Search PubMed⌕ Search

Biomedical subjects

A G Pedersen

Publications and source records attributed to A G Pedersen.

At least 37 records · Page 2Linked to original sources
PubMed1992

Different early effect of irradiation in brain and small cell lung cancer examined by in vivo 31P-magnetic resonance spectroscopy.

Early effects of irradiation were evaluated by non-invasive in vivo 31P-magnetic resonance spectroscopy (31P-MRS) of two small cell lung cancer (SCLC) tumor lines CPH SCCL 54A and 54B, in nude mice. The tumors were originally derived from the same patient and have similar morphology and growth characteristics, but a different radiosensitivity. The 54A tumors are twice as radiosensitive as the 54B's. In the present study the tumors were treated with 2.5, 10, and 40 Gy. For comparison, nude mice were given cranial irradiation at the same three doses, and the effect was evaluated by in vivo 31P-MRS. No effect was observed in brain at any dose level. In contrast, 40 Gy induced a statistically significant reduction in ATP/Pi ratio during the 12-h post-irradiation period. This effect was more pronounced in 54A than in 54B. Some reduction was observed following 10 Gy, whereas 2.5 Gy induced no changes in ATP/Pi. The differential effect on tumors and brain might be relevant for monitoring irradiation effects by in vivo 31P-MRS in patients with brain metastases.

Animals↗
PubMed1991

Combination chemotherapy of limited-stage small-cell lung cancer. A controlled trial on 221 patients comparing two alternating regimens.

The outcome of two different alternating regimens of chemotherapy was investigated in a prospective controlled trial in limited-stage small-cell lung cancer (SCLC). Both regimens comprised cyclophosphamide, lomustine, vincristine, methotrexate, doxorubicin and etoposide administered in different schedules. The investigative regimen (B) included simultaneous administration of cyclophosphamide + lomustine alternating with cyclophosphamide + doxorubicin, and with doxorubicin + lomustine. The hypothetical superiority of this regimen was based on data from experimental animal tumors suggesting potentiated efficacy of the three specific combinations. A total of 234 patients were included, and 113 vs 108 patients were eligible. Median survival in both groups was 48 weeks (p = 0.89). Complete remissions were observed in 36/101 and in 42/99 patients evaluable for response. There was no significant difference in response duration. At restaging after 18 months of chemotherapy 27 patients (16%) and 22 patients (16%), respectively, were free of disease. Six patients, three in each arm, are still alive, 8+ to 10.5+ years after diagnosis. Scheduled doses of the six agents were the same in the two regimens except for a 30% reduction of every second dose of cyclophosphamide in regimen B. Nevertheless, regimen B resulted in significantly more leukopenic patients, septicemic episodes, and blood transfusions, and the dosage of etoposide was more often reduced in arm B than in arm A. The increased toxicity was not associated with improved treatment results.

Adult↗
PubMed1989

Creatine kinase-BB in the cerebrospinal fluid as a marker of CNS metastases and leptomeningeal carcinomatosis in patients with breast cancer.

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.

Biomarkers, Tumor↗
PubMed1987

Detection of liver metastases in small-cell lung cancer: a comparison of peritoneoscopy with liver biopsy and ultrasonography with fine-needle aspiration.

Liver evaluation of 131 patients with small-cell lung cancer (SCLC) was performed both by peritoneoscopy (PS) with liver biopsy and by ultrasonography (US) with fine-needle aspiration. A total of 33 patients (25%) had liver involvement, 82% detected by US and 76% detected by PS. The difference was due to 27 incomplete investigations by PS and two incomplete investigations by US. In 104 patients in whom both investigations were "successful," PS confirmed 86% and US confirmed 79% of the patients with liver metastases. In each of the investigations, 7% (PS) and 14% (US) of patients had false-negative conclusions as compared with histologic evidence obtained by the other method. US found six patients with extrahepatic intraabdominal disease, while PS found none. S-lactic dehydrogenase (s-LDH), SGOT, and s-alkaline phosphatase were found to be too unspecific to indicate liver metastases unless all three tests were normal or abnormal. It is recommended that US should be used as the initial procedure when staging patients with SCLC, and that PS can be considered complementary in patients with negative US.

Biopsy↗
PubMed1986

Acute and long-term nephrotoxicity of cis-platinum in man.

To detect whether the nephrotoxicity of cis-diamminedichloroplatinum (DDP) is acute and can be demonstrated at an early stage in man, a method for estimating the function of the kidneys during intensive hydration was devised. The method includes a calculation of the clearance of 125I-orthoiodohippurate and an estimation of the glomerular filtration rate (GFR) from fast changes of the extracellular volume (ECV) and the mean transit time of 99mTc-DTPA in this volume. We examined nine patients with testicular cancer on 2 consecutive days for acute nephrotoxicity while they were undergoing treatment with cis-platinum. Placebo was given on day 1, cis-platinum on day 2. On both days the patients were hydrated with 4 l saline, glucose, and mannitol (0.51) over a period of 4 h, which resulted in an increase of 125I-orthoiodohippurate clearance on both days (P less than 0.01). The increase was, however, lower on the day of treatment with cis-platinum than on the day with placebo (P less than 0.05). There were no acute changes in the GFR. This indicates that treatment with DDP inhibits the active transport of 125I-orthoiodohippurate in the tubules; that is to say there is an acute effect on the kidney function. There were no acute changes in the GFR, but in the long-term followup study we found that the GFR had decreased significantly (P less than 0.05) after 2 months of treatment. During the first year after the initiation of treatment the GFR changes were found to progress. A significant increase in se-creatinine was not observed until 6 months after the initiation of treatment (P less than 0.05). The degree of chronic nephrotoxicity did not correlate in individual patients with the acute changes in kidney function.

Acute Disease↗
PubMed1986

Cerebrospinal fluid bombesin and calcitonin in patients with central nervous system metastases from small-cell lung cancer.

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.

Bombesin↗
PubMed1986

Teniposide (VM-26), an overlooked highly active agent in small-cell lung cancer. Results of a phase II trial in untreated patients.

Teniposide, VM-26 (Vumon), was administered in a dose of 60 mg/m2 on days 1 to 5 every third week to 36 patients with histologically confirmed small-cell lung cancer. None had previously received chemotherapy or radiotherapy. The median age was 73 years (range, 52 to 79). Thirty-three patients were evaluable; 21 of these had local disease. Five patients had bone marrow metastases, four had liver involvement, and one CNS metastases. All patients had a performance status less than or equal to 2 before the start of treatment. Thirty patients obtained a response (90%), ten of whom had a complete remission (30%). The median duration of remission was 8+ months (range, 1.1 to 17+ months), whereas the median survival was 8.7 months (range, 1.9 to 20 months). Toxicity was primarily hematologic, with leukopenia the only dose-limiting effect. Besides alopecia, all other side effects were minimal including nausea and vomiting. We find these results provocative in regard to the response rate and the duration of response obtained as well as in reference to the dismal results that prior investigations in previously treated patients have shown. These data may indicate the need for reconsideration of the usual strategy for performing phase II trials.

Aged↗
PubMed1986

Tumor markers in patients with lung cancer.

The most examined tumor markers in lung cancer patients are CEA, hormonal peptides, and some neurogenic enzymes in small cell carcinoma. Calcitonin, ACTH, ADH, CEA, neurophysin, oxytocin, beta-endorphin, neuron-specific enolase, and CK BB are elevated in serum specimens in 25-75% of cases of small cell carcinoma. The level of these markers is related to the stage of the disease in groups of patients; elevated pretreatment levels decrease with tumor regression. Marker levels are not valid in defining the tumor load and the presence of disease in the individual patient. It has not yet been documented that the markers can be used for clinical decisions on antineoplastic therapy. A recent development is the finding that measurement of CSF and plasma concentrations of ADH, calcitonin, CK BB, bombesin, and neuron-specific enolase may contribute in the diagnosis of CNS metastases including meningeal carcinomatosis.

ACTH Syndrome, Ectopic↗
PubMed1985

Cerebrospinal fluid ACTH as a marker of central nervous system metastases from small cell carcinoma of the lung.

Adrenocorticotrophic hormone (ACTH) concentrations were measured in the plasma and cerebrospinal fluid (CSF) of 107 consecutive patients with known or suspected central nervous system (CNS) metastases secondary to small cell carcinoma of the lung. The combined results of computerized tomography scans, neurologic examination, and autopsy were used to determine the presence or absence of CNS metastases. On the basis of such an assessment, definitive conclusions were possible in 77 patients. CNS metastases were present in 52 cases and absent in 25. The median CSF ACTH level was 30 ng/ml in both groups. None of five patients with very high CSF ACTH concentrations had elevated ACTH concentrations in plasma. Considering the 95th percentile of patients without CNS metastases as the upper limit of normal, 12 patients with metastases and one without had an elevated CSF ACTH value. Eleven patients with leptomeningeal carcinomatosis (MC) did not constitute a special subgroup in this respect. The median ratio of CSF ACTH and plasma ACTH was 1.0 in patients with CNS metastases and 0.4 in those without (P less than 0.05). Patients with MC had a median ratio of 1.3, which was significantly different from that of both of the other groups (P less than 0.05). Ten patients with CNS metastases (one with MC) and one without exceeded the upper 95th percentile of the CSF/plasma (ACTH) ratio in patients without CNS metastases. The significance levels of these findings disappeared, however, when patients with signs of an elevated ACTH concentration in plasma were excluded. Patients with ectopic ACTH production into CSF do not necessarily have ectopic ACTH production outside the CNS, despite the presence of extracerebral metastases. With the criteria employed in this study, an elevated level of CSF ACTH diagnosed too few patients for the authors to recommend its determination as a single test in diagnosing CNS metastases or MC secondary to small cell carcinoma of the lung.

ACTH Syndrome, Ectopic↗
PubMed1985

Frequency, diagnosis, and prognosis of spinal cord compression in small cell bronchogenic carcinoma. A review of 817 consecutive patients.

A retrospective review of 817 consecutive patients with small cell bronchogenic carcinoma disclosed 29 cases of spinal cord compression (frequency, 3.5%). Twelve patients (group 1) presented with symptom of cord compression, whereas the remaining 17 patients (group 2) developed this complication during therapy. Clinical features differed in the two groups: pain was present in 83% of the patients in group 1 and in 47% of those in group 2. Pain preceded motor dysfunction in 75% and 12% of the two groups, respectively. Radiologic bone destruction of the spine was found in 11 of 12 patients in group 1 and in 3 of 16 patients in group 2. Myelography was performed in 8 patients in group 1 and in 14 patients from group 2. A complete block was found in seven and none of the patients in each of the two groups, respectively. Treatment with irradiation and/or laminectomy rarely resulted in a significant improvement of preexisting neurologic impairment but it frequently prevented the progression of symptoms, leading to preservation of sphincter control and ambulatory function in eight of nine and seven of eight patients, respectively. Careful evaluation is mandatory for patients presenting with back pain and radiographic evidence of bone destruction, as 11 of 26 such patients were found to have spinal cord compression. It is concluded that spinal cord compression presents in two distinct ways. One with early onset, pain, evidence of bone destruction, and complete myelographic block. The second is characterized by motor impairment with no evidence of bone destruction and only partial myelographic block. Treatment rarely ameliorates symptoms but prevents deterioration, making early diagnosis important.

Carcinoma, Bronchogenic↗
PubMed1985

Metrizamide myelography in patients with small cell carcinoma of the lung suspected of meningeal carcinomatosis.

Twenty patients suspected of meningeal carcinomatosis (MC) secondary to small cell carcinoma of the lung were evaluated by myelography and by cytologic examination of cerebrospinal fluid (CSF). In 4 patients both investigations demonstrated MC. Four had positive cytology but a negative myelogram. Five patients had a positive myelogram but negative cytology. Thus 13 of the 20 patients had MC diagnosed by one or both of these investigations. Two additional patients suspected of MC were studied; both had positive myelography, but cytologic examination of CSF was not performed in either case. Six patients underwent autopsy with microscopic examination of the spinal cord; in all cases post-mortem findings supported myelographic findings. In conclusion, myelography is useful in the evaluation of patients suspected of MC secondary to small carcinoma of the lung and complements the diagnostic role of CSF examination.

Carcinoma, Small Cell↗
PubMed1985

Cerebrospinal fluid vasopressin as a marker of central nervous system metastases from small-cell bronchogenic carcinoma.

Vasopressin (ADH) was measured in CSF and plasma in 75 evaluable patients with known or suspected CNS metastases from small-cell bronchogenic carcinoma (SCBC), and in 66 control patients having neither malignant disease nor organic CNS disease. The presence of CNS metastases was confirmed or excluded on the basis of computed tomographic scans, neurologic examination, and autopsy. Twenty-four of the 75 patients had no CNS metastases. Ten of the 51 patients with CNS metastases had leptomeningeal carcinomatosis (MC). CSF-ADH was significantly increased in patients with MC (P less than .05), but not in patients having exclusively parenchymatous CNS metastases. Taking 2 pg/mL (95th percentile of control patients) as the upper limit of normal, 15 SCBC patients had elevated CSF-ADH, including 12 patients with CNS metastases and six patients with MC. The CSF-ADH to plasma ADH ratio was significantly increased in patients with CNS metastases (P less than .05). Patients without CNS metastases had a ratio less than or equal to 0.8 whereas the ratio was greater than 0.8, in 21 of the 51 patients with CNS metastases. The positive and negative predictive values with 95% confidence limits were 84% to 100% and 31% to 59%, respectively. Patients with inappropriate secretion of ADH (SIADH) constituted a significantly greater proportion of patients with elevated CSF-ADH than of patients with normal CSF-ADH levels (P less than .05). In addition, patients with SIADH constituted a significantly greater proportion of patients with MC than of patients with parenchymatous metastases (P less than .05). The diagnostic application of these findings is limited because of the large number of false-negative results, but it may prove to be of value in conjunction with the measurement of other tumor markers.

Carcinoma, Bronchogenic↗
PubMed1985

Creatine kinase BB and beta-2-microglobulin as markers of CNS metastases in patients with small-cell lung cancer.

Creatine kinase (CK) and its BB isoenzyme (CK-BB) were measured in CSF in 65 evaluable patients suspected of CNS metastases secondary to small-cell lung cancer (SCLC). In addition, CSF and plasma levels of beta-2-microglobulin (beta-2-m) were measured in a group of 73 evaluable patients. Of the 65 patients analysed for CK-BB, 17 had meningeal carcinomatosis (MC), 26 had parenchymal metastases only, and 22 had no CNS disease. Patients with MC had a significantly higher CK-BB concentration in CSF than did patients belonging to the other two groups (P less than .01). Taking 0.4 U/L (upper limit in patients without CNS disease) as a cut-off point, 15 patients (88%) with MC had elevated CSF concentrations of CK-BB. Patients without CNS metastases had no CSF levels exceeding this value, whereas five patients with multiple CNS metastases did. Receiver operating characteristic (ROC) analysis suggests that CK-BB may be useful in distinguishing MC among patients suspected of having CNS metastases, and CK-BB appears superior to total CK, CSF protein, and CSF lactic dehydrogenase (LDH). In 12 patients with MC at autopsy, CK-BB was, with the above cut-off point, elevated in six patients with a false negative cytology. Of the 73 patients examined for beta-2-m, 18 had MC, 30 had parenchymatous metastases only, and 25 patients had no CNS metastases. The CSF concentrations in the three groups were not significantly different. The median concentrations in the groups were 133 nmol/L, 125 nmol/L, and 107 nmol/L, respectively. The ratios between beta-2-m in CSF and plasma were also not significantly different between the three groups. Thus, the data on CK-BB are promising, and further studies are warranted to see if the usefulness of CK-BB can be more firmly established. By contrast, beta-2-m has no role as a marker of CNS disease secondary to SCLC.

Brain Neoplasms↗