may be inadequately supplied via diffusion during ischemia or may be subsequently provided by reperfusion.
The interstitial space, separated into tissue clefts and interstitium within bundles of myocytes of left canine ventricle, was investigated qualitatively and morphometrically after using different methods of fixation following aortic cross clamping and 10 min of ischemia at 5 degrees C. In frozen sections, the size of tissue clefts is significantly lower than in semithin sections after immersion fixation. The interstitium within bundles of myocytes shows similar values independent of the fixation technique (r = 0.83). This constancy permits a free choice between the two fixation techniques, there being no loss of information from the material investigated.
Ischemia causes changes in organ tissue (e.g. during operation or transplantation) which may finally lead to irreversible injury, so that the organ can no longer be resuscitated. To the extent that these changes affect the electrical properties of the tissue they are manifested in the impedance spectrum. As an example, the course of impedance of a HTK-protected porcine liver is presented in the frequency range of 0.1 Hz to 10 MHz, which includes two dispersion--alpha- and beta-dispersion. Using a suitable electrical equivalent circuit analogue to the structure of the liver, the behavior of the alpha- and beta-dispersion is explained on the basis of gap junction closure and narrowing of the extracellular space due to cell swelling.
A retrospective study of 398 patients suffering from metastatic compression of the spinal cord or cauda equina is presented. The study comprised almost all relevant medical records of patients admitted to hospital in the eastern part of Denmark in the period 1979 through 1985. Carcinoma of the lung, prostate, breast and kidney were the most frequent primary malignancies causing spinal compression. Most patients were treated with laminectomy, or radiotherapy or with laminectomy and radiotherapy combined. The effect of the treatment was estimated by evaluation of motor function and sphincter control. Treatment with laminectomy followed by radiotherapy was significantly superior to treatment with laminectomy or radiotherapy alone. But if the patients' motor function and primary tumour were taken into account, no significant difference between the treatments was observed. The efficacy of treatment depended upon the symptoms when the diagnosis was established, and accordingly early diagnosis is of the utmost importance. The incidence of metastatic compression increased during the period covered by the study, and since this condition must not go untreated, awareness of the symptoms, primarily pain, is essential.
All medical records of patients treated for metastatic compression of the spinal cord or cauda equina in the eastern part of Denmark from 1979 through 1985 were reviewed. With regard to treatment response and survival, 345 patients could be evaluated. Carcinoma of the lung (19%), prostate (18%), breast (13%), and kidney (10%) were the most frequent primary malignancies causing spinal compression. The outcome of treatment depended primarily on the patients' condition at the time of diagnosis: 79% of the patients who were able to walk before the treatment remained ambulatory, whereas only 21% of the nonambulatory paraplegic patients and 6% of the paralytic patients regained walking ability. Patients treated with laminectomy followed by radiotherapy seemed to respond better than patients treated with radiotherapy or laminectomy alone, but when the patients' pretreatment motor function was taken into account no significant difference was found between the three forms of treatment. In the subgroup of nonambulatory patients, however, a significantly better restoration of gait was observed in patients treated with the combination of laminectomy and radiotherapy than in patients treated with radiotherapy alone. A longer survival in the group treated with the combination of laminectomy and radiotherapy may reflect that these patients were in a lower stage of disease and thus had a better potential of regaining motor function. The results call for prospective randomized studies.
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We reviewed all medical records concerning patients suffering from spinal cord or cauda equina compression (SCC) secondary to cancer, in the eastern part of Denmark, from 1979 through 1985. During the period the incidence of SCC in cancer patients went up from 4.4% to 6%. However, this increase was not significant. The series comprised 398 cases, with carcinoma of the prostate (19%), lung (18%), breast (14%) and kidney (10%) accounting for 61%. The symptoms were evaluated in accordance with the patients rating of pain, motor deficits, sphincter control and paraesthesia, whereas the clinical manifestations were classified on the basis of motor deficit and bladder dysfunction. During the period preceding the diagnosis of SCC, 83% of the patients suffered from back pain, 67% from deteriorating gait and 48% had retention of the urine. In 35% of the patients there was no sphincter disturbance and 10% had normal sensory function. The outcome of treatment was estimated by changes in motor deficits and sphincter function, and depended primarily on the patients condition at the time of the diagnosis. Of the patients who were able to walk before treatment, 79% remained ambulatory, whereas only 18% of the non-ambulatory patients regained walking ability. Patients treated by decompressive laminectomy followed by radiotherapy apparently had a better response than patients treated with surgery or irradiation alone, but when the patients pre-treatment motor function was taken into account, no significant difference was observed. The study may call for a properly randomized trial with careful stratification of tumour biology, performance status and neurological deficits.
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An enzyme-linked immunosorbent assay (ELISA) using monoclonal and polyclonal antibodies against t-PA was used to measure the concentration of tissue-type plasminogen activator (t-PA) in plasma from 34 healthy donors and 92 breast cancer patients with a varying extent of disease. The mean value of t-PA in plasma for the healthy donors was 2.4 +/- 2.1 ng ml-1 (s.d.). The mean value for the breast cancer patients was 5.3 +/- 4.3 ng ml-1. This increase was statistically significant at the 1% level. There was a positive correlation between the mean t-PA plasma concentration and the extent of disease in different groups of patients. Taking 5.0 ng ml-1 as cut-off point, about 40% of the patients were positive, and 6% of the normal controls were false positive. Twenty-five per cent of the patients in complete remission, 28% of the patients with minimal tumour burden, 60% of the patients with moderate tumour burden, and 90% of the patients with massive tumour burden were positive. It is possible that the patients with an elevated plasma t-PA represent a group with a particularly bad prognosis.
TCNU, a new water soluble nitrosourea, has in preclinical studies shown higher activity when given as divided doses compared with one day single treatment. Accordingly, 38 consecutive patients with non-resectable adenocarcinoma of the lung received TCNU 40 mg/m2 p.o. daily for three days every 4 weeks. The response rate among 37 evaluable patients was 14%, median response duration was 17 weeks (range 5-57+ weeks) and median survival 22 weeks (range 3-96+ weeks). Hematologic toxicity was pronounced, especially thrombocytopenia, and 57% of the patients had WHO grade 3 or 4 WBC or platelet count. Overall, dose reduction or delay of treatment due to hematologic toxicity was necessary in 66% of the patients. This, together with the limited activity, renders TCNU in the present dose and schedule unsuitable for further investigations in this disease entity.
To determine whether creatine kinase-BB isoenzyme would be useful in detecting central nervous system metastases secondary to breast cancer, we measured the cerebrospinal fluid (CSF) activity of creatine kinase (CK) and its BB isoenzyme (CK-BB) in 65 consecutive patients suspected of having CNS involvement. All patients underwent neurological evaluation, computer tomography (CT) scan and/or radionuclide scintigraphy and lumbar puncture with CSF examination. Thirty patients had CNS metastases, of whom 18 had parenchymal brain metastases (MET). Twelve had leptomeningeal carcinomatosis (MC), of whom four also had parenchymal brain metastases. Thirty-four patients were concluded not to have CNS involvement, whereas one was considered equivocal. CK-BB activity was significantly higher in patients with CNS metastases than in those without (P less than 0.05). This difference was primarily related to the fact that patients with MC had a significantly higher CK-BB activity than patients without CNS metastases or patients with parenchymal brain metastases only (P less than 0.01 and P less than 0.05, respectively). Taking 0.20 U/l as a tentative cut-off value (the upper limit range of patients without CNS metastases being 0.19 U/l), 10 out of 12 patients with MC had activities above this level. The sensitivity and specificity for having MC were 83% and 87%, and the positive and negative predictive values 60% and 96%, respectively. The sensitivity and negative predictive value for having any CNS metastases were 57% and 72%. Specificity and positive predictive value: 100%. The CSF activity of CK-BB appears to be a contribution in the diagnosis of MC secondary to breast cancer and seems superior to protein and LDH.
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Seroepidemiological studies of hepatitis B were carried out on diverse groups of children (477) and adults (629) from the Pacific Island country of Vanuatu. In children under 14 years, prevalences of HBsAg and of all markers were 6% and 53.3% respectively; in adults greater than or equal to 20 years the prevalences were 15% and 70%. Age specific prevalence of hepatitis B infection (all markers) was low in infancy (less than 1 year) but rose sharply afterwards, suggesting that the main mechanism of transmission was horizontal spread. This finding is consistent with other developing country studies from the Pacific Islands and elsewhere. In view of the main ages and mechanisms of transmission of hepatitis B in children in developing countries and the need for simple and inexpensive immunisation strategies in this context, it is recommended that mass vaccination of all infants with hepatitis B vaccine be undertaken in hyperendemic areas.
An enzyme-linked immunosorbent assay (ELISA) was developed for the measurement of human urokinase-type plasminogen activator (u-PA) in plasma and serum. Microtiter plates were coated with a monoclonal antibody and incubated with standard or sample. Bound u-PA was quantitated with polyclonal antibodies conjugated with biotin, followed by avidin-peroxidase. The assay was 10 times as sensitive as previously reported immunoassays, the detection limit being approximately 1 pg u-PA in a volume of 100 microliter, with a linear dose-response up to 15 pg u-PA. The assay detected active u-PA and its inactive proenzyme form equally well, and the recovery of both forms was higher than 90% in plasma. It also detected u-PA complexed with plasminogen activator inhibitor type 1. Various structurally related proteins, including t-PA, were tested, but no reaction was observed with proteins other than u-PA and its amino-terminal fragment. The intra-assay and interassay coefficients of variation for determination of u-PA in plasma were 7.6% and 8.4%, respectively. The ELISA was used to measure the concentration of u-PA in plasma from 34 healthy donors and 92 patients with breast cancer with a varying extent of disease. The mean value for the healthy donors was 1.1 +/- 0.3 ng/ml (SD) of u-PA in plasma. This value is substantially lower than those previously reported. The mean value for the patients with breast cancer was 1.3 +/- 0.4 ng/ml. This moderate increase was statistically significant at the 1% level. Approximately one quarter of the patients had plasma u-PA concentrations above the range observed for the healthy controls. There was a positive correlation between the mean u-PA plasma concentration and the extent of disease in different groups of patients.
To determine whether levels of mammalian bombesin (MB) or calcitonin would be useful in detecting CNS metastases in patients with small-cell lung cancer (SCLC), we measured their concentrations in the CSF of 94 patients who underwent lumbar puncture for suspected CNS involvement. The MB concentration was significantly elevated in the 51 patients with definite CNS metastases as compared with the 30 patients without apparent CNS involvement (P less than .01). This significance was due to increased levels of MB in 18 patients with meningeal carcinomatosis. Whereas CSF MB was detectable (greater than 10 fmol/mL) in only 7% of patients without apparent CNS involvement, CSF MB was detectable in 21% with parenchymal CNS metastases and in 78% of those with meningeal carcinomatosis. Interestingly, 93% of patients having MB concentrations above 20 fmol/mL had meningeal metastases. The calcitonin concentration was significantly elevated in 42 patients with CNS metastases as compared with 27 patients without CNS involvement (P less than .01). Both the 15 patients with meningeal carcinomatosis and the 27 patients with only parenchymal metastases had significantly elevated levels of CSF calcitonin as compared with those without CNS metastases. Fifty-three percent of patients with meningeal carcinomatosis and 48% with parenchymal metastases had a CSF calcitonin level above 18 fmol/mL, whereas only 7% without apparent CNS metastases exceeded this level. Sixty-seven percent of all patients with CNS metastases had increased CSF levels of one of the two hormonal markers. Thus, in SCLC patients, an elevated CSF calcitonin strongly suggested CNS metastases and an elevated MB was very suggestive of the presence of meningeal carcinomatosis. However, only the latter observation seems of clinical importance due to the difficulties in establishing this diagnosis with current diagnostic measures.