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Biomedical subjects

D Nagel

Publications and source records attributed to D Nagel.

At least 127 records · Page 7Linked to original sources
PubMed1976

Metabolism of the pancreatic carcinogens N-nitroso-bis(2-oxopropyl)amine and N-nitroso-bis(2-hydroxypropyl)amine in the Syrian hamster.

Metabolisms of the potent pancreatic carcinogens N-nitroso-bis(2-oxopropyl)amine (BOP) and N-nitroso-bis(2-hydroxypropyl)amine (BHP) were studied in male Syrian hamsters. BHP and a new metabolite, N-nitroso-(2-hydroxypropyl)(2-oxopropyl)amine (HPOP), were detected in the urine of hamsters administered BOP and BHP. The rates of HPOP formation from BOP and BHP were determined by the measurement of blood and urine levels at various times after each compound was administered: HPOP was formed readily from BOP, but slowly from BHP. This may explain the different organotropic spectra and carcinogenic potencies of BOP and BHP.

Animals↗
PubMed1976

Tumorigenicity of tetramethylhydrazine hydrochloride in Swiss mice.

Tetramethylhydrazine hydrochloride (TEMH) was administered in drinking water as a 0.125% solution to randomly bred Swiss mice for life beginning at 6 weeks of age. As a result of treatment, the incidence of blood vessel tumors rose from 5 to 96% in females and from 6 to 88% in males, while that of lung tumors increased from 21 to 36% in females and from 23 to 28% in males, as compared with untreated controls. The increased incidence of blood vessel tumors, but not of lung neoplasms, was statistically significant. Histopathologically, the tumors exhibited the characteristics of angiomas and angiosarcomas of blood vessels and adenomas of the lung. The investigation proved for the first time the tumorigenicity of TEMH. The possible role of increased methyl substitution on hydrazine in tumorigenesis was also discussed, as well as hydrazine derivatives as a tumor-producing class.

Adenoma↗
PubMed1975

Comparative determination of total serum thyroxine. Radio-immunoassay and protein-binding assay.

The precision, accuracy, sensitivity and clinical results of a radio-immunological method for the determination of total serum thyroxine are compared with similar criteria of a competitive protein-binding assay. Application of both methods in the assay of thyroxine in 150 serum samples gave good agreement between the two techniques. The radio-immunoassay offers certain methodological advantages and is considerably less costly than thyroxine determinations in which commercially available kits are used.

Costs and Cost Analysis↗
PubMed1975

Long-time observations on the Blalock-Taussig operation VIII. 20 to 28 year follow-up on patients with a tetralogy of Fallot.

This study extends our previous observation on patients with a tetralogy of Fallot, operated on by the late Dr; Alfred Blalock and his associates between 1945 and 1951, from a 15 year follow-up to 20 years and assesses the final status of these patients 20 to 28 years after their first operation. This study is mainly concerned with the 432 patients known to be alive at the beginning of the 15th postoperative year. At the beginning of the 20th year, 376 patients were alive, 24 had died, 32 had been lost to follow-up. Review of the final status of those 432 patients showed that 169 had no further cardiac surgery after their initial operation, 36 had further palliative surgery, and 227 had total correction. Thirty-seven percent of the first group, and 79.3% of those with total correction were doing well. These two groups, however, are not comparable. Approximately 250 patients have married; 161 have one or more children. Thirty-five percent have graduated from college and 68.7% are earning substantial incomes. The high scholastic achievement of many of these patients is strong evidence that low oxygen saturation of arterial blood is not a prime cause of mental retardation. The occupations of the patients indicate that the quality of their lives is extremely good and that a cardiac handicap in childhood does not preclude success in adult life. Approximately 69% of these patients have repaid in taxes the cost to society of their rehabilitation.

Educational Status↗
PubMedDate not supplied

Removal of nitrosamines from waste water by potassium ferrate oxidation.

Potassium ferrate (K2FeO4) is useful in the advanced treatment of waste water. Additional evidence of this capability is presented in this study. Potassium ferrate is a very strong oxidant and is highly soluble in water. The nitrosamine studied in this work was toxic and was a potent pancreatic tumorigen in laboratory animals. Nitrosamines, which are potent carcinogens, are widespread throughout the environment and can be eliminated from waste water effluent by the action of potassium ferrate. Potassium ferrate and the nitrosamine was placed in aqueous solution and allowed to react to completion. Analysis by photospectroscopy revealed that the nitrosamine was completely degraded. This result suggests that potassium ferrate is useful for decontamination of some waste water collections.

Iron↗
PubMedDate not supplied

Studies of the tumorigenic potential of 4-substituted phenylhydrazines by the subcutaneous route.

4-Methylphenylhydrazine hydrochloride (4-MPH) was administered to randomly bred Swiss mice as 26 weekly sc injections of 140 microgram per gram of body weight and N'-acetyl-4-(hydroxymethyl)phenylhydrazine (AMPH) as 26 weekly sc injections of 500 microgram/g. As a solvent control, physiological saline was also given as 26 weekly sc injections of 0.01 ml/g. The 4-MPH treatment induced a significant incidence (24%) of fibrosarcomas in males. In the 4-MPH-treated females and some AMPH-treated male mice, a few soft-tissue tumors were observed; however, their appearance could not be related to treatment. 4-MPH is formed under special experimental conditions from 4-hydroxymethylphenyl-hydrazine, which is an in vitro breakdown product of agaritine, an ingredient of the cultivated mushroom Agaricus bisporus. The implications of the findings are discussed.

Animals↗
PubMedDate not supplied

Tumour markers CEA and CA 15-3 as Prognostic factors in breast cancer--univariate and multivariate analysis.

Tumour markers are putative prognostic indicators for patients with breast cancer, but have not been elevated independently by multivariate analysis in a large patient number. In 550 patients with breast cancer without known metastases the levels of the serum tumour markers CEA und CA 15-3 were determined preoperatively and during follow-up. The prognostic relevance of these markers for recurrence (n = 128/487) and death of disease (n = 55/550) was evaluated in relation to established prognostic factors. In univariate analysis tumour size, lymph nodes, histological grading, age, hormone receptors, preoperative value of CEA (cut-off 2 ng/mL) and CA 15-3 (cut-off 25 U/mL) and their decrease of more than 33% within seven months after operation were significant for relapse. The results for death of disease were similar except for age. In multivariate analysis tumour size, lymph nodes and decrease of CEA > 33% (p < 0.001) were independent prognostic factors for recurrence. For overall survival tumour size, lymph nodes, histological grading and preoperative levels of CEA > or = 2 ng/mL (p = 0.038) and of CA 15-3 > or = 25 U/mL (p = 0.007) were independent prognostic factors. Pre- and postoperative values of the tumour markers CEA und CA 15-3 are strong independent prognostic factors for relapse and survival in breast cancer patients.

Analysis of Variance↗
PubMedDate not supplied

Multivariate analysis of the prognostic value of CEA and CA 19-9 serum levels in colorectal cancer.

UNLABELLED: Carcinoembrionic Antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) are the most commonly used tumor-associated antigens in the management of patients with colorectal cancer. The aim of this study was to evaluate the prognostic value of preoperative serum levels of CEA and/or CA 19-9 and the classical prognostic factors (age, sex, tumor infiltration and staging) in 495 patients. PATIENTS AND METHODS: The retrospective study was performed on frozen sera (stored at -70 degrees C) of patients with histologically proven colorectal cancer. Survival function estimates were calculated (Kaplan-Meier). The patients were separated into two groups according to the preoperative marker levels. Cut-off levels calculated at a specificity of 100% versus healthy individuals were used: < 4 ng/mL versus > or = 4 ng/mL for CEA and < 60 U/mL versus > or = 60 U/mL for CA 19-9. Survival curve differences were assessed using the log-rank-test. Mulivariate Cox's proportional hazard regression analysis was performed to examine the association between tumor marker levels and survival time. Classical prognostic factors such as age, sex, tumor infiltration, tumor stage (Dukes' classification) were included as covariants. The mantel-Haenszel method was used to assess the survival rate of patients with colorectal carcinoma and high versus low levels of tumor-associated antigens according to tumor stages. RESULTS: The Dukes' stages (log-rank chi-square = 231.9; p < 0.0001) represent the best prognostic factor besides the preoperative values of CA 19-9 (log-rank chi-square = 162.5). CEA shows a log-rank chi-square of 71.4. Thus, CEA and CA 19-9 can be used to discriminate two groups of patients with significantly different survival times (p < 0.0001). The importance of different parameters in providing additional prognostic information was evaluated by multivariate analysis. Only items of statistically significant prognostic relevance (univariate analysis) were used for this analysis. Estimated relative risks of death adjusted for tumor stage were 5.5 considering Dukes' stage A versus Dukes' stage B/C and Dukes' stage B/C versus Dukes' stage D, respectively, and an increasing relative risk of 27.5 for Dukes' stage A versus Dukes' stage D (p < 0.001). The relative risk for preoperative CA 19-9 serum concentrations (> or = 60 U/mL versus < 60 U/mL) was 2.3 (p < 0.001) and for preoperative CEA concentrations (> or = 4 ng/mL versus < 4 ng/mL) 1.4 (p < 0.07). For CEA the 2-year survival rates in the group of patients with preoperative serum concentrations > 4 ng/mL versus < 4 ng/mL and Dukes' stage D were 16% versus 38%, in Dukes' stage B/C 73% versus 91% and in Dukes' stage A 100% versus 98%. For CA 19-9 the 2-year survival rates in the group of patients with preoperative serum concentrations > or = 60 U/mL versus < 60 U/mL and Dukes' stage D were 10% versus 39%, whilst in Dukes' stage B/C 58% versus 87%. In the group of patients with Dukes' stage A with serum levels > or = 60 U/mL a 2-years survival rate of 100% was found. CONCLUSION: The postoperative Dukes' classification represents the best prognostic information besides the preoperative values of CA 19-9. The predictive information provided by preoperative CA 19-9 serum levels is independent from that obtained by the other factors investigated. Only Dukes' classification and CA 19-9 levels showed statistical significance (p < 0.001).

Biomarkers, Tumor↗
PubMedDate not supplied

Prognostic value of preoperative serum levels of CEA, CA 19-9 and CA 72-4 in gastric carcinoma.

UNLABELLED: We studied the relevance of CEA, CA 19-9, CA 72-4 and the common classical prognostic factors (age, sex, tumor infiltration, N-classification, staging, grading and Lauren classification) in gastric carcinoma. PATIENTS AND METHODS: Survival function estimates were calculated according the method to Kaplan-Meier. The patients were separated into two groups according to preoperative marker levels. Fixing specificity at 100% for healthy people, cut off levels were calculated. Survival curve differences were assessed using the log-rank-test. Multivariate Cox proportional hazards regression analysis was performed. The mantel-Haenszel method was used to assess the 2-year survival rate of patients with gastric carcinoma and high versus low levels of tumor-associated antigens adjusted to tumor stages. The study was performed on the frozen sera (stored at -80 degrees C) of 103 patients with histologically proven gastric carcinoma. RESULTS: The tumor stage (log-rank chi-square = 55.9; P < 0.0001) represents the best prognostic factor besides preoperative values of CA 19-9 (log-rank chi-square = 13.9; P < 0.001) and CEA (log-rank chi-square = 12.2; P < 0.001). CA 72.4 shows a log-rank chi-square of 6.9 (P < 0.01). We found no statistically significant correlation between survival and sex, tumor grade and Lauren classification. The importance of different parameters in providing additional prognostic information was evaluated by multivariate analysis. Only patients after curative surgical intervention (n = 55, R0) were considered. Cox proportional hazards regression analysis yielded an adjusted relative risk of 2.4 in patients with a preoperative CEA concentrations > or = 4 ng/mL vs. < 4 ng/mL, of 2.8 in patients with a preoperative CA 19-9 concentration > or = 60 U/mL vs. < CA 19-9 and of 1.8 for stage III/IV vs. stage I/II (P < 0.05). For CEA the 2-year survival rates in the group of patients with preoperative serum concentrations > or = 4 ng/mL versus < 4 ng/mL and stadium III/IV were 14% versus 29% and in stadium I/II 50% versus 83% (P < 0.05). For CA 19-9 the 2-years survival rates in the group of patients with preoperative serum concentrations > or = 60 U/mL versus < 60 U/mL and stadium III/IV were 14% versus 28% and in stadium I/II 40% versus 83% (P < 0.05). CONCLUSION: The postoperative R-classification and the tumor stage represent the best prognostic information besides the preoperative values of CA 19-9 or CEA, respectively. The predictive information provided by preoperative CEA and CA 19-9 serum levels is additional to that obtained from other factors investigated.

Antigens, Tumor-Associated, Carbohydrate↗
PubMedDate not supplied

Preoperative serum levels of CEA and CA 19-9 and their prognostic significance in colorectal carcinoma.

UNLABELLED: The prognostic information provided by preoperative serum CEA, CA 19-9 antigen assays as compared with the classical prognostic factors (age, sex, tumor infiltration, tumor stage (Dukes') and R-classification) in 495 patients with colorectal carcinoma was analysed. PATIENTS AND METHODS: Survival function estimates were calculated according to Kaplan-Meier. The patients were separated into two groups according to the preoperative marker levels. Fixing specificity at 100% for healthy people, cut off levels were calculated. Survival curve differences were assessed using the log-rank-test. Multivariate Cox's proportional hazard regression analysis was performed. The Mantel-Haenszel method was used to assess the survival rate of patients with colorectal carcinoma and high versus low levels of tumor-associated antigens according to tumor stages. The study was performed on the frozen sera (stored at -80 degrees C) of 495 patients with histologically proven colorectal carcinoma. RESULTS: The Dukes' stages (log-rank chi-square = 231.9; P < 0.0001) represent the best prognostic factor besides the preoperative values of CA 19-9 (log-rank chi-square = 162.5). CEA shows a log-rank chi-square of 71.4. Thus, CEA and CA 19-9 can be used to discriminate two groups of patients with significantly different survival times (P < 0.0001). The importance of different parameters in providing additional prognostic information was evaluated by multivariate analysis (Cox's model). Estimated relative risks of death adjusted for tumor stage were 5.5 for Dukes' stage A versus Dukes' stage B/C and Dukes' stage B/C versus Dukes' stage D, respectively and an increasing relative risk of 27.5 for Dukes' stage A versus Dukes' stage D (P < 0.001). The relative risk for preoperative CA 19-9 serum concentrations (> or = 60 U/mL versus < 60 U/mL) was 2.3 (P < 0.001) for preoperative CEA concentrations (> or = 4 ng/mL versus < 4 ng/mL) 1.4 (P < 0.07). For CEA the 2-years survival rates in the group of patients with preoperative serum concentrations > or = 4 ng/mL versus < 4 ng/mL and Dukes' stage D were 16% versus 38%, in Dukes' stage B/C 73% versus 91% and in Dukes' stage A 100% versus 98%. For CA 19-9 the 2-years survival rates in the group of patients with preoperative serum concentrations > or = 60 U/mL versus < 60 U/mL and Dukes' stage D were 10% versus 39%, in Dukes' stage B/C 58% versus 87%. In the group of patients with Dukes' stage A with serum levels > or = 60 U/mL a 2-year survival rate of 100% was found. In the corresponding group only one patient exists. CONCLUSION: The postoperative Dukes' classification provides the best prognostic information besides the preoperative values of CA 19-9. The predictive information provided by the preoperative CA 19-9 serum level is additional to that obtained from the other factors investigated.

CA-19-9 Antigen↗
PubMedDate not supplied

The ratio of free to total prostate specific antigen: an advantageous addition in the differential diagnosis of benign hyperplasia and cancer of the prostate?

UNLABELLED: This study examined the clinical relevance of the determination of free PSA (f-PSA) in addition to total PSA (t-PSA). PATIENTS AND METHODS: Both total PSA- and free PSA-values of frozen sera obtained pretherapeutically from 80 patients with carcinoma (PC) and 171 patients with benign hyperplasia of the prostate (BPH) were analysed by means of PSA IRMA and FREE PSA IRMA (IMMUNOCORP/IBL). RESULTS: At 95% specificity (true negative test results), a cut-off value of 16.8 [micrograms/L] was obtained for total PSA (9 patients with BPH [5%] were above this value). For this cut-off value we calculated a sensitivity (true positive test results) of 41%. Using the same criteria for the ratio Q = f-PSA:t-PSA a cut-off of 0.083 was found again at a specificity of 95%. In a second step only patients with total PSA values below the cut-off level of 16.8 [micrograms/L]) were considered. Of these patients 11 of 160 with BPH (missing values = 1) and 13 of 33 with PC (missing values = 2) were below the above mentioned ratio (Q = 0.083). Considering both steps (total PSA and Q) 46 patients with PC were detected correctly and 20 patients with BPH would have been biopsied unnecessarily (positive biopsy rate: 70%). CONCLUSION: High total PSA levels are a very good indicator for the presence of prostate cancer. There is still concern to improve the differentiation between the diagnosis between BPH and PC, when an intermediate or low value (< or = 95% specificity) is observed. The determination of Q is only useful in this range and might be helpful for the clinician's decision to apply or avoid biopsy.

Diagnosis, Differential↗